Noncardiac Comorbidities in Heart Failure With Reduced Versus Preserved Ejection Fraction

PubMed Central

Mentz, Robert J.; Kelly, Jacob P.; von Lueder, Thomas G.; Voors, Adriaan A.; Lam, Carolyn S. P.; Cowie, Martin R.; Kjeldsen, Keld; Jankowska, Ewa A.; Atar, Dan; Butler, Javed; Fiuzat, Mona; Zannad, Faiez; Pitt, Bertram; O’Connor, Christopher M.

2014-01-01

Heart failure patients are classified by ejection fraction (EF) into distinct groups: heart failure with preserved EF (HFpEF) or heart failure with reduced EF (HFrEF). Although patients with heart failure commonly have multiple comorbidities that complicate management and may adversely affect outcomes, their role in the HFpEF and HFrEF groups is not well-characterized. This review summarizes the role of noncardiac comorbidities in patients with HFpEF versus HFrEF, emphasizing prevalence, underlying pathophysiologic mechanisms, and outcomes. Pulmonary disease, diabetes mellitus, anemia, and obesity tend to be more prevalent in HFpEF patients, but renal disease and sleep-disordered breathing burdens are similar. These comorbidities similarly increase morbidity and mortality risk in HFpEF and HFrEF patients. Common pathophysiologic mechanisms include systemic and endomyocardial inflammation with fibrosis. We also discuss implications for clinical care and future HF clinical trial design. The basis for this review was discussions between scientists, clinical trialists, and regulatory representatives at the 10th Global CardioVascular Clinical Trialists Forum. PMID:25456761

Heart failure with preserved ejection fraction and systolic dysfunction in the community.

PubMed

Moutinho, Marco Aurélio Esposito; Colucci, Flávio Augusto; Alcoforado, Veronica; Tavares, Leandro Reis; Rachid, Mauricio Bastos Freitas; Rosa, Maria Luisa Garcia; Ribeiro, Mário Luiz; Abdalah, Rosemery; Garcia, Juliana Lago; Mesquita, Evandro Tinoco

2008-02-01

In developed countries, heart failure with preserved ejection fraction (HFpEF) is more prevalent than heart failure with reduced ejection fraction (HFrEF) in the community. However, it has not been completely established if this fact is also observed within our community. To determine the most prevalent form of heart failure (HFpEF or HFrEF) and whether the prevalence of HFpEF is higher in the community. This is a cross-sectional study conducted with patients clinically diagnosed with HF who were seen in community-based health care centers from January to December 2005. Echodopplercardiograms were performed for all patients. The form of HF was stratified according to the presence of abnormalities and the shortening fraction observed on the echodopplercardiogram. The study evaluated 170 patients (61.0 +/- 13.3 years of age), most of them women and elderly. HFpEF was the more prevalent form of HF (64.2%, p<0.001), affecting mostly elderly women (62%, p = 0.07), whereas the opposite condition, HFrEF, was observed mostly in elderly men (63.6%, p = 0.07). Patients with no HF represented one-third of the cases (27.6%). HFrEF patients had more lower-limb edema, coronary disease, diabetes, chronic renal failure, higher Boston scores and hospital readmissions. Use of alcoholic beverages and smoking were also more common among HFrEF patients. HFpEF is the most prevalent form of HF in the community especially among elderly women, whereas HFrEF affects mostly elderly men and is associated with greater clinical severity, main risk factors and no changes in lifestyle. Despite the signs and symptoms of HF, this condition was not confirmed for one-third of the cases.

Metabolomic Fingerprint of Heart Failure with Preserved Ejection Fraction

PubMed Central

Zordoky, Beshay N.; Sung, Miranda M.; Ezekowitz, Justin; Mandal, Rupasri; Han, Beomsoo; Bjorndahl, Trent C.; Bouatra, Souhaila; Anderson, Todd; Oudit, Gavin Y.; Wishart, David S.; Dyck, Jason R. B.

2015-01-01

Background Heart failure (HF) with preserved ejection fraction (HFpEF) is increasingly recognized as an important clinical entity. Preclinical studies have shown differences in the pathophysiology between HFpEF and HF with reduced ejection fraction (HFrEF). Therefore, we hypothesized that a systematic metabolomic analysis would reveal a novel metabolomic fingerprint of HFpEF that will help understand its pathophysiology and assist in establishing new biomarkers for its diagnosis. Methods and Results Ambulatory patients with clinical diagnosis of HFpEF (n = 24), HFrEF (n = 20), and age-matched non-HF controls (n = 38) were selected for metabolomic analysis as part of the Alberta HEART (Heart Failure Etiology and Analysis Research Team) project. 181 serum metabolites were quantified by LC-MS/MS and 1H-NMR spectroscopy. Compared to non-HF control, HFpEF patients demonstrated higher serum concentrations of acylcarnitines, carnitine, creatinine, betaine, and amino acids; and lower levels of phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins. Medium and long-chain acylcarnitines and ketone bodies were higher in HFpEF than HFrEF patients. Using logistic regression, two panels of metabolites were identified that can separate HFpEF patients from both non-HF controls and HFrEF patients with area under the receiver operating characteristic (ROC) curves of 0.942 and 0.981, respectively. Conclusions The metabolomics approach employed in this study identified a unique metabolomic fingerprint of HFpEF that is distinct from that of HFrEF. This metabolomic fingerprint has been utilized to identify two novel panels of metabolites that can separate HFpEF patients from both non-HF controls and HFrEF patients. Clinical Trial Registration ClinicalTrials.gov NCT02052804 PMID:26010610

Risk Factors for Incident Hospitalized Heart Failure With Preserved Versus Reduced Ejection Fraction in a Multiracial Cohort of Postmenopausal Women.

PubMed

Eaton, Charles B; Pettinger, Mary; Rossouw, Jacques; Martin, Lisa Warsinger; Foraker, Randi; Quddus, Abdullah; Liu, Simin; Wampler, Nina S; Hank Wu, Wen-Chih; Manson, JoAnn E; Margolis, Karen; Johnson, Karen C; Allison, Matthew; Corbie-Smith, Giselle; Rosamond, Wayne; Breathett, Khadijah; Klein, Liviu

2016-10-01

Heart failure is an important and growing public health problem in women. Risk factors for incident hospitalized heart failure with preserved ejection fraction (HFpEF) compared with heart failure with reduced ejection fraction (HFrEF) in women and differences by race/ethnicity are not well characterized. We prospectively evaluated the risk factors for incident hospitalized HFpEF and HFrEF in a multiracial cohort of 42 170 postmenopausal women followed up for a mean of 13.2 years. Cox regression models with time-dependent covariate adjustment were used to define risk factors for HFpEF and HFrEF. Differences by race/ethnicity about incidence rates, baseline risk factors, and their population-attributable risk percentage were analyzed. Risk factors for both HFpEF and HFrEF were as follows: older age, white race, diabetes mellitus, cigarette smoking, and hypertension. Obesity, history of coronary heart disease (other than myocardial infarction), anemia, atrial fibrillation, and more than one comorbidity were associated with HFpEF but not with HFrEF. History of myocardial infarction was associated with HFrEF but not with HFpEF. Obesity was found to be a more potent risk factor for African American women compared with white women for HFpEF (P for interaction=0.007). For HFpEF, the population-attributable risk percentage was greatest for hypertension (40.9%) followed by obesity (25.8%), with the highest population-attributable risk percentage found in African Americans for these risk factors. In this multiracial cohort of postmenopausal women, obesity stands out as a significant risk factor for HFpEF, with the strongest association in African American women. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611. © 2016 American Heart Association, Inc.

Diagnosis and Management of Heart Failure with Preserved Ejection Frac-tion: 10 Key Lessons

PubMed Central

A, Afşin Oktay; Shah, Sanjiv J

2015-01-01

Heart failure with preserved ejection fraction (HFpEF) is a common clinical syndrome associated with high rates of morbidi-ty and mortality. Due to the lack of evidence-based therapies and increasing prevalence of HFpEF, clinicians are often con-fronted with these patients and yet have little guidance on how to effectively diagnose and manage them. Here we offer 10 key lessons to assist with the care of patients with HFpEF: (1) Know the difference between diastolic dysfunction, diastolic heart failure, and HFpEF; (2) diagnosing HFpEF is challenging, so be thorough and consider invasive hemodynamic testing to confirm the diagnosis; (3) a normal B-type natriuretic peptide does not exclude the diagnosis of HFpEF; (4) elevated pul-monary artery systolic pressure on echocardiography in the presence of a normal ejection fraction should prompt considera-tion of HFpEF; (5) use dynamic testing in evaluating the possibility of HFpEF in patients with unexplained dyspnea or exer-cise tolerance; (6) all patients with HFpEF should be systematically evaluated for the presence of coronary artery disease; (7) use targeted treatment for HFpEF patients based on their phenotypic classification; (8) treat HFpEF patients now by treating their comorbidities; (9) understand the importance of heart rate in HFpEF—lower is not always better; and (10) do not forget to consider rare diseases (“zebras”) as causes for HFpEF when evaluating and treating patients. Taken together, these 10 key lessons can help clinicians care for challenging patients with HFpEF while we eagerly await the results of ongoing HFpEF clinical trials and observational studies. PMID:24251461

Obesity and heart failure with preserved ejection fraction: A growing problem.

PubMed

Prenner, Stuart B; Mather, Paul J

2017-12-14

Heart Failure with Preserved Ejection Fraction (HFpEF) is increasing in prevalence due to the aging of the United States population as well as the current obesity epidemic. While obesity is very common in patients with HFpEF, obesity may represent a specific phenotype of HFpEF characterized by unique hemodynamics and structural abnormalities. Obesity induces a systemic inflammatory response that may contribute to myocardial fibrosis and endothelial dysfunction. The most obese patients continue to be excluded from HFpEF clinical trials, and thus ongoing research is needed to determine the role of pharmacologic and interventional approaches in this growing population. Copyright © 2017 Elsevier Inc. All rights reserved.

Heart failure: when form fails to follow function.

PubMed

Katz, Arnold M; Rolett, Ellis L

2016-02-01

Cardiac performance is normally determined by architectural, cellular, and molecular structures that determine the heart's form, and by physiological and biochemical mechanisms that regulate the function of these structures. Impaired adaptation of form to function in failing hearts contributes to two syndromes initially called systolic heart failure (SHF) and diastolic heart failure (DHF). In SHF, characterized by high end-diastolic volume (EDV), the left ventricle (LV) cannot eject a normal stroke volume (SV); in DHF, with normal or low EDV, the LV cannot accept a normal venous return. These syndromes are now generally defined in terms of ejection fraction (EF): SHF became 'heart failure with reduced ejection fraction' (HFrEF) while DHF became 'heart failure with normal or preserved ejection fraction' (HFnEF or HFpEF). However, EF is a chimeric index because it is the ratio between SV--which measures function, and EDV--which measures form. In SHF the LV dilates when sarcomere addition in series increases cardiac myocyte length, whereas sarcomere addition in parallel can cause concentric hypertrophy in DHF by increasing myocyte thickness. Although dilatation in SHF allows the LV to accept a greater venous return, it increases the energy cost of ejection and initiates a vicious cycle that contributes to progressive dilatation. In contrast, concentric hypertrophy in DHF facilitates ejection but impairs filling and can cause heart muscle to deteriorate. Differences in the molecular signals that initiate dilatation and concentric hypertrophy can explain why many drugs that improve prognosis in SHF have little if any benefit in DHF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Causes and Temporal Patterns of 30-Day Readmission Among Older Adults Hospitalized With Heart Failure With Preserved or Reduced Ejection Fraction.

PubMed

Goyal, Parag; Loop, Matthew; Chen, Ligong; Brown, Todd M; Durant, Raegan W; Safford, Monika M; Levitan, Emily B

2018-04-23

It is unknown whether causes and temporal patterns of 30-day readmission vary between heart failure (HF) with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). We sought to address this question by examining a 5% national sample of Medicare beneficiaries. We included individuals who experienced a hospitalization for HFpEF or HFrEF between 2007 and 2013. We identified causes of 30-day readmission based on primary discharge diagnosis and further classified causes of readmission as HF-related, non-HF cardiovascular-related, and non-cardiovascular-related. We calculated the cumulative incidence of these classifications for HFpEF and HFrEF in a competing risks model and calculated subdistribution hazard ratios of these classifications by comparing those with HFpEF and those with HFrEF. Among 60 640 Medicare beneficiaries, we identified 13 785 unique older adults hospitalized with HFpEF and 15 205 who were hospitalized with HFrEF. Noncardiovascular diagnoses represented the most common causes of 30-day readmission (HFpEF: 59%; HFrEF: 47%), a pattern that was observed for each week of the 30-day study period for both HFpEF and HFrEF participants. In comparing readmission diagnoses in an adjusted model, non-cardiovascular-related diagnoses were more common and HF-related diagnoses were less common in HFpEF participants. Non-cardiovascular-related diagnoses represented the most common causes of 30-day readmission following HF hospitalization for each week of the 30-day postdischarge period. HF diagnoses were less common among those with HFpEF compared with HFrEF. Future interventions aimed at reducing 30-day readmissions following an HF hospitalization would benefit from an increased focus on noncardiovascular comorbidity and interventions that target HFpEF and HFrEF separately. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Evidence of Microvascular Dysfunction in Heart Failure with Preserved Ejection Fraction

PubMed Central

Lee, Joshua F.; Barrett-O’Keefe, Zachary; Garten, Ryan S.; Nelson, Ashley D.; Ryan, John J.; Nativi, Jose N.; Richardson, Russell S.; Wray, D. Walter

2015-01-01

Objective While vascular dysfunction is well-defined in HF patients with reduced ejection fraction (HFrEF), disease-related alterations in the peripheral vasculature of HF patients with preserved ejection fraction (HFpEF) are not well characterized. Thus, we sought test the hypothesis that HFpEF patients would demonstrate reduced vascular function, at both the conduit artery and microvascular levels, compared to controls. Methods We examined both conduit artery function via brachial artery flow-mediated dilation (FMD) and microvascular function via reactive hyperemia (RH) following 5 min of ischemia in 24 Class II–IV HFpEF patients and 24 healthy controls matched for age, sex, and brachial artery diameter. Results FMD was reduced in HFpEF patients compared to controls (HFpEF: 3.1 ± 0.7%; Controls: 5.1 ± 0.5%; P = 0.03). However, shear rate at time of peak brachial artery dilation was lower in HFpEF patients compared to controls (HFpEF: 42,070 ± 4,018 s−1; Controls: 69,018 ± 9,509 s−1; P = 0.01), and when brachial artery FMD was normalized for the shear stimulus, cumulative area-under-the-curve (AUC) at peak dilation, the between-group differences were eliminated (HFpEF: 0.11 ± 0.03 %/AUC; Controls: 0.09 ± 0.01 %/AUC; P = 0.58). RH, assessed as AUC, was lower in HFpEF patients (HFpEF: 454 ± 35 mL; Controls: 660 ± 63 mL; P < 0.01). Conclusions Collectively, these data suggest that maladaptations at the microvascular level contribute to the pathophysiology of HFpEF, while conduit artery vascular function is not diminished beyond that which occurs with healthy aging. PMID:26567228

Developing Therapies for Heart Failure with Preserved Ejection Fraction: Current State and Future Directions

PubMed Central

Butler, Javed; Fonarow, Gregg C.; Zile, Michael R.; Lam, Carolyn S.; Roessig, Lothar; Schelbert, Erik B.; Shah, Sanjiv J.; Ahmed, Ali; Bonow, Robert O.; Cleland, John GF; Cody, Robert J.; Chioncel, Ovidiu; Collins, Sean P.; Dunnmon, Preston; Filippatos, Gerasimos; Lefkowitz, Martin P.; Marti, Catherine N.; McMurray, John J.; Misselwitz, Frank; Nodari, Savina; O’Connor, Christopher; Pfeffer, Marc A.; Pieske, Burkert; Pitt, Bertram; Rosano, Guiseppe; Sabbah, Hani N.; Senni, Michele; Solomon, Scott D.; Stockbridge, Norman; Teerlink, John R.; Georgiopoulou, Vasiliki V.; Gheorghiade, Mihai

2014-01-01

The burden of heart failure with preserved ejection fraction (HFpEF) is considerable and is projected to worsen. To date, there are no approved therapies available for reducing mortality or hospitalizations for these patients. The pathophysiology of HFpEF is complex and includes alterations in cardiac structure and function, systemic and pulmonary vascular abnormalities, end-organ involvement, and comorbidities. There remain major gaps in our understanding of HFpEF pathophysiology. To facilitate a discussion of how to proceed effectively in future with development of therapies for HFpEF, a meeting was facilitated by the FDA and included representatives from academia, industry and regulatory agencies. This document summarizes the proceedings from this meeting. PMID:24720916

Prognostic value of depressed midwall systolic function in cardiac light-chain amyloidosis.

PubMed

Perlini, Stefano; Salinaro, Francesco; Musca, Francesco; Mussinelli, Roberta; Boldrini, Michele; Raimondi, Ambra; Milani, Paolo; Foli, Andrea; Cappelli, Francesco; Perfetto, Federico; Palladini, Giovanni; Rapezzi, Claudio; Merlini, Giampaolo

2014-05-01

Cardiac amyloidosis represents an archetypal form of restrictive heart disease, characterized by profound diastolic dysfunction. As ejection fraction is preserved until the late stage of the disease, the majority of patients do fulfill the definition of diastolic heart failure, that is, heart failure with preserved ejection fraction (HFpEF). In another clinical model of HFpEF, that is, pressure-overload hypertrophy, depressed midwall fractional shortening (mFS) has been shown to be a powerful prognostic factor. To assess the potential prognostic role of mFS in cardiac light-chain amyloidosis with preserved ejection fraction, we enrolled 221 consecutive untreated patients, in whom a first diagnosis of cardiac light-chain amyloidosis was concluded between 2008 and 2010. HFpEF was present in 181 patients. Patients in whom cardiac involvement was excluded served as controls (n = 121). Prognosis was assessed after a median follow-up of 561 days. When compared with light-chain amyloidosis patients without myocardial involvement, cardiac light-chain amyloidosis was characterized by increased wall thickness (P <0.001), reduced end-diastolic left ventricular volumes (P <0.001), and diastolic dysfunction (P <0.001). In patients with preserved ejection fraction, mFS was markedly depressed [10.6% (8.7-13.5) vs. 17.8% (15.9-19.5) P <0.001]. At multivariable analysis, mFS, troponin I, and NT-pro-brain natriuretic peptide were the only significant prognostic determinants (P <0.001), whereas other indices of diastolic (E/E' ratio, transmitral and pulmonary vein flow velocities) and systolic function (tissue Doppler systolic indices, ejection fraction), or the presence/absence of congestive heart failure did not enter the model. In cardiac light-chain amyloidosis with normal ejection fraction, depressed circumferential mFS, a marker of myocardial contractile dysfunction, is a powerful predictor of survival.

Treating Heart Failure with Preserved Ejection Fraction: A Challenge for Clinicians.

PubMed

Howard, Patricia A

2015-06-01

Despite a decline in many forms of cardiovascular disease, heart failure (HF) continues to increase. Heart failure with preserved ejection fraction (HFpEF) is common, especially among persons with multiple comorbidities. HFpEF presents many challenges for clinicians due to the incomplete understanding of the underlying mechanisms and lack of consensus on the most effective strategies for treatment. Angiotensin and beta receptor-blocking drugs, which form the cornerstone for the treatment of systolic HF, have failed to show similar benefits in patients with impaired diastolic function. This article provides an overview of drug therapy for HFpEF, including newer agents now under investigation.

Atrial fibrillation in heart failure with preserved ejection fraction: Insights into mechanisms and therapeutics.

PubMed

Patel, Ravi B; Vaduganathan, Muthiah; Shah, Sanjiv J; Butler, Javed

2017-08-01

Atrial fibrillation (AF) and heart failure (HF) often coexist, and the outcomes of patients who have both AF and HF are considerably worse than those with either condition in isolation. Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical entity and accounts for approximately one-half of current HF. At least one-third of patients with HFpEF are burdened by comorbid AF. The current understanding of the relationship between AF and HFpEF is limited, but the clinical implications are potentially important. In this review, we explore 1) the pathogenesis that drives AF and HFpEF to coexist; 2) pharmacologic therapies that may attenuate the impact of AF in HFpEF; and 3) future directions in the management of this complex syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

Catheter ablation of atrial fibrillation in patients with heart failure and preserved ejection fraction.

PubMed

Black-Maier, Eric; Ren, Xinru; Steinberg, Benjamin A; Green, Cynthia L; Barnett, Adam S; Rosa, Normita Sta; Al-Khatib, Sana M; Atwater, Brett D; Daubert, James P; Frazier-Mills, Camille; Grant, Augustus O; Hegland, Donald D; Jackson, Kevin P; Jackson, Larry R; Koontz, Jason I; Lewis, Robert K; Sun, Albert Y; Thomas, Kevin L; Bahnson, Tristam D; Piccini, Jonathan P

2018-05-01

Few studies have examined outcomes of catheter ablation for atrial fibrillation (AF) in patients with heart failure (HF) with preserved ejection fraction (HFpEF). The purpose of this study was to compare outcomes of AF ablation in patients with HFpEF vs HF with reduced ejection fraction (HFrEF). We performed a retrospective study of 230 patients with HF who underwent AF ablation, including 97 (42.2%) with HFrEF and 133 (57.8%) with HFpEF. Outcomes included adverse events, symptoms (Mayo AF Symptom Inventory [MAFSI]), New York Heart Association (NYHA) functional class, and freedom from recurrent atrial arrhythmia at 12 months. Overall, 150 of 230 patients had nonparoxysmal AF (62.8% HFpEF vs 63.0% HFrEF). Patients with HFpEF had a smaller mean left atrial diameter (4.4 ± 0.8 cm vs 4.7 ± 0.7 cm; P = .013) and were less likely to be taking a beta-blocker at baseline (72.9% vs 85.6%; P = .022). Median (Q1, Q3) procedure times (233 minutes [192, 290] vs 233.5 minutes [193.0, 297.5]; P = .780) and adverse events such as acute HF (3.8% vs 6.2%; P = .395) were similar between HFpEF and HFrEF patients. Freedom from recurrent atrial arrhythmia was not significantly different in HFpEF vs HFrEF patients (33.9% vs 32.6%; adjusted hazard ratio 1.47; 95% confidence interval 0.72-3.01), with similar improvements in NYHA functional class (-0.32 vs -0.19; P = .135) and MAFSI symptom severity (-0.23 vs -0.09; P = .116) after ablation. Catheter ablation of AF seems to have similar effectiveness in patients with HF, regardless of presence of systolic dysfunction. There were no significant differences in procedural characteristics, arrhythmia-free recurrence, or functional improvements between patients with HFpEF and those with HFrEF. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Value of the QRS complex in assessing left ventricular ejection fraction.

PubMed

Askenazi, J; Parisi, A F; Cohn, P F; Freedman, W B; Braunwald, E

1978-03-01

The relation between electrocardiographic findings and the angiographic left ventricular ejection fraction and the augmented ejection fraction after a premature ventricular contraction was investigated in 73 patients with documented chronic coronary artery disease. The patients were separated into four groups according to the presence or absence of abnormal Q waves. Twenty-four patients had diaphragmatic myocardial infarction, 21 had anterior myocardial infarction, 15 had both and 13 had no myocardial infarction. There was no statistically significant differences in cardiac index, left ventricular end-diastolic pressure or number of coronary vessels showing critical narrowing in the four groups. The sum of R waves (in mv) in leads aVL, aVF and V1 to V6 (sigmaR) was correlated with the ejection fraction (EF) and the augmented ejection fraction (EFa). EF in percent = 6.6 sigmaR mv + 9.4 (no. =73, r = 0.61); and EFa in percent = 8.6 sigmaR mv + 11.0 (no. = 73, r = 0.77). Among patients with sigmaR of less than 4.0 mv, augmented ejection fraction was less than 0.45 in 73 percent; among patients with sigmaR of 4.0 mv or more the augmented ejection fraction was greater than 0.45 in 93 percent (P less than 0.001). Thus, the sigmaR, calculated from six precordial and two augmented leads in patients with chronic coronary artery disease, correlated with both ejection fraction and augmented ejection fraction. The electrocardiogram in patients with coronary artery disease may prove useful as a simple, readily available and noninvasive guide in the assessment of left ventricular function in patients with coronary artery disease.

Cardiac diastolic and autonomic dysfunction are aggravated by central chemoreflex activation in heart failure with preserved ejection fraction rats

PubMed Central

Toledo, Camilo; Andrade, David C.; Lucero, Claudia; Arce‐Alvarez, Alexis; Díaz, Hugo S.; Aliaga, Valentín; Schultz, Harold D.; Marcus, Noah J.; Manríquez, Mónica; Faúndez, Marcelo

2017-01-01

Key points Heart failure with preserved ejection fraction (HFpEF) is associated with disordered breathing patterns, and sympatho‐vagal imbalance.Although it is well accepted that altered peripheral chemoreflex control plays a role in the progression of heart failure with reduced ejection fraction (HFrEF), the pathophysiological mechanisms underlying deterioration of cardiac function in HFpEF are poorly understood.We found that central chemoreflex is enhanced in HFpEF and neuronal activation is increased in pre‐sympathetic regions of the brainstem.Our data showed that activation of the central chemoreflex pathway in HFpEF exacerbates diastolic dysfunction, worsens sympatho‐vagal imbalance and markedly increases the incidence of cardiac arrhythmias in rats with HFpEF. Abstract Heart failure (HF) patients with preserved ejection fraction (HFpEF) display irregular breathing, sympatho‐vagal imbalance, arrhythmias and diastolic dysfunction. It has been shown that tonic activation of the central and peripheral chemoreflex pathway plays a pivotal role in the pathophysiology of HF with reduced ejection fraction. In contrast, no studies to date have addressed chemoreflex function or its effect on cardiac function in HFpEF. Therefore, we tested whether peripheral and central chemoreflexes are hyperactive in HFpEF and if chemoreflex activation exacerbates cardiac dysfunction and autonomic imbalance. Sprague‐Dawley rats (n = 32) were subjected to sham or volume overload to induce HFpEF. Resting breathing variability, chemoreflex gain, cardiac function and sympatho‐vagal balance, and arrhythmia incidence were studied. HFpEF rats displayed [mean ± SD; chronic heart failure (CHF) vs. Sham, respectively] a marked increase in the incidence of apnoeas/hypopnoeas (20.2 ± 4.0 vs. 9.7 ± 2.6 events h−1), autonomic imbalance [0.6 ± 0.2 vs. 0.2 ± 0.1 low/high frequency heart rate variability (LF/HFHRV)] and cardiac arrhythmias (196.0 ± 239.9 vs. 19.8 ± 21.7 events h−1). Furthermore, HFpEF rats showed increase central chemoreflex sensitivity but not peripheral chemosensitivity. Accordingly, hypercapnic stimulation in HFpEF rats exacerbated increases in sympathetic outflow to the heart (229.6 ± 43.2% vs. 296.0 ± 43.9% LF/HFHRV, normoxia vs. hypercapnia, respectively), incidence of cardiac arrhythmias (196.0 ± 239.9 vs. 576.7 ± 472.9 events h−1) and diastolic dysfunction (0.008 ± 0.004 vs. 0.027 ± 0.027 mmHg μl−1). Importantly, the cardiovascular consequences of central chemoreflex activation were related to sympathoexcitation since these effects were abolished by propranolol. The present results show that the central chemoreflex is enhanced in HFpEF and that acute activation of central chemoreceptors leads to increases of cardiac sympathetic outflow, cardiac arrhythmogenesis and impairment in cardiac function in rats with HFpEF. PMID:28181258

Heart failure with recovered ejection fraction: clinical characteristics, determinants and prognosis. CARDIOCHUS-CHOP registry.

PubMed

Agra Bermejo, Rosa; Gonzalez Babarro, Eva; López Canoa, J Nicolás; Varela Román, Alfonso; Gómez Otero, Inés; Oro Ayude, Marcos; Parada Vazquez, Pablo; Gómez Rodríguez, Isabel; Díaz Castro, Oscar; González Juanatey, Jose Ramón

2017-10-05

The magnitude and the prognostic impact of recovering left ventricular ejection fraction (LVEF) in patients with heart failure (HF) and systolic dysfunction is unclear. The aim of this study was to evaluate the clinical characteristics and prognosis of patients with HFrecEF in an HF population. 449 consecutive patients were selected with the diagnosis of HF and an evaluation of LVEF in the 6 months prior to selection who were referred to two HF units. Patients with systolic dysfunction were only considered if a second echocardiogram was performed during the follow-up. At the time of diagnosis, 207 patients had LVEF > 40% (HFpEF) and 242 had LVEF ≤ 40% (HFrEF). After 1 year, the LVEF was re-evaluated in all 242 patients with a LVEF ≤ 40%: in 126 (52%), the second LVEF was > 40% (HFrecEF), and the remaining 116 (48%) had LVEF ≤ 40% (HFrEF). After 1800 ± 900 days of follow-up patients with recovered LVEF had a significantly lower mortality rate (HFpEF vs. HFrecEF: hazard ratio (HR) = 2.286, 95% confidence interval (95% CI) 1.264-4.145, p = 0.019; HFrEF vs. HFrecEF: HR = 2.222, 95% CI 1.189-4.186, p < 0.001) and hospitalization rate (HFpEF vs. HFrecEF: HR = 1.411, 95% CI 1.046-1.903, p = 0.024; HFrEF vs. HFrecEF: HR = 1.388, 95% CI 1.002-1.924, p = 0.049). The following are predictors of LVEF recovery: younger age, lower functional class, treatment with renin-angiotensin-aldosterone system inhibitors and beta-blockers, absence of defibrillator use, and non-ischemic aetiology. Patients with HF and reduced LVEF who were re-evaluated after 1 year, had significant improvement in their LVEF and had a more favourable prognosis than HF with preserved and reduced ejection fraction.

Comparison of Predictors of Heart Failure-related Hospitalization or Death in Patients with versus without Preserved Left Ventricular Ejection Fraction

PubMed Central

Mangla, Ashvarya; Kane, John; Beaty, Elijah; Richardson, DeJuran; Powell, Lynda H.; Calvin, James E.

2013-01-01

Heart failure with preserved ejection fraction (HFpEF) is recognized as a major cause of cardiovascular morbidity and mortality. An ability to identify patients with HFpEF who are at increased risk for adverse outcome can facilitate their more careful management. We studied the patients having heart failure (HF) using data from the Heart Failure Adherence and Retention Trial (HART). HART enrolled 902 NYHA Class II or III patients who had been recently hospitalized for HF to study the impact of self-management counseling on the primary outcome of death or HF hospitalization. In HART 208 patients had HFpEF and 692 had HFrEF (heart failure with reduced ejection fraction), and were followed for median of 1080 days. Two final multivariate models were developed. In patients having HFpEF, predictors of primary outcome were: male sex (OR 3.45, p=0.004), NYHA class III (OR 3.05, p=0.008), distance covered on 6-minute walk test (6-MWT) of< 620 feet (OR 2.81, p=0.013), and <80% adherence to prescribed medications (OR 2.61, p=0.018). In patients having HFrEF, the predictors were: being on diuretics (OR 3.06, p=0.001), having ≥ 3 comorbidities (OR 2.11, p=0.0001), distance covered on 6-MWT of < 620 feet (OR 1.94, p=0.001), NYHA class III (OR 1.90, p=0.001) and age > 65 years (OR 1.63, p=0.01). In conclusion, indicators of functional status(6-MWT and NYHA class) were common to both HFpEF and HFrEF patients while gender and adherence to prescribed therapy were unique to patients having HFpEF in predicting death or HF hospitalization. PMID:24063842

Relationship Between Physical Activity, Body Mass Index, and Risk of Heart Failure

PubMed Central

Pandey, Ambarish; LaMonte, Michael; Klein, Liviu; Ayers, Colby; Psaty, Bruce; Eaton, Charles; Allen, Norrina; de Lemos, James A.; Carnethon, Mercedes; Greenland, Philip; Berry, Jarett D.

2018-01-01

Background Lower leisure-time physical activity (LTPA) and higher body mass index (BMI) are independently associated with risk of heart failure (HF). However, it is unclear if this relationship is consistent for both HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). Objective This study sought to quantify dose-response associations between LTPA, BMI, and the risk of different HF subtypes. Methods Individual-level data from 3 cohort studies (WHI, MESA, and CHS) were pooled and participants were stratified into guideline-recommended categories of LTPA and BMI. Associations between LTPA, BMI, and risk of overall HF, HFpEF (ejection fraction [EF] ≥45%) and HFrEF (EF <45%) were assessed used multivariable adjusted Cox models and restricted cubic splines. Results The study included 51,451 participants with 3,180 HF events (1,252 HFpEF, 914 HFrEF, 1,014 missing EF). In adjusted analysis, there was a dose-dependent association between higher LTPA levels, lower BMI, and overall HF risk. Among HF subtypes, LTPA in any dose range was not associated with HFrEF risk. In contrast, lower levels of LTPA (<500 metabolic equivalents of task [MET]-min/week) were not associated with HFpEF risk, and dose-dependent associations with lower HFpEF risk were observed at higher levels. Compared with no LTPA, higher than twice the guideline-recommended minimum LTPA levels (>1,000 MET-min/week) were associated with an 19% lower risk of HFpEF (HR: 0.81; 95% CI: 0.68 to 0.97). The dose-response relationship for BMI with HFpEF risk was also more consistent than with HFrEF risk, such that increasing BMI above the normal range (≥ 25 kg/m2) was associated with greater increase in risk of HFpEF than HFrEF. Conclusion Our study findings demonstrate strong, dose-dependent associations between LTPA levels, BMI, and risk of overall HF. Among HF subtypes, higher LTPA levels and lower BMI were more consistently associated with lower risk of HFpEF compared with HFrEF. PMID:28254175

Precision Medicine for Heart Failure with Preserved Ejection Fraction: An Overview.

PubMed

Shah, Sanjiv J

2017-06-01

There are few proven therapies for heart failure with preserved ejection fraction (HFpEF). The lack of therapies, along with increased recognition of the disorder and its underlying pathophysiology, has led to the acknowledgement that HFpEF is heterogeneous and is not likely to respond to a one-size-fits-all approach. Thus, HFpEF is a prime candidate to benefit from a precision medicine approach. For this reason, we have assembled a compendium of papers on the topic of precision medicine in HFpEF in the Journal of Cardiovascular Translational Research. These papers cover a variety of topics relevant to precision medicine in HFpEF, including automated identification of HFpEF patients; machine learning, novel molecular approaches, genomics, and deep phenotyping of HFpEF; and clinical trial designs that can be used to advance precision medicine in HFpEF. In this introductory article, we provide an overview of precision medicine in HFpEF with the hope that the work described here and in the other papers in this special theme issue will stimulate investigators and clinicians to advance a more targeted approach to HFpEF classification and treatment.

Precision Medicine for Heart Failure with Preserved Ejection Fraction: An Overview

PubMed Central

Shah, Sanjiv J.

2017-01-01

There are few proven therapies for heart failure with preserved ejection fraction (HFpEF). The lack of therapies, along with increased recognition of the disorder and its underlying pathophysiology, has led to the acknowledgement that HFpEF is heterogeneous and is not likely to respond to a one-size-fits-all approach. Thus, HFpEF is a prime candidate to benefit from a precision medicine approach. For this reason, we have assembled a compendium of papers on the topic of precision medicine in HFpEF in the Journal of Cardiovascular Translational Research. These papers cover a variety of topics relevant to precision medicine in HFpEF, including automated identification of HFpEF patients; machine learning, novel molecular approaches, genomics, and deep phenotyping of HFpEF; and clinical trial designs that can be used to advance precision medicine in HFpEF. In this introductory article, we provide an overview of precision medicine in HFpEF with the hope that the work described here and in the other papers in this special theme issue will stimulate investigators and clinicians to advance a more targeted approach to HFpEF classification and treatment. PMID:28585183

Worsening renal function and outcome in heart failure patients with preserved ejection fraction and the impact of angiotensin receptor blocker treatment.

PubMed

Damman, Kevin; Perez, Ana C; Anand, Inder S; Komajda, Michel; McKelvie, Robert S; Zile, Michael R; Massie, Barrie; Carson, Peter E; McMurray, John J V

2014-09-16

Worsening renal function (WRF) associated with renin-angiotensin-aldosterone system (RAAS) inhibition does not confer excess risk in heart failure patients with reduced ejection fraction (HFrEF). The goal of this study was to investigate the relationship between WRF and outcomes in heart failure patients with preserved ejection fraction (HFpEF) and the interaction with RAAS blockade. In 3,595 patients included in the I-PRESERVE (Irbesartan in Heart Failure With Preserved Ejection Fraction) trial, change in estimated glomerular filtration rate (eGFR) and development of WRF after initiation of irbesartan or placebo were examined. We examined the association between WRF and the first occurrence of cardiovascular death or heart failure hospitalization (primary outcome in this analysis) and the interaction with randomized treatment. Estimated GFR decreased early with irbesartan treatment and remained significantly lower than in the placebo group. WRF developed in 229 (6.4%) patients and occurred more frequently with irbesartan treatment (8% vs. 4%). Overall, WRF was associated with an increased risk of the primary outcome (adjusted hazard ratio [HR]: 1.43; 95% confidence interval [CI]: 1.10 to 1.85; p = 0.008). Although the risk related to WRF was greater in the irbesartan group (HR: 1.66; 95% CI: 1.21 to 2.28; p = 0.002) than with placebo (HR: 1.09; 95% CI: 0.66 to 1.79; p = 0.73), the interaction between treatment and WRF on outcome was not significant in an adjusted analysis. The incidence of WRF in HFpEF was similar to that previously reported in HFrEF but more frequent with irbesartan than with placebo. WRF after initiation of irbesartan treatment in HFpEF was associated with excess risk, in contrast to WRF occurring with RAAS blockade in HFrEF. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Early Adoption of Sacubitril/Valsartan for Patients With Heart Failure With Reduced Ejection Fraction: Insights From Get With the Guidelines-Heart Failure (GWTG-HF).

PubMed

Luo, Nancy; Fonarow, Gregg C; Lippmann, Steven J; Mi, Xiaojuan; Heidenreich, Paul A; Yancy, Clyde W; Greiner, Melissa A; Hammill, Bradley G; Hardy, N Chantelle; Turner, Stuart J; Laskey, Warren K; Curtis, Lesley H; Hernandez, Adrian F; Mentz, Robert J; O'Brien, Emily C

2017-04-01

The aim of this study was to assess the prevalence and variation in angiotensin receptor/neprilysin inhibitor (ARNI) prescription among a real-world population with heart failure with reduced ejection fraction (HFrEF). The U.S. Food and Drug Administration approved sacubitril/valsartan for patients with HFrEF in July 2015. Little is known about the early patterns of use of this novel therapy. The study included patients discharged alive from hospitals in Get With the Guidelines-Heart Failure (GWTG-HF), a registry of hospitalized patients with heart failure, between July 2015 and June 2016 who had documentation of whether ARNIs were prescribed at discharge. Patient and hospital characteristics were compared among patients with HFrEF (ejection fraction ≤40%) with and without ARNI prescription at discharge, excluding those with documented contraindications to ARNIs. To evaluate hospital variation, hospitals with at least 10 eligible hospitalizations during the study period were assessed. Of 21,078 patients hospitalized with HFrEF during the study period, 495 (2.3%) were prescribed ARNIs at discharge. Patients prescribed ARNIs were younger (median age 65 years vs. 70 years; p < 0.001), had lower ejection fractions (median 23% vs. 25%; p < 0.001), and had higher use of aldosterone antagonists (45% vs. 31%; p < 0.001) at discharge. At the 241 participating hospitals with 10 or more eligible admissions, 125 (52%) reported no discharge prescriptions of ARNIs. Approximately 2.3% of patients hospitalized for HFrEF in a national registry were prescribed ARNI therapy in the first 12 months following Food and Drug Administration approval. Further study is needed to identify and overcome barriers to implementing new evidence into practice, such as ARNI use among eligible patients with HFrEF. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Ejection fraction improvement and reverse remodeling achieved with Sacubitril/Valsartan in heart failure with reduced ejection fraction patients.

PubMed

Almufleh, Aws; Marbach, Jeffrey; Chih, Sharon; Stadnick, Ellamae; Davies, Ross; Liu, Peter; Mielniczuk, Lisa

2017-01-01

Sacubitril/Valsartan has been shown to improve mortality and reduce hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF). The effect of Sacubitril/Valsartan on ejection fraction (EF) and reverse remodeling parameters have not been previously described. We performed a single-center, retrospective, cohort study of HFrEF patients (n=48) who were treated with Sacubitril/Valsartan for a median duration of 3 months (Interquartile range 2-6 months). Clinical and echocardiographic parameters were reviewed at three time points (pre-baseline which was median of 18 months before starting Sacubitril/Valsartan, baseline before treatment started, and post-Sacubitril/Valsartan). Paired sample t-test and one-way repeated measures ANOVA were used for normally distributed data, while Wilcoxon Signed Rank test for non-normally distributed data. Sacubitril/Valsartan use was associated with an average 5% (±1.2) increase in EF, from a mean baseline of 25.33% to 30.14% (p<0.001) with a median duration of treatment 3 months. There was no significant change in mean LVEF over a median duration of 11 months (IQR 5.5-15.5) between pre-baseline and baseline time points prior to treatment (p=1.0). The mean increase in ejection fraction tended to be marginally greater in the medium/high dose cohort as compared to the low dose cohort, with a mean increase of 5.09% (±1.36) and 4.03% (±3.17), respectively (p=0.184). There was a 3.36 mm reduction in left ventricular end-systolic diameter (p=0.04), a 2.64 mm reduction in left ventricular end-diastolic diameter (p=0.02), and a 14.4 g/m 2 reduction in left ventricular mass index (p<0.01). Sacubitril/Valsartan was found to improve EF and multiple measures of reverse remodeling beyond the effects of concomitant optimal medical therapy. Though these results are encouraging, our small sample, observational study requires confirmation in larger cohorts with longer follow-up periods.

Extracellular Volume Fraction for Characterization of Patients With Heart Failure and Preserved Ejection Fraction.

PubMed

Rommel, Karl-Philipp; von Roeder, Maximilian; Latuscynski, Konrad; Oberueck, Christian; Blazek, Stephan; Fengler, Karl; Besler, Christian; Sandri, Marcus; Lücke, Christian; Gutberlet, Matthias; Linke, Axel; Schuler, Gerhard; Lurz, Philipp

2016-04-19

Optimal patient characterization in heart failure with preserved ejection fraction (HFpEF) is essential to tailor successful treatment strategies. Cardiac magnetic resonance (CMR)-derived T1 mapping can noninvasively quantify diffuse myocardial fibrosis as extracellular volume fraction (ECV). This study aimed to elucidate the diagnostic performance of T1 mapping in HFpEF by examining the relationship between ECV and invasively measured parameters of diastolic function. It also investigated the potential of ECV to differentiate among pathomechanisms in HFpEF. We performed T1 mapping in 24 patients with HFpEF and 12 patients without heart failure symptoms. Pressure-volume loops were obtained with a conductance catheter during basal conditions and handgrip exercise. Transient pre-load reduction was used to extrapolate the diastolic stiffness constant. Patients with HFpEF showed higher ECV (p < 0.01), elevated load-independent passive left ventricular (LV) stiffness constant (beta) (p < 0.001), and a longer time constant of active LV relaxation (p = 0.02). ECV correlated highly with beta (r = 0.75; p < 0.001). Within the HFpEF cohort, patients with ECV greater than the median showed a higher beta (p = 0.05), whereas ECV below the median identified patients with prolonged active LV relaxation (p = 0.01) and a marked hypertensive reaction to exercise due to pathologic arterial elastance (p = 0.04). On multiple linear regression analyses, ECV independently predicted intrinsic LV stiffness (β = 0.75; p < 0.01). Diffuse myocardial fibrosis, assessed by CMR-derived T1 mapping, independently predicts invasively measured LV stiffness in HFpEF. Additionally, ECV helps to noninvasively distinguish the role of passive stiffness and hypertensive exercise response with impaired active relaxation. (Left Ventricular Stiffness vs. Fibrosis Quantification by T1 Mapping in Heart Failure With Preserved Ejection Fraction [STIFFMAP]; NCT02459626). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Influence of Prior Heart Failure Hospitalization on Cardiovascular Events in Patients with Reduced and Preserved Ejection Fraction

PubMed Central

Bello, Natalie A.; Claggett, Brian; Desai, Akshay S.; McMurray, John J.V.; Granger, Christopher B.; Yusuf, Salim; Swedberg, Karl; Pfeffer, Marc A.; Solomon, Scott D.

2014-01-01

Background Hospitalization for acute heart failure (HF) is associated with high rates of subsequent mortality and readmission. We assessed the influence of the time interval between prior HF hospitalization and randomization in the CHARM trials on clinical outcomes in patients with both reduced and preserved ejection fraction. Methods and Results CHARM enrolled 7,599 patients with NYHA class II-IV heart failure, of whom 5,426 had a history of prior HF hospitalization. Cox proportional hazards regression models were utilized to assess the association between time from prior HF hospitalization and randomization and the primary outcome of cardiovascular death or unplanned admission to hospital for the management of worsening HF over a median of 36.6 months. For patients with HF and reduced (HFrEF) or preserved (HFpEF) ejection fraction, rates of CV mortality and HF hospitalization were higher among patients with prior HF hospitalization than those without. The risk for mortality and hospitalization varied inversely with the time interval between hospitalization and randomization. Rates were higher for HFrEF patients within each category. Event rates for those with HFpEF and a HF hospitalization in the 6 months prior to randomization were comparable to the rate in HFrEF patients with no prior HF hospitalization. Conclusions Rates of CV death or HF hospitalization are greatest in those who have been previously hospitalized for HF. Independent of EF, rates of death and readmission decline as time from HF hospitalization to trial enrollment increased. Recent HF hospitalization identifies a high risk population for future clinical trials in HFrEF and HFpEF. Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00634400. PMID:24874200

Diastolic stiffness as assessed by diastolic wall strain is associated with adverse remodelling and poor outcomes in heart failure with preserved ejection fraction.

PubMed

Ohtani, Tomohito; Mohammed, Selma F; Yamamoto, Kazuhiro; Dunlay, Shannon M; Weston, Susan A; Sakata, Yasushi; Rodeheffer, Richard J; Roger, Veronique L; Redfield, Margaret M

2012-07-01

The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is complex but increased left ventricular (LV) diastolic stiffness plays a key role. A load-independent, non-invasive, direct measure of diastolic stiffness is lacking. The diastolic wall strain (DWS) index is based on the linear elastic theory, which predicts that impaired diastolic wall thinning reflects resistance to deformation in diastole and thus, increased diastolic myocardial stiffness. The objectives of this community-based study were to determine the distribution of this novel index in consecutive HFpEF patients and healthy controls, define the relationship between DWS and cardiac structure and function and determine whether increased diastolic stiffness as assessed by DWS is predictive of the outcome in HFpEF. Consecutive HFpEF patients (n = 327, EF ≥ 50%) and controls (n = 528) from the same community were studied. Diastolic wall strain was lower in HFpEF (0.33 ± 0.08) than in controls (0.40 ± 0.07, P < 0.001). Within HFpEF, those with DWS ≤ median (0.33) had higher LV mass index, relative wall thickness, E/e', Doppler-estimated LV end-diastolic pressure to LV end-diastolic volume ratio, left atrial volume index, and brain natriuretic peptide (BNP) levels than those with DWS > median. Heart failure with preserved ejection fraction patients with DWS ≤ median had higher rate of death or HF hospitalization than those with DWS > median (P = 0.003) even after the adjustment for age, gender, log BNP, LV geometry, or log E/e' (P < 0.01). These data suggest that DWS, a simple index, is useful in assessing diastolic stiffness and that more advanced diastolic stiffness is associated with worse outcomes in HFpEF.

Predictors and Prognostic Value of Worsening Renal Function During Admission in HFpEF Versus HFrEF: Data From the KorAHF (Korean Acute Heart Failure) Registry.

PubMed

Kang, Jeehoon; Park, Jin Joo; Cho, Young-Jin; Oh, Il-Young; Park, Hyun-Ah; Lee, Sang Eun; Kim, Min-Seok; Cho, Hyun-Jai; Lee, Hae-Young; Choi, Jin Oh; Hwang, Kyung-Kuk; Kim, Kye Hun; Yoo, Byung-Su; Kang, Seok-Min; Baek, Sang Hong; Jeon, Eun-Seok; Kim, Jae-Joong; Cho, Myeong-Chan; Chae, Shung Chull; Oh, Byung-Hee; Choi, Dong-Ju

2018-03-13

Worsening renal function (WRF) is associated with adverse outcomes in patients with heart failure. We investigated the predictors and prognostic value of WRF during admission, in patients with preserved ejection fraction (HFpEF) versus those with reduced ejection fraction (HFrEF). A total of 5625 patients were enrolled in the KorAHF (Korean Acute Heart Failure) registry. WRF was defined as an absolute increase in creatinine of ≥0.3 mg/dL. Transient WRF was defined as recovery of creatinine at discharge, whereas persistent WRF was indicated by a nonrecovered creatinine level. HFpEF and HFrEF were defined as a left ventricle ejection fraction ≥50% and ≤40%, respectively. Among the total population, WRF occurred in 3101 patients (55.1%). By heart failure subgroup, WRF occurred more frequently in HFrEF (57.0% versus 51.3%; P <0.001 in HFrEF and HFpEF). Prevalence of WRF increased as creatinine clearance decreased in both heart failure subgroups. Among various predictors of WRF, chronic renal failure was the strongest predictor. WRF was an independent predictor of adverse in-hospital outcomes (HFrEF: odds ratio; 2.75; 95% confidence interval, 1.50-5.02; P =0.001; HFpEF: odds ratio, 9.48; 95% confidence interval, 1.19-75.89; P =0.034) and 1-year mortality (HFrEF: hazard ratio, 1.41; 95% confidence interval, 1.12-1.78; P =0.004 versus HFpEF: hazard ratio, 1.72; 95% confidence interval, 1.23-2.42; P =0.002). Transient WRF was a risk factor for 1-year mortality, whereas persistent WRF had no additive risk compared to transient WRF. In patients with acute heart failure patients, WRF is an independent predictor of adverse in-hospital and follow-up outcomes in both HFrEF and HFpEF, though with a different effect size. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01389843. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Outcomes of de novo and acute decompensated heart failure patients according to ejection fraction.

PubMed

Choi, Ki Hong; Lee, Ga Yeon; Choi, Jin-Oh; Jeon, Eun-Seok; Lee, Hae-Young; Cho, Hyun-Jai; Lee, Sang Eun; Kim, Min-Seok; Kim, Jae-Joong; Hwang, Kyung-Kuk; Chae, Shung Chull; Baek, Sang Hong; Kang, Seok-Min; Choi, Dong-Ju; Yoo, Byung-Su; Kim, Kye Hun; Park, Hyun-Young; Cho, Myeong-Chan; Oh, Byung-Hee

2018-03-01

There are conflicting results among previous studies regarding the prognosis of heart failure with preserved ejection fraction (HFpEF) compared with heart failure with reduced ejection fraction (HFrEF). This study aimed to compare the outcomes of patients with de novo acute heart failure (AHF) or acute decompensated HF (ADHF) according to HFpEF (EF≥50%), or HFrEF (EF<40%) and to define the prognosis of patients with HF with mid-range EF (HFmrEF, 40≤EF<50%). Between March 2011 and February 2014, 5625 consecutive patients with AHF were recruited from 10 university hospitals. A total of 5414 (96.2%) patients with EF data were enrolled, which consisted of 2867 (53.0%) patients with de novo and 2547 (47.0%) with ADHF. Each of the enrolled group was stratified by EF. In de novo, all-cause death rates were not significantly different between HFpEF and HFrEF (HFpEF vs HFrEF, 206/744 (27.7%) vs 438/1631 (26.9%), HR adj 1.15, 95% CI 0.96 to 1.38, p=0.14). However, among patients with ADHF, HFrEF had a significantly higher mortality rate compared with HFpEF (HFpEF vs HFrEF, 245/613 (40.0%) vs 694/1551 (44.7%), HR adj 1.25, 95% CI 1.06 to 1.47, p=0.007). Also, in ADHF, HFmrEF was associated with a significantly lower mortality rate within 1 year compared with HFrEF (HFmrEF vs HFrEF, 88/383 (23.0%) vs 430/1551 (27.7%), HR adj 1.31, 95% CI 1.03 to 1.65, p=0.03), but a significantly higher mortality rate after 1 year compared with HFpEF (HFmrEF vs HFpEF, 83/295 (28.1%) vs 101/469 (21.5%), HR adj 0.70, 95% CI 0.52 to 0.96, p=0.02). HFpEF may indicate a better prognosis compared with HFrEF in ADHF, but not in de novo AHF. For patients with ADHF, the prognosis associated with HFmrEF was similar to that of HFpEF within the first year following hospitalisation and similar to HFrEF 1  year after hospitalisation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Current Perspectives on Systemic Hypertension in Heart Failure with Preserved Ejection Fraction.

PubMed

Tam, Marty C; Lee, Ran; Cascino, Thomas M; Konerman, Matthew C; Hummel, Scott L

2017-02-01

Heart failure with preserved ejection fraction (HFpEF) is a prevalent but incompletely understood syndrome. Traditional models of HFpEF pathophysiology revolve around systemic HTN and other causes of increased left ventricular afterload leading to left ventricular hypertrophy (LVH) and diastolic dysfunction. However, emerging models attribute the development of HFpEF to systemic proinflammatory changes secondary to common comorbidities which include HTN. Alterations in passive ventricular stiffness, ventricular-arterial coupling, peripheral microvascular function, systolic reserve, and chronotropic response occur. As a result, HFpEF is heterogeneous in nature, making it difficult to prescribe uniform therapies to all patients. Nonetheless, treating systemic HTN remains a cornerstone of HFpEF management. Antihypertensive therapies have been linked to LVH regression and improvement in diastolic dysfunction. However, to date, no therapies have definitive mortality benefit in HFpEF. Non-pharmacologic management for HTN, including dietary modification, exercise, and treating sleep disordered breathing, may provide some morbidity benefit in the HFpEF population. Future research is need to identify effective treatments, perhaps in more specific subgroups, and focus may need to shift from reducing mortality to improving exercise capacity and symptoms. Tailoring antihypertensive therapies to specific phenotypes of HFpEF may be an important component of this strategy.

Visually estimated ejection fraction by two dimensional and triplane echocardiography is closely correlated with quantitative ejection fraction by real-time three dimensional echocardiography.

PubMed

Shahgaldi, Kambiz; Gudmundsson, Petri; Manouras, Aristomenis; Brodin, Lars-Ake; Winter, Reidar

2009-08-25

Visual assessment of left ventricular ejection fraction (LVEF) is often used in clinical routine despite general recommendations to use quantitative biplane Simpsons (BPS) measurements. Even thou quantitative methods are well validated and from many reasons preferable, the feasibility of visual assessment (eyeballing) is superior. There is to date only sparse data comparing visual EF assessment in comparison to quantitative methods available. The aim of this study was to compare visual EF assessment by two-dimensional echocardiography (2DE) and triplane echocardiography (TPE) using quantitative real-time three-dimensional echocardiography (RT3DE) as the reference method. Thirty patients were enrolled in the study. Eyeballing EF was assessed using apical 4-and 2 chamber views and TP mode by two experienced readers blinded to all clinical data. The measurements were compared to quantitative RT3DE. There were an excellent correlation between eyeballing EF by 2D and TP vs 3DE (r = 0.91 and 0.95 respectively) without any significant bias (-0.5 +/- 3.7% and -0.2 +/- 2.9% respectively). Intraobserver variability was 3.8% for eyeballing 2DE, 3.2% for eyeballing TP and 2.3% for quantitative 3D-EF. Interobserver variability was 7.5% for eyeballing 2D and 8.4% for eyeballing TP. Visual estimation of LVEF both using 2D and TP by an experienced reader correlates well with quantitative EF determined by RT3DE. There is an apparent trend towards a smaller variability using TP in comparison to 2D, this was however not statistically significant.

Cardiac volumetry in patients with heart failure and reduced ejection fraction: a comparative study correlating multi-slice computed tomography and magnetic resonance tomography. Reasons for intermodal disagreement.

PubMed

Schroeder, Janina; Peterschroeder, Andreas; Vaske, Bernhard; Butz, Thomas; Barth, Peter; Oldenburg, Olaf; Bitter, Thomas; Burchert, Wolfgang; Horstkotte, Dieter; Langer, Christoph

2009-11-01

In humans with normal hearts multi-slice computed tomography (MSCT) based volumetry was shown to correlate well with the gold standard, cardiac magnetic resonance imaging (CMR). We correlated both techniques in patients with various degrees of heart failure and reduced ejection fraction (HFREF) resulting from cardiac dilatation. Twenty-four patients with a left ventricular enddiastolic volume (LV-EDV) of C 150 ml measured by angiography underwent MSCT and CMR scanning for left and right ventricular (LV, RV) volumetry. MSCT based short cardiac axis views were obtained beginning at the cardiac base advancing to the apex. These were reconstructed in 20 different time windows of the RR-interval (0-95%) serving for identification of enddiastole (ED) and end-systole (ES) and for planimetry. ED and ES volumes and the ejection fraction (EF) were calculated for LV and RV. MSCT based volumetry was compared with CMR. MSCT based LV volumetry significantly correlates with CMR as follows: LV-EDV r = 0.94, LV-ESV r = 0.98 and LV-EF r = 0.93, but significantly overestimates LV-EDV and LV-ESV and underestimates EF (P \\ 0.0001). MSCT based RV volumetry significantly correlates with CMR as follows: RV-EDV r = 0.79, RVESV r = 0.78 and RV-EF r = 0.73, but again significantly overestimates RV-EDV and RV-ESV and underestimates RV-EF (P \\ 0.0001). When compared with CMR a continuous overestimation of volumes and underestimation of EF needs to be considered when applying MSCT in HFREF patients.

[Comorbidities of heart failure: sleep apnea].

PubMed

Woehrle, H; Oldenburg, O; Stadler, S; Arzt, M

2018-05-01

Since sleep apnea often occurs in heart failure, physicians regularly need to decide whether further diagnostic procedures and/or treatment are required. Which types of sleep apnea occur in heart failure patients? When is treatment needed? Which treatments and treatment goals are appropriate? Clinical trials and guidelines as well as their implementation in clinical practice are discussed. At least 40% of patients with heart failure, both with reduced and preserved left ventricular ejection fraction (HFrEF and HFpEF, respectively), suffer from relevant sleep apnea. In heart failure patients both obstructive and central sleep apnea are associated with increased mortality. In HFrEF as well as in HFpEF patients with obstructive sleep apnea, treatment with continuous positive airway pressure (CPAP) achieves symptomatic and functional improvements. In patients with HFpEF, positive airway pressure treatment of central sleep apnea may be beneficial. In patients with HFrEF and left ventricular ejection fraction ≤45%, adaptive servoventilation is contraindicated. Sleep apnea is highly prevalent in heart failure patients and its treatment in specific patient groups can improve symptoms and functional outcomes. Thus, testing for sleep apnea is recommended.

Heart rate and outcomes in patients with heart failure with preserved ejection fraction: A dose-response meta-analysis.

PubMed

Shang, Xiaoke; Lu, Rong; Liu, Mei; Xiao, Shuna; Dong, Nianguo

2017-10-01

Although elevated resting heart rate is related to poor outcomes in heart failure (HF) with reduced ejection fraction, the association in HF with preserved ejection fraction (HFpEF) remains inconclusive. Therefore, we conducted a dose-response meta-analysis to examine the prognostic role of heart rate in patients with HFpEF.We searched PubMed and Embase databases until April 2017 and manually reviewed the reference lists of relevant literatures. Random effect models were used to pool the study-specific hazard ratio (HR) of outcomes, including all-cause death, cardiovascular death, and HF hospitalization.Six studies with 7 reports were finally included, totaling 14,054 patients with HFpEF. The summary HR (95% confidence interval [CI]) for every 10 beats/minute increment in heart rate was 1.04 (1.02-1.06) for all-cause death, 1.06 (1.02-1.10) for cardiovascular death, and 1.05 (1.01-1.08) for HF hospitalization. Subgroup analyses indicated that these positive relationships were significant in patients with sinus rhythm but not in those with atrial fibrillation. There was also evidence for nonlinear relationship of heart rate with each of the outcomes (All P for nonlinearity < .05).Higher heart rate in sinus rhythm is a risk factor for adverse outcomes in patients with HFpEF. Future trials are required to determine whether heart rate reduction may improve the prognosis of HFpEF.

Phenotyping of Sleep-Disordered Breathing in Patients With Chronic Heart Failure With Reduced Ejection Fraction-the SchlaHF Registry.

PubMed

Arzt, Michael; Oldenburg, Olaf; Graml, Andrea; Erdmann, Erland; Teschler, Helmut; Wegscheider, Karl; Suling, Anna; Woehrle, Holger

2017-11-29

Different sleep-disordered breathing (SDB) phenotypes, including coexisting obstructive and central sleep apnea (OSA-CSA), have not yet been characterized in a large sample of patients with heart failure and reduced ejection fraction (HFrEF) receiving guideline-based therapies. Therefore, the aim of the present study was to determine the proportion of OSA, CSA, and OSA-CSA, as well as periodic breathing, in HFrEF patients with SDB. The German SchlaHF registry enrolled patients with HFrEF receiving guideline-based therapies, who underwent portable SDB monitoring. Polysomnography (n=2365) was performed in patients with suspected SDB. Type of SDB (OSA, CSA, or OSA-CSA), the occurrence of periodic breathing (proportion of Cheyne-Stokes respiration ≥20%), and blood gases were determined in 1557 HFrEF patients with confirmed SDB. OSA, OSA-CSA, and CSA were found in 29%, 40%, and 31% of patients, respectively; 41% showed periodic breathing. Characteristics differed significantly among SDB groups and in those with versus without periodic breathing. There was a relationship between greater proportions of CSA and the presence of periodic breathing. Risk factors for having CSA rather than OSA were male sex, older age, presence of atrial fibrillation, lower ejection fraction, and lower awake carbon dioxide pressure (pco 2 ). Periodic breathing was more likely in men, patients with atrial fibrillation, older patients, and as left ventricular ejection fraction and awake pco 2 decreased, and less likely as body mass index increased and minimum oxygen saturation decreased. SchlaHF data show that there is wide interindividual variability in the SDB phenotype of HFrEF patients, suggesting that individualized management is appropriate. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01500759. © 2017 The Authors and ResMed Germany Inc. Published on behalf of the American Heart Association, Inc., by Wiley.

Prognostic value of cardiopulmonary exercise testing in heart failure with preserved ejection fraction. The Henry Ford HospITal CardioPulmonary EXercise Testing (FIT-CPX) project.

PubMed

Shafiq, Ali; Brawner, Clinton A; Aldred, Heather A; Lewis, Barry; Williams, Celeste T; Tita, Christina; Schairer, John R; Ehrman, Jonathan K; Velez, Mauricio; Selektor, Yelena; Lanfear, David E; Keteyian, Steven J

2016-04-01

Although cardiopulmonary exercise (CPX) testing in patients with heart failure and reduced ejection fraction is well established, there are limited data on the value of CPX variables in patients with HF and preserved ejection fraction (HFpEF). We sought to determine the prognostic value of select CPX measures in patients with HFpEF. This was a retrospective analysis of patients with HFpEF (ejection fraction ≥ 50%) who performed a CPX test between 1997 and 2010. Selected CPX variables included peak oxygen uptake (VO2), percent predicted maximum oxygen uptake (ppMVO2), minute ventilation to carbon dioxide production slope (VE/VCO2 slope) and exercise oscillatory ventilation (EOV). Separate Cox regression analyses were performed to assess the relationship between each CPX variable and a composite outcome of all-cause mortality or cardiac transplant. We identified 173 HFpEF patients (45% women, 58% non-white, age 54 ± 14 years) with complete CPX data. During a median follow-up of 5.2 years, there were 42 deaths and 5 cardiac transplants. The 1-, 3-, and 5-year cumulative event-free survival was 96%, 90%, and 82%, respectively. Based on the Wald statistic from the Cox regression analyses adjusted for age, sex, and β-blockade therapy, ppMVO2 was the strongest predictor of the end point (Wald χ(2) = 15.0, hazard ratio per 10%, P < .001), followed by peak VO2 (Wald χ(2) = 11.8, P = .001). VE/VCO2 slope (Wald χ(2)= 0.4, P = .54) and EOV (Wald χ(2) = 0.15, P = .70) had no significant association to the composite outcome. These data support the prognostic utility of peak VO2 and ppMVO2 in patients with HFpEF. Additional studies are needed to define optimal cut points to identify low- and high-risk patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Vascular extracellular vesicles in comorbidities of heart failure with preserved ejection fraction in men and women: The hidden players. A mini review.

PubMed

Gohar, Aisha; de Kleijn, Dominique P V; Hoes, Arno W; Rutten, Frans H; Hilfiker-Kleiner, Denise; Ferdinandy, Péter; Sluijter, Joost P G; den Ruijter, Hester M

2018-05-25

Left ventricular diastolic dysfunction, the main feature of heart failure with preserved ejection fraction (HFpEF), is thought to be primarily caused by comorbidities affecting the endothelial function of the coronary microvasculature. Circulating extracellular vesicles, released by the endothelium have been postulated to reflect endothelial damage. Therefore, we reviewed the role of extracellular vesicles, in particularly endothelium microparticles, in these comorbidities, including obesity and hypertension, to identify if they may be potential markers of the endothelial dysfunction underlying left ventricular diastolic dysfunction and HFpEF. Copyright © 2017. Published by Elsevier Inc.

Enhanced pulmonary vasodilator reserve and abnormal right ventricular: pulmonary artery coupling in heart failure with preserved ejection fraction.

PubMed

Andersen, Mads J; Hwang, Seok-Jae; Kane, Garvan C; Melenovsky, Vojtech; Olson, Thomas P; Fetterly, Kenneth; Borlaug, Barry A

2015-05-01

Pulmonary hypertension and right ventricular (RV) dysfunction are common in patients with advanced heart failure with preserved ejection fraction (HFpEF), yet their underlying mechanisms remain poorly understood. We sought to examine RV-pulmonary artery (PA) functional reserve responses and RV-PA coupling at rest and during β-adrenergic stimulation in subjects with earlier stage HFpEF. In a prospective trial, subjects with HFpEF (n=39) and controls (n=18) underwent comprehensive invasive and noninvasive hemodynamic assessment using high fidelity micromanometer catheters, echocardiography, and expired gas analysis at rest and during dobutamine infusion. HFpEF subjects displayed similar RV structure but significantly impaired RV systolic (lower RV dP/dtmax/IP and s') and diastolic function (higher RV τ) coupled with more severe pulmonary vascular disease, manifest by higher PA pressures, higher PA resistance, and lower PA compliance compared with controls. Dobutamine infusion caused greater pulmonary vasodilation in HFpEF compared with controls, with enhanced reductions in PA resistance, greater increase in PA compliance, and a more negative slope in the PA pressure-flow relationship when compared with controls (all P<0.001). RV-PA coupling analysis revealed that dobutamine improved RV ejection in HFpEF subjects through afterload reduction alone, rather than through enhanced contractility, indicating RV systolic reserve dysfunction. Pulmonary hypertension in early stage HFpEF is related to partially reversible pulmonary vasoconstriction coupled with RV systolic and diastolic dysfunction, even in the absence of RV structural remodeling. Pulmonary vascular tone is more favorably responsive to β-adrenergic stimulation in HFpEF than controls, suggesting a potential role for β-agonists in the treatment of patients with HFpEF and pulmonary hypertension. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01418248. © 2015 American Heart Association, Inc.

Visually estimated ejection fraction by two dimensional and triplane echocardiography is closely correlated with quantitative ejection fraction by real-time three dimensional echocardiography

PubMed Central

Shahgaldi, Kambiz; Gudmundsson, Petri; Manouras, Aristomenis; Brodin, Lars-Åke; Winter, Reidar

2009-01-01

Background Visual assessment of left ventricular ejection fraction (LVEF) is often used in clinical routine despite general recommendations to use quantitative biplane Simpsons (BPS) measurements. Even thou quantitative methods are well validated and from many reasons preferable, the feasibility of visual assessment (eyeballing) is superior. There is to date only sparse data comparing visual EF assessment in comparison to quantitative methods available. The aim of this study was to compare visual EF assessment by two-dimensional echocardiography (2DE) and triplane echocardiography (TPE) using quantitative real-time three-dimensional echocardiography (RT3DE) as the reference method. Methods Thirty patients were enrolled in the study. Eyeballing EF was assessed using apical 4-and 2 chamber views and TP mode by two experienced readers blinded to all clinical data. The measurements were compared to quantitative RT3DE. Results There were an excellent correlation between eyeballing EF by 2D and TP vs 3DE (r = 0.91 and 0.95 respectively) without any significant bias (-0.5 ± 3.7% and -0.2 ± 2.9% respectively). Intraobserver variability was 3.8% for eyeballing 2DE, 3.2% for eyeballing TP and 2.3% for quantitative 3D-EF. Interobserver variability was 7.5% for eyeballing 2D and 8.4% for eyeballing TP. Conclusion Visual estimation of LVEF both using 2D and TP by an experienced reader correlates well with quantitative EF determined by RT3DE. There is an apparent trend towards a smaller variability using TP in comparison to 2D, this was however not statistically significant. PMID:19706183

The Benefits of Exercise Training on Aerobic Capacity in Patients with Heart Failure and Preserved Ejection Fraction.

PubMed

do Prado, Danilo Marcelo Leite; Rocco, Enéas Antônio

2017-01-01

Heart failure with preserved ejection fraction (HFpEF) is defined as an inability of the ventricles to optimally accept blood from atria with blunted end- diastolic volume response by limiting the stroke volume and cardiac output. The HEpEF prevalence is higher in elderly and women and may be associated to hypertension, diabetes mellitus and atrial fibrillation. Severe exercise intolerance, manifested by dyspnea and fatigue during physical effort is the important chronic symptom in HFpEF patients, in which is the major determinant of their reduced quality of life. In this sense, several studies demonstrated reduced aerobic capacity in terms of lower peak oxygen consumption (peak VO 2 ) in patients with HFpEF. In addition, the lower aerobic capacity observed in HFpEF may be due to impaired both convective and diffusive O 2 transport (i.e. reduced cardiac output and arteriovenous oxygen difference, respectively).Exercise training program can help restore physiological function in order to increase aerobic capacity and improve the quality of life in HFpEF patients. Therefore, the primary purpose of this chapter was to clarify the physiological mechanisms associated with reduced aerobic capacity in HFpEF patients. Secondly, special focus was devoted to show how aerobic exercise training can improve aerobic capacity and quality of life in HFpEF patients.

HFpEF and HFrEF Display Different Phenotypes as Assessed by IGF-1 and IGFBP-1.

PubMed

Faxén, Ulrika Ljung; Hage, Camilla; Benson, Lina; Zabarovskaja, Stanislava; Andreasson, Anna; Donal, Erwan; Daubert, Jean-Claude; Linde, Cecilia; Brismar, Kerstin; Lund, Lars H

2017-04-01

Anabolic drive is impaired in heart failure with reduced ejection fraction (HFrEF) but insufficiently studied in heart failure with preserved ejection fraction (HFpEF). Insulin-like growth factor 1 (IGF-1) mediates growth hormone effects and IGF binding protein 1 (IGFBP-1) regulates IGF-1 activity. We tested the hypothesis that HFpEF and HFrEF are similar with regard to IGF-1 and IGFBP-1. In patients with HFpEF (n = 79), HFrEF (n = 85), and controls (n = 136), we analyzed serum IGF-1 and IGFBP-1 concentrations, correlations, and associations with outcome. Age-standardized scores of IGF-1 were higher in HFpEF, median arbitrary units (interquartile range); 1.21 (0.57-1.96) vs HFrEF, 0.09 (-1.40-1.62), and controls, 0.22 (-0.47-0.96), P overall <.001. IGFBP-1 was increased in HFpEF, 48 (28-79), and HFrEF, 65 (29-101), vs controls, 27(14-35) µg/L, P overall <.001. These patterns persisted after adjusting for metabolic and HF severity confounders. IGF-1 was associated with outcomes in HFrEF, hazard ratio per natural logarithmic increase in IGF-1 SD score 0.51 (95% confidence interval 0.32-0.82, P = .005), but not significantly in HFpEF. IGFBP-1 was not associated with outcomes in either HFpEF nor HFrEF. HFpEF and HFrEF phenotypes were similar with regard to increased IGFBP-1 concentrations but differed regarding IGF-1 levels and prognostic role. HFrEF and HFpEF may display different impairment in anabolic drive. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of Exercise Training on Peak Oxygen Uptake and its Determinants in Heart Failure with Preserved Ejection Fraction

PubMed Central

Tucker, Wesley J; Nelson, Michael D; Beaudry, Rhys I; Halle, Martin; Sarma, Satyam; Kitzman, Dalane W; Gerche, Andre La

2016-01-01

Heart failure with preserved ejection (HFpEF) accounts for over 50 % of all HF cases, and the proportion is higher among women and older individuals. A hallmark feature of HFpEF is dyspnoea on exertion and reduced peak aerobic power (VO2peak) secondary to central and peripheral abnormalities that result in reduced oxygen delivery to and/or utilisation by exercising skeletal muscle. The purpose of this brief review is to discuss the role of exercise training to improve VO2peak and the central and peripheral adaptations that reduce symptoms following physical conditioning in patients with HFpEF. PMID:28785460

A novel two-dimensional echocardiographic image analysis system using artificial intelligence-learned pattern recognition for rapid automated ejection fraction.

PubMed

Cannesson, Maxime; Tanabe, Masaki; Suffoletto, Matthew S; McNamara, Dennis M; Madan, Shobhit; Lacomis, Joan M; Gorcsan, John

2007-01-16

We sought to test the hypothesis that a novel 2-dimensional echocardiographic image analysis system using artificial intelligence-learned pattern recognition can rapidly and reproducibly calculate ejection fraction (EF). Echocardiographic EF by manual tracing is time consuming, and visual assessment is inherently subjective. We studied 218 patients (72 female), including 165 with abnormal left ventricular (LV) function. Auto EF incorporated a database trained on >10,000 human EF tracings to automatically locate and track the LV endocardium from routine grayscale digital cineloops and calculate EF in 15 s. Auto EF results were independently compared with manually traced biplane Simpson's rule, visual EF, and magnetic resonance imaging (MRI) in a subset. Auto EF was possible in 200 (92%) of consecutive patients, of which 77% were completely automated and 23% required manual editing. Auto EF correlated well with manual EF (r = 0.98; 6% limits of agreement) and required less time per patient (48 +/- 26 s vs. 102 +/- 21 s; p < 0.01). Auto EF correlated well with visual EF by expert readers (r = 0.96; p < 0.001), but interobserver variability was greater (3.4 +/- 2.9% vs. 9.8 +/- 5.7%, respectively; p < 0.001). Visual EF was less accurate by novice readers (r = 0.82; 19% limits of agreement) and improved with trainee-operated Auto EF (r = 0.96; 7% limits of agreement). Auto EF also correlated with MRI EF (n = 21) (r = 0.95; 12% limits of agreement), but underestimated absolute volumes (r = 0.95; bias of -36 +/- 27 ml overall). Auto EF can automatically calculate EF similarly to results by manual biplane Simpson's rule and MRI, with less variability than visual EF, and has clinical potential.

Biomarkers in Acutely Decompensated Heart Failure with Preserved or Reduced Ejection Fraction

PubMed Central

Bishu, Kalkidan; Deswal, Anita; Chen, Horng H.; LeWinter, Martin M.; Lewis, Gregory D.; Semigran, Marc J.; Borlaug, Barry A.; McNulty, Steven; Hernandez, Adrian F.; Braunwald, Eugene; Redfield, Margaret M.

2013-01-01

Background Acute decompensated heart failure (ADHF) occurs with preserved (HFpEF, EF≥50%) or reduced (HFrEF, EF<50%) ejection fraction. Natriuretic peptide (NP) levels are lower in HFpEF than HFrEF. We hypothesized that lower NP levels in HFpEF may be associated with other differences in biomarkers; specifically, renin-angiotensin-aldosterone system (RAAS) activation, oxidative stress and a biomarker that reflects collagen synthesis. Methods In this pre-specified ancillary analysis of ADHF patients enrolled in the Diuretic Optimization Strategies Evaluation (DOSE) study, clinical features and NT-proBNP, cystatin C, plasma renin activity (PRA), aldosterone, oxidative stress (uric acid) and procollagen type III N-terminal peptide (PIIINP) were compared in HFpEF and HFrEF at enrollment and 60 day follow-up. Results Compared to HFrEF (n=219), HFpEF (n=81) patients were older, heavier, more commonly female, less treated with RAAS antagonists, but with similar NYHA class, jugular venous pressure and edema severity. NT-proBNP was lower and systolic blood pressure (BP) and cystatin C were higher in HFpEF. Despite higher systolic BP and less RAAS antagonist use in HFpEF, PRA and aldosterone levels were similar in HFpEF and HFrEF as were uric acid and PIIINP levels. Changes in biomarker levels from enrollment to 60 days were similar between HFrEF (n=149) and HFpEF (n=50). Conclusion Lower NP levels in decompensated HFpEF occur in association with similar ADHF severity, more impaired vascular and renal function but similar elevation of biomarkers that reflect RAAS activation, oxidative stress and collagen synthesis as in HFrEF. PMID:23137508

Clinical utility of automated assessment of left ventricular ejection fraction using artificial intelligence-assisted border detection.

PubMed

Rahmouni, Hind W; Ky, Bonnie; Plappert, Ted; Duffy, Kevin; Wiegers, Susan E; Ferrari, Victor A; Keane, Martin G; Kirkpatrick, James N; Silvestry, Frank E; St John Sutton, Martin

2008-03-01

Ejection fraction (EF) calculated from 2-dimensional echocardiography provides important prognostic and therapeutic information in patients with heart disease. However, quantification of EF requires planimetry and is time-consuming. As a result, visual assessment is frequently used but is subjective and requires extensive experience. New computer software to assess EF automatically is now available and could be used routinely in busy digital laboratories (>15,000 studies per year) and in core laboratories running large clinical trials. We tested Siemens AutoEF software (Siemens Medical Solutions, Erlangen, Germany) to determine whether it correlated with visual estimates of EF, manual planimetry, and cardiac magnetic resonance (CMR). Siemens AutoEF is based on learned patterns and artificial intelligence. An expert and a novice reader assessed EF visually by reviewing transthoracic echocardiograms from consecutive patients. An experienced sonographer quantified EF in all studies using Simpson's method of disks. AutoEF results were compared to CMR. Ninety-two echocardiograms were analyzed. Visual assessment by the expert (R = 0.86) and the novice reader (R = 0.80) correlated more closely with manual planimetry using Simpson's method than did AutoEF (R = 0.64). The correlation between AutoEF and CMR was 0.63, 0.28, and 0.51 for EF, end-diastolic and end-systolic volumes, respectively. The discrepancies in EF estimates between AutoEF and manual tracing using Simpson's method and between AutoEF and CMR preclude routine clinical use of AutoEF until it has been validated in a number of large, busy echocardiographic laboratories. Visual assessment of EF, with its strong correlation with quantitative EF, underscores its continued clinical utility.

Hypertension and Heart Failure with Preserved Ejection Fraction: Connecting the Dots.

PubMed

Tsioufis, Costas; Georgiopoulos, Georgios; Oikonomou, Dimitrios; Thomopoulos, Costas; Katsiki, Niki; Kasiakogias, Alexandros; Chrysochoou, Christina; Konstantinidis, Dimitrios; Kalos, Theodoros; Tousoulis, Dimitrios

2017-01-01

Heart failure (HF) with preserved ejection fraction (EF) (HFpEF) accounts for approximately 50% of HF cases and its prevalence relative to HF with reduced EF is rising. Hypertension (HT) is the most common co-morbidity in HFpEF patients and it is implicated in both the pathogenesis and the prognosis of the disease. Therefore, HT is a modifiable risk factor of high yield in HFpEF. We reviewed the literature for epidemiologic data supporting the co-aggregation of the two entities as well as patho-physiologic mechanisms linking HT to HFpEF. Most importantly, we focused on treatment options targeting HT as a preventive strategy for delaying the progression of diastolic dysfunction or decreasing the odds for developing HFpEF. Along this line, we summarized the evidence and efficacy associated with different classes of antihypertensive medications in HFpEF patients. Finally, non-pharmacological approaches, including renal denervation and lifestyle modifications, to achieve optimal blood pressure (BP) control in HFpEF patients are reported. Unfortunately, no specific antihypertensive treatment has established a major survival benefit in this high risk subjects. Until the results of the efficacy of the novel drug LCZ696 (valsartan/ sacubitril) are available, the continuous monitoring and lowering of the BP by pharmacological and non-pharmacological means should be considered the major preventive and treatment strategy in HFpEF patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Right ventricular function in heart failure with preserved ejection fraction: a community-based study.

PubMed

Mohammed, Selma F; Hussain, Imad; AbouEzzeddine, Omar F; Abou Ezzeddine, Omar F; Takahama, Hiroyuki; Kwon, Susan H; Forfia, Paul; Roger, Véronique L; Redfield, Margaret M

2014-12-23

The prevalence and clinical significance of right ventricular (RV) systolic dysfunction (RVD) in patients with heart failure and preserved ejection fraction (HFpEF) are not well characterized. Consecutive, prospectively identified HFpEF (Framingham HF criteria, ejection fraction ≥50%) patients (n=562) from Olmsted County, Minnesota, underwent echocardiography at HF diagnosis and follow-up for cause-specific mortality and HF hospitalization. RV function was categorized by tertiles of tricuspid annular plane systolic excursion and by semiquantitative (normal, mild RVD, or moderate to severe RVD) 2-dimensional assessment. Whether RVD was defined by semiquantitative assessment or tricuspid annular plane systolic excursion ≤15 mm, HFpEF patients with RVD were more likely to have atrial fibrillation, pacemakers, and chronic diuretic therapy. At echocardiography, patients with RVD had slightly lower left ventricular ejection fraction, worse diastolic dysfunction, lower blood pressure and cardiac output, higher pulmonary artery systolic pressure, and more severe RV enlargement and tricuspid valve regurgitation. After adjustment for age, sex, pulmonary artery systolic pressure, and comorbidities, the presence of any RVD by semiquantitative assessment was associated with higher all-cause (hazard ratio=1.35; 95% confidence interval, 1.03-1.77; P=0.03) and cardiovascular (hazard ratio=1.85; 95% confidence interval, 1.20-2.80; P=0.006) mortality and higher first (hazard ratio=1.99; 95% confidence interval, 1.35-2.90; P=0.0006) and multiple (hazard ratio=1.81; 95% confidence interval, 1.18-2.78; P=0.007) HF hospitalization rates. RVD defined by tricuspid annular plane systolic excursion values showed similar but weaker associations with mortality and HF hospitalizations. In the community, RVD is common in HFpEF patients, is associated with clinical and echocardiographic evidence of more advanced HF, and is predictive of poorer outcomes. © 2014 American Heart Association, Inc.

Assessing the Eligibility Criteria in Phase III Randomized Controlled Trials of Drug Therapy in Heart Failure With Preserved Ejection Fraction: The Critical Play-Off Between a "Pure" Patient Phenotype and the Generalizability of Trial Findings.

PubMed

Patel, Hitesh C; Hayward, Carl; Dungu, Jason N; Papadopoulou, Sofia; Saidmeerasah, Abdel; Ray, Robin; Di Mario, Carlo; Shanmugam, Nesan; Cowie, Martin R; Anderson, Lisa J

2017-07-01

To investigate the effect of the different eligibility criteria used by phase III clinical studies in heart failure with preserved ejection fraction (HFpEF) on patient selection, phenotype, and survival. We applied the key eligibility criteria of 7 phase III HFpEF studies (Digitalis Investigation Group Ancillary, Candesartan in Patients With Chronic Heart Failure and Preserved Left-Ventricular Ejection Fraction, Perindopril in Elderly People With Chronic Heart Failure, Irbesartan in Heart Failure With Preserved Systolic Function, Japanese Diastolic Heart Failure, Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist, and Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF; ongoing]) to a typical and well-characterized HFpEF population (n = 557) seen in modern European cardiological practice. Follow-up was available for a minimum of 24 months in each patient. Increasing the number of study eligibility criteria identifies a progressively smaller group of patients from real-life practice suitable for recruitment into clinical trials; using the J-DHF criteria, 81% of our clinic patients would have been eligible, whereas the PARAGON-HF criteria significantly reduced this proportion to 32%. The patients identified from our clinical population had similar mortality rates using the different criteria, which were consistently higher than those reported in the actual clinic trials. Trial eligibility criteria have become stricter with time, which reduces the number of eligible patients, affecting both generalizability of any findings and feasibility of completing an adequately powered trial. We could not find evidence that the additional criteria used in more recent randomized trials in HFpEF have identified patients at higher risk of all-cause mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

Ventricular-Arterial Coupling and Exercise-Induced Pulmonary Hypertension During Low-Level Exercise in Heart Failure With Preserved or Reduced Ejection Fraction.

PubMed

Obokata, Masaru; Nagata, Yasufumi; Kado, Yuichiro; Kurabayashi, Masahiko; Otsuji, Yutaka; Takeuchi, Masaaki

2017-03-01

Exercise-induced pulmonary hypertension (EIPH) may develop even at low workloads in heart failure (HF) patients. Ventricular-arterial stiffening plays an important role in the pathophysiology of HF with preserved ejection fraction (HFpEF). This study aimed to compare the response of ventricular-arterial coupling and PH during low-level exercise between HFpEF and HF with reduced EF (HFrEF). Echocardiography was performed at rest and during 10 W of bicycle exercise in HFpEF (n = 37) and HFrEF (n = 43). Load-independent contractility (end-systolic elastance [Ees], preload recruitable stroke work [PRSW], and peak power index [PWRI]), arterial afterload (arterial elastance [Ea]), and ventricular-arterial interaction (Ea/Ees) were measured with the use of a noninvasive single-beat technique. EIPH was defined as an estimated pulmonary arterial systolic pressure (PASP) of ≥50 mm Hg at 10 W of exercise. PASP was significantly increased during 10 W of exercise in both HF types, and ~50% of HFpEF patients developed EIPH. Arterial afterload was increased significantly during exercise in both groups. HFrEF and HFpEF patients showed a significant increase in LV contractility assessed by Ees, PRSW, and PWRI during exercise. Although Ea/Ees ratio decreased significantly in HFrEF, reduction in Ea/Ees was attenuated because of blunted Ees increases in patients with HFpEF compared with HFrEF. Even at low-level exercise, ~50% of HFpEF patients developed EIPH. Reduction in Ea/Ees was attenuated owing to less Ees increase in HFpEF compared with HFrEF. Further studies are needed to elucidate the association between ventricular-arterial coupling and EIPH in HFpEF. Copyright © 2016 Elsevier Inc. All rights reserved.

Comorbidity and ventricular and vascular structure and function in heart failure with preserved ejection fraction: a community-based study.

PubMed

Mohammed, Selma F; Borlaug, Barry A; Roger, Véronique L; Mirzoyev, Sultan A; Rodeheffer, Richard J; Chirinos, Julio A; Redfield, Margaret M

2012-11-01

Patients with heart failure and preserved ejection fraction (HFpEF) display increased adiposity and multiple comorbidities, factors that in themselves may influence cardiovascular structure and function. This has sparked debate as to whether HFpEF represents a distinct disease or an amalgamation of comorbidities. We hypothesized that fundamental cardiovascular structural and functional alterations are characteristic of HFpEF, even after accounting for body size and comorbidities. Comorbidity-adjusted cardiovascular structural and functional parameters scaled to independently generated and age-appropriate allometric powers were compared in community-based cohorts of HFpEF patients (n=386) and age/sex-matched healthy n=193 and hypertensive, n=386 controls. Within HFpEF patients, body size and concomitant comorbidity-adjusted cardiovascular structural and functional parameters and survival were compared in those with and without individual comorbidities. Among HFpEF patients, comorbidities (obesity, anemia, diabetes mellitus, and renal dysfunction) were each associated with unique clinical, structural, functional, and prognostic profiles. However, after accounting for age, sex, body size, and comorbidities, greater concentric hypertrophy, atrial enlargement and systolic, diastolic, and vascular dysfunction were consistently observed in HFpEF compared with age/sex-matched normotensive and hypertensive. Comorbidities influence ventricular-vascular properties and outcomes in HFpEF, yet fundamental disease-specific changes in cardiovascular structure and function underlie this disorder. These data support the search for mechanistically targeted therapies in this disease.

Left ventricular ejection fraction to predict early mortality in patients with non-ST-segment elevation acute coronary syndromes.

PubMed

Bosch, Xavier; Théroux, Pierre

2005-08-01

Improvement in risk stratification of patients with non-ST-segment elevation acute coronary syndrome (ACS) is a gateway to a more judicious treatment. This study examines whether the routine determination of left ventricular ejection fraction (EF) adds significant prognostic information to currently recommended stratifiers. Several predictors of inhospital mortality were prospectively characterized in a registry study of 1104 consecutive patients, for whom an EF was determined, who were admitted for an ACS. Multiple regression models were constructed using currently recommended clinical, electrocardiographic, and blood marker stratifiers, and values of EF were incorporated into the models. Age, ST-segment shifts, elevation of cardiac markers, and the Thrombolysis in Myocardial Infarction (TIMI) risk score all predicted mortality (P < .0001). Adding EF into the model improved the prediction of mortality (C statistic 0.73 vs 0.67). The odds of death increased by a factor of 1.042 for each 1% decrement in EF. By receiver operating curves, an EF cutoff of 48% provided the best predictive value. Mortality rates were 3.3 times higher within each TIMI risk score stratum in patients with an EF of 48% or lower as compared with those with higher. The TIMI risk score predicts inhospital mortality in a broad population of patients with ACS. The further consideration of EF adds significant prognostic information.

Multidisciplinary rehabilitation program in recently hospitalized patients with heart failure and preserved ejection fraction: rationale and design of a randomized controlled trial.

PubMed

Koifman, Edward; Grossman, Ehud; Elis, Avishay; Dicker, Dror; Koifman, Bella; Mosseri, Morris; Kuperstein, Rafael; Goldenberg, Ilan; Kamerman, Tamir; Levine-Tiefenbrun, Nava; Klempfner, Robert

2014-12-01

Heart failure with preserved ejection fraction (HFpEF) comprises a large portion of heart failure patients and portends poor prognosis with similar outcome to heart failure with reduced ejection fraction (HFrEF). Thus far, no medical therapy has been shown to improve clinical outcome in this common condition. The study is a randomized-controlled, multicenter clinical trial aimed to determine whether early posthospitalization comprehensive cardiac rehabilitation (CR) including exercise training (ET) in recently hospitalized HFpEF patients reduces the composite end point of all-cause mortality and hospitalizations in comparison with usual care (UC). After undergoing baseline evaluation, patients are randomized to either UC or to ambulatory comprehensive CR program. Patients in the CR arm will participate in a 6-month biweekly ET program according to a predefined protocol, in addition to a complementary home exercise prescribed by a specialist in CR. Exercise training will include endurance and low-intensity resistance training. Patients in the UC arm will be followed up at the outpatient clinic, with management according to current heart failure guidelines. Physician follow-up visits will be conducted at 3, 6, and 12 months for assessment of adherence to therapy and ET, functional status, quality of life, and clinical events. Secondary end points will include quality-of-life questionnaire, economic end points, blood pressure, and hemoglobin A1C levels. Cardiac rehabilitation and ET are relatively inexpensive and accessible and can be beneficial in HFpEF patients. Our trial is designed to evaluate the impact of early posthospitalization comprehensive rehabilitation program on clinical end points of mortality, hospitalization, and quality of life in HFpEF patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Clinical Characteristics, Management, and Outcomes of Japanese Patients Hospitalized for Heart Failure With Preserved Ejection Fraction　- A Report From the Japanese Heart Failure Syndrome With Preserved Ejection Fraction (JASPER) Registry.

PubMed

Nagai, Toshiyuki; Yoshikawa, Tsutomu; Saito, Yoshihiko; Takeishi, Yasuchika; Yamamoto, Kazuhiro; Ogawa, Hisao; Anzai, Toshihisa

2018-05-25

Despite the specific characteristics of heart failure with preserved ejection fraction (HFpEF) having been demonstrated predominantly from registries in Western countries, important international differences exist in terms of patient characteristics, management and medical infrastructure between Western and Asian countries.Methods and Results:We performed nationwide registration of consecutive Japanese hospitalized HFpEF patients with left ventricular EF ≥50% from 15 sites between November 2012 and March 2015. Follow-up data were obtained up to 2 years post-discharge. A total of 535 patients were registered. The median age was 80 years and 50% were female. The most common comorbid conditions were hypertension (77%) and atrial fibrillation (AF: 62%), but body mass index was relatively low. In-hospital mortality rate was 1.3% and the median length of hospitalization was 16 days. By 2 years post-discharge, 40.8% of patients had all-cause death or HF hospitalization. Approximately one-half of deaths had a cardiac cause. Lower serum albumin on admission was one of the strongest independent determinants of worse clinical outcome. Japanese HFpEF patients were less obese, but had a substantially higher prevalence of AF and lower incidence of subsequent events compared with previous reports. Our findings indicated that specific preventative and therapeutic strategies focusing on AF and nutritional status might need to be considered for Japanese hospitalized patients with HFpEF.

Revisiting the physiological effects of exercise training on autonomic regulation and chemoreflex control in heart failure: does ejection fraction matter?

PubMed

Andrade, David C; Arce-Alvarez, Alexis; Toledo, Camilo; Díaz, Hugo S; Lucero, Claudia; Quintanilla, Rodrigo A; Schultz, Harold D; Marcus, Noah J; Amann, Markus; Del Rio, Rodrigo

2018-03-01

Heart failure (HF) is a global public health problem that, independent of its etiology [reduced (HFrEF) or preserved ejection fraction (HFpEF)], is characterized by functional impairments of cardiac function, chemoreflex hypersensitivity, baroreflex sensitivity (BRS) impairment, and abnormal autonomic regulation, all of which contribute to increased morbidity and mortality. Exercise training (ExT) has been identified as a nonpharmacological therapy capable of restoring normal autonomic function and improving survival in patients with HFrEF. Improvements in autonomic function after ExT are correlated with restoration of normal peripheral chemoreflex sensitivity and BRS in HFrEF. To date, few studies have addressed the effects of ExT on chemoreflex control, BRS, and cardiac autonomic control in HFpEF; however, there are some studies that have suggested that ExT has a beneficial effect on cardiac autonomic control. The beneficial effects of ExT on cardiac function and autonomic control in HF may have important implications for functional capacity in addition to their obvious importance to survival. Recent studies have suggested that the peripheral chemoreflex may also play an important role in attenuating exercise intolerance in HFrEF patients. The role of the central/peripheral chemoreflex, if any, in mediating exercise intolerance in HFpEF has not been investigated. The present review focuses on recent studies that address primary pathophysiological mechanisms of HF (HFrEF and HFpEF) and the potential avenues by which ExT exerts its beneficial effects.

Device therapy in heart failure with reduced ejection fraction-cardiac resynchronization therapy and more.

PubMed

Duncker, D; Veltmann, C

2018-05-09

In patients with heart failure with reduced ejection fraction (HFrEF), optimal medical treatment includes beta-blockers, ACE inhibitors/angiotensinreceptor-neprilysin inhibitors (ARNI), mineralocorticoid receptor antagonists, and ivabradine when indicated. In device therapy of HFrEF, implantable cardioverter-defibrillators and cardiac resynchronization therapy (CRT) have been established for many years. CRT is the therapy of choice (class I indication) in symptomatic patients with HFrEF and a broad QRS complex with a left bundle branch block (LBBB) morphology. However, the vast majority of heart failure patients show a narrow QRS complex or a non-LBBB morphology. These patients are not candidates for CRT and alternative electrical therapies such as baroreflex activation therapy (BAT) and cardiac contractility modulation (CCM) may be considered. BAT modulates vegetative dysregulation in heart failure. CCM improves contractility, functional capacity, and symptoms. Although a broad data set is available for BAT and CCM, mortality data are still lacking for both methods. This article provides an overview of the device-based therapeutic options for patients with HFrEF.

Prognostic significance of hemoglobin level in patients with congestive heart failure and normal ejection fraction.

PubMed

Varadarajan, Padmini; Gandhi, Siddharth; Sharma, Sanjay; Umakanthan, Branavan; Pai, Ramdas G

2006-10-01

Previous studies have shown low hemoglobin (Hb) to have an adverse effect on survival in patients with congestive heart failure (CHF) and reduced left ventricular (LV) ejection fraction (EF); but its effect on survival in patients with CHF and normal EF is not known. This study sought to determine whether low Hb has an effect on survival in patients with both CHF and normal EF. Detailed chart reviews were performed by medical residents on 2,246 patients (48% with normal EF) with a discharge diagnosis of CHF in a large tertiary care hospital from 1990 to 1999. The CHF diagnosis was validated using the Framingham criteria. Mortality data were obtained from the National Death Index. Survival analysis was performed using Kaplan-Meier and Cox regression models. By Kaplan-Meier analysis, low Hb (< 12 gm/dl) compared with normal hemoglobin was associated with a lower 5-year survival in patients with CHF and both normal (38 vs. 50%, p = 0.0008) and reduced (35 vs. 48%, p = 0.0009) EF. Using the Cox regression model, low Hb was an independent predictor of mortality after adjusting for age, gender, renal dysfunction, diabetes mellitus, hypertension, and EF in both groups of patients. Low Hb has an independent adverse effect on survival in patients with CHF and both normal and reduced EF in both groups of patients.

Haemodynamics, dyspnoea, and pulmonary reserve in heart failure with preserved ejection fraction.

PubMed

Obokata, Masaru; Olson, Thomas P; Reddy, Yogesh N V; Melenovsky, Vojtech; Kane, Garvan C; Borlaug, Barry A

2018-05-19

Increases in left ventricular filling pressure are a fundamental haemodynamic abnormality in heart failure with preserved ejection fraction (HFpEF). However, very little is known regarding how elevated filling pressures cause pulmonary abnormalities or symptoms of dyspnoea. We sought to determine the relationships between simultaneously measured central haemodynamics, symptoms, and lung ventilatory and gas exchange abnormalities during exercise in HFpEF. Subjects with invasively-proven HFpEF (n = 50) and non-cardiac causes of dyspnoea (controls, n = 24) underwent cardiac catheterization at rest and during exercise with simultaneous expired gas analysis. During submaximal (20 W) exercise, subjects with HFpEF displayed higher pulmonary capillary wedge pressures (PCWP) and pulmonary artery pressures, higher Borg perceived dyspnoea scores, and increased ventilatory drive and respiratory rate. At peak exercise, ventilation reserve was reduced in HFpEF compared with controls, with greater dead space ventilation (higher VD/VT). Increasing exercise PCWP was directly correlated with higher perceived dyspnoea scores, lower peak exercise capacity, greater ventilatory drive, worse New York Heart Association (NYHA) functional class, and impaired pulmonary ventilation reserve. This study provides the first evidence linking altered exercise haemodynamics to pulmonary abnormalities and symptoms of dyspnoea in patients with HFpEF. Further study is required to identify the mechanisms by which haemodynamic derangements affect lung function and symptoms and to test novel therapies targeting exercise haemodynamics in HFpEF.

Sacubitril/Valsartan: A Novel Cardiovascular Combination Agent.

PubMed

Sible, Alexandra M; Nawarskas, James J; Alajajian, David; Anderson, Joe R

2016-01-01

Sacubitril/valsartan [LCZ696 (Entresto), Novartis Pharmaceuticals Corp.] is the first in a new class of drugs that combines neprilysin inhibition with angiotensin II receptor antagonism, the combination of which acts to increase endogenous natriuretic peptides while inhibiting the renin-angiotensin-aldosterone system. Sacubitril/valsartan has been studied in the treatment of hypertension, heart failure with reduced ejection fraction (HFrEF), and heart failure with preserved ejection fraction (HFpEF) and has demonstrated clinical efficacy in blood pressure reduction in hypertensive patients with and without HFpEF and a reduction in hospitalizations and mortality for patients with HFrEF. Research to evaluate clinical outcomes in HFpEF is ongoing. Sacubitril/valsartan is approved to reduce hospitalization and risk of cardiovascular death for patients with HFrEF in New York Heart Association (NYHA) functional class II-IV. The product is as well tolerated as an angiotensin-converting enzyme inhibitor, with the most common side effect being hypotension. Expectedly, it is much more costly than generic angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, which will be a factor in determining how widespread the use of this agent will be. In summary, although the number of published studies evaluating its use is limited, sacubitril/valsartan represents a promising new treatment option for patients with HFrEF. Ongoing studies will continue to refine the role of this agent in clinical practice.

Measurement of Dyspnea in Ambulatory African Americans With Heart Failure and a Preserved or Reduced Ejection Fraction.

PubMed

Vuckovic, Karen M; DeVon, Holli A; Piano, Mariann R

2016-01-01

Dyspnea is a burdensome and disabling heart failure (HF) symptom. Few studies examining dyspnea in HF have included African Americans (AAs), despite their developing HF at a younger age and having the highest mortality rates. The purpose of this cross-sectional study was to examine dyspnea in AA patients with HF and a preserved ejection fraction (HFpEF) compared with those with a reduced ejection fraction (HFrEF), before and after the 6-minute walk test (6MWT). A convenience sample of ambulatory AA patients (HFrEF, n = 26; HFpEF, n = 19) 50 years or older was recruited from an urban HF clinic. The Borg Scale and a visual analog scale (VAS) were used to measure dyspnea intensity before and after the 6MWT. Activity limitations related to dyspnea were described using the modified Medical Research Council Dyspnea Scale. Group comparisons were analyzed using repeated-measures analysis of variance and χ 2tests. Convergent validity was determined between the Borg and VAS using Bland-Altman plots. No significant differences were found in age, gender, and comorbidities between HF groups. Most HFpEF patients reported dyspnea at baseline (Borg, 63%; VAS, 73%) and after the 6MWT (Borg, 78%; VAS, 79%). In the HFrEF group, the prevalence of baseline dyspnea was greater when measured with the VAS (Borg, 34%; VAS, 80%) but was similar between instruments after the 6MWT (Borg, 64%; VAS, 77%). Both groups reported a similar change in dyspnea intensity during and after the 6MWT. The Bland-Altman plots indicated moderate agreement at each time point. Most patients described walking hurriedly or uphill as dyspnea-provoking on the Modified Respiratory Council Dyspnea Scale. The prevalence of dyspnea at baseline and after the 6MWT was high for both groups, but intensity varied with the dyspnea instrument used.

Exercise training in patients with heart disease: review of beneficial effects and clinical recommendations.

PubMed

Gielen, Stephan; Laughlin, M Harold; O'Conner, Christopher; Duncker, Dirk J

2015-01-01

Over the last decades exercise training has evolved into an established evidence-based therapeutic strategy with prognostic benefits in many cardiovascular diseases (CVDs): In stable coronary artery disease (CAD) exercise training attenuates disease progression by beneficially influencing CVD risk factors (i.e., hyperlipidemia, hypertension) and coronary endothelial function. In heart failure (HF) with reduced ejection fraction (HFrEF) training prevents the progressive loss of exercise capacity by antagonizing peripheral skeletal muscle wasting and by promoting left ventricular reverse remodeling with reduction in cardiomegaly and improvement of ejection fraction. Novel areas for exercise training interventions include HF with preserved ejection fraction (HFpEF), pulmonary hypertension, and valvular heart disease. In HFpEF, randomized studies indicate a lusitropic effect of training on left ventricular diastolic function associated with symptomatic improvement of exercise capacity. In pulmonary hypertension, reductions in pulmonary artery pressure were observed following endurance exercise training. Recently, innovative training methods such as high-intensity interval training, resistance training and others have been introduced. Although their prognostic value still needs to be determined, these approaches may achieve superior improvements in aerobic exercise capacity and gain in muscle mass, respectively. In this review, we give an overview of the prognostic and symptomatic benefits of exercise training in the most common cardiac disease entities. Additionally, key guideline recommendations for the initiation of training programs are summarized. Copyright © 2014 Elsevier Inc. All rights reserved.

Model-based cost-effectiveness analysis of B-type natriuretic peptide-guided care in patients with heart failure.

PubMed

Mohiuddin, Syed; Reeves, Barnaby; Pufulete, Maria; Maishman, Rachel; Dayer, Mark; Macleod, John; McDonagh, Theresa; Purdy, Sarah; Rogers, Chris; Hollingworth, William

2016-12-28

Monitoring B-type natriuretic peptide (BNP) to guide pharmacotherapy might improve survival in patients with heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). However, the cost-effectiveness of BNP-guided care is uncertain and guidelines do not uniformly recommend it. We assessed the cost-effectiveness of BNP-guided care in patient subgroups defined by age and ejection fraction. We used a Markov model with a 3-month cycle length to estimate the lifetime health service costs, quality-adjusted life years (QALYs) and incremental net monetary benefits (iNMBs) of BNP-guided versus clinically guided care in 3 patient subgroups: (1) HFrEF patients <75 years; (2) HFpEF patients <75 years; and (3) HFrEF patients ≥75 years. There is no evidence of benefit in patients with HFpEF aged ≥75 years. We used individual patient data meta-analyses and linked primary care, hospital and mortality data to inform the key model parameters. We performed probabilistic analysis to assess the uncertainty in model results. In younger patients (<75 years) with HFrEF, the mean QALYs (5.57 vs 5.02) and costs (£63 527 vs £58 139) were higher with BNP-guided care. At the willingness-to-pay threshold of £20 000 per QALY, the positive iNMB (£5424 (95% CI £987 to £9469)) indicates that BNP-guided care is cost-effective in this subgroup. The evidence of cost-effectiveness of BNP-guided care is less strong for younger patients with HFpEF (£3155 (-£10 307 to £11 613)) and older patients (≥75 years) with HFrEF (£2267 (-£1524 to £6074)). BNP-guided care remained cost-effective in the sensitivity analyses, albeit the results were sensitive to assumptions on its sustained effect. We found strong evidence that BNP-guided care is a cost-effective alternative to clinically guided care in younger patients with HFrEF. It is potentially cost-effective in younger patients with HFpEF and older patients with HFrEF, but more evidence is required, particularly with respect to the frequency, duration and BNP target for monitoring. Cost-effectiveness results from trials in specialist settings cannot be generalised to primary care. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Delayed Repolarization Underlies Ventricular Arrhythmias in Rats With Heart Failure and Preserved Ejection Fraction.

PubMed

Cho, Jae Hyung; Zhang, Rui; Kilfoil, Peter J; Gallet, Romain; de Couto, Geoffrey; Bresee, Catherine; Goldhaber, Joshua I; Marbán, Eduardo; Cingolani, Eugenio

2017-11-21

Heart failure with preserved ejection fraction (HFpEF) represents approximately half of heart failure, and its incidence continues to increase. The leading cause of mortality in HFpEF is sudden death, but little is known about the underlying mechanisms. Dahl salt-sensitive rats were fed a high-salt diet (8% NaCl) from 7 weeks of age to induce HFpEF (n=38). Rats fed a normal-salt diet (0.3% NaCl) served as controls (n=13). Echocardiograms were performed to assess systolic and diastolic function from 14 weeks of age. HFpEF-verified and control rats underwent programmed electrical stimulation. Corrected QT interval was measured by surface ECG. The mechanisms of ventricular arrhythmias (VA) were probed by optical mapping, whole-cell patch clamp to measure action potential duration and ionic currents, and quantitative polymerase chain reaction and Western blotting to investigate changes in ion channel expression. After 7 weeks of a high-salt diet, 31 of 38 rats showed diastolic dysfunction and preserved ejection fraction along with signs of heart failure and hence were diagnosed with HFpEF. Programmed electric stimulation demonstrated increased susceptibility to VA in HFpEF rats ( P <0.001 versus controls). The arrhythmogenicity index was increased ( P <0.001) and the corrected QT interval on ECG was prolonged ( P <0.001) in HFpEF rats. Optical mapping of HFpEF hearts demonstrated prolonged action potentials ( P <0.05) and multiple reentry circuits during induced VA. Single-cell recordings of cardiomyocytes isolated from HFpEF rats confirmed a delay of repolarization ( P =0.001) and revealed downregulation of transient outward potassium current ( I to ; P <0.05). The rapid components of the delayed rectifier potassium current ( I Kr ) and the inward rectifier potassium current ( I K1 ) were also downregulated ( P <0.05), but the current densities were much lower than for I to . In accordance with the reduction of I to , both Kcnd3 transcript and Kv4.3 protein levels were decreased in HFpEF rat hearts. Susceptibility to VA was markedly increased in rats with HFpEF. Underlying abnormalities include QT prolongation, delayed repolarization from downregulation of potassium currents, and multiple reentry circuits during VA. Our findings are consistent with the hypothesis that potassium current downregulation leads to abnormal repolarization in HFpEF, which in turn predisposes to VA and sudden cardiac death. © 2017 American Heart Association, Inc.

Left ventricular markers of global dyssynchrony predict limited exercise capacity in heart failure, but not in patients with preserved ejection fraction.

PubMed

Bajraktari, Gani; Batalli, Arlind; Poniku, Afrim; Ahmeti, Artan; Olloni, Rozafa; Hyseni, Violeta; Vela, Zana; Morina, Besim; Tafarshiku, Rina; Vela, Driton; Rashiti, Premtim; Haliti, Edmond; Henein, Michael Y

2012-09-11

The aim of this study was to prospectively examine echocardiographic parameters that correlate and predict functional capacity assessed by 6 min walk test (6-MWT) in patients with heart failure (HF), irrespective of ejection fraction (EF). In 147 HF patients (mean age 61 ± 11 years, 50.3% male), a 6-MWT and an echo-Doppler study were performed in the same day. Global LV dyssynchrony was indirectly assessed by total isovolumic time - t-IVT [in s/min; calculated as: 60 - (total ejection time + total filling time)], and Tei index (t-IVT/ejection time). Patients were divided into two groups based on the 6-MWT distance (Group I: ≤ 300 m and Group II: >300 m), and also in two groups according to EF (Group A: LVEF ≥ 45% and Group B: LVEF < 45%). In the cohort of patients as a whole, the 6-MWT correlated with t-IVT (r = -0.49, p < 0.001) and Tei index (r = -0.43, p < 0.001) but not with any of the other clinical or echocardiographic parameters. Group I had lower hemoglobin level (p = 0.02), lower EF (p = 0.003), larger left atrium (p = 0.02), thicker interventricular septum (p = 0.02), lower A wave (p = 0.01) and lateral wall late diastolic myocardial velocity a' (p = 0.047), longer isovolumic relaxation time (r = 0.003) and longer t-IVT (p = 0.03), compared with Group II. In the patients cohort as a whole, only t-IVT ratio [1.257 (1.071-1.476), p = 0.005], LV EF [0.947 (0.903-0.993), p = 0.02], and E/A ratio [0.553 (0.315-0.972), p = 0.04] independently predicted poor 6-MWT performance (<300 m) in multivariate analysis. None of the echocardiographic measurements predicted exercise tolerance in HFpEF. In patients with HF, the limited exercise capacity, assessed by 6-MWT, is related mostly to severity of global LV dyssynchrony, more than EF or raised filling pressures. The lack of exercise predictors in HFpEF reflects its multifactorial pathophysiology.

Left ventricular strain and twisting in heart failure with preserved ejection fraction: an updated review.

PubMed

Tadic, Marijana; Pieske-Kraigher, Elisabeth; Cuspidi, Cesare; Genger, Martin; Morris, Daniel A; Zhang, Kun; Walther, Nina Alexandra; Pieske, Burket

2017-05-01

Despite the high prevalence of the patients with heart failure with preserved ejection fraction (HFpEF), our knowledge about this entity, from diagnostic tools to therapeutic approach, is still not well established. The evaluation of patients with HFpEF is mainly based on echocardiography, as the most widely accepted tool in cardiac imaging. Identification of left ventricular (LV) diastolic dysfunction has long been considered as the only responsible for HFpEF, and its evaluation is still "sine qua non" of HFpEF diagnostics. However, one should be aware of the fact that identifying cardiac dysfunction in HFpEF might be very challenging and often needs more complex evaluation of cardiac structure and function. New echocardiographic modalities such as 2D and 3D speckle tracking imaging could help in the diagnosis of HFpEF and provide further information regarding LV function and mechanics. Early diagnosis, medical management, and adequate monitoring of HFpEF patients are prerequisites of modern medical treatment. New healthcare approaches require individualized patient care, which is why clinicians should have all clinical, laboratory, and diagnostic data before making final decisions about the treatment of any patients. This is particularly important for HFpEF that often remains undiagnosed for quite a long time, which further prolongs the beginning of adequate treatment and brings into question outcome of these patients. The aim of this article is to provide the overview of the main principles of LV mechanics and summarize recent data regarding LV strain in patients with HFpEF.

Efficacy and safety of sacubitril/valsartan (LCZ696) in Japanese patients with chronic heart failure and reduced ejection fraction: Rationale for and design of the randomized, double-blind PARALLEL-HF study.

PubMed

Tsutsui, Hiroyuki; Momomura, Shinichi; Saito, Yoshihiko; Ito, Hiroshi; Yamamoto, Kazuhiro; Ohishi, Tomomi; Okino, Naoko; Guo, Weinong

2017-09-01

The prognosis of heart failure patients with reduced ejection fraction (HFrEF) in Japan remains poor, although there is growing evidence for increasing use of evidence-based pharmacotherapies in Japanese real-world HF registries. Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor shown to reduce mortality and morbidity in the recently completed largest outcome trial in patients with HFrEF (PARADIGM-HF trial). The prospectively designed phase III PARALLEL-HF (Prospective comparison of ARNI with ACE inhibitor to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) study aims to assess the clinical efficacy and safety of LCZ696 in Japanese HFrEF patients, and show similar improvements in clinical outcomes as the PARADIGM-HF study enabling the registration of LCZ696 in Japan. This is a multicenter, randomized, double-blind, parallel-group, active controlled study of 220 Japanese HFrEF patients. Eligibility criteria include a diagnosis of chronic HF (New York Heart Association Class II-IV) and reduced ejection fraction (left ventricular ejection fraction ≤35%) and increased plasma concentrations of natriuretic peptides [N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥600pg/mL, or NT-proBNP ≥400pg/mL for those who had a hospitalization for HF within the last 12 months] at the screening visit. The study consists of three phases: (i) screening, (ii) single-blind active LCZ696 run-in, and (iii) double-blind randomized treatment. Patients tolerating LCZ696 50mg bid during the treatment run-in are randomized (1:1) to receive LCZ696 100mg bid or enalapril 5mg bid for 4 weeks followed by up-titration to target doses of LCZ696 200mg bid or enalapril 10mg bid in a double-blind manner. The primary outcome is the composite of cardiovascular death or HF hospitalization and the study is an event-driven trial. The design of the PARALLEL-HF study is aligned with the PARADIGM-HF study and aims to assess the efficacy and safety of LCZ696 in Japanese HFrEF patients. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Heart rate-induced modifications of concentric left ventricular hypertrophy: exploration of a novel therapeutic concept.

PubMed

Klein, Franziska J; Bell, Stephen; Runte, K Elisabeth; Lobel, Robert; Ashikaga, Takamuru; Lerman, Lilach O; LeWinter, Martin M; Meyer, Markus

2016-10-01

Lowering the heart rate is considered to be beneficial in heart failure (HF) with reduced ejection fraction (HFrEF). In a dilated left ventricle (LV), pharmacological heart rate lowering is associated with a reduction in LV chamber size. In patients with HFrEF, this structural change is associated with better survival. HF with preserved ejection fraction (HFpEF) is increasingly prevalent but, so far, without any evidence-based treatment. HFpEF is typically associated with LV concentric remodeling and hypertrophy. The effects of heart rate on this structural phenotype are not known. Analogous with the benefits of a low heart rate on a dilated heart, we hypothesized that increased heart rates could lead to potentially beneficial remodeling of a concentrically hypertrophied LV. This was explored in an established porcine model of concentric LV hypertrophy and fibrosis. Our results suggest that a moderate increase in heart rate can be used to reduce wall thickness, normalize LV chamber volumes, decrease myocardial fibrosis, and improve LV compliance. Our results also indicate that the effects of heart rate can be titrated, are reversible, and do not induce HF. These findings may provide the rationale for a novel therapeutic approach for HFpEF and its antecedent disease substrate. Copyright © 2016 the American Physiological Society.

Reliability of peripheral arterial tonometry in patients with heart failure, diabetic nephropathy and arterial hypertension.

PubMed

Weisrock, Fabian; Fritschka, Max; Beckmann, Sebastian; Litmeier, Simon; Wagner, Josephine; Tahirovic, Elvis; Radenovic, Sara; Zelenak, Christine; Hashemi, Djawid; Busjahn, Andreas; Krahn, Thomas; Pieske, Burkert; Dinh, Wilfried; Düngen, Hans-Dirk

2017-08-01

Endothelial dysfunction plays a major role in cardiovascular diseases and pulse amplitude tonometry (PAT) offers a non-invasive way to assess endothelial dysfunction. However, data about the reliability of PAT in cardiovascular patient populations are scarce. Thus, we evaluated the test-retest reliability of PAT using the natural logarithmic transformed reactive hyperaemia index (LnRHI). Our cohort consisted of 91 patients (mean age: 65±9.7 years, 32% female), who were divided into four groups: those with heart failure with preserved ejection fraction (HFpEF) ( n=25), heart failure with reduced ejection fraction (HFrEF) ( n=22), diabetic nephropathy ( n=21), and arterial hypertension ( n=23). All subjects underwent two separate PAT measurements at a median interval of 7 days (range 4-14 days). LnRHI derived by PAT showed good reliability in subjects with diabetic nephropathy (intra-class correlation (ICC) = 0.863) and satisfactory reliability in patients with both HFpEF (ICC = 0.557) and HFrEF (ICC = 0.576). However, in subjects with arterial hypertension, reliability was poor (ICC = 0.125). We demonstrated that PAT is a reliable technique to assess endothelial dysfunction in adults with diabetic nephropathy, HFpEF or HFrEF. However, in subjects with arterial hypertension, we did not find sufficient reliability, which can possibly be attributed to variations in heart rate and the respective time of the assessments. Clinical Trial Registration Identifier: NCT02299960.

Myocardial Hypertrophy and Its Role in Heart Failure with Preserved Ejection Fraction

PubMed Central

Heinzel, Frank R.; Hohendanner, Felix; Jin, Ge; Sedej, Simon; Edelmann, Frank

2015-01-01

Left ventricular hypertrophy (LVH) is the most common myocardial structural abnormality associated with heart failure with preserved ejection fraction (HFpEF). LVH is driven by neurohumoral activation, increased mechanical load and cytokines associated with arterial hypertension, chronic kidney disease, diabetes and other co-morbidities. Here we discuss the experimental and clinical evidence that links LVH to diastolic dysfunction and qualifies LVH as one diagnostic marker for HFpEF. Mechanisms leading to diastolic dysfunction in LVH are incompletely understood but may include extracellular matrix changes, vascular dysfunction as well as altered cardiomyocyte mechano-elastical properties. Beating cardiomyocytes from HFpEF patients have not yet been studied, but we and others have shown increased Ca2+ turnover and impaired relaxation in cardiomyocytes from hypertrophied hearts. Structural myocardial remodeling can lead to heterogeneity in regional myocardial contractile function, which contributes to diastolic dysfunction in HFpEF. In the clinical setting of patients with compound co-morbidities, diastolic dysfunction may occur independently of LVH. This may be one explanation why current approaches to reduce LVH have not been effective to improve symptoms and prognosis in HFpEF. Exercise training on the other hand, in clinical trials improved exercise tolerance and diastolic function but did not reduce LVH. Thus, current clinical evidence does not support regression of LVH as a surrogate marker for (short-term) improvement of HFpEF. PMID:26183480

RECURRENT STROKE IN THE WARFARIN VERSUS ASPIRIN IN REDUCED EJECTION FRACTION (WARCEF) TRIAL

PubMed Central

Pullicino, Patrick M.; Qian, Min; Sacco, Ralph L.; Freudenberger, Ron; Graham, Susan; Teerlink, John R.; Mann, Douglas; Di Tullio, Marco R.; Ponikowski, Piotr; Lok, Dirk J.; Anker, Stefan D.; Lip, Gregory Y.H.; Estol, Conrado J.; Levin, Bruce; Mohr, J.P.; Thompson, John L. P.; Homma, Shunichi

2014-01-01

Background and Purpose WARCEF randomized 2305 patients in sinus rhythm with ejection fraction (EF) ≤35% to warfarin (INR 2.0–3.5) or aspirin 325 mg. Warfarin reduced the incident ischemic stroke (IIS) hazard rate by 48% over aspirin in a secondary analysis. The IIS rate in heart failure (HF) is too low to warrant routine anticoagulation but epidemiologic studies show that prior stroke increases the stroke risk in HF. We here explore IIS rates in WARCEF patients with and without baseline stroke to look for risk factors for IIS and determine if a subgroup with an IIS rate high enough to give a clinically relevant stroke risk reduction can be identified. Methods We compared potential stroke risk factors between patients with baseline stroke and those without using the exact conditional score test for Poisson variables. We looked for risk factors for IIS, by comparing IIS rates between different risk factors. For EF we tried cutoff points of 10%, 15% and 20%. 15% was used as it was the highest EF that was associated with a significant increase in IIS rate. IIS and EF strata were balanced as to warfarin/aspirin assignment by the stratified randomized design. A multiple Poisson regression examined the simultaneous effects of all risk factors on IIS rate. IIS rates per hundred patient years (/100PY) were calculated in patient groups with significant risk factors. Missing values were assigned the modal value. Results Twenty of 248 (8.1%) patients with baseline stroke and 64 of 2048 (3.1%) without had IIS. IIS rate in patients with baseline stroke (2.37/100PY) was greater than patients without (0.89/100PY)(rate ratio 2.68, p<0.001). Fourteen of 219 (6.4%) patients with ejection fraction (EF)<15% and 70 of 2079 (3.4%) with EF ≥15% had IIS. In the multiple regression analysis stroke at baseline (p<0.001) and EF<15% vs. ≥15% (p=.005) remained significant predictors of IIS. IIS rate was 2.04/100PY in patients with EF<15% and 0.95/100PY in patients with EF ≥15% (p=0.009). IIS rate in patients with baseline stroke and reduced EF was 5.88/100PY with EF<15% decreasing to 2.62/100PY with EF<30%. Conclusions In a WARCEF exploratory analysis, prior stroke and EF<15% were risk factors for IIS. Further research is needed to determine if a clinically relevant stroke risk reduction is obtainable with warfarin in HF patients with prior stroke and reduced EF. PMID:25300706

Noninvasive prediction of left ventricular end-diastolic pressure in patients with coronary artery disease and preserved ejection fraction.

PubMed

Abd-El-Aziz, Tarek A

2012-01-01

The aim of this study was to compare 3 different available methods for estimating left ventricular end-diastolic pressure (LVEDP) noninvasively in patients with coronary artery disease and preserved left ventricular ejection fraction (EF). We used 3 equations for noninvasive estimation of LVEDP: The equation of Mulvagh et al., LVEDP(1) = 46 - 0.22 (IVRT) - 0.10 (AFF) - 0.03 (DT) - (2 ÷ E/A) + 0.05 MAR; the equation of Stork et al., LVEDP(2) = 1.06 + 15.15 × Ai/Ei; and the equation of Abd-El-Aziz, LVEDP(3) = [0.54 (MABP) × (1 - EF)] - 2.23. ( A, A-wave velocity; AFF, atrial filling fraction; Ai, time velocity integral of A wave; DT, deceleration time; E, E-wave velocity; Ei, time velocity integral of E wave; IVRT, isovolumic relaxation time; MABP, mean arterial blood pressure; MAR, time from termination of mitral flow to the electrocardiographic R wave; Ti, time velocity integral of total wave.) LVEDP measured by catheterization was correlated with LVEDP(1) (r = 0.52, P < 0.001), LVEDP(2) (r = 0.31, P < 0.05), and LVEDP(3) (r = 0.81, P < 0.001). The equation described by Abd-El-Aziz, LVEDP = [0.54 MABP × (1 - EF)] - 2.23, appears to be the most accurate, reliable, and easily applied method for estimating LVEDP noninvasively in patients with preserved left ventricular ejection fraction and an LVEDP < 20 mm Hg. Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

The challenge of frailty and sarcopenia in heart failure with preserved ejection fraction.

PubMed

Kinugasa, Yoshiharu; Yamamoto, Kazuhiro

2017-02-01

Frailty is a clinical state in which there is an increase in an individual's vulnerability for developing increased dependency and/or mortality when exposed to stressors. Frailty is often accompanied by heart failure with preserved ejection fraction (HFpEF), and frailty is likely to affect its clinical features and outcomes. Frail patients with HFpEF are frequently associated with sarcopenia (ie, muscle loss and weakness), which is a major component of the pathophysiology of frailty. Sarcopenia is a systemic skeletal muscle disease that impairs the function of limb skeletal muscles, as well as respiratory muscles, and this results in further functional decline. In addition, sarcopenia may contribute to cardiovascular remodelling and dysfunction, leading to the development of HFpEF through several metabolic and endocrine abnormalities. Although there is no established strategy for frail patients with HFpEF, a multidisciplinary approach, including various types of muscular training and nutritional intervention, may provide beneficial effects for these patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Heart Failure, Left Ventricular Remodeling, and Circulating Nitric Oxide Metabolites.

PubMed

Chirinos, Julio A; Akers, Scott R; Trieu, Lien; Ischiropoulos, Harry; Doulias, Paschalis-Thomas; Tariq, Ali; Vassim, Izzah; Koppula, Maheswara R; Syed, Amer Ahmed; Soto-Calderon, Haideliza; Townsend, Raymond R; Cappola, Thomas P; Margulies, Kenneth B; Zamani, Payman

2016-10-14

Stable plasma nitric oxide (NO) metabolites (NO M ), composed predominantly of nitrate and nitrite, are attractive biomarkers of NO bioavailability. NO M levels integrate the influence of NO-synthase-derived NO production/metabolism, dietary intake of inorganic nitrate/nitrite, and clearance of NO M . Furthermore, nitrate and nitrite, the most abundant NO M , can be reduced to NO via the nitrate-nitrite-NO pathway. We compared serum NO M among subjects without heart failure (n=126), subjects with heart failure and preserved ejection fraction (HFpEF; n=43), and subjects with heart failure and reduced ejection fraction (HFrEF; n=32). LV mass and extracellular volume fraction were measured with cardiac MRI. Plasma NO M levels were measured after reduction to NO via reaction with vanadium (III)/hydrochloric acid. Subjects with HFpEF demonstrated significantly lower unadjusted levels of NO M (8.0 μmol/L; 95% CI 6.2-10.4 μmol/L; ANOVA P=0.013) than subjects without HF (12.0 μmol/L; 95% CI 10.4-13.9 μmol/L) or those with HFrEF (13.5 μmol/L; 95% CI 9.7-18.9 μmol/L). There were no significant differences in NO M between subjects with HFrEF and subjects without HF. In a multivariable model that adjusted for age, sex, race, diabetes mellitus, body mass index, current smoking, systolic blood pressure, and glomerular filtration rate, HFpEF remained a predictor of lower NO M (β=-0.43; P=0.013). NO M did not correlate with LV mass, or LV diffuse fibrosis. HFpEF, but not HFrEF, is associated with reduced plasma NO M , suggesting greater endothelial dysfunction, enhanced clearance, or deficient dietary ingestion of inorganic nitrate. Our findings may underlie the salutary effects of inorganic nitrate supplementation demonstrated in recent clinical trials in HFpEF. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Right-Sided Cardiac Dysfunction in Heart Failure With Preserved Ejection Fraction and Worsening Renal Function.

PubMed

Mukherjee, Monica; Sharma, Kavita; Madrazo, Jose A; Tedford, Ryan J; Russell, Stuart D; Hays, Allison G

2017-07-15

In urban populations, worsening renal function (WRF) is well established in patients hospitalized with acute decompensated heart failure with preserved ejection fraction (HFpEF). However, the mechanisms for development of WRF in the setting of acute HF in HFpEF are unclear. In the present study, we sought to characterize conventional echocardiographic measures of right ventricular (RV) chamber size and function to determine whether RV dysfunction and/or adverse RV remodeling is related to WRF in patients with HFpEF. Our study included 104 adult patients with HFpEF (EF ≥ 55%) with technically adequate 2-dimensional echocardiograms performed during their hospitalization for acute decompensated HF to determine echocardiographic predictors of WRF, defined as a serum creatinine (Cr) increase of ≥ 0.3 mg/dl within 72 hours of hospitalization. Thirty-eight of the 104 patients (36%) developed WRF (mean Cr increase = 0.9 ± 0.1 mg/dl) during the hospitalization (mean age ± SD of 64 ± 12 years, 27 women [71%], 29 black [76%]). There were no significant differences in LV medial E/e' ratio and RV systolic pressure by WRF status or in linear dimensions of RV and right atrial size. RV fractional area change, a measure of RV function, however, was significantly decreased in HFpEF patients with WRF compared with the no WRF group (p = 0.003), whereas RV free wall thickness (p = 0.001) was increased. In conclusion, linear and volumetric measures of dimensions of right atrial and RV chamber size did not distinguish HFpEF patients with and without WRF. However, in HFpEF patients with WRF during acute HF hospitalization, there was a significant decrease in RV function and a significant increase in RV free wall thickness compared with matched patients with no WRF. These findings suggest that adverse RV remodeling and RV dysfunction occur in HFpEF patients with WRF. Copyright © 2017 Elsevier Inc. All rights reserved.

Dual Endothelin-A/Endothelin-B Receptor Blockade and Cardiac Remodeling in Heart Failure With Preserved Ejection Fraction

PubMed Central

Valero-Munoz, Maria; Li, Shanpeng; Wilson, Richard M.; Boldbaatar, Batbold; Iglarz, Marc; Sam, Flora

2017-01-01

Background Despite the increasing prevalence of heart failure with preserved ejection fraction (HFpEF) in humans, there remains no evidence-based therapies for HFpEF. Endothelin-1 (ET-1) antagonists are a possibility because elevated ET-1 levels are associated with adverse cardiovascular effects, such as arterial and pulmonary vasoconstriction, impaired left ventricular (LV) relaxation, and stimulation of LV hypertrophy. LV hypertrophy is a common phenotype in HFpEF, particularly when associated with hypertension. Methods and Results In the present study, we found that ET-1 levels were significantly elevated in patients with chronic stable HFpEF. We then sought to investigate the effects of chronic macitentan, a dual ET-A/ET-B receptor antagonist, on cardiac structure and function in a murine model of HFpEF induced by chronic aldosterone infusion. Macitentan caused LV hypertrophy regression independent of blood pressure changes in HFpEF. Although macitentan did not modulate diastolic dysfunction in HFpEF, it significantly reduced wall thickness and relative wall thickness after 2 weeks of therapy. In vitro studies showed that macitentan decreased the aldosterone-induced cardiomyocyte hypertrophy. These changes were mediated by a reduction in the expression of cardiac myocyte enhancer factor 2a. Moreover, macitentan improved adverse cardiac remodeling, by reducing the stiffer cardiac collagen I and titin n2b expression in the left ventricle of mice with HFpEF. Conclusions These findings indicate that dual ET-A/ET-B receptor inhibition improves HFpEF by abrogating adverse cardiac remodeling via antihypertrophic mechanisms and by reducing stiffness. Additional studies are needed to explore the role of dual ET-1 receptor antagonists in patients with HFpEF. PMID:27810862

Dual Endothelin-A/Endothelin-B Receptor Blockade and Cardiac Remodeling in Heart Failure With Preserved Ejection Fraction.

PubMed

Valero-Munoz, Maria; Li, Shanpeng; Wilson, Richard M; Boldbaatar, Batbold; Iglarz, Marc; Sam, Flora

2016-11-01

Despite the increasing prevalence of heart failure with preserved ejection fraction (HFpEF) in humans, there remains no evidence-based therapies for HFpEF. Endothelin-1 (ET-1) antagonists are a possibility because elevated ET-1 levels are associated with adverse cardiovascular effects, such as arterial and pulmonary vasoconstriction, impaired left ventricular (LV) relaxation, and stimulation of LV hypertrophy. LV hypertrophy is a common phenotype in HFpEF, particularly when associated with hypertension. In the present study, we found that ET-1 levels were significantly elevated in patients with chronic stable HFpEF. We then sought to investigate the effects of chronic macitentan, a dual ET-A/ET-B receptor antagonist, on cardiac structure and function in a murine model of HFpEF induced by chronic aldosterone infusion. Macitentan caused LV hypertrophy regression independent of blood pressure changes in HFpEF. Although macitentan did not modulate diastolic dysfunction in HFpEF, it significantly reduced wall thickness and relative wall thickness after 2 weeks of therapy. In vitro studies showed that macitentan decreased the aldosterone-induced cardiomyocyte hypertrophy. These changes were mediated by a reduction in the expression of cardiac myocyte enhancer factor 2a. Moreover, macitentan improved adverse cardiac remodeling, by reducing the stiffer cardiac collagen I and titin n2b expression in the left ventricle of mice with HFpEF. These findings indicate that dual ET-A/ET-B receptor inhibition improves HFpEF by abrogating adverse cardiac remodeling via antihypertrophic mechanisms and by reducing stiffness. Additional studies are needed to explore the role of dual ET-1 receptor antagonists in patients with HFpEF. © 2016 American Heart Association, Inc.

Trends in the use of echocardiography and left ventriculography to assess left ventricular ejection fraction in patients hospitalized with acute myocardial infarction

PubMed Central

Joffe, Samuel W.; Chalian, Armen; Tighe, Dennis A.; Aurigemma, Gerard P.; Yarzebski, Jorge; Gore, Joel M.; Lessard, Darleen; Goldberg, Robert J.

2009-01-01

Background While current guidelines strongly recommend the measurement of ejection fraction (EF) in all patients hospitalized with acute myocardial infarction (AMI), there are little data available describing trends in the use of diagnostic modalities to assess EF in these patients. The purpose of this study was to evaluate trends in the use of ventriculography and echocardiography to measure EF in a community sample of patients hospitalized with AMI. Methods The medical records of 5,380 residents of the Worcester (MA) metropolitan area hospitalized with AMI at 11 greater Worcester medical centers between 1997 and 2005 were reviewed. Results Between 1997 and 2005, the proportion of patients hospitalized with AMI undergoing measurement of EF by both ventriculography and echocardiography increased from 11% to 18%, while the percentage of patients who did not receive an evaluation of EF by either modality decreased from 37% to 27%. The percentage of patients undergoing measurement of EF by ventriculography alone increased from 14% to 20%, while the percentage of patients undergoing measurement of EF by echocardiography alone remained stable at 37%. In 1997, echocardiography was performed prior to ventriculography in approximately two-thirds of hospitalized patients, while in 2005, ventriculography was performed prior to echocardiography in approximately two-thirds of patients with AMI. Conclusions The use of left ventriculography, and the concurrent use of both ventriculography and echocardiography, to assess EF in patients with AMI is increasing. While the proportion of patients who do not have their EF assessed has declined during recent years, many still do not receive a determination of their EF. PMID:19619693

The Singapore Heart Failure Outcomes and Phenotypes (SHOP) study and Prospective Evaluation of Outcome in Patients with Heart Failure with Preserved Left Ventricular Ejection Fraction (PEOPLE) study: rationale and design.

PubMed

Santhanakrishnan, Rajalakshmi; Ng, Tze P; Cameron, Vicky A; Gamble, Greg D; Ling, Lieng H; Sim, David; Leong, Gerard Kui Toh; Yeo, Poh Shuan Daniel; Ong, Hean Yee; Jaufeerally, Fazlur; Wong, Raymond Ching-Chiew; Chai, Ping; Low, Adrian F; Lund, Mayanna; Devlin, Gerry; Troughton, Richard; Richards, A Mark; Doughty, Robert N; Lam, Carolyn S P

2013-03-01

Heart failure (HF) with preserved ejection fraction (EF) accounts for a substantial proportion of cases of HF, and to date no treatments have clearly improved outcome. There are also little data comparing HF cohorts of differing ethnicity within the Asia-Pacific region. The Singapore Heart Failure Outcomes and Phenotypes (SHOP) study and Prospective Evaluation of Outcome in Patients with Heart Failure with Preserved Left Ventricular Ejection Fraction (PEOPLE) study are parallel prospective studies using identical protocols to enroll patients with HF across 6 centers in Singapore and 4 in New Zealand. The objectives are to determine the relative prevalence, characteristics, and outcomes of patients with HF and preserved EF (EF ≥50%) compared with those with HF and reduced EF, and to determine initial data on ethnic differences within and between New Zealand and Singapore. Case subjects (n = 2,500) are patients hospitalized with a primary diagnosis of HF or attending outpatient clinics for management of HF within 6 months of HF decompensation. Control subjects are age- and gender-matched community-based adults without HF from Singapore (n = 1,250) and New Zealand (n = 1,073). All participants undergo detailed clinical assessment, echocardiography, and blood biomarker measurements at baseline, 6 weeks, and 6 months, and are followed over 2 years for death or hospitalization. Substudies include vascular assessment, cardiopulmonary exercise testing, retinal imaging, and cardiac magnetic resonance imaging. The SHOP and PEOPLE studies are the first prospective multicenter studies defining the epidemiology and interethnic differences among patients with HF in the Asia-Oceanic region, and will provide unique insights into the pathophysiology and outcomes for these patients. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of early treatment with ivabradine combined with beta-blockers versus beta-blockers alone in patients hospitalised with heart failure and reduced left ventricular ejection fraction (ETHIC-AHF): A randomised study.

PubMed

Hidalgo, Francisco J; Anguita, Manuel; Castillo, Juan C; Rodríguez, Sara; Pardo, Laura; Durán, Enrique; Sánchez, José J; Ferreiro, Carlos; Pan, Manuel; Mesa, Dolores; Delgado, Mónica; Ruiz, Martín

2016-08-15

To analyse the effect of the early coadministration of ivabradine and beta-blockers (intervention group) versus beta-blockers alone (control group) in patients hospitalised with heart failure and reduced left ventricular ejection fraction (HFrEF). A comparative, randomised study was performed to compare the treatment strategies of beta-blockers alone versus ivabradine and beta-blockers starting 24hours after hospital admission, for acute HF in patients with an left ventricular ejection fraction (EF)<40%, sinus rhythm, and a heart rate (HR)>70bpm. A total of 71 patients were examined, 33 in the intervention group and 38 in the control group. No differences were observed with respect to their baseline characteristics or standard treatment at discharge. HR at 28days (64.3±7.5 vs. 70.3±9.3bpm, p=0.01) and at 4months (60.6±7.5 vs. 67.8±8bpm, p=0.004) after discharge were significantly lower in the intervention group. Significant differences were found with respect to the EF and brain natriuretic peptide levels at 4months. No differences in clinical events (rehospitalisation/death) were reported at 4months. No severe side effects attributable to the early administration of ivabradine were observed. The early coadministration of ivabradine and beta-blockers during hospital admission for acute HFrEF is feasible and safe, and it produces a significant decrease in HR at 28days and at 4months after hospital discharge. It also seemed to improve systolic function and functional and clinical parameters of HF patients at short-term. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hemodynamic responses to small muscle mass exercise in heart failure patients with reduced ejection fraction

PubMed Central

Barrett-O'Keefe, Zachary; Lee, Joshua F.; Berbert, Amanda; Witman, Melissa A. H.; Nativi-Nicolau, Jose; Stehlik, Josef; Richardson, Russell S.

2014-01-01

To better understand the mechanisms responsible for exercise intolerance in heart failure with reduced ejection fraction (HFrEF), the present study sought to evaluate the hemodynamic responses to small muscle mass exercise in this cohort. In 25 HFrEF patients (64 ± 2 yr) and 17 healthy, age-matched control subjects (64 ± 2 yr), mean arterial pressure (MAP), cardiac output (CO), and limb blood flow were examined during graded static-intermittent handgrip (HG) and dynamic single-leg knee-extensor (KE) exercise. During HG exercise, MAP increased similarly between groups. CO increased significantly (+1.3 ± 0.3 l/min) in the control group, but it remained unchanged across workloads in HFrEF patients. At 15% maximum voluntary contraction (MVC), forearm blood flow was similar between groups, while HFrEF patients exhibited an attenuated increase at the two highest intensities compared with controls, with the greatest difference at the highest workload (352 ± 22 vs. 492 ± 48 ml/min, HFrEF vs. control, 45% MVC). During KE exercise, MAP and CO increased similarly across work rates between groups. However, HFrEF patients exhibited a diminished leg hyperemic response across all work rates, with the most substantial decrement at the highest intensity (1,842 ± 64 vs. 2,675 ± 81 ml/min; HFrEF vs. control, 15 W). Together, these findings indicate a marked attenuation in exercising limb perfusion attributable to impairments in peripheral vasodilatory capacity during both arm and leg exercise in patients with HFrEF, which likely plays a role in limiting exercise capacity in this patient population. PMID:25260608

Association Between Use of Long-Acting Nitrates and Outcomes in Heart Failure With Preserved Ejection Fraction.

PubMed

Lim, Shir Lynn; Benson, Lina; Dahlström, Ulf; Lam, Carolyn S P; Lund, Lars H

2017-04-01

Nitrates may be beneficial in heart failure with preserved ejection fraction (HFpEF) by enhancing cGMP signaling and improving hemodynamics, but real-world data on potential efficacy are lacking. We linked the Swedish Heart Failure Registry to national registries with International Classification of Diseases, Tenth Revision comorbidity diagnoses and demographic and socioeconomic data. In HFpEF, defined as left ventricular ejection fraction ≥40%, we derived propensity scores for nitrate use using 52 baseline variables. The association between nitrate use and all-cause mortality and the composite of all-cause mortality or first heart failure hospitalization was assessed in a cohort matched 2:1 untreated to treated based on age and propensity score. In the overall HFpEF cohort (n=19 047; mean [SD] age, 76 [12] years; 46% women), nitrates were used in 17%, and the crude 1-year survival for treated versus untreated patients was 79% (95% confidence interval [CI], 78%-80%) versus 84% (95% CI, 83%-84%) respectively; hazard ratio was 1.48 (95% CI, 1.40-1.56; P <0.001) during a median 755-day follow-up. Matching yielded 2235 treated versus 4470 untreated patients, with 1-year survival of 80% (95% CI, 78%-82%) versus 79% (95% CI, 78%-81%) and hazard ratio of 1.06 (95% CI, 0.98-1.15; P =0.12). Nitrates were associated with worse composite outcome in the matched HFpEF cohort, with 1-year event-free survival of 62% (95% CI, 60%-64%) versus 65% (95% CI, 63%-66%) and hazard ratio of 1.11 (95% CI, 1.04-1.18; P =0.003). These patterns were reproduced in several consistency analyses. In HFpEF, the use of nitrates was not associated with improvements in all-cause mortality or heart failure hospitalization. © 2017 American Heart Association, Inc.

Structural and Functional Phenotyping of the Failing Heart: Is the Left Ventricular Ejection Fraction Obsolete?

PubMed

Bristow, Michael R; Kao, David P; Breathett, Khadijah K; Altman, Natasha L; Gorcsan, John; Gill, Edward A; Lowes, Brian D; Gilbert, Edward M; Quaife, Robert A; Mann, Douglas L

2017-11-01

Diagnosis, prognosis, treatment, and development of new therapies for diseases or syndromes depend on a reliable means of identifying phenotypes associated with distinct predictive probabilities for these various objectives. Left ventricular ejection fraction (LVEF) provides the current basis for combined functional and structural phenotyping in heart failure by classifying patients as those with heart failure with reduced ejection fraction (HFrEF) and those with heart failure with preserved ejection fraction (HFpEF). Recently the utility of LVEF as the major phenotypic determinant of heart failure has been challenged based on its load dependency and measurement variability. We review the history of the development and adoption of LVEF as a critical measurement of LV function and structure and demonstrate that, in chronic heart failure, load dependency is not an important practical issue, and we provide hemodynamic and molecular biomarker evidence that LVEF is superior or equal to more unwieldy methods of identifying phenotypes of ventricular remodeling. We conclude that, because it reliably measures both left ventricular function and structure, LVEF remains the best current method of assessing pathologic remodeling in heart failure in both individual clinical and multicenter group settings. Because of the present and future importance of left ventricular phenotyping in heart failure, LVEF should be measured by using the most accurate technology and methodologic refinements available, and improved characterization methods should continue to be sought. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction.

PubMed

Mohammed, Selma F; Hussain, Saad; Mirzoyev, Sultan A; Edwards, William D; Maleszewski, Joseph J; Redfield, Margaret M

2015-02-10

Characterization of myocardial structural changes in heart failure with preserved ejection fraction (HFpEF) has been hindered by the limited availability of human cardiac tissue. Cardiac hypertrophy, coronary artery disease (CAD), coronary microvascular rarefaction, and myocardial fibrosis may contribute to HFpEF pathophysiology. We identified HFpEF patients (n=124) and age-appropriate control subjects (noncardiac death, no heart failure diagnosis; n=104) who underwent autopsy. Heart weight and CAD severity were obtained from the autopsy reports. With the use of whole-field digital microscopy and automated analysis algorithms in full-thickness left ventricular sections, microvascular density (MVD), myocardial fibrosis, and their relationship were quantified. Subjects with HFpEF had heavier hearts (median, 538 g; 169% of age-, sex-, and body size-expected heart weight versus 335 g; 112% in controls), more severe CAD (65% with ≥1 vessel with >50% diameter stenosis in HFpEF versus 13% in controls), more left ventricular fibrosis (median % area fibrosis, 9.6 versus 7.1) and lower MVD (median 961 versus 1316 vessels/mm(2)) than control (P<0.0001 for all). Myocardial fibrosis increased with decreasing MVD in controls (r=-0.28, P=0.004) and HFpEF (r=-0.26, P=0.004). Adjusting for MVD attenuated the group differences in fibrosis. Heart weight, fibrosis, and MVD were similar in HFpEF patients with CAD versus without CAD. In this study, patients with HFpEF had more cardiac hypertrophy, epicardial CAD, coronary microvascular rarefaction, and myocardial fibrosis than controls. Each of these findings may contribute to the left ventricular diastolic dysfunction and cardiac reserve function impairment characteristic of HFpEF. © 2014 American Heart Association, Inc.

Ejection fraction in myocardial perfusion imaging assessed with a dynamic phantom: comparison between IQ-SPECT and LEHR.

PubMed

Hippeläinen, Eero; Mäkelä, Teemu; Kaasalainen, Touko; Kaleva, Erna

2017-12-01

Developments in single photon emission tomography instrumentation and reconstruction methods present a potential for decreasing acquisition times. One of such recent options for myocardial perfusion imaging (MPI) is IQ-SPECT. This study was motivated by the inconsistency in the reported ejection fraction (EF) and left ventricular (LV) volume results between IQ-SPECT and more conventional low-energy high-resolution (LEHR) collimation protocols. IQ-SPECT and LEHR quantitative results were compared while the equivalent number of iterations (EI) was varied. The end-diastolic (EDV) and end-systolic volumes (ESV) and the derived EF values were investigated. A dynamic heart phantom was used to produce repeatable ESVs, EDVs and EFs. Phantom performance was verified by comparing the set EF values to those measured from a gated multi-slice X-ray computed tomography (CT) scan (EF True ). The phantom with an EF setting of 45, 55, 65 and 70% was imaged with both IQ-SPECT and LEHR protocols. The data were reconstructed with different EI, and two commonly used clinical myocardium delineation software were used to evaluate the LV volumes. The CT verification showed that the phantom EF settings were repeatable and accurate with the EF True being within 1% point from the manufacture's nominal value. Depending on EI both MPI protocols can be made to produce correct EF estimates, but IQ-SPECT protocol produced on average 41 and 42% smaller EDV and ESV when compared to the phantom's volumes, while LEHR protocol underestimated volumes by 24 and 21%, respectively. The volume results were largely similar between the delineation methods used. The reconstruction parameters can greatly affect the volume estimates obtained from perfusion studies. IQ-SPECT produces systematically smaller LV volumes than the conventional LEHR MPI protocol. The volume estimates are also software dependent.

Right atrial volume by cardiovascular magnetic resonance predicts mortality in patients with heart failure with reduced ejection fraction

PubMed Central

Ivanov, Alexander; Mohamed, Ambreen; Asfour, Ahmed; Ho, Jean; Khan, Saadat A.; Chen, Onn; Klem, Igor; Ramasubbu, Kumudha; Brener, Sorin J.; Heitner, John F.

2017-01-01

Background Right Atrial Volume Index (RAVI) measured by echocardiography is an independent predictor of morbidity in patients with heart failure (HF) with reduced ejection fraction (HFrEF). The aim of this study is to evaluate the predictive value of RAVI assessed by cardiac magnetic resonance (CMR) for all-cause mortality in patients with HFrEF and to assess its additive contribution to the validated Meta-Analysis Global Group in Chronic heart failure (MAGGIC) score. Methods and results We identified 243 patients (mean age 60 ± 15; 33% women) with left ventricular ejection fraction (LVEF) ≤ 35% measured by CMR. Right atrial volume was calculated based on area in two- and four -chamber views using validated equation, followed by indexing to body surface area. MAGGIC score was calculated using online calculator. During mean period of 2.4 years 33 patients (14%) died. The mean RAVI was 53 ± 26 ml/m2; significantly larger in patients with than without an event (78.7±29 ml/m2 vs. 48±22 ml/m2, p<0.001). RAVI (per ml/m2) was an independent predictor of mortality [HR = 1.03 (1.01–1.04), p = 0.001]. RAVI has a greater discriminatory ability than LVEF, left atrial volume index and right ventricular ejection fraction (RVEF) (C-statistic 0.8±0.08 vs 0.55±0.1, 0.62±0.11, 0.68±0.11, respectively, all p<0.02). The addition of RAVI to the MAGGIC score significantly improves risk stratification (integrated discrimination improvement 13%, and category-free net reclassification improvement 73%, both p<0.001). Conclusion RAVI by CMR is an independent predictor of mortality in patients with HFrEF. The addition of RAVI to MAGGIC score improves mortality risk stratification. PMID:28369148

Randomized Clinical Trials of Gene Transfer for Heart Failure with Reduced Ejection Fraction.

PubMed

Penny, William F; Hammond, H Kirk

2017-05-01

Despite improvements in drug and device therapy for heart failure, hospitalization rates and mortality have changed little in the past decade. Randomized clinical trials using gene transfer to improve function of the failing heart are the focus of this review. Four randomized clinical trials of gene transfer in heart failure with reduced ejection fraction (HFrEF) have been published. Each enrolled patients with stable symptomatic HFrEF and used either intracoronary delivery of a virus vector or endocardial injection of a plasmid. The initial CUPID trial randomized 14 subjects to placebo and 25 subjects to escalating doses of adeno-associated virus type 1 encoding sarcoplasmic reticulum calcium ATPase (AAV1.SERCA2a). AAV1.SERCA2a was well tolerated, and the high-dose group met a 6 month composite endpoint. In the subsequent CUPID-2 study, 243 subjects received either placebo or the high dose of AAV1.SERCA2a. AAV1.SERCA2a administration, while safe, failed to meet the primary or any secondary endpoints. STOP-HF used plasmid endocardial injection of stromal cell-derived factor-1 to promote stem-cell recruitment. In a 93-subject trial of patients with ischemic etiology heart failure, the primary endpoint (symptoms and 6 min walk distance) failed, but subgroup analyses showed improvements in subjects with the lowest ejection fractions. A fourth trial randomized 14 subjects to placebo and 42 subjects to escalating doses of adenovirus-5 encoding adenylyl cyclase 6 (Ad5.hAC6). There were no safety concerns, and patients in the two highest dose groups (combined) showed improvements in left ventricular function (left ventricular ejection fraction and -dP/dt). The safety data from four randomized clinical trials of gene transfer in patients with symptomatic HFrEF suggest that this approach can be conducted with acceptable risk, despite invasive delivery techniques in a high-risk population. Additional trials are necessary before the approach can be endorsed for clinical practice.

Evaluation of Quality of Life in Patients with and without Heart Failure in Primary Care.

PubMed

Jorge, Antonio José Lagoeiro; Rosa, Maria Luiza Garcia; Correia, Dayse Mary da Silva; Martins, Wolney de Andrade; Ceron, Diana Maria Martinez; Coelho, Leonardo Chaves Ferreira; Soussume, William Shinji Nobre; Kang, Hye Chung; Moscavitch, Samuel Datum; Mesquita, Evandro Tinoco

2017-09-01

Heart failure (HF) is a major public health issue with implications on health-related quality of life (HRQL). To compare HRQL, estimated by the Short-Form Health Survey (SF-36), in patients with and without HF in the community. Cross-sectional study including 633 consecutive individuals aged 45 years or older, registered in primary care. The subjects were selected from a random sample representative of the population studied. They were divided into two groups: group I, HF patients (n = 59); and group II, patients without HF (n = 574). The HF group was divided into HF with preserved ejection fraction (HFpEF - n = 35) and HF with reduced ejection fraction (HFrEF - n = 24). Patients without HF had a mean SF-36 score significantly greater than those with HF (499.8 ± 139.1 vs 445.4 ± 123.8; p = 0.008). Functional capacity - ability and difficulty to perform common activities of everyday life - was significantly worse (p < 0.0001) in patients with HF independently of sex and age. There was no difference between HFpEF and HFrEF. Patients with HF had low quality of life regardless of the syndrome presentation (HFpEF or HFrEF phenotype). Quality of life evaluation in primary care could help identify patients who would benefit from a proactive care program with more emphasis on multidisciplinary and social support. (Arq Bras Cardiol. 2017; [online].ahead print, PP.0-0).

Tensor Factorization for Precision Medicine in Heart Failure with Preserved Ejection Fraction

PubMed Central

Luo, Yuan; Ahmad, Faraz S.; Shah, Sanjiv J.

2017-01-01

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome that may benefit from improved subtyping in order to better characterize its pathophysiology and to develop novel targeted therapies. The United States Precision Medicine Initiative comes amid the rapid growth in quantity and modality of clinical data for HFpEF patients ranging from deep phenotypic to trans-omic data. Tensor factorization, a form of machine learning, allows for the integration of multiple data modalities to derive clinically relevant HFpEF subtypes that may have significant differences in underlying pathophysiology and differential response to therapies. Tensor factorization also allows for better interpretability by supporting dimensionality reduction and identifying latent groups of data for meaningful summarization of both features and disease outcomes. In this narrative review, we analyze the modest literature on the application of tensor factorization to related biomedical fields including genotyping and phenotyping. Based on the cited work including work of our own, we suggest multiple tensor factorization formulations capable of integrating the deep phenotypic and trans-omic modalities of data for HFpEF, or accounting for interactions between genetic variants at different -omic hierarchies. We encourage extensive experimental studies to tackle challenges in applying tensor factorization for precision medicine in HFpEF, including effectively incorporating existing medical knowledge, properly accounting for uncertainty, and efficiently enforcing sparsity for better interpretability. PMID:28116551

CMR reference values for left ventricular volumes, mass, and ejection fraction using computer-aided analysis: the Framingham Heart Study.

PubMed

Chuang, Michael L; Gona, Philimon; Hautvast, Gilion L T F; Salton, Carol J; Breeuwer, Marcel; O'Donnell, Christopher J; Manning, Warren J

2014-04-01

To determine sex-specific reference values for left ventricular (LV) volumes, mass, and ejection fraction (EF) in healthy adults using computer-aided analysis and to examine the effect of age on LV parameters. We examined data from 1494 members of the Framingham Heart Study Offspring cohort, obtained using short-axis stack cine SSFP CMR, identified a healthy reference group (without cardiovascular disease, hypertension, or LV wall motion abnormality) and determined sex-specific upper 95th percentile thresholds for LV volumes and mass, and lower 5th percentile thresholds for EF using computer-assisted border detection. In secondary analyses, we stratified participants by age-decade and tested for linear trend across age groups. The reference group comprised 685 adults (423F; 61 ± 9 years). Men had greater LV volumes and mass, before and after indexation to common measures of body size (all P = 0.001). Women had greater EF (73 ± 6 versus 71 ± 6%; P = 0.0002). LV volumes decreased with greater age in both sexes, even after indexation. Indexed LV mass did not vary with age. LV EF and concentricity increased with greater age in both sexes. We present CMR-derived LV reference values. There are significant age and sex differences in LV volumes, EF, and geometry, whereas mass differs between sexes but not age groups. Copyright © 2013 Wiley Periodicals, Inc.

CMR Reference Values for Left Ventricular Volumes, Mass and Ejection Fraction Using Computer-Aided Analysis: The Framingham Heart Study

PubMed Central

Chuang, Michael L.; Gona, Philimon; Hautvast, Gilion L.T.F.; Salton, Carol J.; Breeuwer, Marcel; O’Donnell, Christopher J.; Manning, Warren J.

2013-01-01

Purpose To determine sex-specific reference values for left ventricular (LV) volumes, mass and ejection fraction (EF) in healthy adults using computer-aided analysis and to examine the effect of age on LV parameters. Methods and Methods We examined data from 1494 members of the Framingham Heart Study Offspring cohort, obtained using short-axis stack cine SSFP CMR, identified a healthy reference group (without cardiovascular disease, hypertension, or LV wall motion abnormality) and determined sex-specific upper 95th percentile thresholds for LV volumes and mass, and lower 5th percentile thresholds for EF using computer-assisted border detection. In secondary analyses we stratified participants by age-decade and tested for linear trend across age groups. Results The reference group comprised 685 adults (423F; 61±9 years). Men had greater LV volumes and mass, before and after indexation to common measures of body size (all p<0.001). Women had greater EF (73±6 vs. 71±6%, p=0.0002). LV volumes decreased with greater age in both sexes, even after indexation. Indexed LV mass did not vary with age. LV EF and concentricity increased with greater age in both sexes. Conclusion We present CMR-derived LV reference values. There are significant age and sex differences in LV volumes, EF and geometry, while mass differs between sexes but not age groups. PMID:24123369

Predictive potential of macrophage migration inhibitory factor (MIF) in patients with heart failure with preserved ejection fraction (HFpEF).

PubMed

Luedike, Peter; Alatzides, Georgios; Papathanasiou, Maria; Heisler, Martin; Pohl, Julia; Lehmann, Nils; Rassaf, Tienush

2018-05-04

Prognostication in heart failure with preserved ejection fraction (HFpEF) is challenging and novel biomarkers are urgently needed. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that plays a crucial role in cardiovascular and various inflammatory diseases. Whether MIF is involved in HFpEF is unknown. Sixty-two patients with HFpEF were enrolled and followed up for 180 days. MIF plasma levels as well as natriuretic peptide (NP) levels were assessed. High MIF levels significantly predicted the combined end-point of all-cause death or hospitalization at 180 days in the univariate analysis (HR 2.41, 95% CI 1.12-5.19, p = 0.025) and after adjustment for relevant covariates in a Cox proportional hazard regression model (HR 2.35, 95% CI 1.05-5.27, p = 0.0374). Furthermore, MIF levels above the median were associated with higher pulmonary artery systolic pressure (PASP) as assessed by echocardiography (PASP 31 mmHg vs 48 mmHg in the low- and high-MIF group, respectively, p = 0.017). NPs significantly correlated with MIF in HFpEF patients (BNP p = 0.011; r = 0.32; NT-proBNP p = 0.027; r = 0.28). MIF was associated with clinical outcomes and might be involved in the pathophysiology of pulmonary hypertension in patients with HFpEF. These first data on MIF in HFpEF should stimulate further research to elucidate the role of this cytokine in heart failure. Trial registration NCT03232671.

Dual Angiotensin Receptor and Neprilysin Inhibition with Sacubitril/Valsartan in Chronic Systolic Heart Failure: Understanding the New PARADIGM.

PubMed

Lillyblad, Matthew P

2015-11-01

To evaluate the clinical role of sacubitril/valsartan, a novel angiotensin-neprilysin inhibitor, for the treatment of chronic heart failure with a reduced ejection fraction (HFrEF). A search of PubMed was conducted using a combination of the search terms sacubitril, valsartan, LCZ696, neprilysin inhibition, natriuretic peptide system, renin-angiotensin system, and heart failure with reduced ejection fraction. Bibliographies of all retrieved articles were reviewed for relevant literature. All references included were published between 1980 and May 2015. All studies and review articles that contained data describing the use of sacubitril/valsartan in HFrEF were reviewed. HFrEF remains a disease of high morbidity and mortality. Natriuretic peptide (NP) augmentation has emerged as a most promising neurohormonal target in HFrEF. NPs provide vasodilatory, natriuretic, diuretic, and antiproliferative actions to help support the failing heart. Neprilysin, a neutral endopeptidase, is a primary pathway for NP metabolism. Combined inhibition of the renin angiotensin aldosterone system and neprilysin augments the beneficial natriuretic peptide pathway while providing direct antagonism to increases in angiotensin II. In the landmark PARADIGM HF trial, the neprilysin inhibitor sacubitril added to valsartan significantly improved morbidity and mortality over enalapril, a standard of care in HFrEF. Application of these results to clinical practice requires careful considerations of trial design, study patient population, and clinical monitoring. Sacubitril/valsartan significantly improved morbidity and mortality in patients with chronic HFrEF but will require careful application to "real-world" populations of HFrEF. © The Author(s) 2015.

Physiological dead space and arterial carbon dioxide contributions to exercise ventilatory inefficiency in patients with reduced or preserved ejection fraction heart failure.

PubMed

Van Iterson, Erik H; Johnson, Bruce D; Borlaug, Barry A; Olson, Thomas P

2017-12-01

Patients with heart failure (HF) with reduced (HFrEF) or preserved (HFpEF) ejection fraction demonstrate an increased ventilatory equivalent for carbon dioxide (V̇ E /V̇CO 2 ) slope. The physiological correlates of the V̇ E /V̇CO 2 slope remain unclear in the two HF phenotypes. We hypothesized that changes in the physiological dead space to tidal volume ratio (V D /V T ) and arterial CO 2 tension (PaCO 2 ) differentially contribute to the V̇ E /V̇CO 2 slope in HFrEF vs. HFpEF. Adults with HFrEF (n = 32) and HFpEF (n = 27) [mean ± standard deviation (SD) left ventricular ejection fraction: 22 ± 7% and 61 ± 9%, respectively; mean ± SD body mass index: 28 ± 4 kg/m 2 and 33 ± 6 kg/m 2 , respectively; P < 0.01] performed cardiopulmonary exercise testing with breath-by-breath ventilation and gas exchange measurements. PaCO 2 was measured via radial arterial catheterization. We calculated the V̇ E /V̇CO 2 slope via linear regression, and V D /V T  = 1 - [(863 × V̇CO 2 )/(V̇ E  × PaCO 2 )]. Resting V D /V T (0.48 ± 0.08 vs. 0.41 ± 0.11; P = 0.04), but not PaCO 2 (38 ± 5 mmHg vs. 40 ± 3 mmHg; P = 0.21) differed between HFrEF and HFpEF. Peak exercise V D /V T (0.39 ± 0.08 vs. 0.32 ± 0.12; P = 0.02) and PaCO 2 (33 ± 6 mmHg vs. 38 ± 4 mmHg; P < 0.01) differed between HFrEF and HFpEF. The V̇ E /V̇CO 2 slope was higher in HFrEF compared with HFpEF (44 ± 11 vs. 35 ± 8; P < 0.01). Variance associated with the V̇ E /V̇CO 2 slope in HFrEF and HFpEF was explained by peak exercise V D /V T (R 2  = 0.30 and R 2  = 0.50, respectively) and PaCO 2 (R 2  = 0.64 and R 2  = 0.28, respectively), but the relative contributions of each differed (all P < 0.01). Relationships between the V̇ E /V̇CO 2 slope and both V D /V T and PaCO 2 are robust, but differ between HFpEF and HFrEF. Increasing V̇ E /V̇CO 2 slope appears to be strongly explained by mechanisms influential in regulating PaCO 2 in HFrEF, which contrasts with the strong role of increased V D /V T in HFpEF. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Left ventricular markers of global dyssynchrony predict limited exercise capacity in heart failure, but not in patients with preserved ejection fraction

PubMed Central

2012-01-01

Background The aim of this study was to prospectively examine echocardiographic parameters that correlate and predict functional capacity assessed by 6 min walk test (6-MWT) in patients with heart failure (HF), irrespective of ejection fraction (EF). Methods In 147 HF patients (mean age 61 ± 11 years, 50.3% male), a 6-MWT and an echo-Doppler study were performed in the same day. Global LV dyssynchrony was indirectly assessed by total isovolumic time - t-IVT [in s/min; calculated as: 60 – (total ejection time + total filling time)], and Tei index (t-IVT/ejection time). Patients were divided into two groups based on the 6-MWT distance (Group I: ≤300 m and Group II: >300 m), and also in two groups according to EF (Group A: LVEF ≥ 45% and Group B: LVEF < 45%). Results In the cohort of patients as a whole, the 6-MWT correlated with t-IVT (r = −0.49, p < 0.001) and Tei index (r = −0.43, p < 0.001) but not with any of the other clinical or echocardiographic parameters. Group I had lower hemoglobin level (p = 0.02), lower EF (p = 0.003), larger left atrium (p = 0.02), thicker interventricular septum (p = 0.02), lower A wave (p = 0.01) and lateral wall late diastolic myocardial velocity a’ (p = 0.047), longer isovolumic relaxation time (r = 0.003) and longer t-IVT (p = 0.03), compared with Group II. In the patients cohort as a whole, only t-IVT ratio [1.257 (1.071-1.476), p = 0.005], LV EF [0.947 (0.903-0.993), p = 0.02], and E/A ratio [0.553 (0.315-0.972), p = 0.04] independently predicted poor 6-MWT performance (<300 m) in multivariate analysis. None of the echocardiographic measurements predicted exercise tolerance in HFpEF. Conclusion In patients with HF, the limited exercise capacity, assessed by 6-MWT, is related mostly to severity of global LV dyssynchrony, more than EF or raised filling pressures. The lack of exercise predictors in HFpEF reflects its multifactorial pathophysiology. PMID:22966942

Left Atrial Remodeling and Atrioventricular Coupling in a Canine Model of Early Heart Failure With Preserved Ejection Fraction

PubMed Central

Zakeri, Rosita; Moulay, Gilles; Chai, Qiang; Ogut, Ozgur; Hussain, Saad; Takahama, Hiroyuki; Lu, Tong; Wang, Xiao-Li; Linke, Wolfgang A.; Lee, Hon-Chi; Redfield, Margaret M.

2016-01-01

Background Left atrial (LA) compliance and contractility influence left ventricular (LV) stroke volume. We hypothesized that diminished LA compliance and contractile function occur early during development of heart failure with preserved ejection fraction (HFpEF) and impair overall cardiac performance. Method and Results Cardiac magnetic resonance imaging, echocardiography, LV and LA pressure-volume studies, and tissue analyses were performed in a model of early HFpEF (elderly dogs, renal wrap-induced hypertension, exogenous aldosterone; n=9) and young control dogs (sham surgery; n=13). Early HFpEF was associated with LA enlargement, cardiomyocyte hypertrophy and enhanced LA contractile function (median active emptying fraction 16% [95% CI 13–24] vs 12[10–14]%, p=0.008; end-systolic pressure-volume relationship slope 2.4[1.9–3.2]mmHg/mL HFpEF vs 1.5[1.2–2.2]mmHg/mL controls, p=0.01). However, atrioventricular coupling was impaired and the curvilinear LA end-reservoir pressure-volume relationship was shifted upward/leftward in HFpEF (LA stiffness constant, βLA, 0.16[0.11–0.18]mmHg/mL vs 0.06[0.04–0.10]mmHg/mL controls, p=0.002) indicating reduced LA compliance. Impaired atrioventricular coupling and lower LA compliance correlated with lower LV stroke volume. Total fibrosis and titin isoform composition were similar between groups, however titin was hyperphosphorylated in HFpEF and correlated with βLA. LA microvascular reactivity was diminished in HFpEF versus controls. LA microvascular density tended to be lower in HFpEF and inversely correlated with βLA. Conclusions In early-stage hypertensive HFpEF, LA cardiomyocyte hypertrophy, titin hyperphosphorylation and microvascular dysfunction occur in association with increased systolic and diastolic LA chamber stiffness, impaired atrioventricular coupling and decreased LV stroke volume. These data indicate that maladaptive LA remodeling occurs early during HFpEF development, supporting a concept of global myocardial remodeling. PMID:27758811

Contractility and Ventricular Systolic Stiffening in Hypertensive Heart Disease: Insights into the Pathogenesis of Heart Failure with Preserved Ejection Fraction

PubMed Central

Borlaug, Barry A.; Lam, Carolyn S.P.; Roger, Véronique L.; Rodeheffer, Richard J.; Redfield, Margaret M.

2009-01-01

Objectives: 1) Compare left ventricular (LV) systolic stiffness and contractility in normal subjects, hypertensives without heart failure, and patients with heart failure and preserved ejection fraction (HFpEF); and 2) Determine whether LV systolic stiffness or myocardial contractility are associated with mortality in HFpEF. Background: Arterial load is increased in hypertension and is matched by increased end-systolic LV stiffness (ventricular-arterial coupling). Increased end-systolic LV stiffness may be mediated by enhanced myocardial contractility or processes which increase passive myocardial stiffness. Methods: Healthy controls (n=617), hypertensives (No HF, n=719) and patients with HFpEF (n=244, 96% hypertensive) underwent echo-Doppler characterization of arterial (Ea) and LV end-systolic (Ees) stiffness (elastance), ventricular-arterial coupling (Ea/Ees ratio), chamber-level and myocardial contractility (stress-corrected midwall shortening). Results: Ea and Ees were similarly elevated in hypertensives with or without HFpEF compared with controls, but ventricular-arterial coupling was similar across groups. In hypertensives, elevated Ees was associated with enhanced chamber-level and myocardial contractility, while in HFpEF, chamber and myocardial contractility were depressed compared with both hypertensives and controls. Group differences persisted after adjusting for geometry. In HFpEF, impaired myocardial contractility (but not Ees) was associated with increased age-adjusted mortality. Conclusions: While arterial load is elevated and matched by increased LV systolic stiffness in hypertension with or without HFpEF, the mechanisms of systolic LV stiffening differ substantially. These data suggest that myocardial contractility increases to match arterial load in asymptomatic hypertensive heart disease, but that progression to HFpEF may be mediated by processes which simultaneously impair myocardial contractility and increase passive myocardial stiffness. PMID:19628115

A prospective evaluation of the repeatability of left ventricular ejection fraction measurement by gated SPECT.

PubMed

Kliner, Dustin; Wang, Li; Winger, Daniel; Follansbee, William P; Soman, Prem

2015-12-01

Gated single-photon emission computed tomography (SPECT) is widely used for myocardial perfusion imaging and provides an automated assessment of left ventricular ejection fraction (LVEF). We prospectively tested the repeatability of serial SPECT-derived LVEF. This information is essential in order to inform the interpretation of a change in LV function on serial testing. Consenting patients (n = 50) from among those referred for clinically indicated gated myocardial perfusion SPECT (MPs) were recruited. Following the clinical rest-stress study, patients were repositioned on the camera table for a second acquisition using identical parameters. Patient positioning, image acquisition and processing for the second scan were independently performed by a technologist blinded to the clinical scan. Quantitative LVEF was generated by Quantitative Gated SPECT and recorded as EF1 and EF2, respectively. Repeatability of serial results was assessed using the Bland-Altman method. The limits of repeatability and repeatability coefficients were generated to determine the maximum variation in LVEF that can be expected to result from test variability. Repeatability was tested across a broad range of LV systolic function and myocardial perfusion. The mean difference between EF1 and EF2 was 1.6% (EF units), with 95% limits of repeatability of +9.1% to -6.0% (repeatability coefficient 7.5%). Correlation between serial EF measurements was excellent (r = 0.9809). Similar results were obtained in subgroups based on normal or abnormal EF and myocardial perfusion. The largest repeatability coefficient of 8.1% was seen in patients with abnormal LV systolic function. When test protocol and acquisition parameters are kept constant, a difference of >8% EF units on serial MPs is indicative of a true change 95% of the time.

Enhancing ejection fraction measurement through 4D respiratory motion compensation in cardiac PET imaging

NASA Astrophysics Data System (ADS)

Tang, Jing; Wang, Xinhui; Gao, Xiangzhen; Segars, W. Paul; Lodge, Martin A.; Rahmim, Arman

2017-06-01

ECG gated cardiac PET imaging measures functional parameters such as left ventricle (LV) ejection fraction (EF), providing diagnostic and prognostic information for management of patients with coronary artery disease (CAD). Respiratory motion degrades spatial resolution and affects the accuracy in measuring the LV volumes for EF calculation. The goal of this study is to systematically investigate the effect of respiratory motion correction on the estimation of end-diastolic volume (EDV), end-systolic volume (ESV), and EF, especially on the separation of normal and abnormal EFs. We developed a respiratory motion incorporated 4D PET image reconstruction technique which uses all gated-frame data to acquire a motion-suppressed image. Using the standard XCAT phantom and two individual-specific volunteer XCAT phantoms, we simulated dual-gated myocardial perfusion imaging data for normally and abnormally beating hearts. With and without respiratory motion correction, we measured the EDV, ESV, and EF from the cardiac-gated reconstructed images. For all the phantoms, the estimated volumes increased and the biases significantly reduced with motion correction compared with those without. Furthermore, the improvement of ESV measurement in the abnormally beating heart led to better separation of normal and abnormal EFs. The simulation study demonstrated the significant effect of respiratory motion correction on cardiac imaging data with motion amplitude as small as 0.7 cm. The larger the motion amplitude the more improvement respiratory motion correction brought about on the EF measurement. Using data-driven respiratory gating, we also demonstrated the effect of respiratory motion correction on estimating the above functional parameters from list mode patient data. Respiratory motion correction has been shown to improve the accuracy of EF measurement in clinical cardiac PET imaging.

Adherence to optimal heart rate control in heart failure with reduced ejection fraction: insight from a survey of heart rate in heart failure in Sweden (HR-HF study).

PubMed

Fu, M; Ahrenmark, U; Berglund, S; Lindholm, C J; Lehto, A; Broberg, A Månsson; Tasevska-Dinevska, G; Wikstrom, G; Ågard, A; Andersson, B

2017-12-01

Despite that heart rate (HR) control is one of the guideline-recommended treatment goals for heart failure (HF) patients, implementation has been painstakingly slow. Therefore, it would be important to identify patients who have not yet achieved their target heart rates and assess possible underlying reasons as to why the target rates are not met. The survey of HR in patients with HF in Sweden (HR-HF survey) is an investigator-initiated, prospective, multicenter, observational longitudinal study designed to investigate the state of the art in the control of HR in HF and to explore potential underlying mechanisms for suboptimal HR control with focus on awareness of and adherence to guidelines for HR control among physicians who focus on the contributing role of beta-blockers (BBs). In 734 HF patients the mean HR was 68 ± 12 beats per minute (bpm) (37.2% of the patients had a HR >70 bpm). Patients with HF with reduced ejection fraction (HFrEF) (n = 425) had the highest HR (70 ± 13 bpm, with 42% >70 bpm), followed by HF with preserved ejection fraction and HF with mid-range ejection fraction. Atrial fibrillation, irrespective of HF type, had higher HR than sinus rhythm. A similar pattern was observed with BB treatment. Moreover, non-achievement of the recommended target HR (<70 bpm) in HFrEF and sinus rhythm was unrelated to age, sex, cardiovascular risk factors, cardiovascular diseases, and comorbidities, but was related to EF and the clinical decision of the physician. Approximately 50% of the physicians considered a HR of >70 bpm optimal and an equal number considered a HR of >70 bpm too high, but without recommending further action. Furthermore, suboptimal HR control cannot be attributed to the use of BBs because there was neither a difference in use of BBs nor an interaction with BBs for HR >70 bpm compared with HR <70 bpm. Suboptimal control of HR was noted in HFrEF with sinus rhythm, which appeared to be attributable to physician decision making rather than to the use of BBs. Therefore, our results underline the need for greater attention to HR control in patients with HFrEF and sinus rhythm and thus a potential for improved HF care.

Prognostic significance of myocardial energy expenditure and myocardial efficiency in patients with heart failure with reduced ejection fraction.

PubMed

Cetin, Mehmet S; Ozcan Cetin, Elif H; Canpolat, Ugur; Sasmaz, Hatice; Temizhan, Ahmet; Aydogdu, Sinan

2018-02-01

In heart failure with reduced ejection fraction (HFrEF) patients, myocardial blood flow (MBF), myocardial energy expenditure (MEE), myocardial efficiency has been poorly evaluated because of the necessity of invasive procedures in the determination of these parameters. Transthoracic echocardiography (TTE) can provide reliable data for MEE, MBF (via coronary sinus (CS) flows). Also, myocardial efficiency can be evaluated by the MEE to MBF ratio. We aim to assess MBF, MEE and energy efficiency and the prognostic value of these parameters in HFrEF. In this prospective study, a total of 80 patients with HFrEF due to either ischemic or non-ischemic etiology and 20 healthy control subjects were included. Median follow-up duration was 901 (27-1004) days. MBF was calculated via coronary sinus blood flow. MEE was measured from circumferential end-systolic stress, stroke volume and left ventricular ejection time. MEE to MBF ratio was determined as MEf. Primary composite end-point (CEP) was cardiovascular mortality, heart transplantation or mechanical circulatory support. MEE and MEf were lower and MBF per minute was higher in HF group compared to control subjects whereas MBF per 100 g left ventricular mass was not different. MEE and MEf have significantly negative correlation with troponin I, BNP, uric acid and positive correlation with epicardial fat thickness. In Cox regression analysis, per one calorie decrease of MEE was associated 4.3 times increased risk [HR 4.396 (95% CI 1.230-15.716)] and per one percent decrease of MEf was associated 3.3 times increased risk of CEP [HR 3.343 (95% CI 1.025-10.905)]. Our study demonstrated that while MEE and MEf diminished in HFrEF, MBF preserved with the symptomatic progression of HF. MEE and MEf were found to be associated with important prognostic markers and independent predictors of CEP in HFrEF. Evaluation of MEE, MBF and MEf with echocardiography may provide an additional data regarding prognostic assessment of HFrEF population.

Diagnostic and Prognostic Value of CMR T1-Mapping in Patients With Heart Failure and Preserved Ejection Fraction.

PubMed

Rommel, Karl-Philipp; Lücke, Christian; Lurz, Philipp

2017-10-01

Heart failure with preserved ejection fraction (HFpEF) presents a major challenge in modern cardiology. Although this syndrome is of increasing prevalence and is associated with unfavorable outcomes, treatment trials have failed to establish effective therapies. Currently, solutions to this dilemma are being investigated, including categorizing and characterizing patients more diversely to individualize treatment. In this regard, new imaging techniques might provide important information. Diastolic dysfunction is a diagnostic and pathophysiological cornerstone in HFpEF and is believed to be caused by systemic inflammation with the development of interstitial myocardial fibrosis and myocardial stiffening. Cardiac magnetic resonance (CMR) T 1 -mapping is a novel tool, which allows noninvasive quantification of the extracellular space and diffuse myocardial fibrosis. This review provides an overview of the potential of myocardial tissue characterization with CMR T 1 mapping in HFpEF patients, outlining its diagnostic and prognostic implications and discussing future directions. We conclude that CMR T 1 mapping is potentially an effective tool for patient characterization in large-scale epidemiological, diagnostic, and therapeutic HFpEF trials beyond traditional imaging parameters. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Recent advances in heart failure.

PubMed

Kassi, Mahwash; Hannawi, Bashar; Trachtenberg, Barry

2018-03-01

Acute heart failure continues to be a challenge as there is limited benefit of numerous agents that have been tested. Cardiac resynchronization therapy remains standard of care, yet timing and need for implantable cardiac defibrillator has been brought into question with the recent randomized trials. Several recent advances have been made towards management of heart failure both in drug and device therapy. The purpose of this review is to provide an update on the most important recent studies on heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Two new drugs have been added to the armamentarium for HFrEF; ivabradine and angiotensin receptor-neprilysin inhibitors (ARNIs). Initial data from a new left ventricular assist device (LVAD) pump, the HeartMate 3 (HM III), have demonstrated no reports of pump thrombosis at 6 months, but stroke and right ventricle failure continue to be a challenge with comparable rates compared with the HeartMate II. Several large studies in HFpEF failed to show improvement in outcomes and management continues to be geared towards lifestyle modification and symptom relief. Newer therapies and devices have met with great success, yet there are several therapies that provide no benefit and even harm. A careful review of the recent literature remains instrumental to the effective management of patients with heart failure.

Prognostic Value of Pulmonary Vascular Resistance by Magnetic Resonance in Systolic Heart Failure

PubMed Central

Fabregat-Andrés, Óscar; Estornell-Erill, Jordi; Ridocci-Soriano, Francisco; Pérez-Boscá, José Leandro; García-González, Pilar; Payá-Serrano, Rafael; Morell, Salvador; Cortijo, Julio

2016-01-01

Background Pulmonary hypertension is associated with poor prognosis in heart failure. However, non-invasive diagnosis is still challenging in clinical practice. Objective We sought to assess the prognostic utility of non-invasive estimation of pulmonary vascular resistances (PVR) by cardiovascular magnetic resonance to predict adverse cardiovascular outcomes in heart failure with reduced ejection fraction (HFrEF). Methods Prospective registry of patients with left ventricular ejection fraction (LVEF) < 40% and recently admitted for decompensated heart failure during three years. PVRwere calculated based on right ventricular ejection fraction and average velocity of the pulmonary artery estimated during cardiac magnetic resonance. Readmission for heart failure and all-cause mortality were considered as adverse events at follow-up. Results 105 patients (average LVEF 26.0 ±7.7%, ischemic etiology 43%) were included. Patients with adverse events at long-term follow-up had higher values of PVR (6.93 ± 1.9 vs. 4.6 ± 1.7estimated Wood Units (eWu), p < 0.001). In multivariate Cox regression analysis, PVR ≥ 5 eWu(cutoff value according to ROC curve) was independently associated with increased risk of adverse events at 9 months follow-up (HR2.98; 95% CI 1.12-7.88; p < 0.03). Conclusions In patients with HFrEF, the presence of PVR ≥ 5.0 Wu is associated with significantly worse clinical outcome at follow-up. Non-invasive estimation of PVR by cardiac magnetic resonance might be useful for risk stratification in HFrEF, irrespective of etiology, presence of late gadolinium enhancement or LVEF. PMID:26840055

Aortic flow conditions predict ejection efficiency in the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE).

PubMed

Doyle, Mark; Pohost, Gerald M; Bairey Merz, C Noel; Farah, Victor; Shaw, Leslee J; Sopko, George; Rogers, William J; Sharaf, Barry L; Pepine, Carl J; Thompson, Diane V; Rayarao, Geetha; Tauxe, Lindsey; Kelsey, Sheryl F; Biederman, Robert W W

2017-06-01

The Windkessel model of the cardiovascular system, both in its original wind-chamber and flow-pipe form, and in its electrical circuit analog has been used for over a century to modeled left ventricular ejection conditions. Using parameters obtained from aortic flow we formed a Flow Index that is proportional to the impedance of such a "circuit". We show that the impedance varies with ejection fraction (EF) in a manner characteristic of a resonant circuit with multiple resonance points, with each resonance point centrally located in a small range of EF values, i.e., corresponding to multiple contiguous EF bands. Two target populations were used: (I) a development group comprising male and female subjects (n=112) undergoing cardiovascular magnetic resonance (CMR) imaging for a variety of cardiac conditions. The Flow Index was developed using aortic flow data and its relationship to left ventricular EF was shown. (II) An illustration group comprised of female subjects from the Women's Ischemia Syndrome Evaluation (WISE) (n=201) followed for 5 years for occurrence of major adverse cardiovascular events (MACE). Flow data was not available in this group but since the Flow Index was related to the EF we noted the MACE rate with respect to EF. The EFs of the development population covered a wide range (9%-76%) traversing six Flow Index resonance bands. Within each Flow Index resonance band the impedance varied from highly capacitive at the lower range of EF through minimal impedance at resonance, to highly inductive at the higher range of EF, which is characteristic of a resonant circuit. When transitioning from one EF band to a higher band, the Flow Index made a sudden transition from highly inductive to capacitive impedance modes. MACE occurred in 26 (13%) of the WISE (illustration) population. Distance in EF units (Delta center ) from the central location between peaks of MACE activity was derived from EF data and was predictive of MACE rate with an area under the receiver operator curve of 0.73. Of special interest, Delta center was highly predictive of MACE in the sub-set of women with EF >60% (AUC 0.79) while EF was no more predictive than random chance (AUC 0.48). A Flow Index that describes impedance conditions of left ventricular ejection can be calculated using data obtained completely from the ascending aorta. The Flow Index exhibits a periodic variation with EF, and in a separate illustration population the occurrence of MACE was observed to exhibit a similar periodic variation with EF, even in cases of normal EF.

Differential Responses of Post-Exercise Recovery of Leg Blood Flow and Oxygen Uptake Kinetics in HFpEF versus HFrEF.

PubMed

Thompson, Richard B; Pagano, Joseph J; Mathewson, Kory W; Paterson, Ian; Dyck, Jason R; Kitzman, Dalane W; Haykowsky, Mark J

2016-01-01

The goals of the current study were to compare leg blood flow, oxygen extraction and oxygen uptake (VO2) after constant load sub-maximal unilateral knee extension (ULKE) exercise in patients with heart failure with reduced ejection fraction (HFrEF) compared to those with preserved ejection fraction (HFpEF). Previously, it has been shown that prolonged whole body VO2 recovery kinetics are directly related to disease severity and all-cause mortality in HFrEF patients. To date, no study has simultaneously measured muscle-specific blood flow and oxygen extraction post exercise recovery kinetics in HFrEF or HFpEF patients; therefore it is unknown if muscle VO2 recovery kinetics, and more specifically, the recovery kinetics of blood flow and oxygen extraction at the level of the muscle, differ between HF phenotypes. Ten older (68±10yrs) HFrEF (n = 5) and HFpEF (n = 5) patients performed sub-maximal (85% of maximal weight lifted during an incremental test) ULKE exercise for 4 minutes. Femoral venous blood flow and venous O2 saturation were measured continuously from the onset of end-exercise, using a novel MRI method, to determine off-kinetics (mean response times, MRT) for leg VO2 and its determinants. HFpEF and HFrEF patients had similar end-exercise leg blood flow (1.1±0.6 vs. 1.2±0.6 L/min, p>0.05), venous saturation (42±12 vs. 41±11%, p>0.05) and VO2 (0.13±0.08 vs. 0.11±0.05 L/min, p>0.05); however HFrEF had significantly delayed recovery MRT for flow (292±135sec. vs 105±63sec., p = 0.004) and VO2 (95±37sec. vs. 47±15sec., p = 0.005) compared to HFpEF. Impaired muscle VO2 recovery kinetics following ULKE exercise differentiated HFrEF from HFpEF patients and suggests distinct underlying pathology and potential therapeutic approaches in these populations.

How are patients with heart failure treated in primary care?
.

PubMed

Vaillant-Roussel, Hélène; Pereira, Bruno; Gibot-Boeuf, Sylvaine; Eschalier, Romain; Dubray, Claude; Boussageon, Rémy; Vorilhon, Philippe

2018-05-24

The aim of this study was to assess the adherence of general practitioners (GPs) to guidelines in patients with heart failure with reduced ejection fraction (HFrEF) and to describe GPs' prescribing behavior regarding patients with heart failure with preserved ejection fraction (HFpEF). Cross-sectional study as part of the ETIC trial. Five classes of drugs were described: angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs); β-blockers (BBs); mineralocorticoid receptor antagonists (MRAs); diuretics (thiazide or loop diuretics); and digoxin. 178 patients were studied: their mean age was 73.5 years (± 10.6). Of the 128 patients with HFpEF, 81.3% received ACEIs or ARBs, 63.3% received BBs, 13.3% received MRAs, 75.8% received diuretics, and 12.5% received digoxin. Of the 50 patients with HFrEF, 84% received ACEIs or ARBs, 74% received BBs, 20% received MRAs, 76% received diuretics, and 2% received digoxin. 25% of the patients were given a drug in accordance with the recommendations for drug class but not a drug authorized for the HFrEF indication. Among the patients with HFrEF who were treated in accordance with the recommendations, target doses were achieved in 1/3 given ACEIs/ARBs, 1/4 given BBs, and 1/2 given MRAs. Only 6% of the patients had a perfect Global Adherence Indicator-3 (GAI-3) with all target doses achieved. Several drugs were prescribed even though they were not recommended, and few patients were treated optimally. It seems to be necessary to develop a pragmatic tool to help GPs and cardiologists in optimizing treatment.
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Ivabradine: Current and Future Treatment of Heart Failure.

PubMed

Thorup, Lene; Simonsen, Ulf; Grimm, Daniela; Hedegaard, Elise R

2017-08-01

In heart failure (HF), the heart cannot pump blood efficiently and is therefore unable to meet the body's demands of oxygen, and/or there is increased end-diastolic pressure. Current treatments for HF with reduced ejection fraction (HFrEF) include angiotensin-converting enzyme (ACE) inhibitors, angiotension receptor type 1 (AT 1 ) antagonists, β-adrenoceptor antagonists, aldosterone receptor antagonists, diuretics, digoxin and a combination drug with AT 1 receptor antagonist and neprilysin inhibitor. In HF, the risk of readmission for hospital and mortality is markedly higher with a heart rate (HR) above 70 bpm. Here, we review the evidence regarding the use of ivabradine for lowering HR in HF. Ivabradine is a blocker of an I funny current (I(f)) channel and causes rate-dependent inhibition of the pacemaker activity in the sinoatrial node. In clinical trials of HFrEF, treatment with ivabradine seems to improve clinical outcome, for example improved ejection fraction (EF) and less readmission for hospital, but the effect appears most pronounced in patients with HRs above 70 bpm, while the effect on cardiovascular death appears less consistent. The adverse effects of ivabradine include bradycardia, atrial fibrillation and visual disturbances, but ivabradine avoids the negative inotrope effects observed with β-adrenoceptor antagonists. In conclusion, in patients with stable HFrEF with EF<35% and HR above 70 bpm, ivabradine improves the outcome and might be a first choice of therapy, if beta-adrenoceptor antagonists are not tolerated. Further studies must show whether that can be extended to HF patients with preserved EF. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Automated extraction of ejection fraction for quality measurement using regular expressions in Unstructured Information Management Architecture (UIMA) for heart failure.

PubMed

Garvin, Jennifer H; DuVall, Scott L; South, Brett R; Bray, Bruce E; Bolton, Daniel; Heavirland, Julia; Pickard, Steve; Heidenreich, Paul; Shen, Shuying; Weir, Charlene; Samore, Matthew; Goldstein, Mary K

2012-01-01

Left ventricular ejection fraction (EF) is a key component of heart failure quality measures used within the Department of Veteran Affairs (VA). Our goals were to build a natural language processing system to extract the EF from free-text echocardiogram reports to automate measurement reporting and to validate the accuracy of the system using a comparison reference standard developed through human review. This project was a Translational Use Case Project within the VA Consortium for Healthcare Informatics. We created a set of regular expressions and rules to capture the EF using a random sample of 765 echocardiograms from seven VA medical centers. The documents were randomly assigned to two sets: a set of 275 used for training and a second set of 490 used for testing and validation. To establish the reference standard, two independent reviewers annotated all documents in both sets; a third reviewer adjudicated disagreements. System test results for document-level classification of EF of <40% had a sensitivity (recall) of 98.41%, a specificity of 100%, a positive predictive value (precision) of 100%, and an F measure of 99.2%. System test results at the concept level had a sensitivity of 88.9% (95% CI 87.7% to 90.0%), a positive predictive value of 95% (95% CI 94.2% to 95.9%), and an F measure of 91.9% (95% CI 91.2% to 92.7%). An EF value of <40% can be accurately identified in VA echocardiogram reports. An automated information extraction system can be used to accurately extract EF for quality measurement.

Effect of Obesity on the Prognostic Impact of Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction.

PubMed

Yagawa, Mayuko; Nagatomo, Yuji; Izumi, Yuki; Mahara, Keitaro; Tomoike, Hitonobu; Shiraishi, Yasuyuki; Kohno, Takashi; Mizuno, Atsushi; Goda, Ayumi; Kohsaka, Shun; Yoshikawa, Tsutomu

2017-06-23

Although obesity is associated with left ventricular hypertrophy, diastolic dysfunction, and occurrence of atrial fibrillation (AF), obese heart failure (HF) patients have a more favorable clinical outcome (obesity paradox). The clinical impact of AF on obese or lean HF patients has not been fully elucidated.Methods and Results:We analyzed 1,681 patients who were enrolled in the West Tokyo Heart Failure Registry (WET-HF Registry), a multicenter, prospective cohort registry from 2005 through 2014. We assigned them to 3 categories based on body mass index (BMI): low, BMI <18.5; medium, BMI ≥18.5 and <25; and high, BMI ≥25 (n=182/915/400). The clinical endpoint was all-cause death or readmission for acute decompensated HF. During 406 days of follow-up (IQR, 116-739 days), AF was associated with a higher risk of the endpoint in the HF with preserved ejection fraction (HFpEF) group (P<0.001, log-rank test), but not in the HF with reduced EF (HFrEF) group. AF was associated with a higher risk of the endpoint in low and medium BMI patients with HFpEF (P=0.016 and 0.009, respectively). On Multivariate Cox proportional hazards analysis, AF was an independent predictor of the endpoint in patients with BMI <25 from the HFpEF group (hazard ratio, 1.74; 95% CI: 1.21-2.54, P=0.003), but not in the other subgroups. AF had a negative impact on clinical outcome in non-obese patients with HFpEF.

Influence of atrial fibrillation on the mortality of patients with heart failure with preserved ejection fraction.

PubMed

Franco, Jonathan; Formiga, Francesc; Cepeda, Jose; Llacer, Pau; Arévalo-Lorido, Juan; Cerqueiro, Jose; González-Franco, Alvaro; Epelde, Francesc; Manzano, Luis; Montero Pérez-Barquero, Manuel

2018-05-23

The impact of atrial fibrillation (AF) on the prognosis of heart failure with preserved ejection fraction (HFpEF) is still the subject of debate. We analysed the influence of AF on the prognosis on mortality and readmission in patients with HFpEF. Prospective observational study in 1,971 patients with HFpEF, who were admitted for acute heart failure. Patients were divided into 2 groups according to the presence or absence of AF. We analysed mortality, readmissions and combined mortality/readmissions at one year follow-up. A total of 1,177 (59%) patients had AF, mean age 80.3 (7.8) years and 1,233 (63%) were women. Patients with HFpEF and AF were older, female, greater valvular aetiology and lower comorbidity measured by the Charlson index. At the one year follow-up, 430 (22%) patients had died and 840 (43%) had been readmitted. In the 2 groups analysed, there was no difference in all-cause mortality (22 vs. 21%; P=.739, AF vs. no-AF, respectively) or cardiovascular causes (9.6 vs. 8.2%; P=.739, AF vs. no-AF, respectively). In the multivariable analysis, factors associated with higher mortality were: age, male, valvular aetiology, uric acid, and comorbidity. In the analysis of the subgroup with HFpEF with AF, the presence of chronic AF compared to de novo AF was associated with higher mortality (HR 1,716; 95% CI 1,099-2,681; P=.018). In patients with HFpEF, the presence of AF is frequent. During the one-year follow-up, the presence of AF does not influence mortality or readmissions in patients with HFpEF. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Heart Failure With Preserved Ejection Fraction in Diabetes: Mechanisms and Management.

PubMed

Meagher, Patrick; Adam, Mohamed; Civitarese, Robert; Bugyei-Twum, Antoinette; Connelly, Kim A

2018-05-01

Diabetes mellitus (DM) is a major cause of heart failure in the Western world, either secondary to coronary artery disease or from a distinct entity known as "diabetic cardiomyopathy." Furthermore, heart failure with preserved ejection fraction (HFpEF) is emerging as a significant clinical problem for patients with DM. Current clinical data suggest that between 30% and 40% of patients with HFpEF suffer from DM. The typical structural phenotype of the HFpEF heart consists of endothelial dysfunction, increased interstitial and perivascular fibrosis, cardiomyocyte stiffness, and hypertrophy along with advanced glycation end products deposition. There is a myriad of mechanisms that result in the phenotypical HFpEF heart including impaired cardiac metabolism and substrate utilization, altered insulin signalling leading to protein kinase C activation, advanced glycated end products deposition, prosclerotic cytokine activation (eg, transforming growth factor-β activation), along with impaired nitric oxide production from the endothelium. Moreover, recent investigations have focused on the role of endothelial-myocyte interactions. Despite intense research, current therapeutic strategies have had little effect on improving morbidity and mortality in patients with DM and HFpEF. Possible explanations for this include a limited understanding of the role that direct cell-cell communication or indirect cell-cell paracrine signalling plays in the pathogenesis of DM and HFpEF. Additionally, integrins remain another important mediator of signals from the extracellular matrix to cells within the failing heart and might play a significant role in cell-cell cross-talk. In this review we discuss the characteristics and mechanisms of DM and HFpEF to stimulate potential future research for patients with this common, and morbid condition. Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Effect of Selective Heart Rate Slowing in Heart Failure With Preserved Ejection Fraction.

PubMed

Pal, Nikhil; Sivaswamy, Nadiya; Mahmod, Masliza; Yavari, Arash; Rudd, Amelia; Singh, Satnam; Dawson, Dana K; Francis, Jane M; Dwight, Jeremy S; Watkins, Hugh; Neubauer, Stefan; Frenneaux, Michael; Ashrafian, Houman

2015-11-03

Heart failure with preserved ejection fraction (HFpEF) is associated with significant morbidity and mortality but is currently refractory to therapy. Despite limited evidence, heart rate reduction has been advocated, on the basis of physiological considerations, as a therapeutic strategy in HFpEF. We tested the hypothesis that heart rate reduction improves exercise capacity in HFpEF. We conducted a randomized, crossover study comparing selective heart rate reduction with the If blocker ivabradine at 7.5 mg twice daily versus placebo for 2 weeks each in 22 symptomatic patients with HFpEF who had objective evidence of exercise limitation (peak oxygen consumption at maximal exercise [o2 peak] <80% predicted for age and sex). The result was compared with 22 similarly treated matched asymptomatic hypertensive volunteers. The primary end point was the change in o2 peak. Secondary outcomes included tissue Doppler-derived E/e' at echocardiography, plasma brain natriuretic peptide, and quality-of-life scores. Ivabradine significantly reduced peak heart rate compared with placebo in the HFpEF (107 versus 129 bpm; P<0.0001) and hypertensive (127 versus 145 bpm; P=0.003) cohorts. Ivabradine compared with placebo significantly worsened the change in o2 peak in the HFpEF cohort (-2.1 versus 0.9 mL·kg(-1)·min(-1); P=0.003) and significantly reduced submaximal exercise capacity, as determined by the oxygen uptake efficiency slope. No significant effects on the secondary end points were discernable. Our observations bring into question the value of heart rate reduction with ivabradine for improving symptoms in a HFpEF population characterized by exercise limitation. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02354573. © 2015 The Authors.

Renal impairment and heart failure with preserved ejection fraction early post-myocardial infarction

PubMed Central

Jorapur, Vinod; Lamas, Gervasio A; Sadowski, Zygmunt P; Reynolds, Harmony R; Carvalho, Antonio C; Buller, Christopher E; Rankin, James M; Renkin, Jean; Steg, Philippe Gabriel; White, Harvey D; Vozzi, Carlos; Balcells, Eduardo; Ragosta, Michael; Martin, C Edwin; Srinivas, Vankeepuram S; Wharton III, William W; Abramsky, Staci; Mon, Ana C; Kronsberg, Shari S; Hochman, Judith S

2010-01-01

AIM: To study if impaired renal function is associated with increased risk of peri-infarct heart failure (HF) in patients with preserved ejection fraction (EF). METHODS: Patients with occluded infarct-related arteries (IRAs) between 1 to 28 d after myocardial infarction (MI) were grouped into chronic kidney disease (CKD) stages based on estimated glomerular filtration rate (eGFR). Rates of early post-MI HF were compared among eGFR groups. Logistic regression was used to explore independent predictors of HF. RESULTS: Reduced eGFR was present in 71.1% of 2160 patients, with significant renal impairment (eGFR < 60 mL/min every 1.73 m2) in 14.8%. The prevalence of HF was higher with worsening renal function: 15.5%, 17.8% and 29.4% in patients with CKD stages 1, 2 and 3 or 4, respectively (P < 0.0001), despite a small absolute difference in mean EF across eGFR groups: 48.2 ± 10.0, 47.9 ± 11.3 and 46.2 ± 12.1, respectively (P = 0.02). The prevalence of HF was again higher with worsening renal function among patients with preserved EF: 10.1%, 13.6% and 23.6% (P < 0.0001), but this relationship was not significant among patients with depressed EF: 27.1%, 26.2% and 37.9% (P = 0.071). Moreover, eGFR was an independent correlate of HF in patients with preserved EF (P = 0.003) but not in patients with depressed EF (P = 0.181). CONCLUSION: A significant proportion of post-MI patients with occluded IRAs have impaired renal function. Impaired renal function was associated with an increased rate of early post-MI HF, the association being strongest in patients with preserved EF. These findings have implications for management of peri-infarct HF. PMID:20885993

Impaired Skeletal Muscle Vasodilation during Exercise in Heart Failure with Preserved Ejection Fraction

PubMed Central

Lee, Joshua F.; Barrett-O’Keefe, Zachary; Nelson, Ashley D.; Garten, Ryan S.; Ryan, John J.; Nativi-Nicolau, Jose N.; Richardson, Russell S.; Wray, D. Walter

2016-01-01

Background Exercise intolerance is a hallmark symptom of heart failure patients with preserved ejection fraction (HFpEF), which may be related to an impaired ability to appropriately increase blood flow to the exercising muscle. Methods We evaluated leg blood flow (LBF, ultrasound Doppler), heart rate (HR), stroke volume (SV), cardiac output (CO), and mean arterial blood pressure (MAP, photoplethysmography) during dynamic, single leg knee-extensor (KE) exercise in HFpEF patients (n = 21; 68 ± 2 yrs) and healthy controls (n = 20; 71 ± 2 yrs). Results HFpEF patients exhibited a marked attrition during KE exercise, with only 60% able to complete the exercise protocol. In participants who completed all exercise intensities (0-5-10-15W; HFpEF, n = 13; Controls, n = 16), LBF was not different at 0W and 5W, but was 15-25% lower in HFpEF compared to controls at 10W and 15W (P < 0.001). Likewise, leg vascular conductance (LVC), an index of vasodilation, was not different at 0W and 5W, but was 15-20% lower in HFpEF compared to controls at 10W and 15W (P < 0.05). In contrast to these peripheral deficits, exercise-induced changes in central variables (HR, SV, CO), as well as MAP, were similar between groups. Conclusions These data reveal a marked reduction in LBF and LVC in HFpEF patients during exercise that cannot be attributed to a disease-related alteration in central hemodynamics, suggesting that impaired vasodilation in the exercising skeletal muscle vasculature may play a key role in the exercise intolerance associated with this patient population. PMID:26970959

Clinical tolerability of generic versus brand beta blockers in heart failure with reduced left ventricular ejection fraction: a retrospective cohort from heart failure clinic.

PubMed

Chanchai, Rattanachai; Kanjanavanit, Rungsrit; Leemasawat, Krit; Amarittakomol, Anong; Topaiboon, Paleerat; Phrommintikul, Arintaya

2018-01-01

Background: Beta-blockers have been shown to decrease mortality and morbidity in heart failure with reduced ejection fraction (HFrEF) patients. However, the side effects are also dose-related, leading to the underdosing. Cost constraint may be one of the limitations of appropriate beta-blocker use; this can be improved with generic drugs. However, the effects in real life practice have not been investigated. Methods and results: This study aimed to compare the efficacy and safety of generic and brand beta-blockers in HFrEF patients. We performed a retrospective cohort analysis in HFrEF patients who received either generic or brand beta-blocker in Chiang Mai Heart Failure Clinic. The primary endpoint was the proportion of patients who received at least 50% target dose of beta-blocker between generic and brand beta-blockers. Adverse events were secondary endpoints. 217 patients (119 and 98 patients received generic and brand beta-blocker, respectively) were enrolled. There were no differences between groups regarding age, gender, etiology of heart failure, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF), rate of receiving angiotensin converting enzyme inhibitor (ACEI), angiotensin recepter blocker (ARB), or spironolactone. Patients receiving brand beta-blockers had lower resting heart rate at baseline (74.9 and 84.2 bpm, p  = .001). Rate of achieved 50% target dose and target daily dose did not differ between groups (40.4 versus 44.5% and 48.0 versus 55.0%, p  > .05, respectively). Rate of side effects was not different between groups (32.3 versus 29.5%, p  > .05) and the most common side effect was hypotension. Conclusion: This study demonstrated that beta-blocker tolerability was comparable between brand and generic formulations. Generic or brand beta-blockers should be prescribed to HFrEF patients who have no contraindications.

Clinical tolerability of generic versus brand beta blockers in heart failure with reduced left ventricular ejection fraction: a retrospective cohort from heart failure clinic

PubMed Central

Chanchai, Rattanachai; Kanjanavanit, Rungsrit; Leemasawat, Krit; Amarittakomol, Anong; Topaiboon, Paleerat; Phrommintikul, Arintaya

2018-01-01

Abstract Background: Beta-blockers have been shown to decrease mortality and morbidity in heart failure with reduced ejection fraction (HFrEF) patients. However, the side effects are also dose-related, leading to the underdosing. Cost constraint may be one of the limitations of appropriate beta-blocker use; this can be improved with generic drugs. However, the effects in real life practice have not been investigated. Methods and results: This study aimed to compare the efficacy and safety of generic and brand beta-blockers in HFrEF patients. We performed a retrospective cohort analysis in HFrEF patients who received either generic or brand beta-blocker in Chiang Mai Heart Failure Clinic. The primary endpoint was the proportion of patients who received at least 50% target dose of beta-blocker between generic and brand beta-blockers. Adverse events were secondary endpoints. 217 patients (119 and 98 patients received generic and brand beta-blocker, respectively) were enrolled. There were no differences between groups regarding age, gender, etiology of heart failure, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF), rate of receiving angiotensin converting enzyme inhibitor (ACEI), angiotensin recepter blocker (ARB), or spironolactone. Patients receiving brand beta-blockers had lower resting heart rate at baseline (74.9 and 84.2 bpm, p = .001). Rate of achieved 50% target dose and target daily dose did not differ between groups (40.4 versus 44.5% and 48.0 versus 55.0%, p > .05, respectively). Rate of side effects was not different between groups (32.3 versus 29.5%, p > .05) and the most common side effect was hypotension. Conclusion: This study demonstrated that beta-blocker tolerability was comparable between brand and generic formulations. Generic or brand beta-blockers should be prescribed to HFrEF patients who have no contraindications. PMID:29379674

Effectiveness of a patient education programme in heart failure with preserved ejection fraction: Results from the ODIN cohort study using propensity score matching.

PubMed

Agrinier, Nelly; Schockmel, Matthieu; Thilly, Nathalie; Laborde-Castérot, Hervé; Jourdain, Patrick; Alla, François; Leclercq, Christophe; Dany, François; Druelle, Justine; Drouet, Emilie; Mulak, Geneviève; Juillière, Yves

2018-01-01

Patient education programmes (PEP) are recommended for patients with heart failure but have not been specifically assessed in heart failure with preserved ejection fraction (HFpEF). To assess the effectiveness of a structured PEP in reducing all-cause mortality in patients with HFpEF. Patients with HFpEF were selected from the ODIN cohort, designed to assess PEP effectiveness in patients with HF whatever their ejection fraction, included from 2007 to 2010, and followed up until 2013. Baseline sociodemographic, clinical, biological and therapeutic characteristics were collected. At inclusion, patients were invited to participate in the PEP, which consisted of educational diagnosis, education sessions and final evaluation. Education focused on HF pathophysiology and medication, symptoms of worsening HF, dietary recommendations and management of exercise. Propensity score matching and Cox models were performed. Of 849 patients with HFpEF, 572 (67.4%) participated in the PEP and 277 (32.6%) did not. Patients who participated in the PEP were younger (67.0±13.1 vs 76.1±13.2 years; standardized difference [StDiff] =-54.6%), less often women (39.7% vs 48.4%; StDiff =-17.6%) and presented more often with hypercholesterolaemia (55.2% vs 35.2%; StDiff 41.2%), smoking (35.1% vs 28.7%; StDiff 13.8%), alcohol abuse (14.1% vs 8.9%; StDiff 16.5%) and ischaemic HF (38.7% vs 29.2%; StDiff 20.0%) than those who did not; they also presented with better clinical cardiovascular variables. After propensity score matching, baseline characteristics were balanced, except hypertension (postmatch StDiff 19.1%). The PEP was associated with lower all-cause mortality (pooled hazard ratio 0.70, 95% confidence interval 0.49-0.99; P=0.042). This association remained significant after adjustment for hypertension (adjusted pooled hazard ratio 0.68, 95% confidence interval 0.48-0.97; P=0.036). In this investigation, a structured PEP was associated with lower all-cause mortality. Patient education might be considered an effective treatment in patients with HFpEF. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Change the management of patients with heart failure: Rationale and design of the CHAMP-HF registry.

PubMed

DeVore, Adam D; Thomas, Laine; Albert, Nancy M; Butler, Javed; Hernandez, Adrian F; Patterson, J Herbert; Spertus, John A; Williams, Fredonia B; Turner, Stuart J; Chan, Wing W; Duffy, Carol I; McCague, Kevin; Mi, Xiaojuan; Fonarow, Gregg C

2017-07-01

Heart failure (HF) with reduced ejection fraction (HFrEF) is a common and costly condition that diminishes patients' health status and confers a poor prognosis. Despite the availability of multiple guideline-recommended pharmacologic and cardiac device therapies for patients with chronic HFrEF, outcomes remain suboptimal. Currently, there is limited insight into the rationale underlying clinical decisions by health care providers and patient factors that guide the use and intensity of outpatient HF treatments. A better understanding of current practice patterns has the potential to improve patients' outcomes. The CHAnge the Management of Patients with Heart Failure (CHAMP-HF) registry will evaluate the care and outcomes of patients with chronic HFrEF by assessing real-world treatment patterns, as well as the reasons for and barriers to medication treatment changes. CHAMP-HF will enroll approximately 5,000 patients with chronic HFrEF (left ventricular ejection fraction ≤40%) at approximately 150 US sites, and patients will be followed for a maximum duration of 24 months. Participating sites will collect data from both providers (HF history, examination findings, results of diagnostic studies, pharmacotherapy treatment patterns, decision-making factors, and clinical outcomes) and patients (medication adherence and patient-reported outcomes). The CHAMP-HF registry will provide a unique opportunity to study practice patterns and the adoption of new HF therapies across a diverse mix of health care providers and outpatient practices in the United States that care for HFrEF patients. Copyright © 2017 Elsevier Inc. All rights reserved.

The Nitrate-nitrite-NO pathway and its implications for Heart Failure and Preserved Ejection Fraction

PubMed Central

Chirinos, Julio A.; Zamani, Payman

2016-01-01

The pathogenesis of exercise intolerance in patients with heart failure and preserved ejection fraction (HFpEF) is likely multifactorial. In addition to cardiac abnormalities (diastolic dysfunction, abnormal contractile reserve, chronotropic incompetence), several peripheral abnormalities are likely to be involved. These include abnormal pulsatile hemodynamics, abnormal arterial vasodilatory responses to exercise, and abnormal peripheral O2 delivery, extraction and utilization. The nitrate-nitrite-NO pathway is emerging as a potential target to modify key physiologic abnormalities, including late systolic LV load from arterial wave reflections (which has deleterious short- and long-term consequences for the LV), arterial vasodilatory reserve, muscle O2 delivery, and skeletal muscle mitochondrial function. In a recently completed randomized trial, the administration of a single dose of exogenous inorganic nitrate has been shown exert various salutary arterial hemodynamic effects, ultimately leading to enhanced aerobic capacity in patients with HFpEF. These effects have the potential for both immediate improvements in exercise tolerance and for long-term “disease-modifying” effects. In this review, we provide an overview of key mechanistic contributors to exercise intolerance in HFpEF, and of the potential therapeutic role of drugs that target the nitrate-nitrite-NO pathway. PMID:26792295

[Sacubitril/valsartan, a new and effective treatment for heart failure with reduced ejection fraction].

PubMed

Senni, Michele; Trimarco, Bruno; Emdin, Michele; De Biase, Luciano

2017-01-01

Despite significant therapeutic advances, patients with chronic heart failure and reduced ejection fraction (HFrEF) remain at high risk for heart failure progression and death. The PARADIGM-HF study, the largest outcome trial in HFrEF, has shown improved cardiovascular outcomes with sacubitril/valsartan (Entresto®, Novartis), previously known as LCZ696, compared with angiotensin-converting enzyme (ACE) inhibitor therapy, possibly leading us to a new era for heart failure treatment. Sacubitril/valsartan represents a first-in-class drug acting through inhibition of angiotensin receptor and neprilysin, thus modulating the renin-angiotensin-aldosterone system and vasoactive substances such as natriuretic peptides. This approach can be considered a "paradigm shift" from neurohumoral inhibition to neurohumoral modulation. Based on the PARADIGM-HF results, the European Society of Cardiology and the American Heart Association/American College of Cardiology guidelines proposed a substitution of ACE-inhibitor/angiotensin receptor blocker therapy rather than an "add-on" strategy in HFrEF. Sacubitril/valsartan can be considered a milestone in cardiovascular therapy, like aspirin, statins, beta-blockers. Of course there are many questions that arise spontaneously from this trial, three recognized experts can help us to answer them.

Left ventricular fluid dynamics in heart failure: echocardiographic measurement and utilities of vortex formation time.

PubMed

Poh, Kian Keong; Lee, Li Ching; Shen, Liang; Chong, Eric; Tan, Yee Leng; Chai, Ping; Yeo, Tiong Cheng; Wood, Malissa J

2012-05-01

In clinical heart failure (HF), inefficient propagation of blood through the left ventricle (LV) may result from suboptimal vortex formation (VF) ability of the LV during early diastole. We aim to (i) validate echocardiographic-derived vortex formation time (adapted) (VFTa) in control subjects and (ii) examine its utility in both systolic and diastolic HF. Transthoracic echocardiography was performed in 32 normal subjects and in 130 patients who were hospitalized with HF [91, reduced ejection fraction (rEF) and 39, preserved ejection fraction (pEF)]. In addition to biplane left ventricular ejection fraction (LVEF) and conventional parameters, the Tei index and tissue Doppler (TD) indices were measured. VFTa was obtained using the formula: 4 × (1 - β)/π × α³ × LVEF, where β is the fraction of total transmitral diastolic stroke volume contributed by atrial contraction (assessed by time velocity integral of the mitral E- and A-waves) and α is the biplane end-diastolic volume (EDV)(1/3) divided by mitral annular diameter during early diastole. VFTa was correlated with demographic, cardiac parameters, and a composite clinical endpoint comprising cardiac death and repeat hospitalization for HF. Mean VFTa was 2.67 ± 0.8 in control subjects; reduced in HF, preserved EF HF, 2.21 ± 0.8; HF with reduced EF, 1.25 ± 0.6 (P< 0.001). It was not affected by age, gender, body surface area but was correlated positively with TD early diastolic myocardial velocities (E', septal, r = 0.46; lateral, r = 0.43), systolic myocardial velocities (S', septal, r = 0.47; lateral, r = 0.41), and inversely with the Tei index (r = -0.41); all Ps < 0.001. Sixty-two HF patients (49%) met the composite endpoint. VFTa of <1.32 was associated with significantly reduced event-free survival (Kaplan Meier log rank = 16.3, P= 0.0001) and predicted the endpoint with a sensitivity and specificity of 65 and 72%, respectively. VFTa, a dimensionless index, incorporating LV geometry, systolic and diastolic parameters, may be useful in the diagnosis and prognosis of HF.

A Critical Evaluation of the Representation of Black Patients With Heart Failure and Preserved Ejection Fraction in Clinical Trials: A Literature Review.

PubMed

Lekavich, Carolyn L; Barksdale, Debra J

2016-01-01

In the United States, heart failure costs $34.4 billion annually and is associated with a mortality rate of 20% within 5 years of diagnosis. Heart failure preserved ejection fraction (HFpEF) accounts for 50% of all hospital admissions for heart failure. Black patients develop HFpEF at a significantly earlier age than do white patients, and the 5-year mortality rate for blacks with HFpEF is 30% to 44% higher compared with white patients. Current trials may not represent black patients proportionately to the general population. The primary aim of this literature review was to critically evaluate the representation of black patients in HFpEF trials and propose solutions for future research. PubMed and CINAHL were queried for peer-reviewed journal articles from 1997 to 2014 using 2 sets of search terms that included HFpEF or preserved left ventricular function and all relevant search terms for black patients. Initially, 182 articles were identified; however, after exclusionary criteria were applied, 22 articles remained. After critical review of each article for relevance, a total of 9 articles remained for the review. For the 9 trials reviewed including a total of 63,065 patients with HFpEF, 10,436 (17%) of the patients were black. Three of the 9 trials included less than 10% black patients, 4 trials included 10% to 20% black patients, and 2 trials included greater than 20% black patients. In 2 studies, the percentage of black patients in the HFpEF trial (13% and 17%) was significantly less than the percentage of black patients in the general regional population (53% and 39%), respectively. Although the mortality rate for black patients with HFpEF is 30% to 45% higher than the rate for white patients, 2 of the 9 studies did not have a representative sample of the general HFpEF population and none of the studies reported the objective of establishing a representative study population.

Quantitation of left ventricular ejection fraction reserve from early gated regadenoson stress Tc-99m high efficiency SPECT

PubMed Central

Brodov, Yafim; Fish, Mathews; Rubeaux, Mathieu; Otaki, Yuka; Gransar, Heidi; Lemley, Mark; Gerlach, Jim; Berman, Daniel; Germano, Guido; Slomka, Piotr

2016-01-01

Background Ejection fraction (EF) reserve has been found to be a useful adjunct for identifying high risk coronary artery disease in cardiac positron emission tomography (PET). We aimed to evaluate EF reserve obtained from technetium-99m sestamibi (Tc-99m) high-efficiency (HE) SPECT. Methods Fifty patients (mean age 69 y) undergoing regadenoson same-day rest (8–11 mCi)/stress (32–42mCi) Tc-99m gated HE SPECT were enrolled. Stress imaging was started one min after sequential intravenous regadenoson 0.4mg and Tc-99m injection, and was composed of five 2 min supine gated acquisitions followed by two 4 min supine and upright images. Ischemic total perfusion deficit (ITPD) ≥ 5 % was considered as significant ischemia. Results Significantly lower mean EF reserve was obtained in the 5th and 9th min after regadenoson bolus in patients with significant ischemia versus patients without (5th min: −4.2 ± 4.6% vs. 1.3 ± 6.6%, p = 0.006; 9th min: −2.7 ± 4.8% vs. 2.0 ± 6.6%, p = 0.03). Conclusions Negative EF reserve obtained between 5th and 9th min of regadenoson stress demonstrated best concordance with significant ischemia and may be a promising tool for detection of myocardial stunning with Tc-99m HE-SPECT. PMID:27387521

Non-Ischemic Heart Failure With Reduced Ejection Fraction Is Associated With Altered Intestinal Microbiota.

PubMed

Katsimichas, Themistoklis; Ohtani, Tomohito; Motooka, Daisuke; Tsukamoto, Yasumasa; Kioka, Hidetaka; Nakamoto, Kei; Konishi, Shozo; Chimura, Misato; Sengoku, Kaoruko; Miyawaki, Hiroshi; Sakaguchi, Taiki; Okumura, Ryu; Theofilis, Konstantinos; Iida, Tetsuya; Takeda, Kiyoshi; Nakamura, Shota; Sakata, Yasushi

2018-05-25

Research suggests that heart failure with reduced ejection fraction (HFrEF) is a state of systemic inflammation that may be triggered by microbial products passing into the bloodstream through a compromised intestinal barrier. However, whether the intestinal microbiota exhibits dysbiosis in HFrEF patients is largely unknown.Methods and Results:Twenty eight non-ischemic HFrEF patients and 19 healthy controls were assessed by 16S rRNA analysis of bacterial DNA extracted from stool samples. After processing of sequencing data, bacteria were taxonomically classified, diversity indices were used to examine microbial ecology, and relative abundances of common core genera were compared between groups. Furthermore, we predicted gene carriage for bacterial metabolic pathways and inferred microbial interaction networks on multiple taxonomic levels.Bacterial communities of both groups were dominated by the Firmicutes and Bacteroidetes phyla. The most abundant genus in both groups wasBacteroides. Although α diversity did not differ between groups, ordination by β diversity metrics revealed a separation of the groups across components of variation.StreptococcusandVeillonellawere enriched in the common core microbiota of patients, whileSMB53was depleted. Gene families in amino acid, carbohydrate, vitamin, and xenobiotic metabolism showed significant differences between groups. Interaction networks revealed a higher degree of correlations between bacteria in patients. Non-ischemic HFrEF patients exhibited multidimensional differences in intestinal microbial communities compared with healthy subjects.

Quantitation of left ventricular ejection fraction reserve from early gated regadenoson stress Tc-99m high-efficiency SPECT.

PubMed

Brodov, Yafim; Fish, Mathews; Rubeaux, Mathieu; Otaki, Yuka; Gransar, Heidi; Lemley, Mark; Gerlach, Jim; Berman, Daniel; Germano, Guido; Slomka, Piotr

2016-12-01

Ejection fraction (EF) reserve has been found to be a useful adjunct for identifying high risk coronary artery disease in cardiac positron emission tomography (PET). We aimed to evaluate EF reserve obtained from technetium-99m sestamibi (Tc-99m) high-efficiency (HE) SPECT. Fifty patients (mean age 69 years) undergoing regadenoson same-day rest (8-11 mCi)/stress (32-42 mCi) Tc-99m gated HE SPECT were enrolled. Stress imaging was started 1 minute after sequential intravenous regadenoson .4 mg and Tc-99m injections, and was composed of five 2 minutes supine gated acquisitions followed by two 4 minutes supine and upright images. Ischemic total perfusion deficit (ITPD) ≥5 % was considered as significant ischemia. Significantly lower mean EF reserve was obtained in the 5th and 9th minute after regadenoson bolus in patients with significant ischemia vs patients without (5th minute: -4.2 ± 4.6% vs 1.3 ± 6.6%, P = .006; 9th minute: -2.7 ± 4.8% vs 2.0 ± 6.6%, P = .03). Negative EF reserve obtained between 5th and 9th minutes of regadenoson stress demonstrated best concordance with significant ischemia and may be a promising tool for detection of transient ischemic functional changes with Tc-99m HE-SPECT.

High Right Ventricular Stroke Work Index Is Associated with Worse Kidney Function in Patients with Heart Failure with Preserved Ejection Fraction.

PubMed

Kanjanahattakij, Napatt; Sirinvaravong, Natee; Aguilar, Francisco; Agrawal, Akanksha; Krishnamoorthy, Parasuram; Gupta, Shuchita

2018-01-01

In patients with heart failure with preserved ejection fraction (HFpEF), worse kidney function is associated with worse overall cardiac mechanics. Right ventricular stroke work index (RVSWI) is a parameter of right ventricular function. The aim of our study was to determine the relationship between RVSWI and glomerular filtration rate (GFR) in patients with HFpEF. This was a single-center cross-sectional study. HFpEF is defined as patients with documented heart failure with ejection fraction > 50% and pulmonary wedge pressure > 15 mm Hg from right heart catheterization. RVSWI (normal value 8-12 g/m/beat/m2) was calculated using the formula: RVSWI = 0.0136 × stroke volume index × (mean pulmonary artery pressure - mean right atrial pressure). Univariate and multivariate linear regression analysis was performed to study the correlation between RVSWI and GFR. Ninety-one patients were included in the study. The patients were predominantly female (n = 64, 70%) and African American (n = 61, 67%). Mean age was 66 ± 12 years. Mean GFR was 59 ± 35 mL/min/1.73 m2. Mean RVSWI was 11 ± 6 g/m/beat/m2. Linear regression analysis showed that there was a significant independent inverse relationship between RVSWI and GFR (unstandardized coefficient = -1.3, p = 0.029). In the subgroup with combined post and precapillary pulmonary hypertension (Cpc-PH) the association remained significant (unstandardized coefficient = -1.74, 95% CI -3.37 to -0.11, p = 0.04). High right ventricular workload indicated by high RVSWI is associated with worse renal function in patients with Cpc-PH. Further prospective studies are needed to better understand this association. © 2018 S. Karger AG, Basel.

Are the effects of drugs to prevent and to treat heart failure always concordant? The statin paradox and its implications for understanding the actions of antidiabetic medications.

PubMed

Packer, Milton

2018-03-22

Most treatments for chronic heart failure are effective both in preventing its onset and reducing its progression. However, statins prevent the development of heart failure, but they do not decrease morbidity and mortality in those with established heart failure. This apparent discordance cannot be explained by an effect to prevent interval myocardial infarctions. Instead, it seems that the disease that statins were preventing in trials of patients with a metabolic disorder was different from the disease that they were treating in trials of chronic heart failure. The most common phenotype of heart failure in patients with obesity and diabetes is heart failure with a preserved ejection fraction (HFpEF). In this disorder, the anti-inflammatory effects of statins might ameliorate myocardial fibrosis and cardiac filling abnormalities, but these actions may have little relevance to patients with heart failure and a reduced ejection fraction (HFrEF), whose primary derangement is cardiomyocyte loss and stretch. These distinctions may explain why statins were ineffective in trials that focused on HFrEF, but have been reported to produce with favourable effects in observational studies of HFpEF. Similarly, selective cytokine antagonists were ineffective in HFrEF, but have been associated with benefits in HFpEF. These observations may have important implications for our understanding of the effects of antihyperglycaemic medications. Glucagon-like peptide-1 receptor agonists have had neutral effects on heart failure events in people at risk for HFpEF, but have exerted deleterious actions in HFrEF. Similarly, sodium-glucose co-transporter 2 inhibitors, which exert anti-inflammatory effects and reduce heart failure events in patients who are prone to HFpEF, may not be effective in HFrEF. The distinctions between HFrEF and HFpEF may explain why the effects of drugs on heart failure events in diabetes trials may not be relevant to their use in patients with systolic dysfunction. © 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.

Comorbidities, risk factors and outcomes in patients with heart failure and an ejection fraction of more than or equal to 40% in primary care- and hospital care-based outpatient clinics.

PubMed

Eriksson, B; Wändell, P; Dahlström, U; Näsman, P; Lund, L H; Edner, M

2018-06-01

The aim of this study is to describe patients with heart failure and an ejection fraction (EF) of more than or equal to 40%, managed in both Primary- and Hospital based outpatient clinics separately with their prognosis, comorbidities and risk factors. Further to compare the heart failure medication in the two groups. We used the prospective Swedish Heart Failure Registry to include 9654 out-patients who had HF and EF ≥40%, 1802 patients were registered in primary care and 7852 in hospital care. Descriptive statistical tests were used to analyze base line characteristics in the two groups and multivariate logistic regression analysis to assess mortality rate in the groups separately. The prospective Swedish Heart Failure Registry. Patients with heart failure and an ejection fraction (EF) of more than or equal to 40%. Comorbidities, risk factors and mortality. Mean-age was 77.5 (primary care) and 70.3 years (hospital care) p < 0.0001, 46.7 vs. 36.3% women respectively (p < 0.0001) and EF ≥50% 26.1 vs. 13.4% (p < 0.0001). Co-morbidities were common in both groups (97.2% vs. 92.3%), the primary care group having more atrial fibrillation, hypertension, ischemic heart disease and COPD. According to the multivariate logistic regression analysis smoking, COPD and diabetes were the most important independent risk factors in the primary care group and valvular disease in the hospital care group. All-cause mortality during mean follow-up of almost 4 years was 31.5% in primary care and 27.8% in hospital care. One year-mortality rates were 7.8%, and 7.0% respectively. Any co-morbidity was noted in 97% of the HF-patients with an EF of more than or equal to 40% managed at primary care based out-patient clinics and these patients had partly other independent risk factors than those patients managed in hospital care based outpatients clinics. Our results indicate that more attention should be payed to manage COPD in the primary care group. KEY POINTS 97% of heart failure patients with an ejection fraction of more than or equal to 40% managed at primary care based out-patient clinics had any comorbidity. Patients in primary care had partly other independent risk factors than those in hospital care. All-cause mortality during mean follow-up of almost 4 years was higher in primary care compared to hospital care. In matched HF-patients RAS-antagonists, beta-blockers as well as the combination of the two drugs were more seldom prescribed when managed in primary care compared with hospital care.

Is the PARADIGM-HF cohort representative of the real-world heart failure patient population?

PubMed

Rodrigues, Gustavo; Tralhão, António; Aguiar, Carlos; Freitas, Pedro; Ventosa, António; Mendes, Miguel

2018-06-01

A new drug with prognostic impact on heart failure, sacubitril/valsartan, has been introduced in current guidelines. However, randomized trial results can be compromised by lack of representativeness. We aimed to assess the representativeness of the PARADIGM-HF trial in a real-world population of patients with heart failure. We reviewed the records of 196 outpatients followed in a heart failure clinic between January 2013 and December 2014. After exclusion of 44 patients with preserved ejection fraction, the inclusion and exclusion criteria of the trial were applied. Of the 152 patients with systolic heart failure, 106 lacked one or more inclusion criteria and 45 had at least one exclusion criterion. Considering only patients with ejection fraction ≤35% (HFrEF) (n=88), 43 patients lacked at least one inclusion criterion and 25 patients had at least one exclusion criterion. Combining the inclusion and exclusion criteria, 24.3% of patients with systolic HF (ejection fraction ≤50%) and 42% of patients with HFrEF would be eligible for the PARADIGM-HF trial. One in four patients with systolic HF followed in a heart failure outpatient clinic would fulfill the reference study criteria for treatment with the new drug, sacubitril/valsartan. Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Liver fibrosis score predicts mortality in heart failure patients with preserved ejection fraction.

PubMed

Yoshihisa, Akiomi; Sato, Yu; Yokokawa, Tetsuro; Sato, Takamasa; Suzuki, Satoshi; Oikawa, Masayoshi; Kobayashi, Atsushi; Yamaki, Takayoshi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Saitoh, Shu-Ichi; Takeishi, Yasuchika

2018-04-01

Heart failure with preserved ejection fraction (HFpEF) has several pathophysiological aspects, including stiffness and/or congestion of multiple organs. Poor prognosis is expected in heart failure patients with liver stiffness, which has recently been assessed by non-alcoholic fatty liver disease fibrosis score (NFS; based on aspartate aminotransferase to alanine aminotransferase ratio, platelet counts, and albumin). We aimed to investigate the impact of NFS on prognosis of HFpEF patients, with consideration for the peripheral collagen markers such as procollagen type III peptide (PIIIP), type IV collagen 7S, and hyaluronic acid. We performed a prospective observational study. Consecutive 492 hospitalized HFpEF patients were divided into four groups based on their NFS: first-fourth quartiles (n = 123). The fourth quartile group had the highest levels of PIIIP, type IV collagen 7S, hyaluronic acid, and B-type natriuretic peptide (P<0.001 each). In addition, there were significant positive correlations between PIIIP, type IV collagen 7S, hyaluronic acid, B-type natriuretic peptide, and NFS (P < 0.001 each). In the follow-up period (mean 1107 days), 93 deaths occurred. All-cause mortality increased in all four quartiles (8.1%, 12.2%, 23.6%, and 31.7%, P < 0.001). In the multivariable Cox proportional hazard analysis, NFS was an independent predictor of all-cause mortality in the HFpEF patients. NFS, a novel indicator of liver fibrosis, correlates with circulating systemic markers of fibrosis and congestion and is associated with higher all-cause mortality in HFpEF patients. NFS can be calculated simply and may be a useful tool to assess liver stiffness and prognosis in HFpEF patients. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction.

PubMed

Borlaug, Barry A; Melenovsky, Vojtech; Russell, Stuart D; Kessler, Kristy; Pacak, Karel; Becker, Lewis C; Kass, David A

2006-11-14

Nearly half of patients with heart failure have a preserved ejection fraction (HFpEF). Symptoms of exercise intolerance and dyspnea are most often attributed to diastolic dysfunction; however, impaired systolic and/or arterial vasodilator reserve under stress could also play an important role. Patients with HFpEF (n=17) and control subjects without heart failure (n=19) generally matched for age, gender, hypertension, diabetes mellitus, obesity, and the presence of left ventricular hypertrophy underwent maximal-effort upright cycle ergometry with radionuclide ventriculography to determine rest and exercise cardiovascular function. Resting cardiovascular function was similar between the 2 groups. Both had limited exercise capacity, but this was more profoundly reduced in HFpEF patients (exercise duration 180+/-71 versus 455+/-184 seconds; peak oxygen consumption 9.0+/-3.4 versus 14.4+/-3.4 mL x kg(-1) x min(-1); both P<0.001). At matched low-level workload, HFpEF subjects displayed approximately 40% less of an increase in heart rate and cardiac output and less systemic vasodilation (all P<0.05) despite a similar rise in end-diastolic volume, stroke volume, and contractility. Heart rate recovery after exercise was also significantly delayed in HFpEF patients. Exercise capacity correlated with the change in cardiac output, heart rate, and vascular resistance but not end-diastolic volume or stroke volume. Lung blood volume and plasma norepinephrine levels rose similarly with exercise in both groups. HFpEF patients have reduced chronotropic, vasodilator, and cardiac output reserve during exercise compared with matched subjects with hypertensive cardiac hypertrophy. These limitations cannot be ascribed to diastolic abnormalities per se and may provide novel therapeutic targets for interventions to improve exercise capacity in this disorder.

Does natriuretic peptide monitoring improve outcomes in heart failure patients? A systematic review and meta-analysis.

PubMed

Khan, Muhammad Shahzeb; Siddiqi, Tariq Jamal; Usman, Muhammad Shariq; Sreenivasan, Jayakumar; Fugar, Setri; Riaz, Haris; Murad, M H; Mookadam, Farouk; Figueredo, Vincent M

2018-07-15

Current guidelines do not support the use of serial natriuretic peptide (NP) monitoring for heart failure with preserved (HFpEF) or reduced ejection fraction (HFrEF) treatment, despite some studies showing benefit. We conducted an updated meta-analysis to address whether medical therapy in HFpEF or HFrEF should be titrated according to NP levels. MEDLINE, Scopus and Cochrane CENTRAL databases were searched for randomized controlled trials (RCTs) comparing NP versus guideline directed titration in HF patients through December 2017. The key outcomes of interest were mortality, HF hospitalizations and all-cause hospitalizations. Risk ratios and 95% confidence intervals were pooled using random effects model. Sub-group analyses were performed for type of NP used, average age and acute or chronic HF. Eighteen trials including 5116 patients were included. Meta-analysis showed no significant difference between the NP-guided arm versus guideline directed titration in all-cause mortality (RR = 0.91 [0.81, 1.03]; p = 0.13), HF hospitalizations (RR = 0.81 [0.65, 1.01]; p = 0.06), and all cause hospitalizations (RR = 0.93 [0.86, 1.01]; p = 0.09). The results were consistent upon subgroup analysis by biomarker type (NT-proBNP or BNP) and type of heart failure (acute or chronic and HFrEF or HFpEF). Sub-group analysis suggested that NP-guided treatment was associated with decreased all-cause hospitalizations in patients younger than 72 years of age. The available evidence suggests that NP-guided therapy provides no additional benefit over guideline directed therapy in terms of all-cause mortality and HF-related hospitalizations in acute or chronic HF patients, regardless of their ejection fraction. Copyright © 2018 Elsevier B.V. All rights reserved.

Design of the effect of adaptive servo-ventilation on survival and cardiovascular hospital admissions in patients with heart failure and sleep apnoea: the ADVENT-HF trial.

PubMed

Lyons, Owen D; Floras, John S; Logan, Alexander G; Beanlands, Robert; Cantolla, Joaquin Durán; Fitzpatrick, Michael; Fleetham, John; John Kimoff, R; Leung, Richard S T; Lorenzi Filho, Geraldo; Mayer, Pierre; Mielniczuk, Lisa; Morrison, Debra L; Ryan, Clodagh M; Series, Frederic; Tomlinson, George A; Woo, Anna; Arzt, Michael; Parthasarathy, Sairam; Redolfi, Stefania; Kasai, Takatoshi; Parati, Gianfranco; Delgado, Diego H; Bradley, T Douglas

2017-04-01

Both types of sleep-disordered breathing (SDB), obstructive and central sleep apnoea (OSA and CSA, respectively), are common in patients with heart failure and reduced ejection fraction (HFrEF). In such patients, SDB is associated with increased cardiovascular morbidity and mortality but it remains uncertain whether treating SDB by adaptive servo-ventilation (ASV) in such patients reduces morbidity and mortality. ADVENT-HF is designed to assess the effects of treating SDB with ASV on morbidity and mortality in patients with HFrEF. ADVENT-HF is a multicentre, multinational, randomized, parallel-group, open-label trial with blinded assessment of endpoints of standard medical therapy for HFrEF alone vs. with the addition of ASV in patients with HFrEF and SDB. Patients with a history of HFrEF undergo echocardiography and polysomnography. Those with a left ventricular ejection fraction ≤45% and SDB (apnoea-hypopnoea index ≥15) are eligible. SDB is stratified into OSA with ≥50% of events obstructive or CSA with >50% of events central. Those with OSA must not have excessive daytime sleepiness (Epworth score of ≤10). Patients are then randomized to receive or not receive ASV. The primary outcome is the composite of all-cause mortality, cardiovascular hospital admissions, new-onset atrial fibrillation requiring anti-coagulation but not hospitalization, and delivery of an appropriate discharge from an implantable cardioverter-defibrillator not resulting in hospitalization during a maximum follow-up time of 5 years. The ADVENT-HF trial will help to determine whether treating SDB by ASV in patients with HFrEF improves morbidity and mortality. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Automated extraction of ejection fraction for quality measurement using regular expressions in Unstructured Information Management Architecture (UIMA) for heart failure

PubMed Central

DuVall, Scott L; South, Brett R; Bray, Bruce E; Bolton, Daniel; Heavirland, Julia; Pickard, Steve; Heidenreich, Paul; Shen, Shuying; Weir, Charlene; Samore, Matthew; Goldstein, Mary K

2012-01-01

Objectives Left ventricular ejection fraction (EF) is a key component of heart failure quality measures used within the Department of Veteran Affairs (VA). Our goals were to build a natural language processing system to extract the EF from free-text echocardiogram reports to automate measurement reporting and to validate the accuracy of the system using a comparison reference standard developed through human review. This project was a Translational Use Case Project within the VA Consortium for Healthcare Informatics. Materials and methods We created a set of regular expressions and rules to capture the EF using a random sample of 765 echocardiograms from seven VA medical centers. The documents were randomly assigned to two sets: a set of 275 used for training and a second set of 490 used for testing and validation. To establish the reference standard, two independent reviewers annotated all documents in both sets; a third reviewer adjudicated disagreements. Results System test results for document-level classification of EF of <40% had a sensitivity (recall) of 98.41%, a specificity of 100%, a positive predictive value (precision) of 100%, and an F measure of 99.2%. System test results at the concept level had a sensitivity of 88.9% (95% CI 87.7% to 90.0%), a positive predictive value of 95% (95% CI 94.2% to 95.9%), and an F measure of 91.9% (95% CI 91.2% to 92.7%). Discussion An EF value of <40% can be accurately identified in VA echocardiogram reports. Conclusions An automated information extraction system can be used to accurately extract EF for quality measurement. PMID:22437073

Rationale and design of the PREFERS (Preserved and Reduced Ejection Fraction Epidemiological Regional Study) Stockholm heart failure study: an epidemiological regional study in Stockholm county of 2.1 million inhabitants.

PubMed

Linde, Cecilia; Eriksson, Maria J; Hage, Camilla; Wallén, Håkan; Persson, Bengt; Corbascio, Matthias; Lundeberg, Joakim; Maret, Eva; Ugander, Martin; Persson, Hans

2016-10-01

Heart failure (HF) with preserved (HFpEF) or reduced (HFrEF) ejection fraction is associated with poor prognosis and quality of life. While the incidence of HFrEF is declining and HF treatment is effective, HFpEF is increasing, with no established therapy. PREFERS Stockholm is an epidemiological study with the aim of improving clinical care and research in HF and to find new targets for drug treatment in HFpEF (https://internwebben.ki.se/sites/default/files/20150605_4d_research_appendix_final.pdf). Patients with new-onset HF (n = 2000) will be characterized at baseline and after 1-year follow-up by standardized protocols for clinical evaluation, echocardiography, and ECG. In one subset undergoing elective coronary bypass surgery (n = 100) and classified according to LV function, myocardial biopsies will be collected during surgery, and cardiac magnetic resonance (CMR) imaging will be performed at baseline and after 1 year. Blood and tissue samples will be stored in a biobank. We will characterize and compare new-onset HFpEF and HFrEF patients regarding clinical findings and cardiac imaging, genomics, proteomics, and transcriptomics from blood and cardiac biopsies, and by established biomarkers of fibrosis, inflammation, haemodynamics, haemostasis, and thrombosis. The data will be explored by state-of-the-art bioinformatics methods to investigate gene expression patterns, sequence variation, DNA methylation, and post-translational modifications, and using systems biology approaches including pathway and network analysis. In this epidemiological HF study with biopsy studies in a subset of patients, we aim to identify new biomarkers of disease progression and to find pathophysiological mechanisms to support explorations of new treatment regimens for HFpEF. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

The combined exercise stress echocardiography and cardiopulmonary exercise test for identification of masked heart failure with preserved ejection fraction in patients with hypertension.

PubMed

Nedeljkovic, Ivana; Banovic, Marko; Stepanovic, Jelena; Giga, Vojislav; Djordjevic-Dikic, Ana; Trifunovic, Danijela; Nedeljkovic, Milan; Petrovic, Milan; Dobric, Milan; Dikic, Nenad; Zlatar, Milan; Beleslin, Branko

2016-01-01

Heart failure with preserved ejection fraction (HFpEF) is commonly associated with hypertension (HTN). However, resting echocardiography (ECHO) can underestimate the severity of disease. Exercise stress echocardiography (ESE) and the cardiopulmonary exercise testing (CPX) appeared to be useful tests in dynamic assessment of HFpEF. The value of combined exercise stress echocardiography cardiopulmonary testing (ESE-CPX) in the identification of masked HFpEF is still undetermined. The purpose of this study was to analyse the value of the combined ESE-CPX in the identification of masked HFpEF in patients with HTN, dyspnoea and normal resting left ventricular (LV) systolic and diastolic function. We studied 87 patients with HTN, exertional dyspnoea and normal resting LV function. They all underwent ESE-CPX testing (supine bicycle, ramp protocol, 15 W/min). ECHO measurements were performed at rest, and at peak load. Achievement of peak E/e' ratio>15 was a marker for masked HFpEF. Increase of E/e'>15 occurred in 8/87 patients (9.2%) during ESE-CPX. Those patients had the lower peak VO2 (p = 0.012), the lower VO2 at anaerobic threshold (p = 0.025), the lower workload (p = 0.026), the lower peak partial pressure end tidal carbon dioxide (PetCO2) (p < 0.0001), and the higher VE/VCO2 slope (p < 0.0001) which was an independent multivariate predictor of HFpEF (p = 0.021), with the cut-off value of 32.95 according to the receiver-operator characteristic (ROC) curve (sensitivity (Sn) 100%, specificity (Sp) 90%). The combined ESE-CPX test is feasible and reliable test that can unmask HFpEF and may become an important aid in the early diagnosis of HFpEF, excluding the other causes of exertional dyspnoea. © The European Society of Cardiology 2015.

Comparison of 5-Year Outcomes After Coronary Artery Bypass Grafting in Heart Failure Patients With Versus Without Preserved Left Ventricular Ejection Fraction (from the CREDO-Kyoto CABG Registry Cohort-2).

PubMed

Marui, Akira; Nishiwaki, Noboru; Komiya, Tatsuhiko; Hanyu, Michiya; Tanaka, Shiro; Kimura, Takeshi; Sakata, Ryuzo

2015-08-15

Heart failure (HF) with reduced left ventricular (LV) ejection fraction (HFrEF) is regarded as an independent risk factor for poor outcomes after coronary artery bypass grafting (CABG). However, the impact of HF with preserved EF (HFpEF) still has been unclear. We identified 1,877 patients who received isolated CABG of 15,939 patients who underwent first coronary revascularization enrolled in the CREDO-Kyoto (Coronary REvascularization Demonstrating Outcome Study in Kyoto) Registry Cohort-2. Of them, 1,489 patients had normal LV function (LVEF >50% without a history of HF; Normal group), 236 had HFrEF (LVEF ≤50% with HF), and 152 had HFpEF (LVEF >50% with HF). Preoperative LVEF was the lowest in the HFrEF group (62 ± 12%, 36 ± 9%, and 61 ± 7% for the Normal, HFrEF, and HFpEF groups, respectively; p <0.001). Unadjusted 30-day mortality rate was the highest in the HFrEF group (0.5%, 3.0%, and 0.7%; p = 0.003). However, cumulative incidences of all-cause death at 5-year was the highest in the HFpEF group (14%, 27%, and 32%, respectively; p <0.001). After adjusting confounders, the risk of all-cause death in the HFpEF group was greater than the Normal group (hazard ratio [HR] 1.42; 95% confidence interval [CI] 1.02 to 1.97; p = 0.04). The risk of all-cause death was not different between the HFpEF and the HFrEF groups (HR 0.88; 95% CI 0.61 to 1.29; p = 0.52). In addition, the risks of cardiac death and sudden death in the HFpEF group were greater than the Normal group (HR 2.14, 95% CI 1.32 to 3.49, p = 0.002; and HR 3.60, 95% CI 1.55 to 8.36, p = 0.003, respectively), and the risks of those end points were not different between the HFrEF and the HFpEF groups. Despite low 30-day mortality rate after CABG in patients with HFpEF, HFpEF was associated with high risks of long-term death and cardiovascular events. Patients with HFpEF, as well as HFrEF, should be carefully operated and followed up. Copyright © 2015 Elsevier Inc. All rights reserved.

Intraventricular filling under increasing left ventricular wall stiffness and heart rates

NASA Astrophysics Data System (ADS)

Samaee, Milad; Lai, Hong Kuan; Schovanec, Joseph; Santhanakrishnan, Arvind; Nagueh, Sherif

2015-11-01

Heart failure with normal ejection fraction (HFNEF) is a clinical syndrome that is prevalent in over 50% of heart failure patients. HFNEF patients show increased left ventricle (LV) wall stiffness and clinical diagnosis is difficult using ejection fraction (EF) measurements. We hypothesized that filling vortex circulation strength would decrease with increasing LV stiffness irrespective of heart rate (HR). 2D PIV and hemodynamic measurements were acquired on LV physical models of varying wall stiffness under resting and exercise HRs. The LV models were comparatively tested in an in vitro flow circuit consisting of a two-element Windkessel model driven by a piston pump. The stiffer LV models were tested in comparison with the least stiff baseline model without changing pump amplitude, circuit compliance and resistance. Increasing stiffness at resting HR resulted in diminishing cardiac output without lowering EF below 50% as in HFNEF. Increasing HR to 110 bpm in addition to stiffness resulted in lowering EF to less than 50%. The circulation strength of the intraventricular filling vortex diminished with increasing stiffness and HR. The results suggest that filling vortex circulation strength could be potentially used as a surrogate measure of LV stiffness. This research was supported by the Oklahoma Center for Advancement of Science and Technology (HR14-022).

β-Blockers on Discharge From Acute Atrial Fibrillation Are Associated With Decreased Mortality and Lower Cerebrovascular Accidents in Patients With Heart Failure and Reduced Ejection Fraction.

PubMed

Abi Khalil, Charbel; Zubaid, Mohammad; Asaad, Nidal; Rashed, Wafa A; Hamad, Adel Khalifa; Singh, Rajvir; Al Suwaidi, Jassim

2018-04-01

The benefits of β-blockers in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and atrial fibrillation (AF) are controversial. The Gulf Survey of Atrial Fibrillation Events was a prospective, multinational, observational registry of consecutive patients with AF recruited from the emergency department (ED). We studied the incidence of 6- and 12-month mortality, hospitalization for HF or AF, and stroke/transient ischemic attacks (TIAs) in patients with HFrEF, in relation to β-blockers on discharge from the ED or the subsequent hospital stay. Of the 344 patients with HFrEF and AF in the GULF-SAFE, 177 patients (53%) were discharged on β-blockers. Mortality was lower in those patients compared with the non-β-blockers group at 6 and 12 months (odds ratios [ORs] 0.31, 95% CI [0.16-0.61]; OR 0.30, 95% CI [0.16-0.55]; P = .001 for both, respectively), so was the risk of stroke/TIAs. However, hospitalizations for AF increased in the β-blockers group. Even after adjustment for several risk variables in 2 different models, the beneficial effect of β-blockers on mortality persisted, at the cost of more hospitalization for AF.

Effect of exercise training program in post-CRET post-CABG patients with normal and subnormal ejection fraction (EF > 50% or < 50%) after coronary artery bypass grafting surgery.

PubMed

Ansari, Basit; Qureshi, Masood A; Zohra, Raheela Rahmat

2014-11-01

The aim of the present study is to compare the effect of exercise training program in post-Cardiac Rehabilitation Exercise Training (CRET), post-CABG patients with normal & subnormal ejection fraction (EF >50% or <50%) who have undergoing coronary artery bypass grafting (CABG) surgery. The study was conducted on 100 cardiac patients of both sexes (age: 57-65 years) who after CABG surgery, were referred to the department of Physiotherapy and Rehabilitation between 2008 and 2010 at Liaquat National Hospital & Medical College, Karachi. The patients undertook exercise training program (using treadmill, Recumbent Bike), keeping in view the Borg's scale of perceived exertion, for 6 weeks. Heart Rate (HR) and Blood Pressure (BP) were measured & compared in post CABG Patients with EF (>50% or <50%) at the start and end of the exercise training program. Statistical formulae were applied to analyze the improvement in cardiac functional indicators. Exercise significantly restores the values of HR and BP (systolic) in post CABGT Patients with EF (>50% or <50%) from the baseline to the last session of the training program. There appeared significant improvement in cardiac function four to six weeks of treadmill exercise training program. After CABG all patients showed similar improvement in cardiac function with exercise training program. The exercise training program is beneficial for improving exercise capacity linked with recovery cardiac function in Pakistani CABG patients.

Heart Rate and Outcomes in Hospitalized Patients With Heart Failure With Preserved Ejection Fraction.

PubMed

Lam, Phillip H; Dooley, Daniel J; Deedwania, Prakash; Singh, Steven N; Bhatt, Deepak L; Morgan, Charity J; Butler, Javed; Mohammed, Selma F; Wu, Wen-Chih; Panjrath, Gurusher; Zile, Michael R; White, Michel; Arundel, Cherinne; Love, Thomas E; Blackman, Marc R; Allman, Richard M; Aronow, Wilbert S; Anker, Stefan D; Fonarow, Gregg C; Ahmed, Ali

2017-10-10

A lower heart rate is associated with better outcomes in patients with heart failure (HF) with reduced ejection fraction (EF). Less is known about this association in patients with HF with preserved ejection fraction (HFpEF). The aims of this study were to examine associations of discharge heart rate with outcomes in hospitalized patients with HFpEF. Of the 8,873 hospitalized patients with HFpEF (EF ≥50%) in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 6,286 had a stable heart rate, defined as ≤20 beats/min variation between admission and discharge. Of these, 2,369 (38%) had a discharge heart rate of <70 beats/min. Propensity scores for discharge heart rate <70 beats/min, estimated for each of the 6,286 patients, were used to assemble a cohort of 2,031 pairs of patients with heart rate <70 versus ≥70 beats/min, balanced on 58 baseline characteristics. The 4,062 matched patients had a mean age of 79 ± 10 years, 66% were women, and 10% were African American. During 6 years (median 2.8 years) of follow-up, all-cause mortality was 65% versus 70% for matched patients with a discharge heart rate <70 versus ≥70 beats/min, respectively (hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.80 to 0.93; p < 0.001). A heart rate <70 beats/min was also associated with a lower risk for the combined endpoint of HF readmission or all-cause mortality (HR: 0.90; 95% CI: 0.84 to 0.96; p = 0.002), but not with HF readmission (HR: 0.93; 95% CI: 0.85 to 1.01) or all-cause readmission (HR: 1.01; 95% CI: 0.95 to 1.08). Similar associations were observed regardless of heart rhythm or receipt of beta-blockers. Among hospitalized patients with HFpEF, a lower discharge heart rate was independently associated with a lower risk of all-cause mortality, but not readmission. Published by Elsevier Inc.

Sudden Death in Heart Failure With Preserved Ejection Fraction: A Competing Risks Analysis From the TOPCAT Trial.

PubMed

Vaduganathan, Muthiah; Claggett, Brian L; Chatterjee, Neal A; Anand, Inder S; Sweitzer, Nancy K; Fang, James C; O'Meara, Eileen; Shah, Sanjiv J; Hegde, Sheila M; Desai, Akshay S; Lewis, Eldrin F; Rouleau, Jean; Pitt, Bertram; Pfeffer, Marc A; Solomon, Scott D

2018-03-04

This study investigated the rates and predictors of SD or aborted cardiac arrest (ACA) in HFpEF. Sudden death (SD) may be an important mode of death in heart failure with preserved ejection fraction (HFpEF). We studied 1,767 patients with HFpEF (EF ≥45%) enrolled in the Americas region of the TOPCAT (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function) trial. We identified independent predictors of composite SD/ACA with stepwise backward selection using competing risks regression analysis that accounted for nonsudden causes of death. During a median 3.0-year (25 th to 75 th percentile: 1.9 to 4.4 years) follow-up, 77 patients experienced SD/ACA, and 312 experienced non-SD/ACA. Corresponding incidence rates were 1.4 events/100 patient-years (25 th to 75 th percentile: 1.1 to 1.8 events/100 patient-years) and 5.8 events/100 patient-years (25 th to 75 th percentile: 5.1 to 6.4 events/100 patient-years). SD/ACA was numerically lower but not statistically reduced in those randomized to spironolactone: 1.2 events/100 patient-years (25 th to 75 th percentile: 0.9 to 1.7 events/100 patient-years) versus 1.6 events/100 patient-years (25 th to 75 th percentile: 1.2 to 2.2 events/100 patient-years); the subdistributional hazard ratio was 0.74 (95% confidence interval: 0.47 to 1.16; p = 0.19). After accounting for competing risks of non-SD/ACA, male sex and insulin-treated diabetes mellitus were independently predictive of composite SD/ACA (C-statistic = 0.65). Covariates, including eligibility criteria, age, ejection fraction, coronary artery disease, left bundle branch block, and baseline therapies, were not independently associated with SD/ACA. Sex and diabetes mellitus status remained independent predictors in sensitivity analyses, excluding patients with implantable cardioverter-defibrillators and when predicting SD alone. SD accounted for ∼20% of deaths in HFpEF. Male sex and insulin-treated diabetes mellitus identified patients at higher risk for SD/ACA with modest discrimination. These data might guide future SD preventative efforts in HFpEF. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]); NCT00094302. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Influence of Ejection Fraction on Outcomes and Efficacy of Sacubitril/Valsartan (LCZ696) in Heart Failure with Reduced Ejection Fraction: The Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) Trial.

PubMed

Solomon, Scott D; Claggett, Brian; Desai, Akshay S; Packer, Milton; Zile, Michael; Swedberg, Karl; Rouleau, Jean L; Shi, Victor C; Starling, Randall C; Kozan, Ömer; Dukat, Andrej; Lefkowitz, Martin P; McMurray, John J V

2016-03-01

The angiotensin receptor neprilysin inhibitor sacubitril/valsartan (LCZ696) reduced cardiovascular morbidity and mortality compared with enalapril in patients with heart failure (HF) and reduced ejection fraction (EF) in the Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. We evaluated the influence of EF on clinical outcomes and on the effectiveness of sacubitril/valsartan compared with enalapril. Eight thousand three hundred ninety-nine patients with New York Heart Association class II to IV HF with reduced EF [left ventricular EF (LVEF) ≤40%] were randomized to sacubitril/valsartan 97/103 mg twice daily versus enalapril 10 mg twice daily and followed for a median of 27 months. The primary study end point was cardiovascular death or HF hospitalization. LVEF was assessed at the sites and recorded on case report forms. We related LVEF to study outcomes and assessed the effectiveness of sacubitril/valsartan across the LVEF spectrum. The mean LVEF in PARADIGM-HF, reported by sites, was 29.5 (interquartile range, 25-34). The risk of all outcomes increased with decreasing LVEF. Each 5-point reduction in LVEF was associated with a 9% increased risk of cardiovascular death or HF hospitalization (hazard ratio, 1.09; 95% confidence interval, 1.05-1.13; P<0.001), a 9% increased risk for CV death (hazard ratio, 1.09; 95% confidence interval, 1.04-1.14), a 9% increased risk in HF hospitalization (hazard ratio, 1.09; 95% confidence interval, 1.04-1.14) and a 7% increased risk in all-cause mortality (hazard ratio, 1.07; 95% confidence interval, 1.03-1.12) in adjusted analyses. Sacubitril/valsartan was effective across the LVEF spectrum, with no evidence of heterogeneity, when modeled either in tertiles (P interaction=0.87) or continuously (P interaction=0.95). In patients with HF and reduced EF enrolled in PARADIGM-HF, LVEF was a significant and independent predictor of all outcomes. Sacubitril/valsartan was effective at reducing cardiovascular death and HF hospitalization throughout the LVEF spectrum. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255. © 2016 American Heart Association, Inc.

Characteristics and circadian distribution of cardiac arrhythmias in patients with heart failure and sleep-disordered breathing.

PubMed

Omran, Hazem; Bitter, Thomas; Horstkotte, Dieter; Oldenburg, Olaf; Fox, Henrik

2018-05-08

Cardiac arrhythmias and sleep-disordered breathing (SDB) are common comorbidities in heart failure with reduced ejection fraction (HFrEF). However, understanding of the association between arrhythmias and SDB is poor. This study assessed the occurrence and circadian distribution of ventricular arrhythmias in HFrEF patients with and without SDB. This retrospective analysis included HFrEF patients admitted for unattended overnight cardiorespiratory polygraphy and 24-h Holter-ECG recording. Holter-ECG data (events/h) were categorized by time of day: morning, 06:00-13:59; afternoon, 14:00-21:59; nighttime, 22:00-05:59. Respiratory events were expressed using the apnea-hypopnea index (AHI) and an AHI ≥ 15/h was categorized as moderate to severe SDB. 167 patients were included (82% male, age 65 ± 10.4 years, left ventricular ejection fraction 30.9 ± 7.9%); SDB was predominantly central sleep apnea (CSA) in 45.5%, obstructive sleep apnea (OSA) in 23.9% or none/mild (nmSDB) in 17.4%. Morning premature ventricular contractions (PVCs) were detected significantly more frequently in CSA versus nmSDB patients (44.4/h versus 1.8/h; p = 0.02). Non-sustained VT was more frequent in patients with CSA versus versus OSA or nmSDB (17.9 versus 3.2 or 3.2%/h; p = 0.003 and p = 0.005, respectively). There was no significant variation in VT occurrence by time of day in HFrEF patients with CSA (p = 0.3). CSA was an independent predictor of VT occurrence in HFrEF in multivariate logistic regression analysis (odds ratio 4.1, 95% confidence interval 1.5-11.4, p = 0.007). CSA was associated with VT occurrence irrespective of sleep/wake status in HFrEF patients, and independently predicted the occurrence of VT. This association may contribute to chances by which CSA increases sudden death risk in HFrEF patients.

Long-term and clinical profile of heart failure with recovered ejection fraction in a non-tertiary hospital.

PubMed

Martínez-Mateo, Virgilio; Fernández-Anguita, Manuel; Cejudo, Laura; Martín-Barrios, Eugenia; Paule, Antonio J

2018-06-05

Heart failure (HF) with recovered ejection fraction (EF) is emerging as a different HF subtype. There is little information about his clinical profile in hospitals that are not a reference. We analysed characteristics and prognosis in patients with recovered HF followed prospectively in the HF Unit of a non-tertiary hospital. A total of 431 patients with HF with reduced EF were followed (median 50 months, 79.3% males, mean age 70.3±12.2years). Of the patients, 26.9% (N 116) recovered EF, mainly in the first year of follow-up (76.7%). Compared with patients that did not recovered EF in the follow-up, they were younger, rate of ischemic origin of cardiomyopathy was less frequent and presented less comorbidity. Mortality was lower in patients with recovered HF (survival median of 85.2±2.1 vs. 74.2±1.9 months [log-rank χ 2 11.5, P=0.001], hazard ratio 0.37, 95% confidence interval [CI]: 0.21-0.67, P=0.002). Aetiology of deaths was not mainly secondary to HF. Younger age of 68 years (odds ratio [OR] 0-98, 95% CI: 0.96-0,99; P=0.025), ischemic origin (OR 1.12, 95% CI: 1.01-1.21; P=0.003) and use of aldosterone antagonists (OR 1.89, 95% CI: 1.09-3.26; P=0.023) were the variables independently associated to normalisation of EF. HF with recovered EF is a frequent phenomenon. It has a more favourable clinical course, prognosis and basal characteristics than HF with persistent reduced EF. Further studies are needed to identify natural history and optimal medications for HF-recovered patients. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Ethnic differences in the association of QRS duration with ejection fraction and outcome in heart failure

PubMed Central

Gijsberts, Crystel M; Benson, Lina; Dahlström, Ulf; Sim, David; Yeo, Daniel P S; Ong, Hean Yee; Jaufeerally, Fazlur; Leong, Gerard K T; Ling, Lieng H; Richards, A Mark; de Kleijn, Dominique P V; Lund, Lars H; Lam, Carolyn S P

2016-01-01

Background QRS duration (QRSd) criteria for device therapy in heart failure (HF) were derived from predominantly white populations and ethnic differences are poorly understood. Methods We compared the association of QRSd with ejection fraction (EF) and outcomes between 839 Singaporean Asian and 11 221 Swedish white patients with HF having preserved EF (HFPEF)and HF having reduced EF (HFREF) were followed in prospective population-based HF studies. Results Compared with whites, Asian patients with HF were younger (62 vs 74 years, p<0.001), had smaller body size (height 163 vs 171 cm, weight 70 vs 80 kg, both p<0.001) and had more severely impaired EF (EF was <30% in 47% of Asians vs 28% of whites). Overall, unadjusted QRSd was shorter in Asians than whites (101 vs 104 ms, p<0.001). Lower EF was associated with longer QRSd (p<0.001), with a steeper association among Asians than whites (pinteraction<0.001), independent of age, sex and clinical covariates (including body size). Excluding patients with left bundle branch block (LBBB) and adjusting for clinical covariates, QRSd was similar in Asians and whites with HFPEF, but longer in Asians compared with whites with HFREF (p=0.001). Longer QRSd was associated with increased risk of HF hospitalisation or death (absolute 2-year event rate for ≤120 ms was 40% and for >120 ms it was 52%; HR for 10 ms increase of QRSd was 1.04 (1.03 to 1.06), p<0.001), with no interaction by ethnicity. Conclusion We found ethnic differences in the association between EF and QRSd among patients with HF. QRS prolongation was similarly associated with increased risk, but the implications for ethnicity-specific QRSd cut-offs in clinical decision-making require further study. PMID:27402805

Association between renal function and cardiovascular structure and function in heart failure with preserved ejection fraction.

PubMed

Gori, Mauro; Senni, Michele; Gupta, Deepak K; Charytan, David M; Kraigher-Krainer, Elisabeth; Pieske, Burkert; Claggett, Brian; Shah, Amil M; Santos, Angela B S; Zile, Michael R; Voors, Adriaan A; McMurray, John J V; Packer, Milton; Bransford, Toni; Lefkowitz, Martin; Solomon, Scott D

2014-12-21

Renal dysfunction is a common comorbidity in patients with heart failure and preserved ejection fraction (HFpEF). We sought to determine whether renal dysfunction was associated with measures of cardiovascular structure/function in patients with HFpEF. We studied 217 participants from the PARAMOUNT study with HFpEF who had echocardiography and measures of kidney function. We evaluated the relationships between renal dysfunction [estimated glomerular filtration rate (eGFR) >30 and <60 mL/min/1.73 m(2) and/or albuminuria] and cardiovascular structure/function. The mean age of the study population was 71 years, 55% were women, 94% hypertensive, and 40% diabetic. Impairment of at least one parameter of kidney function was present in 62% of patients (16% only albuminuria, 23% only low eGFR, 23% both). Renal dysfunction was associated with abnormal LV geometry (defined as concentric hypertrophy, or eccentric hypertrophy, or concentric remodelling) (adjusted P = 0.048), lower midwall fractional shortening (MWFS) (P = 0.009), and higher NT-proBNP (P = 0.006). Compared with patients without renal dysfunction, those with low eGFR and no albuminuria had a higher prevalence of abnormal LV geometry (P = 0.032) and lower MWFS (P < 0.01), as opposed to those with only albuminuria. Conversely, albuminuria alone was associated with greater LV dimensions (P < 0.05). Patients with combined renal impairment had mixed abnormalities (higher LV wall thicknesses, NT-proBNP; lower MWFS). Renal dysfunction, as determined by both eGFR and albuminuria, is highly prevalent in HFpEF, and associated with cardiac remodelling and subtle systolic dysfunction. The observed differences in cardiac structure/function between each type of renal damage suggest that both parameters of kidney function might play a distinct role in HFpEF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Pattern of endothelial progenitor cells and apoptotic endothelial cell-derived microparticles in chronic heart failure patients with preserved and reduced left ventricular ejection fraction.

PubMed

Berezin, Alexander E; Kremzer, Alexander A; Martovitskaya, Yulia V; Berezina, Tatyana A; Gromenko, Elena A

2016-02-01

Chronic heart failure (HF) remains a leading cause of cardiovascular (CV) mortality and morbidity worldwide. The aim of the study was to investigate whether the pattern of angiogenic endothelial progenitor cells (EPCs) and apoptotic endothelial cell-derived microparticles (EMPs) would be able to differentiate HF with reduced (HFrEF) and preserved (HFpEF) ejection fraction. One hundred sixty four chronic HF subjects met inclusion criteria. Patients with global left ventricular ejection fraction ≥ 50% were categorized as the HFpEF group (n = 79) and those with ≤ 45% as the HFrEF group (n = 85). Therefore, to compare the circulating levels of biological markers 35 control subjects without HF were included in the study. All control individuals were age- and sex-matched chronic HF patients. The serum level of biomarkers was measured at baseline. The flow cytometric technique was used for predictably distinguishing circulating cell subsets depending on expression of CD45, CD34, CD14, Tie-2, and CD309 antigens and determining endothelial cell-derived microparticles. CD31(+)/annexin V(+) was defined as apoptotic endothelial cell-derived MPs, MPs labeled for CD105(+) or CD62E(+) were determined as MPs produced due to activation of endothelial cells. In multivariate logistic regression model T2DM (R(2) = 0.26; P = 0.001), obesity (R(2) = 0.22; P = 0.001), previous MI (R(2) = 0.17; P = 0.012), galectin-3 (R(2) = 0.67; P = 0.012), CD31(+)/annexin V(+) EMPs (R(2) = 0.11; P = 0.001), NT-proBNP (R(2) = 0.11; P = 0.046), CD14(+) CD309(+) cells (R(2) = 0.058; P = 0.001), and CD14(+) СD309(+) Tie-2(+) cells (R(2) = 0.044; P = 0.028) were found as independent predictors of HFpEF. Using multivariate Cox-regression analysis adjusted etiology (previous myocardial infarction), cardiovascular risk factors (obesity, type 2 diabetes mellitus) we found that NT-proBNP (OR 1.08; 95% CI = 1.03-1.12; P = 0.001) and CD31(+)/annexin V(+) EMPs to CD14(+) CD309(+) cell ratio (OR 1.06; 95% CI = 1.02-1.11; P = 0.02) were independent predictors for HFpEF. We found that CD31(+)/annexin V(+) EMPs to CD14(+) CD309(+) cell ratio added to NT-proBNP, clinical data, and cardiovascular risk factors has exhibited the best discriminate value and higher reliability to predict HFpEF compared with NT-proBNP and clinical data/cardiovascular risk factors alone.

Measurement of aortic valve calcification using multislice computed tomography: correlation with haemodynamic severity of aortic stenosis and clinical implication for patients with low ejection fraction.

PubMed

Cueff, Caroline; Serfaty, Jean-Michel; Cimadevilla, Claire; Laissy, Jean-Pierre; Himbert, Dominique; Tubach, Florence; Duval, Xavier; Iung, Bernard; Enriquez-Sarano, Maurice; Vahanian, Alec; Messika-Zeitoun, David

2011-05-01

Measurement of the degree of aortic valve calcification (AVC) using electron beam computed tomography (EBCT) is an accurate and complementary method to transthoracic echocardiography (TTE) for assessment of the severity of aortic stenosis (AS). Whether threshold values of AVC obtained with EBCT could be extrapolated to multislice computed tomography (MSCT) was unclear and AVC diagnostic value in patients with low ejection fraction (EF) has never been specifically evaluated. Patients with mild to severe AS underwent prospectively within 1 week MSCT and TTE. Severe AS was defined as an aortic valve area (AVA) of less than 1 cm(2). In 179 patients with EF greater than 40% (validation set), the relationship between AVC and AVA was evaluated. The best threshold of AVC for the diagnosis of severe AS was then evaluated in a second subset (testing set) of 49 patients with low EF (≤40%). In this subgroup, AS severity was defined based on mean gradient, natural history or dobutamine stress echocardiography. Correlation between AVC and AVA was good (r=-0.63, p<0.0001). A threshold of 1651 arbitrary units (AU) provided 82% sensitivity, 80% specificity, 88% negative-predictive value and 70% positive-predictive value. In the testing set (patients with low EF), this threshold correctly differentiated patients with severe AS from non-severe AS in all but three cases. These three patients had an AVC score close to the threshold (1206, 1436 and 1797 AU). In this large series of patients with a wide range of AS, AVC was shown to be well correlated to AVA and may be a useful adjunct for the evaluation of AS severity especially in difficult cases such as patients with low EF.

Use of Hydralazine‐Isosorbide Dinitrate Combination in African American and Other Race/Ethnic Group Patients With Heart Failure and Reduced Left Ventricular Ejection Fraction

PubMed Central

Golwala, Harsh B.; Thadani, Udho; Liang, Li; Stavrakis, Stavros; Butler, Javed; Yancy, Clyde W.; Bhatt, Deepak L.; Hernandez, Adrian F.; Fonarow, Gregg C.

2013-01-01

Background Hydralazine‐isosorbide dinitrate (H‐ISDN) therapy is recommended for African American patients with moderate to severe heart failure with reduced ejection fraction (<40%) (HFrEF), but use, temporal trends, and clinical characteristics associated with H‐ISDN therapy in clinical practice are unknown. Methods and Results An observational analysis of 54 622 patients admitted with HFrEF and discharged home from 207 hospitals participating in the Get With The Guidelines–Heart Failure registry from April 2008 to March 2012 was conducted to assess prescription, trends, and predictors of use of H‐ISDN among eligible patients. Among 11 185 African American patients eligible for H‐ISDN therapy, only 2500 (22.4%) received H‐ISDN therapy at discharge. In the overall eligible population, 5115 of 43 498 (12.6%) received H‐ISDN at discharge. Treatment rates increased over the study period from 16% to 24% among African Americans and from 10% to 13% among the entire HFrEF population. In a multivariable model, factors associated with H‐ISDN use among the entire cohort included younger age; male sex; African American/Hispanic ethnicity; and history of diabetes, hypertension, anemia, renal insufficiency, higher systolic blood pressure, and lower heart rate. In African American patients, these factors were similar; in addition, being uninsured was associated with lower use. Conclusions Overall, few potentially eligible patients with HFrEF are treated with H‐ISDN, and among African‐Americans fewer than one‐fourth of eligible patients received guideline‐recommended H‐ISDN therapy. Improved ways to facilitate use of H‐ISDN therapy in African American patients with HFrEF are needed. PMID:23966379

[Clinical examination and the Valsalva maneuver in heart failure].

PubMed

Liniado, Guillermo E; Beck, Martín A; Gimeno, Graciela M; González, Ana L; Cianciulli, Tomás F; Castiello, Gustavo G; Gagliardi, Juan A

2018-01-01

Congestion in heart failure patients with reduced ejection fraction (HFrEF) is relevant and closely linked to the clinical course. Bedside blood pressure measurement during the Valsalva maneuver (Val) added to clinical examination may improve the assessment of congestion when compared to NT-proBNP levels and left atrial pressure (LAP) estimation by Doppler echocardiography, as surrogate markers of congestion in HFrEF. A clinical examination, LAP and blood tests were performed in 69 HFrEF ambulatory patients with left ventricular ejection fraction ≤ 40% and sinus rhythm. Framingham Heart Failure Score (HFS) was used to evaluate clinical congestion; Val was classified as normal or abnormal, NT-proBNP was classified as low (< 1000 pg/ml) or high (≥ 1000 pg/ml) and the ratio between Doppler early mitral inflow and tissue diastolic velocity was used to estimate LAP and was classified as low (E/e'< 15) or high (E/e' ≥ 15). A total of 69 patients with HFrEF were included; 27 had a HFS ≥ 2 and 13 of them had high NT-proBNP. HFS ≥ 2 had a 62% sensitivity, 70% specificity and a positive likelihood ratio of 2.08 (p=0.01) to detect congestion. When Val was added to clinical examination, the presence of a HFS ≥ 2 and abnormal Val showed a 100% sensitivity, 64% specificity and a positive likelihood ratio of 2.8 (p = 0.0004). Compared with LAP, the presence of HFS = 2 and abnormal Val had 86% sensitivity, 54% specificity and a positive likelihood ratio of 1.86 (p = 0.03). In conclusion, an integrated clinical examination with the addition Valsalva maneuver may improve the assessment of congestion in patients with HFrEF.

Peripheral vascular function, oxygen delivery and utilization: the impact of oxidative stress in aging and heart failure with reduced ejection fraction

PubMed Central

Wray, D. Walter; Amann, Markus

2016-01-01

The aging process appears to be a precursor to many age-related diseases, perhaps the most impactful of which is cardiovascular disease (CVD). Heart disease, a manifestation of CVD, is the leading cause of death in the USA, and heart failure (HF), a syndrome that develops as a consequence of heart disease, now affects almost six million American. Importantly, as this is an age-related disease, this number is likely to grow along with the ever-increasing elderly population. Hallmarks of the aging process and HF patients with a reduced ejection fraction (HFrEF) include exercise intolerance, premature fatigue, and limited oxygen delivery and utilization, perhaps as a consequence of diminished peripheral vascular function. Free radicals and oxidative stress have been implicated in this peripheral vascular dysfunction, as a redox imbalance may directly impact the function of the vascular endothelium. This review aims to bring together studies that have examined the impact of oxidative stress on peripheral vascular function and oxygen delivery and utilization with both healthy aging and HFrEF. PMID:27392715

Sacubitril/Valsartan: A Review in Chronic Heart Failure with Reduced Ejection Fraction.

PubMed

McCormack, Paul L

2016-03-01

Sacubitril/valsartan (Entresto™; LCZ696) is an orally administered supramolecular sodium salt complex of the neprilysin inhibitor prodrug sacubitril and the angiotensin receptor blocker (ARB) valsartan, which was recently approved in the US and the EU for the treatment of chronic heart failure (NYHA class II-IV) with reduced ejection fraction (HFrEF). In the large, randomized, double-blind, PARADIGM-HF trial, sacubitril/valsartan reduced the incidence of death from cardiovascular causes or first hospitalization for worsening heart failure (composite primary endpoint) significantly more than the angiotensin converting enzyme (ACE) inhibitor enalapril. Sacubitril/valsartan was also superior to enalapril in reducing death from any cause and in limiting the progression of heart failure. Sacubitril/valsartan was generally well tolerated, with no increase in life-threatening adverse events. Symptomatic hypotension was significantly more common with sacubitril/valsartan than with enalapril; the incidence of angio-oedema was low. Therefore, sacubitril/valsartan is a more effective replacement for an ACE inhibitor or an ARB in the treatment of HFrEF, and is likely to influence the basic approach to treatment.

Evolution of Functional Mitral Regurgitation and Prognosis in Medically Managed Heart Failure Patients With Reduced Ejection Fraction.

PubMed

Nasser, Riwa; Van Assche, Lauranne; Vorlat, Anne; Vermeulen, Tom; Van Craenenbroeck, Emeline; Conraads, Viviane; Van der Meiren, Vicky; Shivalkar, Bharati; Van Herck, Paul; Claeys, Marc J

2017-09-01

The purpose of this study was to assess whether medical management may alter the severity of functional mitral regurgitation (FMR) and its prognosis in patients who have heart failure with reduced ejection fraction (HFrEF). FMR in patients who have HFrEF is associated with a worse prognosis. It is uncertain to what extent medical management may alter the severity of FMR and its prognosis. The extent of FMR was assessed at baseline and after a median follow-up period of 50 months in 163 consecutive HFrEF patients (left ventricular ejection fraction <40%). Severe FMR was defined as mitral regurgitation (MR) grade 3-4. All of the patients received the maximal tolerable doses of their heart failure (HF) medications. Major adverse cardiac events were defined as a composite of all-cause death and the need for heart transplantation or hospitalization for HF and/or malignant arrhythmias. A total of 50 (31%) patients had severe MR at baseline. During the follow-up period, 38% of the severe FMR patients showed an improvement to nonsevere FMR (MR grade <3), whereas 18% of the nonsevere FMR patients developed severe FMR despite optimal HF treatment. Cox regression analysis revealed that the presence of sustained severe FMR or worsening of FMR was the most important independent prognostic determinant with an adjusted odds ratio of 2.5 (95% confidence interval: 1.5 to 4.3, major adverse cardiac events 83% vs. 43%). In addition, those patients showed a 13% increase in left ventricular end-diastolic volume index (LVEDVI), whereas the patients with improvement in their severe MR showed a 2% decrease in LVEDVI (p = 0.01). Severe FMR was successfully treated with medication in almost 40% and was associated with prevention of left ventricular adverse remodeling and with an improved long-term prognosis. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Bleeding Risk and Antithrombotic Strategy in Patients with Sinus Rhythm Heart Failure with Reduced Ejection Fraction Treated with Warfarin or Aspirin

PubMed Central

Ye, Siqin; Cheng, Bin; Lip, Gregory Y. H.; Buchsbaum, Richard; Sacco, Ralph L.; Levin, Bruce; Di Tullio, Marco R.; Qian, Min; Mann, Douglas L.; Pullicino, Patrick M.; Freudenberger, Ronald S.; Teerlink, John R.; Mohr, J.P.; Graham, Susan; Labovitz, Arthur J.; Estol, Conrado J.; Lok, Dirk J.; Ponikowski, Piotr; Anker, Stefan D.; Thompson, John L.P.; Homma, Shunichi

2015-01-01

We sought to assess the performance of existing bleeding risk scores, such as HAS-BLED or OBRI, in patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm (SR) treated with warfarin or aspirin. We calculated HAS-BLED and OBRI risk scores for 2,305 patients with HFrEF in SR enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial. Proportional hazards models were used to test whether each score predicted major bleeding, and comparison of different risk scores was performed using Harell’s c-statistic and net-reclassification improvement (NRI) index. For the warfarin arm, both scores predicted bleeding risk, with OBRI having significantly higher c-statistic (0.72 vs 0.61; p=0.03) compared to HAS-BLED, though the NRI for comparing OBRI to HAS-BLED was not significant (0.32, 95% CI - 0.18-0.37). Performance of the OBRI and HAS-BLED risk scores were similar for the aspirin arm. For participants with OBRI score of 0 to 1, warfarin compared with aspirin reduced ischemic stroke (HR 0.51, 95% CI 0.26-0.98, p=0.042) without significantly increasing major bleeding (HR 1.24, 95% CI 0.66-2.30, p=0.51). For those with OBRI score of ≥2, there was a trend for reduced ischemic stroke with warfarin compared to aspirin (HR 0.56, 95% CI 0.27-1.15, p=0.12), but major bleeding was increased (HR 4.04, 95% CI 1.99-8.22, p<0.001). In conclusion, existing bleeding risk scores can identify bleeding risk in HFrEF patients in SR, and could be tested for potentially identifying patients with a favorable risk / benefit profile for antithrombotic therapy with warfarin. PMID:26189039

Current use of guideline-based medical therapy in elderly patients admitted with acute heart failure with reduced ejection fraction and its impact on event-free survival.

PubMed

Akita, Keitaro; Kohno, Takashi; Kohsaka, Shun; Shiraishi, Yasuyuki; Nagatomo, Yuji; Izumi, Yuki; Goda, Ayumi; Mizuno, Atsushi; Sawano, Mitsuaki; Inohara, Taku; Fukuda, Keiichi; Yoshikawa, Tsutomu

2017-05-15

Acute heart failure (HF) is a frequently encountered cardiac condition. Its prevalence increases exponentially with age. In spite of this, elderly patients are underrepresented in clinical trials and the implementation of guideline-based medical therapy (GBMT) in them is not well established. We investigated the current use of GBMT and its effects on mortality and HF rehospitalization among elderly patients with acute HF with reduced ejection fraction (HFrEF) using data obtained from a contemporary multi-center registry. We analyzed data from 1,441 consecutive acute HF patients registered in the West Tokyo Heart Failure (WET-HF) registry (mean age 73.2 ± 13.6 years). Reduced ejection fraction (<45%) was noted in 803 patients (55.7%), of which 237 were aged ≥80 years (elderly group). The prescription rate of GBMT (use of renin-angiotensin system inhibitors and β-blockers at discharge) was significantly lower in the elderly than in the younger (aged < 80 years) group (46.8% vs. 66.9%, p<0.001). Although GBMT at discharge was associated with reductions in HF readmission or the composite endpoint of cardiac death and HF readmission (HR 0.49, 95% CI 0.30-0.80; and HR 0.53, 95% CI 0.32-0.89, respectively) in the younger group, this association was not observed in the elderly group (HR 1.41, 95% CI 0.68-2.92; and HR 1.54, 95% CI 0.76-3.13, respectively) CONCLUSIONS: GBMT implementation in elderly patients with HFrEF was found to be suboptimal. However, the underuse of GBMT did not appear to be responsible for poorer outcomes in elderly HFrEF patients. Further research is required to establish an ideal therapeutic approach for this population. URL: http://www.umin.ac.jp/icdr/index-j.html. Unique identifier: UMIN000001171. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

A Simple, Evidence-Based Approach to Help Guide Diagnosis of Heart Failure with Preserved Ejection Fraction.

PubMed

Reddy, Yogesh N V; Carter, Rickey E; Obokata, Masaru; Redfield, Margaret M; Borlaug, Barry A

2018-05-23

Background -Diagnosis of heart failure with preserved ejection fraction (HFpEF) is challenging in euvolemic patients with dyspnea, and no evidence-based criteria are available. We sought to develop and then validate non-invasive diagnostic criteria that could be used to estimate the likelihood that HFpEF is present among patients with unexplained dyspnea in order to guide further testing. Methods -Consecutive patients with unexplained dyspnea referred for invasive hemodynamic exercise testing were retrospectively evaluated. Diagnosis of HFpEF (case) or non-cardiac dyspnea (control) was ascertained by invasive hemodynamic exercise testing. Logistic regression was performed to evaluate the ability of clinical findings to discriminate cases from controls. A scoring system was developed and then validated in a separate test cohort. Results -The derivation cohort included 414 consecutive patients (267 HFpEF and 147 controls, HFpEF prevalence 64%). The test cohort included 100 consecutive patients (61 HFpEF, prevalence 61%). Obesity, atrial fibrillation, age>60 years, treatment with 2 or more antihypertensives, echocardiographic E/e' ratio>9 and echocardiographic pulmonary artery systolic pressure>35 mmHg were selected as the final set of predictive variables. A weighted score based on these six variables was used to create a composite score (H 2 FPEF score) ranging from 0-9. The odds of HFpEF doubled for each 1 unit score increase [OR 1.98 [1.74-2.30], p<0.0001], with an AUC of 0.841 (p<0.0001). The H 2 FPEF score was superior to a currently-used algorithm based upon expert consensus (increase in AUC of +0.169 [+0.120 to +0.217], p<0.0001). Performance in the independent test cohort was maintained [AUC 0.886, p<0.0001]. Conclusions -The H 2 FPEF score, which relies upon simple clinical characteristics and echocardiography, enables discrimination of HFpEF from non-cardiac causes of dyspnea, and can assist in determination of the need for further diagnostic testing in the evaluation of patients with unexplained exertional dyspnea.

Differing prognostic value of pulse pressure in patients with heart failure with reduced or preserved ejection fraction: results from the MAGGIC individual patient meta-analysis.

PubMed

Jackson, Colette E; Castagno, Davide; Maggioni, Aldo P; Køber, Lars; Squire, Iain B; Swedberg, Karl; Andersson, Bert; Richards, A Mark; Bayes-Genis, Antoni; Tribouilloy, Christophe; Dobson, Joanna; Ariti, Cono A; Poppe, Katrina K; Earle, Nikki; Whalley, Gillian; Pocock, Stuart J; Doughty, Robert N; McMurray, John J V

2015-05-07

Low pulse pressure is a marker of adverse outcome in patients with heart failure (HF) and reduced ejection fraction (HF-REF) but the prognostic value of pulse pressure in patients with HF and preserved ejection fraction (HF-PEF) is unknown. We examined the prognostic value of pulse pressure in patients with HF-PEF [ejection fraction (EF) ≥ 50%] and HF-REF. Data from 22 HF studies were examined. Preserved left ventricular ejection fraction (LVEF) was defined as LVEF ≥ 50%. All-cause mortality at 3 years was evaluated in 27 046 patients: 22 038 with HF-REF (4980 deaths) and 5008 with HF-PEF (828 deaths). Pulse pressure was analysed in quintiles in a multivariable model adjusted for the previously reported Meta-Analysis Global Group in Chronic Heart Failure prognostic variables. Heart failure and reduced ejection fraction patients in the lowest pulse pressure quintile had the highest crude and adjusted mortality risk (adjusted hazard ratio 1.68, 95% confidence interval 1.53-1.84) compared with all other pulse pressure groups. For patients with HF-PEF, higher pulse pressure was associated with the highest crude mortality, a gradient that was eliminated after adjustment for other prognostic variables. Lower pulse pressure (especially <53 mmHg) was an independent predictor of mortality in patients with HF-REF, particularly in those with an LVEF < 30% and systolic blood pressure <140 mmHg. Overall, this relationship between pulse pressure and outcome was not consistently observed among patients with HF-PEF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Safe Hydration Volume to Prevent Contrast-induced Acute Kidney Injury and Worsening Heart Failure in Patients With Heart Failure and Preserved Ejection Fraction After Cardiac Catheterization.

PubMed

Bei, Wei-Jie; Wang, Kun; Li, Hua-Long; Lin, Kai-Yang; Guo, Xiao-Sheng; Chen, Shi-Qun; Liu, Yong; Yi, Shi-Xin; Luo, De-Mou; Chen, Ji-Yan; Tan, Ning

2017-09-01

Few studies have investigated the efficacy and safety of hydration to prevent contrast-induced acute kidney injury (CI-AKI) and worsening heart failure (WHF) after cardiac catheterization in heart failure and preserved ejection fraction (HFpEF; HF and EF ≥50%) patients. We recruited 1206 patients with HFpEF undergoing cardiac catheterization with periprocedural hydration volume/weight (HV/W) ratio data and investigated the relationship between hydration volumes and risk of CI-AKI and WHF. Incidence of CI-AKI was not significantly reduced in individuals with higher HV/W [quartile (Q) 1, Q2, Q3, and Q4: 9.7%, 10.2%, 12.7%, and 12.2%, respectively; P = 0.219]. Multivariate analysis indicated that higher HV/W ratios were not associated with decreased CI-AKI risks [Q2 vs. Q1: odds ratio (OR), 0.95; Q3 vs. Q1: OR, 1.07; Q4 vs. Q1: OR, 0.92; all P > 0.05]. According to multivariate analysis, higher HV/W significantly increased the WHF risk (Q4 vs. Q1: adjusted OR, 8.13 and 95% confidence interval, 1.03-64.02; P = 0.047). CI-AKI and WHF were associated with a significantly increased risk of long-term mortality (mean follow-up, 2.33 years). For HFpEF patients, an excessively high hydration volume might not be associated with lower risk of CI-AKI but may increase the risk of postprocedure WHF.

In-hospital and 3-year outcomes of heart failure patients in South India: The Trivandrum Heart Failure Registry.

PubMed

Sanjay, Ganapathi; Jeemon, Panniyammakal; Agarwal, Anubha; Viswanathan, Sunitha; Sreedharan, Madhu; Govindan, Vijayaraghavan; Gopalan, Bahuleyan Charantharalyil; Biju, R; Nair, Tiny; Prathapkumar, N; Krishnakumar, G; Rajalekshmi, N; Suresh, Krishnan; Park, Lawrence P; Huffman, Mark D; Harikrishnan, Sivadasanpillai

2018-06-06

Long-term data on outcomes of participants hospitalized with heart failure (HF) from low and middle-income countries are limited. In the Trivandrum Heart Failure Registry (THFR) in 2013, 1205 participants from 18 hospitals in Trivandrum, India were enrolled. Data were collected on demographics, clinical presentation, treatment and outcomes. We performed survival analyses, compared groups and evaluated the association between HF type and mortality, adjusting for covariates that predicted mortality in a global HF risk score. The mean (SD) age of participants was 61.2 (13.7) years. Ischemic heart disease was the most common etiology (72%). In-hospital mortality was higher for participants with heart-failure with reduced ejection fraction (HFrEF) (9.7%) compared to those with heart-failure with preserved ejection fraction (HFpEF) (4.8%, p = 0.003). After three years, 540 (44.8%) of all participants had died. All-cause mortality was lower for participants with HFpEF (40.8%) compared to HFrEF (46.2%, p = 0.049). In multivariable models, older age (hazard ratio [HR] 1.24 per decade, 95% CI 1.15, 1.33), NYHA class-IV symptoms (HR 2.80, 95% CI 1.43, 5.48), and higher serum creatinine (HR 1.12 per mg/dl, 95%CI 1.04, 1.22) were associated with all-cause mortality. Participants with HF in the THFR have high three-year all-cause mortality. Targeted hospital-based quality improvement initiatives are needed to improve survival during and after hospitalization for heart failure. Copyright © 2018 Elsevier Ltd. All rights reserved.

Association of chronic kidney disease with abnormal cardiac mechanics and adverse outcomes in patients with heart failure and preserved ejection fraction.

PubMed

Unger, Erin D; Dubin, Ruth F; Deo, Rajat; Daruwalla, Vistasp; Friedman, Julie L; Medina, Crystal; Beussink, Lauren; Freed, Benjamin H; Shah, Sanjiv J

2016-01-01

Chronic kidney disease (CKD) is associated with worse outcomes in heart failure with preserved ejection fraction (HFpEF). Whether this association is due the effect of CKD on intrinsic abnormalities in cardiac function is unknown. We hypothesized that CKD is independently associated with worse cardiac mechanics in HFpEF. We prospectively studied 299 patients enrolled in the Northwestern University HFpEF Program. Using the creatinine-based CKD-Epi equation to calculate estimated glomerular filtration rate (eGFR), study participants were analysed by CKD status (using eGFR <60 mL/min/1.73 m(2) to denote CKD). Indices of cardiac mechanics (longitudinal strain parameters) were measured using speckle-tracking echocardiography. Using multivariable-adjusted linear and Cox regression analyses, we determined the association between CKD and echocardiographic parameters and clinical outcomes (cardiovascular hospitalization or death). Of 299 study participants, 48% had CKD. CKD (dichotomous variable) and reduced eGFR (continuous variable) were both associated with worse cardiac mechanics indices including left atrial (LA) reservoir strain, LV longitudinal strain, and right ventricular free wall strain even after adjusting for potential confounders, including co-morbidities, EF, and volume status. For example, for each 1-SD decrease in eGFR, LA reservoir strain was 3.52% units lower (P < 0.0001) after multivariable adjustment. Reduced eGFR was also associated with worse outcomes [adjusted hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.01-1.61 per 1-SD decrease in eGFR; P = 0.039]. The association was attenuated after adjustment for indices of cardiac mechanics (P = 0.064). In HFpEF, CKD is independently associated with worse cardiac mechanics, which may explain why HFpEF patients with CKD have worse outcomes. NCT01030991. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Quality of life questionnaire predicts poor exercise capacity only in HFpEF and not in HFrEF.

PubMed

Ahmeti, Artan; Henein, Michael Y; Ibrahimi, Pranvera; Elezi, Shpend; Haliti, Edmond; Poniku, Afrim; Batalli, Arlind; Bajraktari, Gani

2017-10-17

The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is the most widely used measure of quality of life (QoL) in HF patients. This prospective study aimed to assess the relationship between QoL and exercise capacity in HF patients. The study subjects were 118 consecutive patients with chronic HF (62 ± 10 years, 57 females, in NYHA I-III). Patients answered a MLHFQ questionnaire in the same day of complete clinical, biochemical and echocardiographic assessment. They also underwent a 5 min walk test (6-MWT), in the same day, which grouped them into; Group I: ≤ 300 m and Group II: >300 m. In addition, left ventricular (LV) ejection fraction (EF), divided them into: Group A, with preserved EF (HFpEF) and Group B with reduced EF (HFrEF). The mean MLHFQ total scale score was 48 (±17). The total scale, and the physical and emotional functional MLHFQ scores did not differ between HFpEF and HFpEF. Group I patients were older (p = 0.003), had higher NYHA functional class (p = 0.002), faster baseline heart rate (p = 0.006), higher prevalence of smoking (p = 0.015), higher global, physical and emotional MLHFQ scores (p < 0.001, for all), larger left atrial (LA) diameter (p = 0.001), shorter LV filling time (p = 0.027), higher E/e' ratio (0.02), shorter isovolumic relaxation time (p = 0.028), lower septal a' (p = 0.019) and s' (p = 0.023), compared to Group II. Independent predictors of 6-MWT distance for the group as a whole were increased MLHFQ total score (p = 0.005), older age (p = 0.035), and diabetes (p = 0.045), in HFpEF were total MLHFQ (p = 0.007) and diabetes (p = 0.045) but in HFrEF were only LA enlargement (p = 0.005) and age (p = 0.013. A total MLHFQ score of 48.5 had a sensitivity of 67% and specificity of 63% (AUC on ROC analysis of 72%) for limited exercise performance in HF patients. Quality of life, assessment by MLHFQ, is the best correlate of exercise capacity measured by 6-MWT, particularly in HFpEF patients. Despite worse ejection fraction in HFrEF, signs of raised LA pressure independently determine exercise capacity in these patients.

Association of physical activity and heart failure with preserved vs. reduced ejection fraction in the elderly: the Framingham Heart Study.

PubMed

Kraigher-Krainer, Elisabeth; Lyass, Asya; Massaro, Joseph M; Lee, Douglas S; Ho, Jennifer E; Levy, Daniel; Kannel, William B; Vasan, Ramachandran S

2013-07-01

Reduced physical activity is associated with increased risk of heart failure (HF) in middle-aged individuals. We hypothesized that physical inactivity is also associated with greater HF risk in older individuals, and examined if the association was consistent for HF with preserved ejection fraction (HFPEF) vs. HF with a reduced ejection fraction (HFREF). We evaluated 1142 elderly participants (mean age 76 years) from the Framingham Study without prior myocardial infarction and who attended a routine examination when daily physical activity was assessed systematically with a questionnaire. A composite score, the physical activity index (PAI), was calculated and modelled as tertiles, and related to incidence of HF, HFPEF, and HFREF on follow-up using proportional hazards regression models adjusting for age and sex, and then additionally for standard HF risk factors. Participants with HF and EF <45% vs. ≥45% were categorized as HFREF and HFPEF, respectively. On follow-up (mean 10 years), 250 participants developed HF (108 with HFPEF, 106 with HFREF, 36 with unavailable EF). In age- and sex-adjusted models, the middle and highest PAI tertiles were associated with a 15-56% lower risk of any HF, of HFREF, and of HFPEF, with a graded response across tertiles. In multivariable models, the association of higher PAI with lower risk of any HF and with HFPEF was maintained, whereas the association with HFREF was attenuated. Our study of an older community-based sample extends to the elderly and to HFPEF previous findings of a protective effect of physical activity on HF risk.

New echocardiographic predictors of clinical outcome in patients presenting with heart failure and a preserved left ventricular ejection fraction: a subanalysis of the Ka (Karolinska) Ren (Rennes) Study.

PubMed

Donal, Erwan; Lund, Lars H; Oger, Emmanuel; Hage, Camilla; Persson, Hans; Reynaud, Amélie; Ennezat, Pierre-Vladimir; Bauer, Fabrice; Drouet, Elodie; Linde, Cecilia; Daubert, Claude

2015-07-01

To identify electrocardiographic and echocardiographic predictors of mortality and hospitalizations for heart failure (HF) in the KaRen study. KaRen is a prospective, observational study of the long-term outcomes of patients presenting with heart failure and a preserved ejection fraction (HFpEF). We identified 538 patients who presented with acute cardiac decompensation, a >100 pg/mL serum b-type natriuretic peptide (BNP) or >300 pg/mL N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration and a left ventricular ejection fraction (LVEF) >45%. After 4-8 weeks of standard treatment, 413 patients (mean age = 76 ± 9 years, 55.9% women) returned for analyses of their clinical status, laboratory screen, and detailed electrocardiographic and Doppler echocardiographic recordings. They were followed for a mean of 28 months thereafter. The primary study endpoint was time to death from all causes or first hospitalization for heart failure. Mean LVEF was 62.4 ± 6.9% and median NT-proBNP 1410 pmol/L. PR interval >200 ms was present in 11.2% of patients and 14.9% had a >120 ms QRS duration, with left bundle branch block in only 6.3%. Over a mean follow-up of 28 months, 177 patients (42.9%) reached a primary study endpoint, including 61 deaths and 116 hospitalizations for heart failure. After adjustment for age, gender, New York Heart Association class, atrial fibrillation history, creatinine, sodium, BNP, ejection fraction, and right ventricular fractional shortening, only E/e' remained as a predictor, with a hazard ratio = 1.49 and P = 0.0012. The incidence of hospitalizations for HF and deaths in KaRen was high and E/e' predicted adverse clinical outcomes. These observations should help in the risk stratification and therapy of HFpEF. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.

Risk of Heart Failure With Preserved Ejection Fraction in Older Women After Contemporary Radiotherapy for Breast Cancer.

PubMed

Saiki, Hirofumi; Petersen, Ivy A; Scott, Christopher G; Bailey, Kent R; Dunlay, Shannon M; Finley, Randi R; Ruddy, Kathryn J; Yan, Elizabeth; Redfield, Margaret M

2017-04-11

Cardiomyocytes are resistant to radiation. However, cardiac radiation exposure causes coronary microvascular endothelial inflammation, a perturbation implicated in the pathogenesis of heart failure (HF) and particularly HF with preserved ejection fraction (HFpEF). Radiotherapy for breast cancer results in variable cardiac radiation exposure and may increase the risk of HF. We conducted a population-based case-control study of incident HF in 170 female residents of Olmsted County, Minnesota (59 cases and 111 controls), who underwent contemporary (1998-2013) radiotherapy for breast cancer with computed tomography-assisted radiotherapy planning. Controls were matched to cases for age, tumor side, chemotherapy use, diabetes mellitus, and hypertension. Mean cardiac radiation dose (MCRD) in each patient was calculated from the patient's computed tomography images and radiotherapy plan. Mean age at radiotherapy was 69±9 years. Of HF cases, 38 (64%) had EF≥50% (HFpEF), 18 (31%) had EF<50% (HF with reduced EF), and 3 (5%) did not have EF measured. The EF was ≥40% in 50 of the 56 HF cases (89%) with an EF measurement. The mean interval from radiotherapy to HF was 5.8±3.4 years. The odds of HF was higher in patients with a history of ischemic heart disease or atrial fibrillation. The MCRD was 2.5 Gy (range, 0.2-13.1 Gy) and higher in cases (3.3±2.7 Gy) than controls (2.1±2.0 Gy; P =0.004). The odds ratio (95% confidence interval) for HF per log MCRD was 9.1 (3.4-24.4) for any HF, 16.9 (3.9-73.7) for HFpEF, and 3.17 (0.8-13.0) for HF with reduced EF. The increased odds of any HF or HFpEF with increasing MCRD remained significant after adjustment for HF risk factors and in sensitivity analyses matching by cancer stage rather than tumor side. Only 18.6% of patients experienced new or recurrent ischemic events between radiotherapy and the onset of HF. The relative risk of HFpEF increases with increasing cardiac radiation exposure during contemporary conformal breast cancer radiotherapy. These data emphasize the importance of radiotherapy techniques that limit MCRD during breast cancer treatment. Moreover, these data provide further support for the importance of coronary microvascular compromise in the pathophysiology of HFpEF. © 2017 American Heart Association, Inc.

Pattern of endothelial progenitor cells and apoptotic endothelial cell-derived microparticles in chronic heart failure patients with preserved and reduced left ventricular ejection fraction

PubMed Central

Berezin, Alexander E.; Kremzer, Alexander A.; Martovitskaya, Yulia V.; Berezina, Tatyana A.; Gromenko, Elena A.

2016-01-01

Background Chronic heart failure (HF) remains a leading cause of cardiovascular (CV) mortality and morbidity worldwide. The aim of the study was to investigate whether the pattern of angiogenic endothelial progenitor cells (EPCs) and apoptotic endothelial cell-derived microparticles (EMPs) would be able to differentiate HF with reduced (HFrEF) and preserved (HFpEF) ejection fraction. Methods One hundred sixty four chronic HF subjects met inclusion criteria. Patients with global left ventricular ejection fraction ≥ 50% were categorized as the HFpEF group (n = 79) and those with ≤ 45% as the HFrEF group (n = 85). Therefore, to compare the circulating levels of biological markers 35 control subjects without HF were included in the study. All control individuals were age- and sex-matched chronic HF patients. The serum level of biomarkers was measured at baseline. The flow cytometric technique was used for predictably distinguishing circulating cell subsets depending on expression of CD45, CD34, CD14, Tie-2, and CD309 antigens and determining endothelial cell-derived microparticles. CD31+/annexin V+ was defined as apoptotic endothelial cell-derived MPs, MPs labeled for CD105+ or CD62E+ were determined as MPs produced due to activation of endothelial cells. Results In multivariate logistic regression model T2DM (R2 = 0.26; P = 0.001), obesity (R2 = 0.22; P = 0.001), previous MI (R2 = 0.17; P = 0.012), galectin-3 (R2 = 0.67; P = 0.012), CD31+/annexin V+ EMPs (R2 = 0.11; P = 0.001), NT-proBNP (R2 = 0.11; P = 0.046), CD14+ CD309+ cells (R2 = 0.058; P = 0.001), and CD14+ СD309+ Tie-2+ cells (R2 = 0.044; P = 0.028) were found as independent predictors of HFpEF. Using multivariate Cox-regression analysis adjusted etiology (previous myocardial infarction), cardiovascular risk factors (obesity, type 2 diabetes mellitus) we found that NT-proBNP (OR 1.08; 95% CI = 1.03–1.12; P = 0.001) and CD31+/annexin V+ EMPs to CD14+ CD309+ cell ratio (OR 1.06; 95% CI = 1.02–1.11; P = 0.02) were independent predictors for HFpEF. Conclusion We found that CD31+/annexin V+ EMPs to CD14+ CD309+ cell ratio added to NT-proBNP, clinical data, and cardiovascular risk factors has exhibited the best discriminate value and higher reliability to predict HFpEF compared with NT-proBNP and clinical data/cardiovascular risk factors alone. PMID:26981573

Ethnic differences in the association of QRS duration with ejection fraction and outcome in heart failure.

PubMed

Gijsberts, Crystel M; Benson, Lina; Dahlström, Ulf; Sim, David; Yeo, Daniel P S; Ong, Hean Yee; Jaufeerally, Fazlur; Leong, Gerard K T; Ling, Lieng H; Richards, A Mark; de Kleijn, Dominique P V; Lund, Lars H; Lam, Carolyn S P

2016-09-15

QRS duration (QRSd) criteria for device therapy in heart failure (HF) were derived from predominantly white populations and ethnic differences are poorly understood. We compared the association of QRSd with ejection fraction (EF) and outcomes between 839 Singaporean Asian and 11 221 Swedish white patients with HF having preserved EF (HFPEF)and HF having reduced EF (HFREF) were followed in prospective population-based HF studies. Compared with whites, Asian patients with HF were younger (62 vs 74 years, p<0.001), had smaller body size (height 163 vs 171 cm, weight 70 vs 80 kg, both p<0.001) and had more severely impaired EF (EF was <30% in 47% of Asians vs 28% of whites). Overall, unadjusted QRSd was shorter in Asians than whites (101 vs 104 ms, p<0.001). Lower EF was associated with longer QRSd (p<0.001), with a steeper association among Asians than whites (pinteraction<0.001), independent of age, sex and clinical covariates (including body size). Excluding patients with left bundle branch block (LBBB) and adjusting for clinical covariates, QRSd was similar in Asians and whites with HFPEF, but longer in Asians compared with whites with HFREF (p=0.001). Longer QRSd was associated with increased risk of HF hospitalisation or death (absolute 2-year event rate for ≤120 ms was 40% and for >120 ms it was 52%; HR for 10 ms increase of QRSd was 1.04 (1.03 to 1.06), p<0.001), with no interaction by ethnicity. We found ethnic differences in the association between EF and QRSd among patients with HF. QRS prolongation was similarly associated with increased risk, but the implications for ethnicity-specific QRSd cut-offs in clinical decision-making require further study. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Comparison of Gated SPECT Myocardial Perfusion Imaging with Echocardiography for the Measurement of Left Ventricular Volumes and Ejection Fraction in Patients With Severe Heart Failure

PubMed Central

Shojaeifard, Maryam; Ghaedian, Tahereh; Yaghoobi, Nahid; Malek, Hadi; Firoozabadi, Hasan; Bitarafan-Rajabi, Ahmad; Haghjoo, Majid; Amin, Ahmad; Azizian, Nasrin; Rastgou, Feridoon

2015-01-01

Background: Gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is known as a feasible tool for the measurement of left ventricular ejection fraction (EF) and volumes, which are of great importance in the management and follow-up of patients with coronary artery diseases. However, considering the technical shortcomings of SPECT in the presence of perfusion defect, the accuracy of this method in heart failure patients is still controversial. Objectives: The aim of the present study was to compare the results from gated SPECT MPI with those from echocardiography in heart failure patients to compare echocardiographically-derived left ventricular dimension and function data to those from gated SPECT MPI in heart failure patients. Patients and Methods: Forty-one patients with severely reduced left ventricular systolic function (EF ≤ 35%) who were referred for gated SPECT MPI were prospectively enrolled. Quantification of EF, end-diastolic volume (EDV), and end-systolic volume (ESV) was performed by using quantitative gated spect (QGS) (QGS, version 0.4, May 2009) and emory cardiac toolbox (ECTb) (ECTb, revision 1.0, copyright 2007) software packages. EF, EDV, and ESV were also measured with two-dimensional echocardiography within 3 days after MPI. Results: A good correlation was found between echocardiographically-derived EF, EDV, and ESV and the values derived using QGS (r = 0.67, r = 0.78, and r = 0.80 for EF, EDV, and ESV, respectively; P < 0.001) and ECTb (r = 0.68, 0.79, and r = 0.80 for EF, EDV, and ESV, respectively; P < 0.001). However, Bland-Altman plots indicated significantly different mean values for EF, 11.4 and 20.9 using QGS and ECTb, respectively, as compared with echocardiography. ECTb-derived EDV was also significantly higher than the EDV measured with echocardiography and QGS. The highest correlation between echocardiography and gated SPECT MPI was found for mean values of ESV different. Conclusions: Gated SPECT MPI has a good correlation with echocardiography for the measurement of left ventricular EF, EDV, and ESV in patients with severe heart failure. However, the absolute values of these functional parameters from echocardiography and gated SPECT MPI measured with different software packages should not be used interchangeably. PMID:26889455

The management of diagnosed heart failure in older people in primary care.

PubMed

Jones, Nicholas R; Hobbs, F D Richard; Taylor, Clare J

2017-12-01

Heart failure (HF) is a common condition affecting predominantly older people. Symptoms include breathlessness and fatigue, and can significantly reduce quality of life. HF rarely occurs in isolation, with most patients having several co-existing diseases requiring multiple medications. There is a large evidence base for treatment of HF with reduced ejection fraction, or HFrEF; however, many of the trials did not include older people with multimorbidity so their findings should be applied to this group with some caution. The evidence for treatment of HF with preserved ejection fraction, or HFpEF, is much less well established in all age groups. Older people with HF are usually managed in primary care with input from specialist HF teams when needed. General practitioners are trained to take a generalist approach, which allows them to deliver holistic, person-centred care. The wider multidisciplinary team is also important during the patient's HF journey, with a particular need to consider palliative care towards the end of life. This article summarises the important aspects of HF management in older people from the perspective of primary care. Copyright © 2017 Elsevier B.V. All rights reserved.

Cardiac Amyloidosis and its New Clinical Phenotype: Heart Failure with Preserved Ejection Fraction

PubMed Central

Mesquita, Evandro Tinoco; Jorge, Antonio José Lagoeiro; Souza Junior, Celso Vale; de Andrade, Thais Ribeiro

2017-01-01

Heart failure with preserved ejection fraction (HFpEF) is now an emerging cardiovascular epidemic, being identified as the main phenotype observed in clinical practice. It is more associated with female gender, advanced age and comorbidities such as hypertension, diabetes, obesity and chronic kidney disease. Amyloidosis is a clinical disorder characterized by the deposition of aggregates of insoluble fibrils originating from proteins that exhibit anomalous folding. Recently, pictures of senile amyloidosis have been described in patients with HFpEF, demonstrating the need for clinical cardiologists to investigate this etiology in suspect cases. The clinical suspicion of amyloidosis should be increased in cases of HFPS where the cardio imaging methods are compatible with infiltrative cardiomyopathy. Advances in cardio imaging methods combined with the possibility of performing genetic tests and identification of the type of amyloid material allow the diagnosis to be made. The management of the diagnosed patients can be done in partnership with centers specialized in the study of amyloidosis, which, together with the new technologies, investigate the possibility of organ or bone marrow transplantation and also the involvement of patients in clinical studies that evaluate the action of the new emerging drugs. PMID:28678923

Real-life indications to ivabradine treatment for heart rate optimization in patients with chronic systolic heart failure.

PubMed

Tondi, Lara; Fragasso, Gabriele; Spoladore, Roberto; Pinto, Giuseppe; Gemma, Marco; Slavich, Massimo; Godino, Cosmo; Salerno, Anna; Montanaro, Claudia; Margonato, Alberto

2018-05-11

: Ivabradine is a selective and specific inhibitor of If current. With its pure negative chronotropic action, it is recommended by European Society of Cardiology and American College of Cardiology/American Heart Association guidelines in symptomatic heart failure patients (NYHA ≥ 2) with ejection fraction 35% or less, sinus rhythm and heart rate (HR) at least 70 bpm, despite maximally titrated β-blocker therapy. Data supporting this indication mainly derive from the SHIFT study, in which ivabradine reduced the combined endpoint of mortality and hospitalization, despite the fact that only 26% of patients enrolled were on optimal β-blocker doses. The aim of the present analysis is to establish the real-life eligibility for ivabradine in a population of patients with systolic heart failure, regularly attending a single heart failure clinic and treated according to guideline-directed medical therapy (GDMT). The clinical cards of 308 patients with heart failure with reduced ejection fraction (HFrEF) through a 68-month period of observation were retrospectively analyzed. GDMT, including β-blocker up-titration to maximal tolerated dose, was implemented during consecutive visits at variable intervals. Demographic, clinical and echocardiographic data were collected at each visit, together with 12-leads ECG and N-terminal pro-B-type natriuretic peptide levels. Out of 308 analyzed HFrEF patients, 220 (71%) were on effective β-blocker therapy, up-titrated to effective/maximal tolerated dose (55 ± 28% of maximal dose) (HR 67 ± 10 bpm). Among the remaining 88 patients, 10 (3.2%) were on maximally tolerated β blocker and ivabradine; 21 patients (6.8%), despite being on maximal tolerated β-blocker dose, had still HR ≥70 bpm, ejection fraction 35% or less and were symptomatic NYHA ≥2, being therefore eligible for ivabradine treatment. The remaining 57 (18%) patients were not on β blocker due to either intolerance or major contraindications. Among them, 13 (4%) were taking ivabradine alone. Of the final 44 (14%) patients, 27 (9%) showed an inadequate HR control (74 ± 6 bpm). Of these, only eight (3%) patients resulted to be eligible for ivabradine introduction according to HR and ejection fraction parameters. Overall ivabradine was indicated in 52 patients (16.8%) out of 308 enrolled.In conclusion, in a carefully managed population of patients with moderate and stable HFrEF, in which optimal GDMT is properly attained, indication to ivabradine treatment is around 17%.

Estimating fat mass in heart failure patients.

PubMed

Trippel, Tobias Daniel; Lenk, Julian; Gunga, Hanns-Christian; Doehner, Wolfram; von Haehling, Stephan; Loncar, Goran; Edelmann, Frank; Pieske, Burkert; Stahn, Alexander; Duengen, Hans-Dirk

2016-01-01

Body composition (BC) assessments in heart failure (HF) patients are mainly based on body weight, body mass index and waist-to-hip ratio. The present study compares BC assessments by basic anthropometry, dual energy X-ray absorptiometry (DXA), bioelectrical impedance spectroscopy (BIS), and air displacement plethysmography (ADP) for the estimation of fat (FM) and fat-free mass (FFM) in a HF population. In this single-centre, observational pilot study we enrolled 52 patients with HF (33 HF with reduced ejection fraction (HFrEF), 19 HF with preserved ejection fraction (HFpEF); mean age was 67.7 ±9.9 years, 41 male) and 20 healthy controls. DXA was used as a reference standard for the measurement of FM and FFM. In the HF population, linear regression for DXA-FM and waist-to-hip ratio ( r = -0.05, 95% CI: (-0.32)-0.23), body mass index ( r = 0.47, 95% CI: 0.23-0.669), and body density ( r = -0.87, 95% CI: (-0.93)-(-0.87)) was obtained. In HF, Lin's concordance correlation coefficient of DXA-FM (%) with ADP-FM (%) was 0.76 (95% CI: 0.64-0.85) and DXA-FFM [kg] with DXA-ADP [kg] was 0.93 (95% CI: 0.88-0.96). DXA-FM (%) for BIS-FM (%) was 0.69 (95% CI: 0.54-0.80) and 0.73 (95% CI: 0.60-0.82) for DXA-FFM [kg] and BIS-FFM [kg]. Body density is a useful surrogate for FM. ADP was found suitable for estimating FM (%) and FFM [kg] in HF patients. BIS showed acceptable results for the estimation of FM (%) in HFrEF and for FFM [kg] in HFpEF patients. We encourage selecting a suitable method for BC assessment according to the compartment of interest in the HF population.

Non-volumetric echocardiographic indices and qualitative assessment of right ventricular systolic function in Ebstein's anomaly: comparison with CMR-derived ejection fraction in 49 patients.

PubMed

Kühn, Andreas; Meierhofer, Christian; Rutz, Tobias; Rondak, Ina-Christine; Röhlig, Christoph; Schreiber, Christian; Fratz, Sohrab; Ewert, Peter; Vogt, Manfred

2016-08-01

Ebstein's anomaly (EA) is often associated with right ventricular (RV) dysfunction. Data on echocardiographic quantification of RV function are, however, rare. The aim of this study was to determine how non-volumetric echocardiographic indices and qualitative assessment of global systolic RV function correlate with cardiovascular magnetic resonance (CMR)-derived RV ejection fraction (EF). We compared six echocardiographic indices and qualitative assessment of RV function with the gold standard CMR. A total of 49 unoperated patients with EA and a mean age of 32 ± 18 years were examined. Tricuspid annular plane systolic excursion, tissue Doppler myocardial velocities (peak S and IVA) and 2D strain and strain rate measures for the RV were compared with CMR-derived EF. Only 2D global longitudinal strain (2D-GLS), out of the six parameters investigated, showed a weak, although statistically significant correlation with CMR-derived RVEF (R = -0.4, P = 0.01). Using a cut-off value of -20.15, 2D-GLS sensitivity (77%) and specificity (46%) in detecting patients with a CMR-derived EF of <50% were comparable with qualitative assessment (sensitivity 77%, specificity 45%). Overall echocardiographic parameters of RV function correlate poorly with CMR-derived EF in patients with EA. Only 2D global longitudinal RV strain correlated weakly with CMR-derived RVEF. However, the sensitivity and specificity for detecting RV dysfunction using 2D strain imaging were comparable with qualitative RV functional assessment. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Presence of ´isolated´ tricuspid regurgitation should prompt the suspicion of heart failure with preserved ejection fraction

PubMed Central

Mascherbauer, Julia; Kammerlander, Andreas A.; Zotter-Tufaro, Caroline; Aschauer, Stefan; Duca, Franz; Dalos, Daniel; Winkler, Susanne; Schneider, Matthias; Bergler-Klein, Jutta; Bonderman, Diana

2017-01-01

Background Diastolic dysfunction of the left ventricle is common but frequently under-diagnosed. Particularly in advanced stages affected patients may present with significant functional tricuspid regurgitation (TR) as the most prominent sign on echocardiography. The underlying left ventricular pathology may eventually be missed and symptoms of heart failure are attributed to TR, with respective therapeutic consequences. The aim of the present study was to determine prevalence and mechanisms underlying TR evolution in heart failure with preserved ejection fraction (HFpEF). Methods and results Consecutive HFpEF patients were enrolled in this prospective, observational study. Confirmatory diagnostic tests including echocardiography and invasive hemodynamic assessments were performed. Of the 175 patients registered between 2010 and 2014, 51% had significant (moderate or severe) TR without structural abnormalities of the tricuspid valve. Significant hemodynamic differences between patients with and without relevant TR were encountered. These included elevated pulmonary vascular resistance (p = 0.038), reduced pulmonary arterial compliance (PAC, p = 0.005), and elevated left ventricular filling pressures (p = 0.039) in the TR group. Multivariable binary logistic regression analysis revealed diastolic pulmonary artery pressure (p = 0.029) and PAC (p = 0.048) as independent determinants of TR. Patients were followed for 18.1±14.1 months, during which 32% had a cardiac event. While TR was associated with outcome in the univariable analysis, it failed to predict event-free survival in the multivariable model. Conclusions The presence of ´isolated´ functional TR should prompt the suspicion of HFpEF. Our data show that significant TR is a marker of advanced HFpEF but neither an isolated entity nor independently associated with event-free survival. PMID:28199339

Effects of Ramadan fasting on the symptoms of chronic heart failure.

PubMed

Abazid, Rami M; Khalaf, Hassan H; Sakr, Haitham I; Altorbak, Nora A; Alenzi, Habiba S; Awad, Zaki M; Smettei, Osama A; Elsanan, Moataz A; Widyan, Adel M; Azazy, Ahmed S; Chamsi-Pasha, Hassan W

2018-04-01

To investigate the effect of Ramadan fasting on the symptoms of chronic heart failure with a reduced ejection fraction (HFrEF). Globally, more than one billion Muslims fast during Ramadan. Data regarding the effect of fasting in heart failure patients with a reduced ejection fraction are limited. We prospectively studied 249 outpatients with HFrEF who undertook Ramadan fasting at tertiary care cardiac center in Saudi Arabia in 2017. We obtained information regarding the clinical assessment, diagnosis, emergency department visits, and hospitalization during and in the month preceding Ramadan. We enrolled 249 patients, 227 (91%) undertook the fast for the entire month. During Ramadan, 209 (92%) patients remained hemodynamically stable, whereas 18 (8%) developed instability. The mean New York Heart Association (NYHA) functional class was significantly lower in the stable than in the unstable group (1.46±0.7 vs. 3.22±0.55, p less than 0.0001), although no intergroup differences were observed before Ramadan. Patients from the unstable vs. the stable group showed significantly less adherence to medications (67% vs. 94%, p less than 0.0001) and to diet (39% vs. 79%, p less than 0.0001), and a lower likelihood of demonstrating ischemic cardiomyopathy as an underlying etiology of HFrEF (33% vs. 57%, p=0.046). Dependent t-test analysis including all patients showed that the NYHA classification before Ramadan was significantly higher than during Ramadan (2.19±0.9 vs. 1.6±0.8, t-value 8.5, p less than 0.0001). In most patients with chronic HFrEF, Ramadan fasting is considered safe. Non-adherence to medication and diet are significantly associated with decompensated heart failure during Ramadan.

Effect of Switching from Cilnidipine to Azelnidipine on Cardiac Sympathetic Nerve Function in Patients with Heart Failure Preserved Ejection Fraction.

PubMed

Kiuchi, Shunsuke; Hisatake, Shinji; Kabuki, Takayuki; Oka, Takashi; Dobashi, Shintaro; Fujii, Takahiro; Ikeda, Takanori

2018-01-27

Cardiac sympathetic nerve activity is known to play a key role in the development and progression of heart failure (HF). Azelnidipine, an L-type calcium channel blocker (CCB), inhibits the sympathetic nerve activity of the central system. In contrast, cilnidipine, an N-type CCB, inhibits the sympathetic nerve activity of the peripheral system. CCBs are recommended as class IIa in patients with HF preserved ejection fraction (HFpEF); however, there are no comparative data on the difference in effect of cilnidipine and azelnidipine in patients with HFpEF and hypertension. We investigated the difference in effect of azelnidipine compared with cilnidipine in patients with HFpEF. Twenty-four consecutive HF patients who received angiotensin II type1a receptor blocker and beta blocker from April 2013 to January 2015 were enrolled. Cilnidipine was switched to azelnidipine during the follow-up period. Blood pressures, heart rate, blood tests, echocardiography, and 123 I-metaiodobenzylguanidine (MIBG) cardiac-scintigraphy were measured before and after 6 months from azelnidipine administration. B-type natriuretic peptide tended to decrease after switching to azelnidipine; however, there were no significant differences between the pre-state and post-state (pre-state: 118.5 pg/mL and post-state: 78.4 pg/mL, P = 0.137). Other laboratory findings, including catecholamine, also did not change significantly. In echocardiography, there were no significant differences in systolic and diastolic functions at the pre-state and post-state. As for MIBG, there were no significant changes in heart/mediastinum ratio. However, washout rate was significantly reduced (pre-state: 42.9 and post-state: 39.6, P = 0.030). Azelnidipine improved the dysfunction of cardiac sympathetic nerve activity compared with cilnidipine in patients with HFpEF.

Barriers to Beta-Blocker Use and Up-Titration Among Patients with Heart Failure with Reduced Ejection Fraction.

PubMed

Levitan, Emily B; Van Dyke, Melissa K; Loop, Matthew Shane; O'Beirne, Ronan; Safford, Monika M

2017-12-01

For patients with heart failure with reduced ejection fraction (HFrEF), guidelines recommend use of beta-blockers with gradual up-titration. However, many patients with HFrEF do not use beta-blockers and up-titration is rare. Our purpose was to identify and rank barriers to beta-blocker use and up-titration from the perspective of primary care physicians. We conducted 4 moderated, structured group discussions among 19 primary care physicians using the nominal group technique; 16 participants also completed a survey. Participants generated lists of barriers to beta-blocker use and up-titration among patients with HFrEF. Each participant had six votes with three votes assigned to the item ranked most important, two to the second most important item, and one to the third most important item. Investigators characterized items into themes. The percentage of available votes was calculated for each theme. Fifteen of 16 participating primary care physicians who completed the survey reported that management of beta-blockers was their responsibility. Treatment/side effects, particularly hypotension, were identified as the most important barrier for beta-blocker use (72% of available votes) followed by polypharmacy (11%), healthcare system barriers (10%), and comorbidities (6%). Barriers to up-titration included treatment/side effects (49% of available votes), patient communication/buy-in (21%), polypharmacy (13%), and healthcare system barriers (8%). Many barriers to guideline concordant use of beta-blockers among patients with HFrEF identified by primary care providers are not readily modifiable. Addressing these barriers may require development, testing, and dissemination of protocols for beta-blocker initiation and up-titration that are safe and appropriate in primary care.

Low diastolic blood pressure and adverse outcomes in heart failure with preserved ejection fraction.

PubMed

Tsujimoto, Tetsuro; Kajio, Hiroshi

2018-07-15

It remains unknown whether a low diastolic blood pressure (DBP) increases the risks of cardiovascular events and death in patients with heart failure with preserved ejection fraction (HFpEF). We used data from the TOPCAT trial. The primary outcome was a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure. Hazard ratios (HRs) were analyzed for DBPs of <60, 60-69, 70-79, and ≥90 mm Hg in comparison with a DBP of 80-89 mm Hg using multivariable Cox proportional hazard models. This study included 3417 patients with HFpEF who had a controlled blood pressure. In the mean follow-up period of 3.0 years, 881 patients experienced at least one confirmed primary outcome event. Compared with patients with a DBP of 80-89 mm Hg, the adjusted HRs for primary outcome events were significantly higher in those with DBPs of <60 mm Hg (HR: 2.19 [95% confidence interval,1.72-2.78]) and 60-69 mm Hg (HR: 1.52 [1.23-1.87]). Similarly, the adjusted HRs for all-cause death, major cardiovascular events, and hospitalization for heart failure, but not stroke, were significantly higher in patients with a DBP of <70 mm Hg. A relationship between a low DBP and adverse outcomes was found in HFpEF patients with a systolic blood pressure of ≥120 mm Hg; however, a low systolic blood pressure with a DBP of ≥70 mm Hg was not associated with these event risks. A low DBP increased the risks of adverse outcomes in patients with HFpEF. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

The importance of integrated left atrial evaluation: From hypertension to heart failure with preserved ejection fraction.

PubMed

Beltrami, Matteo; Palazzuoli, Alberto; Padeletti, Luigi; Cerbai, Elisabetta; Coiro, Stefano; Emdin, Michele; Marcucci, Rossella; Morrone, Doralisa; Cameli, Matteo; Savino, Ketty; Pedrinelli, Roberto; Ambrosio, Giuseppe

2018-02-01

Functional analysis and measurement of left atrium are an integral part of cardiac evaluation, and they represent a key element during non-invasive analysis of diastolic function in patients with hypertension (HT) and/or heart failure with preserved ejection fraction (HFpEF). However, diastolic dysfunction remains quite elusive regarding classification, and atrial size and function are two key factors for left ventricular (LV) filling evaluation. Chronic left atrial (LA) remodelling is the final step of chronic intra-cavitary pressure overload, and it accompanies increased neurohormonal, proarrhythmic and prothrombotic activities. In this systematic review, we aim to purpose a multi-modality approach for LA geometry and function analysis, which integrates diastolic flow with LA characteristics and remodelling through application of both traditional and new diagnostic tools. The most important studies published in the literature on LA size, function and diastolic dysfunction in patients with HFpEF, HT and/or atrial fibrillation (AF) are considered and discussed. In HFpEF and HT, pulsed and tissue Doppler assessments are useful tools to estimate LV filling pressure, atrio-ventricular coupling and LV relaxation but they need to be enriched with LA evaluation in terms of morphology and function. An integrated evaluation should be also applied to patients with a high arrhythmic risk, in whom eccentric LA remodelling and higher LA stiffness are associated with a greater AF risk. Evaluation of LA size, volume, function and structure are mandatory in the management of patients with HT, HFpEF and AF. A multi-modality approach could provide additional information, identifying subjects with more severe LA remodelling. Left atrium assessment deserves an accurate study inside the cardiac imaging approach and optimised measurement with established cut-offs need to be better recognised through multicenter studies. © 2017 John Wiley & Sons Ltd.

Evaluating the Safety and Tolerability of Sacubitril/Valsartan for HFrEF Managed Within a Pharmacist Clinic.

PubMed

Pogge, Elizabeth K; Davis, Lindsay E

2018-04-01

The objective of this research was to describe the use of pharmacist-managed sacubitril/valsartan therapy in a multi-center, outpatient cardiac group. Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNi), is a novel agent for the treatment of heart failure. An ARNi is recommended by national guidelines to be used in place of angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) therapy for patients who remain symptomatic. A retrospective chart review was performed to identify patients initiated and fully titrated on sacubitril/valsartan therapy from July 7, 2015 to March 7, 2017. Fifty-two of the 72 symptomatic heart failure with reduced ejection fraction (HFrEF) patients prescribed sacubitril/valsartan during the 21-month period were included in this analysis. The average ejection fraction was 26%. The average age was 69 years. At baseline, 26.9% of patients were not on ACEi/ARB therapy and 13.5% were on target-dose therapy. After completing the uptitration process, the maximally tolerated dose of sacubitril/valsartan was 5.8% low-dose, 7.7% mid-dose, and 86.5% target-dose. Loop and thiazide diuretic use decreased significantly. There was a significant mean reduction in systolic blood pressure of 6 mmHg with no significant changes in serum creatinine, blood urea nitrogen, or potassium levels. With close monitoring and follow-up, ARNi therapy was a safe alternative to ACEi/ARB therapy for chronic symptomatic HFrEF when initiated within a pharmacist clinic.

Do sodium-glucose co-transporter-2 inhibitors prevent heart failure with a preserved ejection fraction by counterbalancing the effects of leptin? A novel hypothesis.

PubMed

Packer, Milton

2018-06-01

Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of serious heart failure events in patients with type 2 diabetes, but little is known about mechanisms that might mediate this benefit. The most common heart failure phenotype in type 2 diabetes is obesity-related heart failure with a preserved ejection fraction (HFpEF). It has been hypothesized that the synthesis of leptin in this disorder leads to sodium retention and plasma volume expansion as well as to cardiac and renal inflammation and fibrosis. Interestingly, leptin-mediated neurohormonal activation appears to enhance the expression of SGLT2 in the renal tubules, and SGLT2 inhibitors exert natriuretic actions at multiple renal tubular sites in a manner that can oppose the sodium retention produced by leptin. In addition, SGLT2 inhibitors reduce the accumulation and inflammation of perivisceral adipose tissue, thus minimizing the secretion of leptin and its paracrine actions on the heart and kidneys to promote fibrosis. Such fibrosis probably contributes to the impairment of cardiac distensibility and glomerular function that characterizes obesity-related HFpEF. Ongoing clinical trials with SGLT2 inhibitors in heart failure are positioned to confirm or refute the hypothesis that these drugs may favourably influence the course of obesity-related HFpEF by their ability to attenuate the secretion and actions of leptin. © 2018 John Wiley & Sons Ltd.

Heart Failure with Preserved Ejection Fraction: Molecular Pathways of the Aging Myocardium

PubMed Central

Loffredo, Francesco S.; Nikolova, Andriana P.; Pancoast, James R.; Lee, Richard T.

2014-01-01

Age-related diastolic dysfunction is a major factor in the epidemic of heart failure. In patients hospitalized with heart failure, diastolic heart failure is now as common as systolic heart failure. We now have many successful treatments for HFrEF, while specific treatment options for HFpEF patients remain elusive. The lack of treatments for HFpEF reflects our very incomplete understanding of this constellation of diseases. There are many pathophysiological factors in HFpEF, but aging appears to play an important role. Here we propose that aging of the myocardium is itself a specific pathophysiological process. New insights into the aging heart, including hormonal controls and specific molecular pathways such as microRNAs, are pointing to myocardial aging as a potentially reversible process. While the overall process of aging remains mysterious, understanding the molecular pathways of myocardial aging has never been more important. Unraveling these pathways could lead to new therapies for the enormous and growing problem of HFpEF. PMID:24951760

Galectin-3 in heart failure with preserved ejection fraction. A RELAX trial substudy (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure).

PubMed

AbouEzzeddine, Omar F; Haines, Phillip; Stevens, Susanna; Nativi-Nicolau, Jose; Felker, G Michael; Borlaug, Barry A; Chen, Horng H; Tracy, Russell P; Braunwald, Eugene; Redfield, Margaret M

2015-03-01

This study hypothesized that elevated galectin-3 (Gal-3) levels would identify patients with more advanced heart failure (HF) with preserved ejection fraction (HFpEF) as assessed by key pathophysiological domains. Gal-3 is implicated in the pathogenesis of cardiac fibrosis but is also increased with normal aging and renal dysfunction. Cardiac fibrosis may contribute to cardiac dysfunction, exercise intolerance, and congestion in HFpEF. Two hundred eight patients from the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial of sildenafil in HFpEF had Gal-3 measured at enrollment. Pathophysiological domains assessed included biomarkers of neurohumoral activation, fibrosis, inflammation and myocardial necrosis, congestion severity and quality of life, cardiac structure and function, and exercise performance. Analysis adjusted for age, sex, and/or cystatin-C levels. Potential interaction between baseline Gal-3 and treatment (sildenafil) effect on the RELAX study primary endpoint (change in peak oxygen consumption) was tested. Gal-3 levels were associated with age and severity of renal dysfunction. Adjusting for age, sex, and/or cystatin-C, Gal-3 was not associated with biomarkers of neurohumoral activation, fibrosis, inflammation or myocardial necrosis, congestion or quality-of-life impairment, cardiac remodeling or dysfunction, or exercise intolerance. Gal-3 did not identify patients who responded to phosphodiesterase type 5 (PDE-5) inhibitors (interaction p = 0.53). In overt HFpEF, Gal-3 was related to severity of renal dysfunction and accounting for this, was not independently associated with severity of pathophysiological derangements or response PDE-5 inhibition. These findings underscore the need to adjust for renal function when interpreting Gal-3 levels, and call into question the value of Gal-3 to quantify disease severity in overt HFpEF. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Impaired Right Ventricular-Pulmonary Arterial Coupling and Effect of Sildenafil in Heart Failure With Preserved Ejection Fraction: An Ancillary Analysis From the Phosphodiesterase-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) Trial.

PubMed

Hussain, Imad; Mohammed, Selma F; Forfia, Paul R; Lewis, Gregory D; Borlaug, Barry A; Gallup, Dianne S; Redfield, Margaret M

2016-04-01

Right ventricular (RV) dysfunction (RVD) is a poor prognostic factor in heart failure with preserved ejection fraction (HFpEF). The physiological perturbations associated with RVD or RV function indexed to load (RV-pulmonary arterial [PA] coupling) in HFpEF have not been defined. HFpEF patients with marked impairment in RV-PA coupling may be uniquely sensitive to sildenafil. In a subset of HFpEF patients enrolled in the Phosphodiesteas-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) trial, physiological variables and therapeutic effect of sildenafil were examined relative to the severity of RVD (tricuspid annular plane systolic excursion [TAPSE]) and according to impairment in RV-PA coupling (TAPSE/pulmonary artery systolic pressure) ratio. The prevalence of atrial fibrillation and diuretic use, n-terminal probrain natriuretic peptide levels, renal dysfunction, neurohumoral activation, myocardial necrosis and fibrosis biomarkers, and the severity of diastolic dysfunction all increased with severity of RVD. Peak oxygen consumption decreased and ventilatory inefficiency (VE/VCO2 slope) increased with increasing severity of RVD. Many but not all physiological derangements were more closely associated with the TAPSE/pulmonary artery systolic pressure ratio. Compared with placebo, at 24 weeks, TAPSE decreased, and peak oxygen consumption and VE/CO2 slope were unchanged with sildenafil. There was no interaction between RV-PA coupling and treatment effect, and sildenafil did not improve TAPSE, peak oxygen consumption, or VE/VCO2 in patients with pulmonary hypertension and RVD. HFpEF patients with RVD and impaired RV-PA coupling have more advanced heart failure. In RELAX patients with RVD and impaired RV-PA coupling, sildenafil did not improve RV function, exercise capacity, or ventilatory efficiency. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00763867. © 2016 American Heart Association, Inc.

Management of heart failure with preserved ejection fraction in a local public hospital in Hong Kong.

PubMed

Leung, Angel W; Chan, Cherise Y; Yan, Bryan P; Yu, Cheuk Man; Lam, Yat Yin; Lee, Vivian W

2015-02-25

Heart failure (HF) is one of the most debilitating chronic illnesses. The prevalence is expected to increase due to aging population. The current study aimed to examine the management of heart failure with preserved ejection fraction (HFpEF) including drug use pattern, direct medical cost and humanistic outcome in a local public hospital in Hong Kong. The current study adopted the retrospective observational study design. Subjects were recruited from the Heart Failure Registry of the Prince of Wales Hospital in Hong Kong between 2006 and 2008 and completed the Minnesota Living with Heart Failure Questionnaire (MLHFQ) at 3 designated time-points conferred eligibility. Patients with significant valvular disorder were excluded. Each patient's medical record was reviewed for 12 months after the date of admission. Heart failure related admissions, clinic visits, cardiovascular drugs, laboratory tests and diagnostic tests were documented. Costs and MLHFQ scores in patients with or without hypertension, diabetes and renal impairment were compared. A total of 73 HFpEF patients were included. It was found that loop diuretics (93.1%, 78.1%) was the most frequently used agent for HFpEF management in both in-patient and out-patient settings. The mean 1-year direct medical cost was USD$ 19969 (1 US $ = 7.8 HK$), with in-patient ward care contributing to the largest proportion (72.2%) of the total cost. Patients with diabetes or renal impairment were associated with a higher cost of HFpEF management. Significant difference was found in the renal impairment group (median cost: USD$ 24604.2 versus USD$ 12706.8 in no impairment group, p = 0.023). The MLHFQ scores of the subjects improved significantly during the study period (p < 0.0005). The cost of management of HFpEF was enormous and further increased in the presence of comorbidities.

Prevalence of left ventricular systolic dysfunction and heart failure with reduced ejection fraction in men and women with type 2 diabetes mellitus: a systematic review and meta-analysis.

PubMed

Bouthoorn, Selma; Gohar, Aisha; Valstar, Gideon; den Ruijter, Hester M; Reitsma, J B; Hoes, Arno W; Rutten, Frans H

2018-04-18

Type 2 diabetes mellitus (T2D) is associated with the development of left ventricular systolic dysfunction (LVSD) and heart failure with reduced ejection fraction (HFrEF). T2D patients with LVSD are at higher risk of mortality and morbidity than patients without LVSD, while progression of LVSD can be delayed or halted by the use of proven therapies. As estimates of the prevalence are scarce and vary considerably, the aim of this study was to retrieve summary estimates of the prevalence of LVSD/HFrEF in T2D and to see if there were any sex differences. A systematic search of Medline and Embase was performed to extract the prevalence of LVSD/HFrEF in T2D (17 studies, mean age 50.1 ± 6.3 to 71.5 ± 7.5), which were pooled using random-effects meta-analysis. The pooled prevalence of LVSD was higher in hospital populations (13 studies, n = 5835, 18% [95% CI 17-19%]), than in the general population (4 studies, n = 1707, 2% [95% CI 2-3%]). Seven studies in total reported sex-stratified prevalence estimates (men: 7% [95% CI 5-8%] vs. women: 1.3% [95% CI 0.0.2.2%]). The prevalence of HFrEF was available in one general population study (5.8% [95% CI 3.7.6%], men: 6.8% vs. women: 3.0%). The summary prevalence of LVSD is higher among T2D patients from a hospital setting compared with from the general population, with a higher prevalence in men than in women in both settings. The prevalence of HFrEF among T2D in the population was only assessed in a single study and again was higher among men than women.

A Global Assessment of Circulating Prolysyl Oxidase in Nonischemic Patients With Garden-variety Heart Failure With Preserved Ejection Fraction.

PubMed

Muñoz Calvo, Benjamín; Villa Martínez, Ana; López Orgil, Susana; López Andrés, Natalia; Román García, Feliciano; Víctor Palomares, Virginia; de la Calle de la Villa, Esther; Nadador Patiño, Verónica; Arribas-Gómez, Ignacio

2018-05-25

Lysyl oxidase is overexpressed in the myocardium of patients with hypertensive cardiomyopathy. We aimed to explore whether patients with hypertensive-metabolic heart failure with preserved ejection fraction (HM-HFpEF) also have increased concentrations of circulating prolysyl oxidase (cpLOX) and its possible consequences. We quantified cpLOX concentrations in 85 nonischemic patients with stage C, HM-HFpEF, and compared them with those of 51 healthy controls. We also assessed the correlations of cpLOX with myocardial stiffness parameters, collagen turnover products and fibrogenic cytokines, as well as the predictive value of plasma proenzyme levels at 1-year of follow-up. We detected raised cpLOX values and found that they correlated with calculated E/E' ratios and stiffness constants. The subgroup of patients with type I diastolic dysfunction showed a single negative correlation between cpLOX and B-type natriuretic peptide whereas patients with a restrictive diastolic pattern showed a strong correlation between cpLOX and galectin-3. Kaplan-Meier analysis revealed that cpLOX > 52.20 ng/mL slightly increased the risk of a fatal outcome (log-rank = 4.45; P = .034). When Cox regression was used, cpLOX was found to be a significant independent predictor of cardiovascular death or hospitalization due to the decompensation of HM-HFpEF (HR, 1.360; 95%CI, 1.126-1.638; P = .046). Patients with symptomatic HM-HFpEF show high cpLOX serum levels associated with restrictive diastolic filling indices. These levels represent a moderate risk factor for poor clinical outcome. Throughout the natural history of HM-HFpEF, we observed that cpLOX concentrations were initially negatively correlated with B-type natriuretic peptide but positively correlated with galectin-3 as advanced diastolic dysfunction developed. Copyright © 2018. Published by Elsevier España, S.L.U.

Peak Exercise Oxygen Uptake Predicts Recurrent Admissions in Heart Failure With Preserved Ejection Fraction.

PubMed

Palau, Patricia; Domínguez, Eloy; Núñez, Eduardo; Ramón, José María; López, Laura; Melero, Joana; Sanchis, Juan; Bellver, Alejandro; Santas, Enrique; Bayes-Genis, Antoni; Chorro, Francisco J; Núñez, Julio

2018-04-01

Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent syndrome with an elevated risk of morbidity and mortality. To date, there is scarce evidence on the role of peak exercise oxygen uptake (peak VO 2 ) for predicting the morbidity burden in HFpEF. We sought to evaluate the association between peak VO 2 and the risk of recurrent hospitalizations in patients with HFpEF. A total of 74 stable symptomatic patients with HFpEF underwent a cardiopulmonary exercise test between June 2012 and May 2016. A negative binomial regression method was used to determine the association between the percentage of predicted peak VO 2 (pp-peak VO 2 ) and recurrent hospitalizations. Risk estimates are reported as incidence rate ratios. The mean age was 72.5 ± 9.1 years, 53% were women, and all patients were in New York Heart Association functional class II to III. Mean peak VO 2 and median pp-peak VO 2 were 10 ± 2.8mL/min/kg and 60% (range, 47-67), respectively. During a median follow-up of 276 days [interquartile range, 153-1231], 84 all-cause hospitalizations in 31 patients (41.9%) were registered. A total of 15 (20.3%) deaths were also recorded. On multivariate analysis, accounting for mortality as a terminal event, pp-peak VO 2 was independently and linearly associated with the risk of recurrent admission. Thus, and modeled as continuous, a 10% decrease of pp-peak VO 2 increased the risk of recurrent hospitalizations by 32% (IRR, 1.32; 95%CI, 1.03-1.68; P = .028). In symptomatic elderly patients with HFpEF, pp-peak VO 2 predicts all-cause recurrent admission. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

The Prognostic Importance of Impaired Systolic Function in Heart Failure with Preserved Ejection Fraction and the Impact of Spironolactone

PubMed Central

Shah, Amil M.; Claggett, Brian; Sweitzer, Nancy K.; Shah, Sanjiv J.; Anand, Inder S.; Liu, Li; Pitt, Bertram; Pfeffer, Marc A.; Solomon, Scott D.

2015-01-01

Background Impairment in left ventricular (LV) systolic function has been described in heart failure with preserved ejection fraction (HFpEF), but its prognostic relevance is not known. We determined whether LV longitudinal strain (LS) is predictive of cardiovascular (CV) outcomes in HFpEF beyond clinical and conventional echocardiographic measures. Methods and Results LS was assessed by 2D speckle-tracking echocardiography at baseline in 447 HFpEF patients enrolled in the Treatment Of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. At a median follow-up of 2.6 (IQR 1.5–3.9) years, 115 patients experienced the primary composite outcome of CV death, HF hospitalization, or aborted cardiac arrest. Impaired LS, defined as an absolute LS<15.8%, was present in 52% of patients and was predictive of the composite outcome (adjusted HR 2.14, 95% CI 1.26–3.66; p=0.005), CV death alone (adjusted HR 3.20, 95% CI 1.44–7.12; p=0.004), and HF hospitalization alone (adjusted HR 2.23, 95% CI 1.16–4.28; p=0.016) after adjusting for clinical and conventional echocardiographic variables. LS was the strongest echocardiographic predictor of the composite outcome. Exploratory analysis in a subset of 131 patients with follow-up LS assessed after 12–18 months demonstrated a trend towards improvement in LS associated with spironolactone in patients enrolled in the Americas but not in Russia or Georgia. Conclusions Impaired LV systolic function is a powerful predictor of HF hospitalization, CV death, or aborted cardiac arrest in HFpEF, independent of clinical predictors. Impaired LS represents a novel imaging biomarker to identify HFpEF patients at particularly high risk for CV morbidity and mortality. Clinical Trial Registration Information Clinicaltrials.gov. Identifier NCT00094302. PMID:26130119

Heart Failure with Preserved Ejection Fraction: Comparison of Patients With and Without Angina Pectoris (From the Duke Databank for Cardiovascular Disease)

PubMed Central

Mentz, Robert J.; Broderick, Samuel; Shaw, Linda K.; Fiuzat, Mona; O'Connor, Christopher M.

2013-01-01

Objectives We aimed to investigate the characteristics and outcomes of patients with heart failure with preserved ejection fraction (HFpEF) and angina pectoris (AP). Background AP is a predictor of adverse events in patients with heart failure with reduced EF. The implications of AP in HFpEF are unknown. Methods We analyzed HFpEF patients (EF≥50%) who underwent coronary angiography at Duke University Medical Center from 2000–2010 with and without AP in the previous 6 weeks. Time to first event was examined using Kaplan-Meier methods for the primary endpoint of death/myocardial infarction (MI)/revascularization/stroke (i.e., MACE) and secondary endpoints of death/MI/revascularization, death/MI/stroke, death/MI, death and cardiovascular death/cardiovascular hospitalization. Results In the Duke Databank, 3517 patients met criteria for inclusion and 1402 (40%) had AP. Those with AP were older with more comorbidities, and prior revascularization vs. non-AP patients. AP patients more often received beta-blockers, ACE-inhibitors, nitrates, and statins (all P<0.05). In unadjusted analysis, AP patients had increased MACE and death/MI/revascularization (both P <0.001), lower rates of death and death/MI (both P<0.05), and similar rates of death/MI/stroke and cardiovascular death/cardiovascular hospitalization (both P>0.1). After multivariable adjustment, those with AP remained at increased risk for MACE (Hazard Ratio [HR] 1.30; 95% Confidence Interval [CI], 1.17–1.45) and death/MI/revascularization (HR 1.29; 95% CI, 1.15–1.43), but were at similar risk for other endpoints (P>0.06). Conclusions AP in HFpEF patients with a history of coronary artery disease is common despite medical therapy and is independently associated with increased MACE due to revascularization with similar risk of death, MI, and hospitalization. PMID:24161322

The Prognostic Value of the Left Ventricular Ejection Fraction Is Dependent upon the Severity of Mitral Regurgitation in Patients with Acute Myocardial Infarction

PubMed Central

Cho, Jung Sun; Youn, Ho-Joong; Her, Sung-Ho; Park, Maen Won; Kim, Chan Joon; Park, Gyung-Min; Cho, Jae Yeong; Ahn, Youngkeun; Kim, Kye Hun; Park, Jong Chun; Seung, Ki Bae; Cho, Myeong Chan; Kim, Chong Jin; Kim, Young Jo; Han, Kyoo Rok; Kim, Hyo Soo

2015-01-01

The prognostic value of the left ventricle ejection fraction (LVEF) after acute myocardial infarction (AMI) has been questioned even though it is an accurate marker of left ventricle (LV) systolic dysfunction. This study aimed to examine the prognostic impact of LVEF in patients with AMI with or without high-grade mitral regurgitation (MR). A total of 15,097 patients with AMI who received echocardiography were registered in the Korean Acute Myocardial Infarction Registry (KAMIR) between January 2005 and July 2011. Patients with low-grade MR (grades 0-2) and high-grade MR (grades 3-4) were divided into the following two sub-groups according to LVEF: LVEF ≤ 40% (n = 2,422 and 197, respectively) and LVEF > 40% (n = 12,252 and 226, respectively). The primary endpoints were major adverse cardiac events (MACE), cardiac death, and all-cause death during the first year after registration. Independent predictors of mortality in the multivariate analysis in AMI patients with low-grade MR were age ≥ 75 yr, Killip class ≥ III, N-terminal pro-B-type natriuretic peptide > 4,000 pg/mL, high-sensitivity C-reactive protein ≥ 2.59 mg/L, LVEF ≤ 40%, estimated glomerular filtration rate (eGFR), and percutaneous coronary intervention (PCI). However, PCI was an independent predictor in AMI patients with high-grade MR. No differences in primary endpoints between AMI patients with high-grade MR (grades 3-4) and EF ≤ 40% or EF > 40% were noted. MR is a predictor of a poor outcome regardless of ejection fraction. LVEF is an inadequate method to evaluate contractile function of the ischemic heart in the face of significant MR. PMID:26130953

Computer-assisted determination of left ventricular endocardial borders reduces variability in the echocardiographic assessment of ejection fraction

PubMed Central

Maret, Eva; Brudin, Lars; Lindstrom, Lena; Nylander, Eva; Ohlsson, Jan L; Engvall, Jan E

2008-01-01

Background Left ventricular size and function are important prognostic factors in heart disease. Their measurement is the most frequent reason for sending patients to the echo lab. These measurements have important implications for therapy but are sensitive to the skill of the operator. Earlier automated echo-based methods have not become widely used. The aim of our study was to evaluate an automatic echocardiographic method (with manual correction if needed) for determining left ventricular ejection fraction (LVEF) based on an active appearance model of the left ventricle (syngo®AutoEF, Siemens Medical Solutions). Comparisons were made with manual planimetry (manual Simpson), visual assessment and automatically determined LVEF from quantitative myocardial gated single photon emission computed tomography (SPECT). Methods 60 consecutive patients referred for myocardial perfusion imaging (MPI) were included in the study. Two-dimensional echocardiography was performed within one hour of MPI at rest. Image quality did not constitute an exclusion criterion. Analysis was performed by five experienced observers and by two novices. Results LVEF (%), end-diastolic and end-systolic volume/BSA (ml/m2) were for uncorrected AutoEF 54 ± 10, 51 ± 16, 24 ± 13, for corrected AutoEF 53 ± 10, 53 ± 18, 26 ± 14, for manual Simpson 51 ± 11, 56 ± 20, 28 ± 15, and for MPI 52 ± 12, 67 ± 26, 35 ± 23. The required time for analysis was significantly different for all four echocardiographic methods and was for uncorrected AutoEF 79 ± 5 s, for corrected AutoEF 159 ± 46 s, for manual Simpson 177 ± 66 s, and for visual assessment 33 ± 14 s. Compared with the expert manual Simpson, limits of agreement for novice corrected AutoEF was lower than for novice manual Simpson (0.8 ± 10.5 vs. -3.2 ± 11.4 LVEF percentage points). Calculated for experts and with LVEF (%) categorized into < 30, 30–44, 45–54 and ≥ 55, kappa measure of agreement was moderate (0.44–0.53) for all method comparisons (uncorrected AutoEF not evaluated). Conclusion Corrected AutoEF reduces the variation in measurements compared with manual planimetry, without increasing the time required. The method seems especially suited for unexperienced readers. PMID:19014461

High-intensity interval training vs. moderate-intensity continuous exercise training in heart failure with preserved ejection fraction: a pilot study.

PubMed

Angadi, Siddhartha S; Mookadam, Farouk; Lee, Chong D; Tucker, Wesley J; Haykowsky, Mark J; Gaesser, Glenn A

2015-09-15

Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality. Exercise training is an established adjuvant therapy in heart failure; however, the effects of high-intensity interval training (HIIT) in HFpEF are unknown. We compared the effects of HIIT vs. moderate-intensity aerobic continuous training (MI-ACT) on peak oxygen uptake (V̇o₂peak), left ventricular diastolic dysfunction, and endothelial function in patients with HFpEF. Nineteen patients with HFpEF (age 70 ± 8.3 yr) were randomized to either HIIT (4 × 4 min at 85-90% peak heart rate, with 3 min active recovery) or MI-ACT (30 min at 70% peak heart rate). Fifteen patients completed exercise training (HIIT: n = 9; MI-ACT: n = 6). Patients trained 3 days/wk for 4 wk. Before and after training patients underwent a treadmill test for V̇o₂peak determination, 2D-echocardiography for assessment of left ventricular diastolic dysfunction, and brachial artery flow-mediated dilation (FMD) for assessment of endothelial function. HIIT improved V̇o₂peak (pre = 19.2 ± 5.2 ml·kg(-1)·min(-1); post = 21.0 ± 5.2 ml·kg(-1)·min(-1); P = 0.04) and left ventricular diastolic dysfunction grade (pre = 2.1 ± 0.3; post = 1.3 ± 0.7; P = 0.02), but FMD was unchanged (pre = 6.9 ± 3.7%; post = 7.0 ± 4.2%). No changes were observed following MI-ACT. A trend for reduced left atrial volume index was observed following HIIT compared with MI-ACT (-3.3 ± 6.6 vs. +5.8 ± 10.7 ml/m(2); P = 0.06). In HFpEF patients 4 wk of HIIT significantly improved V̇o₂peak and left ventricular diastolic dysfunction. HIIT may provide a more robust stimulus than MI-ACT for early exercise training adaptations in HFpEF. Copyright © 2015 the American Physiological Society.

Ghrelin and hormonal markers under exercise training in patients with heart failure with preserved ejection fraction: results from the Ex-DHF pilot study.

PubMed

Trippel, Tobias Daniel; Holzendorf, Volker; Halle, Martin; Gelbrich, Götz; Nolte, Kathleen; Duvinage, Andre; Schwarz, Silja; Rutscher, Tinka; Wiora, Julian; Wachter, Rolf; Herrmann-Lingen, Christoph; Duengen, Hans-Dirk; Hasenfuß, Gerd; Pieske, Burkert; Edelmann, Frank

2017-02-01

Over 50% of patients with symptomatic heart failure (HF) experience HF with preserved ejection fraction (HFpEF) . Exercise training (ET) is effective in improving cardiorespiratory fitness and dimensions of quality of life in patients with HFpEF. A systemic pro-inflammatory state induced by comorbidities as the cause of myocardial structural and functional alterations has been proposed in HFpEF. ET modifies myocardial structure and has been related to inflammatory state. We investigated Ghrelin, related adipokines, markers of inflammation, and neuro-hormonal activation in patients undergoing a structured ET vs. usual care are with HFpEF . Ex-DHF-P was a prospective, controlled, randomized multi-centre trial on structured and supervised ET in patients with HFpEF. We performed a post hoc analysis in 62 patients from Ex-DHF-P. Ghrelin, adiponectin, leptin, IL-1 ß , IL-6, IL-10, tumour necrosis factor-alpha, MR-proANP, MR-proADM, CT-proET1, and CT-proAVP were assessed to seize the impact of ET on these markers in patients with HFpEF. Thirty-six (58%) patients were female, mean age was 64 years, and median ghrelin was 928 pg/mL (interquartile range 755-1156). When stratified for high versus low ghrelin, groups significantly differed at baseline in presence obesity, waist circumference, and adiponectin levels ( P  < 0.05, respectively). Overall, ghrelin levels rose significantly to 1013 pg/mL (interquartile range 813-1182) ( P  < 0.001). Analysis of covariance modelling for change in ghrelin identified ET ( P  = 0.013) and higher baseline adiponectin levels ( P  = 0.035) as influencing factors. Exercise training tended to increase ghrelin levels in Ex-DHF-P. This increase was especially pronounced in patients with higher baseline adiponectin levels. Future trials are needed to investigate the effect of ET on endogenous ghrelin levels in regard to interactions with cardiac structure and clinically meaningful surrogate parameters.

Therapeutic Approach to Patients with Heart Failure with Reduced Ejection Fraction and End-stage Renal Disease.

PubMed

Inampudi, Chakradhari; Alvarez, Paulino; Asleh, Rabea; Briasoulis, Alexandros

2018-03-14

Several risk factors including Ischemic heart disease, uncontrolled hypertension, high output Heart Failure (HF) from shunting through vascular hemodialysis access, and anemia, contribute to development of HF in patients with End-Stage Renal Disease (ESRD). Guidelinedirected medical and device therapy for Heart Failure with Reduced Ejection Fraction (HFrEF) has not been extensively studied and may have limited safety and efficacy in patients with ESRD. Maintenance of interdialytic and intradialytic euvolemia is a key component of HF management in these patients but often difficult to achieve. Beta-blockers, especially carvedilol which is poorly dialyzed is associated with cardiovascular benefit in this population. Despite paucity of data, Angiotensin-converting Enzyme Inhibitors (ACEI) or Angiotensin II Receptor Blockers (ARBs) when appropriately adjusted by dose and with close monitoring of serum potassium can also be administered to these patients who tolerate beta-blockers. Mineralocorticoid receptors in patients with HFrEF and ESRD have been shown to reduce mortality in a large randomized controlled trial without any significantly increased risk of hyperkalemia. Implantable Cardiac-defibrillators (ICDs) should be considered for primary prevention of sudden cardiac death in patients with HFrEF and ESRD who meet the implant indications. Furthermore in anemic iron-deficient patients, intravenous iron infusion may improve functional status. Finally, mechanical circulatory support with leftventricular assist devices may be related to increased mortality risk and the presence of ESRD poses a relative contraindication to further evaluation of these devices. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Study protocol, randomized controlled trial: reducing symptom burden in patients with heart failure with preserved ejection fraction using ubiquinol and/or D-ribose.

PubMed

Pierce, Janet D; Mahoney, Diane E; Hiebert, John B; Thimmesch, Amanda R; Diaz, Francisco J; Smith, Carol; Shen, Qiuhua; Mudaranthakam, Dinesh Pal; Clancy, Richard L

2018-04-02

Heart failure (HF), the leading cause of morbidity and mortality in the US, affects 6.6 million adults with an estimated additional 3 million people by 2030. More than 50% of HF patients have heart failure with preserved left ventricular ejection fraction (HFpEF). These patients have impaired cardiac muscle relaxation and diastolic filling, which investigators have associated with cellular energetic impairment. Patients with HFpEF experience symptoms of: (1) fatigue; (2) shortness of breath; and (3) swelling (edema) of the lower extremities. However, current HF guidelines offer no effective treatment to address these underlying pathophysiologic mechanisms. Thus, we propose a biobehavioral symptom science study using ubiquinol and D-ribose (therapeutic interventions) to target mitochondrial bioenergetics to reduce the complex symptoms experienced by patients with HFpEF. Using a randomized, double-blind, placebo-controlled design, the overall objective is to determine if administering ubiquinol and/or D-ribose to HFpEF patients for 12 weeks would decrease the severity of their complex symptoms and improve their cardiac function. The measures used to assess patients' perceptions of their health status and level of vigor (energy) will be the Kansas City Cardiomyopathy Questionnaire (KCCQ) and Vigor subscale of the Profile of Mood States. The 6-min walk test will be used to test exercise tolerance. Left ventricular diastolic function will be assessed using innovative advanced echocardiography software called speckle tracking. We will measure B-type natriuretic peptides (secreted from ventricles in HF) and lactate/ATP ratio (measure of cellular energetics). Ubiquinol (active form of Coenzyme Q10) and D-ribose are two potential treatments that can positively affect cellular energetic impairment, the major underlying mechanism of HFpEF. Ubiquinol, the reduced form of CoQ10, is more effective in adults over the age of 50. In patients with HFpEF, mitochondrial deficiency of ubiquinol results in decreased adenosine triphosphate (ATP) synthesis and reduced scavenging of reactive oxygen species. D-ribose is a substrate required for ATP synthesis and when administered has been shown to improve impaired myocardial bioenergetics. Therefore, if the biological underpinning of deficient mitochondrial ATP in HFpEF is not addressed, patients will suffer major symptoms including lack of energy, fatigue, exertional dyspnea, and exercise intolerance. ClinicalTrials.gov Identifier: NCT03133793 ; Data of Registration: April 28, 2017.

Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction: Association With Exercise Capacity, Left Ventricular Filling Pressures, Natriuretic Peptides, and Left Atrial Volume.

PubMed

Lam, Carolyn S P; Rienstra, Michiel; Tay, Wan Ting; Liu, Licette C Y; Hummel, Yoran M; van der Meer, Peter; de Boer, Rudolf A; Van Gelder, Isabelle C; van Veldhuisen, Dirk J; Voors, Adriaan A; Hoendermis, Elke S

2017-02-01

This study sought to study the association of atrial fibrillation (AF) with exercise capacity, left ventricular filling pressure, natriuretic peptides, and left atrial size in heart failure with preserved ejection fraction (HFpEF). The diagnosis of HFpEF in patients with AF remains a challenge because both contribute to impaired exercise capacity, and increased natriuretic peptides and left atrial volume. We studied 94 patients with symptomatic heart failure and left ventricular ejection fractions ≥45% using treadmill cardiopulmonary exercise testing and right- and/or left-sided cardiac catheterization with simultaneous echocardiography. During catheterization, 62 patients were in sinus rhythm, and 32 patients had AF. There were no significant differences in age, sex, body size, comorbidities, or medications between groups; however, patients with AF had lower peak oxygen consumption (VO 2 ) compared with those with sinus rhythm (10.8 ± 3.1 ml/min/kg vs. 13.5 ± 3.8 ml/min/kg; p = 0.002). Median (25th to 75th percentile) N-terminal pro-B-type natriuretic peptide (NT-proBNP) was higher in AF versus sinus rhythm (1,689; 851 to 2,637 pg/ml vs. 490; 272 to 1,019 pg/ml; p < 0.0001). Left atrial volume index (LAVI) was higher in AF than sinus rhythm (57.8 ± 17.0 ml/m 2 vs. 42.5 ± 15.1 ml/m 2 ; p = 0.001). Invasive hemodynamics showed higher mean pulmonary capillary wedge pressure (PCWP) (19.9 ± 3.7 vs. 15.2 ± 6.8) in AF versus sinus rhythm (all p < 0.001), with a trend toward higher left ventricular end-diastolic pressure (17.7 ± 3.0 mm Hg vs. 15.7 ± 6.9 mm Hg; p = 0.06). After adjusting for clinical covariates and mean PCWP, AF remained associated with reduced peak VO 2 increased log NT-proBNP, and enlarged LAVI (all p ≤0.005). AF is independently associated with greater exertional intolerance, natriuretic peptide elevation, and left atrial remodeling in HFpEF. These data support the application of different thresholds of NT-proBNP and LAVI for the diagnosis of HFpEF in the presence of AF versus the absence of AF. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The reverse remodeling response to sacubitril/valsartan therapy in heart failure with reduced ejection fraction.

PubMed

Martens, Pieter; Beliën, Hanne; Dupont, Matthias; Vandervoort, Pieter; Mullens, Wilfried

2018-05-17

Major classes of medical therapy for heart failure with reduced ejection fraction (HFrEF) induce reverse remodeling. The revere remodeling response to sacubitril/valsartan remains unstudied. We performed a single-center, prospective assessor-blinded study to determine the reverse remodeling response of sacubitril/valsartan therapy in HFrEF patients with a class I indication (New York heart Association [NYHA]-class II-IV, Left ventricular ejection fraction [LVEF] < 35%, optimal dose with Renin-Angiotensin-System-Blocker [RAS-blocker]). Doses of sacubitril/valsartan were optimized to individual tolerance. Echocardiographic images were assessed offline by 2 investigators blinded to both the clinical data and timing of echocardiograms. One-hundred-twenty-five HFrEF patients (66 ± 10 years) were prospectively included. The amount of RAS-blocker before and after switch to sacubitril/valsartan was similar(P = .290), indicating individual optimal dosing of sacubitril/valsartan. Over a median(IQR) follow-up of 118(77-160) days after initiation of sacubitril/valsartan, LVEF improved (29.6 ± 6% vs 34.8 ± 6%; P < .001) and Left ventricular end-systolic (LVESV) and end-diastolic volume (LVEDV) decreased (LVESV; 147 ± 57 mL vs 129 ± 55 mL; P < .001 and LVEDV; 206 ± 71 mL vs197 ± 72 mL; P = .027). Volumetric remodeling was associated with a reduction in the degree of mitral regurgitation (1.59 ± 1.0 vs 1.11 ± 0.8; P < .001; [scale from 0-4]). Metrics of diastolic function improved; including a drop in the E/A-wave ratio (1.75 ± 1.13 vs 1.38 ± 0.88; P = .002) and diastolic filling time (% of cycle length) prolonged (48 ± 9% vs 52 ± 1%; P = .005). The percent of patients with a restrictive mitral filling pattern dropped from 47% to 23% (P = .004). A dose-dependent effect was noted for changes in LVEF (P < .001) and LVESV (P = .031), with higher doses of sacubitril/valsartan leading to more reverse remodeling. Switching therapy in eligible HFrEF patients from a RAS-blocker to sacubitril/valsartan induces beneficial reverse remodeling of both metrics of systolic as diastolic function. © 2018 John Wiley & Sons Ltd.

The Potential of Clinical Phenotyping of Heart Failure With Imaging Biomarkers for Guiding Therapies: A Focused Update.

PubMed

Sengupta, Partho P; Kramer, Christopher M; Narula, Jagat; Dilsizian, Vasken

2017-09-01

The need for noninvasive assessment of cardiac volumes and ejection fraction (EF) ushered in the use of cardiac imaging techniques in heart failure (HF) trials that investigated the roles of pharmacological and device-based therapies. However, in contrast to HF with reduced EF (HFrEF), modern HF pharmacotherapy has not improved outcomes in HF with preserved EF (HFpEF), largely attributed to patient heterogeneity and incomplete understanding of pathophysiological insights underlying the clinical presentations of HFpEF. Modern cardiac imaging methods offer insights into many sets of changes in cardiac tissue structure and function that can precisely link cause with cardiac remodeling at organ and tissue levels to clinical presentations in HF. This has inspired investigators to seek a more comprehensive understanding of HF presentations using imaging techniques. This article summarizes the available evidence regarding the role of cardiac imaging in HF. Furthermore, we discuss the value of cardiac imaging techniques in identifying HF patient subtypes who share similar causes and mechanistic pathways that can be targeted using specific HF therapies. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Pathophysiological understanding of HFpEF: microRNAs as part of the puzzle.

PubMed

Rech, Monika; Barandiarán Aizpurua, Arantxa; van Empel, Vanessa; van Bilsen, Marc; Schroen, Blanche

2018-05-01

Half of all heart failure patients have preserved ejection fraction (HFpEF). Comorbidities associated with and contributing to HFpEF include obesity, diabetes and hypertension. Still, the underlying pathophysiological mechanisms of HFpEF are unknown. A preliminary consensus proposes that the multi-morbidity triggers a state of systemic, chronic low-grade inflammation, and microvascular dysfunction, causing reduced nitric oxide bioavailability to adjacent cardiomyocytes. As a result, the cardiomyocyte remodels its contractile elements and fails to relax properly, causing diastolic dysfunction, and eventually HFpEF. HFpEF is a complex syndrome for which currently no efficient therapies exist. This is notably due to the current one-size-fits-all therapy approach that ignores individual patient differences. MicroRNAs have been studied in relation to pathophysiological mechanisms and comorbidities underlying and contributing to HFpEF. As regulators of gene expression, microRNAs may contribute to the pathophysiology of HFpEF. In addition, secreted circulating microRNAs are potential biomarkers and as such, they could help stratify the HFpEF population and open new ways for individualized therapies. In this review, we provide an overview of the ever-expanding world of non-coding RNAs and their contribution to the molecular mechanisms underlying HFpEF. We propose prospects for microRNAs in stratifying the HFpEF population. MicroRNAs add a new level of complexity to the regulatory network controlling cardiac function and hence the understanding of gene regulation becomes a fundamental piece in solving the HFpEF puzzle.

New diagnostic and therapeutic possibilities for diastolic heart failure.

PubMed

Jeong, Euy-Myoung; Dudley, Samuel C

2014-02-03

Despite the fact that up to half of all heart failure occurs in patients without evidence of systolic cardiac dysfunction, there are no universally accepted diagnostic markers and no approved therapies for heart failure with preserved ejection fraction (HFpEF). HFpEF, otherwise known as diastolic heart failure, has nearly the same grim prognosis as systolic heart failure, and diastolic heart failure is increasing in incidence and prevalence. Major trials have shown that many of the treatments that are salutary in systolic heart failure have no beneficial effects in diastolic heart failure, suggesting different underlying mechanisms for these two disorders. Even criteria for diagnosis of HFpEF are still debated, and there is still no gold standard marker to detect diastolic dysfunction. Here, we will review some promising new insights into the pathogenesis of diastolic dysfunction that may lead to new diagnostic and therapeutic tools.

Comparison of echocardiographic and cardiac magnetic resonance imaging measurements of functional single ventricular volumes, mass, and ejection fraction (from the Pediatric Heart Network Fontan Cross-Sectional Study).

PubMed

Margossian, Renee; Schwartz, Marcy L; Prakash, Ashwin; Wruck, Lisa; Colan, Steven D; Atz, Andrew M; Bradley, Timothy J; Fogel, Mark A; Hurwitz, Lynne M; Marcus, Edward; Powell, Andrew J; Printz, Beth F; Puchalski, Michael D; Rychik, Jack; Shirali, Girish; Williams, Richard; Yoo, Shi-Joon; Geva, Tal

2009-08-01

Assessment of the size and function of a functional single ventricle (FSV) is a key element in the management of patients after the Fontan procedure. Measurement variability of ventricular mass, volume, and ejection fraction (EF) among observers by echocardiography and cardiac magnetic resonance imaging (CMR) and their reproducibility among readers in these patients have not been described. From the 546 patients enrolled in the Pediatric Heart Network Fontan Cross-Sectional Study (mean age 11.9 +/- 3.4 years), 100 echocardiograms and 50 CMR studies were assessed for measurement reproducibility; 124 subjects with paired studies were selected for comparison between modalities. Interobserver agreement for qualitative grading of ventricular function by echocardiography was modest for left ventricular (LV) morphology (kappa = 0.42) and weak for right ventricular (RV) morphology (kappa = 0.12). For quantitative assessment, high intraclass correlation coefficients were found for echocardiographic interobserver agreement (LV 0.87 to 0.92, RV 0.82 to 0.85) of systolic and diastolic volumes, respectively. In contrast, intraclass correlation coefficients for LV and RV mass were moderate (LV 0.78, RV 0.72). The corresponding intraclass correlation coefficients by CMR were high (LV 0.96, RV 0.85). Volumes by echocardiography averaged 70% of CMR values. Interobserver reproducibility for the EF was similar for the 2 modalities. Although the absolute mean difference between modalities for the EF was small (<2%), 95% limits of agreement were wide. In conclusion, agreement between observers of qualitative FSV function by echocardiography is modest. Measurements of FSV volume by 2-dimensional echocardiography underestimate CMR measurements, but their reproducibility is high. Echocardiographic and CMR measurements of FSV EF demonstrate similar interobserver reproducibility, whereas measurements of FSV mass and LV diastolic volume are more reproducible by CMR.

Inspiratory Muscle Training and Functional Electrical Stimulation for Treatment of Heart Failure With Preserved Ejection Fraction: The TRAINING-HF Trial.

PubMed

Palau, Patricia; Domínguez, Eloy; López, Laura; Ramón, José María; Heredia, Raquel; González, Jessika; Santas, Enrique; Bodí, Vicent; Miñana, Gema; Valero, Ernesto; Mollar, Anna; Bertomeu González, Vicente; Chorro, Francisco J; Sanchis, Juan; Lupón, Josep; Bayés-Genís, Antoni; Núñez, Julio

2018-03-16

Despite the prevalence of heart failure with preserved ejection fraction (HFpEF), there is currently no evidence-based effective therapy for this disease. This study sought to evaluate whether inspiratory muscle training (IMT), functional electrical stimulation (FES), or a combination of both (IMT + FES) improves 12- and 24-week exercise capacity as well as left ventricular diastolic function, biomarker profile, and quality of life in HFpEF. A total of 61 stable symptomatic patients (New York Heart Association II-III) with HFpEF were randomized (1:1:1:1) to receive a 12-week program of IMT, FES, or IMT + FES vs usual care. The primary endpoint of the study was to evaluate change in peak exercise oxygen uptake at 12 and 24 weeks. Secondary endpoints were changes in quality of life, echocardiogram parameters, and prognostic biomarkers. We used a mixed-effects model for repeated-measures to compare endpoints changes. Mean age and peak exercise oxygen uptake were 74 ± 9 years and 9.9 ± 2.5mL/min/kg, respectively. The proportion of women was 58%. At 12 weeks, the mean increase in peak exercise oxygen uptake (mL/kg/min) compared with usual care was 2.98, 2.93, and 2.47 for IMT, FES, and IMT + FES, respectively (P < .001) and this beneficial effect persisted after 6 months (1.95, 2.08, and 1.56; P < .001). Significant increases in quality of life scores were found at 12 weeks (P < .001). No other changes were found. In HFpEF patients with low aerobic capacity, IMT and FES were associated with a significant improvement in exercise capacity and quality of life. This trial was registered at ClinicalTrials.gov (Identifier: NCT02638961).. Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Renin–angiotensin blockade in heart failure with preserved ejection fraction: a systematic review and meta‐analysis

PubMed Central

Khan, Muhammad Shahzeb; Fonarow, Gregg C.; Khan, Hassan; Greene, Stephen J.; Anker, Stefan D.; Gheorghiade, Mihai

2017-01-01

Abstract Studies with angiotensin‐converting enzyme inhibitors (ACE‐Is) and angiotensin receptor blockers (ARBs) in patients with heart failure with preserved ejection fraction (HFpEF) have yielded inconsistent results. To conduct a systematic review and meta‐analysis of all evidence for ACE‐I and ARBs in patients with HFpEF, we searched PubMed, Ovid SP, Embase, and Cochrane database to identify randomized trials and observational studies that compared ACE‐I or ARBs against placebo or standard therapy in HFpEF patients. Random‐effect models were used to pool the data, and I 2 testing was performed to assess the heterogeneity of the included studies. A total of 13 studies (treatment arm = 8676 and control arm = 8608) were analysed. Pooled analysis of randomized trials for ACE‐I and ARBs (n = 6) did not show any effect on all‐cause mortality [relative risk (RR) = 1.02, 95% confidence interval (CI) = 0.93–1.11, P = 0.68, I 2 = 0%], while results from observational studies showed a significant improvement (RR = 0.91, 95% CI = 0.87–0.95, P = 0.005, I 2 = 81.5%). In pooled analyses of all studies, ACE‐I showed a reduction of all‐cause mortality (RR = 0.91, 95% CI = 0.87–0.95, P = 0.01). There was no reduction in cardiovascular mortality seen, but in pooled analysis of randomized trials, there was a trend towards reduced HF hospitalization risk (RR = 0.91, 95% CI = 0.83–1.01, I 2 = 0%, P = 0.074). These data suggest that ACE‐I and ARBs may have a role in improving outcomes of patients with HFpEF, underscoring the need for future research with careful patient selection, and trial design and conduct. PMID:28869332

Comparative effectiveness of enalapril, lisinopril, and ramipril in the treatment of patients with chronic heart failure: a propensity score-matched cohort study.

PubMed

Fröhlich, Hanna; Henning, Felix; Täger, Tobias; Schellberg, Dieter; Grundtvig, Morten; Goode, Kevin; Corletto, Anna; Kazmi, Syed; Hole, Torstein; Katus, Hugo A; Atar, Dan; Cleland, John G F; Agewall, Stefan; Frankenstein, Lutz; Clark, Andrew L

2018-04-01

Angiotensin-converting enzyme inhibitors (ACEIs) are recommended as first-line therapy in patients with heart failure with reduced ejection fraction (HFrEF). The comparative effectiveness of different ACEIs is not known. A total of 4723 outpatients with stable HFrEF prescribed enalapril, lisinopril, or ramipril were identified from three registries in Norway, England, and Germany. In three separate matching procedures, patients were individually matched with respect to both dose equivalents and their respective propensity scores for ACEI treatment. During a follow-up of 21 939 patient-years, 360 (49.5%), 337 (52.4%), and 1119 (33.4%) patients died among those prescribed enalapril, lisinopril, and ramipril, respectively. In univariable analysis of the general sample, enalapril and lisinopril were both associated with higher mortality when compared with ramipril treatment [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.30-1.65, P < 0.001 and HR 1.38, 95% CI 1.22-1.56, P < 0.001, respectively). Patients prescribed enalapril or lisinopril had similar mortality (HR 1.06, 95% CI 0.92-1.24, P = 0.41). However, there was no significant association between ACEI choice and all-cause mortality in any of the matched samples (HR 1.07, 95% CI 0.91-1.25, P = 0.40; HR 1.12, 95% CI 0.96-1.32, P = 0.16; and HR 1.10, 95% CI 0.93-1.31, P = 0.25 for enalapril vs. ramipril, lisinopril vs. ramipril, and enalapril vs. lisinopril, respectively). Results were confirmed in subgroup analyses with respect to age, sex, left ventricular ejection fraction, New York Class Association functional class, cause of HFrEF, rhythm, and systolic blood pressure. Our results suggest that enalapril, lisinopril, and ramipril are equally effective in the treatment of patients with HFrEF when given at equivalent doses.

Pharmacodynamic and Pharmacokinetic Profiles of Sacubitril/Valsartan (LCZ696) in Patients with Heart Failure and Reduced Ejection Fraction.

PubMed

Kobalava, Zhanna; Kotovskaya, Yulia; Averkov, Oleg; Pavlikova, Elena; Moiseev, Valentine; Albrecht, Diego; Chandra, Priya; Ayalasomayajula, Surya; Prescott, Margaret F; Pal, Parasar; Langenickel, Thomas H; Jordaan, Pierre; Rajman, Iris

2016-08-01

Concomitant renin-angiotensin-aldosterone system blockade and natriuretic peptide system enhancement may provide unique therapeutic benefits to patients with heart failure and reduced ejection fraction (HFrEF). This study assessed the pharmacodynamics and pharmacokinetics of LCZ696 in patients with HFrEF. This was an open-label, noncontrolled single-sequence study. After a 24-h run-in period, patients (n = 30) with HFrEF (EF ≤ 40%; NYHA class II-IV) received LCZ696 100 mg twice daily (bid) for 7 days and 200 mg bid for 14 days, along with standard treatment for heart failure (HF) (except angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin receptor blockers [ARBs]). On Day 21, significant increases were observed in the plasma biomarkers indicative of neprilysin and RAAS inhibition (ratio-to-baseline: cyclic guanosine monophosphate [cGMP], 1.38; renin concentration and activity, 3.50 and 2.27, respectively; all, P < 0.05). Plasma NT-proBNP levels significantly decreased at all the time points on Days 7 and 21; plasma aldosterone and endothelin-1 levels significantly decreased on Day 21 (all, P < 0.05). Following administration of LCZ696, the Cmax of sacubitril (neprilysin inhibitor prodrug), LBQ657 (active neprilysin inhibitor), and valsartan were reached within 0.5, 2.5, and 2 h. Between 100- and 200-mg doses, the Cmax and AUC0-12 h for sacubitril and LBQ657 were approximately dose-proportional while that of valsartan was less than dose-proportional. Treatment with LCZ696 for 21 days was well tolerated and resulted in plasma biomarker changes indicative of neprilysin and RAAS inhibition in patients with HF. The pharmacokinetic exposure of the LCZ696 analytes in patients with HF observed in this study is comparable to that observed in the pivotal Phase III study. © 2016 John Wiley & Sons Ltd.

Relation of Carotid Artery Diameter With Cardiac Geometry and Mechanics in Heart Failure With Preserved Ejection Fraction

PubMed Central

Liao, Zhen‐Yu; Peng, Ming‐Cheng; Yun, Chun‐Ho; Lai, Yau‐Huei; Po, Helen L.; Hou, Charles Jia‐Yin; Kuo, Jen‐Yuan; Hung, Chung‐Lieh; Wu, Yih‐Jer; Bulwer, Bernard E.; Yeh, Hung‐I; Tsai, Cheng‐Ho

2012-01-01

Background Central artery dilation and remodeling are associated with higher heart failure and cardiovascular risks. However, data regarding carotid artery diameter from hypertension to heart failure have remained elusive. We sought to investigate this issue by examining the association between carotid artery diameter and surrogates of ventricular dysfunction. Methods and Results Two hundred thirteen consecutive patients including 49 with heart failure and preserved ejection fraction (HFpEF), 116 with hypertension, and an additional 48 healthy participants underwent comprehensive echocardiography and tissue Doppler imaging. Ultrasonography of the common carotid arteries was performed for measurement of intima‐media thickness and diameter (CCAD). Cardiac mechanics, including LV twist, were assessed by novel speckle‐tracking software. A substantial graded enlargement of CCAD was observed across all 3 groups (6.8±0.6, 7.7±0.73, and 8.7±0.95 mm for normal, hypertension, and HFpEF groups, respectively; ANOVA P<0.001) and correlated with serum brain natriuretic peptide level (R2=0.31, P<0.001). Multivariable models showed that CCAD was associated with increased LV mass, LV mass‐to‐volume ratio (β‐coefficient=10.9 and 0.11, both P<0.001), reduced LV longitudinal and radial strain (β‐coeffficient=0.81 and −3.1, both P<0.05), and twist (β‐coefficient=−0.84, P<0.05). CCAD set at 8.07 mm as a cut‐off had a 77.6% sensitivity, 82.3% specificity, and area under the receiver operating characteristic curves (AUROC) of 0.86 (95% CI 0.80 to 0.92) in discriminating HFpEF. In addition, CCAD superimposed on myocardial deformation significantly expanded AUROC (for longitudinal strain, from 0.84 to 0.90, P of ΔAUROC=0.02) in heart failure discrimination models. Conclusions Increased carotid artery diameter is associated with worse LV geometry, higher brain natriuretic peptide level, and reduced contractile mechanics in individuals with HFpEF. PMID:23316319

Global longitudinal strain corrected by RR interval is a superior predictor of all-cause mortality in patients with systolic heart failure and atrial fibrillation.

PubMed

Modin, Daniel; Sengeløv, Morten; Jørgensen, Peter Godsk; Bruun, Niels Eske; Olsen, Flemming Javier; Dons, Maria; Fritz Hansen, Thomas; Jensen, Jan Skov; Biering-Sørensen, Tor

2018-04-01

Quantification of systolic function in patients with atrial fibrillation (AF) is challenging. A novel approach, based on RR interval correction, to counteract the varying heart cycle lengths in AF has recently been proposed. Whether this method is superior in patients with systolic heart failure (HFrEF) with AF remains unknown. This study investigates the prognostic value of RR interval-corrected peak global longitudinal strain {GLSc = GLS/[RR^(1/2)]} in relation to all-cause mortality in HFrEF patients displaying AF during echocardiographic examination. Echocardiograms from 151 patients with HFrEF and AF during examination were analysed offline. Peak global longitudinal strain (GLS) was averaged from 18 myocardial segments obtained from three apical views. GLS was indexed with the square root of the RR interval {GLSc = GLS/[RR^(1/2)]}. Endpoint was all-cause mortality. During a median follow-up of 2.7 years, 40 patients (26.5%) died. Neither uncorrected GLS (P = 0.056) nor left ventricular ejection fraction (P = 0.053) was significantly associated with all-cause mortality. After RR^(1/2) indexation, GLSc became a significant predictor of all-cause mortality (hazard ratio 1.16, 95% confidence interval 1.02-1.22, P = 0.014, per %/s^(1/2) decrease). GLSc remained an independent predictor of mortality after multivariable adjustment (age, sex, mean heart rate, mean arterial blood pressure, left atrial volume index, and E/e') (hazard ratio 1.17, 95% confidence interval 1.05-1.31, P = 0.005 per %/s^(1/2) decrease). Decreasing {GLSc = GLS/[RR^(1/2)]}, but not uncorrected GLS nor left ventricular ejection fraction, was significantly associated with increased risk of all-cause mortality in HFrEF patients with AF and remained an independent predictor after multivariable adjustment. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Right ventricular stroke work correlates with outcomes in pediatric pulmonary arterial hypertension.

PubMed

Yang, Weiguang; Marsden, Alison L; Ogawa, Michelle T; Sakarovitch, Charlotte; Hall, Keeley K; Rabinovitch, Marlene; Feinstein, Jeffrey A

2018-01-01

Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary artery pressures (PAP) and pulmonary vascular resistance (PVR). Optimizing treatment strategies and timing for transplant remains challenging. Thus, a quantitative measure to predict disease progression would be greatly beneficial in treatment planning. We devised a novel method to assess right ventricular (RV) stroke work (RVSW) as a potential biomarker of the failing heart that correlates with clinical worsening. Pediatric patients with idiopathic PAH or PAH secondary to congenital heart disease who had serial, temporally matched cardiac catheterization and magnetic resonance imaging (MRI) data were included. RV and PA hemodynamics were numerically determined by using a lumped parameter (circuit analogy) model to create pressure-volume (P-V) loops. The model was tuned using optimization techniques to match MRI and catheterization derived RV volumes and pressures for each time point. RVSW was calculated from the corresponding P-V loop and indexed by ejection fraction and body surface area (RVSW EF ) to compare across patients. Seventeen patients (8 boys; median age = 9.4 years; age range = 4.4-16.3 years) were enrolled. Nine were clinically stable; the others had clinical worsening between the time of their initial matched studies and their most recent follow-up (mean time = 3.9 years; range = 1.1-8.0 years). RVSW EF and the ratio of pulmonary to systemic resistance (Rp:Rs) values were found to have more significant associations with clinical worsening within one, two, and five years following the measurements, when compared with PVR index (PVRI). A receiver operating characteristic analysis showed RVSW EF outperforms PVRI, Rp:Rs and ejection fraction for predicting clinical worsening. RVSW EF correlates with clinical worsening in pediatric PAH, shows promising results towards predicting adverse outcomes, and may serve as an indicator of future clinical worsening.

The effect of exercise training on biventricular myocardial strain in heart failure with preserved ejection fraction.

PubMed

Angadi, Siddhartha S; Jarrett, Catherine L; Sherif, Moustafa; Gaesser, Glenn A; Mookadam, Farouk

2017-08-01

High-intensity interval training (HIIT) improves peak oxygen uptake and left ventricular diastology in patients with heart failure with preserved ejection fraction (HFpEF). However, its effects on myocardial strain in HFpEF remain unknown. We explored the effects of HIIT and moderate-intensity aerobic continuous training (MI-ACT) on left and right ventricular strain parameters in patients with HFpEF. Furthermore, we explored their relationship with peak oxygen uptake (VO 2peak ). Fifteen patients with HFpEF (age = 70 ± 8.3 years) were randomized to either: (i) HIIT (4 × 4 min, 85-90% peak heart rate, interspersed with 3 min of active recovery; n = 9) or (ii) MI-ACT (30 min at 70% peak heart rate; n = 6). Patients were trained 3 days/week for 4 weeks and underwent VO 2peak testing and 2D echocardiography at baseline and after completion of the 12 sessions of supervised exercise training. Left ventricular (LV) and right ventricular (RV) average global peak systolic longitudinal strain (GLS) and peak systolic longitudinal strain rate (GSR) were quantified. Paired t-tests were used to examine within-group differences and unpaired t-tests used for between-group differences (α = 0.05). Right ventricular average global peak systolic longitudinal strain improved significantly in the HIIT group after training (pre = -18.4 ± 3.2%, post = -21.4 ± 1.7%; P = 0.02) while RV-GSR, LV-GLS, and LV-GSR did not (P > 0.2). No significant improvements were observed following MI-ACT. No significant between-group differences were observed for any strain measure. ΔLV-GLS and ΔRV-GLS were modestly correlated with ΔVO 2peak (r = -0.48 and r = -0.45; P = 0.1, respectively). In patients with HFpEF, 4 weeks of HIIT significantly improved RV-GLS. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Heart failure with preserved ejection fraction: comparison of patients with and without angina pectoris (from the Duke Databank for Cardiovascular Disease).

PubMed

Mentz, Robert J; Broderick, Samuel; Shaw, Linda K; Fiuzat, Mona; O'Connor, Christopher M

2014-01-28

This study investigated the characteristics and outcomes of patients with heart failure with preserved ejection fraction (HFpEF) and angina pectoris (AP). AP is a predictor of adverse events in patients with heart failure with reduced EF. The implications of AP in HFpEF are unknown. We analyzed HFpEF patients (EF ≥50%) who underwent coronary angiography at Duke University Medical Center from 2000 through 2010 with and without AP in the previous 6 weeks. Time to first event was examined using Kaplan-Meier methods for the primary endpoint of death/myocardial infarction (MI)/revascularization/stroke (i.e., major adverse cardiac events [MACE]) and secondary endpoints of death/MI/revascularization, death/MI/stroke, death/MI, death, and cardiovascular death/cardiovascular hospitalization. In the Duke Databank, 3,517 patients met criteria for inclusion and 1,402 (40%) had AP. Those with AP were older with more comorbidities and prior revascularization compared with non-AP patients. AP patients more often received beta-blockers, angiotensin-converting enzyme inhibitors, nitrates, and statins (all p < 0.05). In unadjusted analysis, AP patients had increased MACE and death/MI/revascularization (both p < 0.001), lower rates of death and death/MI (both p < 0.05), and similar rates of death/MI/stroke and cardiovascular death/cardiovascular hospitalization (both p > 0.1). After multivariable adjustment, those with AP remained at increased risk for MACE (hazard ratio [HR]: 1.30, 95% confidence interval [CI]: 1.17 to 1.45) and death/MI/revascularization (HR: 1.29, 95% CI: 1.15 to 1.43), but they were at similar risk for other endpoints (p > 0.06). AP in HFpEF patients with a history of coronary artery disease is common despite medical therapy and is independently associated with increased MACE due to revascularization with similar risk of death, MI, and hospitalization. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Self-assessed symptoms in chronic heart failure--important information for clinical management.

PubMed

Ekman, Inger; Kjörk, Ewa; Andersson, Bert

2007-04-01

To compare the patients' self-assessment of the severity of their symptoms with a physicians assessment and to evaluate the ability of self-assessed symptoms and ejection fraction (EF) to predict long-term survival in heart failure patients. Patients (n=332) evaluated symptoms using a self-administered functional classification scale (Specific Activity Scale, SAS), which is equivalent to the NYHA scale. EF and NYHA functional class was also recorded. All patients were followed over a 3-year period. Approximately 50% of patients classified themselves into SAS class I. In contrast, the cardiologists classified only 9% of the patients as NYHA class I. In patients with severe left ventricular dysfunction (EF

A Feline HFpEF Model with Pulmonary Hypertension and Compromised Pulmonary Function.

PubMed

Wallner, Markus; Eaton, Deborah M; Berretta, Remus M; Borghetti, Giulia; Wu, Jichuan; Baker, Sandy T; Feldsott, Eric A; Sharp, Thomas E; Mohsin, Sadia; Oyama, Mark A; von Lewinski, Dirk; Post, Heiner; Wolfson, Marla R; Houser, Steven R

2017-11-29

Heart Failure with preserved Ejection Fraction (HFpEF) represents a major public health problem. The causative mechanisms are multifactorial and there are no effective treatments for HFpEF, partially attributable to the lack of well-established HFpEF animal models. We established a feline HFpEF model induced by slow-progressive pressure overload. Male domestic short hair cats (n = 20), underwent either sham procedures (n = 8) or aortic constriction (n = 12) with a customized pre-shaped band. Pulmonary function, gas exchange, and invasive hemodynamics were measured at 4-months post-banding. In banded cats, echocardiography at 4-months revealed concentric left ventricular (LV) hypertrophy, left atrial (LA) enlargement and dysfunction, and LV diastolic dysfunction with preserved systolic function, which subsequently led to elevated LV end-diastolic pressures and pulmonary hypertension. Furthermore, LV diastolic dysfunction was associated with increased LV fibrosis, cardiomyocyte hypertrophy, elevated NT-proBNP plasma levels, fluid and protein loss in pulmonary interstitium, impaired lung expansion, and alveolar-capillary membrane thickening. We report for the first time in HFpEF perivascular fluid cuff formation around extra-alveolar vessels with decreased respiratory compliance. Ultimately, these cardiopulmonary abnormalities resulted in impaired oxygenation. Our findings support the idea that this model can be used for testing novel therapeutic strategies to treat the ever growing HFpEF population.

Mitral annular longitudinal function preservation after mitral valve repair: the MARTE study.

PubMed

Lisi, M; Ballo, P; Cameli, M; Gandolfo, F; Galderisi, M; Chiavarelli, M; Henein, M Y; Mondillo, S

2012-05-31

In patients with chronic mitral regurgitation (MR), undergoing surgical mitral valve repair, current Guidelines only recommend standard echocardiographic indices i.e. left ventricular (LV) ejection fraction (EF), and LV end-systolic and end-diastolic diameters as preoperative variables. However LV EF is often preserved until advanced stages of the valve disease. Aim of this study was to evaluate changes in LV systolic longitudinal function, 3 months after mitral valve repair in patients with chronic degenerative MR and normal preoperative EF. We measured M-mode mitral lateral annulus systolic excursion (MAPSE) and Tissue Doppler (TD) peak systolic annular velocity (S(m)) in 31 patients with moderate to severe MR and normal EF (59.9 ± 4.7%) candidates for mitral valve repair, preoperatively and 3 months after surgery. After mitral valve repair, S(m) increased from 7.8 ± 1.4 to 9.6 ± 2.2 cm/s (p<0.0001) and MAPSE increased from 1.33 ± 0.26 to 1.55 ± 0.25 cm (p=0.0013). EF decreased from 59.9 ± 4.7 to 51.3 ± 5.9% (p<0.0001). As expected, LV diameters and volumes, wall thicknesses, midwall fractional shortening (mFS), and left atrial (LA) size were all reduced after surgery. This study suggests that assessment of LV long axis systolic velocity and amplitude of excursion by echocardiography is more sensitive than simple determination of EF for revealing the beneficial impact of MR surgery on overall systolic function. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

A randomised controlled trial of a facilitated home-based rehabilitation intervention in patients with heart failure with preserved ejection fraction and their caregivers: the REACH-HFpEF Pilot Study.

PubMed

Lang, Chim C; Smith, Karen; Wingham, Jennifer; Eyre, Victoria; Greaves, Colin J; Warren, Fiona C; Green, Colin; Jolly, Kate; Davis, Russell C; Doherty, Patrick Joseph; Miles, Jackie; Britten, Nicky; Abraham, Charles; Van Lingen, Robin; Singh, Sally J; Paul, Kevin; Hillsdon, Melvyn; Sadler, Susannah; Hayward, Christopher; Dalal, Hayes M; Taylor, Rod S

2018-04-09

Home-based cardiac rehabilitation may overcome suboptimal rates of participation. The overarching aim of this study was to assess the feasibility and acceptability of the novel Rehabilitation EnAblement in CHronic Hear Failure (REACH-HF) rehabilitation intervention for patients with heart failure with preserved ejection fraction (HFpEF) and their caregivers. Patients were randomised 1:1 to REACH-HF intervention plus usual care (intervention group) or usual care alone (control group). REACH-HF is a home-based comprehensive self-management rehabilitation programme that comprises patient and carer manuals with supplementary tools, delivered by trained healthcare facilitators over a 12 week period. Patient outcomes were collected by blinded assessors at baseline, 3 months and 6 months postrandomisation and included health-related quality of life (primary) and psychological well-being, exercise capacity, physical activity and HF-related hospitalisation (secondary). Outcomes were also collected in caregivers.We enrolled 50 symptomatic patients with HF from Tayside, Scotland with a left ventricular ejection fraction ≥45% (mean age 73.9 years, 54% female, 100% white British) and 21 caregivers. Study retention (90%) and intervention uptake (92%) were excellent. At 6 months, data from 45 patients showed a potential direction of effect in favour of the intervention group, including the primary outcome of Minnesota Living with Heart Failure Questionnaire total score (between-group mean difference -11.5, 95% CI -22.8 to 0.3). A total of 11 (4 intervention, 7 control) patients experienced a hospital admission over the 6 months of follow-up with 4 (control patients) of these admissions being HF-related. Improvements were seen in a number intervention caregivers' mental health and burden compared with control. Our findings support the feasibility and rationale for delivering the REACH-HF facilitated home-based rehabilitation intervention for patients with HFpEF and their caregivers and progression to a full multicentre randomised clinical trial to test its clinical effectiveness and cost-effectiveness. ISRCTN78539530. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Impact of metoprolol treatment on cardiac function and exercise tolerance in heart failure patients with neuropsychiatric disorders.

PubMed

Huang, Jingjing; Zhang, Ran; Liu, Xuelu; Meng, Yong

2018-01-01

To investigate the impact of neuropsychiatric disorders on the effect of metoprolol on cardiac and motor function in chronic heart failure (CHF) patients. From February 2013 to April 2016, CHF patients with clinical mental disorders received metoprolol (23.75 or 47.5 mg, once daily, orally) at the Second Affiliated Hospital of Kunming Medical University. Mental status was confirmed by means of the Hospital Anxiety and Depression Scale (HADS) and the Copenhagen Burnout Inventory (CBI) scale. Cardiac function parameters such as systolic blood pressure (SBP), ejection fraction (EF) and cardiac index (CI) as well as motor function including the 6 meter walk test (6MWT) and the Veteran's Specific Activity Questionnaire (VSAQ) were assessed as primary outcomes of the study. A total of 154 patients (median age, 66.39 years; men, n = 101) were allocated into eight groups based on their mental status. There were no significant differences in heart rate (HR) or SBP control achieved by metoprolol in any groups compared with the control (patients with normal mental status). Furthermore, biphasic ejection fraction (EF) changes were observed in all the groups with a decrease in the first month and increase from the sixth month. However, this increase was significantly lower (p < .001) than the EF achieved with metoprolol treatment in the control group except for the anxiety group. A similar pattern was seen for CI, 6MWT and VSAQ changes in all the groups. Patients in the anxiety group responded similarly to the patients with normal mental status. Depressive and high burnout symptoms, but not anxiety, lower the improvement of cardiac and motor function by metoprolol treatment in CHF.

Acute Hemodynamic Effects of Riociguat in Patients With Pulmonary Hypertension Associated With Diastolic Heart Failure (DILATE-1)

PubMed Central

Pretsch, Ingrid; Steringer-Mascherbauer, Regina; Jansa, Pavel; Rosenkranz, Stephan; Tufaro, Caroline; Bojic, Andja; Lam, Carolyn S. P.; Frey, Reiner; Ochan Kilama, Michael; Unger, Sigrun; Roessig, Lothar; Lang, Irene M.

2014-01-01

BACKGROUND: Deficient nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate signaling results from endothelial dysfunction and may underlie impaired cardiac relaxation in patients with heart failure with preserved left ventricular ejection fraction (HFpEF) and pulmonary hypertension (PH). The acute hemodynamic effects of riociguat, a novel soluble guanylate cyclase stimulator, were characterized in patients with PH and HFpEF. METHODS: Clinically stable patients receiving standard HF therapy with a left ventricular ejection fraction > 50%, mean pulmonary artery pressure (mPAP) ≥ 25 mm Hg, and pulmonary arterial wedge pressure (PAWP) > 15 mm Hg at rest were randomized to single oral doses of placebo or riociguat (0.5, 1, or 2 mg). The primary efficacy variable was the peak decrease in mPAP from baseline up to 6 h. Secondary outcomes included hemodynamic and echocardiographic parameters, safety, and pharmacokinetics. RESULTS: There was no significant change in peak decrease in mPAP with riociguat 2 mg (n = 10) vs placebo (n = 11, P = .6). However, riociguat 2 mg significantly increased stroke volume (+9 mL [95% CI, 0.4-17]; P = .04) and decreased systolic BP (−12 mm Hg [95% CI, −22 to −1]; P = .03) and right ventricular end-diastolic area (−5.6 cm2 [95% CI, −11 to −0.3]; P = .04), without significantly changing heart rate, PAWP, transpulmonary pressure gradient, or pulmonary vascular resistance. Riociguat was well tolerated. CONCLUSIONS: In patients with HFpEF and PH, riociguat was well tolerated, had no significant effect on mPAP, and improved exploratory hemodynamic and echocardiographic parameters. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01172756; URL: www.clinicaltrials.gov PMID:24991733

Effect of Optimizing Guideline-Directed Medical Therapy Before Discharge on Mortality and Heart Failure Readmission in Patients Hospitalized With Heart Failure With Reduced Ejection Fraction.

PubMed

Yamaguchi, Tetsuo; Kitai, Takeshi; Miyamoto, Takamichi; Kagiyama, Nobuyuki; Okumura, Takahiro; Kida, Keisuke; Oishi, Shogo; Akiyama, Eiichi; Suzuki, Satoshi; Yamamoto, Masayoshi; Yamaguchi, Junji; Iwai, Takamasa; Hijikata, Sadahiro; Masuda, Ryo; Miyazaki, Ryoichi; Hara, Nobuhiro; Nagata, Yasutoshi; Nozato, Toshihiro; Matsue, Yuya

2018-04-15

Guideline-directed medical therapy (GDMT) is recommended for patients with heart failure with reduced ejection fraction (HFrEF). However, the prognostic impact of medication optimization at the time of discharge in patients hospitalized with heart failure (HF) is unclear. We analyzed 534 patients (73 ± 13 years old) with HFrEF. The status of GDMT at the time of discharge (prescription of angiotensin converting enzyme inhibitor [ACE-I]/angiotensin receptor blocker [ARB] and β blocker [BB]) and its association with 1-year all-cause mortality and HF readmission were investigated. Patients were divided into 3 groups: those treated with both ACE-I/ARB and BB (Both group: n = 332, 62%), either ACE-I/ARB or BB (Either group: n = 169, 32%), and neither ACE-I/ARB nor BB (None group: n = 33, 6%), respectively. One-year mortality, but not 1-year HF readmission rate, was significantly different in the 3 groups, in favor of the Either and Both groups. A favorable impact of being on GDMT at the time of discharge on 1-year mortality was retained even after adjustment for covariates (Either group: hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.21 to 0.90, p = 0.025 and Both group: HR 0.29, 95% CI 0.13-0.65, p = 0.002, vs None group). For 1-year HF readmission, no such association was found. In conclusion, optimization of GDMT before the time of discharge was associated with a lower 1-year mortality, but not with HF readmission rate, in patients hospitalized with HFrEF. Copyright © 2018 Elsevier Inc. All rights reserved.

Impact of Exhaled Breath Acetone in the Prognosis of Patients with Heart Failure with Reduced Ejection Fraction (HFrEF). One Year of Clinical Follow-up

PubMed Central

Saldiva, Paulo H. N.; Mangini, Sandrigo; Issa, Victor S.; Ayub-Ferreira, Silvia M.; Bocchi, Edimar A.

2016-01-01

Background The identification of new biomarkers of heart failure (HF) could help in its treatment. Previously, our group studied 89 patients with HF and showed that exhaled breath acetone (EBA) is a new noninvasive biomarker of HF diagnosis. However, there is no data about the relevance of EBA as a biomarker of prognosis. Objectives To evaluate whether EBA could give prognostic information in patients with heart failure with reduced ejection fraction (HFrEF). Methods After breath collection and analysis by gas chromatography-mass spectrometry and by spectrophotometry, the 89 patients referred before were followed by one year. Study physicians, blind to the results of cardiac biomarker testing, ascertained vital status of each study participant at 12 months. Results The composite endpoint death and heart transplantation (HT) were observed in 35 patients (39.3%): 29 patients (32.6%) died and 6 (6.7%) were submitted to HT within 12 months after study enrollment. High levels of EBA (≥3.7μg/L, 50th percentile) were associated with a progressively worse prognosis in 12-month follow-up (log-rank = 11.06, p = 0.001). Concentrations of EBA above 3.7μg/L increased the risk of death or HT in 3.26 times (HR = 3.26, 95%CI = 1.56–6.80, p = 0.002) within 12 months. In a multivariable cox regression model, the independent predictors of all-cause mortality were systolic blood pressure, respiratory rate and EBA levels. Conclusions High EBA levels could be associated to poor prognosis in HFrEF patients. PMID:28030609

Reduced variability of visual left ventricular ejection fraction assessment with reference images: The Japanese Association of Young Echocardiography Fellows multicenter study.

PubMed

Kusunose, Kenya; Shibayama, Kentaro; Iwano, Hiroyuki; Izumo, Masaki; Kagiyama, Nobuyuki; Kurosawa, Koji; Mihara, Hirotsugu; Oe, Hiroki; Onishi, Tetsuari; Onishi, Toshinari; Ota, Mitsuhiko; Sasaki, Shunsuke; Shiina, Yumi; Tsuruta, Hikaru; Tanaka, Hidekazu

2018-07-01

Visual estimation of left ventricular ejection fraction (LVEF) is widely applied to confirm quantitative EF. However, visual assessment is subjective, and variability may be influenced by observer experience. We hypothesized that a learning session might reduce the misclassification rate. Protocol 1: Visual LVEFs for 30 cases were measured by 79 readers from 13 cardiovascular tertiary care centers. Readers were divided into 3 groups by their experience: limited (1-5 years, n=28), intermediate (6-11 years, n=26), and highly experienced (12-years, n=25). Protocol 2: All readers were randomized to assess the effect of a learning session with reference images only or feedback plus reference images. After the session, 20 new cases were shown to all readers following the same methodology. To assess the concordance and accuracy pre- and post-intervention, each visual LVEF measurement was compared to overall average values as a reference. Experience affected the concordance in visual EF values among the readers. Groups with intermediate and high experience showed significantly better mean difference (MD), standard deviation (SD), and coefficient of variation (CV) than those with limited experience at baseline. The learning session with reference image reduced the MD, SD, and CV in readers with limited experience. The learning session with reference images plus feedback also reduced proportional bias. Importantly, the misclassification rate for mid-range EF cases was reduced regardless of experience. This large multicenter study suggested that a simple learning session with reference images can successfully reduce the misclassification rate for LVEF assessment. Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Cost-effectiveness of sacubitril/valsartan in chronic heart-failure patients with reduced ejection fraction.

PubMed

Ademi, Zanfina; Pfeil, Alena M; Hancock, Elizabeth; Trueman, David; Haroun, Rola Haroun; Deschaseaux, Celine; Schwenkglenks, Matthias

2017-11-29

We aimed to assess the cost effectiveness of sacubitril/valsartan compared to angiotensin-converting enzyme inhibitors (ACEIs) for the treatment of individuals with chronic heart failure and reduced-ejection fraction (HFrEF) from the perspective of the Swiss health care system. The cost-effectiveness analysis was implemented as a lifelong regression-based cohort model. We compared sacubitril/valsartan with enalapril in chronic heart failure patients with HFrEF and New York-Heart Association Functional Classification II-IV symptoms. Regression models based on the randomised clinical phase III PARADIGM-HF trials were used to predict events (all-cause mortality, hospitalisations, adverse events and quality of life) for each treatment strategy modelled over the lifetime horizon, with adjustments for patient characteristics. Unit costs were obtained from Swiss public sources for the year 2014, and costs and effects were discounted by 3%. The main outcome of interest was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life years (QALYs) gained. Deterministic sensitivity analysis (DSA) and scenario and probabilistic sensitivity analysis (PSA) were performed. In the base-case analysis, the sacubitril/valsartan strategy showed a decrease in the number of hospitalisations (6.0% per year absolute reduction) and lifetime hospital costs by 8.0% (discounted) when compared with enalapril. Sacubitril/valsartan was predicted to improve overall and quality-adjusted survival by 0.50 years and 0.42 QALYs, respectively. Additional net-total costs were CHF 10 926. This led to an ICER of CHF 25 684. In PSA, the probability of sacubitril/valsartan being cost-effective at thresholds of CHF 50 000 was 99.0%. The treatment of HFrEF patients with sacubitril/valsartan versus enalapril is cost effective, if a willingness-to-pay threshold of CHF 50 000 per QALY gained ratio is assumed.

Cost-Effectiveness of Sacubitril-Valsartan Combination Therapy Compared With Enalapril for the Treatment of Heart Failure With Reduced Ejection Fraction.

PubMed

King, Jordan B; Shah, Rashmee U; Bress, Adam P; Nelson, Richard E; Bellows, Brandon K

2016-05-01

The objective of this study was to determine the cost-effectiveness and cost per quality-adjusted life year (QALY) gained of sacubitril-valsartan relative to enalapril for treatment of heart failure with reduced ejection fraction (HFrEF). Compared with enalapril, combination angiotensin receptor-neprilysin inhibition (ARNI), as is found in sacubitril-valsartan, reduces cardiovascular death and heart failure hospitalization rates in patients with HFrEF. Using a Markov model, costs, effects, and cost-effectiveness were estimated for sacubitril-valsartan and enalapril therapies for the treatment of HFrEF. Patients were 60 years of age at model entry and were modeled over a lifetime (40 years) from a third-party payer perspective. Clinical probabilities were derived predominantly from PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). All costs and effects were discounted at a 3% rate annually and are presented in 2015 U.S. dollars. In the base case, sacubitril-valsartan, compared with enalapril, was more costly ($60,391 vs. $21,758) and more effective (6.49 vs. 5.74 QALYs) over a lifetime. The cost-effectiveness of sacubitril-valsartan was highly dependent on duration of treatment, ranging from $249,411 per QALY at 3 years to $50,959 per QALY gained over a lifetime. Sacubitril-valsartan may be a cost-effective treatment option depending on the willingness-to-pay threshold. Future investigations should incorporate real-world evidence with sacubitril-valsartan to further inform decision making. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Pulmonary vascular response to exercise in symptomatic heart failure with reduced ejection fraction and pulmonary hypertension.

PubMed

Verbrugge, Frederik H; Dupont, Matthias; Bertrand, Philippe B; Nijst, Petra; Grieten, Lars; Dens, Joseph; Verhaert, David; Janssens, Stefan; Tang, W H Wilson; Mullens, Wilfried

2015-03-01

To study pulmonary vascular response patterns to exercise in heart failure with reduced ejection fraction (HFrEF) and pulmonary hypertension (PH). In this prospective single-centre cohort study, consecutive symptomatic HFrEF patients (n = 40) with mean pulmonary arterial pressure (MPAP) ≥25 mmHg, pulmonary artery wedge pressure (PAWP) >15 mmHg, and cardiac index <2.5 L/min.m(2) , received protocol-driven titrated sodium nitroprusside (SNP) and diuretics to reach mean arterial blood pressure 65-75 mmHg and PAWP ≤15 mmHg. Patients performed symptom-limited supine bicycle testing under continued SNP administration. Afterwards, SNP was gradually withdrawn, renin-angiotensin system blockers uptitrated, and hydralazine added to maintain haemodynamic targets. Subsequently, bicycle testing was repeated. Patients presented with pulmonary vascular resistance (PVR) = 3.8 ± 1.4 Wood Units at rest, decreasing to 2.9 ± 0.9 Wood Units after decongestion, with PH was completely reversed (MPAP <25 mmHg) in 22%. From rest to maximal exercise, the cardiac index did not change significantly (P = 0.334 under SNP; P-value = 0.552 under oral therapy). A dynamic exercise-induced PVR increase >3.5 Wood Units was noted in 19 patients (48%) under oral therapy vs. five (13%) under SNP. Such exercise-induced PVR increase was associated with a 33% relative decrease in right ventricular stroke work index (P = 0.037). Even after thorough decongestion and under continuous afterload reduction, PH secondary to HFrEF is completely reversible in only a minority of patients. Others demonstrate an exercise-induced PVR increase, associated with impaired right ventricular stroke work, which might be ameliorated by nitric oxide donor support. © 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.

Role of baseline echocardiography prior to initiation of anthracycline-based chemotherapy in breast cancer patients.

PubMed

Mina, Alain; Rafei, Hind; Khalil, Maya; Hassoun, Yasmine; Nasser, Zeina; Tfayli, Arafat

2015-01-21

Anthracycline adjuvant therapy has taken a particular role in the treatment of early stage breast cancer with an associated decrease in rates of both relapse and death. Their success however has been limited by their myelosuppression and their well-established risk of cardiac dysfunction. Guidelines have emerged that would limit the maximum lifetime dose of anthracyclines and make a baseline assessment and periodic monitoring of cardiac function part of the routine practice, which could be cumbersome, and may condemn the patient to an unwarranted modification of his/her regimen. Our study aimed at assessing the incidence of abnormal baseline echocardiography in asymptomatic women with breast cancer prior to anthracycline therapy and establishing risk criteria associated with abnormal echocardiograms at baseline. 220 Patients seen at AUBMC (American University of Beirut Medical Center) who had non- metastatic breast cancer, and had an echocardiography performed before starting anthracycline chemotherapy were chosen. Data about demographic characteristics, tumor characteristics, baseline echocardiography results, and change in clinical decision was collected. Patients with suboptimal (less than 50%) ejection fraction (EF) on baseline echocardiography were analyzed for the prevalence of cardiac risk factors. Results were compared to those among the overall study group using Fisher's Exact test. A p- value of = < 0.05 was used as reference for statistical significance. All 220 of our patients had received a baseline echo prior to initiation of anthracycline therapy. 6.7% of these patients had already some abnormality in wall motion but only 2.7% had a suboptimal ejection fraction. 1.3% had a change in chemotherapy regimen based on ejection fraction. The patients with depressed EF had higher rates of CAD (coronary artery disease), diabetes, hypertension and dyslipidemia than the overall study group but without statistical significance. Our study, as well as the previous contingent studies raise the question about routine echocardiography prior to anthracycline therapy and might eventually lead to a modification of current practice guidelines.

Baroreflex activation therapy for the treatment of heart failure with a reduced ejection fraction: safety and efficacy in patients with and without cardiac resynchronization therapy.

PubMed

Zile, Michael R; Abraham, William T; Weaver, Fred A; Butter, Christian; Ducharme, Anique; Halbach, Marcel; Klug, Didier; Lovett, Eric G; Müller-Ehmsen, Jochen; Schafer, Jill E; Senni, Michele; Swarup, Vijay; Wachter, Rolf; Little, William C

2015-10-01

Increased sympathetic and decreased parasympathetic activity contribute to heart failure (HF) symptoms and disease progression. Carotid baroreceptor stimulation (baroreflex activation therapy, BAT) results in centrally mediated reduction of sympathetic and increase in parasympathetic activity. Because patients treated with cardiac resynchronization therapy (CRT) may have less sympathetic/parasympathetic imbalance, we hypothesized that there would be differences in the response to BAT in patients with CRT vs. those without CRT. New York Heart Association (NYHA) Class III patients with an ejection fraction (EF) ≤35% were randomized (1 : 1) to ongoing guideline-directed medical and device therapy (GDMT, control) or ongoing GDMT plus BAT. Safety endpoint was system-/procedure-related major adverse neurological and cardiovascular events (MANCE). Efficacy endpoints were Minnesota Living with Heart Failure Quality of Life (QoL), 6-min hall walk distance (6MHWD), N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), and HF hospitalization rate. In this sample, 146 patients were randomized (70 control; 76 BAT) and were 140 activated (45 with CRT and 95 without CRT). MANCE-free rate at 6 months was 100% in CRT and 96% in no-CRT group. At 6 months, in the no-CRT group, QoL score, 6MHWD, LVEF, NT-proBNP and HF hospitalizations were significantly improved in BAT patients compared with controls. Changes in efficacy endpoints in the CRT group favoured BAT; however, the improvements were less than in the no-CRT group and were not statistically different from control. BAT is safe and significantly improved QoL, exercise capacity, NTpro-BNP, EF, and rate of HF hospitalizations in GDMT-treated NYHA Class III HF patients. These effects were most pronounced in patients not treated with CRT. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Worsening renal function and outcome in heart failure patients with reduced and preserved ejection fraction and the impact of angiotensin receptor blocker treatment: data from the CHARM-study programme.

PubMed

Damman, Kevin; Solomon, Scott D; Pfeffer, Marc A; Swedberg, Karl; Yusuf, Salim; Young, James B; Rouleau, Jean L; Granger, Christopher B; McMurray, John J V

2016-12-01

We investigated the association between worsening renal function (WRF) that occurs during renin-angiotensin-aldosterone system inhibition initation and outcome in heart failure (HF) patients with preserved ejection fraction (HFPEF) and compared this with HF patients with reduced ejection fraction (HFREF). We examined changes in estimated glomerular filtration rate (GFR) and the relationship between WRF (defined as ≥26.5 µmol/L and ≥25% increase in serum creatinine from baseline to 6 weeks) and outcome, according to randomized treatment, in patients with HFREF (EF <45%; n = 1569) and HFPEF (EF ≥45%; n = 836) in the CHARM programme. The primary outcome was cardiovascular death or HF hospitalization. Estimated GFR decreased 9.0 ± 21 vs. 4.0 ± 21 mL/min/1.73 m 2 with candesartan and placebo, respectively, and this was similar in HFREF and HFPEF. WRF developed more frequently with candesartan, 16% vs. 7%, P < 0.001, with similar findings in patients with HFREF and HFPEF. WRF was associated with a higher risk of the primary outcome: multivariable hazard ratio (HR) 1.26, 95% confidence interval 1.03-1.54, P = 0.022, in both treatment groups, and in both HFREF and HFPEF (P for interaction 0.98). In HFREF, WRF was mostly related to HF hospitalization, while in HFPEF, WRF seemed more associated with mortality. GFR decreased more and WRF was more common with candesartan compared with placebo, and this was similar in HFREF and HFPEF. WRF was associated with worse outcomes in HFREF and HFPEF. Although no formal interaction was present, the association between candesartan treatment, WRF, and type of clinical outcome was slightly different between HFREF and HFPEF. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

Cardiac resynchronization therapy with His bundle pacing as a method of treatment of chronic heart failure in patients with permanent atrial fibrillation and left bundle branch block.

PubMed

Boczar, Krzysztof; Sławuta, Agnieszka; Ząbek, Andrzej; Dębski, Maciej; Gajek, Jacek; Lelakowski, Jacek; Małecka, Barbara

CRT is a therapeutic option for patients with heart failure, sinus rhythm, prolonged QRS complex duration and reduced ejection fraction. We present a case of 71-year-old woman with dilated cardiomyopathy, NYHA functional class III and AF. We implanted CRT combined with direct His-bundle pacing. The indication for such a therapy was a left bundle branch block with a QRS complex of 178ms and a left ventricular EF of 15%, left ventricular end-diastolic diameter (LVEDD) of 75mm. After 8months of follow-up the LVEDD was 60mm with EF 35-40%. Copyright © 2017. Published by Elsevier Inc.

First third filling parameters of left ventricle assessed from gated equilibrium studies in patients with various heart diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adatepe, M.H.; Nichols, K.; Powell, O.M.

1984-01-01

The authors determined the first third filling fraction (1/3 FF), the maximum filling rate (1/3 FR) and the mean filling rate (1/3 MFR) for the first third diastolic filling period of the left ventricle in patients with coronary artery disease (CAD), valvular heart disease (VHD), pericardial effusion (PE), cardiomyopathies (CM), chronic obstructive lung disease (COPD) and in 5 normals-all from resting gated equilibrium studies. Parameters are calculated from the third order Fourier fit to the LV volume curve and its derivative. 1/3 FF% = 1/3 diastolic count - end systolic count / 1/3 diastolic count x 100. Patients with CADmore » are divided into two groups: Group I with normal ejection fraction (EF) and wall motion (WM); Group II with abnormal EF and WM. Results are shown in the table. Abnormal filling parameters are found not only in CAD but in VHD, PE and CM. The authors conclude that the first third LV filling parameters are sensitive but non-specific indicators of filling abnormalities caused by diverse etiologic factors. Abnormal first third filling parameters may occur in the presence of a normal resting EF and WM in CAD.« less

Comparison of Echocardiographic Measurements Before and After Short and Long Duration Spaceflight

NASA Technical Reports Server (NTRS)

Fritsch-Yelle, Janice M.; South, Donna A.; Wood, Margie L.; Bungo, Michael W.

2000-01-01

Previous echocardiography studies in astronauts before and after short duration (4 - 17 days) missions have demonstrated a decrease in resting left ventricular (LV) stroke volume (SV), but maintained ejection fraction (EF) and cardiac output. Similar studies before and after long duration (129 - 144 days) spaceflight have been rare and their overall results equivocal. The purpose of this work was to compare the echocardiographic measurements (M-mode, 2-D and Doppler) from short duration (n = 13) and long duration (n = 4) crewmembers. Compared to short duration astronauts, long duration crewmembers had a significantly greater percent decrease in EF (+6+/-0.02 vs.-10.5+/-0.03, p = 0.005) and percent fractional shortening (+7+/-0.03 vs. -11+/-0.07, p = 0.0 15), and an increase in LV end systolic volume (-12+/-0.06 vs. +39+/-0.24, p = 0.011). These data suggest a reduction in cardiac function that relates to mission duration. As the changes in blood pressure and circulating blood volume (9% - 12%) are reported to be similar after short and long duration flights, the drop in EF after longer spaceflights is likely due to a decrease in cardiac function rather than altered blood volume.

Histone deacetylase activity governs diastolic dysfunction through a nongenomic mechanism

PubMed Central

Jeong, Mark Y.; Lin, Ying H.; Wennersten, Sara A.; Demos-Davies, Kimberly M.; Cavasin, Maria A.; Mahaffey, Jennifer H.; Monzani, Valmen; Saripalli, Chandrasekhar; Mascagni, Paolo; Reece, T. Brett; Ambardekar, Amrut V.; Granzier, Henk L.; Dinarello, Charles A.; McKinsey, Timothy A.

2018-01-01

There are no approved drugs for the treatment of heart failure with preserved ejection fraction (HFpEF), which is characterized by left ventricular (LV) diastolic dysfunction. We demonstrate that ITF2357 (givinostat), a clinical-stage inhibitor of histone deacetylase (HDAC) catalytic activity, is efficacious in two distinct murine models of diastolic dysfunction with preserved EF. ITF2357 blocked LV diastolic dysfunction due to hypertension in Dahl salt-sensitive (DSS) rats and suppressed aging-induced diastolic dysfunction in normotensive mice. HDAC inhibitor–mediated efficacy was not due to lowering blood pressure or inhibiting cellular and molecular events commonly associated with diastolic dysfunction, including cardiac fibrosis, cardiac hypertrophy, or changes in cardiac titin and myosin isoform expression. Instead, ex vivo studies revealed impairment of cardiac myofibril relaxation as a previously unrecognized, myocyte-autonomous mechanism for diastolic dysfunction, which can be ameliorated by HDAC inhibition. Translating these findings to humans, cardiac myofibrils from patients with diastolic dysfunction and preserved EF also exhibited compromised relaxation. These data suggest that agents such as HDAC inhibitors, which potentiate cardiac myofibril relaxation, hold promise for the treatment of HFpEF in humans. PMID:29437146

PATHOPHYSIOLOGY AND THE CARDIORENAL CONNECTION IN HEART FAILURE. CIRCULATING HORMONES: BIOMARKERS OR MEDIATORS

PubMed Central

BUGLIONI, ALESSIA; BURNETT, JOHN C.

2014-01-01

Heart failure (HF) is a syndrome characterized by a complex pathophysiology which involves multiple organ systems, with the kidney playing a major role. HF can present with reduced ejection fraction (EF), HFrEF, or with preserved EF (HFpEF). The interplay between diverse organ systems contributing to HF is mediated by the activation of counteracting neurohormonal pathways focused to re-establishing hemodynamic homeostasis. During early stages of HF, these biochemical signals, consisting mostly of hormones and neurotransmitters secreted by a variety of cell types, are compensatory and the patient is asymptomatic. However, with disease progression, the attempt to reverse or delay cardiac dysfunction is deleterious, leading to multi-organ congestion, fibrosis and decompensation and finally symptomatic HF. In conclusion, these neurohormonal pathways mediate the evolution of HF and have become a way to monitor HF. Specifically, these mediators have become important in the diagnosis and prognosis of this highly fatal cardiovascular disease. Finally, while these multiple neurohumoral factors serve as important HF biomarkers, they can also be targeted for more effective and curative HF treatments. PMID:25445413

Mineralocorticoid receptor antagonists for heart failure: a real‐life observational study

PubMed Central

Bruno, Noemi; Sinagra, Gianfranco; Paolillo, Stefania; Bonomi, Alice; Corrà, Ugo; Piepoli, Massimo; Veglia, Fabrizio; Salvioni, Elisabetta; Lagioia, Rocco; Metra, Marco; Limongelli, Giuseppe; Cattadori, Gaia; Scardovi, Angela B.; Carubelli, Valentina; Scrutino, Domenico; Badagliacca, Roberto; Guazzi, Marco; Raimondo, Rosa; Gentile, Piero; Magrì, Damiano; Correale, Michele; Parati, Gianfranco; Re, Federica; Cicoira, Mariantonietta; Frigerio, Maria; Bussotti, Maurizio; Vignati, Carlo; Oliva, Fabrizio; Mezzani, Alessandro; Vergaro, Giuseppe; Di Lenarda, Andrea; Passino, Claudio; Sciomer, Susanna; Pacileo, Giuseppe; Ricci, Roberto; Contini, Mauro; Apostolo, Anna; Palermo, Pietro; Mapelli, Massimo; Carriere, Cosimo; Clemenza, Francesco; Binno, Simone; Belardinelli, Romualdo; Lombardi, Carlo; Perrone Filardi, Pasquale; Emdin, Michele

2018-01-01

Abstract Aims Mineralocorticoid receptor antagonists (MRAs) have been demonstrated to improve outcomes in reduced ejection fraction heart failure (HFrEF) patients. However, MRAs added to conventional treatment may lead to worsening of renal function and hyperkalaemia. We investigated, in a population‐based analysis, the long‐term effects of MRA treatment in HFrEF patients. Methods and results We analysed data of 6046 patients included in the Metabolic Exercise Cardiac Kidney Index score dataset. Analysis was performed in patients treated (n = 3163) and not treated (n = 2883) with MRA. The study endpoint was a composite of cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation. Ten years' survival was analysed through Kaplan–Meier, compared by log‐rank test and propensity score matching. At 10 years' follow‐up, the MRA‐untreated group had a significantly lower number of events than the MRA‐treated group (P < 0.001). MRA‐treated patients had more severe heart failure (higher New York Heart Association class and lower left ventricular ejection fraction, kidney function, and peak VO2). At a propensity‐score‐matching analysis performed on 1587 patients, MRA‐treated and MRA‐untreated patients showed similar study endpoint values. Conclusions In conclusion, MRA treatment does not affect the composite of cardiovascular death, urgent heart transplantation or left ventricular assist device implantation in a real‐life setting. A meticulous patient follow‐up, as performed in trials, is likely needed to match the positive MRA‐related benefits observed in clinical trials. PMID:29397584

Hemodynamic responses to etomidate versus ketamine-thiopental sodium combination for anesthetic induction in coronary artery bypass graft surgery patients with low ejection fraction: a double-blind, randomized, clinical trial.

PubMed

Habibi, Mohammad Reza; Baradari, Afshin Gholipour; Soleimani, Aria; Emami Zeydi, Amir; Nia, Hamid Sharif; Habibi, Ali; Onagh, Naser

2014-10-01

During induction of anesthesia and intubation, hemodynamic changes are very important; especially in patients with coronary artery disease (CAD) and left ventricular dysfunction. A little information is available on the hemodynamic effects of a combination of ketamine-thiopental for induction of anesthesia in patients undergoing coronary artery bypass graft (CABG) surgery, with impaired ventricular function. The aim of this study was to compare the hemodynamic responses to etomidate versus ketamine-thiopental sodium combination for anesthetic induction in CABG surgery patients with low ejection fraction (EF<45%). In a double blind randomized clinical trial, a total of 100 patients, scheduled for elective CABG surgery were randomly assigned into two groups. These patients received either etomidate or ketamine-thiopental sodium combination at induction of anesthesia. Hemodynamics variable were measured and recorded at baseline, immediately before and after laryngoscopy and intubation, one, two and three minutes after intubation. Also, muscle twitching incidence among patients in two groups was evaluated. No significant differences between the two groups regarding the changes of hemodynamic variables including systolic and diastolic arterial blood pressure, mean arterial pressure and heart rate, were notice (p>0.05). Muscle twitching was not observed in the two groups. Hemodynamic stability after administration of ketamine-thiopental sodium combination for induction of anesthesia in patients undergoing CABG surgery, with impaired ventricular function, supports the clinical impression that this combination is safe in CABG surgery patients with low EF.

Pulmonary hypertension due to left heart disease: diagnostic and prognostic value of CT in chronic systolic heart failure.

PubMed

Colin, Geoffrey C; Gerber, Bernhard L; de Meester de Ravenstein, Christophe; Byl, David; Dietz, Anna; Kamga, Michele; Pasquet, Agnes; Vancraeynest, David; Vanoverschelde, Jean-Louis; D'Hondt, Anne-Marie; Ghaye, Benoit; Pouleur, Anne-Catherine

2018-05-14

To evaluate the ability of chest computed tomography (CT) to predict pulmonary hypertension (PH) and outcome in chronic heart failure with reduced ejection fraction (HFrEF). We reviewed 119 consecutive patients with HFrEF by CT, transthoracic echocardiography (TTE) and right heart catheterization (RHC). CT-derived pulmonary artery (PA) diameter and PA to ascending aorta diameter ratio (PA:A ratio), left atrial, right atrial, right ventricular (RV) and left ventricular volumes were correlated with RHC mean pulmonary arterial pressure (mPAP) . Diagnostic accuracy to predict PH and ability to predict primary composite endpoint of all-cause mortality and HF events were evaluated. RV volume was significantly higher in 81 patients with PH compared to 38 patients without PH (133 ml/m 2 vs. 79 ml/m 2 , p < 0.001) and was moderately correlated with mPAP (r=0.55, p < 0.001). Also, RV volume had higher ability to predict PH (area under the curve: 0.88) than PA diameter (0.79), PA:A ratio (0.76) by CT and tricuspid regurgitation gradient (0.83) and RV basal diameter by TTE (0.84, all p < 0.001). During the follow-up period (median: 3.4 years), 51 patients (43%) had HF events or died. After correction for important clinical, TTE and RHC parameters, RV volume (adjusted hazard ratio [HR]: 1.71, 95% CI 1.31-2.23, p < 0.001) and PA diameter (HR: 1.61, 95% CI 1.18-2.22, p = 0.003) were independent predictors of the primary endpoint. In patients with HFrEF, measurement of RV volume and PA diameter on ungated CT are non-invasive markers of PH and may help to predict the patient outcome. • Right ventricular (RV) volume measured by chest CT has good ability to identify pulmonary hypertension (PH) in patients with chronic heart failure (HF) and reduced ejection fraction (HFrEF). • The accuracy of pulmonary artery (PA) diameter and PA to ascending aorta diameter ratio (PA:A ratio) to predict PH was similar to previous studies, however, with lower cut-offs (28.1 mm and 0.92, respectively). • Chest CT-derived PA diameter and RV volume independently predict all-cause mortality and HF events and improve outcome prediction in patients with advanced HFrEF.

Rehabilitation Enablement in Chronic Heart Failure-a facilitated self-care rehabilitation intervention in patients with heart failure with preserved ejection fraction (REACH-HFpEF) and their caregivers: rationale and protocol for a single-centre pilot randomised controlled trial.

PubMed

Eyre, V; Lang, C C; Smith, K; Jolly, K; Davis, R; Hayward, C; Wingham, J; Abraham, C; Green, C; Warren, F C; Britten, N; Greaves, C J; Doherty, P; Austin, J; Van Lingen, R; Singh, S; Buckingham, S; Paul, K; Taylor, R S; Dalal, H M

2016-10-25

The Rehabilitation EnAblement in CHronic Heart Failure in patients with Heart Failure (HF) with preserved ejection fraction (REACH-HFpEF) pilot trial is part of a research programme designed to develop and evaluate a facilitated, home-based, self-help rehabilitation intervention to improve self-care and quality of life (QoL) in heart failure patients and their caregivers. We will assess the feasibility of a definitive trial of the REACH-HF intervention in patients with HFpEF and their caregivers. The impact of the REACH-HF intervention on echocardiographic outcomes and bloodborne biomarkers will also be assessed. A single-centre parallel two-group randomised controlled trial (RCT) with 1:1 individual allocation to the REACH-HF intervention plus usual care (intervention) or usual care alone (control) in 50 HFpEF patients and their caregivers. The REACH-HF intervention comprises a REACH-HF manual with supplementary tools, delivered by trained facilitators over 12 weeks. A mixed methods approach will be used to assess estimation of recruitment and retention rates; fidelity of REACH-HF manual delivery; identification of barriers to participation and adherence to the intervention and study protocol; feasibility of data collection and outcome burden. We will assess the variance in study outcomes to inform a definitive study sample size and assess methods for the collection of resource use and intervention delivery cost data to develop the cost-effectiveness analyses framework for any future trial. Patient outcomes collected at baseline, 4 and 6 months include QoL, psychological well-being, exercise capacity, physical activity and HF-related hospitalisation. Caregiver outcomes will also be assessed, and a substudy will evaluate impact of the REACH-HF manual on resting global cardiovascular function and bloodborne biomarkers in HFpEF patients. The study is approved by the East of Scotland Research Ethics Service (Ref: 15/ES/0036). Findings will be disseminated via journals and presentations to clinicians, commissioners and service users. ISRCTN78539530; Pre-results . Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Do Optimal Prognostic Thresholds in Continuous Physiological Variables Really Exist? Analysis of Origin of Apparent Thresholds, with Systematic Review for Peak Oxygen Consumption, Ejection Fraction and BNP

PubMed Central

Leong, Tora; Rehman, Michaela B.; Pastormerlo, Luigi Emilio; Harrell, Frank E.; Coats, Andrew J. S.; Francis, Darrel P.

2014-01-01

Background Clinicians are sometimes advised to make decisions using thresholds in measured variables, derived from prognostic studies. Objectives We studied why there are conflicting apparently-optimal prognostic thresholds, for example in exercise peak oxygen uptake (pVO2), ejection fraction (EF), and Brain Natriuretic Peptide (BNP) in heart failure (HF). Data Sources and Eligibility Criteria Studies testing pVO2, EF or BNP prognostic thresholds in heart failure, published between 1990 and 2010, listed on Pubmed. Methods First, we examined studies testing pVO2, EF or BNP prognostic thresholds. Second, we created repeated simulations of 1500 patients to identify whether an apparently-optimal prognostic threshold indicates step change in risk. Results 33 studies (8946 patients) tested a pVO2 threshold. 18 found it prognostically significant: the actual reported threshold ranged widely (10–18 ml/kg/min) but was overwhelmingly controlled by the individual study population's mean pVO2 (r = 0.86, p<0.00001). In contrast, the 15 negative publications were testing thresholds 199% further from their means (p = 0.0001). Likewise, of 35 EF studies (10220 patients), the thresholds in the 22 positive reports were strongly determined by study means (r = 0.90, p<0.0001). Similarly, in the 19 positives of 20 BNP studies (9725 patients): r = 0.86 (p<0.0001). Second, survival simulations always discovered a “most significant” threshold, even when there was definitely no step change in mortality. With linear increase in risk, the apparently-optimal threshold was always near the sample mean (r = 0.99, p<0.001). Limitations This study cannot report the best threshold for any of these variables; instead it explains how common clinical research procedures routinely produce false thresholds. Key Findings First, shifting (and/or disappearance) of an apparently-optimal prognostic threshold is strongly determined by studies' average pVO2, EF or BNP. Second, apparently-optimal thresholds always appear, even with no step in prognosis. Conclusions Emphatic therapeutic guidance based on thresholds from observational studies may be ill-founded. We should not assume that optimal thresholds, or any thresholds, exist. PMID:24475020

Heart rate response and functional capacity in patients with chronic heart failure with preserved ejection fraction.

PubMed

Domínguez, Eloy; Palau, Patricia; Núñez, Eduardo; Ramón, José María; López, Laura; Melero, Joana; Bellver, Alejandro; Santas, Enrique; Chorro, Francisco J; Núñez, Julio

2018-03-24

The mechanisms of exercise intolerance in heart failure with preserved ejection fraction (HFpEF) are not yet elucidated. Chronotropic incompetence has emerged as a potential mechanism. We aimed to evaluate whether heart rate (HR) response to exercise is associated to functional capacity in patients with symptomatic HFpEF. We prospectively studied 74 HFpEF patients [35.1% New York Heart Association Class III, 53% female, age (mean ± standard deviation) 72.5 ± 9.1 years, and 59.5% atrial fibrillation]. Functional performance was assessed by peak oxygen consumption (peak VO 2 ). The mean (standard deviation) peak VO 2 was 10 ± 2.8 mL/min/kg. The following chronotropic parameters were calculated: Delta-HR (HR at peak exercise - HR at rest), chronotropic index (CI) = (HR at peak exercise - resting HR)/[(220 - age) - resting HR], and CI according to the equation developed by Keteyian et al. (CIK) (HR at peak exercise - HR at rest)/[119 + (HR at rest/2) - (age/2) - 5 - HR at rest]. In a bivariate setting, peak VO 2 was positively and significantly correlated with Delta-HR (r = 0.35, P = 0.003), CI (r = 0.27, P = 0.022), CIK (r = 0.28, P = 0.018), and borderline with HR at peak exercise (r = 0.22, P = 0.055). In a multivariable linear regression analysis that included clinical, analytical, echocardiographic, and functional capacity covariates, the chronotropic parameters were positively associated with peak VO 2 . We found a linear relationship between Delta-HR and peak VO 2 (β coefficient of 0.03; 95% confidence interval: 0.004-0.05; P = 0.030); conversely, the association among CIs and peak VO 2 was exponentially shaped. In patients with chronic HFpEF, the HR response to exercise was positively associated to patient's functional capacity. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Decreased Mortality With Beta-Blockers in Patients With Heart Failure and Coexisting Atrial Fibrillation: An AF-CHF Substudy.

PubMed

Cadrin-Tourigny, Julia; Shohoudi, Azadeh; Roy, Denis; Talajic, Mario; Tadros, Rafik; Mondésert, Blandine; Dyrda, Katia; Rivard, Léna; Andrade, Jason G; Macle, Laurent; Guerra, Peter G; Thibault, Bernard; Dubuc, Marc; Khairy, Paul

2017-02-01

The impact of beta-blockers on mortality and hospitalizations was assessed in the largest randomized trial of patients with both atrial fibrillation (AF) and heart failure with a reduced ejection fraction (HFrEF): the Atrial Fibrillation-Congestive Heart Failure trial. Although beta-blockers are the cornerstone of therapy for HFrEF, a recent patient-level meta-analysis cast doubt on their efficacy in patients with coexisting AF. From a total of 1,376 subjects randomized in the AF-CHF trial, those without beta-blockers at baseline were propensity matched to a maximum of 2 exposed patients. All absolute standardized differences after matching were ≤10%. Primary analyses respected the intention-to-treat principle. In on-treatment sensitivity analyses, beta-blocker status was modeled as a time-dependent covariate. Baseline characteristics were comparable among the matched cohorts (mean age 70 ± 11 years, 81% male, and mean left ventricular ejection fraction 27 ± 6%). During a median follow-up of 37 months, beta-blockers were associated with significantly lower all-cause mortality (hazard ratio [HR]: 0.721, 95% confidence interval [CI]: 0.549 to 0.945; p = 0.0180) but not hospitalizations (HR: 0.886; 95% CI: 0.715 to 1.100; p = 0.2232). Similar results were obtained in sensitivity analyses that modeled beta-blockers as a time-dependent variable (HR: 0.668 for all-cause mortality; 95% CI: 0.511 to 0.874; p = 0.0032; HR: 0.814 for hospitalizations; 95% CI: 0.653 to 1.014; p = 0.0658). There were no significant interactions between beta-blockers and patterns (i.e., persistent vs. paroxysmal) or burden of AF with respect to mortality or hospitalizations. In propensity-matched analyses, beta-blockers were associated with significantly lower mortality but not hospitalizations in patients with HFrEF and AF, irrespective of the pattern or burden of AF. These results support current evidence-based recommendations for beta-blockers in patients with HFrEF, whether or not they have associated AF. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Left ventricular remodeling and change of systolic function after closure of patent ductus arteriosus in adults: device and surgical closure.

PubMed

Jeong, Young-Hoon; Yun, Tae-Jin; Song, Jong-Min; Park, Jung-Jun; Seo, Dong-Man; Koh, Jae-Kon; Lee, Se-Whan; Kim, Mi-Jeong; Kang, Duk-Hyun; Song, Jae-Kwan

2007-09-01

Left ventricular (LV) remodeling and predictors of LV systolic function late after closure of patent ductus arteriosus (PDA) in adults remain to be clearly demonstrated. In 45 patients with PDA, including 28 patients who received successful occlusion using the Amplatzer device (AD group) (AGA, Golden Valley, MN) and 17 patients who received surgical closure (OP group), echocardiography studies were performed before closure and 1 day (AD group) or within 7 days (OP group) after closure, and then were repeated at > or = 6 months (17 +/- 13 months). In both groups, LV ejection fraction (EF) and end-diastolic volume index were significantly decreased immediately after closure, whereas end-systolic volume index did not change. During the long-term follow-up period, end-systolic as well as end-diastolic volume indices decreased significantly in both groups and LV EF recovered compared to the immediate postclosure state. However, LV EF remained low compared to the preclosure state. Five patients (11.1%) including 3 patients in the AD group and 2 patients in the OP group showed persistent late LV systolic dysfunction (EF <50%). In stepwise, multiple logistic regression analysis, preclosure EF was the only independent predictor of late normal postclosure EF (odds ratio, 1.230; 95% CI, 1.054-1.434; P = .008). Receiver operating characteristic curve analysis showed that preclosure EF > or = 62% had a sensitivity of 72% and a specificity of 83% for predicting late normal LV EF after closure. Left ventricular EF remains low late after PDA closure compared with preclosure state in adults. Preclosure LV EF is the best index to predict late postclosure LV EF.

Regional nonuniformity of normal adult human left ventricle.

PubMed

Bogaert, J; Rademakers, F E

2001-02-01

Regional nonuniformity is a feature of both diseased and normal left ventricles (LV). With the use of magnetic resonance (MR) myocardial tagging, we performed three-dimensional strain analysis on 87 healthy adults in local cardiac and fiber coordinate systems (radial, circumferential, longitudinal, and fiber strains) to characterize normal nonuniformities and to test the validity of wall thickening as a parameter of regional function. Regional morphology included wall thickness and radii of curvature measurements. With respect to transmural nonuniformity, subendocardial strains exceeded subepicardial strains. Going from base to apex, wall thickness and circumferential radii of curvature decreased, whereas longitudinal radii of curvature increased. All of the strains increased from LV base to apex, resulting in a higher ejection fraction (EF) at the apex than at the base (70.9 +/- 0.4 vs. 62.4 +/- 0.4%; means +/- SE, P < 0.0001). When we looked around the circumference of the ventricle, the anterior part of the LV was the flattest and thinnest and showed the largest wall thickening (46.6 +/- 1.2%) but the lowest EF (64.7 +/- 0.5%). The posterior LV wall was thicker, more curved, and showed a lower wall thickening (32.8 +/- 1.0%) but a higher EF (71.3 +/- 0.5%). The regional contribution of the LV wall to the ejection of blood is thus highly variable and is not fully characterized by wall thickening alone. Differences in regional LV architecture and probably local stress are possible explanations for this marked functional nonuniformity.

Inflammatory Biomarkers Predict Heart Failure Severity and Prognosis in Patients With Heart Failure With Preserved Ejection Fraction: A Holistic Proteomic Approach.

PubMed

Hage, Camilla; Michaëlsson, Erik; Linde, Cecilia; Donal, Erwan; Daubert, Jean-Claude; Gan, Li-Ming; Lund, Lars H

2017-02-01

Underlying mechanisms in heart failure (HF) with preserved ejection fraction remain unknown. We investigated cardiovascular plasma biomarkers in HF with preserved ejection fraction and their correlation to diastolic dysfunction, functional class, pathophysiological processes, and prognosis. In 86 stable patients with HF and EF ≥45% in the Karolinska Rennes (KaRen) biomarker substudy, biomarkers were quantified by a multiplex immunoassay. Orthogonal projection to latent structures by partial least square analysis was performed on 87 biomarkers and 240 clinical variables, ranking biomarkers associated with New York Heart Association (NYHA) Functional class and the composite outcome (all-cause mortality and HF hospitalization). Biomarkers significantly correlated with outcome were analyzed by multivariable Cox regression and correlations with echocardiographic measurements performed. The orthogonal partial least square outcome-predicting biomarker pattern was run against the Ingenuity Pathway Analysis (IPA) database, containing annotated data from the public domain. The orthogonal partial least square analyses identified 32 biomarkers correlated with NYHA class and 28 predicting outcomes. Among outcome-predicting biomarkers, growth/differentiation factor-15 was the strongest and an additional 7 were also significant in Cox regression analyses when adjusted for age, sex, and N-terminal probrain natriuretic peptide: adrenomedullin (hazard ratio per log increase 2.53), agouti-related protein; (1.48), chitinase-3-like protein 1 (1.35), C-C motif chemokine 20 (1.35), fatty acid-binding protein (1.33), tumor necrosis factor receptor 1 (2.29), and TNF-related apoptosis-inducing ligand (0.34). Twenty-three of them correlated with diastolic dysfunction (E/e') and 5 with left atrial volume index. The IPA suggested that increased inflammation, immune activation with decreased necrosis and apoptosis preceded poor outcome. In HF with preserved ejection fraction, novel biomarkers of inflammation predict HF severity and prognosis that may complement or even outperform traditional markers, such as N-terminal probrain natriuretic peptide. These findings lend support to a hypothesis implicating global systemic inflammation in HF with preserved ejection fraction. URL: http://www.clinicaltrials.gov; Unique identifier: NCT00774709. © 2017 American Heart Association, Inc.

Temporal trends and factors associated with diabetes mellitus among patients hospitalized with heart failure: Findings from Get With The Guidelines-Heart Failure registry.

PubMed

Echouffo-Tcheugui, Justin B; Xu, Haolin; DeVore, Adam D; Schulte, Phillip J; Butler, Javed; Yancy, Clyde W; Bhatt, Deepak L; Hernandez, Adrian F; Heidenreich, Paul A; Fonarow, Gregg C

2016-12-01

The contribution of diabetes to the burden of heart failure (HF) remains largely undescribed. Assessing diabetes temporal trends among US patients hospitalized with HF and their relation with quality measures in real-world practice can help to define this burden. Using data from the Get With the Guidelines-Heart Failure registry, we assessed temporal trends in diabetes prevalence among patients with HF and in subgroups with reduced ejection fraction (HFrEF; EF < 40%), borderline EF (HFbEF; 40%≤EF <50%), or preserved EF (HFpEF; EF ≥ 50%), hospitalized between 2005 and 2015. Logistic regression was used to assess whether in-hospital outcomes and HF quality of care were related to trends. Among 364,480 HF hospitalizations, 160,171 had diabetes (44.0% overall, 41.8% in HFrEF, 46.7% in HFbEF, 45.5% in HFpEF). There was a temporal increase in diabetes frequency in HF patients (43.2%-45.8%; P trend <.0001), including among those with HFrEF (42.0%-43.6%; P trend <.0001), HFbEF (46.0%-49.2%; P trend <.0001), or HFpEF (43.6%-46.8%, P trend <.0001). Diabetic patients had a longer hospital stay (adjusted odds ratio 1.14, 95% CI 1.12-1.16), but lower in-hospital mortality (adjusted odds ratio 0.93 [0.89-0.97]) compared with those without diabetes, with limited differences in quality measures. Temporal trends in diabetes were not associated with in-hospital mortality or length of stay. There were no temporal interactions of most HF quality measures with diabetes status. Approximately 44% of hospitalized HF patients have diabetes, and this proportion has been increasing over the past 10years, particularly among those patients with new-onset HFpEF. Copyright © 2016 Elsevier Inc. All rights reserved.

A comparison of HFrEF vs HFpEF's clinical workload and cost in the first year following hospitalization and enrollment in a disease management program.

PubMed

Murphy, T M; Waterhouse, D F; James, S; Casey, C; Fitzgerald, E; O'Connell, E; Watson, C; Gallagher, J; Ledwidge, M; McDonald, K

2017-04-01

Admission with heart failure (HF) is a milestone in the progression of the disease, often resulting in higher intensity medical care and ensuing readmissions. Whilst there is evidence supporting enrolling patients in a heart failure disease management program (HF-DMP), not all reported HF-DMPs have systematically enrolled patients with HF with preserved ejection fraction (HFpEF) and there is a scarcity of literature differentiating costs based on HF-phenotype. 1292 consenting, consecutive patients admitted with a primary diagnosis of HF were enrolled in a hospital based HF-DMP and categorized as HFpEF (EF≥45%) or HFrEF (EF<45%). Hospitalizations, primary care, medications, and DMP workload with associated costs were evaluated assessing DMP clinic-visits, telephonic contact, medication changes over 1year using a mixture of casemix and micro-costing techniques. The total average annual cost per patient was marginally higher in patients with HFrEF €13,011 (12,011, 14,078) than HFpEF, €12,206 (11,009, 13,518). However, emergency non-cardiovascular admission rates and average cost per patient were higher in the HFpEF vs HFrEF group (0.46 vs 0.31 per patient/12months) & €655 (318, 1073) vs €584 (396, 812). In the first 3months of the outpatient HF-DMP the HFrEF population cost more on average €791 (764, 819) vs €693 (660, 728). There are greater short-term (3-month) costs of HFrEF versus HFpEF as part of a HF-DMP following an admission. However, long-term (3-12month) costs of HFpEF are greater because of higher non-cardiovascular rehospitalisations. As HFpEF becomes the dominant form of HF, more work is required in HF-DMPs to address prevention of non-cardiovascular rehospitalisations and to integrate hospital based HF-DMPs into primary healthcare structures. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Presence and Implication of Temporal Nonuniformity of Early Diastolic Left Ventricular Wall Expansion in Patients With Heart Failure.

PubMed

Iwano, Hiroyuki; Kamimura, Daisuke; Fox, Ervin R; Hall, Michael E; Vlachos, Pavlos; Little, William C

2016-12-01

Early-diastolic left ventricular (LV) longitudinal expansion is delayed with diastolic dysfunction. We hypothesized that, in patients with heart failure (HF), regardless of LV ejection fraction (EF), there is diastolic temporal nonuniformity with a delay of longitudinal relative to circumferential expansion. Echocardiography was performed in 143 HF patients-50 with preserved EF (HFpEF) and 93 with reduced EF (HFrEF)-as well as 31 normal control subjects. The delay of early-diastolic mitral annular velocity from the mitral Doppler E (T E-e' ) was measured as a parameter of the longitudinal expansion delay. The delay of the longitudinal early-diastolic global strain rate (SR E ) relative to circumferential SR E (Delay C-L ) was calculated as a parameter of temporal nonuniformity. Intra-LV pressure difference (IVPD) was estimated with the use of color M-mode Doppler data as a parameter of LV diastolic suction. Although normal control subjects had symmetric LV expansion in early diastole, T E-e' and Delay C-L were significantly prolonged in HF regardless of EF (P < .01 vs control for all). Multivariate analysis revealed that Delay C-L was the independent determinant of IVPD among the parameters of LV geometry and contraction (β = -0.21; P < .05). An abnormal temporal nonuniformity of early-diastolic expansion is present in HF regardless of EF, which was associated with reduced LV suction. Copyright © 2016 Elsevier Inc. All rights reserved.

Pharmacotherapy Treatment Patterns, Outcomes, and Health Resource Utilization Among Patients with Heart Failure with Reduced Ejection Fraction at a U.S. Academic Medical Center.

PubMed

Bress, Adam P; King, Jordan B; Brixner, Diana; Kielhorn, Adrian; Patel, Harshali K; Maya, Juan; Lee, Vinson C; Biskupiak, Joseph; Munger, Mark

2016-02-01

To assess clinical characteristics, pharmacotherapy treatment patterns, resource utilization and associated charges, and morbidity and mortality outcomes among a real-world cohort of patients with heart failure with reduced ejection fraction (HFrEF) in an academic medical center setting. Retrospective analysis. Electronic health record database that includes clinical, laboratory, and administrative data for all facilities of the University of Utah Health Care System. A total of 989 adults with prevalent (preexisting) HFrEF, identified by using the International Classification of Diseases, Ninth Revision, Clinical Modification code 428.x (heart failure) between January 1, 2007, and June 30, 2013, and who had a left ventricular ejection fraction of 40% or lower. The cohort had a mean age of 64 ± 15 years and was predominantly white (71%) and male (74%). Patients received β-blockers, angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), and aldosterone receptor antagonists (ARAs) at rates of 79%, 69%, and 29%, respectively. Patients achieved target doses of β-blockers, ACEIs, and ARBs at rates of only 24%, 31%, and 13%, respectively. Overall, 58% of patients were prescribed dual therapy with a β-blocker and an ACEI or ARB, and 19% were prescribed triple therapy (β-blocker, an ACEI or ARB, and an ARA). Univariate and multivariate logistic regression models were used to assess the association between baseline characteristics with the presence of triple therapy. Two variables were statistically significant in both models: increasing age was associated with a lower odds of triple therapy (univariate: odds ratio [OR] 0.760, 95% confidence interval [CI] 0.673-0.857; multivariate: OR 0.768, 95% CI 0.625-0.942), whereas receipt of an implantable cardiac device was associated with a 2-fold increase in the odds of triple therapy (univariate: OR 2.1, 95% CI 1.4-3.1; multivariate: OR 2.1, 95% CI 1.3-3.5). During a mean ± SD follow-up of 36 ± 27 months, all-cause mortality was 0.12 per person-year. There were 1311 all-cause hospitalizations of which 611 (47%) were for worsening heart failure. The rate of all-cause and heart failure-specific hospitalizations was 0.44 and 0.21 per person-year of follow-up, respectively. The median length of stay was 6.4 ± 8.8 days, and the median charge was $22,310. The 30-day all-cause readmission rate was 20%, and the primary reason for readmission was heart failure in 65% of cases. This study demonstrates the continuing significant disease and economic burden for patients with HFrEF. Challenges remain in utilization of established disease-modifying therapy and in the treatment of patients with HFrEF and multiple comorbidities. © 2016 Pharmacotherapy Publications, Inc.

Effect of age and sex on efficacy and tolerability of β blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis

PubMed Central

Manzano, Luis; Krum, Henry; Rosano, Giuseppe; Holmes, Jane; Altman, Douglas G; Collins, Peter D; Packer, Milton; Wikstrand, John; Coats, Andrew J S; Cleland, John G F; Kirchhof, Paulus; von Lueder, Thomas G; Rigby, Alan S; Andersson, Bert; Lip, Gregory YH; van Veldhuisen, Dirk J; Shibata, Marcelo C; Wedel, Hans; Böhm, Michael; Flather, Marcus D

2016-01-01

Objectives To determine the efficacy and tolerability of β blockers in a broad age range of women and men with heart failure with reduced ejection fraction (HFrEF) by pooling individual patient data from placebo controlled randomised trials. Design Prospectively designed meta-analysis of individual patient data from patients aged 40-85 in sinus rhythm at baseline, with left ventricular ejection fraction <0.45. Participants 13 833 patients from 11 trials; median age 64; 24% women. Main outcome measures The primary outcome was all cause mortality; the major secondary outcome was admission to hospital for heart failure. Analysis was by intention to treat with an adjusted one stage Cox proportional hazards model. Results Compared with placebo, β blockers were effective in reducing mortality across all ages: hazard ratios were 0.66 (95% confidence interval 0.53 to 0.83) for the first quarter of age distribution (median age 50); 0.71 (0.58 to 0.87) for the second quarter (median age 60); 0.65 (0.53 to 0.78) for the third quarter (median age 68); and 0.77 (0.64 to 0.92) for the fourth quarter (median age 75). There was no significant interaction when age was modelled continuously (P=0.1), and the absolute reduction in mortality was 4.3% over a median follow-up of 1.3 years (number needed to treat 23). Admission to hospital for heart failure was significantly reduced by β blockers, although this effect was attenuated at older ages (interaction P=0.05). There was no evidence of an interaction between treatment effect and sex in any age group. Drug discontinuation was similar regardless of treatment allocation, age, or sex (14.4% in those give β blockers, 15.6% in those receiving placebo). Conclusion Irrespective of age or sex, patients with HFrEF in sinus rhythm should receive β blockers to reduce the risk of death and admission to hospital. Registration PROSPERO CRD42014010012; Clinicaltrials.gov NCT00832442. PMID:27098105

Effect of age and sex on efficacy and tolerability of β blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis.

PubMed

Kotecha, Dipak; Manzano, Luis; Krum, Henry; Rosano, Giuseppe; Holmes, Jane; Altman, Douglas G; Collins, Peter D; Packer, Milton; Wikstrand, John; Coats, Andrew J S; Cleland, John G F; Kirchhof, Paulus; von Lueder, Thomas G; Rigby, Alan S; Andersson, Bert; Lip, Gregory Y H; van Veldhuisen, Dirk J; Shibata, Marcelo C; Wedel, Hans; Böhm, Michael; Flather, Marcus D

2016-04-20

To determine the efficacy and tolerability of β blockers in a broad age range of women and men with heart failure with reduced ejection fraction (HFrEF) by pooling individual patient data from placebo controlled randomised trials. Prospectively designed meta-analysis of individual patient data from patients aged 40-85 in sinus rhythm at baseline, with left ventricular ejection fraction <0.45. 13,833 patients from 11 trials; median age 64; 24% women. The primary outcome was all cause mortality; the major secondary outcome was admission to hospital for heart failure. Analysis was by intention to treat with an adjusted one stage Cox proportional hazards model. Compared with placebo, β blockers were effective in reducing mortality across all ages: hazard ratios were 0.66 (95% confidence interval 0.53 to 0.83) for the first quarter of age distribution (median age 50); 0.71 (0.58 to 0.87) for the second quarter (median age 60); 0.65 (0.53 to 0.78) for the third quarter (median age 68); and 0.77 (0.64 to 0.92) for the fourth quarter (median age 75). There was no significant interaction when age was modelled continuously (P=0.1), and the absolute reduction in mortality was 4.3% over a median follow-up of 1.3 years (number needed to treat 23). Admission to hospital for heart failure was significantly reduced by β blockers, although this effect was attenuated at older ages (interaction P=0.05). There was no evidence of an interaction between treatment effect and sex in any age group. Drug discontinuation was similar regardless of treatment allocation, age, or sex (14.4% in those give β blockers, 15.6% in those receiving placebo). Irrespective of age or sex, patients with HFrEF in sinus rhythm should receive β blockers to reduce the risk of death and admission to hospital.Registration PROSPERO CRD42014010012; Clinicaltrials.gov NCT00832442. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Sex hormone levels and change in left ventricular structure among men and post-menopausal women: The Multi-Ethnic Study of Atherosclerosis (MESA).

PubMed

Subramanya, Vinita; Zhao, Di; Ouyang, Pamela; Lima, Joao A; Vaidya, Dhananjay; Ndumele, Chiadi E; Bluemke, David A; Shah, Sanjiv J; Guallar, Eliseo; Nwabuo, Chike C; Allison, Matthew A; Heckbert, Susan R; Post, Wendy S; Michos, Erin D

2018-02-01

Sex hormone (SH) levels may contribute to sex differences in the risk of heart failure with preserved ejection fraction (HFpEF). We examined the associations of SH levels with left ventricular mass (LVM) and mass (M):volume (V) ratio, which are risk markers for HFpEF. We studied 1941 post-menopausal women and 2221 men, aged 45-84 years, participating in the Multi-Ethnic Study of Atherosclerosis (MESA). Serum SH levels, cardiac magnetic resonance imaging (MRI) and ejection fraction (EF) ≥50% had been recorded at baseline (2000-2002). Of these participants, 2810 underwent repeat MRI at Exam 5 (2010-2012). Stratified by sex, linear mixed-effect models were used to test associations between SH and sex hormone binding globulin (SHBG) level [per 1 SD greater log-transformed (SH)] with baseline and change in LV structure. Models were adjusted for age, race/ethnicity, center, height, weight, education, physical activity and smoking, and, in women, for hormone therapy and years since menopause. LVM and M:V ratio. After a median of 9.1 years, higher free testosterone levels were independently associated with a modest increase in LVM (g/yr) in women [0.05 (95% CI 0.01, 0.10)] and men [0.16 (0.03, 0.28)], while higher SHBG levels were associated with less LVM change (g/yr) in women [-0.07 (-0.13, -0.01)] and men [-0.15 (-0.27, -0.02)]. In men, higher dehydroepiandrosterone and estradiol levels were associated with increased LVM. Among women, free testosterone levels were positively and SHBG levels inversely associated with change in M:V ratio. A more androgenic profile (higher free testosterone and lower SHBG levels) is associated with a greater increase in LVM in men and women and greater increase in M:V ratio in women over the course of 9 years. Copyright © 2017 Elsevier B.V. All rights reserved.

Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial.

PubMed

Lam, Phillip H; Dooley, Daniel J; Fonarow, Gregg C; Butler, Javed; Bhatt, Deepak L; Filippatos, Gerasimos S; Deedwania, Prakash; Forman, Daniel E; White, Michel; Fletcher, Ross D; Arundel, Cherinne; Blackman, Marc R; Adamopoulos, Chris; Kanonidis, Ioannis E; Aban, Inmaculada B; Patel, Kanan; Aronow, Wilbert S; Allman, Richard M; Anker, Stefan D; Pitt, Bertram; Ahmed, Ali

2018-02-01

To examine associations of below-target and target dose of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, with outcomes in patients with heart failure and reduced ejection fraction (HFrEF) in the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial. Two thousand five hundred and sixty-nine patients with HFrEF (ejection fraction ≤35%) were randomized to below-target (5-10 mg/day) dose placebo (n = 1284) or enalapril (n = 1285). One month post-randomization, blind up-titration to target (20 mg/day) dose was attempted for both study drugs in 2458 patients. Among the 1444 patients who achieved dose up-titration (placebo, n = 748; enalapril, n = 696; mean dose for both groups, 20.0 mg/day), target dose enalapril (vs. target dose placebo) was associated with a 9% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality [adjusted hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.60-0.81; P < 0.001] during 4 years of follow-up. Among the 1014 patients who could not achieve target dose (placebo, n = 486; enalapril, n = 528; mean dose for both groups, 8.8 mg/day), below-target dose enalapril (vs. below-target dose placebo) was associated with a 12% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 0.68; 95% CI 0.57-0.81; P < 0.001). Among the 1224 patients receiving enalapril, target (vs. below-target) dose had no association with the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 1.04; 95% CI 0.87-1.23; P = 0.695). In patients with HFrEF, the clinical benefits of ACE inhibitors appear to be similar at both below-target and target doses. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Medicare Expenditures by Race/Ethnicity After Hospitalization for Heart Failure With Preserved Ejection Fraction.

PubMed

Ziaeian, Boback; Heidenreich, Paul A; Xu, Haolin; DeVore, Adam D; Matsouaka, Roland A; Hernandez, Adrian F; Bhatt, Deepak L; Yancy, Clyde W; Fonarow, Gregg C

2018-05-01

The purpose of this study was to analyze cumulative Medicare expenditures at index admission and after discharge by race or ethnicity. Heart failure with preserved ejection fraction (HFpEF) is a growing proportion of heart failure (HF) admissions. Research on health care expenditures for patients with HFpEF is limited. Records of patients discharged from the Get With The Guidelines-Heart Failure registry between 2006 and 2014 were linked to Medicare data. The primary outcome was unadjusted payments for acute care services. Comparisons between race/ethnic groups were made using generalized linear mixed models. Cost ratios were reported by race/ethnicity, and adjustments were made sequentially for patient characteristics, hospital factors, and regional socioeconomic status. Median Medicare costs for index hospitalizations were $7,241 for the entire cohort, $7,049 for whites, $8,269 for blacks, $8,808 for Hispanics, $8,477 for Asians, and $8,963 for other races. Median costs at 30 days for readmitted patients were $9,803 and $17,456 for the entire cohort at 1-year. No significant differences were seen in index admission cost ratios by race/ethnicity. At 30 days among readmitted patients, costs were 9% higher (95% confidence interval [CI]: 1% to 17%; p = 0.020) for blacks in the fully adjusted model than whites. At 1 year, costs were 14% higher (95% CI: 9% to 18%; p < 0.001) for blacks, 7% higher (95% CI: 0% to 14%; p = 0.041) for Hispanics, and 24% higher (95% CI: 8% to 42%; p = 0.003) for patients of other races. No significant differences between white and Asian expenditures were noted. Minority patients with HFpEF have greater acute care service costs. Further research of improving care delivery is needed to reduce acute care use for vulnerable populations. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Myocardial and Cardiocirculatory Reserve in Asymptomatic Aortic Stenosis and Preserved Ejection Fraction.

PubMed

Schulz, Olaf; Brala, Debora; Allison, Thomas G; Schimke, Ingolf

2015-07-01

Managing patients with asymptomatic severe aortic stenosis (AS) remains a major challenge. Myocardial as well as cardiocirculatory reserve have been hypothesized to predict outcome in patients with asymptomatic AS. A total of 48 patients (indexed aortic valve area 0.39 +/- 0.12 cm2/m2; ejection fraction (EF) 67 +/- 7%) underwent spiroergometry and dobutamine stress echocardiography. Death or valve surgery served as a combined endpoint for follow up. Thirty-seven patients reached the endpoint after a mean of 756 days (range: 100-2146 days). Age- and gender-corrected univariate Cox proportional analysis revealed the presence of mild obstructive lung disease, stroke work loss (SWL), end-systolic diameter index, and E/Flow propagation velocity as the best predictive clinical, valvular, cardiostructural, and left ventricular filling pressure parameters, respectively. After inclusion of these parameters into a baseline multivariable Cox proportional hazard model, SWL (HR 1.21 per rise of 1 unit, CI 1.08-1.35, p = 0.0005) and female gender (HR 3.37, CI 1.50-7.59, p = 0.0044) were independently predictive. Similarly, the best-performing myocardial parameter, EF after dobutamine, was independently predictive (HR 0.75 per 5 units, CI 0.57-0.99, p = 0.035) after inclusion. The best-performing exercise capacity parameter, Watt(max), was of borderline significance (HR 0.93 per 5 units, CI 0.86-1.00, p = 0.0505). For each parameter, cut-off values were determined by time-dependent receiver-operator characteristics. The Kaplan-Meier curves of the patients above versus below the cut-offs differed significantly for SWL (p = 0.001), Wattm (p = 0.001), and gender (p = 0.013). Besides SWL and female gender, the EF after dobutamine as well as highest exercise stress intensity reached are helpful in determining the prognosis of asymptomatic patients with moderate-severe AS.

High intensity interval training versus moderate intensity continuous training on exercise capacity and quality of life in patients with heart failure with reduced ejection fraction: A systematic review and meta-analysis.

PubMed

Gomes Neto, Mansueto; Durães, André Rodrigues; Conceição, Lino Sergio Rocha; Saquetto, Micheli Bernardone; Ellingsen, Øyvind; Carvalho, Vitor Oliveira

2018-06-15

The aim of this study was to investigate the effects of high intensity interval training (HIIT) versus moderate intensity continuous training (MICT) in heart failure patients with reduced ejection fraction (HFrEF). Despite the well-known positive effects of exercise in heart failure patients, the best mode of exercise is still under discussion. We searched Pubmed/MEDLINE, Cochrane Central Register of Controlled Trials, PEDro data base, and SciELO (from the earliest date available to October 2017) for randomized controlled trials that evaluated the effects of HIIT versus MICT in HFrEF patients. Weighted mean differences (WMD) with 95% confidence interval (CI) were calculated, and heterogeneity was assessed using the I 2 test. 13 studies met the study criteria, including 411 patients. Compared to MICT, HIIT resulted in improvement in Peak VO 2 WMD (1.35 mL·kg -1 ·min -1 95% CI: 0.03 to 2.64 N = 411). HIIT resulted in no difference in VE/VCO 2 slope WMD (-1.21 95% CI: -3.0 to 0.58 N = 135), and quality of life measured by Minnesota Living with Heart Failure questionnaire WMD (1.19 95% CI: -5.81 to 8.19 N = 79). Sub-group analyses comparing studies with and without isocaloric exercise training protocol also showed a nonsignificant difference in peak VO 2 for participants in the HIIT group compared with MICT group. HIIT improves peak VO 2 and should be considered as a component of care of HFrEF patients. However, its superiority versus MICT disappears when isocaloric protocols are compared. An important caveat is uncertainty and variation of actual training intensities compared to program targets. Copyright © 2018 Elsevier B.V. All rights reserved.

Troponin and Anti-Troponin Autoantibody Levels in Patients with Ventricular Noncompaction

PubMed Central

Erer, Hatice Betül; Güvenç, Tolga Sinan; Kemik, Ahu Sarbay; Yılmaz, Hale Yaka; Kul, Şeref; Altay, Servet; Sayar, Nurten; Kaya, Yüksel; Eren, Mehmet

2013-01-01

Ventricular hypertrabeculation/noncompaction is a morphologic and functional anomaly of myocardium characterized by prominent trabeculae accompanied by deep recessus. Dilated cardiomyopathy with left ventricular failure is observed in these patients, while the cause or pathophysiologic nature of this complication is not known. Anti-troponin antibodies are formed against circulating cardiac troponins after an acute coronary event or conditions associated with chronic myocyte necrosis, such as dilated cardiomyopathy. In present study, we aimed to investigate cardiac troponins and anti troponin autoantibodies in ventricular noncompaction/hypertrabeculation patients with/without reduced ejection fraction. A total of 50 patients with ventricular noncompaction and 23 healthy volunteers were included in this study. Noncompaction/hypertrabeculation was diagnosed with two-dimensional echocardiography using appropriate criteria. Depending on ejection fraction, patients were grouped into noncompaction with preserved EF (LVEF >50%, n = 24) and noncompaction with reduced EF (LVEF <35%, n = 26) groups. Troponin I, troponin T, anti-troponin I IgM and anti-troponin T IgM were measured with sandwich immunoassay method using a commercially available kit. Patients with noncompaction had significantly higher troponin I (28.98±9.21 ng/ml in NCNE group and 28.11±10.42 ng/ml in NCLE group), troponin T (22.17±6.97 pg/ml in NCNE group and 22.78±7.76 pg/ml in NCLE group) and antitroponin I IgM (1.92±0.43 µg/ml in NCNE group and 1.79±0.36 µg/ml in NCLE group) levels compared to control group, while antitroponin T IgM and IgG were only elevated in patients with noncompaction and reduced EF (15.81±6.52 µg/ml for IgM and 16.46±6.25 µg/ml for IgG). Elevated cardiac troponins and anti-troponin I autoantibodies were observed in patients with noncompaction preceding the decline in systolic function and could indicate ongoing myocardial damage in these patients. PMID:23469039

Initial clinical experience with the first drug (sacubitril/valsartan) in a new class - angiotensin receptor neprilysin inhibitors in patients with heart failure with reduced left ventricular ejection fraction in Poland.

PubMed

Kałużna-Oleksy, Marta; Kolasa, Jolanta; Migaj, Jacek; Pawlak, Agnieszka; Lelonek, Małgorzata; Nessler, Jadwiga; Straburzyńska-Migaj, Ewa

2018-01-01

Sacubitril/valsartan is the first drug from a new class of angiotensin receptor neprilysin inhibitors (ARNIs) recommended in the new European Society of Cardiology guidelines instead of angiotensin converting enzyme inhibitors (ACEI), or angiotensin receptor blockers (ARB) that are used if ACEI are not tolerated. Sacubitril/valsartan is recommended for further reduction in the risk of hospitalisation or death in outpatients with heart failure with reduced ejection fraction (HFrEF) if symptoms continue despite optimal treatment with ACEI/ARB, beta-blockers, and mineralocorticoid antagonists. The aim of this study is to present the initial experience with regard to the effectiveness, tolerance, and safety of sacubitril/valsartan in the outpatient cardiology practice in Poland. The study is a retrospective analysis of data obtained through a questionnaire filled in by the physicians who initiated the sacubitril/valsartan treatment in patients with HFrEF between 1 June 2016 and 30 September 2016. Patients were followed-up for three months. The analysis included data on 28 patients aged 61 ± 16 years, of whom 85.7% were males. The drug was used in patients in New York Heart Association (NYHA) class I-III. In 25 (89.2%) patients sacubitril/valsartan was started at the lowest dose (24/26 mg BID). During follow-up the sacubitril/valsartan-treated patients had a reduction in HF symptoms assessed using the NYHA functional class (p = 0.001), a significant drop in N-terminal-pro B-type natriuretic peptide levels (mean, from 2900 to 2270 pg/mL; p = 0.008), and improved exercise tolerance, which occurred shortly after treatment initiation - after a mean of 28 days. It was demonstrated that the use of sacubitril/valsartan in outpatients with HFrEF is safe and is associated with a significant clinical improvement.

Cardiovascular magnetic resonance of cardiac function and myocardial mass in preterm infants: a preliminary study of the impact of patent ductus arteriosus

PubMed Central

2014-01-01

Background Many pathologies seen in the preterm population are associated with abnormal blood supply, yet robust evaluation of preterm cardiac function is scarce and consequently normative ranges in this population are limited. The aim of this study was to quantify and validate left ventricular dimension and function in preterm infants using cardiovascular magnetic resonance (CMR). An initial investigation of the impact of the common congenital defect patent ductus arteriosus (PDA) was then carried out. Methods Steady State Free Procession short axis stacks were acquired. Normative ranges of left ventricular end diastolic volume (EDV), stroke volume (SV), left ventricular output (LVO), ejection fraction (EF), left ventricular (LV) mass, wall thickness and fractional thickening were determined in “healthy” (control) neonates. Left ventricular parameters were then investigated in PDA infants. Unpaired student t-tests compared the 2 groups. Multiple linear regression analysis assessed impact of shunt volume in PDA infants, p-value ≤ 0.05 being significant. Results 29 control infants median (range) corrected gestational age at scan 34+6(31+1-39+3) weeks were scanned. EDV, SV, LVO, LV mass normalized by weight and EF were shown to decrease with increasing corrected gestational age (cGA) in controls. In 16 PDA infants (cGA 30+3(27+3-36+1) weeks) left ventricular dimension and output were significantly increased, yet there was no significant difference in ejection fraction and fractional thickening between the two groups. A significant association between shunt volume and increased left ventricular mass correcting for postnatal age and corrected gestational age existed. Conclusion CMR assessment of left ventricular function has been validated in neonates, providing more robust normative ranges of left ventricular dimension and function in this population. Initial investigation of PDA infants would suggest that function is relatively maintained. PMID:25160730

Clinical significance of a presystolic wave on Doppler examination of the left ventricular outflow tract.

PubMed

Joshi, Kamal R; Kabirdas, Deepa; Romero-Corral, Abel; Shah, Mahek; Figueredo, Vincent M; Pressman, Gregg S

2014-11-15

A presystolic wave (PSW) is commonly seen on Doppler examination of the left ventricular outflow tract (LVOT), but is little studied. We conducted a retrospective study to assess the prevalence of the PSW, correlations with various Doppler parameters, and its clinical significance. Two hundred echocardiograms, 100 with ejection fraction (EF) >55% and 100 with EF <45%, were reviewed. Mitral inflow velocities, septal annular velocities, LVOT, and PSW velocities were measured. Major adverse cardiovascular events (MACE [death, heart failure hospitalization, atrial fibrillation, and stroke]) were compared between those with and without a PSW, in both EF groups. Mean age was 58 ± 15 years; 56% were men and 69% were African-American. PSW prevalence was similar between normal (68%) and reduced EF groups (62%). However, its velocity was less in the low EF group (37 ± 10 vs 48 ± 16 cm/s, p <0.0001). In subjects with normal EF PSW velocity correlated with mitral A velocity (rho = 0.43, p = 0.0003). In subjects with reduced EF the association with A velocity was not significant (rho = 0.22, p = 0.09), but there was a significant association with annular a' velocity (rho = 0.38, p = 0.002). Over a mean follow-up of 1.7 ± 0.3 years, 57 subjects (28%) experienced MACE. Those without a PSW had more MACE (39% vs 23%, p = 0.02); PSW absence remained predictive of MACE after adjustment for multiple variables, especially in patients with reduced EF. In conclusion, PSW is common in the LVOT. Its presence and magnitude are associated with measures of atrial contraction. Its absence is associated with increased rates of adverse events, especially in patients with low EF. Copyright © 2014 Elsevier Inc. All rights reserved.

New insights into SERCA2a gene therapy in heart failure: pay attention to the negative effects of B-type natriuretic peptides.

PubMed

Zhai, Yuting; Luo, Yuanyuan; Wu, Pei; Li, Dongye

2018-05-01

Sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a) is a target of interest in gene therapy for heart failure with reduced ejection fraction (HFrEF). However, the results of an important clinical study, the Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) trial, were controversial. Promising results were observed in the CUPID 1 trial, but the results of the CUPID 2 trial were negative. The factors that caused the controversial results remain unclear. Importantly, enrolled patients were required to have a higher plasma level of B-type natriuretic peptide (BNP) in the CUPID 2 trial. Moreover, BNP was shown to inhibit SERCA2a expression. Therefore, it is possible that high BNP levels interact with treatment effects of SERCA2a gene transfer and accordingly lead to negative results of CUPID 2 trial. From this point of view, effects of SERCA2a gene therapy should be explored in heart failure with preserved ejection fraction, which is characterised by lower BNP levels compared with HFrEF. In this review, we summarise the current knowledge of SERCA2a gene therapy for heart failure, analyse potential interaction between BNP levels and therapeutic effects of SERCA2a gene transfer and provide directions for future research to solve the identified problems. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Analysis of a large cohort of health maintenance organization patients with congestive heart failure.

PubMed

Gladowski, Patricia; Fetterolf, Donald; Beals, Susan; Holleran, Mary Kay; Reich, Sanford

2003-01-01

The aim of this article was to measure guideline compliance in the care of health plan members diagnosed with congestive heart failure (CHF). Chart review was conducted on members with a discharge diagnosis of CHF (n = 2,697). Information was entered onto a scannable form designed by the health plan, which was coupled to an optical character recognition reader and entered into a database. Eighty-four percent of the patients had an ejection fraction (EF) measured. An angiotensin-converting enzyme inhibitor was prescribed to 72% of patients with an EF less than 40%. Comorbidities and other measures were evaluated and based on guideline recommendations. Most of the CHF patients in this health plan are being treated appropriately during posthospitalization for CHF. The use of a novel, cost-effective method for data collection resulted in the rapid acquisition of clinical data for analysis.

Sacubitril/Valsartan: From Clinical Trials to Real-world Experience.

PubMed

Joly, Joanna M; Desai, Akshay S

2018-04-23

Compared to enalapril, use of angiotensin-receptor blocker and neprilysin inhibitor sacubitril/valsartan to treat patients with heart failure and reduced ejection fraction (HFrEF) is associated with substantial reductions in both cardiovascular mortality and heart failure progression. The purpose of this review is to discuss the real-world experience of sacubitril/valsartan. In the years following the publication of the landmark PARADIGM-HF trial in 2014 and its subsequent FDA approval, a growing evidence base supports the safety and efficacy of sacubitril/valsartan in a broad spectrum of patients with HFrEF. Updated clinical practice guidelines have embraced the use of sacubitril/valsartan in preference to ACE inhibitors or ARBs in selected patients. In this review, we highlight the clinical trials that led to these key updates to clinical guidelines, offer practical strategies for patient selection and utilization in clinical practice, and identify important areas of uncertainty that require future research.

Utility of Cardiovascular Magnetic Resonance-Derived Wave Intensity Analysis As a Marker of Ventricular Function in Children with Heart Failure and Normal Ejection Fraction.

PubMed

Ntsinjana, Hopewell N; Chung, Robin; Ciliberti, Paolo; Muthurangu, Vivek; Schievano, Silvia; Marek, Jan; Parker, Kim H; Taylor, Andrew M; Biglino, Giovanni

2017-01-01

This study sought to explore the diagnostic insight of cardiovascular magnetic resonance (CMR)-derived wave intensity analysis to better study systolic dysfunction in young patients with chronic diastolic dysfunction and preserved ejection fraction (EF), comparing it against other echocardiographic and CMR parameters. Evaluating systolic and diastolic dysfunctions in children is challenging, and a gold standard method is currently lacking. Patients with presumed diastolic dysfunction [ n  = 18; nine aortic stenosis (AS), five hypertrophic, and four restrictive cardiomyopathies] were compared with age-matched control subjects ( n  = 18). All patients had no mitral or aortic incompetence, significant AS, or reduced systolic EF. E / A ratio, E / E ' ratio, deceleration time, and isovolumetric contraction time were assessed on echocardiography, and indexed left atrial volume (LAVi), acceleration time (AT), ejection time (ET), and wave intensity analyses were calculated from CMR. The latter was performed on CMR phase-contrast flow sequences, defining a ratio of the peaks of the early systolic forward compression wave (FCW) and the end-systolic forward expansion wave (FEW). Significant differences between patients and controls were seen in the E / E ' ratio (8.7 ± 4.0 vs. 5.1 ± 1.3, p  = 0.001) and FCW/FEW ratio (2.5 ± 1.6 vs. 7.2 ± 4.2 × 10 -5 m/s, p  < 0.001), as well as-as expected-LAVi (80.7 ± 22.5 vs. 51.0 ± 10.9 mL/m 2 , p  < 0.001). In particular, patients exhibited a lower FCW (2.5 ± 1.6 vs. 7.2 ± 4.2 × 10 -5 m/s, p  < 0.001) in the face of preserved EF (67 ± 11 vs. 69 ± 5%, p  = 0.392), as well as longer isovolumetric contraction time (49 ± 7 vs. 34 ± 7 ms, p  < 0.001) and ET/AT (0.35 ± 0.04 vs. 0.27 ± 0.04, p  < 0.001). This study shows that the wave intensity-derived ratio summarizing systolic and diastolic function could provide insight into ventricular function in children, on top of CMR and echocardiography, and it was here able to identify an element of ventricular dysfunction with preserved EF in a small group of young patients.

Scores for post-myocardial infarction risk stratification in the community.

PubMed

Singh, Mandeep; Reeder, Guy S; Jacobsen, Steven J; Weston, Susan; Killian, Jill; Roger, Véronique L

2002-10-29

Several scores, most of which were derived from clinical trials, have been proposed for stratifying risk after myocardial infarctions (MIs). Little is known about their generalizability to the community, their respective advantages, and whether the ejection fraction (EF) adds prognostic information to the scores. The purpose of this study is to evaluate the Thrombolysis in Myocardial Infarction (TIMI) and Predicting Risk of Death in Cardiac Disease Tool (PREDICT) scores in a geographically defined MI cohort and determine the incremental value of EF for risk stratification. MIs occurring in Olmsted County were validated with the use of standardized criteria and stratified with the ECG into ST-segment elevation (STEMI) and non-ST-segment elevation (NSTEMI) MI. Logistic regression examined the discriminant accuracy of the TIMI and PREDICT scores to predict death and recurrent MI and assessed the incremental value of the EF. After 6.3+/-4.7 years, survival was similar for the 562 STEMIs and 717 NSTEMIs. The discriminant accuracy of the TIMI score was good in STEMI but only fair in NSTEMI. Across time and end points, irrespective of reperfusion therapy, the discriminant accuracy of the PREDICT score was consistently superior to that of the TIMI scores, largely because PREDICT includes comorbidity; EF provided incremental information over that provided by the scores and comorbidity. In the community, comorbidity and EF convey important prognostic information and should be included in approaches for stratifying risk after MI.

Effect of chronic right ventricular apical pacing on left ventricular function.

PubMed

O'Keefe, James H; Abuissa, Hussam; Jones, Philip G; Thompson, Randall C; Bateman, Timothy M; McGhie, A Iain; Ramza, Brian M; Steinhaus, David M

2005-03-15

The determinants of change in left ventricular (LV) ejection fraction (EF) over time in patients with impaired LV function at baseline have not been clearly established. Using a nuclear database to assess changes in LV function over time, we included patients with a baseline LVEF of 25% to 40% on a gated single-photon emission computed tomographic study at rest and only if second-gated photon emission computed tomography performed approximately 18 months after the initial study showed an improvement in LVEF at rest of > or =10 points or a decrease in LVEF at rest of > or =7 points. In all, 148 patients qualified for the EF increase group and 59 patients for the EF decrease group. LVEF on average increased from 33 +/- 4% to 51 +/- 8% in the EF increase group and decreased from 35 +/- 4% to 25 +/- 5% in the EF decrease group. The strongest multivariable predictor of improvement of LVEF was beta-blocker therapy (odds ratio 3.9, p = 0.002). The strongest independent predictor of LVEF decrease was the presence of a permanent right ventricular apical pacemaker (odds ratio 6.6, p = 0.002). Thus, this study identified beta-blocker therapy as the major independent predictor for improvement in LVEF of > or =10 points, whereas a permanent pacemaker (right ventricular apical pacing) was the strongest predictor of a LVEF decrease of > or =7 points.

Sacubitril/valsartan and short-term changes in the 6-minute walk test: A pilot study.

PubMed

Beltrán, Paola; Palau, Patricia; Domínguez, Eloy; Faraudo, Mercedes; Núñez, Eduardo; Guri, Olga; Mollar, Anna; Sanchis, Juan; Bayés-Genís, Antoni; Núñez, Julio

2018-02-01

Impaired exercise capacity is the most disabling symptom in patients with heart failure with reduced ejection fraction (HFrEF). Despite sacubitril/valsartan showing reduced long-term morbidity and mortality over enalapril in HFrEF, its effects on short-term functional capacity remain uncertain. We sought to evaluate the effects of sacubitril/valsartan on a 30-day six-minute walk test in eligible patients with HFrEF. From November 1, 2016 to February 1, 2017, a total of 58 stable symptomatic patients with HFrEF were eligible for sacubitril/valsartan and underwent 6-MWT before and 30days after initiation of sacubitril/valsartan therapy. A mixed-effects model for repeated-measures was used to analyze the changes. Mean age was 70±11years. 72.4% males, 46.6% with ischemic heart disease, and 51.7% on NYHA functional class III were included. The mean (SD) values of baseline LVEF and 6MWT were 30±7%, and 300±89m, respectively. The median (IQR) of NT-proBNP at baseline was 2701pg/ml (1087-4200). Compared with baseline, the 6-MWT distance increased significantly at 30days by 13.9% (+∆=41.8m (33.4-50.2); p<0.001). In this pilot study, sacubitril/valsartan was associated with an improvement in exercise tolerance in symptomatic patients with HFrEF. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Heart failure in patients with coronary heart disease: Prevalence, characteristics and guideline implementation - Results from the German EuroAspire IV cohort.

PubMed

Morbach, Caroline; Wagner, Martin; Güntner, Stefan; Malsch, Carolin; Oezkur, Mehmet; Wood, David; Kotseva, Kornelia; Leyh, Rainer; Ertl, Georg; Karmann, Wolfgang; Heuschmann, Peter U; Störk, Stefan

2017-05-05

Adherence to pharmacotherapeutic treatment guidelines in patients with heart failure (HF) is of major prognostic importance, but thorough implementation of guidelines in routine care remains insufficient. Our aim was to investigate prevalence and characteristics of HF in patients with coronary heart disease (CHD), and to assess the adherence to current HF guidelines in patients with HF stage C, thus identifying potential targets for the optimization of guideline implementation. Patients from the German sample of the European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EuroAspire) IV survey with a hospitalization for CHD within the previous six to 36 months providing valid data on echocardiography as well as on signs and symptoms of HF were categorized into stages of HF: A, prevalence of risk factors for developing HF; B, asymptomatic but with structural heart disease; C, symptomatic HF. A Guideline Adherence Indicator (GAI-3) was calculated for patients with reduced (≤40%) left ventricular ejection fraction (HFrEF) as number of drugs taken per number of drugs indicated; beta-blockers, angiotensin converting enzyme inhibitors/angiotensin receptor blockers, and mineralocorticoid receptor antagonists (MRA) were considered. 509/536 patients entered analysis. HF stage A was prevalent in n = 20 (3.9%), stage B in n = 264 (51.9%), and stage C in n = 225 (44.2%) patients; 94/225 patients were diagnosed with HFrEF (42%). Stage C patients were older, had a longer duration of CHD, and a higher prevalence of arterial hypertension. Awareness of pre-diagnosed HF was low (19%). Overall GAI-3 of HFrEF patients was 96.4% with a trend towards lower GAI-3 in patients with lower LVEF due to less thorough MRA prescription. In our sample of CHD patients, prevalence of HF stage C was high and a sizable subgroup suffered from HFrEF. Overall, pharmacotherapy was fairly well implemented in HFrEF patients, although somewhat worse in patients with more reduced ejection fraction. Two major targets were identified possibly suited to further improve the implementation of HF guidelines: 1) increase patients´ awareness of diagnosis and importance of HF; and 2) disseminate knowledge about the importance of appropriately implementing the use of mineralocorticoid receptor antagonists. This is a cross-sectional analysis of a non-interventional study. Therefore, it was not registered as an interventional trial.

Effect of Oral Iron Repletion on Exercise Capacity in Patients With Heart Failure With Reduced Ejection Fraction and Iron Deficiency: The IRONOUT HF Randomized Clinical Trial.

PubMed

Lewis, Gregory D; Malhotra, Rajeev; Hernandez, Adrian F; McNulty, Steven E; Smith, Andrew; Felker, G Michael; Tang, W H Wilson; LaRue, Shane J; Redfield, Margaret M; Semigran, Marc J; Givertz, Michael M; Van Buren, Peter; Whellan, David; Anstrom, Kevin J; Shah, Monica R; Desvigne-Nickens, Patrice; Butler, Javed; Braunwald, Eugene

2017-05-16

Iron deficiency is present in approximately 50% of patients with heart failure with reduced left ventricular ejection fraction (HFrEF) and is an independent predictor of reduced functional capacity and mortality. However, the efficacy of inexpensive readily available oral iron supplementation in heart failure is unknown. To test whether therapy with oral iron improves peak exercise capacity in patients with HFrEF and iron deficiency. Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with HFrEF (<40%) and iron deficiency, defined as a serum ferritin level of 15 to 100 ng/mL or a serum ferritin level of 101 to 299 ng/mL with transferrin saturation of less than 20%. Participants were enrolled between September 2014 and November 2015 at 23 US sites. Oral iron polysaccharide (n = 111) or placebo (n = 114), 150 mg twice daily for 16 weeks. The primary end point was a change in peak oxygen uptake (V̇o2) from baseline to 16 weeks. Secondary end points were change in 6-minute walk distance, plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and health status as assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ, range 0-100, higher scores reflect better quality of life). Among 225 randomized participants (median age, 63 years; 36% women) 203 completed the study. The median baseline peak V̇o2 was 1196 mL/min (interquartile range [IQR], 887-1448 mL/min) in the oral iron group and 1167 mL/min (IQR, 887-1449 mL/min) in the placebo group. The primary end point, change in peak V̇o2 at 16 weeks, did not significantly differ between the oral iron and placebo groups (+23 mL/min vs -2 mL/min; difference, 21 mL/min [95% CI, -34 to +76 mL/min]; P = .46). Similarly, at 16 weeks, there were no significant differences between treatment groups in changes in 6-minute walk distance (-13 m; 95% CI, -32 to 6 m), NT-proBNP levels (159; 95% CI, -280 to 599 pg/mL), or KCCQ score (1; 95% CI, -2.4 to 4.4), all P > .05. Among participants with HFrEF with iron deficiency, high-dose oral iron did not improve exercise capacity over 16 weeks. These results do not support use of oral iron supplementation in patients with HFrEF. clinicaltrials.gov Identifier: NCT02188784.

N-terminal pro brain natriuretic peptide-guided management in patients with heart failure and preserved ejection fraction: findings from the Trial of Intensified versus standard medical therapy in elderly patients with congestive heart failure (TIME-CHF).

PubMed

Maeder, Micha T; Rickenbacher, Peter; Rickli, Hans; Abbühl, Heidi; Gutmann, Marc; Erne, Paul; Vuilliomenet, André; Peter, Martin; Pfisterer, Matthias; Brunner-La Rocca, Hans-Peter

2013-10-01

To assess the effects of an NT-proBNP-guided medical management on 18-month outcomes in patients with heart failure (HF) and preserved LVEF ( HFpEF). Patients with HFpEF (LVEF >45%; n = 123) and HF with reduced LVEF (HFrEF; LVEF ≤45%; n = 499) with age ≥60 years, NYHA class ≥ II, and elevated NT-proBNP (>400 ng/L or >800 ng/L depending on age) were randomized to medical therapy titrated only to reduce symptoms to NYHA ≤II (symptom-guided) or also to reduce NT-proBNP below the inclusion threshold (NT-proBNP-guided) during a 6-month period. Patients were followed for an additional 12 months. Despite similar treatment escalation, NT-proBNP reduction and symptom relief were less in HFpEF than in HFrEF. Hospitalization-free survival at 18 months was worse in HFpEF than in HFrEF (P = 0.02), while survival and HF hospitalization-free survival did not differ. Among HFpEF patients, NT-proBNP reduction and symptom relief were similar in the symptom-guided (n = 59) and NT-proBNP-guided (n = 64) group despite more aggressive treatment in the NT-proBNP-guided group. In contrast to effects in HFrEF, NT-proBNP-guided management tended to worsen 18-month outcomes in HFpEF, with P-values for the interactions between LVEF stratum and management strategy of 0.2 for hospitalization-free survival, 0.03 for survival, and 0.01 for HF hospitalization-free survival. Outcomes in HFpEF were not better than in HFrEF, and opposite effects of NT-proBNP-guided management were observed in HFpEF compared with HFrEF. These preliminary findings suggest that, in contrast to HFrEF, NT-proBNP-guided therapy may not be beneficial in HFpEF. Trial registration ISRCTN43596477.

Prevalence and Clinical Significance of an E-Reversal Wave in the Left Ventricular Outflow Tract.

PubMed

Pressman, Gregg S; Matejkova, Magdalena; Horrow, Jay C; Pai, Ramdas G

2016-11-15

Diastolic waves are commonly seen in the left ventricular outflow tract on echocardiography. This work focuses on the E-reversal wave (Er) that occurs early in diastole, shortly after the mitral E wave. Factors associated with Er presence and velocity were investigated in a broad patient sample: 100 subjects with normal ejection fraction (EF >55%) and 100 subjects with reduced EF (<45%). Er presence was noted in 58% of the total cohort and correlated inversely with age. It was more common with normal EF (70% vs 45%, p = 0.0005) and was associated with higher mitral E velocity (78.3 ± 23.3 vs 68.4 ± 19.0 cm/s; p = 0.002) and septal e' velocity (6.7 ± 2.5 vs 5.3 ± 2.3 cm/s; p <0.0001). Er velocity was higher in the normal EF group (50 ± 18 vs 34 ± 13 cm/s, p <0.0001) and showed moderate correlation with septal e' velocity (r = 0.43; p <0.0001); 56 subjects experienced major adverse cardiovascular events (MACE) over 1.7 ± 0.3 years of follow-up. Those with an Er had less MACE (particularly heart failure), even after adjustment for multiple clinical and echocardiographic variables (OR 0.28, 95% CI 0.11 to 0.65; p = 0.003). When stratified by EF, the association between Er presence and MACE was significant only in the low EF group. Thus, Er occurs more commonly in younger subjects and those with preserved EF. It is associated with less MACE although this effect appears to be limited to patients with reduced EF. Copyright © 2016 Elsevier Inc. All rights reserved.

Transcatheter Interatrial Shunt Device for the Treatment of Heart Failure: Rationale and Design of the Randomized Trial to REDUCE Elevated Left Atrial Pressure in Heart Failure (REDUCE LAP-HF I).

PubMed

Feldman, Ted; Komtebedde, Jan; Burkhoff, Daniel; Massaro, Joseph; Maurer, Mathew S; Leon, Martin B; Kaye, David; Silvestry, Frank E; Cleland, John G F; Kitzman, Dalane; Kubo, Spencer H; Van Veldhuisen, Dirk J; Kleber, Franz; Trochu, Jean-Noël; Auricchio, Angelo; Gustafsson, Finn; Hasenfuβ, Gerd; Ponikowski, Piotr; Filippatos, Gerasimos; Mauri, Laura; Shah, Sanjiv J

2016-07-01

Heart failure with preserved ejection fraction (HFpEF), a major public health problem with high morbidity and mortality rates, remains difficult to manage because of a lack of effective treatment options. Although HFpEF is a heterogeneous clinical syndrome, elevated left atrial pressure-either at rest or with exertion-is a common factor among all forms of HFpEF and one of the primary reasons for dyspnea and exercise intolerance in these patients. On the basis of clinical experience with congenital interatrial shunts in mitral stenosis, it has been hypothesized that the creation of a left-to-right interatrial shunt to decompress the left atrium (without compromising left ventricular filling or forward cardiac output) is a rational, nonpharmacological strategy for alleviating symptoms in patients with HFpEF. A novel transcatheter interatrial shunt device has been developed and evaluated in patients with HFpEF in single-arm, nonblinded clinical trials. These studies have demonstrated the safety and potential efficacy of the device. However, a randomized, placebo-controlled evaluation of the device is required to further evaluate its safety and efficacy in patients with HFpEF. In this article, we give the rationale for a therapeutic transcatheter interatrial shunt device in HFpEF, and we describe the design of REDUCE Elevated Left Atrial Pressure in Heart Failure (REDUCE LAP-HF I), the first randomized controlled trial of a device-based therapy to reduce left atrial pressure in HFpEF. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02600234. © 2016 American Heart Association, Inc.

Effects of supervised exercise and dietary nitrate in older adults with controlled hypertension and/or heart failure with preserved ejection fraction.

PubMed

Shaltout, Hossam A; Eggebeen, Joel; Marsh, Anthony P; Brubaker, Peter H; Laurienti, Paul J; Burdette, Jonathan H; Basu, Swati; Morgan, Ashley; Dos Santos, Patricia C; Norris, James L; Morgan, Timothy M; Miller, Gary D; Rejeski, W Jack; Hawfield, Amret T; Diz, Debra I; Becton, J Thomas; Kim-Shapiro, Daniel B; Kitzman, Dalane W

2017-09-30

Aerobic exercise training is an effective therapy to improve peak aerobic power (peak VO 2 ) in individuals with hypertension (HTN, AHA/ACC class A) and heart failure patients with preserved ejection fraction (HFpEF). High nitrate containing beetroot juice (BRJ) also improves sub-maximal endurance and decreases blood pressure in both HTN and HFpEF. We hypothesized that combining an aerobic exercise and dietary nitrate intervention would result in additive or even synergistic positive effects on exercise tolerance and blood pressure in HTN or HFpEF. We report results from two pilot studies examining the effects of supervised aerobic exercise combined with dietary nitrate in patients with controlled HTN (n = 26, average age 65 ± 5 years) and in patients with HFpEF (n = 20, average age 69 ± 7 years). All patients underwent an aerobic exercise training regimen; half were randomly assigned to consume a high nitrate-containing beet juice beverage (BRJ containing 6.1 mmol nitrate for the HFpEF study consumed three times a week and 8 mmol nitrate for the HTN study consumed daily) while the other half consumed a beet juice beverage with the nitrate removed (placebo). The main result was that there was no added benefit observed for any outcomes when comparing BRJ to placebo in either HTN or HFpEF patients undergoing exercise training (p ≥ 0.14). There were within-group benefits. In the pilot study in patients with HFpEF, aerobic endurance (primary outcome), defined as the exercise time to volitional exhaustion during submaximal cycling at 75% of maximal power output, improved during exercise training within each group from baseline to end of study, 369 ± 149 s vs 520 ± 257 s (p = 0.04) for the placebo group and 384 ± 129 s vs 483 ± 258 s for the BRJ group (p = 0.15). Resting systolic blood pressure in patients with HFpEF also improved during exercise training in both groups, 136 ± 16 mm Hg vs 122 ± 3 mm Hg for the placebo group (p < 0.05) and 132 ± 12 mm Hg vs 119 ± 9 mm Hg for the BRJ group (p < 0.05). In the HTN pilot study, during a treadmill graded exercise test, peak oxygen consumption (primary outcome) did not change significantly, but time to exhaustion (also a primary outcome) improved in both groups, 504 ± 32 s vs 601 ± 38 s (p < 0.05) for the placebo group and 690 ± 38 s vs 772 ± 95 s for the BRJ group (p < 0.05) which was associated with a reduction in supine resting systolic blood pressure in BRJ group. Arterial compliance also improved during aerobic exercise training in both the HFpEF and the HTN patients for both BRJ and placebo groups. Future work is needed to determine if larger nitrate doses would provide an added benefit to supervised aerobic exercise in HTN and HFpEF patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Meta-analysis of the effects of carvedilol versus metoprolol on all-cause mortality and hospitalizations in patients with heart failure.

PubMed

Briasoulis, Alexandros; Palla, Mohan; Afonso, Luis

2015-04-15

Long-term treatment with appropriate doses of carvedilol or metoprolol is currently recommended for patients with heart failure with reduced ejection fraction (HFrEF) to decrease the risk of death, hospitalizations, and patients' symptoms. It remains unclear if the β blockers used in patients with HFrEF are equal or carvedilol is superior to metoprolol types. We performed a meta-analysis of the comparative effects of carvedilol versus metoprolol tartrate and succinate on all-cause mortality and/or hospitalization. We conducted an Embase and MEDLINE search for prospective controlled trials and cohort studies of patients with HFrEF who were received to treatment with carvedilol versus metoprolol. We identified 4 prospective controlled and 6 cohort studies with 30,943 patients who received carvedilol and 69,925 patients on metoprolol types (tartrate and succinate) with an average follow-up duration of 36.4 months. All-cause mortality was reduced in prospective studies with carvedilol versus metoprolol tartrate. Neither all-cause mortality nor hospitalizations were significantly different between carvedilol and metoprolol succinate in the cohort studies. In conclusion, in patients with HFrEF, carvedilol and metoprolol succinate have similar effects in reducing all-cause mortality. Copyright © 2015 Elsevier Inc. All rights reserved.

Exercise Training in Group 2 Pulmonary Hypertension: Which Intensity and What Modality.

PubMed

Arena, Ross; Lavie, Carl J; Borghi-Silva, Audrey; Daugherty, John; Bond, Samantha; Phillips, Shane A; Guazzi, Marco

2016-01-01

Pulmonary hypertension (PH) due to left-sided heart disease (LSHD) is a common and disconcerting occurrence. For example, both heart failure (HF) with preserved and reduced ejection fraction (HFpEF and HFrEF) often lead to PH as a consequence of a chronic elevation in left atrial filling pressure. A wealth of literature demonstrates the value of exercise training (ET) in patients with LSHD, which is particularly robust in patients with HFrEF and growing in patients with HFpEF. While the effects of ET have not been specifically explored in the LSHD-PH phenotype (i.e., composite pathophysiologic characteristics of patients in this advanced disease state), the overall body of evidence supports clinical application in this subgroup. Moderate intensity aerobic ET significantly improves peak oxygen consumption, quality of life and prognosis in patients with HF. Resistance ET significantly improves muscle strength and endurance in patients with HF, which further enhance functional capacity. When warranted, inspiratory muscle training and neuromuscular electrical stimulation are becoming recognized as important components of a comprehensive rehabilitation program. This review will provide a detailed account of ET programing considerations in patients with LSHD with a particular focus on those concomitantly diagnosed with PH. Copyright © 2015 Elsevier Inc. All rights reserved.

New and Evolving Concepts Regarding the Prognosis and Treatment of Cardiac Amyloidosis.

PubMed

Perlini, Stefano; Mussinelli, Roberta; Salinaro, Francesco

2016-12-01

Systemic amyloidoses are rare and proteiform diseases, caused by extracellular accumulation of insoluble misfolded fibrillar proteins. Prognosis is dictated by cardiac involvement, which is especially frequent in light chain (AL) and in transthyretin variants (ATTR, both mutated, (ATTRm), and wild-type, (ATTRwt)). Recently, ATTRwt has emerged as a potentially relevant cause of a heart failure with preserved ejection fraction (HFpEF). Cardiac amyloidosis is an archetypal example of restrictive cardiomyopathy, with signs and symptoms of global heart failure and diastolic dysfunction. Independent of the aetiology, cardiac amyloidosis is associated with left ventricular concentric "hypertrophy" (i.e. increased wall thickness), preserved (or mildly depressed) ejection fraction, reduced midwall fractional shortening and global longitudinal function, as well as evident diastolic dysfunction, up to an overly restrictive pattern of the left ventricular filling. Cardiac biomarkers such as troponins and natriuretic peptides are very robust and widely accepted diagnostic as well as prognostic tools. Owing to its dismal prognosis, accurate and early diagnosis is mandatory and potentially life-saving. Although pathogenesis is still not completely understood, direct cardiomyocyte toxicity of the amyloidogenic precursor proteins and/or oligomer aggregates adds on tissue architecture disruption caused by amyloid deposition. The clarification of mechanisms of cardiac damage is offering new potential therapeutic targets, and several treatment options with a relevant impact on prognosis are now available.

Effect of exercise on diastolic function in heart failure patients: a systematic review and meta-analysis.

PubMed

Pearson, M J; Mungovan, S F; Smart, N A

2017-03-01

Diastolic dysfunction contributes to the development and progression of heart failure. Conventional echocardiography and tissue Doppler imaging are widely utilised in clinical research providing a number of indices of diastolic function valuable in the diagnosis and prognosis of heart failure patients. The aim of this meta-analysis was to quantify the effect of exercise training on diastolic function in patients with heart failure. Exercise training studies that investigate different indices of diastolic function in patients with heart failure have reported that exercise training improves diastolic function in these patients. We sought to add to the current literature by quantifying, where possible, the effect of exercise training on diastolic function. We conducted database searches (PubMed, EBSCO, EMBASE, and Cochrane Trials Register to 31 July 2016) for exercise based rehabilitation trials in heart failure, using the search terms 'exercise training, diastolic function and diastolic dysfunction'. Data from six studies, with a total of 266 heart failure with reduced ejection fraction (HFrEF) participants, 144 in intervention groups and 122 in control groups, indicated a significant reduction in the ratio of early diastolic transmitral velocity (E) to early diastolic tissue velocity (E') (E/E' ratio) with exercise training, exercise vs. control mean difference (MD) of -2.85 (95% CI -3.66 to -2.04, p < 0.00001). Data from five studies in heart failure with preserved ejection fraction (HFpEF) patients, with a total of 204 participants, 115 in intervention groups and 89 in control groups, also demonstrated a significant improvement in E/E' in exercise vs. control MD of -2.38 (95% CI -3.47 to -1.28, p < 0.0001).

Rationale and design of the SOluble guanylate Cyclase stimulatoR in heArT failurE Studies (SOCRATES).

PubMed

Pieske, Burkert; Butler, Javed; Filippatos, Gerasimos; Lam, Carolyn; Maggioni, Aldo Pietro; Ponikowski, Piotr; Shah, Sanjiv; Solomon, Scott; Kraigher-Krainer, Elisabeth; Samano, Eliana Tibana; Scalise, Andrea Viviana; Müller, Katharina; Roessig, Lothar; Gheorghiade, Mihai

2014-09-01

The clinical outcomes for patients with worsening chronic heart failure (WCHF) remain exceedingly poor despite contemporary evidence-based therapies, and effective therapies are urgently needed. Accumulating evidence supports augmentation of cyclic guanosine monophosphate (cGMP) signalling as a potential therapeutic strategy for HF with reduced or preserved ejection fraction (HFrEF and HFpEF, respectively). Direct soluble guanylate cyclase (sGC) stimulators target reduced cGMP generation due to insufficient sGC stimulation and represent a promising method for cGMP enhancement. The phase II SOluble guanylate Cyclase stimulatoR in heArT failurE Study (SOCRATES) programme consists of two randomized, parallel-group, placebo-controlled, double-blind, multicentre studies, SOCRATES-REDUCED (in patients with LVEF <45%) and SOCRATES-PRESERVED (in those with LVEF ≥ 45%), that will explore the pharmacodynamic effects, safety and tolerability, and pharmacokinetics of four dose regimens of the once-daily oral sGC stimulator vericiguat (BAY 1021189) over 12 weeks compared with placebo. These studies will enrol patients stabilized during hospitalization for HF at the time of discharge or within 4 weeks thereafter. The primary endpoint in SOCRATES-REDUCED is change in NT-proBNP at 12 weeks. The primary endpoints in SOCRATES-PRESERVED are change in NT-proBNP and left atrial volume at 12 weeks. SOCRATES will be the first programme to enrol specifically both inpatients and outpatients with WCHF and patients with reduced or preserved ejection fraction. Results will inform the benefits of pursuing subsequent event-driven clinical outcome trials with sGC stimulators in this patient population. © 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.

Prognostic impact of heart rate in elderly with systolic heart failure and concomitant atrial fibrillation.

PubMed

Barywani, Salim; Petzold, Max

2017-08-01

The present study aimed to investigate the impact of resting heart rate (HR) on 5-year all-cause mortality in patients ≥80 years with heart failure (HF) with reduced ejection fraction (HFrEF) and concomitant atrial fibrillation (AF) after optimal up-titration of beta-blockers (BBs). Patients (n = 185) aged ≥80 years with HF and left ventricular ejection fraction ≤40% were included between January 2000 and January 2008 from two university hospitals, Sahlgrenska and Östra and retrospectively studied from January 2 to May 30, 2013. Up-titrations of guideline recommended medications were performed at HF outpatient clinics. Of whole study population, 54% (n= 100) had AF. After optimal up-titration of BBs and angiotensin converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), mean HR in patients with AF was 73 ± 15 beats/minute (bpm), 36% had resting HR ≤65 bpm. Five-year all-cause mortality among patients with AF was significantly lower in patients with HR ≤65 bpm (63%) compared to HR >65 (80%). Cox proportional-hazard regression analysis adjusted for clinically important baseline variables and doses of ACEIs/ARBs and BBs demonstrated resting HR ≤65 bpm as an independent predictor of improved survival compared to resting HR >65 bpm (HR 0.3, 95%CI 0.1-0.7, P 0.005). In octogenarians with HFrEF and concomitant AF, lowering resting HR to levels as low as HR ≤65 bpm was still associated with improved survival from all-cause mortality. Our data indicate that mortality in AF became comparable to SR when patients were on maximally up-titrated beta-blocker doses with HR as low as 75 bpm.

Adaptive Servo-Ventilation Treatment Increases Stroke Volume in Stable Systolic Heart Failure Patients With Low Tricuspid Annular Plane Systolic Excursion.

PubMed

Iwasaku, Toshihiro; Ando, Tomotaka; Eguchi, Akiyo; Okuhara, Yoshitaka; Naito, Yoshiro; Mano, Toshiaki; Masuyama, Tohru; Hirotani, Shinichi

2017-05-31

We hypothesized that the effects of adaptive servo-ventilation (ASV) therapy were influenced by right-sided heart performance. This study aimed to clarify the interaction between the effects of ASV and right-sided heart performance in patients with stable heart failure (HF) with reduced ejection fraction (HFrEF).Twenty-six stable HF inpatients (left ventricular ejection fraction < 0.45, without moderate to severe mitral regurgitation (MR) were analyzed. Echocardiography was performed before and after 30 minutes of ASV. ASV increased stroke volume index (SVI) in 14 patients (30.0 ± 11.9 to 41.1 ± 16.1 mL/m 2 ) and reduced SVI in 12 patients (36.0 ± 10.1 to 31.9 ± 12.2 mL/m 2 ). Multivariate linear regression analysis revealed that tricuspid annular plane systolic excursion (TAPSE) before ASV was an independent association factor for (SV during ASV - SV before ASV)/LVEDV × 100 (%) (%ΔSV/LVEDV). ROC analysis of TAPSE for %ΔSV/LVEDV > 0 showed that the cut-off point was 16.5 mm. All patients were divided into 2 groups according to the TAPSE value. Although no significant differences were found in the baseline characteristics and blood tests, there were significant differences in tricuspid lateral annular systolic velocity, TAPSE, right atrial area, and right ventricular (RV) area before ASV between patients with TAPSE ≤ 16.5 mm and those with TAPSE > 16.5 mm. Interestingly, ASV reduced RV area and increased TAPSE in patients with TAPSE ≤ 16.5 mm, while it reduced TAPSE in those > 16.5 mm.ASV therapy has the potential to increase SVI in stable HFrEF patients with low TAPSE.

Independence of the blood pressure lowering effect and efficacy of the angiotensin receptor neprilysin inhibitor, LCZ696, in patients with heart failure with preserved ejection fraction: an analysis of the PARAMOUNT trial.

PubMed

Jhund, Pardeep S; Claggett, Brian; Packer, Milton; Zile, Michael R; Voors, Adriaan A; Pieske, Burkert; Lefkowitz, Martin; Shi, Victor; Bransford, Toni; McMurray, John J V; Solomon, Scott D

2014-06-01

The first in class angiotensin receptor neprilysin inhibitor, LCZ696 has been shown to reduce levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), reduce left atrial size and improve New York Heart Association (NYHA) class in patients with heart failure with preserved ejection fraction (HFpEF). We examined whether the effects of LCZ696 were independent of systolic blood pressure (SBP) lowering. In the Prospective comparison of ARNi (angiotensin receptor neprilysin inhibitor) with ARB (angiotensin receptor blocker) on Management Of heart failUre with preserved ejectioN fracTion (PARAMOUNT) trial 301 patients were randomly assigned to LCZ696 or valsartan. We examined the relationship between SBP lowering and LCZ696 on NT-proBNP level, left atrial size, NYHA class and estimated glomerular filtration rate (eGFR). By 12 weeks blood pressure was reduced by 9 mmHg (SD 15)/5 mmHg (SD 11) in patients receiving LCZ696 in comparison with 3 mmHg (SD 17)/2 mmHg (SD 12) in those receiving valsartan. The change in NT-proBNP was poorly correlated with change in SBP (LCZ696, r = 0.17, P = 0.06; valsartan, r = 0.05, P = 0.58) After adjustment for change in SBP, the ratio of change in NT-proBNP at 12 weeks for LCZ696 vs. valsartan was 0.76 (95% CI 0.63-0.93, P = 0.008), and similar to the ratio not adjusting for SBP (0.76, 95% CI 0.63-0.92, P = 0.006); P for interaction was 0.38). Similarly, reduction in left atrial volume index at 36 weeks, improvement in NYHA class and eGFR were all independent of the change in SBP. In patients with HFpEF, the effect of the angiotensin receptor neprilysin inhibitor LCZ696 on NT-proBNP, left atrial volume, functional class, and eGFR was independent of reduction in SBP. © 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.

Associations Between Neutrophil Gelatinase Associated Lipocalin, Neutrophil-to-Lymphocyte Ratio, Atrial Fibrillation and Renal Dysfunction in Chronic Heart Failure

PubMed Central

Argan, Onur; Ural, Dilek; Kozdag, Guliz; Sahin, Tayfun; Bozyel, Serdar; Aktas, Mujdat; Karauzum, Kurtulus; Yılmaz, Irem; Dervis, Emir; Agir, Aysen

2016-01-01

Background Atrial fibrillation (AF) and renal dysfunction are two common comorbidities in patients with chronic heart failure with reduced ejection fraction (HFrEF). This study evaluated the effect of permanent AF on renal function in HFrEF and investigated the associations of atrial fibrillation, neutrophil gelatinase-associated lipocalin (NGAL), and neutrophil-to-lymphocyte ratio (NLR) with adverse clinical outcome. Material/Methods Serum NGAL levels measured by ELISA and NLR were compared between patients with sinus rhythm (HFrEF-SR, n=68), with permanent AF (HFrEF-AF, n=62), and a healthy control group (n=50). Results Mean eGFR levels were significantly lower, and NLR and NGAL levels were significantly higher in the HFrEF patients than in the control patients but the difference between HFrEF-SR and HFrEF-AF was not statistically significant (NGAL: 95 ng/mL in HFrEF-SR, 113 ng/mL in HFrEF-AF and 84 ng/mL in the control group; p<0.001). Independent associates of baseline eGFR were age, hemoglobin, NLR, triiodothyronine, and pulmonary artery systolic pressure. In a mean 16 months follow-up, adverse clinical outcome defined as progression of kidney dysfunction and composite of all-cause mortality and re-hospitalization were not different between HFrEF-SR and HFrEF-AF patients. Although NGAL was associated with clinical endpoints in the univariate analysis, Cox regression analysis showed that independent predictors of increased events were the presence of signs right heart failure, C-reactive protein, NLR, triiodothyronine, and hemoglobin. In ROC analysis, a NLR >3 had a 68% sensitivity and 75% specificity to predict progression of kidney disease (AUC=0.72, 95% CI 0.58–0.85, p=0.001). Conclusions Presence of AF in patients with HFrEF was not an independent contributor of adverse clinical outcome (i.e., all-cause death, re-hospitalization) or progression of renal dysfunction. Renal dysfunction in HFrEF was associated with both NLR and NGAL levels, but systemic inflammation reflected by NLR seemed to be a more important determinant of progression of kidney dysfunction. PMID:27918494

The value of hemodynamic measurements by air plethysmography in diagnosing venous obstruction of the lower limb.

PubMed

Kurstjens, Ralph L M; de Wolf, Mark A F; Alsadah, Sarah A; Arnoldussen, Carsten W K P; Strijkers, Rob H W; Toonder, Irwin M; Wittens, Cees H A

2016-07-01

Air plethysmography (APG) is a functional, noninvasive test that can assess volumetric changes in the lower limb and might therefore be used as a diagnostic tool in chronic deep venous disease. However, use of APG in chronic deep venous obstructive disease remains debatable. This study assessed the clinical value of APG in identifying chronic deep venous obstruction. All patients referred to our tertiary, outpatient clinic between January 2011 and August 2013 with chronic venous complaints and suspected outflow obstruction underwent an outflow fraction (OF), ejection fraction (EF), and residual volume fraction (RVF) test using APG. Duplex ultrasound and magnetic resonance venography were used to establish whether and where obstruction was present. Diagnostic values of these tests were assessed for obstructions at different levels of the deep venous system. A total of 312 limbs in 248 patients were tested. Mean age was 45.5 ± 14.0 years, and 62.5% were female. In post-thrombotic disease, specificity and positive predictive value for OF were as high as 98.4% and 95.0%, respectively; however, sensitivity was 34.8% and negative predictive value was 29.6%, with no clinically relevant positive or negative likelihood ratios. No clinically relevant differences were observed in stratifying for level of obstruction. EF and RVF were as inconclusive. Neither could these parameters be used in diagnosing nonthrombotic iliac vein compression. We found a poor correlation between OF, EF, or RVF, determined by APG, and the presence of chronic deep venous obstruction. Therefore, use of its relative parameters is unwarranted in daily clinical practice. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

The large-scale placebo-controlled beta-blocker studies in systolic heart failure revisited: results from CIBIS-II, COPERNICUS and SENIORS-SHF compared with stratified subsets from MERIT-HF.

PubMed

Wikstrand, J; Wedel, H; Castagno, D; McMurray, J J V

2014-02-01

The four pivotal beta-blocker trials in heart failure (HF) had different inclusion criteria, making comparison difficult without patient stratifying. The aim of this study was to compare, in similar patients, the effects of bisoprolol, metoprolol controlled release/extended release (CR/XL), carvedilol and nebivolol on (i) total mortality, (ii) all-cause mortality or hospitalization due to cardiovascular causes (time to first event), (iii) all-cause mortality or hospitalization because of HF and (iv) tolerability, defined as discontinuation of randomized treatment. We compared stratified (s ) subsets in MERIT-HF with patients in CIBIS-II [New York Heart Association (NYHA) class III/IV and ejection fraction (EF) ≤ 35%] and COPERNICUS (NYHA III/IV and EF <25%) and in patients with systolic HF in SENIORS-SHF (age ≥ 70 years and EF ≤ 35%). The annual mortality rates in the placebo and beta-blocker arms were: (i) CIBIS-II (n = 2647), 13.2% vs. 8.8% (relative risk reduction 34%, 95% CI: 19-46, P < 0.0001) and MERIT-HFs (n = 2002), 14.8% vs. 8.6% (relative risk reduction 42%, 95% CI: 24-56, P < 0.0001); (ii) COPERNICUS (n = 2289), 19.7% vs. 12.8% (relative risk reduction 35%, 95% CI: 19-48, P = 0.0014) and MERIT-HFs (n = 795), 19.1% vs. 11.7% (relative risk reduction 39%; 95% CI: 11-58, P = 0.0086); (iii) SENIORS-SHF (n = 1359), 11.3% vs. 9.7% (relative risk reduction 16%, NS) and MERIT-HFs (n = 985), 14.8% vs. 10.1% (relative risk reduction 32%, 95% CI: 2-53, P = 0.038). The effects on the other outcomes assessed were similar. Analyses indicated fewer discontinuations from randomized treatment on beta-blockers compared with placebo in COPERNICUS and the MERIT-HFs subsets. The efficacy and tolerability of bisoprolol, carvedilol and metoprolol CR/XL are similar in patients with systolic HF, irrespective of NYHA class or ejection fraction. Nebivolol is less effective and not better tolerated. © 2013 The Association for the Publication of the Journal of Internal Medicine.

Furosemide Prescription During the Dry State Is a Predictor of Long-Term Survival of Stable, Optimally Medicated Patients With Systolic Heart Failure.

PubMed

Sargento, Luis; Simões, Andre Vicente; Longo, Susana; Lousada, Nuno; Reis, Roberto Palma Dos

2017-05-01

Furosemide is associated with poor prognosis in patients with heart failure and reduced ejection fraction (HFrEF). To evaluate the association between daily furosemide dose prescribed during the dry state and long-term survival in stable, optimally medicated outpatients with HFrEF. Two hundred sixty-six consecutive outpatients with left ventricular ejection fraction <40%, clinically stable in the dry state and on optimal heart failure therapy, were followed up for 3 years in a heart failure unit. The end point was all-cause death. There were no changes in New York Heart Association class and therapeutics, including diuretics, and no decompensation or hospitalization during 6 months. Furosemide doses were categorized as low or none (0-40 mg/d), intermediate (41-80 mg/d), and high (>80 mg). Cox regression was adjusted for significant confounders. The 3-year mortality rate was 33.8%. Mean dose of furosemide was 57.3 ± 21.4 mg/d. A total of 47.6% of patients received the low dose, 42.1% the intermediate dose, and 2.3% the high dose. Receiver operating characteristics for death associated with furosemide dose showed an area under the curve of 0.74 (95% confidence interval [CI]: 0.68-0.79; P < .001), and the best cutoff was >40 mg/d. An increasing daily dose of furosemide was associated with worse prognosis. Those receiving the intermediate dose (hazard ratio [HR] = 4.1; 95% CI: 2.57-6.64; P < .001) or high dose (HR = 19.8; 95% CI: 7.9-49.6; P < .001) had a higher risk of mortality compared to those receiving a low dose. Patients receiving >40 mg/d, in a propensity score-matched cohort, had a greater risk of mortality than those receiving a low dose (HR = 4.02; 95% CI: 1.8-8.8; P = .001) and those not receiving furosemide (HR = 3.9; 95% CI: 0.07-14.2; P = .039). Furosemide administration during the dry state in stable, optimally medicated outpatients with HFrEF is unfavorably associated with long-term survival. The threshold dose was 40 mg/d.

CARDIAC STRUCTURAL AND FUNCTIONAL ABNORMALITIES IN FEMALES WITH UNTREATED HYPOPITUITARISM DUE TO SHEEHAN SYNDROME: RESPONSE TO HORMONE REPLACEMENT THERAPY.

PubMed

Laway, Bashir Ahmad; Ramzan, Mahroosa; Allai, Mohd Sultan; Wani, Arshad Iqbal; Misgar, Raiz Ahmad

2016-09-01

Data on cardiac abnormalities in females with untreated hypopituitarism are limited. We investigated echocardiographic abnormalities in females with untreated hypopituitarism and their response to treatment. Twenty-three females with treatment-naïve hypopituitarism and 30 matched healthy controls were evaluated for cardiac structure and function. Echocardiographic evaluation was done at presentation and after achieving a euthyroid and eucortisol state. Fourteen (61%) patients had mitral regurgitation, and 11 (48%) had pericardial effusion as against none among controls. Indices of left ventricular (LV) size like LV end diastolic dimension (LVEDD; 44.5 ± 3.5 mm in cases vs. 47.6 ± 3.8 mm in controls, P = .004), and LV diastolic volume (LVEDV; 91.8 ± 18.0 mL versus 106.5 ± 20.4 mL, P = .009) were significantly lower in the SS group compared with controls. LV mass (LVM) was 70.8 ± 19.2 g in cases and 108.0 ± 33.2 g in controls (P = .02). Similarly, indices of LV systolic function like stroke volume (SV; 59.1 ± 12.0 mL in cases and 74.4 ± 15.8 mL in controls; P = .000), ejection fraction (EF; 64.3 ± 6.2 % in cases against 69.9 ± 9.2 % in controls; P = .03), and fractional shortening (FS; 34.9 ± 4.7% versus 40.1 ± 4.4%, P = .000) were significantly decreased in patients compared with controls. Cardiac abnormalities normalized with restoration of a euthyroid and eucortisol state. Pericardial effusion, mitral regurgitation, and diminished LVM are common in females with untreated hypopituitarism. ACTH = adrenocorticotrophic hormone BMI = body mass index DT = deceleration time EDV = end-diastolic volume EF = ejection fraction FS = fractional shortening GH = growth hormone IGF-1 = insulin growth factor-1 ITT = insulin tolerance test IVSd = interventricular septal diameter LH = luteinizing hormone LV = left ventricular LVEDD = LV end diastolic dimension LVEDV = LV end diastolic volume LVM = LV mass MRI = magnetic resonance imaging MVP = mitral value prolapse PPH = postpartum hemorrhage PWd = posterior wall diameter SS = Sheehan syndrome SV = stroke volume T3 = triiodothyronine T4 = thyroxine TSH = thyroid-stimulating hormone.

Prognostic indicators for dogs with dilated cardiomyopathy.

PubMed

Borgarelli, Michele; Santilli, Roberto A; Chiavegato, David; D'Agnolo, Gino; Zanatta, Renato; Mannelli, Alessandro; Tarducci, Alberto

2006-01-01

The purpose of this study was to investigate the prognostic value of various clinical, ECG, echocardiographic, and Doppler echocardiographic variables in dogs with dilated cardiomyopathy. The relationship to survival of 11 variables was evaluated in 63 dogs. Studied variables were age at time of diagnosis, class of heart failure (HF), dyspnea, ascites, atrial fibrillation (AF), ejection fraction (EF), E-point septal separation, end-diastolic volume index, end-systolic volume index (ESV-I), and restrictive or nonrestrictive transmitral flow (TMF) pattern. Median survival time was 671 days (lower 95% confidence limit, 350 days). Survival curves showed that severity of HF, ascites, ESV-I greater than 140 mL/m2, EF less than 25%, and restrictive TMF pattern had a significant negative relation to survival time. Thirty-nine dogs with both sinus rhythm and AF presented adequate TMF recordings; in these dogs, after stratification by TMF pattern, the restrictive TMF pattern was the most important negative prognostic indicator. We conclude that in dogs with dilated cardiomyopathy the restrictive TMF pattern appears to represent a useful prognostic indicator. Class of HF, ascites, ESV-I, and EF are also useful indexes if an adequate TMF pattern is not recorded.

Practical considerations on the introduction of sacubitril/valsartan in clinical practice: Current evidence and early experience.

PubMed

Farmakis, Dimitrios; Bistola, Vassiliki; Karavidas, Apostolos; Parissis, John

2016-11-15

The combination of neprilysin inhibitor sacubitril with the angiotensin II receptor 1 blocker valsartan is the first agent from the angiotensin receptor neprilysin inhibitors (ARNI) class authorized for clinical use in heart failure (HF) patients with reduced ejection fraction (HFrEF). Sacubitril/valsartan resulted in 20% reduction in the incidence rate of death or HF hospitalization compared to enalapril in symptomatic HFrEF patients in the seminal PARADIGM-HF trial. As a result, the recently updated European and American HF guidelines granted this agent a class IB indication for the treatment of ambulatory/chronic symptomatic HFrEF patients. However, translating the positive results of trials into true clinical benefit is often challenging. This is particularly true in the case of sacubitril/valsartan, as HF is a heterogeneous syndrome including many severely ill patients who are prone to decompensation, while this new agent comes to replace a cornerstone of current evidence-based HF therapy. In the present paper, we address a number of practical issues regarding the introduction of sacubitril/valsartan and propose an algorithm based on available evidence and early clinical experience. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Implantable cardioverter defibrillator does not cure the heart.

PubMed

Sławuta, Agnieszka; Boczar, Krzysztof; Ząbek, Andrzej; Gajek, Jacek; Lelakowski, Jacek; Vijayaraman, Pugazhendhi; Małecka, Barbara

2018-01-23

A man with non-ischemic cardiomyopathy, EF 22%, permanent AF and ICD was admitted for elective device replacement. The need for the optimization of the ventricular rate and avoidance of right ventricular pacing made it necessary to up-grade the existing pacing system using direct His bundle pacing and dual chamber ICD. This enabled the regularization of ventricular rate, avoiding the RV pacing and optimize the beta-blocker dose. The one month follow-up already showed reduction in left ventricle diameter, improvement in ejection fraction, NYHA class decrease to II. The His bundle pacing enabled the optimal treatment of the patient resulting in excellent clinical improvement.

Left ventricular eccentricity index measured with SPECT myocardial perfusion imaging: An additional parameter of adverse cardiac remodeling.

PubMed

Gimelli, Alessia; Liga, Riccardo; Clemente, Alberto; Marras, Gavino; Kusch, Annette; Marzullo, Paolo

2017-01-12

Single-photon emission computed-tomography (SPECT) allows the quantification of LV eccentricity index (EI), a measure of cardiac remodeling. We sought to evaluate the feasibility of EI measurement with SPECT myocardial perfusion imaging and its interactions with relevant LV functional and structural parameters. Four-hundred and fifty-six patients underwent myocardial perfusion imaging on a Cadmium-Zinc-Telluride (CZT) camera. The summed rest, stress, and difference scores were calculated. From rest images, the LV end-diastolic (EDV) and end-systolic volumes, ejection fraction (EF), and peak filling rate (PFR) were calculated. In every patient, the EI, ranging from 0 (sphere) to 1 (line), was computed using a dedicated software (QGS/QPS; Cedars-Sinai Medical Center). Three-hundred and thirty-eight/456 (74%) patients showed a normal EF (>50%), while 26% had LV systolic dysfunction. The EI was computed from CZT images with excellent reproducibility (interclass correlation coefficient: 0.99, 95% CI 0.98-0.99). More impaired EI values correlated with the presence of a more abnormal LV perfusion (P < .001), function (EF and PFR, P < .001), and structure (EDV, P < .001). On multivariate analysis, higher EDV (P < .001) and depressed EF (P = .014) values were independent predictors of abnormal EI. The evaluation of LV eccentricity is feasible on gated CZT images. Abnormal EI associates with significant cardiac structural and functional abnormalities.

A semi-automatic method for left ventricle volume estimate: an in vivo validation study

NASA Technical Reports Server (NTRS)

Corsi, C.; Lamberti, C.; Sarti, A.; Saracino, G.; Shiota, T.; Thomas, J. D.

2001-01-01

This study aims to the validation of the left ventricular (LV) volume estimates obtained by processing volumetric data utilizing a segmentation model based on level set technique. The validation has been performed by comparing real-time volumetric echo data (RT3DE) and magnetic resonance (MRI) data. A validation protocol has been defined. The validation protocol was applied to twenty-four estimates (range 61-467 ml) obtained from normal and pathologic subjects, which underwent both RT3DE and MRI. A statistical analysis was performed on each estimate and on clinical parameters as stroke volume (SV) and ejection fraction (EF). Assuming MRI estimates (x) as a reference, an excellent correlation was found with volume measured by utilizing the segmentation procedure (y) (y=0.89x + 13.78, r=0.98). The mean error on SV was 8 ml and the mean error on EF was 2%. This study demonstrated that the segmentation technique is reliably applicable on human hearts in clinical practice.

The a´ velocity in the tissue Doppler predicts S/D ratio <1 in patients with a normal ejection fraction.

PubMed

Johansson, Benny; Lundin, Fredrik; Tegeback, Rolf; Bojö, Leif

2018-04-13

To compare the ability of the a´ velocity and the e´ velocity in predicting a dominant diastolic pulmonary vein flow (S/D ratio <1) in patients with normal ejection fraction. We retrospectively evaluated the diastolic function according to the ASE/EACVI guidelines, the S/D ratio and the septal, lateral and average a´ velocity in 293 unselected in-hospital patients, aged 39-86 years, in sinus rhythm and with no or mild valve disease, having a normal systolic function (EF >50%). There was a good linear correlation between the S/D ratio and the a´ velocity, but a tendency towards a negative correlation between the S/D ratio and the e´ velocity. S/D ratio <1 was seen in 43 patients. These patients had a significantly lower a´ velocity compared to those with S/D-ratio ≥1, septal (6,1 ± 2,4 v 8,8 ± 2,1 cm/s; p < .001) and lateral (6,0 ± 2,6 v 9,3 ± 2,5 cm/s; p < .001) No significant difference was seen in the septal e´ velocity (6,8 ± 2,4 v 6,8 ± 2,1 cm/s), lateral e´ velocity (9,4 ± 2,6 v 9,1 ± 2,8 cm/s) or in the ejection fraction (58,6 ± 4,4% v 58,7 ± 4,0%). A diastolic dysfunction was present in 62 patients, normal diastolic function in 231 patients. The a´ velocity was significantly lower in patients with S/D ratio <1 in both groups (p < .01). The a´ velocity is superior to the e´ velocity in predicting S/D ratio <1 in patients with normal ejection fraction regardless the ASE/EACVI diastolic classification. A failing left atrium seems to be the explanation.

Echocardiographic strain and mortality in Black Americans with end-stage renal disease on hemodialysis.

PubMed

Pressman, Gregg S; Seetha Rammohan, Harish Raj; Romero-Corral, Abel; Fumo, Peter; Figueredo, Vincent M; Gorcsan, John

2015-11-15

End-stage renal disease (ESRD) presents a significant health burden and is associated with high cardiovascular morbidity and mortality. This is particularly true in African Americans who generally have higher rates of cardiovascular mortality. Outcomes in ESRD are related to extent of cardiovascular disease, but markers for outcome are not clearly established. Global longitudinal strain (GLS) has emerged as an important measure of left ventricular systolic function that is additive to traditional ejection fraction (EF). It can be measured on routine digital echocardiography and is reproducible. This study tested the hypothesis that GLS is associated with mortality in black Americans with ESRD and preserved EF. Forty-eight outpatients undergoing hemodialysis, 59.4 ± 13.3 years, with EF ≥50% were prospectively enrolled. GLS, measured by an offline speckle tracking algorithm, ranged from -8.6% to -22.0% with a mean of -13.4%, substantially below normal (-16% or more negative). The prevalence of left ventricular systolic dysfunction, as determined by GLS, was 89%. Patients were followed for an average of 1.9 years; all-cause mortality was 19% (9 deaths). GLS was significantly associated with mortality (hazard ratio 1.15, 95% confidence interval 1.02 to 1.30, p = 0.02), whereas EF was not. After adjustment for multiple potential confounders (age, gender, race, smoking, hypertension, diabetes, hyperlipidemia, coronary disease, heart failure, and EF), GLS remained strongly associated with mortality (hazard ratio 1.30, 95% confidence interval 1.10 to 1.56, p = 0.002). In conclusion, GLS is an important index in patients with ESRD, which is additive to EF as a marker for mortality in this high-risk group. Copyright © 2015 Elsevier Inc. All rights reserved.

Effectiveness of late gadolinium enhancement to improve outcomes prediction in patients referred for cardiovascular magnetic resonance after echocardiography

PubMed Central

2013-01-01

Background Echocardiography (echo) is a first line test to assess cardiac structure and function. It is not known if cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) ordered during routine clinical practice in selected patients can add additional prognostic information after routine echo. We assessed whether CMR improves outcomes prediction after contemporaneous echo, which may have implications for efforts to optimize processes of care, assess effectiveness, and allocate limited health care resources. Methods and results We prospectively enrolled 1044 consecutive patients referred for CMR. There were 38 deaths and 3 cardiac transplants over a median follow-up of 1.0 years (IQR 0.4-1.5). We first reproduced previous survival curve strata (presence of LGE and ejection fraction (EF) < 50%) for transplant free survival, to support generalizability of any findings. Then, in a subset (n = 444) with contemporaneous echo (median 3 days apart, IQR 1–9), EF by echo (assessed visually) or CMR were modestly correlated (R2 = 0.66, p < 0.001), and 30 deaths and 3 transplants occurred over a median follow-up of 0.83 years (IQR 0.29-1.40). CMR EF predicted mortality better than echo EF in univariable Cox models (Integrated Discrimination Improvement (IDI) 0.018, 95% CI 0.008-0.034; Net Reclassification Improvement (NRI) 0.51, 95% CI 0.11-0.85). Finally, LGE further improved prediction beyond EF as determined by hazard ratios, NRI, and IDI in all Cox models predicting mortality or transplant free survival, adjusting for age, gender, wall motion, and EF. Conclusions Among those referred for CMR after echocardiography, CMR with LGE further improves risk stratification of individuals at risk for death or death/cardiac transplant. PMID:23324403

Assessment of LVEF using a new 16-segment wall motion score in echocardiography.

PubMed

Lebeau, Real; Serri, Karim; Lorenzo, Maria Di; Sauvé, Claude; Le, Van Hoai Viet; Soulières, Vicky; El-Rayes, Malak; Pagé, Maude; Zaïani, Chimène; Garot, Jérôme; Poulin, Frédéric

2018-06-01

Simpson biplane method and 3D by transthoracic echocardiography (TTE), radionuclide angiography (RNA) and cardiac magnetic resonance imaging (CMR) are the most accepted techniques for left ventricular ejection fraction (LVEF) assessment. Wall motion score index (WMSI) by TTE is an accepted complement. However, the conversion from WMSI to LVEF is obtained through a regression equation, which may limit its use. In this retrospective study, we aimed to validate a new method to derive LVEF from the wall motion score in 95 patients. The new score consisted of attributing a segmental EF to each LV segment based on the wall motion score and averaging all 16 segmental EF into a global LVEF. This segmental EF score was calculated on TTE in 95 patients, and RNA was used as the reference LVEF method. LVEF using the new segmental EF 15-40-65 score on TTE was compared to the reference methods using linear regression and Bland-Altman analyses. The median LVEF was 45% (interquartile range 32-53%; range from 15 to 65%). Our new segmental EF 15-40-65 score derived on TTE correlated strongly with RNA-LVEF ( r  = 0.97). Overall, the new score resulted in good agreement of LVEF compared to RNA (mean bias 0.61%). The standard deviations (s.d.s) of the distributions of inter-method difference for the comparison of the new score with RNA were 6.2%, indicating good precision. LVEF assessment using segmental EF derived from the wall motion score applied to each of the 16 LV segments has excellent correlation and agreement with a reference method. © 2018 The authors.

Effect of coenzyme Q10 supplementation on heart failure: a meta-analysis123

PubMed Central

Thompson-Paul, Angela M; Bazzano, Lydia A

2013-01-01

Background: Coenzyme Q10 (CoQ10; also called ubiquinone) is an antioxidant that has been postulated to improve functional status in congestive heart failure (CHF). Several randomized controlled trials have examined the effects of CoQ10 on CHF with inconclusive results. Objective: The objective of this meta-analysis was to evaluate the impact of CoQ10 supplementation on the ejection fraction (EF) and New York Heart Association (NYHA) functional classification in patients with CHF. Design: A systematic review of the literature was conducted by using databases including MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and manual examination of references from selected studies. Studies included were randomized controlled trials of CoQ10 supplementation that reported the EF or NYHA functional class as a primary outcome. Information on participant characteristics, trial design and duration, treatment, dose, control, EF, and NYHA classification were extracted by using a standardized protocol. Results: Supplementation with CoQ10 resulted in a pooled mean net change of 3.67% (95% CI: 1.60%, 5.74%) in the EF and −0.30 (95% CI: −0.66, 0.06) in the NYHA functional class. Subgroup analyses showed significant improvement in EF for crossover trials, trials with treatment duration ≤12 wk in length, studies published before 1994, and studies with a dose ≤100 mg CoQ10/d and in patients with less severe CHF. These subgroup analyses should be interpreted cautiously because of the small number of studies and patients included in each subgroup. Conclusions: Pooled analyses of available randomized controlled trials suggest that CoQ10 may improve the EF in patients with CHF. Additional well-designed studies that include more diverse populations are needed. PMID:23221577

Long-Term Preservation of Left Ventricular Systolic Function in Patients With Refractory Angina Pectoris and Inducible Myocardial Ischemia on Optimal Medical Therapy.

PubMed

Slavich, Massimo; Maranta, Francesco; Fumero, Andrea; Godino, Cosmo; Giannini, Francesco; Oppizzi, Michele; Colombo, Antonio; Fragasso, Gabriele; Margonato, Alberto

2016-05-15

Refractory angina pectoris (RAP) represents a clinical condition characterized by frequent episodes of chest pain despite therapy optimization. According to myocardial stunning and myocardial hibernation definitions, RAP should represent the ideal condition for systolic dysfunction development. We aim to investigate the evolution of left ventricular (LV) function in patients with RAP. A retrospective study which encompasses 144 patients with RAP referred to our institution from 1999 to December 2014 was performed. Of them, 88 met the inclusion criteria, and LV function was assessed by echocardiography. All of them had persistent angina episodes on top of optimal medical therapy and evidence of significant inducible myocardial ischemia and no further revascularization options. Nitrates consumption rate, time of angina duration, and the number of angina attacks were evaluated. In the whole population, ejection fraction (EF) was 44% ± 2. EF was significantly lower in patients with previous myocardial infarction (41% ± 1.5 vs 51% ± 1.8, p <0.0001). The duration time and the number of angina attacks did not correlate with EF in the whole population and in patients without previous myocardial infarction. In patients with previous myocardial infarction, the number of anginal attacks did not correlate with EF, but EF appeared higher in patients with angina duration >5 years (<5 years EF 37% ± 1 [n = 26]; >5 years 44% ± 2 [n = 44]; p 0.02). Long-term LV function in patients with RAP is generally preserved. A previous history of myocardial infarction is the only determinant in the development of systolic dysfunction. In conclusion, frequent angina attacks and a long-term history of angina are not apparently associated to worse LV function. Copyright © 2016 Elsevier Inc. All rights reserved.

Spectrum and clinical significance of systolic function and myocardial fibrosis assessed by cardiovascular magnetic resonance in hypertrophic cardiomyopathy.

PubMed

Olivotto, Iacopo; Maron, Barry J; Appelbaum, Evan; Harrigan, Caitlin J; Salton, Carol; Gibson, C Michael; Udelson, James E; O'Donnell, Christopher; Lesser, John R; Manning, Warren J; Maron, Martin S

2010-07-15

In hypertrophic cardiomyopathy (HCM), the clinical significance attributable to the broad range of left ventricular (LV) systolic function, assessed as the ejection fraction (EF), is incompletely resolved. We evaluated the EF using cardiovascular magnetic resonance (CMR) imaging in a large cohort of patients with HCM with respect to the clinical status and evidence of left ventricular remodeling with late gadolinium enhancement (LGE). CMR imaging was performed in 310 consecutive patients, aged 42 +/- 17 years. The EF in patients with HCM was 71 +/- 10% (range 28% to 89%), exceeding that of 606 healthy controls without cardiovascular disease (66 +/- 5%, p <0.001). LGE reflecting LV remodeling showed an independent, inverse relation to the EF (B-0.69, 95% confidence interval -0.86 to -0.52; p <0.001) and was greatest in patients with an EF <50%, in whom it constituted a median value of 29% of the LV volume (interquartile range 16% to 40%). However, the substantial subgroup with low-normal EF values of 50% to 65% (n = 45; 15% of the whole cohort), who were mostly asymptomatic or mildly symptomatic (37 or 82% with New York Heart Association functional class I to II), showed substantial LGE (median 5% of LV volume, interquartile range 2% to 10%). This overlapped with the subgroup with systolic dysfunction and significantly exceeded that of patients with an EF of 66% to 75% and >75% (median 2% of the LV volume, interquartile range 1.5% to 4%; p <0.01). In conclusion, in a large cohort of patients with HCM, a subset of patients with low-normal EF values (50% to 65%) was identified by contrast-enhanced CMR imaging as having substantial degrees of LGE, suggesting a transition phase, potentially heralding advanced LV remodeling and systolic dysfunction, with implications for clinical surveillance and management. Copyright (c) 2010. Published by Elsevier Inc.

Effects of gender, ejection fraction and weight on cardiac force development in patients undergoing cardiac surgery--an experimental examination.

PubMed

Bening, Constanze; Weiler, Helge; Vahl, Christian-Friedrich

2013-11-18

It has long been recognized that differences exist between men and women in the impact of risc factors, symptoms, development and outcome of special diseases like the cardiovascular disease. Gender determines the cardiac baseline parameters like the number of cardiac myocyte, size and demand and may suggest differences in myofilament function among genders, which might be pronounced under pathological conditions. Does gender impact and maybe impair the contractile apparatus? Are the differences more prominent when other factors like weight, age, ejection fraction are added?Therefore we performed a study on 36 patients (21 male, 15 female) undergoing aortic valve replacement (AVR) or aortocoronary bypass operation (CABG) to examine the influence of gender, ejection fraction, surgical procedure and body mass index (BMI) on cardiac force development. Tissue was obtained from the right auricle and was stored in a special solution to prevent any stretching of the fibers. We used the skinned muscle fiber model and single muscle stripes, which were mounted on the "muscle machine" and exposed to a gradual increase of calcium concentration calculated by an attached computer program. 1.) In general female fibers show more force than male fibers: 3.9 mN vs. 2.0 mN (p = 0.03) 2.) Female fibers undergoing AVR achieved more force than those undergoing CABG operation: 5.7 mN vs. 2.8 mN (p = 0.02) as well as male fibers with AVR showed more force values compared to those undergoing CABG: 2.0 mN vs. 0.5 mN (p = 0.01). 3.) Male and female fibers of patients with EF > 55% developed significantly more force than from those with less ejection fraction than 30%: p = 0.002 for the male fibers (1.6 vs. 2.8 mN) and p = 0.04 for the female fibers (5.7 vs. 2.8 mN). 4.) Patients with a BMI between 18 till 25 develop significant more force than those with a BMI > 30: Females 5.1 vs. 2.6 mN; p 0.03, Males 3.8 vs. 0.8 mN; p 0.04). Our data suggest that female patients undergoing AVR or CABG develop significantly more force than male fibers. Additionally we could image the clinical impression of negative impact of overweight and obesity as well as low ejection fraction on cardiac function on level of the myofilaments and observed a reduced force capacity, which is more prominent in male fibers.

Echocardiography vs magnetic resonance imaging in assessing ventricular function and systemic atrioventricular valve status in adults with congenitally corrected transposition of the great arteries.

PubMed

Kowalik, Ewa; Mazurkiewicz, Łukasz; Kowalski, Mirosław; Klisiewicz, Anna; Marczak, Magdalena; Hoffman, Piotr

2016-11-01

The survival in adults with congenitally corrected transposition of the great arteries (ccTGA) might be reduced due to dysfunction of the systemic right ventricle (sRV). The quantitative echocardiographic assessment of sRV function and tricuspid (systemic atrioventricular valve) regurgitation (TR) is still a diagnostic challenge. Thus, the aim of this study was to compare echocardiographic indices of sRV function and the degree of TR with corresponding MRI (magnetic resonance imaging)-derived parameters in adults with ccTGA. A prospective cross-sectional study of adults with ccTGA referred to a tertiary congenital heart disease center was conducted. All patients underwent transthoracic echocardiography and MRI examinations. Thirty-three adults (19F/14M, mean age 34.1 years) were included. We found significantly lower fractional area change (FAC) and global longitudinal strain (GLS) values in patients with MRI-derived RV ejection fraction (EF) <45%. A cutoff GLS<-16.3% identified sRV EF ≥45% with a sensitivity of 77.3% and specificity of 72.7%. A very strong correlation between MRI- and echocardiography-derived TR volume was observed (r=.84; P<.0001). GLS is the variable with the best sensitivity but less specificity to distinguish between systemic RV EF ≥45% and below 45%, and it seems to be the preferred echocardiographic index of systemic RV function in adults with ccTGA. The quantitative assessment of TR by MRI and echocardiography showed a very strong agreement in patients with ccTGA. © 2016, Wiley Periodicals, Inc.

The prognostic role of exercise echocardiography in heart failure.

PubMed

Rubiś, Paweł; Drabik, Leszek; Kopeć, Grzegorz; Olszowska, Maria; Płazak, Wojciech; Podolec, Piotr

2011-01-01

Gradual impairment of exercise tolerance is the commonest sign of heart failure (HF). Little is known as to which cardiac contributors of poor exercise capacity carry an independent prognostic information in HF. We investigated the prognostic role of exercise echocardiography (ex-echo) in HF patients. We studied 85 consecutive, symptomatic HF patients (66 males, mean age 62.5 ± 11.8 [range 21-83] years, mean left ventricular ejection fraction [LVEF] 27.2 ± 9.5%). The end-point was all-cause mortality. During the follow-up period (mean 43 ± 21 months) 21 patients died. Resting echocardiography and ex-echo, with the simultaneous measurement of peak oxygen uptake (VO(2peak)), was performed in each patient using a semi-supine ergometer (20 W, 2-min increments). Apart from conventional assessment of systolic and diastolic function (EF, E/A, DT, IVRT) or right ventricular systolic pressure (RVSP), tissue Doppler imaging was used for the assessment of LV and RV peak velocity (IVV) as well as acceleration during isovolumic contraction (IVA), peak velocity during ejection phase (S'), peak early diastolic velocity (E'), peak late diastolic velocity (A'), and ratio of early diastolic mitral/tricuspid velocity to peak early diastolic velocity (E/E'). Patients who died were significantly older, had lower exercise capacity, more advanced HF, greater impairment of baseline systolic function, higher baseline pulmonary artery systolic pressure, and most importantly a lack of improvement in EF, diastolic function, and further increase of RVSP during exercise. Out of all echocardiographic parameters, only peak stress EF (x(2) 6.1; p = 0.01), baseline and peak exercise RVSP (x(2) 12.5 and c(2) 18.7; p 〈 0.001; respectively), and mitral E/E' ratio (x(2) 8.9; p 〈 0.01) were univariate predictors of prognosis and remained independently prognostic when adjusted for age and sex but were eliminated from the model by NT-proBNP. During exercise, more severe systolic and diastolic dysfunction with the elevation of pulmonary arterial pressure is more prevalent in HF patients who have a poorer outcome. The estimation of common parameters such as EF, RVSP and E/E' using ex-echo, provides prognostic information in HF.

Carfilzomib and the cardiorenal system in myeloma: an endothelial effect?

PubMed Central

Rosenthal, A; Luthi, J; Belohlavek, M; Kortüm, K M; Mookadam, F; Mayo, A; Fonseca, R; Bergsagel, P L; Reeder, C B; Mikhael, J R; Stewart, A K

2016-01-01

Carfilzomib (Cfz) has been associated with an ~5% incidence of unexplained and unpredictable cardiovascular toxicity in clinical trials. We therefore implemented a detailed, prospective, clinical cardiac and renal evaluation of 62 Cfz-treated myeloma patients, including serial blood pressure (BP), creatinine, troponin, NT-proBNP and pre- and post-treatment echocardiograms, including ejection fraction (EF), average global longitudinal strain and compliance. Pre-treatment elevations in NT-proBNP and BP, as well as abnormal cardiac strain were common. A rise in NT-proBNP occurred frequently post-treatment often without corresponding cardiopulmonary symptoms. A rise in creatinine was common, lessened with hydration and often reversible. All patients had a normal EF pre-treatment. Five patients experienced a significant cardiac event (four decline in EF and one myocardial infarction), of which 2 (3.2%) were considered probably attributable to Cfz. None were rechallenged with Cfz. The ideal strategy for identifying patients at risk for cardiac events, and parameters by which to monitor for early toxicity have not been established; however, it appears baseline echocardiographic testing is not consistently predictive of toxicity. The toxicities observed suggest an endothelial mechanism and further clinical trials are needed to determine whether or not this represents a class effect or is Cfz specific. PMID:26771810

Arterial stiffness as a predictor of recovery of left ventricular systolic function after acute myocardial infarction treated with primary percutaneous coronary intervention.

PubMed

Imbalzano, Egidio; Vatrano, Marco; Mandraffino, Giuseppe; Ghiadoni, Lorenzo; Gangemi, Sebastiano; Bruno, Rosa Maria; Ciconte, Vincenzo Antonio; Paunovic, Nevena; Costantino, Rossella; Mormina, Enrico Maria; Ceravolo, Roberto; Saitta, Antonino; Dattilo, Giuseppe

2015-12-01

Left ventricular ejection fraction (LVEF) and pulse wave velocity (PWV) are acknowledged as independent risk factors in different high-risk populations. We investigated the effects of arterial stiffness on LV function at 3 and 6 months after acute myocardial infarction. Changes in LVEF were evaluated in 136 consecutive patients who were diagnosed with ST-segment elevation coronary syndrome and treated with primary percutaneous coronary intervention. Doppler guided by 2D ultrasound was used to measure carotid-femoral PWV. According to tertiles of arterial stiffness, a significant correlation between higher PWV and worse recovery in LVEF was found (3 months EF change: 9.9 ± 5.0% vs 5.9 ± 3.4 vs 3.8 ± 1.6; p < 0.001 and 6 months EF change: 18.5 ± 7.0% vs 11.5 ± 5.2 vs 7.3 ± 3.0; p = 0.002). In the multivariate analysis PWV showed the ability to predict the outcome in terms of EF recovery at 3 and 6 months also after any correction for age and other variables (β = -0.566, p < 0.001). Arterial stiffening may result in a less effective recovery of LV function after acute myocardial infarction.

Galectin-3 Reflects the Echocardiographic Grades of Left Ventricular Diastolic Dysfunction.

PubMed

Ansari, Uzair; Behnes, Michael; Hoffmann, Julia; Natale, Michele; Fastner, Christian; El-Battrawy, Ibrahim; Rusnak, Jonas; Kim, Seung Hyun; Lang, Siegfried; Hoffmann, Ursula; Bertsch, Thomas; Borggrefe, Martin; Akin, Ibrahim

2018-07-01

The level of Galectin-3 (Gal-3) protein purportedly reflects an ongoing cardiac fibrotic process and has been associated with ventricular remodeling, which is instrumental in the development of heart failure with preserved ejection fraction (HFpEF) syndrome. The aim of this study was to investigate the potential use of Gal-3 in improved characterization of the grades of diastolic dysfunction as defined by echocardiography. Seventy HFpEF patients undergoing routine echocardiography were prospectively enrolled in the present monocentric study. Blood samples for measurements of Gal-3 and amino-terminal pro-brain natriuretic peptide (NT-proBNP) were collected within 24 hours pre- or post-echocardiographic examination. The classification of patients into subgroups based on diastolic dysfunction grade permitted detailed statistical analyses of the derived data. The Gal-3 serum levels of all patients corresponded to echocardiographic indices, suggesting HFpEF (E/A, P=0.03 and E/E', P=0.02). Gal-3 was also associated with progressive diastolic dysfunction, and increased levels corresponded to the course of disease (P=0.012). Detailed analyses of ROC curves suggested that Gal-3 levels could discriminate patients with grade III diastolic dysfunction (area under the curve [AUC]=0.770, P=0.005). Gal-3 demonstrates remarkable effectiveness in the diagnosis of patients suffering from severe grade diastolic dysfunction. Increasing levels of Gal-3 possibly reflect the progressive course of HFpEF, as classified by the echocardiographic grades of diastolic dysfunction. © The Korean Society for Laboratory Medicine.

EPA, not DHA, prevents fibrosis in pressure overload-induced heart failure: potential role of free fatty acid receptor 4[S

PubMed Central

Eclov, Julie A.; Qian, Qingwen; Redetzke, Rebecca; Chen, Quanhai; Wu, Steven C.; Healy, Chastity L.; Ortmeier, Steven B.; Harmon, Erin; Shearer, Gregory C.; O’Connell, Timothy D.

2015-01-01

Heart failure with preserved ejection fraction (HFpEF) is half of all HF, but standard HF therapies are ineffective. Diastolic dysfunction, often secondary to interstitial fibrosis, is common in HFpEF. Previously, we found that supra-physiologic levels of ω3-PUFAs produced by 12 weeks of ω3-dietary supplementation prevented fibrosis and contractile dysfunction following pressure overload [transverse aortic constriction (TAC)], a model that resembles aspects of remodeling in HFpEF. This raised several questions regarding ω3-concentration-dependent cardioprotection, the specific role of EPA and DHA, and the relationship between prevention of fibrosis and contractile dysfunction. To achieve more clinically relevant ω3-levels and test individual ω3-PUFAs, we shortened the ω3-diet regimen and used EPA- and DHA-specific diets to examine remodeling following TAC. The shorter diet regimen produced ω3-PUFA levels closer to Western clinics. Further, EPA, but not DHA, prevented fibrosis following TAC. However, neither ω3-PUFA prevented contractile dysfunction, perhaps due to reduced uptake of ω3-PUFA. Interestingly, EPA did not accumulate in cardiac fibroblasts. However, FFA receptor 4, a G protein-coupled receptor for ω3-PUFAs, was sufficient and required to block transforming growth factor β1-fibrotic signaling in cultured cardiac fibroblasts, suggesting a novel mechanism for EPA. In summary, EPA-mediated prevention of fibrosis could represent a novel therapy for HFpEF. PMID:26435012

Effects of renin-angiotensin-aldosterone system inhibitors on mortality, hospitalization, and diastolic function in patients with HFpEF. A meta-analysis of 13 randomized controlled trials.

PubMed

Zhang, Q; Chen, Y; Liu, Q; Shan, Q

2016-02-01

The purpose of this meta-analysis was to evaluate the effects of renin-angiotensin-aldosterone system (RAAS) inhibitors on mortality, hospitalization, diastolic function, and exercise capacity in heart failure with preserved ejection fraction (HFpEF). Thirteen randomized controlled trials (RCTs), totaling 12,532 patients with HFpEF, were selected. All-cause and cardiovascular mortality, all-cause and heart failure-related hospitalization, diastolic function, and the 6-min walk distance were assessed. The risk ratios (RR) of the dichotomous data, weighted mean difference (WMD) of continuous data, and 95 % confidence intervals (CI) were calculated to assess the effects of RAAS inhibitors. RAAS inhibitors significantly decreased heart failure-related hospitalization (RR 0.89; 95 % CI 0.82-0.97; p = 0.01) and improved the diastolic function, as reflected in a reduced E/e' index (MD -1.38; 95 % CI -2.01 to -0.74; p < 0.0001). However, there were no beneficial effects on all-cause cardiovascular mortality and all-cause hospitalization. Other diastolic parameters had few changes compared with the controls. The 6-min walk distance was not improved by the use of RAAS inhibitors. In patients with HFpEF, RAAS inhibitors decreased heart-failure hospitalization and the E/e' index without affecting mortality, all-cause hospitalization, other diastolic function parameters, and the 6-min walk distance.

Chemical profiles and anticancer effects of saponin fractions of different polarity from the leaves of Panax notoginseng.

PubMed

Qian, Mao; Yi, Li; Song-Lin, Li; Jie, Yang; Ping-Hu, Zhang; Qiang, Wang

2014-01-01

To evaluate the chemical profiles and cytotoxic effects among the total saponin fraction (TSF), 25% ethanol fraction (25EF), 50% ethanol fraction (50EF), and 85% ethanol fraction (85EF) prepared by macroporous resin from the leaves of Panax notoginseng. The simultaneous determination of thirteen main saponins, as well as the chemical profiles of saponin fractions of different polarity, was made by HPLC-DAD and LC-ESI-MS(n) analysis. The cytotoxic effects were determined against KP4 cells (human pancreatic cancer), NCI-H727 cells (human lung cancer), HepG2 cells (human hepatocellular cancer), and SGC-7901 cells (human gastric adenocarcinoma). Chemical analysis indicated that 85EF possessed the most abundant cytotoxic protopanaxadiol saponins, including the marker saponins F2, 20(R)-Rg3, 20(S)-Rg3, and Rh2. The MTT assay showed that 85EF also had the strongest cytotoxic effects among the four fractions. 25EF showed no anti-proliferative effects, while 50EF and TSF exhibited weak anti-proliferative activity. From the aspect of comprehensive utilization of resources, 85EF, enriched with low polarity PPD group saponins, is a new alternative source of anticancer saponins, and a promising botanical preparation for further anticancer studies. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

A randomized trial of hemodiafiltration and change in cardiovascular parameters.

PubMed

Mostovaya, Irina M; Bots, Michiel L; van den Dorpel, Marinus A; Grooteman, Muriel P C; Kamp, Otto; Levesque, Renée; Ter Wee, Piet M; Nubé, Menso J; Blankestijn, Peter J

2014-03-01

Increased left ventricular mass (LVM), low ventricular ejection fraction (EF), and high pulse-wave velocity (PWV) relate to overall and cardiovascular mortality in patients with ESRD. The aim of this study was to determine the effect of online hemodiafiltration (HDF) versus low-flux hemodialysis (HD) on LVM, EF, and PWV. Echocardiography was used to assess LVM and EF in 342 patients in the CONvective TRAnsport STudy followed for up to 4 years. PWV was measured in 189 patients for up to 3 years. Effect of HDF versus HD on LVM, EF, and PWV was evaluated using linear mixed models. Patients had a mean age of 63 years, and 61% were male. At baseline, median LVM was 227 g (interquartile range [IQR], 183-279 g), and median EF was 65% (IQR, 55%-72%). Median PWV was 9.8 m/s (IQR, 7.5-12.0 m/s). There was no significant difference between the HDF and HD treatment groups in rate of change in LVM (HDF: change, -0.9 g/yr [95% confidence interval (95% CI), -8.9 to 7.7 g]; HD: change, 12.5 g/yr [95% CI, -3.0 to 27.5 g]; P for difference=0.13), EF (HDF: change, -0.3%/yr [95% CI, -2.3% to 1.8%]; HD: change, -3.4%/yr [95% CI, -5.9% to -0.9%]; P=0.17), or PWV (HDF: change, -0.0 m/s per year [95% CI, -0.4 to 0.4 m/s); HD: change, 0.0 m/s per year [95% CI, -0.3 to 0.2 m/s]; P=0.89). No differences in rate of change between treatment groups were observed for subgroups of age, sex, residual kidney function, dialysis vintage, history of cardiovascular disease, diabetes, or convection volume. Treatment with online HDF did not affect changes in LVM, EF, or PWV over time compared with HD.

Air pollution and heart failure: Relationship with the ejection fraction

PubMed Central

Dominguez-Rodriguez, Alberto; Abreu-Afonso, Javier; Rodríguez, Sergio; Juarez-Prera, Ruben A; Arroyo-Ucar, Eduardo; Gonzalez, Yenny; Abreu-Gonzalez, Pedro; Avanzas, Pablo

2013-01-01

AIM: To study whether the concentrations of particulate matter in ambient air are associated with hospital admission due to heart failure in patients with heart failure with preserved ejection fraction and reduced ejection fraction. METHODS: We studied 353 consecutive patients admitted into a tertiary care hospital with a diagnosis of heart failure. Patients with ejection fraction of ≥ 45% were classified as having heart failure with preserved ejection fraction and those with an ejection fraction of < 45% were classified as having heart failure with reduced ejection fraction. We determined the average concentrations of different sizes of particulate matter (< 10, < 2.5, and < 1 μm) and the concentrations of gaseous pollutants (carbon monoxide, sulphur dioxide, nitrogen dioxide and ozone) from 1 d up to 7 d prior to admission. RESULTS: The heart failure with preserved ejection fraction population was exposed to higher nitrogen dioxide concentrations compared to the heart failure with reduced ejection fraction population (12.95 ± 8.22 μg/m3 vs 4.50 ± 2.34 μg/m3, P < 0.0001). Multivariate analysis showed that nitrogen dioxide was a significant predictor of heart failure with preserved ejection fraction (odds ratio ranging from (1.403, 95%CI: 1.003-2.007, P = 0.04) to (1.669, 95%CI: 1.043-2.671, P = 0.03). CONCLUSION: This study demonstrates that short-term nitrogen dioxide exposure is independently associated with admission in the heart failure with preserved ejection fraction population. PMID:23538391

Performance of AHEAD Score in an Asian Cohort of Acute Heart Failure With Either Preserved or Reduced Left Ventricular Systolic Function.

PubMed

Chen, Yu-Jen; Sung, Shih-Hsien; Cheng, Hao-Min; Huang, Wei-Ming; Wu, Chung-Li; Huang, Chi-Jung; Hsu, Pai-Feng; Yeh, Jong-Shiuan; Guo, Chao-Yu; Yu, Wen-Chung; Chen, Chen-Huan

2017-05-04

AHEAD (A: atrial fibrillation; H: hemoglobin; E: elderly; A: abnormal renal parameters; D: diabetes mellitus) score has been related to clinical outcomes of acute heart failure. However, the prognostic value of the AHEAD score in acute heart failure patients with either reduced or preserved left ventricular ejection fraction (HFrEF and HFpEF) remain to be elucidated. The study population consisted of 2143 patients (age 77±12 years, 68% men, 38% HFrEF) hospitalized primarily for acute heart failure with a median follow-up of 23.75 months. The performance of the AHEAD score (atrial fibrillation, hemoglobin <13 mg/dL for men and 12 mg/dL for women, age >70 years, creatinine >130 μmol/L, and diabetes mellitus) was evaluated by Cox's regression analysis for predicting cardiovascular and all-cause mortality. The mean AHEAD scores were 2.7±1.2 in the total study population, 2.6±1.3 in the HFrEF group, and 2.7±1.1 in the HFpEF group. After accounting for sex, sodium, uric acid, and medications, the AHEAD score remained significantly associated with all-cause and cardiovascular mortality (hazard ratio and 95% CI: 1.49, 1.38-1.60 and 1.48, 1.33-1.64), respectively. The associations of AHEAD score with mortality remained significant in the subgroups of HFrEF (1.63, 1.47-1.82) and HFpEF (1.34, 1.22-1.48). Moreover, when we calculated a new AHEAD-U score by considering uric acid (>8.6 mg/dL) in addition to the AHEAD score, the net reclassification was improved by 19.7% and 20.1% for predicting all-cause and cardiovascular mortality, respectively. The AHEAD score was useful in predicting long-term mortality in the Asian acute heart failure cohort with either HFrEF or HFpEF. The new AHEAD-U score may further improve risk stratification. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Short- and Long-term Therapeutic Efficacies of Intravenous Transplantation of Bone Marrow Stem Cells on Cardiac Function in Rats with Acute Myocardial Infarction: A Meta-analysis of Randomized Controlled Trials.

PubMed

Jiang, Can; Zheng, Dong; Feng, Yun-Lu; Guo, Jun; Li, Hai-Rui; Zhang, Ai-Dong

2016-09-20

Objective To investigate the short- and long-term therapeutic efficacies of intravenous trans- plantation of bone marrow stem cells (MSCs) in rats with experimental myocardial infarction by meta- analysis. Methods Randomized controlled trials were systematically searched from PubMed, Science Citation Index (SCI), Chinese journal full-text database (CJFD) up to December 2014. While the experimental groups (MSCs groups) were injected MSCs intravenously, the control groups were injected Delubecco's minimum essential medium (DMEM) or phosphate buffered saline (PBS). Subgroup analysis for each outcome measure was performed for the observing time point after the transplantation of MSCs. Weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated for outcome parameters including ejection fraction (EF) and fractional shortening (FS), which were measured by echocardiogram after intravenous injection and analyzed by RevMan 5.2 and STATA 12.0. Results Data from 9 studies (190 rats) were included in the meta-analysis. As compared to the control groups, the cardiac function of the experimental groups were not improved at day 7 (EF: WMD=0.08, 95%CI -1.32 to 1.16, P>0.01; FS: WMD=-0.12, 95%CI -0.90 to 0.65, P>0.01) until at day 14 after MSCs' transplantation (EF: WMD=10.79, 95%CI 9.16 to 12.42, P<0.01; FS: WMD=11.34, 95%CI 10.44 to 12.23, P<0.01), and it lasted 4 weeks or more after transplantation of MSCs (EF: WMD=13.94, 95%CI 12.24 to 15.64, P<0.01; FS: WMD=9.64, 95%CI 7.98 to 11.31, P<0.01). Conclusion The therapeutic efficacies of MSCs in rats with myocardid infarction become increasing apparent as time advances since 2 weeks after injection.

Myocardial performance index in female rats with myocardial infarction: relationship with ventricular function parameters by Doppler echocardiography.

PubMed

Cury, Alexandre Ferreira; Bonilha, Andre; Saraiva, Roberto; Campos, Orlando; Carvalho, Antonio Carlos C; De Paola, Angelo Amato V; Fischer, Claudio; Tucci, Paulo Ferreira; Moises, Valdir Ambrosio

2005-05-01

The aim of the study was to analyze the myocardial performance index (MPI), its relationship with the standard variables of systolic and diastolic functions, and the influence of time intervals in an experimental model of female rats with myocardial infarction (MI). Forty-one Wistar female rats were submitted to surgery to induce MI. Six weeks later, Doppler echocardiography was performed to assess infarct size (IS,%), fractional area change (FAC,%), ejection fraction biplane Simpson (EF), E/A ratio of mitral inflow, MPI and its time intervals: isovolumetric contraction (IVCT, ms) and relaxation (IVRT, ms) times, and ejection time (ET, ms); MPI = IVCT + IVRT/ET. EF and FAC were progressively lower in rats with small, medium and large-size MI ( P < .001). E/A ratio was higher only in rats with large-size MI (6.25 +/- 2.69; P < .001). MPI was not different between control rats and small-size MI (0.37 +/- 0.03 vs 0.34 +/- 0.06, P = .87), but different between large and medium-size MI (0.69 +/- 0.08 vs 0.47 +/- 0.07; P < .001) and between these two compared to small-size MI. MPI correlated with IS (r = 0.85; P < .001), EF (r = -0.86; P < .001), FAC (r = -0.77; P < .001) and E/A ratio (r = 0.77; P < .001, non-linear). IVCT was longer in large size MI compared to medium-size MI (31.87 +/- 7.99 vs 15.92 +/- 5.88; P < .001) and correlated with IS (r = 0.85; P < .001) and MPI (r = 0.92; P < .001). ET was shorter only in large-size MI (81.07 +/- 7.23; P < .001), and correlated with IS (r = -0.70; P < .001) and MPI (r = -0.85; P < .001). IVRT was shorter only in large-size compared to medium-size MI (24.40 +/- 5.38 vs 29.69 +/- 5.92; P < .037), had borderline correlation with MPI (r = 0.34; P = .0534) and no correlation with IS (r = 0.26; p = 0.144). The MPI increased with IS, correlated inversely with systolic function parameters and had a non-linear relationship with diastolic function. These changes were due to the increase of IVCT and a decrease of ET, without significant influence of IVRT.

LCZ696, an angiotensin receptor-neprilysin inhibitor, improves cardiac function with the attenuation of fibrosis in heart failure with reduced ejection fraction in streptozotocin-induced diabetic mice.

PubMed

Suematsu, Yasunori; Miura, Shin-Ichiro; Goto, Masaki; Matsuo, Yoshino; Arimura, Tadaaki; Kuwano, Takashi; Imaizumi, Satoshi; Iwata, Atsushi; Yahiro, Eiji; Saku, Keijiro

2016-04-01

Angiotensin receptor-neprilysin inhibitors (ARNis) acts an ARB and neprilysin inhibitor. Diabetes mellitus significantly increases the risk of cardiovascular disease and heart failure (HF). Therefore, we evaluated the effects and mechanisms of ARNi in HF with reduced ejection fraction (HFrEF) in streptozotocin-induced diabetic mice. Male C57BL/6J mice were injected with streptozotocin to produce diabetic mice. After myocardial reperfusion injury, diabetic mice were randomized to treatment for 4 weeks with LCZ696 (60 mg/kg), valsartan (30 mg/kg), or no treatment (n = 26-28 in each group). Cardiac function was assessed by a pressure-volume Millar catheter. The ratios of heart weight to body weight in the valsartan (P = 0.02) and LCZ696 (P = 0.005) groups were significantly less than that in the control group. Treatment with LCZ696 improved LVEF (43 ± 3.4%) with a significantly reduction of atrial natriuretic peptide mRNA in the left ventricle compared with that in the control group (29 ± 3.2%) (P = 0.006). The fibrotic area in the LCZ696 group was significantly suppressed compared with those in the control (P = 0.003) and valsartan (P = 0.04) groups. Moreover, the mRNA level of transforming growth factor-β (TGF-β) in the left ventricle was suppressed in the LCZ696 group compared with that in the control (P = 0.002) group. The ARNi LCZ696 improved cardiac function with the reduction of fibrosis in an HF-rEF model in diabetic mice, by suppressing TGF-β. This effect may be due to the specific inhibition of neprilysin, beyond the ARB effect of LCZ696. © 2016 The Authors European Journal of Heart Failure © 2016 European Society of Cardiology.

Plasma osmolality predicts mortality in patients with heart failure with reduced ejection fraction.

PubMed

Kaya, HakkI; Yücel, Oğuzhan; Ege, Meltem Refiker; Zorlu, Ali; Yücel, Hasan; Güneş, Hakan; Ekmekçi, Ahmet; Yılmaz, Mehmet Birhan

2017-01-01

Heart failure (HF) is a fatal disease. Plasma osmolality with individual impacts of sodium, blood urea nitrogen (BUN), and glucose has not been studied prognostically in patients with HF. This study aims to investigate the impact of serum osmolality on clinical endpoints in HF patients. A total of 509 patients (383 males, 126 females) with HF with reduced ejection fraction in three HF centres were retrospectively analysed between January 2007 and December 2013. Follow-up data were completed for 496 patients. Plasma osmolality was calculated as (2 × Na) + (BUN/2.8) + (Glucose/18). Quartiles of plasma osmolality were produced, and the possible relationship between plasma osmolality and cardiovascular mortality was investigated. The mean follow-up was 25 ± 22 months. The mean age was 56.5 ± 17.3 years with a mean EF of 26 ± 8%. The mean levels of plasma osmolality were as follows in the quartiles: 1st % = 280 ± 6, 2nd % = 288 ± 1, 3rd % = 293 ± 2 (95% confidence interval [CI] 292.72-293.3), and 4th % = 301 ± 5 mOsm/kg. The EF and B-type natriuretic peptide levels were similar in the four quartiles. Univariate and multivariate analyses in the Cox proportional hazard model revealed a significantly higher rate of mortality in the patients with hypo-osmolality. The Kaplan-Meier plot showed graded mortality curves with the 1st quartile having the worst prognosis, followed by the 4th quartile and the 2nd quartile, while the 3rd quartile was shown to have the best prognosis. Our study results suggest that normal plasma osmolality is between 275 and 295 mOsm/kg. However, being close to the upper limit of normal range (292-293 mOsm/kg) seems to be the optimal plasma osmolality level in terms of cardiovascular prognosis in patients with HF.

Diagnostic and Prognostic Value of Long-Axis Strain and Myocardial Contraction Fraction Using Standard Cardiovascular MR Imaging in Patients with Nonischemic Dilated Cardiomyopathies.

PubMed

Arenja, Nisha; Riffel, Johannes H; Fritz, Thomas; André, Florian; Aus dem Siepen, Fabian; Mueller-Hennessen, Matthias; Giannitsis, Evangelos; Katus, Hugo A; Friedrich, Matthias G; Buss, Sebastian J

2017-06-01

Purpose To assess the utility of established functional markers versus two additional functional markers derived from standard cardiovascular magnetic resonance (MR) images for their incremental diagnostic and prognostic information in patients with nonischemic dilated cardiomyopathy (NIDCM). Materials and Methods Approval was obtained from the local ethics committee. MR images from 453 patients with NIDCM and 150 healthy control subjects were included between 2005 and 2013 and were analyzed retrospectively. Myocardial contraction fraction (MCF) was calculated by dividing left ventricular (LV) stroke volume by LV myocardial volume, and long-axis strain (LAS) was calculated from the distances between the epicardial border of the LV apex and the midpoint of a line connecting the origins of the mitral valve leaflets at end systole and end diastole. Receiver operating characteristic curve, Kaplan-Meier method, Cox regression, and classification and regression tree (CART) analyses were performed for diagnostic and prognostic performances. Results LAS (area under the receiver operating characteristic curve [AUC] = 0.93, P < .001) and MCF (AUC = 0.92, P < .001) can be used to discriminate patients with NIDCM from age- and sex-matched control subjects. A total of 97 patients reached the combined end point during a median follow-up of 4.8 years. In multivariate Cox regression analysis, only LV ejection fraction (EF) and LAS independently indicated the combined end point (hazard ratio = 2.8 and 1.9, respectively; P < .001 for both). In a risk stratification approach with classification and regression tree analysis, combined LV EF and LAS cutoff values were used to stratify patients into three risk groups (log-rank test, P < .001). Conclusion Cardiovascular MR-derived MCF and LAS serve as reliable diagnostic and prognostic markers in patients with NIDCM. LAS, as a marker for longitudinal contractile function, is an independent parameter for outcome and offers incremental information beyond LV EF and the presence of myocardial fibrosis. © RSNA, 2017 Online supplemental material is available for this article.

Usefulness of the Left Ventricular Myocardial Contraction Fraction in Healthy Men and Women to Predict Cardiovascular Morbidity and Mortality

PubMed Central

Chuang, Michael L.; Gona, Philimon; Salton, Carol J.; Yeon, Susan B.; Kissinger, Kraig V.; Blease, Susan J.; Levy, Daniel; O'Donnell, Christopher J.; Manning, Warren J.

2013-01-01

We sought to determine whether depressed myocardial contraction fraction (MCF, the ratio of left ventricular (LV) stroke volume to myocardial volume) predicts cardiovascular disease (CVD) events in initially healthy adults. A subset (N=318, 60±9 yrs, 158 men) of the Framingham Heart Study Offspring cohort free of clinical CVD underwent volumetric cardiovascular magnetic resonance (CMR) imaging in 1998–1999. LV ejection fraction (EF), mass and MCF were determined. “Hard” CVD events comprised cardiovascular death, myocardial infarction, stroke or new heart failure. A Cox proportional hazards model adjusting for Framingham Coronary Risk Score (FCRS) was used to estimate hazard ratios for incident hard CVD events for sex-specific quartiles of MCF, LV mass and LVEF. The lowest quartile of LV mass and highest quartiles of MCF and EF served as referent. Kaplan-Meier survival plots and the log rank test were used to compare event-free survival. MCF was greater in women (0.58±0.13) than men (0.52±0.11), p<0.01. Nearly all (99%) participants had EF ≥ 0.55. Over up to 9-year (median 5.2) follow-up, 31 participants (10%) experienced an incident hard CVD event. Lowest-quartile MCF was 7 times more likely to develop hard CVD (hazard ratio 7.11, p=0.010) compared to the lowest quartile, and the elevated hazards persisted even after adjustment for LV mass (hazard ratio=6.09, p=0.020). The highest-quartile LV mass/height2.7 had nearly five-fold risk (hazard ratio 4.68, p=0.016). Event-free survival was shorter in lowest-quartile MCF, p = 0.0006, but not in lowest-quartile LVEF. Conclusion: In a cohort of adults initially without clinical CVD, lowest-quartile MCF conferred an increased hazard for hard CVD events after adjustment for traditional CVD risk factors and LV mass. PMID:22381161

Usefulness of the left ventricular myocardial contraction fraction in healthy men and women to predict cardiovascular morbidity and mortality.

PubMed

Chuang, Michael L; Gona, Philimon; Salton, Carol J; Yeon, Susan B; Kissinger, Kraig V; Blease, Susan J; Levy, Daniel; O'Donnell, Christopher J; Manning, Warren J

2012-05-15

We sought to determine whether depressed myocardial contraction fraction (MCF; ratio of left ventricular [LV] stroke volume to myocardial volume) predicts cardiovascular disease (CVD) events in initially healthy adults. A subset (n = 318, 60 ± 9 years old, 158 men) of the Framingham Heart Study Offspring cohort free of clinical CVD underwent volumetric cardiovascular magnetic resonance imaging in 1998 through 1999. LV ejection fraction (EF), mass, and MCF were determined. "Hard" CVD events consisted of cardiovascular death, myocardial infarction, stroke, or new heart failure. A Cox proportional hazards model adjusting for Framingham Coronary Risk Score was used to estimate hazard ratios for incident hard CVD events for gender-specific quartiles of MCF, LV mass, and LVEF. The lowest quartile of LV mass and highest quartiles of MCF and EF served as referents. Kaplan-Meier survival plots and log-rank test were used to compare event-free survival. MCF was greater in women (0.58 ± 0.13) than in men (0.52 ± 0.11, p <0.01). Nearly all participants (99%) had EF ≥0.55. During an up to 9-year follow-up (median 5.2), 31 participants (10%) developed an incident hard CVD event. Lowest-quartile MCF was 7 times more likely to develop a hard CVD (hazard ratio 7.11, p = 0.010) compared to the remaining quartiles, and increased hazards persisted even after adjustment for LV mass (hazard ratio 6.09, p = 0.020). The highest-quartile LV mass/height 2.7 had a nearly fivefold risk (hazard ratio 4.68, p = 0.016). Event-free survival was shorter in lowest-quartile MCF (p = 0.0006) but not in lowest-quartile LVEF. In conclusion, in a cohort of adults initially without clinical CVD, lowest-quartile MCF conferred an increased hazard for hard CVD events after adjustment for traditional CVD risk factors and LV mass. Copyright © 2012 Elsevier Inc. All rights reserved.

The relationship between ischemia-induced left ventricular dysfunction, coronary flow reserve, and coronary steal on regadenoson stress-gated (82)Rb PET myocardial perfusion imaging.

PubMed

Van Tosh, Andrew; Votaw, John R; Reichek, Nathaniel; Palestro, Christopher J; Nichols, Kenneth J

2013-12-01

Gated rubidium-82 ((82)Rb) positron emission tomography (PET) imaging studies are acquired both at rest and during pharmacologic stress. Stress-induced ischemic left ventricular dysfunction (LVD) can produce a significant decrease in left ventricular ejection fraction (LVEF) from rest to stress. We determined the prevalence on PET of stress LVD with reduced ejection fraction (EF) and its association with absolute global and regional coronary flow reserve (CFR), and with relative perfusion defect summed difference score (SDS). We studied 205 patients with known or suspected coronary disease (120 M, 75 F, age 69 ± 13 years) who had clinically indicated rest/regadenoson stress (82)Rb PET/CT studies. Data were acquired in dynamic gated list mode. Global and 17-segment regional CFR values were computed from first-pass flow data using a 2-compartment model and factor analysis applied to auto-generated time-activity curves. Rest and stress LVEF and SDS were quantified from gated equilibrium myocardial perfusion tomograms using Emory Cardiac Toolbox software. LVD was defined as a change in LVEF of ≤-5% from rest to stress. A subgroup of 109 patients also had coronary angiography. Stress LVD developed in 32 patients (16%), with mean EF change of -10 ± 5%, vs +6 ± 7% for patients without LVD (P < .0001). EF was similar at rest in patients with and without stress LVD (57 ± 18% vs 56 ± 16%, P = .63), but lower during stress for patients with LVD (47 ± 20% vs 61 ± 16%, P = .0001). CFR was significantly lower in patients with LVD (1.61 ± 0.67 vs 2.21 ± 1.03, Wilcoxon P = .002), and correlated significantly with change in EF (r = 0.35, P < .0001), but not with SDS (r = -0.13, P = .07). The single variable most strongly associated with high risk of CAD (i.e., left main stenosis ≥50%, LAD % stenosis ≥70%, and/or 3-vessel disease) was stress EF (χ(2) = 17.3, P < .0001). There was a higher prevalence of patients with territorial CFR values ≤1.0, consistent with coronary steal, in the LVD group than in the non-LVD group (39% vs 12%, P = .001). LVD developed in 16% of patients undergoing (82)Rb PET myocardial perfusion imaging, and was associated with multivessel coronary artery disease. There was a significant relationship between LVD and coronary blood flow during stress, with LVD corresponding to a low CFR. Territorial CFR ≤1.0 was more common in patients with LVD than those without, suggesting that coronary steal is an important pathophysiologic mechanism contributing to pharmacologic stress-induced LVD.

From Statistical Significance to Clinical Relevance: A Simple Algorithm to Integrate BNP and the Seattle Heart Failure Model for Risk Stratification in Heart Failure

PubMed Central

AbouEzzeddine, Omar F.; French, Benjamin; Mirzoyev, Sultan A.; Jaffe, Allan S; Levy, Wayne C.; Fang, James C.; Sweitzer, Nancy K.; Cappola, Thomas P.; Redfield, Margaret M.

2016-01-01

Background Heart failure (HF) guidelines recommend brain natriuretic peptide (BNP) and multivariable risk-scores such as the Seattle HF Model (SHFM) to predict risk in HF with reduced ejection fraction (HFrEF). A practical way to integrate information from these two prognostic tools is lacking. We sought to establish a SHFM+BNP risk-stratification algorithm. Methods The retrospective derivation cohort included consecutive patients with HFrEF at Mayo. One-year outcome (death, transplantation or ventricular assist device) was assessed. The SHFM+BNP algorithm was derived by stratifying patients within SHFM-predicted risk categories (≤2.5%, 2.6–≤10%, >10%) according to BNP above or below 700 pg/mL and comparing SHFM-predicted and observed event rates within each SHFM+BNP category. The algorithm was validated in a prospective, multicenter HFrEF registry (Penn HF Study). Results Derivation (n=441; one-year event rate 17%) and validation (n=1513; one-year event rate 12%) cohorts differed with the former being older and more likely ischemic with worse symptoms, lower EF, worse renal function, higher BNP and SHFM scores. In both cohorts, across the three SHFM-predicted risk strata, a BNP>700 pg/ml consistently identified patients with approximately three-fold the risk that the SHFM would have otherwise estimated regardless stage of HF, intensity and duration of HF-therapy, and comorbidities. Conversely, the SHFM was appropriately calibrated in patients with a BNP<700 pg/ml. Conclusion The simple SHFM+BNP algorithm displays stable performance across diverse HFrEF cohorts and may enhance risk stratification to enable appropriate decisions regarding HF therapeutic or palliative strategies. PMID:27021278

Evaluation of Chronic Obstructive Pulmonary Disease (COPD) and reduced ejection fraction heart failure (HFrEF) discharge medication prescribing: Is drug therapy concordant with national guidelines associated with a reduction in 30-day readmissions?

PubMed

Richardson, Amy; Tolley, Elizabeth; Hartmann, Jonathan; Reedus, Jasmine; Bowlin, Brandi; Finch, Christopher; Sands, Christopher W; Self, Timothy

2016-10-01

Approximately 1 in 5 hospitalized COPD patients are readmitted within 30 days of discharge. CHF coexists in more than 20% of patients with COPD, and is associated with early readmission for COPD. Reducing 30-day hospital readmissions for COPD is of intense current interest. A retrospective chart review was performed to identify patients discharged with COPD exacerbation and HFrEF. The primary objective was to evaluate if discharge medication prescribing following guidelines for both COPD and HFrEF correlates with reduced 30-day readmission rates. The study included 281 admissions with 39.1% prescribed appropriate discharge medications for both COPD and HFrEF; 30-day readmission rate was 24.5% for these patients compared to 31.1% that were not prescribed appropriate medications (p = 0.24). Beta blockers, ACE inhibitors or ARBS, and aldosterone antagonists were under-prescribed, but this did not significantly associate with increased readmission (p = 0.51, p = 0.23 or 0.99, and p = 0.18, respectively). Those prescribed hydralazine or nitrates were more likely to readmit (both p = 0.01). Diabetes and hyperlipidemia were associated with increased readmission (p = 0.01 and 0.05). This study did not show a significant difference in 30-day readmission rate based on appropriate discharge medications for both COPD and HFrEF. The comorbidities diabetes and hyperlipidemia and prescription of hydralazine or nitrates were significantly associated with increased readmission rate. Larger patient populations may be needed to assess if guideline based discharge medication prescribing is associated with reduced 30-day readmissions for COPD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial.

PubMed

Pitt, Bertram; Kober, Lars; Ponikowski, Piotr; Gheorghiade, Mihai; Filippatos, Gerasimos; Krum, Henry; Nowack, Christina; Kolkhof, Peter; Kim, So-Young; Zannad, Faiez

2013-08-01

Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced left ventricular ejection fraction (HFrEF), but their use is limited by hyperkalaemia and/or worsening renal function (WRF). BAY 94-8862 is a highly selective and strongly potent non-steroidal MRA. We investigated its safety and tolerability in patients with HFrEF associated with mild or moderate chronic kidney disease (CKD). This randomized, controlled, phase II trial consisted of two parts. In part A, the safety and tolerability of oral BAY 94-8862 [2.5, 5, or 10 mg once daily (q.d.)] was assessed in 65 patients with HFrEF and mild CKD. In part B, BAY 94-8862 (2.5, 5, or 10 mg q.d., or 5 mg twice daily) was compared with placebo and open-label spironolactone (25 or 50 mg/day) in 392 patients with HFrEF and moderate CKD. BAY 94-8862 was associated with significantly smaller mean increases in serum potassium concentration than spironolactone (0.04-0.30 and 0.45 mmol/L, respectively, P < 0.0001-0.0107) and lower incidences of hyperkalaemia (5.3 and 12.7%, respectively, P = 0.048) and WRF. BAY 94-8862 decreased the levels of B-type natriuretic peptide (BNP), amino-terminal proBNP, and albuminuria at least as much as spironolactone. Adverse events related to BAY 94-8862 were infrequent and mostly mild. In patients with HFrEF and moderate CKD, BAY 94-8862 5-10 mg/day was at least as effective as spironolactone 25 or 50 mg/day in decreasing biomarkers of haemodynamic stress, but it was associated with lower incidences of hyperkalaemia and WRF.

Laparoscopic cholecystectomy for biliary dyskinesia in children: frequency increasing.

PubMed

Lacher, Martin; Yannam, Govardhana R; Muensterer, Oliver J; Aprahamian, Charles J; Haricharan, Ramanath N; Perger, Lena; Bartle, Donna; Talathi, Sonia S; Beierle, Elizabeth A; Anderson, Scott A; Chen, Mike K; Harmon, Carroll M

2013-08-01

The treatment of children with biliary dyskinesia (BD) is controversial. As we recently observed an increasing frequency of referrals for BD in our institution the aim of the study was to re-evaluate the long-term outcome in children with BD. Children with laparoscopic cholecystectomy (LC) for suspected BD between 8/2006 and 5/2011 were included. A pathologic ejection fraction (EF) was defined as <35%. The long-term effect of cholecystectomy was assessed via a Likert scale symptom questionnaire. 82 children (median age 13.5 years, mean BMI 25.8) were included. CCK-HIDA scan was pathologic in 74 children (90.2%). Mean EF was 16.4%. Histology revealed chronic cholecystitis in 48 (58.5%) children and was normal in 30 children (36.5%). The frequency of LC for suspected BD increased by a factor of 4.3 in the last 10 years. Long term follow-up showed that only 23/52 children (44.2%) were symptom-free after LC. Patients with chronic inflammation were more likely to have persistent symptoms (p=0.017). An EF<15% was associated with a resolution of symptoms (p=0.031). The frequency of LC for suspected BD in our institution has increased significantly during recent years. The long-term efficacy in our cohort was only 44.2%. We believe that laparoscopic cholecystectomy is likely helpful in patients with an EF<15%. However, in children with an EF of 15%-35%, based upon our data, we would highly recommend an appropriately thorough pre-op testing to exclude other gastrointestinal disorders prior to consideration of operative management. Copyright © 2013 Elsevier Inc. All rights reserved.

Sacubitril/Valsartan (LCZ696) in Heart Failure.

PubMed

Khder, Yasser; Shi, Victor; McMurray, John J V; Lefkowitz, Martin P

2017-01-01

It has been known since the 1990s that long-term morbidity and mortality is improved in patients with heart failure with reduced ejection fraction (HFrEF) by treatments that target the renin-angiotensin-aldosterone system (RAAS). It has also long been thought that enhancement of the activity of natriuretic peptides (NPs) could potentially benefit patients with HFrEF, but multiple attempts to realize this benefit had failed over the years - until 2014, when a large, phase III, randomized, controlled clinical trial (PARADIGM-HF) was completed comparing sacubitril/valsartan with enalapril, a well-established treatment for HFrEF. Sacubitril/valsartan (formerly known as LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) that simultaneously suppresses RAAS activation through blockade of angiotensin II type 1 receptors and enhances vasoactive peptides including NPs through inhibition of neprilysin, the enzyme responsible for their degradation. In PARADIGM-HF, patients with HFrEF treated with sacubitril/valsartan had 20% less risk for cardiovascular death or hospitalization for heart failure (the primary endpoint), 20% less risk for cardiovascular death, 21% less risk for first hospitalization for heart failure, and 16% less risk for death from any cause, compared with enalapril (all p < 0.001). Concerning tolerability, the sacubitril/valsartan group had higher proportions of patients with hypotension and nonserious angioedema but lower proportions with renal impairment, hyperkalemia, and cough, compared with the enalapril group. The use of sacubitril/valsartan has been endorsed by the latest heart failure treatment guidelines in Europe and the USA. This chapter reviews the discoveries, scientific reasoning, and clinical evidence that led to the development of sacubitril/valsartan, the first novel therapy in a new drug class to improve survival in HFrEF in the last 15 years.

The relationship between potency of oxidative stress and severity of dilated cardiomyopathy.

PubMed

Demirbag, Recep; Yilmaz, Remzi; Erel, Ozcan; Gultekin, Unal; Asci, Durmus; Elbasan, Zafer

2005-08-01

It has been suggested that oxidative stress may have a role in the etiopathogenesis of congestive heart failure. To investigate and compare the oxidative-antioxidative status and oxidative stress index (OSI) of patients with idiopathic dilated cardiomyopathy (IDC) with those of healthy volunteers, and to determine the relationship between total antioxidant capacity (TAC) and ejection fraction (EF). Twenty-eight patients with IDC and 24 control subjects were enrolled in the study. Antioxidative status was evaluated by measuring the TAC and the vitamin C and thiol levels in the plasma. Oxidative status was evaluated by measuring the total peroxide level. The per cent ratio of TAC to total peroxide level was accepted as the OSI. EF was measured using Simpson's method. TAC and vitamin C and thiol levels of plasma were found to be significantly lower in patients with IDC than in control subjects (P < 0.001). In contrast, total peroxide levels and OSIs were significantly higher in patients with IDC than in control subjects (P = 0.002 and P = 0.002, respectively). An important positive correlation was found between TAC and EF (r = 0.772; P < 0.001). On the other hand, significant negative correlations were found between EF and OSI and between EF and total peroxide levels in patients. Oxidants are increased and antioxidants are decreased in patients with IDC; as a result, the oxidative-antioxidative balance is shifted to the oxidative side. There is a significant correlation between the potency of oxidative stress and the severity of IDC. It is believed that supplementation of antioxidants in the treatment of IDC may be helpful to these patients.

Enalapril and losartan are more effective than carvedilol in preventing dilated cardiomyopathy in the Syrian cardiomyopathic hamster.

PubMed

Crespo, Maria J; Cruz, Nildris; Altieri, Pablo I; Escobales, Nelson

2008-09-01

To assess the role of the renin-angiotensin (RAS) and adrenergic systems in the development and progression of dilated cardiomyopathy in the Syrian cardiomyopathic hamster (SCH), echocardiographic parameters were evaluated in 6-month-old animals after 5 months of treatment with enalapril (25 mg/kg/day) plus losartan (10 mg/kg/day), or with carvedilol (1 mg/kg/day). Cardiac output indexes (COI) increased by 53% after RAS blockade and by 20% after beta-blockade in SCH. Moreover, LVEDV and LVESV decreased 30% and 62%, respectively (P < .05) during RAS blockade, whereas ejection fraction (EF) increased by 48%. By contrast, carvedilol reduced LVESV by only 28% (P < .05) and increased EF by only 15% (P < .05). These results suggest that RAS activation plays a critical role in the development of cardiac dysfunction in SCH and that suppression of RAS may be more effective than beta-blockade in retarding the development of cardiomyopathy in SCH. Owing to timing (pre-heart failure stage) and to the single dose protocol, the implications of this study for human subjects remain to be clarified.

Finerenone : third-generation mineralocorticoid receptor antagonist for the treatment of heart failure and diabetic kidney disease.

PubMed

Liu, Licette C Y; Schutte, Elise; Gansevoort, Ron T; van der Meer, Peter; Voors, Adriaan A

2015-01-01

The mineralocorticoid receptor antagonists (MRAs) spironolactone and eplerenone reduce the risk of hospitalizations and mortality in patients with heart failure (HF) with reduced ejection fraction (HFrEF), and attenuate progression of diabetic kidney disease. However, their use is limited by the fear of inducing hyperkalemia, especially in patients with renal dysfunction. Finerenone is a novel nonsteroidal MRA, with higher selectivity toward the mineralocorticoid receptor (MR) compared to spironolactone and stronger MR-binding affinity than eplerenone. This paper discusses the chemistry, pharmacokinetics, clinical efficacy and safety of finerenone. The selectivity and greater binding affinity of finerenone to the MR may reduce the risk of hyperkalemia and renal dysfunction and thereby overcome the reluctance to start and uptitrate MRAs in patients with HF and diabetic kidney disease. Studies conducted in patients with HFrEF and moderate chronic kidney disease and diabetic kidney disease, showed promising results. Phase III trials will have to show whether finerenone might become the third-generation MRA for the treatment of HF and diabetic kidney disease.

The intraventricular filling vortex under heightened aortic blood pressure

NASA Astrophysics Data System (ADS)

Nelsen, Nicholas; Gaddam, Manikantam; Santhanakrishnan, Arvind

2017-11-01

Hypertension, or high aortic blood pressure, can induce structural changes in the left ventricle (LV) such as concentric hypertrophy. Previous studies have identified that the intraventricular filling vortex serves as an effective means of blood transport during diastolic filling. However, a fundamental understanding of how hypertension affects this vortex is unavailable. This knowledge can be useful for improving diagnosis and treatment of related heart disease conditions, including hypertensive heart failure. In this experimental study, we hypothesized that the circulation of the filling vortex would diminish with increased aortic pressure. Using a LV physical model within a left heart simulator, we performed hemodynamic measurements to acquire pressure and volumetric inflow profiles and 2D particle image velocimetry to visualize the intraventricular flow fields. Peak aortic pressures of 120 mm Hg, 140 mm Hg, and 160 mm Hg were each tested at heart rates of 70, 100, and 110 beats per minute, under: 1) reduced ejection fraction (EF), and 2) constant EF. Our results indicate that peak vortex circulation is reduced under elevated aortic pressures. Hemodynamics and characteristics of the intraventricular filling vortex in all examined experimental cases will be presented.

Value of speckle tracking for the assessment of right ventricular function in patients operated on for tetralogy of fallot. Comparison with magnetic resonance imaging.

PubMed

Bernard, Yvette; Morel, Mathilde; Descotes-Genon, Vincent; Jehl, Jerome; Meneveau, Nicolas; Schiele, Francois

2014-04-01

Right ventricular (RV) function is a major prognostic factor in patients (pts) with operated tetralogy of Fallot (TOF). We compared the results of RV speckle tracking (two-dimensional [2D] strain) with those of magnetic resonance imaging (MRI) in this setting. At transthoracic echocardiogram (echo), RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), velocity of S-wave at tricuspid annulus with tissue Doppler, and 2D strain (longitudinal maximal systolic strain) were recorded. Their results were compared to RV indexed end-diastolic volume (EDV), indexed end-systolic volume (ESV), and RV ejection fraction (EF) at MRI. Twenty-two pts (16 M) aged 11-62 years (mean 23.2 ± 10.8) were included. Parameters of RV systolic function were as follows: RVFAC = 40 ± 10%, TAPSE = 18 ± 4 mm, S-wave = 10 ± 0.2 cm/sec, and RV EF at MRI = 43 ± 11%. Global RV systolic strain was -15.5 ± 4.2%, free wall strain was -15.1 ± 6.3%, and septal strain was -15.8 ± 3.8% on average for the whole group. Echo indexed RV end-diastolic area correlated with EDV at MRI (r = 0.73), as well as echo indexed RV end-systolic area and ESV at MRI (r = 0.71). Global RV 2D strain correlated well with RV EF at MRI: r = 0.68; P < 0.05, and with ESV at MRI: r = 0.63. Feasibility, intra- and inter-observer reproducibility of 2D strain were adequate. Speckle tracking is a promising method to estimate RV systolic function in pts operated on for TOF. © 2013, Wiley Periodicals, Inc.

Correlation of trabeculae and papillary muscles with clinical and cardiac characteristics and impact on CMR measures of LV anatomy and function.

PubMed

Chuang, Michael L; Gona, Philimon; Hautvast, Gilion L T F; Salton, Carol J; Blease, Susan J; Yeon, Susan B; Breeuwer, Marcel; O'Donnell, Christopher J; Manning, Warren J

2012-11-01

The goal of this study was to assess the relationship of left ventricular (LV) trabeculae and papillary muscles (TPM) with clinical characteristics in a community-based, free-living adult cohort and to determine the effect of TPM on quantitative measures of LV volume, mass, and ejection fraction (EF). Hypertrabeculation has been associated with adverse cardiovascular events, but the distribution and clinical correlates of the volume and mass of the TPM in a normal left ventricle have not been well characterized. Short-axis cine cardiac magnetic resonance images, obtained using a steady-state free precession sequence from 1,494 members of the Framingham Heart Study Offspring cohort, were analyzed with software that automatically segments TPM. Absolute TPM volume, TPM as a fraction of end-diastolic volume (EDV) (TPM/EDV), and TPM mass as a fraction of LV mass were determined in all offspring and in a referent group of offspring free of clinical cardiovascular disease and hypertension. In the referent group (mean age 61 ± 9 years; 262 men and 423 women), mean TPM was 23 ± 3% of LV EDV in both sexes (p = 0.9). TPM/EDV decreased with age (p < 0.02) but was not associated with body mass index. TPM mass as a fraction of LV mass was inversely correlated with age (p < 0.0001), body mass index (p < 0.018), and systolic blood pressure (p < 0.0001). Among all 1,494 participants (699 men), LV volumes decreased 23%, LV mass increased 28%, and EF increased by 7.5 EF units (p < 0.0001) when TPM were considered myocardial mass rather than part of the LV blood pool. Global cardiac magnetic resonance LV parameters were significantly affected by whether TPM was considered as part of the LV blood pool or as part of LV mass. Our cross-sectional data from a healthy referent group of adults free of clinical cardiovascular disease demonstrated that TPM/EDV decreases with increasing age in both sexes but is not related to hypertension or obesity. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Noninvasive iPhone Measurement of Left Ventricular Ejection Fraction Using Intrinsic Frequency Methodology.

PubMed

Pahlevan, Niema M; Rinderknecht, Derek G; Tavallali, Peyman; Razavi, Marianne; Tran, Thao T; Fong, Michael W; Kloner, Robert A; Csete, Marie; Gharib, Morteza

2017-07-01

The study is based on previously reported mathematical analysis of arterial waveform that extracts hidden oscillations in the waveform that we called intrinsic frequencies. The goal of this clinical study was to compare the accuracy of left ventricular ejection fraction derived from intrinsic frequencies noninvasively versus left ventricular ejection fraction obtained with cardiac MRI, the most accurate method for left ventricular ejection fraction measurement. After informed consent, in one visit, subjects underwent cardiac MRI examination and noninvasive capture of a carotid waveform using an iPhone camera (The waveform is captured using a custom app that constructs the waveform from skin displacement images during the cardiac cycle.). The waveform was analyzed using intrinsic frequency algorithm. Outpatient MRI facility. Adults able to undergo MRI were referred by local physicians or self-referred in response to local advertisement and included patients with heart failure with reduced ejection fraction diagnosed by a cardiologist. Standard cardiac MRI sequences were used, with periodic breath holding for image stabilization. To minimize motion artifact, the iPhone camera was held in a cradle over the carotid artery during iPhone measurements. Regardless of neck morphology, carotid waveforms were captured in all subjects, within seconds to minutes. Seventy-two patients were studied, ranging in age from 20 to 92 years old. The main endpoint of analysis was left ventricular ejection fraction; overall, the correlation between ejection fraction-iPhone and ejection fraction-MRI was 0.74 (r = 0.74; p < 0.0001; ejection fraction-MRI = 0.93 × [ejection fraction-iPhone] + 1.9). Analysis of carotid waveforms using intrinsic frequency methods can be used to document left ventricular ejection fraction with accuracy comparable with that of MRI. The measurements require no training to perform or interpret, no calibration, and can be repeated at the bedside to generate almost continuous analysis of left ventricular ejection fraction without arterial cannulation.

Effect of Shenxinning decoction on ventricular remodeling in AT1 receptor-knockout mice with chronic renal insufficiency.

PubMed

Yang, Xuejun; Zhou, Hua; Qu, Huiyan; Liu, Weifang; Huang, Xiaojin; Shun, Yating; He, Liqun

2014-01-01

To observe the efficacy of Shenxinning Decoction (SXND) in ventricular remodeling in AT1 receptor-knockout (AT1-KO) mice with chronic renal insufficiency (CRI). AT1-KO mice modeled with subtotal (5/6) nephrectomy were intervened with SXND for 12 weeks. Subsequently, blood urea nitrogen (BUN), serum creatinine (SCr), brain natriuretic peptide (BNP), echocardiography (left ventricular end-diastolic diameter, LVDD; left ventricular end-systolic diameter, LVDS; fractional shortening, FS; and ejection fraction, EF), collagen types I and III in the heart and kidney, myocardial mitochondria, and cardiac transforming growth factor-β1 (TGF-β1) of the AT1-KO mice were compared with the same model with nephrectomy only and untreated with SXND. AT1-KO mice did not affect the process of CRI but it could significantly affect cardiac remodeling process. SXND decreased to some extent the AT1-KO mice's BUN, SCr, BNP, and cardiac LVDD, LVDS, and BNP, improved FS and EF, lowered the expression of collagen type I and III in heart and kidney, increased the quantity of mitochondria and ameliorated their structure, and down-regulated the expression of TGF-β1. SXND may antagonize the renin-angiotensin system (RAS) and decrease uremia toxins, thereby ameliorating ventricular remodeling in CRI. Furthermore, SXND has a mechanism correlated with the improvement of myocardial energy metabolism and the down-regulation of TGF-β1.

A prospective study of venous hemodynamics and quality of live at least five years after varicose vein stripping.

PubMed

Uema, Rogerio Takeyoshi; Dezotti, Nei Rodrigues Alves; Joviliano, Edwaldo Edner; Dalio, Marcelo Bellini; Moriya, Takachi; Piccinato, Carlos Eli

2013-11-01

To assess venous hemodynamics and quality of life at lest five years after varicose vein stripping. We conducted a prospective study with 39 patients (63 limbs) with primary lower limbs varicose veins. Preoperatively, all patients were subjected to clinical evaluation, duplex ultrassound, air plethysmography (APG), and CIVIQ questionnaire of quality of life. By APG, venous filling index (VFI), ejection fraction (EF), and residual volume fraction (RVF) were determined. CIVIQ addresses four domains in course of 20 questions, including states of physical, social, and psychological well-being, and pain level. Varicose veins were treated by standard venous stripping. At least five years after surgery (77.9 ± 10.9 months), patients were reassessed and had clinical examination, duplex ultrasound, APG, and CIVIQ repeated. No late follow-up data was available for 24 patients. Preoperative and late postoperative VFI levels were similar, whereas EF (P=0.05) and RVF (P=0.01), as hemodynamic variables, significantly improved following surgery. In the late postoperative period, overall CIVIQ scores were significantly lower (P=0.005), as were scores in all four domains: pain (P=0.001), physical (P=0.007), social (P=0.008), and psychological (P= 0.05). In a small prospective cohort, improvements in venous hemodynamics and in quality of life of patients submitted to standard varicose veins stripping were maintained five years after the procedure.

Validation of gated blood-pool SPECT cardiac measurements tested using a biventricular dynamic physical phantom.

PubMed

De Bondt, Pieter; Nichols, Kenneth; Vandenberghe, Stijn; Segers, Patrick; De Winter, Olivier; Van de Wiele, Christophe; Verdonck, Pascal; Shazad, Arsalan; Shoyeb, Abu H; De Sutter, Johan

2003-06-01

We have developed a biventricular dynamic physical cardiac phantom to test gated blood-pool (GBP) SPECT image-processing algorithms. Such phantoms provide absolute values against which to assess accuracy of both right and left computed ventricular volume and ejection fraction (EF) measurements. Two silicon-rubber chambers driven by 2 piston pumps simulated crescent-shaped right ventricles wrapped partway around ellopsoid left ventricles. Twenty experiments were performed at Ghent University, for which right and left ventricular true volume and EF ranges were 65-275 mL and 55-165 mL and 7%-49% and 12%-69%, respectively. Resulting 64 x 64 simulated GBP SPECT images acquired at 16 frames per R-R interval were sent to Columbia University, where 2 observers analyzed images independently of each other, without knowledge of true values. Algorithms automatically segmented right ventricular activity volumetrically from left ventricular activity. Automated valve planes, midventricular planes, and segmentation regions were presented to observers, who accepted these choices or modified them as necessary. One observer repeated measurements >1 mo later without reference to previous determinations. Linear correlation coefficients (r) of the mean of the 3 GBP SPECT observations versus true values for right and left ventricles were 0.80 and 0.94 for EF and 0.94 and 0.95 for volumes, respectively. Correlations for right and left ventricles were 0.97 and 0.97 for EF and 0.96 and 0.89 for volumes, respectively, for interobserver agreement and 0.97 and 0.98 for EF and 0.96 and 0.90 for volumes, respectively, for intraobserver agreement. No trends were detected, though volumes and right ventricular EFs were significantly higher than true values. Overall, GBP SPECT measurements correlated strongly with true values. The phantom evaluated shows considerable promise for helping to guide algorithm developments for improved GBP SPECT accuracy.

Copeptin in patients with heart failure and preserved ejection fraction: a report from the prospective KaRen-study

PubMed Central

Hage, Camilla; Lund, Lars H; Donal, Erwan; Daubert, Jean-Claude; Linde, Cecilia; Mellbin, Linda

2015-01-01

Introduction Underlying mechanisms of heart failure (HF) with preserved ejection fraction (HFPEF) remain unknown. We explored copeptin, a biomarker of the arginine vasopressin system, hypothesising that copeptin in HFPEF is elevated, associated with diastolic dysfunction and N-terminal pro-brain natriuretic peptide (NT-proBNP) and predictive of HF hospitalisation and mortality. Methods and analysis In a prospective observational substudy of the The Karolinska Rennes (KaRen) 86 patients with symptoms of acute HF and ejection fraction (EF) ≥45% were enrolled. After 4–8 weeks, blood sampling and echocardiography was performed. Plasma-copeptin was analysed in 86 patients and 62 healthy controls. Patients were followed in median 579 days (quartile 1; quartile 3 (Q1;Q3) 276;1178) regarding the composite end point all-cause mortality or HF hospitalisation. Ethics and dissemination The patients with HFPEF had higher copeptin levels, median 13.56 pmol/L (Q1;Q3 8.56;20.55) than controls 5.98 pmol/L (4.15;9.42; p<0.001). Diastolic dysfunction, assessable in 75/86 patients, was present in 45 and absent in 30 patients. Copeptin did not differ regarding diastolic dysfunction and did not correlate with cardiac function but with NT-proBNP (r=0.223; p value=0.040). In univariate Cox regression analysis log copeptin predicted the composite end point (HR 1.56 (95% CI 1.03 to 2.38; p value=0.037)) but not after adjusting for NT-proBNP (HR 1.39 (95% CI 0.91 to 2.12; p value=0.125)). Conclusions In the present patients with HFPEF, copeptin is elevated, correlates with NT-proBNP but not markers of diastolic dysfunction, and has prognostic implications, however blunted after adjustment for NT-proBNP. The HFPEF pathophysiology may be better reflected by markers of neurohormonal activation than by diastolic dysfunction. Trial registration number ClinicalTrials.gov NCT00774709. PMID:26568833

Baseline characteristics of patients with heart failure and preserved ejection fraction included in the Karolinska Rennes (KaRen) study.

PubMed

Donal, Erwan; Lund, Lars H; Oger, Emmanuel; Hage, Camilla; Persson, Hans; Reynaud, Amélie; Ennezat, Pierre-Vladimir; Bauer, Fabrice; Sportouch-Dukhan, Catherine; Drouet, Elodie; Daubert, Jean-Claude; Linde, Cecilia

2014-02-01

Karolinska Rennes (KaRen) is a prospective observational study to characterize heart failure patients with preserved ejection fraction (HFpEF) and to identify prognostic factors for long-term mortality and morbidity. To report characteristics and echocardiography at entry and after 4-8 weeks of follow-up. Patients were included following an acute heart failure presentation with B-type natriuretic peptide (BNP)>100 ng/L or N-terminal pro-BNP (NT-proBNP)>300 ng/L and left ventricular ejection fraction (LVEF)>45%. The mean ± SD age of 539 included patients was 77 ± 9 years and 56% were women. Patient history included hypertension (78%), atrial tachyarrhythmia (44%), prior heart failure (40%) and anemia (37%), but left bundle branch block was rare (3.8%). Median NT-proBNP was 2448 ng/L (n=438), and median BNP 429 ng/L (n=101). Overall, 101 patients did not return for the follow-up visit, including 13 patients who died (2.4%). Apart from older age (80 ± 9 vs. 76 ± 9 years; P=0.006), there were no significant differences in baseline characteristics between patients who did and did not return for follow-up. Mean LVEF was lower at entry than follow-up (56% vs. 62%; P<0.001). At follow-up, mean E/e' was 12.9 ± 6.1, left atrial volume index 49.4±17.8mL/m(2). Mean global left ventricular longitudinal strain was -14.6 ± 3.9%; LV mass index was 126.6 ± 36.2g/m(2). Patients in KaRen were old with slight female dominance and hypertension as the most prevalent etiological factor. LVEF was preserved, but with increased LV mass and depressed LV diastolic and longitudinal systolic functions. Few patients had signs of electrical dyssynchrony (ClinicalTrials.gov.- NCT00774709). Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Sport socks do not enhance calf muscle pump function but inelastic wraps do.

PubMed

Partsch, H; Mosti, G

2014-12-01

Aim of the study was to measure the effect of elastic and inelastic compression on calf muscle pump function in healthy male athletes. This was an experimental study which included 21 healthy male athletes. The ejection fraction (EF) of the venous calf pump was measured comparing the effects of a variety of compression materials: 1) sport compression stockings; 2) light zinc paste bandages; 3) sport compression stockings with additional Velcro® wraps over the calf. The influence of sport stocking and wraps on the venous calibre at the largest calf circumference in the lying and standing position was investigated using MRI. Inelastic compression exerting a median pressure in the standing position of 37.5 mmHg (zinc paste) and 48 mmHg (loosely applied straps over a sport stocking) achieved a significant increase of EF up to 100%. Sport stockings alone with a standing pressure of 19-24 mmHg did not show a significant change of EF. MRI demonstrated some venous narrowing in the lying but not in the standing position. By wrapping inelastic straps over the stocking an emptying of the veins in the lying and a considerable narrowing in the standing position could be observed. Venous calf pump function in athletes is not influenced by elastic sport stockings, but inelastic wraps either alone or applied over sport stockings lead to a significant enhancement.

The Design of the Understanding Outcomes with the S-ICD in Primary Prevention Patients with Low EF Study (UNTOUCHED).

PubMed

Gold, Michael R; Knops, Reinoud; Burke, Martin C; Lambiase, Pier D; Russo, Andrea M; Bongiorni, Maria Grazia; Deharo, Jean-Claude; Aasbo, Johan; El Chami, Mikhael F; Husby, Michael; Carter, Nathan; Boersma, Lucas

2017-01-01

The UNTOUCHED study will assess the safety and efficacy of the subcutaneous implantable cardioverter defibrillator (S-ICD) in the most common cohort of patients receiving ICDs. The primary goal is to evaluate the inappropriate shock (IAS)-free rate in primary prevention patients with a reduced ejection fraction (EF) and compare with a historical control of transvenous ICD patients with similar programming. The UNTOUCHED study is a global, multicenter, prospective, nonrandomized study of patients undergoing de novo S-ICD implantation for primary prevention of sudden cardiac death with a left ventricular EF ≤35%. The primary end point of this trial is freedom from IAS at 18 months. The lower 95% confidence bound of the observed incidence will be compared to a performance goal of 91.6%, which was derived from the IAS rate in MADIT-RIT. The secondary end points are all-cause shock-free rate at 18 months, and system- and procedure-related complication-free rate at 1 month and 6 months. Enrollment of a minimum of 1,100 subjects from up to 200 centers worldwide is planned based on power calculations of the primary and principal secondary end points. This trial will provide important data regarding the rates of inappropriate and appropriate shock therapy in real-world use of the S-ICD in the most common group of patients receiving ICDs. © 2016 Wiley Periodicals, Inc.

Systolic versus diastolic heart failure in community practice: clinical features, outcomes, and the use of angiotensin-converting enzyme inhibitors.

PubMed

Philbin, E F; Rocco, T A; Lindenmuth, N W; Ulrich, K; Jenkins, P L

2000-12-01

Among patients with heart failure, there is controversy about whether there are clinical features and laboratory tests that can differentiate patients who have low ejection fractions from those with normal ejection fractions. The usefulness of angiotensin-converting enzyme (ACE) inhibitors among heart failure patients who have normal left ventricular ejection fractions is also not known. From a registry of 2,906 unselected consecutive patients with heart failure who were admitted to 10 acute-care community hospitals during 1995 and 1997, we identified 1291 who had a quantitative measurement of their left ventricular ejection fraction. Patients were separated into three groups based on ejection fraction: < or =0.39 (n = 741, 57%), 0.40 to 0.49 (n = 238, 18%), and > or =0.50 (n = 312, 24%). In-hospital mortality, prescription of ACE inhibitors at discharge, subsequent rehospitalization, quality of life, and survival were measured; survivors were observed for at least 6 months after hospitalization. The mean (+/- SD) age of the sample was 75+/-11 years; the majority (55%) of patients were women. In multivariate models, age >75 years, female sex, weight >72.7 kg, and a valvular etiology for heart failure were associated with an increased probability of having an ejection fraction > or =0.50; a prior history of heart failure, an ischemic or idiopathic cause of heart failure, and radiographic cardiomegaly were associated with a lower probability of having an ejection fraction > or =0.50. Total mortality was lower in patients with an ejection fraction > or =0.50 than in those with an ejection fraction < or =0.39 (odds ratio [OR] = 0.69, 95% confidence interval [CI 0.49 to 0.98, P = 0.04). Among hospital survivors with an ejection fraction of 0.40 to 0.49, the 65% who were prescribed ACE inhibitors at discharge had better mean adjusted quality-of-life scores (7.0 versus 6.2, P = 0.02), and lower adjusted mortality (OR = 0.34, 95% CI: 0.17 to 0.70, P = 0.01) during follow-up than those who were not prescribed ACE inhibitors. Among hospital survivors with an ejection fraction > or =0.50, the 45% who were prescribed ACE inhibitors at discharge had better (lower) adjusted New York Heart Association (NYHA) functional class (2.1 versus 2.4, P = 0.04) although there was no significant improvement in survival. Among patients treated for heart failure in community hospitals, 42% of those whose ejection fraction was measured had a relatively normal systolic function (ejection fraction > or 0.40). The clinical characteristics and mortality of these patients differed from those in patients with low ejection fractions. Among the patients with ejection fractions > or =0.40, the prescription of ACE inhibitors at discharge was associated favorable effects.

First report of atretic coronary sinus stenting in a 5-kg infant resulting in dramatic improvement of ventricular function in functional single ventricle.

PubMed

El-Said, Howaida; Hegde, Sanjeet; Moore, John

2014-01-01

The patient was a male infant with L-transposition of great arteries (L-TGA), Ebstein's anomaly of the tricuspid valve, subvalvar aortic stenosis, ventricular septal defect (VSD), hypoplastic right ventricle, arch hypoplasia, and congenital complete heart block. He underwent a Norwood procedure, aortic arch repair, permanent pacemaker implantation, and a 3.5-mm aortopulmonary shunt at 4 days of age. At the time of his surgery, left ventricular function was in the normal range (ejection fraction [EF] = 67%). However by 3 months of age, he was noted to have developed moderate-severe biventricular dysfunction (left ventricular ejection fraction [LVEF] = 34%). Atresia of the coronary sinus with a small left superior venacava (LSVC) and a bridging vein was discovered during cardiac catheterization at this time. The coronary sinus mean pressure was 17 mm Hg, and the common atrial mean pressure was 6 mmHg. We opened the atretic coronary sinus ostium using radiofrequency ablation and stent placement. There was dramatic improvement in ventricular function observed over a 2-month period. Follow-up cardiac catheterization 5 months later revealed the stent in the coronary sinus to be widely patent with no intimal buildup, and the ventricular function was normal (LVEF = 58%). The patient had a bidirectional Glenn procedure with an uncomplicated postoperative course and is currently awaiting Fontan completion. © 2013 Wiley Periodicals, Inc.

Ejection Fraction: What Does It Measure?

MedlinePlus

... does the term "ejection fraction" mean? What does it measure? Answers from Rekha Mankad, M.D. Ejection fraction ... percentage of blood leaving your heart each time it contracts. During each heartbeat pumping cycle, the heart ...

Impaired left ventricular systolic function reserve limits cardiac output and exercise capacity in HFpEF patients due to systemic hypertension.

PubMed

Henein, Michael; Mörner, Stellan; Lindmark, Krister; Lindqvist, Per

2013-09-30

Heart failure (HF) patients with preserved left ventricular (LV) ejection fraction (EF) (HFpEF) due to systemic hypertension (SHT) are known to have limited exercise tolerance. Despite having normal EF at rest, we hypothesize that these patients have abnormal systolic function reserve limiting their exercise capacity. Seventeen patients with SHT (mean age 68 ± 9 years) but no valve disease and 14 healthy individuals (mean age of 65 ± 10 years) underwent resting and peak exercise echocardiography using conventional, tissue Doppler and speckle tracking techniques. The differences between resting and peak exercise values were also analyzed (Δ). Exercise capacity was determined as the workload divided by body surface area. Resting values for left atrial (LA) volume/BSA (r=-0.66, p<0.001) and global longitudinal strain rate (GLSR) in early (e) and late (a) diastole (r=0.47 and 0.46, p<0.05 for both) correlated with exercise capacity. LVEF increased during exercise in normals (mean Δ EF=10 ± 8%) but failed to do so in patients (mean Δ EF=0.6 ± 9%, p<0.001 between groups). LV GLSR during systole (s) also failed to increase with exercise in patients, to the same extent as it did in normals (0.2 ± 0.2 vs. 0.6 ± 0.3 1/s, p<0.001). The difference between rest and exercise (Δ) in LV lateral wall systolic velocity from tissue Doppler (s') (0.71, p<0.001), Δ in cardiac output (r=0.60, p<0.001) and Δ GLSRs (r=0.48, p<0.05) all correlated with exercise capacity independent of changes in heart rate. HFpEF patients with hypertensive LV disease have significantly limited exercise capacity which is related to left atrial enlargement as well as compromised LV systolic function at the time of the symptoms. The limited myocardial systolic function reserve seems to be underlying important explanation for their limited exercise capacity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A Randomized Trial of Hemodiafiltration and Change in Cardiovascular Parameters

PubMed Central

Bots, Michiel L.; van den Dorpel, Marinus A.; Grooteman, Muriel P.C.; Kamp, Otto; Levesque, Renée; ter Wee, Piet M.; Nubé, Menso J.; Blankestijn, Peter J.

2014-01-01

Background and objective Increased left ventricular mass (LVM), low ventricular ejection fraction (EF), and high pulse-wave velocity (PWV) relate to overall and cardiovascular mortality in patients with ESRD. The aim of this study was to determine the effect of online hemodiafiltration (HDF) versus low-flux hemodialysis (HD) on LVM, EF, and PWV. Design, setting, participants, & measurements Echocardiography was used to assess LVM and EF in 342 patients in the CONvective TRAnsport STudy followed for up to 4 years. PWV was measured in 189 patients for up to 3 years. Effect of HDF versus HD on LVM, EF, and PWV was evaluated using linear mixed models. Results Patients had a mean age of 63 years, and 61% were male. At baseline, median LVM was 227 g (interquartile range [IQR], 183–279 g), and median EF was 65% (IQR, 55%–72%). Median PWV was 9.8 m/s (IQR, 7.5–12.0 m/s). There was no significant difference between the HDF and HD treatment groups in rate of change in LVM (HDF: change, −0.9 g/yr [95% confidence interval (95% CI), −8.9 to 7.7 g]; HD: change, 12.5 g/yr [95% CI, −3.0 to 27.5 g]; P for difference=0.13), EF (HDF: change, −0.3%/yr [95% CI, −2.3% to 1.8%]; HD: change, −3.4%/yr [95% CI, −5.9% to −0.9%]; P=0.17), or PWV (HDF: change, −0.0 m/s per year [95% CI, −0.4 to 0.4 m/s); HD: change, 0.0 m/s per year [95% CI, −0.3 to 0.2 m/s]; P=0.89). No differences in rate of change between treatment groups were observed for subgroups of age, sex, residual kidney function, dialysis vintage, history of cardiovascular disease, diabetes, or convection volume. Conclusions Treatment with online HDF did not affect changes in LVM, EF, or PWV over time compared with HD. PMID:24408114

Rate of change of left ventricular ejection fraction during exercise is superior to the peak ejection fraction for predicting functionally significant coronary artery disease.

PubMed Central

Sridhara, B S; Bhattacharya, S; Liu, X J; Broadhurst, P; Lahiri, A

1993-01-01

OBJECTIVE--To detect and characterise rapid temporal changes in the left ventricular response to exercise in patients with ischaemic heart disease and to relate these changes to the functional severity of coronary artery disease. BACKGROUND--The gamma camera does not allow the detection of rapid changes in cardiac function during exercise radionuclide ventriculography, the monitoring of which may improve the assessment of patients with ischaemic heart disease. METHODS--A miniature nuclear probe (Cardioscint) was used to monitor continuously left ventricular function during exercise in 31 patients who had coronary angiography for suspected coronary artery disease. A coronary angiographic jeopardy score was calculated for each patient. RESULTS--The coronary jeopardy score ranged from 0 to 12 (median 4). Ejection fraction fell significantly during exercise from 46% to 34%. Patients were divided into two groups based on the response of their ejection fraction to exercise. In 14 patients (group I), the peak change in ejection fraction coincided with the end of exercise, whereas in the other 17 patients (group II) the peak change in ejection fraction occurred before the end of exercise, resulting in a brief plateau. The peak change in ejection fraction and the time to its occurrence were independent predictors of coronary jeopardy (r = -0.59, p < 0.001 for peak change and r = -0.69, p < 0.001 for time to that change). The rate of change in ejection fraction was the strongest predictor of coronary jeopardy (r = -0.81, p < 0.001). In group I the peak change in ejection fraction was a poor predictor severity of coronary disease (r = -0.28, NS), whereas the time to peak and the rate of change in ejection fraction were good predictors (r = -0.65 and r = -0.73, p < 0.01). In group II the peak, the time to the peak, and the rate of change in ejection fraction were good predictors of coronary jeopardy (r = -0.75, r = -0.61, and r = -0.83, p < 0.01). CONCLUSION--The rate of change of ejection fraction during exercise can be assessed by continuous monitoring of left ventricular function with the nuclear probe, and is the best predictor of functionally significant coronary artery disease. PMID:8280514

Left ventricular diastolic dysfunction in women with nonobstructive ischemic heart disease: insights from magnetic resonance imaging and spectroscopy.

PubMed

Nelson, Michael D

2017-10-01

Ischemic heart disease, in the absence of obstructive coronary artery disease, is prevalent in women and constitutes a major risk factor for developing major adverse cardiovascular events, including myocardial infarction, stroke, and heart failure. For decades, diagnosis was considered benign and often minimized; however, it is now known that this etiology carries much risk and is a significant burden to the health care system. This review summarizes the current state of knowledge on nonobstructive ischemic heart disease (NOIHD), the association between NOIHD and left ventricular diastolic dysfunction, potential links between NOIHD and the development of heart failure with preserved ejection fraction (HFpEF), and therapeutic options and knowledge gaps for patients living with NOIHD. Copyright © 2017 the American Physiological Society.

Sacubitril/Valsartan in Clinical Practice: A Report of 2 Cases.

PubMed

Cosentino, Eugenio

Following the results of the PARADIGM-HF trial, the European Society of Cardiology (ESC) guidelines recommend sacubitril/valsartan to replace ACE inhibitors in ambulatory patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal therapy and who fit trial criteria. However, the optimal use of sacubitril/valsartan in clinical practice needs further investigation. We report here the cases of 2 patients with HFrEH successfully treated with sacubitril/valsartan in our daily practice. Both subjects presented multiple comorbidities and received an implantable cardioverter defibrillator in primary prevention. In both patients, therapy with sacubitril/valsartan led to prompt (30 days) amelioration of heart function, with a corresponding decrease in NHYA class and without any relevant safety issue. © 2017 S. Karger AG, Basel.

Effect of Shenxinning decoction on ventricular remodeling in AT1 receptor-knockout mice with chronic renal insufficiency

PubMed Central

Yang, Xuejun; Zhou, Hua; Qu, Huiyan; Liu, Weifang; Huang, Xiaojin; Shun, Yating; He, Liqun

2014-01-01

Objective: To observe the efficacy of Shenxinning Decoction (SXND) in ventricular remodeling in AT1 receptor-knockout (AT1-KO) mice with chronic renal insufficiency (CRI). Materials and Methods: AT1-KO mice modeled with subtotal (5/6) nephrectomy were intervened with SXND for 12 weeks. Subsequently, blood urea nitrogen (BUN), serum creatinine (SCr), brain natriuretic peptide (BNP), echocardiography (left ventricular end-diastolic diameter, LVDD; left ventricular end-systolic diameter, LVDS; fractional shortening, FS; and ejection fraction, EF), collagen types I and III in the heart and kidney, myocardial mitochondria, and cardiac transforming growth factor-β1 (TGF-β1) of the AT1-KO mice were compared with the same model with nephrectomy only and untreated with SXND. Results: AT1-KO mice did not affect the process of CRI but it could significantly affect cardiac remodeling process. SXND decreased to some extent the AT1-KO mice's BUN, SCr, BNP, and cardiac LVDD, LVDS, and BNP, improved FS and EF, lowered the expression of collagen type I and III in heart and kidney, increased the quantity of mitochondria and ameliorated their structure, and down-regulated the expression of TGF-β1. Conclusion: SXND may antagonize the renin–angiotensin system (RAS) and decrease uremia toxins, thereby ameliorating ventricular remodeling in CRI. Furthermore, SXND has a mechanism correlated with the improvement of myocardial energy metabolism and the down-regulation of TGF-β1. PMID:25097276

Left ventricular filling under elevated left atrial pressure

NASA Astrophysics Data System (ADS)

Gaddam, Manikantam; Samaee, Milad; Santhanakrishnan, Arvind

2017-11-01

Left atrial pressure (LAP) is elevated in diastolic dysfunction, where left ventricular (LV) filling is impaired due to increase in ventricular stiffness. The impact of increasing LAP and LV stiffness on intraventricular filling hemodynamics remains unclear. We conducted particle image velocimetry and hemodynamics measurements in a left heart simulator (LHS) under increasing LAP and LV stiffness at a heart rate of 70 bpm. The LHS consisted of a flexible-walled LV physical model fitted within a fluid-filled chamber. LV wall motion was generated by a piston pump that imparted pressure fluctuations in the chamber. Resistance and compliance elements in the flow loop were adjusted to obtain bulk physiological hemodynamics in the least stiff LV model. Two LV models of increasing stiffness were subsequently tested under unchanged loop settings. LAP was varied between 5-20 mm Hg for each LV model, by adjusting fluid level in a reservoir upstream of the LV. For constant LV stiffness, increasing LAP lowered cardiac output (CO), while ejection fraction (EF) and E/A ratio were increased. For constant LAP, increasing LV stiffness lowered CO and EF, and increased E/A ratio. The implications of these altered hemodynamics on intraventricular filling vortex characteristics will be presented.

Potential role of biventricular pacing beyond advanced systolic heart failure.

PubMed

Fang, Fang; Sanderson, John E; Yu, Cheuk-Man

2013-01-01

Cardiac resynchronization therapy (CRT) is an effective therapy for advanced heart failure (HF) patients. The indications are well defined in recent guidelines and broadly indicate that CRT is suitable for chronic HF patients with left ventricular ejection fraction (EF) ≤35% and in NYHA class III or IV (Class I), and those with prolonged QRS duration ≥120 ms with left bundle branch block (LBBB) QRS morphology, or QRS duration ≥150 ms irrespective of QRS morphology (Class IIa). For patients with NYHA class II symptoms, CRT is recommended for patients with EF ≤30% and QRS duration ≥130 ms with LBBB QRS morphology (Class I, level of evidence: A), or QRS duration ≥150 ms irrespective of QRS morphology (Class IIa, level of evidence: A). However, CRT may benefit additional patients outside these criteria. In this review, we summarize the role of CRT in some subgroups, including patients with mild and moderate HF, upgrading to CRT from right ventricular (RV) pacing, bradycardia patients with routine pacing indications, congenital heart disease and specific cardiomyopathies. It is possible that CRT can give symptomatic and mortality benefits in some of these subgroups in the future and further clinical trials are warranted.  

Evaluation of Pharmacokinetic and Pharmacodynamic Drug–Drug Interaction of Sacubitril/Valsartan (LCZ696) and Sildenafil in Patients With Mild‐to‐Moderate Hypertension

PubMed Central

Langenickel, TH; Petruck, J; Kode, K; Ayalasomayajula, S; Schuehly, U; Greeley, M; Pal, P; Zhou, W; Prescott, MF; Sunkara, G; Rajman, I

2017-01-01

Sacubitril/valsartan (LCZ696) is indicated for the treatment of patients with heart failure and reduced ejection fraction (HFrEF). Since patients with HFrEF may receive sacubitril/valsartan and sildenafil, both increasing cyclic guanosine monophosphate, the present study evaluated the pharmacokinetic and pharmacodynamic drug interaction potential between sacubitril/valsartan and sildenafil. In this open‐label, three‐period, single sequence study, patients with mild‐to‐moderate hypertension (153.8 ± 8.2 mmHg mean systolic blood pressure (SBP)) received a single dose of sildenafil 50 mg, sacubitril/valsartan 400 mg once daily for 5 days, and sacubitril/valsartan and sildenafil coadministration. When coadministered with sildenafil, the AUC and Cmax of valsartan decreased by 29% and 39%, respectively. Coadministration of sacubitril/valsartan and sildenafil resulted in a greater decrease in BP (–5/–4/–4 mmHg mean ambulatory SBP/DBP/MAP (mean arterial pressure)) than with sacubitril/valsartan alone. Both treatments were generally safe and well tolerated in this study; however, the additional BP reduction suggests that sildenafil should be administered cautiously in patients receiving sacubitril/valsartan. Unique identifier: NCT01601470. PMID:28599060

A new twist on an old idea part 2: cyclosporine preserves normal mitochondrial but not cardiomyocyte function in mini‐swine with compensated heart failure

PubMed Central

Hiemstra, Jessica A.; Gutiérrez‐Aguilar, Manuel; Marshall, Kurt D.; McCommis, Kyle S.; Zgoda, Pamela J.; Cruz‐Rivera, Noelany; Jenkins, Nathan T.; Krenz, Maike; Domeier, Timothy L.; Baines, Christopher P.; Emter, Craig A.

2014-01-01

Abstract We recently developed a clinically relevant mini‐swine model of heart failure with preserved ejection fraction (HFpEF), in which diastolic dysfunction was associated with increased mitochondrial permeability transition (MPT). Early diastolic function is ATP and Ca2+‐dependent, thus, we hypothesized chronic low doses of cyclosporine (CsA) would preserve mitochondrial function via inhibition of MPT and subsequently maintain normal cardiomyocyte Ca2+ handling and contractile characteristics. Left ventricular cardiomyocytes were isolated from aortic‐banded Yucatan mini‐swine divided into three groups; control nonbanded (CON), HFpEF nontreated (HF), and HFpEF treated with CsA (HF‐CsA). CsA mitigated the deterioration of mitochondrial function observed in HF animals, including functional uncoupling of Complex I‐dependent mitochondrial respiration and increased susceptibility to MPT. Attenuation of mitochondrial dysfunction in the HF‐CsA group was not associated with commensurate improvement in cardiomyocyte Ca2+ handling or contractility. Ca2+ transient amplitude was reduced and transient time to peak and recovery (tau) prolonged in HF and HF‐CsA groups compared to CON. Alterations in Ca2+ transient parameters observed in the HF and HF‐CsA groups were associated with decreased cardiomyocyte shortening and shortening rate. Cellular function was consistent with impaired in vivo systolic and diastolic whole heart function. A significant systemic hypertensive response to CsA was observed in HF‐CsA animals, and may have played a role in the accelerated the development of heart failure at both the whole heart and cellular levels. Given the significant detriment to cardiac function observed in response to CsA, our findings suggest chronic CsA treatment is not a viable therapeutic option for HFpEF. PMID:24963034

Assessment of Right Atrium Function in Patients With Systemic Lupus Erythematosus With Different Pulmonary Artery Systolic Pressures by 2-Dimensional Speckle-Tracking Echocardiography.

PubMed

Sun, Lihua; Wang, Ying; Dong, Yu; Song, Shengda; Luo, Runlan; Li, Guangsen

2018-02-26

To assess right atrium (RA) function of patients with systemic lupus erythematosus (SLE) and pulmonary artery hypertension (PAH) by 2-dimensional speckle-tracking echocardiography. Thirty matched healthy adults were selected as group A. Then, 102 patients with SLE were divided into 3 groups according to the severity of PAH. Group B included 37 patients without PAH (pulmonary artery [PA] systolic pressure ≤ 30 mm Hg); group C included 34 patients with PAH (PA systolic pressure of 30-50 mm Hg); and group D included 31 patients with PAH (PA systolic pressure ≥ 50 mm Hg). Parameters evaluated included RA maximum volume, minimum volume, preatrial contraction volume, passive ejection fraction (EF), and active EF. The global peak longitudinal systolic strain rate and early and late diastolic strain rates of the RA were obtained by 2-dimensional speckle-tracking echocardiography. No significant differences were found in all parameters between groups B and A (P > .05). The RA maximum volume, minimum volume, preatrial contraction volume, active EF, and late diastolic strain rate in groups C and D were significantly increased compared with those in groups A and B, and the parameters in group D were significantly higher than those in group C (P < .05). Although the RA passive EF, early diastolic strain rate, and systolic strain rate in groups C and D were significantly decreased compared with those in groups A and B, those in group D were significantly lower than those in group C (P < .05). Two-dimensional speckle-tracking echocardiography could effectively assess RA function in patients with SLE who have different severities of PAH. © 2018 by the American Institute of Ultrasound in Medicine.

Shared biomarkers between female diastolic heart failure and pre‐eclampsia: a systematic review and meta‐analysis

PubMed Central

Bokslag, Anouk; Maas, Angela H.E.M.; Franx, Arie; Paulus, Walter J.; de Groot, Christianne J.M.

2017-01-01

Abstract Evidence accumulates for associations between hypertensive pregnancy disorders and increased cardiovascular risk later. The main goal of this study was to explore shared biomarkers representing common pathogenic pathways between heart failure with preserved ejection fraction (HFpEF) and pre‐eclampsia where these biomarkers might be potentially eligible for cardiovascular risk stratification in women after hypertensive pregnancy disorders. We sought for blood markers in women with diastolic dysfunction in a first literature search, and through a second search, we investigated whether these same biochemical markers were present in pre‐eclampsia.This systematic review and meta‐analysis presents two subsequent systematic searches in PubMed and EMBASE. Search I yielded 3014 studies on biomarkers discriminating women with HFpEF from female controls, of which 13 studies on 11 biochemical markers were included. Cases had HFpEF, and controls had no heart failure. The second search was for studies discriminating women with pre‐eclampsia from women with non‐hypertensive pregnancies with at least one of the biomarkers found in Search I. Search II yielded 1869 studies, of which 51 studies on seven biomarkers were included in meta‐analyses and 79 studies on 12 biomarkers in systematic review.Eleven biological markers differentiated women with diastolic dysfunction from controls, of which the following 10 markers differentiated women with pre‐eclampsia from controls as well: C‐reactive protein, HDL, insulin, fatty acid‐binding protein 4, brain natriuretic peptide, N terminal pro brain natriuretic peptide, adrenomedullin, mid‐region pro adrenomedullin, cardiac troponin I, and cancer antigen 125.Our study supports the hypothesis that HFpEF in women shares a common pathogenic background with pre‐eclampsia. The biomarkers representing inflammatory state, disturbances in myocardial function/structure, and unfavourable lipid metabolism may possibly be eligible for future prognostic tools. PMID:28451444

Low-dose dobutamine gated-SPECT analysis of left ventricular segmental wall thickening in ischemic cardiomyopathy.

PubMed

Candell-Riera, Jaume; Romero-Farina, Guillermo; Milá, Marta; Aguadé-Bruix, Santiago

2008-10-01

The objective of this study was to use low-dose dobutamine (LDD) gated single-photon emission computed tomography (SPECT) to evaluate segmental thickening of the left ventricle (LV) and its relationship with changes in ejection fraction (EF) and ventricular volumes in patients with ischemic cardiomyopathy. This prospective multicenter study involved 89 patients with ischemic cardiomyopathy (i.e., EF < or =40%) who underwent LDD gated-SPECT at rest. The LV was divided into 17 segments and systolic thickening was assessed in a total of 1513 segments during LDD infusion. RESULTS; A significant increase in LVEF (33.2% vs. 30.8%; P< .001) was observed during LDD infusion and occurred at the expense of a reduction in end-systolic volume (130.5 mL vs. 136.4 mL; P=.005). The increase in EF was > or =5% in 33.7% of patients, while the EF decreased by > or =5% in 5.6% of patients. With LDD infusion, both an improvement in > or =3 segments with severely decreased baseline thickening (odds ratio [OR] = 18.3; 95% confidence interval [CI], 5.3-63) and an improvement in > or =10 segments with mild-to-moderate alterations in baseline thickening (OR = 4.53; 95% CI, 1.26-16.16) were associated with a > or =5% increase in LVEF. During the assessment of global left ventricular contractile reserve by LDD gated-SPECT, attention should be paid not only to the behavior of segments with severely decreased baseline thickening, which are generally regarded as indicating viability, but also to segments with mild-to-moderate alterations and to those in which thickening decreases.

Sacubitril/valsartan: An important piece in the therapeutic puzzle of heart failure.

PubMed

Marques da Silva, Pedro; Aguiar, Carlos

2017-09-01

Sacubitril/valsartan (LCZ696), a supramolecular sodium salt complex of the neprilysin inhibitor prodrug sacubitril and the angiotensin receptor blocker (ARB) valsartan, was recently approved in the EU and the USA for the treatment of chronic heart failure (HF) with reduced ejection fraction (HFrEF) (NYHA class II-IV). Inhibition of chronically activated neurohormonal pathways (the renin-angiotensin-aldosterone system [RAAS] and sympathetic nervous system [SNS]) is central to the treatment of chronic HFrEF. Furthermore, enhancement of the natriuretic peptide (NP) system, with favorable cardiovascular (CV) and renal effects in HF, is a desirable therapeutic goal to complement RAAS and SNS blockade. Sacubitril/valsartan represents a novel pharmacological approach that acts by enhancing the NP system via inhibition of neprilysin (an enzyme that degrades NPs) and by suppressing the RAAS via AT1 receptor blockade, thereby producing more effective neurohormonal modulation than can be achieved with RAAS inhibition alone. In the large, randomized, double-blind PARADIGM-HF trial, replacement of an angiotensin-converting enzyme inhibitor (ACEI) (enalapril) with sacubitril/valsartan resulted in a significant improvement in morbidity and mortality in patients with HFrEF. Sacubitril/valsartan was superior to enalapril in reducing the risk of CV death or HF hospitalization (composite primary endpoint) and all-cause death, and in limiting progression of HF. Sacubitril/valsartan was generally well tolerated, with a comparable safety profile to enalapril; symptomatic hypotension was more common with sacubitril/valsartan, whereas renal dysfunction, hyperkalemia and cough were less common compared with enalapril. In summary, sacubitril/valsartan is a superior alternative to ACEIs/ARBs in the treatment of HFrEF, a recommendation that is reflected in many HF guidelines. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Value of gated SPECT in the analysis of regional wall motion of the interventricular septum after coronary artery bypass grafting.

PubMed

Giubbini, Raffaele; Rossini, Pierluigi; Bertagna, Francesco; Bosio, Giovanni; Paghera, Barbara; Pizzocaro, Claudio; Canclini, Silvana; Terzi, Arturo; Germano, Guido

2004-10-01

The aim of this study was the evaluation of septal wall motion, perfusion and wall thickening after CABG in two groups of consecutive patients, one with grafted left anterior coronary artery and no history of myocardial infarction, and the other with previous anteroseptal myocardial infarction and impaired septal motion before surgery. The issue addressed was the ability of gated SPECT to differentiate between true paradoxical septal motion, characterised by paradoxical wall motion, depressed ejection fraction (EF), poor viability and compromised wall thickening, and pseudo-paradoxical motion, characterised by abnormal wall motion and regional EF but preserved perfusion and wall thickening. One hundred and thirty-two patients with previous anterior myocardial infarction, 82 patients with left anterior descending coronary disease and no history of myocardial infarction and 27 normal subjects underwent rest gated SPECT after 99mTc-sestamibi injection, according to the standard QGS protocol. Quantitative regional EF, regional perfusion, regional wall motion and regional wall thickening were determined using a 20-segment model. Despite the presence of similar regional wall motion impairment in patients with and patients without septal infarction, in terms of regional EF (2.5%+/-3% vs 1.9%+/-4.9% p=NS) and inward septal motion (3+/-4.9 mm vs 2.3+/-6.1 mm p=NS), significant differences were observed in both perfusion (74.7%+/-6.2% vs 63.3%+/-13%, p>0.0001) and regional wall thickening (17.2%+/-7.4% vs 12.6%+/-7.2%, p>0.0001). Gated SPECT with perfusion tracers can reliably differentiate pseudo-paradoxical from true paradoxical septal motion in patients with previous CABG, and it may be the method of choice for evaluating left ventricular performance in this patient population.

Aortic Valve Replacement for Moderate Aortic Stenosis with Severe Calcification and Left Ventricualr Dysfunction-A Case Report and Review of the Literature.

PubMed

Narang, Nikhil; Lang, Roberto M; Liarski, Vladimir M; Jeevanandam, Valluvan; Hofmann Bowman, Marion A

2017-01-01

A 55-year-old man with a history of erosive, seropositive rheumatoid arthritis (RA), and interstitial lung disease presented with shortness of breath. Echocardiography showed new-onset severe left ventricular (LV) dysfunction with an ejection fraction (EF) of 15% and moderately increased mean aortic valve gradient of 20 mmHg in a trileaflet aortic valve with severe sclero-calcific degeneration. Coronary angiography revealed no significant obstructive coronary disease. Invasive hemodynamic studies and dobutamine stress echocardiography were consistent with moderate aortic stenosis. Guideline directed medical therapy for heart failure with reduced EF was initiated; however, diuretics and neurohormonal blockade (beta-blocker and angiotensin receptor blocker) provided minimal improvement, and the patient remained functionally limited. Of interest, echocardiography performed 1 year prior to his presentation showed normal LV EF and mild aortic leaflet calcification with moderate stenosis, suggesting a rapid progressing of calcific aortic valve disease. Subsequently, the patient underwent surgical aortic valve replacement and demonstrated excellent postsurgical recovery of LV EF (55%). Calcific aortic valve disease is commonly associated with aging, bicuspid aortic valve, and chronic kidney disease. Pathophysiological mechanism for valvular calcification is incompletely understood but include osteogenic transformation of valvular interstitial cells mediated by local and systemic inflammatory processes. Several rheumatologic diseases including RA are associated with premature atherosclerosis and arterial calcification, and we speculated a similar role of RA accelerating calcific aortic valve disease. We present a case of accelerated aortic valve calcification with (only) moderate stenosis, complicated by a rapid decline in LV systolic performance. Guidelines for AVR in moderate stenosis without concomitant cardiac surgery are not well established, although it should be considered in selected patients.

Global longitudinal strain and long-term outcomes in asymptomatic extracardiac sarcoid patients with no apparent cardiovascular disease.

PubMed

Felekos, Ioannis; Aggeli, Constantina; Gialafos, Elias; Kouranos, Vasileios; Rapti, Aggeliki; Sfikakis, Petros; Koulouris, Nikolaos; Tousoulis, Dimitris

2018-06-01

Global longitudinal strain (GLS) is increasingly accepted as a predictor of mortality in various clinical settings. This study tested the hypothesis that GLS is associated with increased event rate in patients with extracardiac sarcoidosis, who have no overt symptoms of cardiovascular disease and preserved ejection fraction (EF). We retrospectively studied 117 patients with extracardiac sarcoidosis and 45 age- and sex-matched controls, who underwent comprehensive echocardiographic study, while GLS was measured by an offline speckle tracking algorithm. Patients who had signs and symptoms of cardiovascular disease at the time of the examination were excluded from the study. Patients were followed for an average of 57.1 months. Primary endpoint was defined as a composite endpoint of heart failure-related hospitalizations, need for device therapy, arrhythmias, and all-cause mortality. The age of patients was 42 ± 6 years old (43 men). Events were recorded in 10 patients (8.5%). Tissue Doppler revealed E/Em 7.9 ± 3.5, while EF was 54.2 ± 3.5%. Global longitudinal strain was 14.4 ± 3%, and a cutoff value ≤-13.6% for GLS was considered more associated with adverse outcomes (AUC 0.84). After adjustment for multiple potential confounders (age, gender, hypertension, diabetes, E/Em, and EF), GLS remained strongly associated with adverse outcomes (HR 0.8, 0.63 to 0.98 95% C.I, P = .04). In conclusion, among patients with extracardiac sarcoidosis and no symptoms of cardiovascular disease, even when EF is preserved, GLS seems to be strongly associated with adverse future events. © 2018 Wiley Periodicals, Inc.

Independent and incremental prognostic value of Doppler-derived left ventricular total isovolumic time in patients with systolic heart failure.

PubMed

Bajraktari, Gani; Dini, Frank Lloyd; Fontanive, Paolo; Elezi, Shpend; Berisha, Venera; Napoli, Anna Maria; Ciuti, Manrico; Henein, Michael

2011-05-05

A prolonged total isovolumic time (T-IVT) has been shown to be associated with worsening survival in patients submitted to coronary artery surgery. However, it is not known whether it has prognostic significance in patients with chronic systolic heart failure (HF). To determine the prognostic value of T-IVT in comparison with other clinical, biochemical and echocardiographic variables in patients with chronic systolic HF. Patients (n=107; age 68±12 years, 25% women) with chronic systolic HF, left ventricular ejection fraction (EF)<45%, and sinus rhythm, underwent a complete Doppler echocardiographic study, that included tissue Doppler long axis velocities and total isovolumic time (T-IVT), determined as [60-(total ejection time+total filling time)]. Plasma N-terminal pro-B natriuretic peptide (NT-pro-BNP) was also measured. The associations of dichotomous variables selected according to the Receiver Operator Characteristic analysis were assessed using the Cox proportional hazard model. Follow-up period was 37±18 months. Multivariate predictors of events were T-IVT≥12.3% s/min, mean E/Em ratio≥10, log NT-pro-BNP levels≥2.47 pg/ml and LV EF≤32.5%. On Kaplan-Meier analysis, patients with prolonged T-IVT, high mean E/Em ratio, increased NT-pro-BNP levels and decreased LV EF had a worse outcome compared with those without. The addition of T-IVT and NT-pro-BNP to conventional clinical and echocardiographic variables significantly improved the chi-square for the prediction of the outcome from 33.1 to 38.0, (P<0.001). Prolonged T-IVT added to the prognostic stratification of patients with systolic HF. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Extracting and analyzing ejection fraction values from electronic echocardiography reports in a large health maintenance organization.

PubMed

Xie, Fagen; Zheng, Chengyi; Yuh-Jer Shen, Albert; Chen, Wansu

2017-12-01

The left ventricular ejection fraction value is an important prognostic indicator of cardiovascular outcomes including morbidity and mortality and is often used clinically to indicate severity of heart disease. However, it is usually reported in free-text echocardiography reports. We developed and validated a computerized algorithm to extract ejection fraction values from echocardiography reports and applied the algorithm to a large volume of unstructured echocardiography reports between 1995 and 2011 in a large health maintenance organization. A total of 621,856 echocardiography reports with a description of ejection fraction values or systolic functions were identified, of which 70 percent contained numeric ejection fraction values and the rest (30%) were text descriptions explicitly indicating the systolic left ventricular function. The 12.1 percent (16.0% for male and 8.4% for female) of these extracted ejection fraction values are <45 percent. Validation conducted based on a random sample of 200 reports yielded 95.0 percent sensitivity and 96.9 percent positive predictive value.

Impact of Cardiac Progenitor Cells on Heart Failure and Survival in Single Ventricle Congenital Heart Disease.

PubMed

Sano, Toshikazu; Ousaka, Daiki; Goto, Takuya; Ishigami, Shuta; Hirai, Kenta; Kasahara, Shingo; Ohtsuki, Shinichi; Sano, Shunji; Oh, Hidemasa

2018-03-30

Intracoronary administration of cardiosphere-derived cells (CDCs) in patients with single ventricles resulted in a short-term improvement in cardiac function. To test the hypothesis that CDC infusion is associated with improved cardiac function and reduced mortality in patients with heart failure. We evaluated the effectiveness of CDCs using an integrated cohort study in 101 patients with single ventricles, including 41 patients who received CDC infusion and 60 controls treated with staged palliation alone. Heart failure with preserved ejection fraction (EF) or reduced EF was stratified by the cardiac function after surgical reconstruction. The main outcome measure was to evaluate the magnitude of improvement in cardiac function and all-cause mortality at 2 years. Animal studies were conducted to clarify the underlying mechanisms of heart failure with preserved EF and heart failure with reduced EF phenotypes. At 2 years, CDC infusion increased ventricular function (stage 2: +8.4±10.0% versus +1.6±6.4%, P =0.03; stage 3: +7.9±7.5% versus -1.1±5.5%, P <0.001) compared with controls. In all available follow-up data, survival did not differ between the 2 groups (log-rank P =0.225), whereas overall patients treated by CDCs had lower incidences of late failure ( P =0.022), adverse events ( P =0.013), and catheter intervention ( P =0.005) compared with controls. CDC infusion was associated with a lower risk of adverse events (hazard ratio, 0.411; 95% CI, 0.179-0.942; P =0.036). Notably, CDC infusion reduced mortality ( P =0.038) and late complications ( P <0.05) in patients with heart failure with reduced EF but not with heart failure with preserved EF. CDC-treated rats significantly reversed myocardial fibrosis with differential collagen deposition and inflammatory responses between the heart failure phenotypes. CDC administration in patients with single ventricles showed favorable effects on ventricular function and was associated with reduced late complications except for all-cause mortality after staged procedures. Patients with heart failure with reduced EF but not heart failure with preserved EF treated by CDCs resulted in significant improvement in clinical outcome. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01273857 and NCT01829750. © 2018 American Heart Association, Inc.

Factors That Impact Evaluation of Left Ventricular Systolic Parameters in Myocardial Perfusion Gated SPECT with 16 Frame and 8 Frame Acquisition Models.

PubMed

Ansari, Mojtaba; Hashemi, Hoda; Soltanshahi, Mehdi; Qutbi, Mohsen; Azizmohammadi, Zahra; Tabeie, Faraj; Javadi, Hamid; Jafari, Esmail; Barekat, Maryam; Assadi, Majid

2018-06-07

Evaluating the effects of heart cavity volume, presence and absence of perfusion defect, gender and type of study (stress and rest) on the difference of systolic parameters of myocardial perfusion scan in 16 and 8 framing gated SPECT imaging. Cardiac gated SPECT in both 16 and 8 framing simultaneously and both stress and rest phases at one-day protocol was performed for 50 patients. Data have been reconstructed by filter back projection (FBP) method and left ventricular (LV) systolic parameters were calculated by using QGS software. The effect of some factors such as LV cavity volume, presence and absence of perfusion defect, gender and type of study on data difference between 8 and 16 frames were evaluated. The differences in ejection fraction (EF), end-diastolic volume (EDV) and end-systolic volume (ESV) in both stress and rest were statistically significant. Difference in both framing was more in stress for EF and ESV, and was more in rest for EDV. Study type had a significant effect on differences in systolic parameters while gender had a significant effect on differences in EF and ESV in rest between both framings. In conclusion, results of this study revealed that difference of both 16 and 8 frames data in systolic phase were statistically significant and it seems that because of better efficiency of 16 frames, it cannot be replaced by 8 frames. Further well-designed studies are required to verify these findings.

Left ventricular volume analysis as a basic tool to describe cardiac function.

PubMed

Kerkhof, Peter L M; Kuznetsova, Tatiana; Ali, Rania; Handly, Neal

2018-03-01

The heart is often regarded as a compression pump. Therefore, determination of pressure and volume is essential for cardiac function analysis. Traditionally, ventricular performance was described in terms of the Starling curve, i.e., output related to input. This view is based on two variables (namely, stroke volume and end-diastolic volume), often studied in the isolated (i.e., denervated) heart, and has dominated the interpretation of cardiac mechanics over the last century. The ratio of the prevailing coordinates within that paradigm is termed ejection fraction (EF), which is the popular metric routinely used in the clinic. Here we present an insightful alternative approach while describing volume regulation by relating end-systolic volume (ESV) to end-diastolic volume. This route obviates the undesired use of metrics derived from differences or ratios, as employed in previous models. We illustrate basic principles concerning ventricular volume regulation by data obtained from intact animal experiments and collected in healthy humans. Special attention is given to sex-specific differences. The method can be applied to the dynamics of a single heart and to an ensemble of individuals. Group analysis allows for stratification regarding sex, age, medication, and additional clinically relevant covariates. A straightforward procedure derives the relationship between EF and ESV and describes myocardial oxygen consumption in terms of ESV. This representation enhances insight and reduces the impact of the metric EF, in favor of the end-systolic elastance concept advanced 4 decades ago.

Calpain inhibition preserves myocardial structure and function following myocardial infarction.

PubMed

Mani, Santhosh K; Balasubramanian, Sundaravadivel; Zavadzkas, Juozas A; Jeffords, Laura B; Rivers, William T; Zile, Michael R; Mukherjee, Rupak; Spinale, Francis G; Kuppuswamy, Dhandapani

2009-11-01

Cardiac pathology, such as myocardial infarction (MI), activates intracellular proteases that often trigger programmed cell death and contribute to maladaptive changes in myocardial structure and function. To test whether inhibition of calpain, a Ca(2+)-dependent cysteine protease, would prevent these changes, we used a mouse MI model. Calpeptin, an aldehydic inhibitor of calpain, was intravenously administered at 0.5 mg/kg body wt before MI induction and then at the same dose subcutaneously once per day. Both calpeptin-treated (n = 6) and untreated (n = 6) MI mice were used to study changes in myocardial structure and function after 4 days of MI, where end-diastolic volume (EDV) and left ventricular ejection fraction (EF) were measured by echocardiography. Calpain activation and programmed cell death were measured by immunohistochemistry, Western blotting, and TdT-mediated dUTP nick-end labeling (TUNEL). In MI mice, calpeptin treatment resulted in a significant improvement in EF [EF decreased from 67 + or - 2% pre-MI to 30 + or - 4% with MI only vs. 41 + or - 2% with MI + calpeptin] and attenuated the increase in EDV [EDV increased from 42 + or - 2 microl pre-MI to 73 + or - 4 microl with MI only vs. 55 + or - 4 microl with MI + calpeptin]. Furthermore, calpeptin treatment resulted in marked reduction in calpain- and caspase-3-associated changes and TUNEL staining. These studies indicate that calpain contributes to MI-induced alterations in myocardial structure and function and that it could be a potential therapeutic target in treating MI patients.

[Effects of trimetazidine on serum oxygen free radicals in congestive heart failure].

PubMed

Ma, Qi-lin; Xie, Yong; Zhang, Sai-dan

2002-12-28

To investigate the level of serum superoxide dismutase (SOD) and maiondialdehyde (MDA) and left ventricular systolic function in congestive heart failure (CHF) and to evaluate the influence of trimetazidine on them. Serum SOD and MDA were measured in 50 patients with heart function from grade two to four and 15 normal subjects. All the persons underwent echocardiography to determine the left ventricular end-systolic volume index (LVESVI) and the left ventricular ejection fraction (EF). The patients with CHF were randomly treated with trimetazidine plus routine therapy (n = 25) or routine therapy only (n = 25) for 8 weeks with evaluations made before and after the treatment. The SOD level and EF in the patients with CHF significantly decreased and the MDA level and LVESVI in those patients significantly increased compared with the normal subjects (P < 0.05); the severer the CHF, the greater the changes. After the treatment, the SOD level and EF increased significantly and MDA and LVESVI decreased significantly (P < 0.01) in both the trimetazidine and the conventional groups. And these changes were more obvious in the trimetazidine group than in the conventional group(P < 0.01). Oxygen free radicals play an important role in the pathophysiologic changes of CHF. The level of serum SOD and MDA can indicate the degree of CHF. Trimetazidine not only increases the level of SOD and decreases the level of MDA, but also improves the left ventricular systolic function.

Ramipril and Losartan Exert a Similar Long-Term Effect upon Markers of Heart Failure, Endogenous Fibrinolysis, and Platelet Aggregation in Survivors of ST-Elevation Myocardial Infarction: A Single Centre Randomized Trial.

PubMed

Marinšek, Martin; Sinkovič, Andreja

2016-01-01

Blocking the renin-angiotensin-aldosterone system in ST-elevation myocardial infarction (STEMI) patients prevents heart failure and recurrent thrombosis. Our aim was to compare the effects of ramipril and losartan upon the markers of heart failure, endogenous fibrinolysis, and platelet aggregation in STEMI patients over the long term. After primary percutaneous coronary intervention (PPCI), 28 STEMI patients were randomly assigned ramipril and 27 losartan, receiving therapy for six months with dual antiplatelet therapy (DAPT). We measured N-terminal proBNP (NT-proBNP), ejection fraction (EF), plasminogen-activator-inhibitor type 1 (PAI-1), and platelet aggregation by closure times (CT) at the baseline and after six months. Baseline NT-proBNP ≥ 200 pmol/mL was observed in 48.1% of the patients, EF < 55% in 49.1%, and PAI-1 ≥ 3.5 U/mL in 32.7%. Six-month treatment with ramipril or losartan resulted in a similar effect upon PAI-1, NT-proBNP, EF, and CT levels in survivors of STEMI, but in comparison to control group, receiving DAPT alone, ramipril or losartan treatment with DAPT significantly increased mean CT (226.7 ± 80.3 sec versus 158.1 ± 80.3 sec, p < 0.05). Ramipril and losartan exert a similar effect upon markers of heart failure and endogenous fibrinolysis, and, with DAPT, a more efficient antiplatelet effect in long term than DAPT alone.

Prognostic significance of anaemia in patients with heart failure with preserved and reduced ejection fraction: results from the MAGGIC individual patient data meta-analysis.

PubMed

Berry, C; Poppe, K K; Gamble, G D; Earle, N J; Ezekowitz, J A; Squire, I B; McMurray, J J V; McAlister, F A; Komajda, M; Swedberg, K; Maggioni, A P; Ahmed, A; Whalley, G A; Doughty, R N; Tarantini, L

2016-06-01

Anaemia is common among patients with heart failure (HF) and is an important prognostic marker. We sought to determine the prognostic importance of anaemia in a large multinational pooled dataset of prospectively enrolled HF patients, with the specific aim to determine the prognostic role of anaemia in HF with preserved and reduced ejection fraction (HF-PEF and HF-REF, respectively). Individual person data meta-analysis. Patients with haemoglobin (Hb) data from the MAGGIC dataset were used. Anaemia was defined as Hb < 120 g/l in women and <130 g/l in men. HF-PEF was defined as EF ≥ 50%; HF-REF was EF < 50%. Cox proportional hazard modelling, with adjustment for clinically relevant variables, was undertaken to investigate factors associated with 3-year all-cause mortality. Thirteen thousand two hundred and ninety-five patients with HF from 19 studies (9887 with HF-REF and 3408 with HF-PEF). The prevalence of anaemia was similar among those with HF-REF and HF-PEF (42.8 and 41.6% respectively). Compared with patients with normal Hb values, those with anaemia were older, were more likely to have diabetes, ischaemic aetiology, New York Heart Association class IV symptoms, lower estimated glomerular filtration rate and were more likely to be taking diuretic and less likely to be taking a beta-blocker. Patients with anaemia had higher all-cause mortality (adjusted hazard ratio [aHR] 1.38, 95% confidence interval [CI] 1.25-1.51), independent of EF group: aHR 1.67 (1.39-1.99) in HF-PEF and aHR 2.49 (2.13-2.90) in HF-REF. Anaemia is an adverse prognostic factor in HF irrespective of EF. The prognostic importance of anaemia was greatest in patients with HF-REF. © The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of organic and inorganic nitrate on aortic and carotid haemodynamics in heart failure with preserved ejection fraction.

PubMed

Chirinos, Julio A; Londono-Hoyos, Francisco; Zamani, Payman; Beraun, Melissa; Haines, Philip; Vasim, Izzah; Varakantam, Swapna; Phan, Timothy S; Cappola, Thomas P; Margulies, Kenneth B; Townsend, Raymond R; Segers, Patrick

2017-11-01

To assess the haemodynamic effects of organic vs. inorganic nitrate administration among patients with heart failure with preserved ejection fraction (HFpEF). We assessed carotid and aortic pressure-flow relations non-invasively before and after the administration of 0.4 mg of sublingual nitroglycerin (n = 26), and in a separate sub-study, in response to 12.9 mmoL of inorganic nitrate (n = 16). Nitroglycerin did not consistently reduce wave reflections arriving at the proximal aorta (change in real part of reflection coefficient, 1st harmonic: -0.09; P = 0.01; 2nd harmonic: -0.045, P = 0.16; 3rd harmonic: +0.087; P = 0.05), but produced profound vasodilatation in the carotid territory, with a significant reduction in systolic blood pressure (133.6 vs. 120.5 mmHg; P = 0.011) and a marked reduction in carotid bed vascular resistance (19 580 vs. 13 078 dynes · s/cm 5 ; P = 0.001) and carotid characteristic impedance (3440 vs. 1923 dynes · s/cm 5 ; P = 0.002). Inorganic nitrate, in contrast, consistently reduced wave reflections across the first three harmonics (change in real part of reflection coefficient, 1st harmonic: -0.12; P = 0.03; 2nd harmonic: -0.11, P = 0.01; 3rd harmonic: -0.087; P = 0.09) and did not reduce blood pressure, carotid bed vascular resistance, or carotid characteristic impedance (P = NS). Nitroglycerin produces marked vasodilatation in the carotid circulation, with a pronounced reduction in blood pressure and inconsistent effects on central wave reflections. Inorganic nitrate, in contrast, produces consistent reductions in wave reflections, and unlike nitroglycerin, it does so without significant hypotension or cerebrovascular dilatation. These haemodynamic differences may underlie the different effects on exercise capacity and side effect profile of inorganic vs. organic nitrate in HFpEF. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Echocardiographic evaluation of cardiac dyssynchrony in patients with congestive heart failure.

PubMed

Qin, Chuan; Zhang, Li; Zhang, Zi-Ming; Wang, Bin; Ye, Zhou; Wang, Yong; Nanda, Navin C; Xie, Ming-Xing

2016-06-01

The present study investigated the application of echocardiography to evaluation of cardiac dyssynchrony in patients with congestive heart failure (CHF). A total of 348 consecutive CHF patients who were admitted for cardiac resynchronization (CRT) and presented with low ejection fraction (EF) and wide QRS duration were enrolled in this study, along with 388 healthy individuals. Dyssynchrony was assessed based on filling time ratio (FT/RR), left ventricular pre-ejection delay (PED), interventricular mechanical delay (IVMD), longitudinal opposing wall delay (LOWD) and radial septal to posterior wall delay (RSPWD). Response to CRT was defined as a ≥15% increase in EF. The results showed that FT/RR was decreased while PED, IVMD, LOWD and RSPWD were increased in the CHF group compared with the control group (P<0.01). In the CHF group, FT/RR was negatively correlated with the QRS duration, LV end-diastolic diameter (LVESd), LV end-diastolic volume (LVEDV) and LV end-systolic volume (LVESV) (P<0.01), but positively with the LVEF (P<0.01). Additionally, PED, IVMD, LOWD and RSPWD were positively correlated with the QRS duration, LVESd, LVEDV and LVESV (P<0.01), but negatively with the LVEF (P<0.01). The CHF group was divided into three subgroups according to the varying degrees of LVEF. FT/RR decreased successively from the LVEF-1 group to the LVEF-2 group to the LVEF-3 group, while the PED, IVMD, LOWD and RSPWD successively increased in the same order (P<0.01). The CHF group was divided into three subgroups according to the varying degrees of QRS duration, and FT/RR decreased successively in a sequence from the QRS-1 group to the QRS-2 group to the QRS-3 group, while the PED, IVMD, LOWD and RSPWD successively increased in the same order (P<0.01). Speckle tracking radial dyssynchrony ≥130 ms was predictive of an EF response in patients in QRS-1 group (78% sensitivity, 83% specificity), those in QRS-2 group (83% sensitivity, 77% specificity) and in QRS-3 group (89% sensitivity, 79% specificity). In conclusion, echocardiography is a convenient and sensitive method for evaluating cardiac dyssynchrony in patients with CHF.

Ivabradine, a novel heart rate slower: is it a sword of double blades in patients with idiopathic dilated cardiomyopathy?

PubMed

Rayan, Mona; Tawfik, Mazen; Alabd, Ali; Gamal, Amr

2011-08-01

To prospectively assess the safety and efficacy of ivabradine in patients with idiopathic dilated cardiomyopathy. We included 35 patients with idiopathic dilated cardiomyopathy with an ejection fraction (EF) <40% and heart rate >70 beats/min despite optimal medical therapy, according to the international guidelines in this prospective, non-randomized, single-arm, open-label safety study. Ivabradine was used as an add-on therapy to the maximally tolerated b-blocker in an increasing titrated dose till a target dose of 15 mg/day or resting heart rate of 60 beats/min for 3 months. During follow-up period the safety, patient tolerance and efficacy of this drug were assessed. All patients underwent 12-lead resting electrocardiography and Holter monitoring at inclusion and after 3 months. Statistical analysis was accomplished using paired t-test and Pearson correlation analysis. We found a significant reduction in the resting heart rate by a mean of 25.9 ± 9.4%, without a significant change of blood pressure. There was no prolongation of PR, QTc or QRS durations. Ventricular ectopic activity showed significant reduction (p<0.001). There was a significant correlation between the resting heart rate, NYHA and left ventricular ejection fraction (p<0.001 for both). One patient developed photopsia and decompensation was observed in another patient. Ivabradine is a safe and effective drug in reducing resting heart rate, improving NYHA functional class without undesirable effects on conduction parameters or ectopic activity.

Endurance sport and "cardiac injury": a prospective study of recreational ironman athletes.

PubMed

Leischik, Roman; Spelsberg, Norman

2014-09-03

Participation in triathlon competitions has increased in recent years. Many studies have described left or right ventricular injury in endurance athletes. The goal of this study was to examine the right and left ventricular cardiac structures and function and dynamic cardio-pulmonary performance in a large cohort of middle- and long-distance triathletes. 87 triathletes (54 male and 33 female) were examined using spiroergometry and echocardiography. The inclusion criterion was participation in at least one middle- or long distance triathlon. Male triathletes showed a maximum oxygen absorption of 58.1 ± 8.6 mL/min/kg (female triathletes 52.8 ± 5.7 mL/min/kg), maximum ergometer performance of 347.8 ± 49.9 W (female triathletes 264.5 ± 26.1 W). Left ventricular ejection fraction (EF) was normal (male triathletes EF: 61.9% ± 3%, female triathletes EF: 63.0% ± 2.7%) and systolic right ventricular area change fraction (RV AFC%) showed normal values (males RV AFC%: 33.5% ± 2.2%, females 32.2% ± 2.8%). Doppler indices of diastolic function were normal in both groups. With respect to the echocardiographic readings the left ventricular mass for males and females were 217.7 ± 41.6 g and 145.9 ± 31.3 g, respectively. The relative wall thickness for males was 0.50 ± 0.07, whereas it was 0.47 ± 0.09 for females. The probability of left ventricular mass >220 g increased with higher blood pressure during exercise (OR: 1.027, CI 1.002-1.052, p = 0.034) or with higher training volume (OR: 1.23, CI 1.04-1.47, p = 0.019). Right or left ventricular dysfunction could not be found, although the maximal participation in triathlon competitions was 29 years. A left ventricular mass >220 g is more likely to occur with higher arterial pressure during exercise and with a higher training volume.

Endurance Sport and “Cardiac Injury”: A Prospective Study of Recreational Ironman Athletes

PubMed Central

Leischik, Roman; Spelsberg, Norman

2014-01-01

Background: Participation in triathlon competitions has increased in recent years. Many studies have described left or right ventricular injury in endurance athletes. The goal of this study was to examine the right and left ventricular cardiac structures and function and dynamic cardio-pulmonary performance in a large cohort of middle- and long-distance triathletes. Methods: 87 triathletes (54 male and 33 female) were examined using spiroergometry and echocardiography. The inclusion criterion was participation in at least one middle- or long distance triathlon. Results: Male triathletes showed a maximum oxygen absorption of 58.1 ± 8.6 mL/min/kg (female triathletes 52.8 ± 5.7 mL/min/kg), maximum ergometer performance of 347.8 ± 49.9 W (female triathletes 264.5 ± 26.1 W). Left ventricular ejection fraction (EF) was normal (male triathletes EF: 61.9% ± 3%, female triathletes EF: 63.0% ± 2.7%) and systolic right ventricular area change fraction (RV AFC%) showed normal values (males RV AFC%: 33.5% ± 2.2%, females 32.2% ± 2.8%). Doppler indices of diastolic function were normal in both groups. With respect to the echocardiographic readings the left ventricular mass for males and females were 217.7 ± 41.6 g and 145.9 ± 31.3 g, respectively. The relative wall thickness for males was 0.50 ± 0.07, whereas it was 0.47 ± 0.09 for females. The probability of left ventricular mass >220 g increased with higher blood pressure during exercise (OR: 1.027, CI 1.002–1.052, p = 0.034) or with higher training volume (OR: 1.23, CI 1.04–1.47, p = 0.019). Conclusions: Right or left ventricular dysfunction could not be found, although the maximal participation in triathlon competitions was 29 years. A left ventricular mass >220 g is more likely to occur with higher arterial pressure during exercise and with a higher training volume. PMID:25192145

Coronary artery disease detection - limitations of stress testing in left ventricular dysfunction

PubMed Central

Bomb, Ritin; Kumar, Senthil; Chockalingam, Anand

2017-01-01

Incidental diagnosis of left ventricular systolic dysfunction (LVD) is common in clinical practice. The prevalence of asymptomatic LVD (Ejection Fraction, EF < 50%) is 6.0% in men and 0.8% in women and is twice as common as symptomatic LVD. The timely and definitive exclusion of an ischemic etiology is central to optimizing care and reducing mortality in LVD. Advances in cardiovascular imaging provide many options for imaging of patients with left ventricular dysfunction. Clinician experience, patient endurance, imaging modality characteristics, cost and safety determine the choice of testing. In this review, we have compared the diagnostic utility of established tests - nuclear and echocardiographic stress testing with newer techniques like coronary computerized tomography and cardiac magnetic resonance imaging and highlight their inherent limitations in patients with underlying left ventricular dysfunction. PMID:28515848

Tumor necrosis factor and interleukin-6 levels in hypertensive patients with and without left ventricular hypertrophy.

PubMed

Leibowitz, David; Planer, David; Ben-Ivgi, Fanny; Weiss, A Teddy; Bursztyn, Michael

2005-01-01

The objective of this prospective study was to examine the association between serum levels of TNF (tumor-necrosis factor) and IL-6 (interleukin-6) and left ventricular mass in hypertensive patients. Hypertensive patients currently receiving medical therapy were eligible. All subjects underwent echocardiography with measurements of left ventricular (LV) mass and ejection fraction (EF) and had serum levels of TNF and IL-6 measured by ELISA immunoassay. 35 subjects (20F, 15M; mean age 56.4 +/- 10.5 yrs) were studied. 19 patients (54%) had elevated LV mass. Of these patients, 6 (32%) had detectable serum TNF levels and 1 (7%) had detectable IL-6 levels, (p = NS). Hypertensive patients with elevated LV mass do not consistently exhibit elevated cytokine levels when compared to those with normal LV mass.

Automated processing of first-pass radioisotope ventriculography data to determine essential central circulation parameters

NASA Astrophysics Data System (ADS)

Krotov, Aleksei; Pankin, Victor

2017-09-01

The assessment of central circulation (including heart function) parameters is vital in the preventive diagnostics of inherent and acquired heart failures and during polychemotherapy. The protocols currently applied in Russia do not fully utilize the first-pass assessment (FPRNA) and that results in poor data formalization, while the FPRNA is the one of the fastest, affordable and compact methods among other radioisotope diagnostics protocols. A non-imaging algorithm basing on existing protocols has been designed to use the readings of an additional detector above vena subclavia to determine the total blood volume (TBV), not requiring blood sampling in contrast to current protocols. An automated processing of precordial detector readings is presented, in order to determine the heart strike volume (SV). Two techniques to estimate the ejection fraction (EF) of the heart are discussed.

Implantation of a cardiac resynchronization therapy-defibrillator device in a patient with persistent left superior vena cava.

PubMed

Atar, İlyas; Karaçağlar, Emir; Özçalık, Emre; Özin, Bülent; Müderrisoğlu, Haldun

2015-06-01

Presence of a persistent left superior vena cava (PLSVC) is generally clinically asymptomatic and discovered incidentally during central venous catheterization. However, PLSVC may cause technical difficulties during cardiac device implantation. An 82-year-old man with heart failure symptoms and an ejection fraction (EF) of 20% was scheduled for resynchronization therapy-defibrillator device (CRT-D) implantation. A PLSVC draining via a dilated coronary sinus into an enlarged right atrium was diagnosed. First, an active-fixation right ventricular lead was inserted into the right atrium through the PLSVC. The stylet was preshaped to facilitate its passage to the right ventricular apex. An atrial lead was positioned on the right atrium free wall, and an over-the-wire coronary sinus lead deployed to a stable position. CRT-D implantation procedure was successfully completed.

Right Ventricular Ejection Fraction Is Incremental to Left Ventricular Ejection Fraction for the Prediction of Future Arrhythmic Events in Patients With Systolic Dysfunction.

PubMed

Mikami, Yoko; Jolly, Umjeet; Heydari, Bobak; Peng, Mingkai; Almehmadi, Fahad; Zahrani, Mohammed; Bokhari, Mahmoud; Stirrat, John; Lydell, Carmen P; Howarth, Andrew G; Yee, Raymond; White, James A

2017-01-01

Left ventricular ejection fraction remains the primary risk stratification tool used in the selection of patients for implantable cardioverter defibrillator therapy. However, this solitary marker fails to identify a substantial portion of patients experiencing sudden cardiac arrest. In this study, we examined the incremental value of considering right ventricular ejection fraction for the prediction of future arrhythmic events in patients with systolic dysfunction using the gold standard of cardiovascular magnetic resonance. Three hundred fourteen consecutive patients with ischemic cardiomyopathy or nonischemic dilated cardiomyopathy undergoing cardiovascular magnetic resonance were followed for the primary outcome of sudden cardiac arrest or appropriate implantable cardioverter defibrillator therapy. Blinded quantification of left ventricular and right ventricular (RV) volumes was performed from standard cine imaging. Quantification of fibrosis from late gadolinium enhancement imaging was incrementally performed. RV dysfunction was defined as right ventricular ejection fraction ≤45%. Among all patients (164 ischemic cardiomyopathy, 150 nonischemic dilated cardiomyopathy), the mean left ventricular ejection fraction was 32±12% (range, 6-54%) with mean right ventricular ejection fraction of 48±15% (range, 7-78%). At a median of 773 days, 49 patients (15.6%) experienced the primary outcome (9 sudden cardiac arrest, 40 appropriate implantable cardioverter defibrillator therapies). RV dysfunction was independently predictive of the primary outcome (hazard ratio=2.98; P=0.002). Among those with a left ventricular ejection fraction >35% (N=121; mean left ventricular ejection fraction, 45±6%), RV dysfunction provided an adjusted hazard ratio of 4.2 (P=0.02). RV dysfunction is a strong, independent predictor of arrhythmic events. Among patients with mild to moderate LV dysfunction, a cohort greatly contributing to global sudden cardiac arrest burden, this marker provides robust discrimination of high- versus low-risk subjects. © 2017 American Heart Association, Inc.

Right ventricular strain in heart failure: Clinical perspective.

PubMed

Tadic, Marijana; Pieske-Kraigher, Elisabeth; Cuspidi, Cesare; Morris, Daniel A; Burkhardt, Franziska; Baudisch, Ana; Haßfeld, Sabine; Tschöpe, Carsten; Pieske, Burket

2017-10-01

The number of studies demonstrating the importance of right ventricular remodelling in a wide range of cardiovascular diseases has increased in the past two decades. Speckle-tracking imaging provides new variables that give comprehensive information about right ventricular function and mechanics. In this review, we summarize current knowledge of right ventricular mechanics in heart failure with reduced ejection fraction and preserved ejection fraction. We searched PubMed, MEDLINE, Ovid and Embase databases for studies published from January 2000 to December 2016 in the English language using the following keywords: "right ventricle"; "strain"; "speckle tracking"; "heart failure with reduced ejection fraction"; and "heart failure with preserved ejection fraction". Investigations showed that right ventricular dysfunction is associated with higher cardiovascular and overall mortality in patients with heart failure, irrespective of ejection fraction. The number of studies investigating right ventricular strain in patients with heart failure with reduced ejection fraction is constantly increasing, whereas data on right ventricular mechanics in patients with heart failure with preserved ejection fraction are limited. Given the high feasibility, accuracy and clinical implications of right ventricular strain in the population with heart failure, it is of great importance to try to include the evaluation of right ventricular strain as a regular part of each echocardiographic examination in patients with heart failure. However, further investigations are necessary to establish right ventricular strain as a standard variable for decision-making. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Myocardial dysfunction in mitochondrial diabetes treated with Coenzyme Q10.

PubMed

Salles, João Eduardo; Moisés, Valdir A; Almeida, Dirceu R; Chacra, Antonio R; Moisés, Regina S

2006-04-01

Maternally-inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial tRNA Leu (UUR) gene at the base pair 3243. Although some previous articles have reported that this mutation may be a cause of cardiomyopathy in diabetes, the degree of cardiac involvement and a specific treatment has not been established. Here, we reported a case of a patient with MIDD who developed congestive heart failure and the therapeutic usefulness of Coenzyme Q10 (CoQ10). In our patient, after the introduction of Coenzyme Q10 150 mg/day, there was a gradual improvement on left ventricular function evaluated by echocardiography. The fractional shortening (FS) and ejection fraction (EF) increased from 26 to 34% and from 49 to 64%, respectively. No side effects were noted. Three months after CoQ10 discontinuation, the parameters of systolic function evaluated by echocardiography decreased, suggesting that CoQ10 had a beneficial effect. Identification of diabetes and cardiomyopathy due to mitochondrial gene mutation may have therapeutic implications and Coenzyme Q10 is a possible adjunctive treatment in such patients.

Echocardiograms during six hours of bedrest at head-down and head-up tilt and during space flight

NASA Technical Reports Server (NTRS)

Lathers, C. M.; Riddle, J. M.; Mulvagh, S. L.; Mukai, C.; Diamandis, P. H.; Dussack, L. G.; Bungo, M. W.; Charles, J. B.

1993-01-01

Left ventricular end-diastolic volume increased after 4 1/2 to 6 hours of space flight, but was significantly decreased after 5 to 6 days of space flight. To determine the role of acute gravitational effects in this phenomenon, responses to a 6-hour bedrest model of 0 gravity (G; 5 degrees head-down tilt) were compared with those of fractional gravity loads of 1/6 G, 1/3 G, and 2/3 G by using head-up tilts of 10 degrees, 20 degrees, and 42 degrees, respectively. On 4 different days, six healthy male subjects were tilted at one of the four angles for 6 hours. Cardiac dimensions and volumes were determined from two-dimensional and M-mode echocardiograms in the left lateral decubitus position at control (0), 2, 4, and 6 hours. Stroke volume decreased with time (P < .05) for all tilt angles when compared with control. Ejection fraction (EF) at -5 degrees was greater than at +20 degrees and +42 degrees (not significant); EF at +10 degrees was greater than at +42 degrees (not significant). For the tilt angles of -5 degrees, +10 degrees, and +20 degrees, mean heart rate decreased during the first 2 hours, and returned to control or was slightly elevated above control (+20 degrees) by 6 hours (not significant). At the +42 degrees angle of tilt, heart rate was increased above control at hours 2, 4, and 6. There were no significant differences in cardiac output at any time point for any tilt angle.(ABSTRACT TRUNCATED AT 250 WORDS).

Change of heart dimensions and function during pregnancy in goats.

PubMed

Szaluś-Jordanow, Olga; Czopowicz, Michał; Witkowski, Lucjan; Moroz, Agata; Mickiewicz, Marcin; Frymus, Tadeusz; Markowska-Daniel, Iwona; Bagnicka, Emilia; Kaba, Jarosław

2018-03-08

The study aimed to evaluate the effect of pregnancy on heart diameters and function in goats. Transthoracic echocardiography of 12 female dairy goats of two Polish regional breeds was performed. A Mindray M7 diagnostic ultrasound system with Phased Array transducer was used. Simultaneously, electrocardiography was recorded. All animals were examined four times - at mating season, at the end of the first trimester, at the end of the second trimester and just before kidding. Eleven measurements were taken each time: aortic and left atrial diameter (AoD and LAD), right and left ventricular internal diameter in diastole (RVIDd and LVIDd), left ventricular internal diameter in systole (LVIDs), inter-ventricular septum thickness in diastole and systole (IVSd and IVSd) and left ventricular posterior wall in diastole and systole (LVPWd and LVPWs), maximum left and right ventricular outflow tract velocity (RVOT Vmax and LVOT Vmax). Nine consecutive measurements were derived: the ratio of the left atrial diameter to the aortic diameter (AoD/LAD), left ventricular fractional shortening (FS%), left ventricular ejection fraction (EF%), maximum outflow tract pressure gradients (RVOT PGmax and LVOT PGmax), left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV), stroke volume (SV) and cardiac output (CO). HR, LAD, LVPWs, IVSs increased significantly in the first trimester. AoD and RVIDd were significantly higher around parturition. LVIDd, FS%, EF%, SV and CO rose both in the first and third trimester. No measurement decreased during pregnancy. The study confirms that pregnancy causes changes in the heart size and functioning. Copyright © 2018. Published by Elsevier Ltd.

Diastolic dysfunction and heart failure with a preserved ejection fraction: Relevance in critical illness and anaesthesia

PubMed Central

Maharaj, R.

2012-01-01

Epidemiological and clinical studies suggest that HF with a preserved ejection fraction will become the more common form of HF which clinicians will encounter. The spectrum of diastolic disease extends from the asymptomatic phase to fulminant cardiac failure. These patients are commonly encountered in operating rooms and critical care units. A clearer understanding of the underlying pathophysiology and clinical implications of HF with a preserved ejection fraction is fundamental to directing further research and to evaluate interventions. This review highlights the impact of diastolic dysfunction and HF with a preserved ejection fraction during the perioperative period and during critical illness. PMID:23960679

Right ventricular function after coronary artery bypass graft surgery--a magnetic resonance imaging study.

PubMed

Joshi, Subodh B; Roswell, Robert O; Salah, Ali K; Zeman, Peter R; Corso, Paul J; Lindsay, Joseph; Fuisz, Anthon R

2010-01-01

A reduction in right ventricular function commonly occurs in the early postoperative period after coronary artery bypass graft surgery (CABG). We sought to determine the longer-term effect of CABG on right ventricular function. Cardiac magnetic resonance imaging was performed before and approximately 3 months after surgery in 28 patients undergoing elective CABG. Right ventricular (RV) ejection fraction was assessed by planimetry of electrocardiographically gated cine images. There was a statistically significant increase in left ventricular ejection fraction from 50% to 58% (P=.003) after CABG. RV ejection fraction also increased from 54% to 60% (P=.002). In patients with lower baseline RV ejection fraction (below the median, < 53%), this parameter improved from 47% to 57% (P<.001). Both on-pump (47% vs. 62%, P=.003) as well as off-pump CABG (47% vs. 55%, P=.009) lead to an improvement in RV function in patients in the initial low RV ejection fraction group. Long-term right ventricular function was not adversely affected by CABG. An improvement in RV function occurred after surgery in patients with low baseline RV ejection fraction and was similar in patients who underwent surgery with or without cardiopulmonary bypass.

Dimensional correlates of left ventricular dilation in the presence of hypertrophy.

PubMed

Al-Nouri, M B; Ford, L E; Wix, H

1983-01-01

Twelve normal subjects, 50 patients with valvular heart disease, and 14 with hypertension were studied. Those with valvular disease were divided into two groups: 28 with angiographically measured ejection fractions greater than or equal to 0.6 and 22 with ejection fractions less than 0.6. The echocardiographically measured ventricular thickness divided by radius ratio (t/r) was approximately proportional to peak systolic pressure (P) in all groups having ejection fractions greater than or equal to 0.6, so that the t/r divided by P ratios were nearly the same. Patients with ejection fractions less than 0.6 had significantly lower t/r divided by P values. No single component of the t/r divided by P ratio would identify the patients with lower ejection fractions. The t/r divided by P ratios in 14 hypertensive patients were nearly identical to the ratios in six patients with aortic stenosis and ejection fractions greater than or equal to 0.6, indicating that an aortic valve gradient does not cause a grossly abnormal form of pressure hypertrophy. The t/r ratio is thus a double sensitive, noninvasive index of dilation when correlated with systolic pressure.

Transesophageal Echocardiography, 3-Dimensional and Speckle Tracking Together as Sensitive Markers for Early Outcome in Patients With Left Ventricular Dysfunction Undergoing Cardiac Surgery.

PubMed

Kumar, Alok; Puri, Goverdhan Dutt; Bahl, Ajay

2017-10-01

Speckle tracking, when combined with 3-dimensional (3D) left ventricular ejection fraction, might prove to be a more sensitive marker for postoperative ventricular dysfunction. This study investigated early outcomes in a cohort of patients with left ventricular dysfunction undergoing cardiac surgery. Prospective, blinded, observational study. University hospital; single institution. The study comprised 73 adult patients with left ventricular ejection fraction <50% undergoing cardiac surgery using cardiopulmonary bypass. Routine transesophageal echocardiography before and after bypass. Global longitudinal strain using speckle tracking and 3D left ventricular ejection fraction were computed using transesophageal echocardiography. Mean prebypass global longitudinal strain and 3D left ventricle ejection fraction were significantly lower in patients with postoperative low-cardiac-output syndrome compared with patients who did not develop low cardiac output (global longitudinal strain -7.5% v -10.7% and 3D left ventricular ejection fraction 29% v 39%, respectively; p < 0.0001). The cut-off value of global longitudinal strain predicting postoperative low-cardiac-output syndrome was -6%, with 95% sensitivity and 68% specificity; and 3D left ventricular ejection fraction was 19% with 98% sensitivity and 81% specificity. Preoperative left ventricular global longitudinal strain (-6%) and 3D left ventricular ejection fraction (19%) together could act as predictor of postoperative low-cardiac-output states with high sensitivity (99.9%) in patients undergoing cardiac surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of Pharmacokinetic and Pharmacodynamic Drug-Drug Interaction of Sacubitril/Valsartan (LCZ696) and Sildenafil in Patients With Mild-to-Moderate Hypertension.

PubMed

Hsiao, H-L; Langenickel, T H; Petruck, J; Kode, K; Ayalasomayajula, S; Schuehly, U; Greeley, M; Pal, P; Zhou, W; Prescott, M F; Sunkara, G; Rajman, I

2018-03-01

Sacubitril/valsartan (LCZ696) is indicated for the treatment of patients with heart failure and reduced ejection fraction (HFrEF). Since patients with HFrEF may receive sacubitril/valsartan and sildenafil, both increasing cyclic guanosine monophosphate, the present study evaluated the pharmacokinetic and pharmacodynamic drug interaction potential between sacubitril/valsartan and sildenafil. In this open-label, three-period, single sequence study, patients with mild-to-moderate hypertension (153.8 ± 8.2 mmHg mean systolic blood pressure (SBP)) received a single dose of sildenafil 50 mg, sacubitril/valsartan 400 mg once daily for 5 days, and sacubitril/valsartan and sildenafil coadministration. When coadministered with sildenafil, the AUC and C max of valsartan decreased by 29% and 39%, respectively. Coadministration of sacubitril/valsartan and sildenafil resulted in a greater decrease in BP (-5/-4/-4 mmHg mean ambulatory SBP/DBP/MAP (mean arterial pressure)) than with sacubitril/valsartan alone. Both treatments were generally safe and well tolerated in this study; however, the additional BP reduction suggests that sildenafil should be administered cautiously in patients receiving sacubitril/valsartan. Unique identifier: NCT01601470. © 2017 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Effect of a Reminder Statement on Echocardiography Reports on Referrals for Implantable Cardioverter-Defibrillators for Primary Prevention.

PubMed

Chokshi, Moulin; McNamara, Robert L; Rajeswaran, Yasotha; Lampert, Rachel

2017-02-01

Numerous trials show the benefit of implantable cardioverter-defibrillators (ICDs) for primary prevention in patients with low ejection fraction (EF), a class I indication. However, underutilization is well documented. We retrospectively reviewed charts to see whether placing a reminder statement into echocardiogram reports for appropriate patients increased adherence to guidelines. From January through June 2013, a brief reminder of the ICD guidelines was automatically inserted into echocardiogram reports with EF ≤ 35% (reminder period). Charts were reviewed to determine if these patients (1) were referred to Electrophysiology (EP) within 6 months of the index echo and (2) received an ICD within 6 months of EP referral. Chart review of all patients who had an echocardiogram performed between March and August 2012 with an EF ≤ 35% provided a control period. More patients were referred to EP in the reminder period compared with control period, 68% (54 of 80) versus 51% (53 of 104), p = 0.03. There was also a higher rate of discussions in the reminder period between patients and physicians about ICD therapy (71% vs 54%, p = 0.02). Among patients appropriate for ICD, 52% of patients during the reminder period received an ICD versus 38% of patients during the control period (p = 0.11). A simple reminder statement on echocardiography reports led to a significant improvement in appropriate EP referrals and a trend toward increased ICD implantation in appropriate patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Intra coronary freshly isolated bone marrow cells transplantation improve cardiac function in patients with ischemic heart disease

PubMed Central

2012-01-01

Background Autologous bone marrow cell transplantation (BMCs-Tx) is a promising novel option for treatment of cardiovascular disease. In this study we analyzed whether intracoronary autologous freshly isolated BMCs-Tx have beneficial effects on cardiac function in patients with ischemic heart disease (IHD). Results In this prospective nonrandomized study we treated 12 patients with IHD by freshly isolated BMCs-Tx by use of point of care system and compared them with a representative 12 control group without cell therapy. Global ejection fraction (EF) and infarct size area were determined by left ventriculography. Intracoronary transplantation of autologous freshly isolated BMCs led to a significant reduction of infarct size (p < 0.001) and an increase of global EF (p = 0.003) as well as infarct wall movement velocity (p < 0.001) after 6 months follow-up compared to control group. In control group there were no significant differences of global EF, infarct size and infarct wall movement velocity between baseline and 6 months after coronary angiography. Furthermore, we found significant decrease in New York Heart Association (NYHA) as well as significant decrease of B-type natriuretic peptide (BNP) level 6 months after intracoronary cell therapy (p < 0.001), whereas there were no significant differences in control group 6 months after coronary angiography. Conclusions These results demonstrate that intracoronary transplantation of autologous freshly isolated BMCs by use of point of care system is safe and may lead to improvement of cardiac function in patients with IHD. Trial registration Registration number: ISRCTN54510226 PMID:22534049

WHO’s in Second?

PubMed Central

Groskreutz, Dayna J.; Gehlbach, Brian K.

2013-01-01

World Health Organization (WHO) group 2 pulmonary hypertension (PH) due to left-side heart disease (ie, heart failure or left-sided valvular heart disease) is the most common form of PH in western countries. Distinguishing patients with WHO group 2 PH, particularly the subset of patients with PH due to heart failure with preserved ejection fraction (HFpEF), from those with WHO group 1 pulmonary arterial hypertension (PAH) is challenging. Separating the two conditions is of vital importance because treatment strategies differ completely. Furthermore, therapies that are indicated for WHO group 1 PAH may be harmful in patients with WHO group 2 PH. We review the somewhat confusing PH nomenclature and the WHO classification system and rationale behind it. We then focus on left-side heart disorders that cause PH. An aging population and advances in the medical management of common cardiovascular disorders have caused the prevalence of heart failure to rise significantly, with more than one-half of patients having HFpEF. We review contemporary studies that focus on clinical and echocardiographic findings that help to distinguish HFpEF from PAH in the patient with PH. We discuss the typical, and sometimes atypical, hemodynamic profiles that characterize these two groups, review challenges in the interpretation of data obtained by right-sided heart catheterization, and highlight special maneuvers that may be required for accurate diagnosis. Finally, we review the largely disappointing studies on the use of PAH-specific therapies in patients with WHO group 2 PH, including the use of prostacyclins, endothelin receptor antagonists, and the more promising phosphodiesterase-5 inhibitors. PMID:23918108

Doppler Assessment of Diastolic Function Reflect the Severity of Injury in Rats With Chronic Heart Failure.

PubMed

Sanchez, Pablo; Lancaster, Jordan J; Weigand, Kyle; Mohran, Saffie-Alrahman Ezz-Eldin; Goldman, Steven; Juneman, Elizabeth

2017-10-01

For chronic heart failure (CHF), more emphasis has been placed on evaluation of systolic as opposed to diastolic function. Within the study of diastology, measurements of left ventricular (LV) longitudinal myocardial relaxation have the most validation. Anterior wall radial myocardial tissue relaxation velocities along with mitral valve inflow (MVI) patterns are applicable diastolic parameters in the differentiation between moderate and severe disease in the ischemic rat model of CHF. Myocardial tissue relaxation velocities correlate with traditional measurements of diastolic function (ie, hemodynamics, Tau, and diastolic pressure-volume relationships). Male Sprague-Dawley rats underwent left coronary artery ligation or sham operation. Echocardiography was performed at 3 and 6 weeks after coronary ligation to evaluate LV ejection fraction (EF) and LV diastolic function through MVI patterns (E, A, and E/A) and Doppler imaging of the anterior wall (e' and a'). The rats were categorized into moderate or severe CHF according to their LV EF at 3 weeks postligation. Invasive hemodynamic measurements with solid-state pressure catheters were obtained at the 6-week endpoint. Moderate (N = 20) and severe CHF (N = 22) rats had significantly (P < .05) different EFs, hemodynamics, and diastolic pressure-volume relationships. Early diastolic anterior wall radial relaxation velocities as well as E/e' ratios separated moderate from severe CHF and both diastolic parameters had strong correlations with invasive hemodynamic measurements of diastolic function. Radial anterior wall e' and E/e' can be used for serial assessment of diastolic function in rats with moderate and severe CHF. Copyright © 2017 Elsevier Inc. All rights reserved.

Central Hemodynamics Measured During 5 Repetition Maximum Free Weight Resistance Exercise.

PubMed

Howard, Jonathan S; McLester, Cherilyn N; Evans, Thomas W; McLester, John R; Calloway, Jimmy P

2018-01-01

The PhysioFlow™ is a piece of equipment that uses bioimpedance cardiography to measure central hemodynamics. The purpose of this research was to explore the novel approach of monitoring central hemodynamics during free weight resistance exercise using bioimpedance cardiography throughout a 5 repetition maximum (5RM). Thirty participants ranging from beginner to advanced lifters (16 males and 14 females) completed a 5RM for back squat, seated push press, and bicep curl while connected to the PhysioFlow™ to assess the response of heart rate (HR), stroke volume (SV), cardiac output (Q), and ejection fraction (EF). Participants were cued for form and to breathe normally throughout the lifts. The PhysioFlow™ detected an increase in HR and Q for all lifts between rest and each repetition ( p < 0.05). There was also an increase in HR and Q from repetition 1 to repetition 5 for all lifts ( p < 0.05). No changes in EF or SV were detected between resting measurements and each repetition for all lifts ( p > 0.05) and no changes in EF or SV were detected when all repetitions were compared to each other for all lifts ( p > 0.05). In conclusion, the PhysioFlow™ was able to detect changes in HR and Q during dynamic free weight resistance exercise. This novel approach may provide a mechanism for monitoring central hemodynamics during free weight resistance training. However, more research needs to be conducted as the exercise protocol for this investigation did not allow for a comparison to a reference method.

Assessment of myocardial viability by dynamic tomographic iodine 123 iodophenylpentadecanoic acid imaging: comparison with rest-redistribution thallium 201 imaging.

PubMed

Iskandrian, A S; Powers, J; Cave, V; Wasserleben, V; Cassell, D; Heo, J

1995-01-01

This study examined the ability of dynamic 123I-labeled iodophenylpentadecanoic acid (IPPA) imaging to detect myocardial viability in patients with left ventricular (LV) dysfunction caused by coronary artery disease. Serial 180-degree single-photon emission computed tomographic (SPECT) images (five sets, 8 minutes each) were obtained starting 4 minutes after injection of 2 to 6 mCi 123I at rest in 21 patients with LV dysfunction (ejection fraction [EF] 34% +/- 11%). The segmental uptake was compared with that of rest-redistribution 201Tl images (20 segments/study). The number of perfusion defects (reversible and fixed) was similar by IPPA and thallium (11 +/- 5 vs 10 +/- 5 segments/patient; difference not significant). There was agreement between IPPA and thallium for presence or absence (kappa = 0.78 +/- 0.03) and nature (reversible, mild fixed, or severe fixed) of perfusion defects (kappa = 0.54 +/- 0.04). However, there were more reversible IPPA defects than reversible thallium defects (7 +/- 4 vs 3 +/- 4 segments/patient; p = 0.001). In 14 patients the EF (by gated pool imaging) improved after coronary revascularization from 33% +/- 11% to 39% +/- 12% (p = 0.002). The number of reversible IPPA defects was greater in the seven patients who had improvement in EF than in the patients without such improvement (10 +/- 4 vs 5 +/- 4 segments/patient; p = 0.075). 123I-labeled IPPA SPECT imaging is a promising new technique for assessment of viability. Reversible defects predict recovery of LV dysfunction after coronary revascularization.

Evaluation of training nurses to perform semi-automated three-dimensional left ventricular ejection fraction using a customised workstation-based training protocol.

PubMed

Guppy-Coles, Kristyan B; Prasad, Sandhir B; Smith, Kym C; Hillier, Samuel; Lo, Ada; Atherton, John J

2015-06-01

We aimed to determine the feasibility of training cardiac nurses to evaluate left ventricular function utilising a semi-automated, workstation-based protocol on three dimensional echocardiography images. Assessment of left ventricular function by nurses is an attractive concept. Recent developments in three dimensional echocardiography coupled with border detection assistance have reduced inter- and intra-observer variability and analysis time. This could allow abbreviated training of nurses to assess cardiac function. A comparative, diagnostic accuracy study evaluating left ventricular ejection fraction assessment utilising a semi-automated, workstation-based protocol performed by echocardiography-naïve nurses on previously acquired three dimensional echocardiography images. Nine cardiac nurses underwent two brief lectures about cardiac anatomy, physiology and three dimensional left ventricular ejection fraction assessment, before a hands-on demonstration in 20 cases. We then selected 50 cases from our three dimensional echocardiography library based on optimal image quality with a broad range of left ventricular ejection fractions, which was quantified by two experienced sonographers and the average used as the comparator for the nurses. Nurses independently measured three dimensional left ventricular ejection fraction using the Auto lvq package with semi-automated border detection. The left ventricular ejection fraction range was 25-72% (70% with a left ventricular ejection fraction <55%). All nurses showed excellent agreement with the sonographers. Minimal intra-observer variability was noted on both short-term (same day) and long-term (>2 weeks later) retest. It is feasible to train nurses to measure left ventricular ejection fraction utilising a semi-automated, workstation-based protocol on previously acquired three dimensional echocardiography images. Further study is needed to determine the feasibility of training nurses to acquire three dimensional echocardiography images on real-world patients to measure left ventricular ejection fraction. Nurse-performed evaluation of left ventricular function could facilitate the broader application of echocardiography to allow cost-effective screening and monitoring for left ventricular dysfunction in high-risk populations. © 2014 John Wiley & Sons Ltd.

Benefits of Permanent His Bundle Pacing Combined With Atrioventricular Node Ablation in Atrial Fibrillation Patients With Heart Failure With Both Preserved and Reduced Left Ventricular Ejection Fraction.

PubMed

Huang, Weijian; Su, Lan; Wu, Shengjie; Xu, Lei; Xiao, Fangyi; Zhou, Xiaohong; Ellenbogen, Kenneth A

2017-04-01

Clinical benefits from His bundle pacing (HBP) in heart failure patients with preserved and reduced left ventricular ejection fraction are still inconclusive. This study evaluated clinical outcomes of permanent HBP in atrial fibrillation patients with narrow QRS who underwent atrioventricular node ablation for heart failure symptoms despite rate control by medication. The study enrolled 52 consecutive heart failure patients who underwent attempted atrioventricular node ablation and HBP for symptomatic atrial fibrillation. Echocardiographic left ventricular ejection fraction and left ventricular end-diastolic dimension, New York Heart Association classification and use of diuretics for heart failure were assessed during follow-up visits after permanent HBP. Of 52 patients, 42 patients (80.8%) received permanent HBP and atrioventricular node ablation with a median 20-month follow-up. There was no significant change between native and paced QRS duration (107.1±25.8 versus 105.3±23.9 milliseconds, P =0.07). Left ventricular end-diastolic dimension decreased from the baseline ( P <0.001), and left ventricular ejection fraction increased from baseline ( P <0.001) in patients with a greater improvement in heart failure with reduced ejection fraction patients (N=20) than in heart failure with preserved ejection fraction patients (N=22). New York Heart Association classification improved from a baseline 2.9±0.6 to 1.4±0.4 after HBP in heart failure with reduced ejection fraction patients and from a baseline 2.7±0.6 to 1.4±0.5 after HBP in heart failure with preserved ejection fraction patients. After 1 year of HBP, the numbers of patients who used diuretics for heart failure decreased significantly ( P <0.001) when compared to the baseline diuretics use. Permanent HBP post-atrioventricular node ablation significantly improved echocardiographic measurements and New York Heart Association classification and reduced diuretics use for heart failure management in atrial fibrillation patients with narrow QRS who suffered from heart failure with preserved or reduced ejection fraction. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Tailor-made heart simulation predicts the effect of cardiac resynchronization therapy in a canine model of heart failure.

PubMed

Panthee, Nirmal; Okada, Jun-ichi; Washio, Takumi; Mochizuki, Youhei; Suzuki, Ryohei; Koyama, Hidekazu; Ono, Minoru; Hisada, Toshiaki; Sugiura, Seiryo

2016-07-01

Despite extensive studies on clinical indices for the selection of patient candidates for cardiac resynchronization therapy (CRT), approximately 30% of selected patients do not respond to this therapy. Herein, we examined whether CRT simulations based on individualized realistic three-dimensional heart models can predict the therapeutic effect of CRT in a canine model of heart failure with left bundle branch block. In four canine models of failing heart with dyssynchrony, individualized three-dimensional heart models reproducing the electromechanical activity of each animal were created based on the computer tomographic images. CRT simulations were performed for 25 patterns of three ventricular pacing lead positions. Lead positions producing the best and the worst therapeutic effects were selected in each model. The validity of predictions was tested in acute experiments in which hearts were paced from the sites identified by simulations. We found significant correlations between the experimentally observed improvement in ejection fraction (EF) and the predicted improvements in ejection fraction (P<0.01) or the maximum value of the derivative of left ventricular pressure (P<0.01). The optimal lead positions produced better outcomes compared with the worst positioning in all dogs studied, although there were significant variations in responses. Variations in ventricular wall thickness among the dogs may have contributed to these responses. Thus CRT simulations using the individualized three-dimensional heart models can predict acute hemodynamic improvement, and help determine the optimal positions of the pacing lead. Copyright © 2016 Elsevier B.V. All rights reserved.

Usefulness of admission gamma-glutamyltransferase level for predicting new-onset heart failure in patients with acute coronary syndrome with left ventricular systolic dysfunction.

PubMed

Sarıkaya, Savaş; Aydın, Gülay; Yücel, Hasan; Kaya, Hakkı; Yıldırımlı, Kutay; Başaran, Ahmet; Zorlu, Ali; Sahin, Safak; Akyol, Lütfü; Bulut, Musa

2014-04-01

Our aim was to determine whether there is a relationship between admission gamma-glutamyltransferase (GGT) and subsequent heart failure hospitalizations in patients with acute coronary syndrome. We selected 123 patients with newly diagnosed acute coronary syndrome of ejection fraction (EF) <45%. Patients were followed 15±10 months, and the relationship between admission GGT level and hospitalization because of heart failure during the follow-up was examined. Twenty-three (18.7%) patients were hospitalized during the follow-up of 15±10 months. Receiver operating characteristic (ROC) curve analysis showed that the cut-off point of admission GGT related to predict hospitalization was 49 IU/L, with a sensitivity of 81.7% and specificity of 65.2%. Increased GGT >49 IU/L on admission, presence of hypertension and hyperlipidemia, left ventricular ejection fraction (LVEF), right ventricular dysfunction, moderate-to-severe mitral regurgitation, alanine aminotransferase level, and antiplatelet agent usage were found to have prognostic significance in univariate Cox proportional hazards analysis. In multivariate Cox proportional-hazards model, increased GGT >49 IU/L on admission (hazard ratio [HR] 2.663, p=0.047), presence of hypertension (HR 4.107, p=0.007), and LVEF (HR 0.911, p=0.002) were found to be independent factors to predict new-onset heart failure requiring hospitalization. Hospitalization in heart failure was associated with increased admission GGT levels. Increased admission GGT level in acute coronary syndrome with heart failure should be monitored closely and treated aggressively.

Tailoring therapy for ischemic cardiomyopathy: is Laplace's law enough?

PubMed

Adhyapak, Srilakshmi M; Parachuri, V Rao

2017-09-01

The burden of heart failure has long plagued the productive years of the population, with therapeutic advances in the timely treatment of ischemic heart disease decreasing its associated mortality. Angiotensin-converting enzyme inhibitors and β-blockers have impacted heart failure therapeutics in a revolutionary way. The importance of blockade of the renin-angiotensin system and adrenergic stimulation are fully accepted concepts that apply in young and old, symptomatic and asymptomatic, borderline low and very low Ejection Fraction (EF), left ventricular failure and biventricular failure. Despite several interventions, both pharmaceutical and device based for the treatment of ensuing heart failure, the incidence is increasing in large proportions. Newer molecules like sacubitril show more promise. Despite these novel therapies, several patients relentlessly progress to a stage of advanced heart failure. The use of left-ventricular-assist devices has variable clinical benefit, with some patients progressing to heart transplantation.

The value of right ventricular longitudinal strain in the evaluation of adult patients with repaired tetralogy of Fallot: a new tool for a contemporary challenge.

PubMed

Almeida-Morais, Luís; Pereira-da-Silva, Tiago; Branco, Luísa; Timóteo, Ana T; Agapito, Ana; de Sousa, Lídia; Oliveira, José A; Thomas, Boban; Jalles-Tavares, Nuno; Soares, Rui; Galrinho, Ana; Cruz-Ferreira, Rui

2017-04-01

The role of right ventricular longitudinal strain for assessing patients with repaired tetralogy of Fallot is not fully understood. In this study, we aimed to evaluate its relation with other structural and functional parameters in these patients. Patients followed-up in a grown-up CHD unit, assessed by transthoracic echocardiography, cardiac MRI, and treadmill exercise testing, were retrospectively evaluated. Right ventricular size and function and pulmonary regurgitation severity were assessed by echocardiography and MRI. Right ventricular longitudinal strain was evaluated in the four-chamber view using the standard semiautomatic method. In total, 42 patients were included (61% male, 32±8 years). The mean right ventricular longitudinal strain was -16.2±3.7%, and the right ventricular ejection fraction, measured by MRI, was 42.9±7.2%. Longitudinal strain showed linear correlation with tricuspid annular systolic excursion (r=-0.40) and right ventricular ejection fraction (r=-0.45) (all p<0.05), which in turn showed linear correlation with right ventricular fractional area change (r=0.50), pulmonary regurgitation colour length (r=0.35), right ventricular end-systolic volume (r=-0.60), and left ventricular ejection fraction (r=0.36) (all p<0.05). Longitudinal strain (β=-0.72, 95% confidence interval -1.41, -0.15) and left ventricular ejection fraction (β=0.39, 95% confidence interval 0.11, 0.67) were independently associated with right ventricular ejection fraction. The best threshold of longitudinal strain for predicting a right ventricular ejection fraction of <40% was -17.0%. Right ventricular longitudinal strain is a powerful method for evaluating patients with tetralogy of Fallot. It correlated with echocardiographic right ventricular function parameters and was independently associated with right ventricular ejection fraction derived by MRI.

Hyperdynamic left ventricular ejection fraction in the intensive care unit.

PubMed

Paonessa, Joseph R; Brennan, Thomas; Pimentel, Marco; Steinhaus, Daniel; Feng, Mengling; Celi, Leo Anthony

2015-08-07

Limited information exists on the etiology, prevalence, and significance of hyperdynamic left ventricular ejection fraction (HDLVEF) in the intensive care unit (ICU). Our aim in the present study was to compare characteristics and outcomes of patients with HDLVEF with those of patients with normal left ventricular ejection fraction in the ICU using a large, public, deidentified critical care database. We conducted a longitudinal, single-center, retrospective cohort study of adult patients who underwent echocardiography during a medical or surgical ICU admission at the Beth Israel Deaconess Medical Center using the Multiparameter Intelligent Monitoring in Intensive Care II database. The final cohort had 2867 patients, of whom 324 had HDLVEF, defined as an ejection fraction >70%. Patients with an ejection fraction <55% were excluded. Compared with critically ill patients with normal left ventricular ejection fraction, the finding of HDLVEF in critically ill patients was associated with female sex, increased age, and the diagnoses of hypertension and cancer. Patients with HDLVEF had increased 28-day mortality compared with those with normal ejection fraction in multivariate logistic regression analysis adjusted for age, sex, Sequential Organ Failure Assessment score, Elixhauser score for comorbidities, vasopressor use, and mechanical ventilation use (odds ratio 1.38, 95% confidence interval 1.039-1.842, p =0.02). The presence of HDLVEF portended increased 28-day mortality, and may be helpful as a gravity marker for prognosis in patients admitted to the ICU. Further research is warranted to gain a better understanding of how these patients respond to common interventions in the ICU and to determine if pharmacologic modulation of HDLVEF improves outcomes.

Emulsifier of Arthrobacter RAG-1: specificity of hydrocarbon substrate.

PubMed Central

Rosenberg, E; Perry, A; Gibson, D T; Gutnick, D L

1979-01-01

The purified extracellular emulsifying factor produced by Arthrobacter RAG-1 (EF-RAG) emulsified light petroleum oil, diesel oil, and a variety of crude oils and gas oils. Although kerosine and gasoline were emulsified poorly by EF-RAG, they were converted into good substrates for emulsification by addition of aromatic compounds, such as 2-methylnaphthalene. Neither aromatic nor aliphatic fractions of crude oil were emulsified by EF-RAG; however, mixtures containing both fractions were emulsified. Pure aliphatic or aromatic hydrocarbons were emulsified poorly by EF-RAG. Binary mixtures containing an aliphatic and an aromatic hydrocarbon, however, were excellent substrates for EF-RAG-induced emulsification. Of a variety of alkylcyclohexane and alkylbenzene derivatives tested, only hexyl- or heptylbenzene and octyl- or decylcyclohexane were effectively emulsified by EF-RAG. These data indicate that for EF-RAG to induce emulsification of hydrocarbons in water, the hydrocarbon substrate must contain both aliphatic and cyclic components. With binary mixtures of methylnaphthalene and hexadecane, maximum emulsion was obtained with 25% hexadecane. PMID:453821

Evaluation of right ventricular function by coronary computed tomography angiography using a novel automated 3D right ventricle volume segmentation approach: a validation study.

PubMed

Burghard, Philipp; Plank, Fabian; Beyer, Christoph; Müller, Silvana; Dörler, Jakob; Zaruba, Marc-Michael; Pölzl, Leo; Pölzl, Gerhard; Klauser, Andrea; Rauch, Stefan; Barbieri, Fabian; Langer, Christian-Ekkehardt; Schgoer, Wilfried; Williamson, Eric E; Feuchtner, Gudrun

2018-06-04

To evaluate right ventricle (RV) function by coronary computed tomography angiography (CTA) using a novel automated three-dimensional (3D) RV volume segmentation tool in comparison with clinical reference modalities. Twenty-six patients with severe end-stage heart failure [left ventricle (LV) ejection fraction (EF) <35%] referred to CTA were enrolled. A specific individually tailored biphasic contrast agent injection protocol was designed (80%/20% high/low flow) was designed. Measurement of RV function [EF, end-diastolic volume (EDV), end-systolic volume (ESV)] by CTA was compared with tricuspid annular plane systolic excursion (TAPSE) by transthoracic echocardiography (TTE) and right heart invasive catheterisation (IC). Automated 3D RV volume segmentation was successful in 26 (100%) patients. Read-out time was 3 min 33 s (range, 1 min 50s-4 min 33s). RV EF by CTA was stronger correlated with right atrial pressure (RAP) by IC (r = -0.595; p = 0.006) but weaker with TAPSE (r = 0.366, p = 0.94). When comparing TAPSE with RAP by IC (r = -0.317, p = 0.231), a weak-to-moderate non-significant inverse correlation was found. Interobserver correlation was high with r = 0.96 (p < 0.001), r = 0.86 (p < 0.001) and r = 0.72 (p = 0.001) for RV EDV, ESV and EF, respectively. CT attenuation of the right atrium (RA) and right ventricle (RV) was 196.9 ± 75.3 and 217.5 ± 76.1 HU, respectively. Measurement of RV function by CTA using a novel 3D volumetric segmentation tool is fast and reliable by applying a dedicated biphasic injection protocol. The RV EF from CTA is a closer surrogate of RAP than TAPSE by TTE. • Evaluation of RV function by cardiac CTA by using a novel 3D volume segmentation tool is fast and reliable. • A biphasic contrast agent injection protocol ensures homogenous RV contrast attenuation. • Cardiac CT is a valuable alternative modality to CMR for the evaluation of RV function.

Variable Phenotype in Murine Transverse Aortic Constriction (TAC)

PubMed Central

Mohammed, Selma F.; Storlie, Jimmy R.; Oehler, Elise A.; Bowen, Lorna A.; Korinek, Josef; Lam, Carolyn SP; Simari, Robert D.; Burnett, John C.; Redfield, Margaret M.

2012-01-01

Background In mice, transverse aortic constriction (TAC) is variably characterized as a model of pressure overload induced hypertrophy (LVH) or heart failure (HF). While commonly used, variability in the TAC model is poorly defined. The objectives of this study were to characterize the variability in the TAC model and to define a simple, non-invasive method of prospectively identifying mice with HF versus compensated LVH after TAC. Methods Eight week old, male C57BL/6J mice underwent TAC or SHAM and then echo at three weeks post-TAC. A group of SHAM and TAC mice were sacrificed after the three week echocardiogram, while the remainder underwent repeat echo and sacrifice at nine weeks post-TAC. The presence of TAC was assessed with 2 dimensional echo, anatomic aortic m-mode and color flow and pulsed-wave Doppler examination of the transverse aorta (TA) and by LV systolic pressure (LVP). Trans-TAC pressure gradient was assessed invasively in a subset. HF was defined as lung/body weight > upper limit in SHAM operated mice. Results As compared to SHAM, TAC mice had higher TA velocity, LVP and LV weight and lower ejection fraction (EF) at three or nine weeks post-TAC. Only a subset of TAC mice (28%) developed HF. As compared to compensated LVH, HF mice were characterized by similar TA velocity and higher percent TA stenosis, but lower LVP, higher LV weight, larger LV cavity, lower EF and stress-corrected midwall fiber shortening and more fibrosis. Both EF and LV mass measured by echo at three weeks post-TAC were predictive of the presence of HF at three or nine weeks post-TAC. Conclusions In wild type mice, TAC produces a variable cardiac phenotype. Marked abnormalities in LV mass and EF at echo three weeks post-TAC identify mice with HF at autopsy. These data are relevant to appropriate design and interpretation of murine studies. PMID:21764606

Variable phenotype in murine transverse aortic constriction.

PubMed

Mohammed, Selma F; Storlie, Jimmy R; Oehler, Elise A; Bowen, Lorna A; Korinek, Josef; Lam, Carolyn S P; Simari, Robert D; Burnett, John C; Redfield, Margaret M

2012-01-01

In mice, transverse aortic constriction (TAC) is variably characterized as a model of pressure overload-induced hypertrophy (left ventricular [LV] hypertrophy, or LVH) or heart failure (HF). While commonly used, variability in the TAC model is poorly defined. The objectives of this study were to characterize the variability in the TAC model and to define a simple, noninvasive method of prospectively identifying mice with HF versus compensated LVH after TAC. Eight-week-old male C57BL/6J mice underwent TAC or sham and then echocardiography at 3 weeks post-TAC. A group of sham and TAC mice were euthanized after the 3-week echocardiogram, while the remainder underwent repeat echocardiography and were euthanized at 9 weeks post-TAC. The presence of TAC was assessed with two-dimensional echocardiography, anatomic aortic m-mode and color flow, and pulsed-wave Doppler examination of the transverse aorta (TA) and by LV systolic pressure (LVP). Trans-TAC pressure gradient was assessed invasively in a subset of mice. HF was defined as lung/body weight>upper limit in sham-operated mice. As compared with sham, TAC mice had higher TA velocity, LVP and LV weight, and lower ejection fraction (EF) at 3 or 9 weeks post-TAC. Only a subset of TAC mice (28%) developed HF. As compared with compensated LVH, HF mice were characterized by similar TA velocity and higher percent TA stenosis, but lower LVP, higher LV weight, larger LV cavity, lower EF and stress-corrected midwall fiber shortening, and more fibrosis. Both EF and LV mass measured by echocardiography at 3 weeks post-TAC were predictive of the presence of HF at 3 or 9 weeks post-TAC. In wild-type mice, TAC produces a variable cardiac phenotype. Marked abnormalities in LV mass and EF at echocardiography 3 weeks post-TAC identify mice with HF at autopsy. These data are relevant to appropriate design and interpretation of murine studies. Copyright © 2012 Elsevier Inc. All rights reserved.

Triheptanoin Treatment in Patients with Pediatric Cardiomyopathy Associated with Long Chain-Fatty Acid Oxidation Disorders

PubMed Central

Vockley, J; Charrow, J; Ganesh, J; Eswara, M; Diaz, GA; McCracken, E; Conway, R; Enns, GM; Starr, J; Wang, R; Abdenur, JE.; Sanchez-de-Toledo, J; Marsden, DL

2016-01-01

Long-chain fatty acid oxidation disorders (LC-FAOD) can cause cardiac hypertrophy and cardiomyopathy, often presenting in infancy, typically leading to death or heart transplant despite ongoing treatment. Previous data on triheptanoin treatment of cardiomyopathy in LC-FAOD suggested a clinical benefit on heart function during acute failure. An additional series of LC-FAOD patients with critical emergencies associated with cardiomyopathy were treated with triheptanoin under emergency treatment or compassionate use protocols. Case reports from 10 patients (8 infants) with moderate or severe cardiomyopathy associated with LC-FAOD are summarized. The majority of these patients were detected by newborn screening, with follow up confirmatory testing, including mutation analysis; all patients were managed with standard treatment, including medium chain triglyceride (MCT) oil. While on this regimen, they presented with acute heart failure requiring hospitalization and cardiac support (ventilation, ECMO, vasopressors) and, in some cases, resuscitation. The patients discontinued MCT oil and began treatment with triheptanoin, an investigational drug. Triheptanoin is expected to provide anaplerotic metabolites, to replace deficient TCA cycle intermediates and improve effective energy metabolism. Cardiac function was measured by echocardiography and ejection fraction (EF) was assessed. EF was moderately to severely impaired prior to triheptanoin treatment, ranging from 12–45%. Improvements in EF began between 2 and 21 days following initiation of triheptanoin, and peaked at 33–71%, with 9 of 10 patients achieving EF in the normal range. Continued treatment was associated with longer-term stabilization of clinical signs of cardiomyopathy. The most common adverse event observed was gastrointestinal distress. Of the 10 patients, 7 have continued on treatment, 1 elected to discontinue due to tolerability issues, and 2 patients died from other causes. Two of the case histories illustrate that cardiomyopathy may also develop later in childhood and/or persist into adulthood. Overall, the presented cases suggest a therapeutic effect of triheptanoin in the management of acute cardiomyopathy associated with LC-FAOD. PMID:27590926

Effects of testosterone undecanoate replacement and withdrawal on cardio-metabolic, hormonal and body composition outcomes in severely obese hypogonadal men: a pilot study.

PubMed

Francomano, D; Bruzziches, R; Barbaro, G; Lenzi, A; Aversa, A

2014-04-01

Modifications of cardiovascular and metabolic parameters during testosterone (T) replacement and withdrawal have never been investigated in severely obese hypogonadal men. Twenty-four severely obese (mean BMI 42; mean age 54.5) hypogonadal men (mean T = 245 ± 52 ng/dL) were enrolled in an observational, parallel-arm, open-label, 54-week study of hypocaloric diet plus physical activity (DPE; n = 12) or DPE plus T injections (DPE + T; n = 12), followed by 24 weeks of DPE alone. Primary endpoints were variations from baseline of cardiovascular (cardiac performance, blood pressure, endothelial function, carotid intima-media thickness, CIMT; epicardial fat thickness, EF) and body composition (fat/lean mass) parameters. Secondary endpoints were variations from baseline of hormonal (T and GH) and metabolic (oral glucose tolerance test, lipids, fibrinogen) parameters. At 54 weeks, DPE + T showed improvements in EF, ejection fraction, diastolic function, CIMT and endothelial function (p < 0.01 vs. controls). Also, hormonal (T, p < 0.0001; GH, p < 0.01), metabolic (HOMA, p < 0.01; microalbuminuria, p < 0.01), lipid (total cholesterol, p < 0.05) and inflammatory (fibrinogen, p < 0.05) parameters improved. After 24 weeks from T withdrawal, all cardiac and hormonal parameters returned to baseline, while fat but not lean mass and blood pressure ameliorations were maintained. An inverse relationship either between EF vs. endothelial function and EF vs. T levels was found (r (2) = -0.46, p < 0.001 and r (2) = -0.56, p < 0.0005, respectively) while direct relationship between T vs. endothelial function occurred (r (2) = 0.43, p < 0.005) in DPE + T. A 33 % dropout rate was reported in DPE without serious adverse events. In middle-aged hypogonadal obese men, 1-year T treatment was safe and improved cardio-metabolic and hormonal parameters. We firstly demonstrated that T withdrawal determines a return back to hypogonadism within 6 months, with loss of cardiovascular and some body composition improvements attained.

Effects of single antegrade hot shot in comparison with no hot shot administration during coronary artery bypass grafting

PubMed Central

Mirmohammadsadeghi, Pouya; Mirmohammadsadeghi, Mohsen

2015-01-01

BACKGROUND Superior results will be achieved from cardiac surgery by minimizing the effect of ischemia/reperfusion injury during cross-clamping of the aorta. Different cardioplegia solutions have been introduced, but the optimum one is still ambiguous. The aim of this study is to determine the effect of single antegrade hot shot terminal warm blood cardioplegia (TWBC) on patients who had undergone coronary artery bypass grafting (CABG). METHODS In total, 2488 patients who had CABG surgery in Sina Hospital, Isfahan, Iran, from 2003 to 2011 were enrolled in this case-control study. They were divided into two groups, those who received cold cardioplegia only and those who received a hot shot following cold cardioplegia. Demographics, and clinical data, such as; premature atrial contraction (PAC) arrhythmia, diabetes treatment, and left ventricular ejection fraction (EF), were collected and logistic regression analysis was used to analyze the data. RESULTS There were significant differences found between subjects receiving antegrade hot shot based on direct current (DC) shocks, with regard to; female, EF levels, diabetes treatment (P < 0.050). Those who did not receive the hot shot and were not diabetic received more DC shock (P = 0.019). The prevalence of subjects who did no need DC shock was significantly higher among male subjects who had good EF and acceptable diabetic treatment. Multiple logistic regression showed that PAC arrhythmia did not have a significant effect on receiving DC shock during CAGB [0.84 (0.25, 2.85), (P = 0.780)]. Having poor EF increased the risk of receiving DC shock among subjects by 2.81 [(1.69, 4.69), (P ≤ 0.001)] (P < 0.001). Among the diabetic subjects, receiving insulin decreased the risk of receiving DC shock by 0.54 (0.29, 0.98) (P = 0.042). CONCLUSION It was concluded that single antegrade hot shot following cold cardioplegia was not particularly effective in the CABG group. TWBC will decrease the need for DC shock. PMID:26405451

Effects of single antegrade hot shot in comparison with no hot shot administration during coronary artery bypass grafting.

PubMed

Mirmohammadsadeghi, Pouya; Mirmohammadsadeghi, Mohsen

2015-05-01

Superior results will be achieved from cardiac surgery by minimizing the effect of ischemia/reperfusion injury during cross-clamping of the aorta. Different cardioplegia solutions have been introduced, but the optimum one is still ambiguous. The aim of this study is to determine the effect of single antegrade hot shot terminal warm blood cardioplegia (TWBC) on patients who had undergone coronary artery bypass grafting (CABG). In total, 2488 patients who had CABG surgery in Sina Hospital, Isfahan, Iran, from 2003 to 2011 were enrolled in this case-control study. They were divided into two groups, those who received cold cardioplegia only and those who received a hot shot following cold cardioplegia. Demographics, and clinical data, such as; premature atrial contraction (PAC) arrhythmia, diabetes treatment, and left ventricular ejection fraction (EF), were collected and logistic regression analysis was used to analyze the data. There were significant differences found between subjects receiving antegrade hot shot based on direct current (DC) shocks, with regard to; female, EF levels, diabetes treatment (P < 0.050). Those who did not receive the hot shot and were not diabetic received more DC shock (P = 0.019). The prevalence of subjects who did no need DC shock was significantly higher among male subjects who had good EF and acceptable diabetic treatment. Multiple logistic regression showed that PAC arrhythmia did not have a significant effect on receiving DC shock during CAGB [0.84 (0.25, 2.85), (P = 0.780)]. Having poor EF increased the risk of receiving DC shock among subjects by 2.81 [(1.69, 4.69), (P ≤ 0.001)] (P < 0.001). Among the diabetic subjects, receiving insulin decreased the risk of receiving DC shock by 0.54 (0.29, 0.98) (P = 0.042). It was concluded that single antegrade hot shot following cold cardioplegia was not particularly effective in the CABG group. TWBC will decrease the need for DC shock.

Influence of Cardiovascular Risk in the Prediction and Timing of Cardiac Events After Exercise Echocardiogram Testing Without Ischemia.

PubMed

Velasco Del Castillo, Sonia; Antón Ladislao, Ane; Gómez Sánchez, Verónica; Onaindia Gandarias, José Juan; Cacicedo Fernández de Bobadilla, Ángela; Rodríguez Sánchez, Ibon; Laraudogoitia Zaldumbide, Eva

2017-09-01

There have been no analyses of the influence of cardiovascular risk as a predictor of events in patients with exercise echocardiography (EE) without ischemia. Our objective was to determine the predictors of cardiac events, paying special attention to cardiovascular risk. This study included 1640 patients with EE without ischemia. Of these, there were 1206 with no previously known coronary artery disease (CAD), whose risk of a fatal cardiovascular disease event was estimated according to the European SCORE (Systematic COronary Risk Evaluation) risk assessment system, and 434 with known CAD. The primary endpoint was cardiac event-free survival (EFS) (cardiac death, nonfatal acute coronary syndrome, and coronary revascularization). After a median follow-up of 35 [23-54] months, no differences were found in cardiac EFS between patients with a SCORE ≥ 10 or diabetes and patients with previous CAD (89.8% vs 87.1%). In the first year, cardiac EFS was high in all groups (99.4% if SCORE < 5; 100% if 5-9; 98% if ≥ 10 or diabetes and 97% in patients with CAD). In the third year, cardiac EFS was similar in the group with SCORE ≥ 10 or diabetes (94.5%) and patients with CAD (91.1%, P = NS). In these patients, the annualized event rate was 2.8% and 2.55%, respectively, and was significantly higher than in groups with SCORE < 5 (0.6%) and SCORE 5-9 (0.12%). The most frequent events were non-ST-segment elevation acute coronary syndrome and late revascularization. Predictors of cardiac events were previous CAD, SCORE ≥ 10 or diabetes mellitus, creatinine clearance, left ventricular ejection fraction, and chest pain during EE. Initial outcome after an EE without ischemia is favorable but is subsequently modulated by cardiovascular risk. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Type 2 diabetes mellitus and heart failure: a position statement from the Heart Failure Association of the European Society of Cardiology.

PubMed

Seferović, Petar M; Petrie, Mark C; Filippatos, Gerasimos S; Anker, Stefan D; Rosano, Giuseppe; Bauersachs, Johann; Paulus, Walter J; Komajda, Michel; Cosentino, Francesco; de Boer, Rudolf A; Farmakis, Dimitrios; Doehner, Wolfram; Lambrinou, Ekaterini; Lopatin, Yuri; Piepoli, Massimo F; Theodorakis, Michael J; Wiggers, Henrik; Lekakis, John; Mebazaa, Alexandre; Mamas, Mamas A; Tschöpe, Carsten; Hoes, Arno W; Seferović, Jelena P; Logue, Jennifer; McDonagh, Theresa; Riley, Jillian P; Milinković, Ivan; Polovina, Marija; van Veldhuisen, Dirk J; Lainscak, Mitja; Maggioni, Aldo P; Ruschitzka, Frank; McMurray, John J V

2018-05-01

The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF), either with reduced (HFrEF) or preserved ejection fraction (HFpEF), is frequent (30-40% of patients) and associated with a higher risk of HF hospitalization, all-cause and cardiovascular (CV) mortality. The most important causes of HF in T2DM are coronary artery disease, arterial hypertension and a direct detrimental effect of T2DM on the myocardium. T2DM is often unrecognized in HF patients, and vice versa, which emphasizes the importance of an active search for both disorders in the clinical practice. There are no specific limitations to HF treatment in T2DM. Subanalyses of trials addressing HF treatment in the general population have shown that all HF therapies are similarly effective regardless of T2DM. Concerning T2DM treatment in HF patients, most guidelines currently recommend metformin as the first-line choice. Sulphonylureas and insulin have been the traditional second- and third-line therapies although their safety in HF is equivocal. Neither glucagon-like preptide-1 (GLP-1) receptor agonists, nor dipeptidyl peptidase-4 (DPP4) inhibitors reduce the risk for HF hospitalization. Indeed, a DPP4 inhibitor, saxagliptin, has been associated with a higher risk of HF hospitalization. Thiazolidinediones (pioglitazone and rosiglitazone) are contraindicated in patients with (or at risk of) HF. In recent trials, sodium-glucose co-transporter-2 (SGLT2) inhibitors, empagliflozin and canagliflozin, have both shown a significant reduction in HF hospitalization in patients with established CV disease or at risk of CV disease. Several ongoing trials should provide an insight into the effectiveness of SGLT2 inhibitors in patients with HFrEF and HFpEF in the absence of T2DM. © 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.

Advances in the management of heart failure: the role of ivabradine

PubMed Central

Müller-Werdan, Ursula; Stöckl, Georg; Werdan, Karl

2016-01-01

A high resting heart rate (≥70–75 b.p.m.) is a risk factor for patients with heart failure (HF) with reduced ejection fraction (EF), probably in the sense of accelerated atherosclerosis, with an increased morbidity and mortality. Beta-blockers not only reduce heart rate but also have negative inotropic and blood pressure-lowering effects, and therefore, in many patients, they cannot be given in the recommended dose. Ivabradine specifically inhibits the pacemaker current (funny current, If) of the sinoatrial node cells, resulting in therapeutic heart rate lowering without any negative inotropic and blood pressure-lowering effect. According to the European Society of Cardiology guidelines, ivabradine should be considered to reduce the risk of HF hospitalization and cardiovascular death in symptomatic patients with a reduced left ventricular EF ≤35% and sinus rhythm ≥70 b.p.m. despite treatment with an evidence-based dose of beta-blocker or a dose below the recommended dose (recommendation class “IIa” = weight of evidence/opinion is in favor of usefulness/efficacy: “should be considered”; level of evidence “B” = data derived from a single randomized clinical trial or large nonrandomized studies). Using a heart rate cutoff of ≥ 75 b.p.m., as licensed by the European Medicines Agency, treatment with ivabradine 5–7.5 mg b.i.d. reduces cardiovascular mortality by 17%, HF mortality by 39% and HF hospitalization rate by 30%. A high resting heart rate is not only a risk factor in HF with reduced EF but also at least a risk marker in HF with preserved EF, in acute HF and also in special forms of HF. In this review, we discuss the proven role of ivabradine in the validated indication “HF with reduced EF” together with interesting preliminary findings, and the potential role of ivabradine in further, specific forms of HF. PMID:27895488

Association of ACE gene D polymorphism with left ventricular hypertrophy in patients with diastolic heart failure: a case-control study.

PubMed

Bahramali, Ehsan; Rajabi, Mona; Jamshidi, Javad; Mousavi, Seyyed Mohammad; Zarghami, Mehrdad; Manafi, Alireza; Firouzabadi, Negar

2016-02-09

To explore the association between ACE gene insertion/deletion (I/D) polymorphism with left ventricular hypertrophy (LVH) in patients with hypertension who have developed heart failure with preserved ejection fraction (HFpEF). Being a major contributor to the development of diastolic heart dysfunction, the renin angiotensin aldosterone system and its genetic variations are thought to induce LVH in hypertensive hearts apart from haemodynamic factors. Case control study. An Iranian referral university hospital. 176 patients with hypertension and a diagnosis of HFpEF on presence of symptoms of heart failure plus Doppler echocardiographic documentation of left ventricular (LV) diastolic dysfunction and/or elevated NT-proBNP levels. Those with significant coronary, valvular, pericardial and structural heart diseases were excluded as well as patients with atrial fibrillation, renal failure and pulmonary causes of dyspnoea. They were divided into two cohorts of 88 cases with and 88 controls without LVH, after determination of LV mass index, using two-dimensional and M-mode echocardiography. The I/D polymorphism of the ACE gene was determined using the PCR method. The D allele was significantly more prevalent among cases with compared with controls without LVH (p=0.0007). Genotype distributions also differed significantly under additive (p=0.005, OR=0.53, 95% CI 0.34 to 0.84) and recessive (p=0.001, OR=0.29, 95% CI 0.13 to 0.66) models. In patients with hypertension who develop HFpEF, the D allele of the ACE gene is probably associated with the development of LVH. With the detrimental effects of LVH on the heart's diastolic properties, this can signify the role of genetic contributors to the development of HFpEF in patients with hypertension and may serve as a future risk predictor for the disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Oxygen Uptake Efficiency Slope and Breathing Reserve, Not Anaerobic Threshold, Discriminate Between Patients With Cardiovascular Disease Over Chronic Obstructive Pulmonary Disease.

PubMed

Barron, Anthony; Francis, Darrel P; Mayet, Jamil; Ewert, Ralf; Obst, Anne; Mason, Mark; Elkin, Sarah; Hughes, Alun D; Wensel, Roland

2016-04-01

The study sought to compare the relative discrimination of various cardiopulmonary exercise testing (CPX) variables between cardiac and respiratory disease. CPX testing is used in many cardiorespiratory diseases. However, discrimination of cardiac and respiratory dysfunction can be problematic. Anaerobic threshold (AT) and oxygen-uptake to work-rate relationship (VO2/WR slope) have been proposed as diagnostic of cardiac dysfunction, but multiple variables have not been compared. A total of 73 patients with chronic obstructive pulmonary disease (COPD) (n = 25), heart failure with reduced ejection fraction (HFrEF) (n = 40), or combined COPD and HFrEF (n = 8) were recruited and underwent CPX testing on a bicycle ergometer. Following a familiarization test, each patient underwent a personalized second test aiming for maximal exercise after ∼10 min. Measurements from this test were used to calculate area under the receiver-operator characteristic curve (AUC). Peak VO2 was similar between the 2 principal groups (COPD 17.1 ± 4.6 ml/min/kg; HFrEF 16.4 ± 3.6 ml/min/kg). Breathing reserve (AUC: 0.91) and percent predicted oxygen uptake efficiency slope (OUES) (AUC: 0.87) had the greatest ability to discriminate between COPD and HFrEF. VO2/WR slope performed significantly worse (AUC: 0.68). VO2 at the AT did not discriminate (AUC for AT as percent predicted peak VO2: 0.56). OUES and breathing reserve remained strong discriminators when compared with an external cohort of healthy matched controls, and were comparable to B-type natriuretic peptide. Breathing reserve and OUES discriminate heart failure from COPD. Despite it being considered an important determinant of cardiac dysfunction, the AT could not discriminate these typical clinical populations while the VO2/WR slope showed poor to moderate discriminant ability. (Identifying an Ideal Cardiopulmonary Exercise Test Parameter [PVA]; NCT01162083). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Oxygen Uptake Efficiency Slope and Breathing Reserve, Not Anaerobic Threshold, Discriminate Between Patients With Cardiovascular Disease Over Chronic Obstructive Pulmonary Disease

PubMed Central

Barron, Anthony; Francis, Darrel P.; Mayet, Jamil; Ewert, Ralf; Obst, Anne; Mason, Mark; Elkin, Sarah; Hughes, Alun D.; Wensel, Roland

2016-01-01

Objectives The study sought to compare the relative discrimination of various cardiopulmonary exercise testing (CPX) variables between cardiac and respiratory disease. Background CPX testing is used in many cardiorespiratory diseases. However, discrimination of cardiac and respiratory dysfunction can be problematic. Anaerobic threshold (AT) and oxygen-uptake to work-rate relationship (VO2/WR slope) have been proposed as diagnostic of cardiac dysfunction, but multiple variables have not been compared. Methods A total of 73 patients with chronic obstructive pulmonary disease (COPD) (n = 25), heart failure with reduced ejection fraction (HFrEF) (n = 40), or combined COPD and HFrEF (n = 8) were recruited and underwent CPX testing on a bicycle ergometer. Following a familiarization test, each patient underwent a personalized second test aiming for maximal exercise after ∼10 min. Measurements from this test were used to calculate area under the receiver-operator characteristic curve (AUC). Results Peak VO2 was similar between the 2 principal groups (COPD 17.1 ± 4.6 ml/min/kg; HFrEF 16.4 ± 3.6 ml/min/kg). Breathing reserve (AUC: 0.91) and percent predicted oxygen uptake efficiency slope (OUES) (AUC: 0.87) had the greatest ability to discriminate between COPD and HFrEF. VO2/WR slope performed significantly worse (AUC: 0.68). VO2 at the AT did not discriminate (AUC for AT as percent predicted peak VO2: 0.56). OUES and breathing reserve remained strong discriminators when compared with an external cohort of healthy matched controls, and were comparable to B-type natriuretic peptide. Conclusions Breathing reserve and OUES discriminate heart failure from COPD. Despite it being considered an important determinant of cardiac dysfunction, the AT could not discriminate these typical clinical populations while the VO2/WR slope showed poor to moderate discriminant ability. (Identifying an Ideal Cardiopulmonary Exercise Test Parameter [PVA]; NCT01162083) PMID:26874378

Impact of moderate functional mitral insufficiency in patients undergoing surgical revascularization.

PubMed

Grossi, Eugene A; Crooke, Gregory A; DiGiorgi, Paul L; Schwartz, Charles F; Jorde, Ulrich; Applebaum, Robert M; Ribakove, Greg H; Galloway, Aubrey C; Grau, Juan B; Colvin, Stephen B

2006-07-04

Mild and moderate functional ischemic mitral insufficiency present at the time of surgical revascularization present clinical uncertainty. It is unclear whether the relatively poor outcomes in this cohort are dependent on valvular function or related to left ventricular dysfunction. The purpose of this study was to examine the early and late outcomes in patients with less-than-severe functional ischemic mitral insufficiency at the time of isolated coronary artery bypass grafting (CABG). From 1996 through 2004, 2242 consecutive patients undergoing isolated CABG were identified as having none to moderate mitral regurgitation (MR) and no valve leaflet pathology. All of the patients at this single institution routinely had an intraoperative transesophageal echocardiography, prospectively quantified MR, and ejection fraction (EF). The New York State Cardiac Surgery Reporting System infrastructure was used to prospectively collect in-hospital patient variables and outcomes. Social Security Death Benefit Index was used to determine long-term survival. Odds ratio and significance (P value) are presented for each determined risk factor. There were 841 patients (37.5%) with no MR, 1137 (50.7%) with mild MR, and 264 (11.8%) with moderate MR. The patients with moderate MR were more likely to be older, female, and have more renal disease, previous MI, congestive heart failure, previous cardiac surgery, and lower EFs. Hospital mortality was independently and significantly associated with renal disease, decreasing EF, increasing age, previous cardiac operation, and cerebral vascular disease. Multivariable analysis revealed decreased survival with increasing age, previous operation, congestive heart failure, diabetes, nonelective operation, decreasing EF, and the presence of moderate MR (expbeta = 1.49; P=0.007) and mild MR (expbeta = 1.34; P=0.033). Independent of ventricular function, mild and moderate functional mitral insufficiency are associated with significantly decreased survival in patients undergoing CABG. Whether correction of moderate functional MR at the time of CABG improves outcome still needs to be determined.

Rationale and design of TRANSITION: a randomized trial of pre‐discharge vs. post‐discharge initiation of sacubitril/valsartan

PubMed Central

Wachter, Rolf; Senni, Michele; Belohlavek, Jan; Noè, Adele; Carr, David; Butylin, Dmytro

2017-01-01

Abstract Aims The prognosis after hospitalization for acute decompensated heart failure (ADHF) remains poor, especially <30 days post‐discharge. Evidence‐based medications with prognostic impact administered at discharge improve survival and hospital readmission, but robust studies comparing pre‐discharge with post‐discharge initiation are rare. The PARADIGM‐HF trial established sacubitril/valsartan as a new evidence‐based therapy in patients with heart failure (HF) and reduced left ventricular ejection fraction (<40%) (rEF). In common with other landmark studies, it enrolled patients who were ambulatory at the time of inclusion. In addition, there is also still limited knowledge of initiation and up‐titration of sacubitril/valsartan in ACEi/ARB‐ naïve patients and in de novo HF with rEF patients. Methods and results TRANSITION is a multicentre, open‐label study in which ~1000 adults hospitalized for ADHF with rEF are randomized to start sacubitril/valsartan in a pre‐discharge arm (initiated ≥24 h after haemodynamic stabilization) or a post‐discharge arm (initiated within Days 1–14 after discharge). The protocol allows investigators to select the appropriate starting dose and dose adjustments according to clinical circumstances. Over a 10 week treatment period, the primary and secondary objectives assess the feasibility and safety of starting sacubitril/valsartan in‐hospital, early after haemodynamic stabilization. Exploratory objectives also include assessment of HF signs and symptoms, readmissions, N‐terminal pro‐B‐type natriuretic peptide and high‐sensitivity troponin T levels, and health resource utilization parameters. Conclusions TRANSITION will provide new evidence about initiating sacubitril/valsartan following hospitalization for ADHF, occurring either as de novo ADHF or as deterioration of chronic HF, and in patients with or without prior ACEI/ARB therapy. The results of TRANSITION will thus be highly relevant to the management of patients hospitalized for ADHF with rEF. PMID:29239515

Profile of sacubitril/valsartan in the treatment of heart failure: patient selection and perspectives

PubMed Central

Yandrapalli, Srikanth; Andries, Gabriela; Biswas, Medha; Khera, Sahil

2017-01-01

With an estimated prevalence of 5.8 million in the USA and over 23 million people worldwide, heart failure (HF) is growing in epidemic proportions. Despite the use of guideline-directed medical therapies such as angiotensin-converting enzyme inhibitors, beta-adrenergic blockers, angiotensin receptor blockers, and mineralocorticoid receptor antagonists for chronic systolic HF for almost two decades, HF remains a leading cause of morbidity, mortality, and health care expenditures. The Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial provided compelling evidence for the cardiovascular and mortality benefit of sacubitril/valsartan when compared to enalapril in patients with heart failure and reduced ejection fraction (HFrEF). Sacubitril/valsartan performed better than enalapril across various HFrEF patient characteristics and showed substantial benefit in patients with other common comorbidities. Following the trial, the US Food and Drug Administration approved this drug for the treatment of HF. Various international HF consensus guidelines endorse sacubitril/valsartan as a class I recommendation for the management of symptomatic HFrEF. Although this high-quality clinical study is the largest and the most globally represented trial in HFrEF patients, concerns have been raised regarding the generalizability of the trial results in real-world HF population. The gaps in US Food and Drug Administration labeling and guideline recommendations might lead to this medication being used in a larger population than it was studied in. In this review, we will discuss the current role of sacubitril/valsartan in the management of HF, concerns related to PARADIGM-HF and answers, shortcomings of this novel drug, effects on patient characteristics, real-world eligibility, and the role of ongoing and further investigations to clarify the profile of sacubitril/valsartan in the management of HF. PMID:29042791

Rationale and design of TRANSITION: a randomized trial of pre-discharge vs. post-discharge initiation of sacubitril/valsartan.

PubMed

Pascual-Figal, Domingo; Wachter, Rolf; Senni, Michele; Belohlavek, Jan; Noè, Adele; Carr, David; Butylin, Dmytro

2018-04-01

The prognosis after hospitalization for acute decompensated heart failure (ADHF) remains poor, especially <30 days post-discharge. Evidence-based medications with prognostic impact administered at discharge improve survival and hospital readmission, but robust studies comparing pre-discharge with post-discharge initiation are rare. The PARADIGM-HF trial established sacubitril/valsartan as a new evidence-based therapy in patients with heart failure (HF) and reduced left ventricular ejection fraction (<40%) (rEF). In common with other landmark studies, it enrolled patients who were ambulatory at the time of inclusion. In addition, there is also still limited knowledge of initiation and up-titration of sacubitril/valsartan in ACEi/ARB- naïve patients and in de novo HF with rEF patients. TRANSITION is a multicentre, open-label study in which ~1000 adults hospitalized for ADHF with rEF are randomized to start sacubitril/valsartan in a pre-discharge arm (initiated ≥24 h after haemodynamic stabilization) or a post-discharge arm (initiated within Days 1-14 after discharge). The protocol allows investigators to select the appropriate starting dose and dose adjustments according to clinical circumstances. Over a 10 week treatment period, the primary and secondary objectives assess the feasibility and safety of starting sacubitril/valsartan in-hospital, early after haemodynamic stabilization. Exploratory objectives also include assessment of HF signs and symptoms, readmissions, N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T levels, and health resource utilization parameters. TRANSITION will provide new evidence about initiating sacubitril/valsartan following hospitalization for ADHF, occurring either as de novo ADHF or as deterioration of chronic HF, and in patients with or without prior ACEI/ARB therapy. The results of TRANSITION will thus be highly relevant to the management of patients hospitalized for ADHF with rEF. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Profile of sacubitril/valsartan in the treatment of heart failure: patient selection and perspectives.

PubMed

Yandrapalli, Srikanth; Andries, Gabriela; Biswas, Medha; Khera, Sahil

2017-01-01

With an estimated prevalence of 5.8 million in the USA and over 23 million people worldwide, heart failure (HF) is growing in epidemic proportions. Despite the use of guideline-directed medical therapies such as angiotensin-converting enzyme inhibitors, beta-adrenergic blockers, angiotensin receptor blockers, and mineralocorticoid receptor antagonists for chronic systolic HF for almost two decades, HF remains a leading cause of morbidity, mortality, and health care expenditures. The Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial provided compelling evidence for the cardiovascular and mortality benefit of sacubitril/valsartan when compared to enalapril in patients with heart failure and reduced ejection fraction (HFrEF). Sacubitril/valsartan performed better than enalapril across various HFrEF patient characteristics and showed substantial benefit in patients with other common comorbidities. Following the trial, the US Food and Drug Administration approved this drug for the treatment of HF. Various international HF consensus guidelines endorse sacubitril/valsartan as a class I recommendation for the management of symptomatic HFrEF. Although this high-quality clinical study is the largest and the most globally represented trial in HFrEF patients, concerns have been raised regarding the generalizability of the trial results in real-world HF population. The gaps in US Food and Drug Administration labeling and guideline recommendations might lead to this medication being used in a larger population than it was studied in. In this review, we will discuss the current role of sacubitril/valsartan in the management of HF, concerns related to PARADIGM-HF and answers, shortcomings of this novel drug, effects on patient characteristics, real-world eligibility, and the role of ongoing and further investigations to clarify the profile of sacubitril/valsartan in the management of HF.

Influence of activated carbon preloading by EfOM fractions from treated wastewater on adsorption of pharmaceutically active compounds.

PubMed

Hu, Jingyi; Shang, Ran; Heijman, Bas; Rietveld, Luuk

2016-05-01

In this study, the preloading effects of different fractions of wastewater effluent organic matter (EfOM) on the adsorption of trace-level pharmaceutically active compounds (PhACs) onto granular activated carbon (GAC) were investigated. A nanofiltration (NF) membrane was employed to separate the EfOM by size, and two GACs with distinct pore structures were chosen for comparison. The results showed that preloading with EfOM substantially decreased PhAC uptake of the GACs; however, comparable PhAC adsorption capacities were achieved on GACs preloaded by feed EfOM and the NF-permeating EfOM. This indicates that: (1) the NF-rejected, larger EfOM molecules with an expectation to block the PhAC adsorption pores exerted little impact on the adsorbability of PhACs; (2) the smaller EfOM molecules present in the NF permeate contributed mainly to the decrease in PhAC uptake, mostly due to site competition. Of the two examined GACs, the wide pore-size-distributed GAC was found to be more susceptible to EfOM preloading than the microporous GAC. Furthermore, among the fourteen investigated PhACs, the negatively charged hydrophilic PhACs were generally subjected to a greater EfOM preloading impact. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exercise testing in asymptomatic or minimally symptomatic aortic regurgitation: relationship of left ventricular ejection fraction to left ventricular filling pressure during exercise

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boucher, C.A.; Wilson, R.A.; Kanarek, D.J.

Exercise radionuclide angiography is being used to evaluate left ventricular function in patients with aortic regurgitation. Ejection fraction is the most common variable analyzed. To better understand the rest and exercise ejection fraction in this setting, 20 patients with asymptomatic or minimally symptomatic severe aortic regurgitation were studied. All underwent simultaneous supine exercise radionuclide angiography and pulmonary gas exchange measurement and underwent rest and exercise measurement of pulmonary artery wedge pressure (PAWP) during cardiac catheterization. Eight patients had a peak exercise PAWP less than 15 mm Hg (group 1) and 12 had a peak exercise PAWP greater than or equalmore » to 15 mm Hg (group 2). Group 1 patients were younger and more were in New York Heart Association class I. The two groups had similar cardiothoracic ratios, changes in ejection fractions with exercise, and rest and exercise regurgitant indexes. Using multiple regression analysis, the best correlate of the exercise PAWP was peak oxygen uptake (r . -0.78, p less than 0.01). No other measurement added significantly to the regression. When peak oxygen uptake was excluded, rest and exercise ejection fraction also correlated significantly (r . -0.62 and r . -0.60, respectively, p less than 0.01). Patients with asymptomatic or minimally symptomatic severe aortic regurgitation have a wide spectrum of cardiac performance in terms of the PAWP during exercise. The absolute rest and exercise ejection fraction and the level of exercise achieved are noninvasive variables that correlate with exercise PAWP in aortic regurgitation, but the change in ejection fraction with exercise by itself is not.« less

Patients with left bundle branch block and left axis deviation show a specific left ventricular asynchrony pattern: Implications for left ventricular lead placement during CRT implantation.

PubMed

Sciarra, Luigi; Golia, Paolo; Palamà, Zefferino; Scarà, Antonio; De Ruvo, Ermenegildo; Borrelli, Alessio; Martino, Anna Maria; Minati, Monia; Fagagnini, Alessandro; Tota, Claudia; De Luca, Lucia; Grieco, Domenico; Delise, Pietro; Calò, Leonardo

Left bundle branch block (LBBB) and left axis deviation (LAD) patients may have poor response to resynchronization therapy (CRT). We sought to assess if LBBB and LAD patients show a specific pattern of mechanical asynchrony. CRT candidates with non-ischemic cardiomyopathy and LBBB were categorized as having normal QRS axis (within -30° and +90°) or LAD (within -30° and -90°). Patients underwent tissue Doppler imaging (TDI) to measure time interval between onset of QRS complex and peak systolic velocity in ejection period (Q-peak) at basal segments of septal, inferior, lateral and anterior walls, as expression of local timing of mechanical activation. Thirty patients (mean age 70.6years; 19 males) were included. Mean left ventricular ejection fraction was 0.28±0.06. Mean QRS duration was 172.5±13.9ms. Fifteen patients showed LBBB with LAD (QRS duration 173±14; EF 0.27±0.06). The other 15 patients had LBBB with a normal QRS axis (QRS duration 172±14; EF 0.29±0.05). Among patients with LAD, Q-peak interval was significantly longer at the anterior wall in comparison to each other walls (septal 201±46ms, inferior 242±58ms, lateral 267±45ms, anterior 302±50ms; p<0.0001). Conversely, in patients without LAD Q-peak interval was longer at lateral wall, when compared to each other (septal 228±65ms, inferior 250±64ms, lateral 328±98ms, anterior 291±86ms; p<0.0001). Patients with heart failure, presenting LBBB and LAD, show a specific pattern of ventricular asynchrony, with latest activation at anterior wall. This finding could affect target vessel selection during CRT procedures in these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Wave intensity analysis in mice: an ultrasound-based study in the abdominal aorta and common carotid artery

NASA Astrophysics Data System (ADS)

Di Lascio, N.; Kusmic, C.; Stea, F.; Faita, F.

2017-03-01

Wave Intensity Analysis (WIA) can provide parameters representative of the interaction between the vascular network and the heart. It has been already demonstrated that WIA-derived biomarkes have a quantitative physiological meaning. Aim of this study was to develop an image process algorithm for performing non-invasive WIA in mice and correlate commonly used cardiac function parameters with WIA-derived indexes. Sixteen wild-type male mice (8 weeks-old) were imaged with high-resolution ultrasound (Vevo 2100). Abdominal aorta and common carotid pulse wave velocities (PWVabd, PWVcar) were obtained processing B-Mode and PW-Doppler images and employed to assess WIA. Amplitudes of the first (W1abd, W1car) and the second (W2abd, W2car) local maxima and minimum (Wbabd,Wbcar) were evaluated; areas under the negative part of the curve were also calculated (NAabd, NAcar). Cardiac output (CO), ejection fraction (EF) fractional shortening (FS) and stroke volume (SV) were estimated; strain analysis provided strain and strain rate values for longitudinal, radial and circumferential directions (LS, LSR, RS, RSR, CS, CSR). Isovolumetric relaxation time (IVRT) was calculated from mitral inflow PW-Doppler images; IVRT values were normalized for cardiac cycle length. W1abd was correlated with LS (R=0.65) and LSR (R=0.59), while W1car was correlated with CO (R=0.58), EF (R=0.72), LS (R=0.65), LSR (R=0.89), CS (R=0.71), CSR (R=0.70). Both W2abd and W2car were not correlated with IVRT. Carotid artery WIA-derived parameters are more representative of cardiac function than those obtained from the abdominal aorta. The described US-based method can provide information about cardiac function and cardio-vascular interaction simply studying a single vascular site.

Ultrasound contrast and real-time perfusion in conjunction with supine bicycle stress echocardiography for comprehensive evaluation of surgically corrected congenital heart disease.

PubMed

Kutty, Shelby; Olson, Joan; Danford, Christopher J; Sandene, Erin K; Xie, Feng; Fletcher, Scott E; Erickson, Christopher C; Kugler, John D; Danford, David A; Porter, Thomas R

2012-06-01

We sought to evaluate the efficacy of ultrasound contrast (UC) and low mechanical index real-time perfusion (RTP) in the haemodynamic and anatomic assessment of repaired congenital heart disease (CHD) at rest and during supine bicycle stress echocardiography (BSE). Patients with CHD (n = 51, median age 21.5 years) were prospectively studied. All had compromised image quality, 20 (39%) had arrhythmias, and 10 (20%) had pacemakers. RTP was performed at rest and during BSE using Definity and Contrast Pulse Sequencing, with assessment of Doppler pressure gradients. Diagnoses included tetralogy of Fallot (n = 27), transposition of the great arteries (TGA) atrial switch (n = 10), TGA arterial switch (n = 2), aortic valve disease (n = 4), Fontan (n = 4), and Kawasaki disease (n = 4). UC with RTP improved endocardial border definition, with increased number of left ventricular (LV) and right ventricular (RV) segments visualized at rest (P < 0.0001) and during stress. LV ejection fraction (EF) and RV fractional area change (FAC) were measurable at rest and peak stress, RV FAC correlating closely with same-day magnetic resonance EFs (r = 0.72; P < 0.001). UC enhanced Doppler signals, enabling subpulmonary ventricular systolic pressure measurements at rest and stress. In six patients, marked elevations of subpulmonary ventricular systolic pressure were detected with UC during BSE, and quantifiable ventricular dysfunction. No adverse events occurred, other than transient low back pain in one patient. UC at rest and with supine BSE enables safe and comprehensive assessment of anatomy, haemodynamics, and biventricular functional and perfusion reserve in adolescents and young adults with surgically modified CHD.

Three-dimensional Echocardiography of Right Ventricular Function Correlates with Severity of Pediatric Pulmonary Hypertension.

PubMed

Jone, Pei-Ni; Patel, Sonali S; Cassidy, Courtney; Ivy, David Dunbar

2016-12-01

Right ventricular function and biomarkers of B-type natriuretic peptide (BNP) and N-Terminal pro-BNP (NT pro-BNP) are used to determine the severity of right ventricular failure and outcomes from pulmonary hypertension. Real-time three-dimensional echocardiography (3DE) is a novel quantitative measure of the right ventricle and decreases the geometric assumptions from conventional two-dimensional echocardiography (2DE). We correlated right ventricular functional measures using 2DE and single-beat 3DE with biomarkers and hemodynamics to determine the severity of pediatric pulmonary hypertension. We retrospectively evaluated 35 patients (mean age 12.67 ± 5.78 years) with established pulmonary hypertension who had echocardiograms and biomarkers on the same day. Ten out of 35 patients had hemodynamic evaluation within 3 days. 2DE evaluation included tricuspid annular plane systolic excursion (TAPSE), right ventricular myocardial performance index from tissue Doppler imaging (RV TDI MPI), and right ventricular fractional area change (FAC). Three-dimensional echocardiography evaluation included right ventricular ejection fraction (EF), end-systolic volume, and end-diastolic volume. The quality of the 3DE was graded as good, fair, or poor. Pearson correlation coefficients were utilized to evaluate between biomarkers and echocardiographic parameters and between hemodynamics and echocardiography. Three-dimensional echocardiography and FAC correlated significantly with BNP and NT pro-BNP. TAPSE and RV TDI MPI did not correlate significantly with biomarkers. 3D right ventricular EF correlated significantly with hemodynamics. Two-dimensional echocardiography did not correlate with hemodynamics. Single-beat 3DE is a noninvasive, feasible tool in the quantification of right ventricular function and maybe more accurate than conventional 2DE in evaluating severity of pulmonary hypertension. © 2016 Wiley Periodicals, Inc.

Meta-Analysis of the Relation of Baseline Right Ventricular Function to Response to Cardiac Resynchronization Therapy.

PubMed

Sharma, Abhishek; Bax, Jerome J; Vallakati, Ajay; Goel, Sunny; Lavie, Carl J; Kassotis, John; Mukherjee, Debabrata; Einstein, Andrew; Warrier, Nikhil; Lazar, Jason M

2016-04-15

Right ventricular (RV) dysfunction has been associated with adverse clinical outcomes in patients with heart failure (HF). Cardiac resynchronization therapy (CRT) improves left ventricular (LV) size and function in patients with markedly abnormal electrocardiogram QRS duration. However, relation of baseline RV function with response to CRT has not been well described. In this study, we aim to investigate the relation of baseline RV function with response to CRT as assessed by change in LV ejection fraction (EF). A systematic search of studies published from 1966 to May 31, 2015 was conducted using PubMed, CINAHL, Cochrane CENTRAL, and the Web of Science databases. Studies were included if they have reported (1) parameters of baseline RV function (tricuspid annular plane systolic excursion [TAPSE] or RVEF or RV basal strain or RV fractional area change [FAC]) and (2) LVEF before and after CRT. Random-effects metaregression was used to evaluate the effect of baseline RV function parameters and change in LVEF. Sixteen studies (n = 1,764) were selected for final analysis. Random-effects metaregression analysis showed no significant association between the magnitude of the difference in EF before and after CRT with baseline TAPSE (β = 0.005, p = 0.989); baseline RVEF (β = 0.270, p = 0.493); baseline RVFAC (β = -0.367, p = 0.06); baseline basal strain (β = -0.342, p = 0.462) after a mean follow-up period of 10.5 months. In conclusion, baseline RV function as assessed by TAPSE, FAC, basal strain, or RVEF does not determine response to CRT as assessed by change in LVEF. Copyright © 2016 Elsevier Inc. All rights reserved.

Posterior leaflet preservation during mitral valve replacement for rheumatic mitral stenosis.

PubMed

Djukić, P L; Obrenović-Kirćanski, B B; Vranes, M R; Kocica, M J; Mikić, A Dj; Velinović, M M; Kacar, S M; Kovacević, N S; Parapid, B J

2006-01-01

Mitral valve replacement with posterior leaflet preservation was shown beneficial for postoperative left vetricular (LV) performance in patients with mitral regurgitation. Some authors find it beneficial even for the long term LV function. We investigated a long term effect of this technique in patients with rheumatic mitral stenosis. We studied 20 patents with mitral valve replacement due to rheumatic mitral stenosis, in the period from January 1988 to December 1989. In group A (10 patients) both leaflets and coresponding chordal excision was performed, while in group B (10 patients) the posterior leaflet was preserved. In all patients a Carbomedics valve was inserted. We compared clinical pre and postoperative status, as well as hemodynamic characteristics of the valve and left ventricle in both groups. Control echocardiographyc analysis included: maximal (PG) and mean (MG) gradients; effective valve area (AREA); telediastolic (TDV) and telesystolic (TSV) LV volume; stroke volume (SV); ejection fraction (EF); fractional shortening (FS) and segmental LV motion. The mean size of inserted valve was 26.6 in group A and 27.2 in group B. Hemodynamic data: PG (10.12 vs 11.1); MG (3.57 vs 3.87); AREA (2.35 vs 2.30); TDV 126.0 vs 114.5); TSV (42.2 vs 36.62); SV (83.7 vs 77.75); EF (63.66 vs 67.12); FS (32.66 vs 38.25). Diaphragmal segmental hypokinesis was evident in one patient from group A and in two patients from group B. In patients with rheumatic stenosis, posterior leaflet preservation did not have increased beneficial effect on left ventricular performance during long-term follow-up. An adequate posterior leaflet preservation does not change hemodynamic valvular characteristics even after long-term follow-up.

Effects of carvedilol therapy in patients with heart failure with preserved ejection fraction - Results from the Croatian heart failure (CRO-HF) registry.

PubMed

Domagoj, Markovic; Branka, Jurcevic Zidar; Jelena, Macanovic; Davor, Milicic; Duska, Glavas

2018-04-17

According to recent guidelines, the best approach for treatment of heart failure patients with preserved ejection function is still not defined. The aim of this study was to investigate how carvedilol therapy influences the survival rate, ejection fraction and NYHA class in these patients. We conducted study on heart failure patients with preserved systolic function from the Croatian heart failure registry who were hospitalized in the period between 2005 and 2010. We enrolled patients with carvedilol listed as treatment on their discharge letters and patients who had been using carvedilol for at least 4 years, while for the control group we selected patients with no beta-blockers on their discharge letters (113 vs 204 respectively). The primary outcome was the overall survival rate and the secondary outcome was the change in ejection fraction of the left ventricle and NYHA class during the study. Patients in the carvedilol group had a higher overall survival rate compared to patients in the control group (chi-square=14.1, P<0.001). Patients in the carvedilol group in two measurements had a significantly higher ejection fraction compared to the control group (F=148.04, P<0.001). Also, patients in the carvedilol group showed improvement in NYHA class (chi-square=29.768, P<0.001). Long term carvedilol therapy appears to be associated with a higher overall survival rate, improvement in ejection fraction and NYHA class in heart failure patients with preserved ejection fraction. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Patient-Specific MRI-Based Right Ventricle Models Using Different Zero-Load Diastole and Systole Geometries for Better Cardiac Stress and Strain Calculations and Pulmonary Valve Replacement Surgical Outcome Predictions.

PubMed

Tang, Dalin; Del Nido, Pedro J; Yang, Chun; Zuo, Heng; Huang, Xueying; Rathod, Rahul H; Gooty, Vasu; Tang, Alexander; Wu, Zheyang; Billiar, Kristen L; Geva, Tal

2016-01-01

Accurate calculation of ventricular stress and strain is critical for cardiovascular investigations. Sarcomere shortening in active contraction leads to change of ventricular zero-stress configurations during the cardiac cycle. A new model using different zero-load diastole and systole geometries was introduced to provide more accurate cardiac stress/strain calculations with potential to predict post pulmonary valve replacement (PVR) surgical outcome. Cardiac magnetic resonance (CMR) data were obtained from 16 patients with repaired tetralogy of Fallot prior to and 6 months after pulmonary valve replacement (8 male, 8 female, mean age 34.5 years). Patients were divided into Group 1 (n = 8) with better post PVR outcome and Group 2 (n = 8) with worse post PVR outcome based on their change in RV ejection fraction (EF). CMR-based patient-specific computational RV/LV models using one zero-load geometry (1G model) and two zero-load geometries (diastole and systole, 2G model) were constructed and RV wall thickness, volume, circumferential and longitudinal curvatures, mechanical stress and strain were obtained for analysis. Pairwise T-test and Linear Mixed Effect (LME) model were used to determine if the differences from the 1G and 2G models were statistically significant, with the dependence of the pair-wise observations and the patient-slice clustering effects being taken into consideration. For group comparisons, continuous variables (RV volumes, WT, C- and L- curvatures, and stress and strain values) were summarized as mean ± SD and compared between the outcome groups by using an unpaired Student t-test. Logistic regression analysis was used to identify potential morphological and mechanical predictors for post PVR surgical outcome. Based on results from the 16 patients, mean begin-ejection stress and strain from the 2G model were 28% and 40% higher than that from the 1G model, respectively. Using the 2G model results, RV EF changes correlated negatively with stress (r = -0.609, P = 0.012) and with pre-PVR RV end-diastole volume (r = -0.60, P = 0.015), but did not correlate with WT, C-curvature, L-curvature, or strain. At begin-ejection, mean RV stress of Group 2 was 57.4% higher than that of Group 1 (130.1±60.7 vs. 82.7±38.8 kPa, P = 0.0042). Stress was the only parameter that showed significant differences between the two groups. The combination of circumferential curvature, RV volume and the difference between begin-ejection stress and end-ejection stress was the best predictor for post PVR outcome with an area under the ROC curve of 0.855. The begin-ejection stress was the best single predictor among the 8 individual parameters with an area under the ROC curve of 0.782. The new 2G model may be able to provide more accurate ventricular stress and strain calculations for potential clinical applications. Combining morphological and mechanical parameters may provide better predictions for post PVR outcome.

Assessment of left ventricular ejection fraction by radionuclide angiography. Comparison to echocardiography and serial measurements in patients with myocardial infarction

NASA Technical Reports Server (NTRS)

Schelbert, H. R.; Henning, H.; Orourke, R. A.; Ashburn, W. L.

1975-01-01

Measurements of the left ventricular ejection fraction were compared in patients with previous myocardial infarctions. Left ventricular ejection fraction was measured by the radioisotopic method serially in patients early after an acute myocardial infarction and during the convalescence period. Ultrasound recordings were obtained utilizing a commercially available ultrasonoscope and a 1/9 cm transducer focused at 10 cm with a repetition rate of 1000 impulses per second. All recordings were made on a visicorder oscillography.

Repeated doses of cardiac mesenchymal cells are therapeutically superior to a single dose in mice with old myocardial infarction.

PubMed

Guo, Yiru; Wysoczynski, Marcin; Nong, Yibing; Tomlin, Alex; Zhu, Xiaoping; Gumpert, Anna M; Nasr, Marjan; Muthusamy, Senthikumar; Li, Hong; Book, Michael; Khan, Abdur; Hong, Kyung U; Li, Qianhong; Bolli, Roberto

2017-03-01

We have recently demonstrated that repeated administrations of c-kit POS cardiac progenitor cells (CPCs) have cumulative beneficial effects in rats with old myocardial infarction (MI), resulting in markedly greater improvement in left ventricular (LV) function compared with a single administration. To determine whether this paradigm applies to other species and cell types, mice with a 3-week-old MI received one or three doses of cardiac mesenchymal cells (CMCs), a novel cell type that we have recently described. CMCs or vehicle were infused percutaneously into the LV cavity, 14 days apart. Compared with vehicle-treated mice, the single-dose group exhibited improved LV ejection fraction (EF) after the 1st infusion (consisting of CMCs) but not after the 2nd and 3rd (vehicle). In contrast, in the multiple-dose group, LV EF improved after each CMC infusion, so that at the end of the study, LV EF averaged 35.5 ± 0.7% vs. 32.7 ± 0.6% in the single-dose group (P < 0.05). The multiple-dose group also exhibited less collagen in the non-infarcted region vs. the single-dose group. Engraftment and differentiation of CMCs were negligible in both groups, indicating paracrine effects. These results demonstrate that, in mice with ischemic cardiomyopathy, the beneficial effects of three doses of CMCs are significantly greater than those of one dose, supporting the concept that multiple treatments are necessary to properly evaluate the full therapeutic potential of cell therapy. Thus, the repeated-treatment paradigm is not limited to c-kit POS CPCs or to rats, but applies to other cell types and species. The generalizability of this concept dramatically augments its significance.

Usefulness of the brain natriuretic peptide to atrial natriuretic peptide ratio in determining the severity of mitral regurgitation.

PubMed

Shimamoto, Ken; Kusumoto, Miyako; Sakai, Rieko; Watanabe, Hirota; Ihara, Syunichi; Koike, Natsuka; Kawana, Masatoshi

2007-03-15

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels were characterized in subjects with mitral regurgitation (MR). Sixty-two cases of moderate or severe chronic MR were studied. The blood levels of neurohormonal factors were stratified by the known MR prognostic factors of New York Heart Association (NYHA) functional class, left ventricular end-diastolic diameters, left ventricular end-systolic diameter (LVDs), ejection fraction (EF), left atrial diameter and presence of atrial fibrillation (AF). ANP levels were higher in NYHA class II and lower in classes I and III/IV (P=0.0206). BNP levels were higher in NYHA class II than class I (P=0.0355). The BNP/ANP ratio was significantly higher in NYHA classes II and III/IV than in class I (P=0.0007). To differentiate between NYHA classes I/II and III/IV, a cut-off BNP/ANP ratio of 2.97 produced a sensitivity of 78% and specificity of 87%. Compared with subjects in sinus rhythm, patients with AF had an enlarged left atrium and lower ANP levels. The BNP/ANP ratio correlated significantly with left atrial diameter, LVDs and EF (r=0.429, P=0.0017; r=0.351, P=0.0117; and r=-0.349, P=0.0122; respectively), and was significantly higher among all the known operative indications for MR tested (LVDs 45 mm or more, EF 60% or less, NYHA class II or greater and AF; P=0.0073, P=0.003, P=0.0102 and P=0.0149, respectively). In chronic MR, levels of ANP and BNP, and the BNP/ANP ratio are potential indicators of disease severity.

Interatrial septum motion but not Doppler assessment predicts elevated pulmonary capillary wedge pressure in patients undergoing cardiac surgery.

PubMed

Haji, Darsim L; Ali, Mohamed M; Royse, Alistair; Canty, David J; Clarke, Sandy; Royse, Colin F

2014-10-01

Left atrial pressure and its surrogate, pulmonary capillary wedge pressure (PCWP), are important for determining diastolic function. The role of transthoracic echocardiography (TTE) in assessing diastolic function is well established in awake subjects. The objective was to assess the accuracy of predicting PCWP by TTE and transesophageal echocardiography (TEE) during coronary artery surgery. In 27 adult patients undergoing on-pump coronary artery surgery, simultaneous echocardiographic and hemodynamic measurements were obtained immediately before anesthesia (TTE), after anesthesia and mechanical ventilation (TTE and TEE), during conduit harvest (TEE), and after separation from cardiopulmonary bypass (TEE). Twenty patients had an ejection fraction (EF) of 0.5 or greater. With the exception of E/e' and S/D ratios, echocardiographic values changed over the echocardiographic studies. In patients with low EF, E velocity, deceleration time, pulmonary vein D, S/D, and E/e' ratios correlated well with PCWP before anesthesia. After induction of anesthesia using TTE or TEE, correlations were poor. In normal EF patients, correlations were poor for both TEE and TTE at all five stages. The sensitivity and specificity of echocardiographic values were not high enough to predict raised PCWP except for a fixed curve pattern of interatrial septum (area under the curve 0.89 for PCWP ≥ 17, and 0.98 for ≥ 18 mmHg) and S/D less than 1 (area under the curve 0.74 for PCWP ≥ 17, and 0.78 for ≥ 18 mmHg). Doppler assessment of PCWP was neither sensitive nor specific enough to be clinically useful in anesthetized patients with mechanical ventilation. The fixed curve pattern of the interatrial septum was the best predictor of raised PCWP.

Effect of balloon mitral valvotomy on left ventricular function in rheumatic mitral stenosis.

PubMed

Rajesh, Gopalan Nair; Sreekumar, Pradeep; Haridasan, Vellani; Sajeev, C G; Bastian, Cicy; Vinayakumar, D; Kadermuneer, P; Mathew, Dolly; George, Biju; Krishnan, M N

Mitral stenosis (MS) is found to produce left ventricular (LV) dysfunction in some studies. We sought to study the left ventricular function in patients with rheumatic MS undergoing balloon mitral valvotomy (BMV). Ours is the first study to analyze effect of BMV on mitral annular plane systolic excursion (MAPSE), and to quantify prevalence of longitudinal left ventricular dysfunction in rheumatic MS. In this prospective cohort study, we included 43 patients with severe rheumatic mitral stenosis undergoing BMV. They were compared to twenty controls whose distribution of age and gender were similar to that of patients. The parameters compared were LV ejection fraction (EF) by modified Simpson's method, mitral annular systolic velocity (MASV), MAPSE, mitral annular early diastolic velocity (E'), and myocardial performance index (MPI). These parameters were reassessed immediately following BMV and after 3 months of procedure. MASV, MAPSE, E', and EF were significantly lower and MPI was higher in mitral stenosis group compared to controls. Impaired longitudinal LV function was present in 77% of study group. MAPSE and EF did not show significant change after BMV while MPI, MASV, and E' improved significantly. MASV and E' showed improvement immediately after BMV, while MPI decreased only at 3 months follow-up. There were significantly lower mitral annular motion parameters including MAPSE in patients with rheumatic mitral stenosis. Those with atrial fibrillation had higher MPI. Immediately after BMV, there was improvement in LV long axis function with a gradual improvement in global LV function. There was no significant change of MAPSE after BMV. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Gender and survival in patients with heart failure: interactions with diabetes and aetiology. Results from the MAGGIC individual patient meta-analysis.

PubMed

Martínez-Sellés, Manuel; Doughty, Robert N; Poppe, Katrina; Whalley, Gillian A; Earle, Nikki; Tribouilloy, Christophe; McMurray, John J V; Swedberg, Karl; Køber, Lars; Berry, Colin; Squire, Iain

2012-05-01

The aim of this study was to investigate the relationship between gender and survival of patients with heart failure, using data from both randomized trials and observational studies, and the relative contribution of age, left ventricular systolic function, aetiology, and diabetes to differences in prognosis between men and women. Data from 31 studies (41 949 patients; 28 052 men, 13 897 women) from the Meta-Analysis Global Group In Chronic Heart Failure (MAGGIC) individual patient meta-analysis were used. We performed survival analysis to assess the association of gender with mortality, adjusting for predictors of mortality, including age, reduced or preserved ejection fraction (EF), and ischaemic or non-ischaemic aetiology. Women were older [70.5 ( standard deviation 12.1) vs. 65.6 (standard deviation 11.6) years], more likely to have a history of hypertension (49.9% vs. 40.0%), and less likely to have a history of ischaemic heart disease (46.3% vs. 58.7%) and reduced EF (62.6% vs. 81.6%) compared with men. During 3 years follow-up, 3521 (25%) women and 7232 (26%) men died. After adjustment, male gender was an independent predictor of mortality, and the better prognosis associated with female gender was more marked in patients with heart failure of non-ischaemic, compared with ischaemic, aetiology (P-value for interaction = 0.03) and in patients without, compared with those with, diabetes (P-value for interaction <0.0001). This large, individual patient data meta-analysis has demonstrated that survival is better for women with heart failure compared with men, irrespective of EF. This survival benefit is slightly more marked in non-ischaemic heart failure but is attenuated by concomitant diabetes.

Resting Heart Rate as Predictor for Left Ventricular Dysfunction and Heart Failure: The Multi-Ethnic Study of Atherosclerosis

PubMed Central

Opdahl, Anders; Venkatesh, Bharath Ambale; Fernandes, Veronica R. S.; Wu, Colin O.; Nasir, Khurram; Choi, Eui-Young; Almeida, Andre L. C.; Rosen, Boaz; Carvalho, Benilton; Edvardsen, Thor; Bluemke, David A.; Lima, Joao A. C.

2014-01-01

OBJECTIVE To investigate the relationship between baseline resting heart rate and incidence of heart failure (HF) and global and regional left ventricular (LV) dysfunction. BACKGROUND The association of resting heart rate to HF and LV function is not well described in an asymptomatic multi-ethnic population. METHODS Participants in the Multi-Ethnic Study of Atherosclerosis had resting heart rate measured at inclusion. Incident HF was registered (n=176) during follow-up (median 7 years) in those who underwent cardiac MRI (n=5000). Changes in ejection fraction (ΔEF) and peak circumferential strain (Δεcc) were measured as markers of developing global and regional LV dysfunction in 1056 participants imaged at baseline and 5 years later. Time to HF (Cox model) and Δεcc and ΔEF (multiple linear regression models) were adjusted for demographics, traditional cardiovascular risk factors, calcium score, LV end-diastolic volume and mass in addition to resting heart rate. RESULTS Cox analysis demonstrated that for 1 bpm increase in resting heart rate there was a 4% greater adjusted relative risk for incident HF (Hazard Ratio: 1.04 (1.02, 1.06 (95% CI); P<0.001). Adjusted multiple regression models demonstrated that resting heart rate was positively associated with deteriorating εcc and decrease in EF, even in analyses when all coronary heart disease events were excluded from the model. CONCLUSION Elevated resting heart rate is associated with increased risk for incident HF in asymptomatic participants in MESA. Higher heart rate is related to development of regional and global LV dysfunction independent of subclinical atherosclerosis and coronary heart disease. PMID:24412444

Is rhythm-control superior to rate-control in patients with atrial fibrillation and diastolic heart failure?

PubMed

Kong, Melissa H; Shaw, Linda K; O'Connor, Christopher; Califf, Robert M; Blazing, Michael A; Al-Khatib, Sana M

2010-07-01

Although no clinical trial data exist on the optimal management of atrial fibrillation (AF) in patients with diastolic heart failure, it has been hypothesized that rhythm-control is more advantageous than rate-control due to the dependence of these patients' left ventricular filling on atrial contraction. We aimed to determine whether patients with AF and heart failure with preserved ejection fraction (EF) survive longer with rhythm versus rate-control strategy. The Duke Cardiovascular Disease Database was queried to identify patients with EF > 50%, heart failure symptoms and AF between January 1,1995 and June 30, 2005. We compared baseline characteristics and survival of patients managed with rate- versus rhythm-control strategies. Using a 60-day landmark view, Kaplan-Meier curves were generated and results were adjusted for baseline differences using Cox proportional hazards modeling. Three hundred eighty-two patients met the inclusion criteria (285 treated with rate-control and 97 treated with rhythm-control). The 1-, 3-, and 5-year survival rates were 93.2%, 69.3%, and 56.8%, respectively in rate-controlled patients and 94.8%, 78.0%, and 59.9%, respectively in rhythm-controlled patients (P > 0.10). After adjustments for baseline differences, no significant difference in mortality was detected (hazard ratio for rhythm-control vs rate-control = 0.696, 95% CI 0.453-1.07, P = 0.098). Based on our observational data, rhythm-control seems to offer no survival advantage over rate-control in patients with heart failure and preserved EF. Randomized clinical trials are needed to verify these findings and examine the effect of each strategy on stroke risk, heart failure decompensation, and quality of life.

Effects of percutaneous renal sympathetic denervation on cardiac function and exercise tolerance in patients with chronic heart failure.

PubMed

Gao, Jun-Qing; Xie, Yun; Yang, Wei; Zheng, Jian-Pu; Liu, Zong-Jun

2017-01-01

Sympathetic hyperactivity, a vital factor in the genesis and development of heart failure (HF), has been reported to be effectively reduced by percutaneous renal denervation (RDN), which may play an important role in HF treatment. To determine the effects of percutaneous RDN on cardiac function in patients with chronic HF (CHF). Fourteen patients (mean age 69.6 years; ejection fraction [EF] <45%) with CHF received bilateral RDN. Adverse cardiac events, blood pressure (BP), and biochemical parameters were assessed before and six months after percutaneous operation. Patients also underwent echocardiographic assessment of cardiac function and 6-min walk test before and at six months after percutaneous operation. The distance achieved by the 14 patients in the 6-min walk test increased significantly from 152.9±38.0 m before RDN to 334.3±94.4 m at six months after RDN (p<0.001), while EF increased from 36.0±4.1% to 43.8±7.9% (p=0.003) on echocardiography. No RDN-related complications were observed during the follow-up period. In 6-month follow-up, systolic BP decreased from 138.6±22.1 mmHg to 123.2±10.5 mmHg (p=0.026) and diastolic BP from 81.1±11.3 mmHg to 72.9±7.5 mmHg (p=0.032). Creatinine levels did not change significantly (1.3±0.65 mg/dl to 1.2±0.5 mg/dl, p=0.8856). RDN is potentially an effective technique for the treatment of severe HF that can significantly increase EF and improve exercise tolerance. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Reversible non-ischaemic cardiomyopathy and left ventricular dysfunction after liver transplantation: a single-centre experience.

PubMed

Yataco, Maria L; Difato, Thomas; Bargehr, Johannes; Rosser, Barry G; Patel, Tushar; Trejo-Gutierrez, Jorge F; Pungpapong, Surakit; Taner, C Burcin; Aranda-Michel, Jaime

2014-07-01

Non-ischaemic cardiomyopathy (NIC) is an early complication of liver transplantation (LT). Our aims were to define the prevalence, associated clinical factors, and prognosis of this condition. A retrospective study was performed on patients undergoing LT at our institution from January 2005 to December 2012. Patients who developed NIC were identified. Data collected included demographic and clinical data. A total 1460 transplants were performed in this period and seventeen patients developed NIC. Pretransplant median QTc interval was 459 (range, 405-530), and median E/A ratio was 1 (range, 0.71-1.67). Fourteen patients (82%) were severely malnourished and required nutritional support. Thirteen patients (76%) had renal insufficiency. Median time to onset was 2 days post-transplant (range, 0-20). Echocardiograms showed global left ventricular hypokinesis and a decrease in ejection fraction (EF) from a median of 65% (range, 50-81) pretransplant to a median of 21% (range, 15-32). Median raw model for end-stage liver disease (MELD) score was 29 in patients with NIC vs. 18 in patients without cardiomyopathy (P = 0.01). There was no significant difference between recipients with NIC vs. recipients without cardiomyopathy regarding donor age, donor risk index, and cold and warm ischaemia time. Recovery of cardiac function occurred in 16 patients, with a median EF of 44% (range, 25-65%) at the time of discharge. The last echocardiogram available showed a median EF of 59% (range, 49-73%). One-year survival of NIC patients was 94.1%. Non-ischaemic cardiomyopathy is a rare complication after LT. Patients with NIC are critically ill, with high MELD score, and severe malnutrition. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Feasibility Study of Smartphone-Based Telesonography for Evaluating Cardiac Dynamic Function and Diagnosing Acute Appendicitis with Control of the Image Quality of the Transmitted Videos.

PubMed

Kim, Changsun; Cha, Hyunmin; Kang, Bo Seung; Choi, Hyuk Joong; Lim, Tae Ho; Oh, Jaehoon

2016-06-01

Our aim was to prove the feasibility of the remote interpretation of real-time transmitted ultrasound videos of dynamic and static organs using a smartphone with control of the image quality given a limited internet connection speed. For this study, 100 cases of echocardiography videos (dynamic organ)-50 with an ejection fraction (EF) of ≥50 s and 50 with EF <50 %-and 100 cases of suspected pediatric appendicitis (static organ)-50 with signs of acute appendicitis and 50 with no findings of appendicitis-were consecutively selected. Twelve reviewers reviewed the original videos using the liquid crystal display (LCD) monitor of an ultrasound machine and using a smartphone, to which the images were transmitted from the ultrasound machine. The resolution of the transmitted echocardiography videos was reduced by approximately 20 % to increase the frame rate of transmission given the limited internet speed. The differences in diagnostic performance between the two devices when evaluating left ventricular (LV) systolic function by measuring the EF and when evaluating the presence of acute appendicitis were investigated using a five-point Likert scale. The average areas under the receiver operating characteristic curves for each reviewer's interpretations using the LCD monitor and smartphone were respectively 0.968 (0.949-0.986) and 0.963 (0.945-0.982) (P = 0.548) for echocardiography and 0.972 (0.954-0.989) and 0.966 (0.947-0.984) (P = 0.175) for abdominal ultrasonography. We confirmed the feasibility of remotely interpreting ultrasound images using smartphones, specifically for evaluating LV function and diagnosing pediatric acute appendicitis; the images were transferred from the ultrasound machine using image quality-controlled telesonography.

Vasopressin V2 receptor antagonist tolvaptan is effective in heart failure patients with reduced left ventricular systolic function and low blood pressure.

PubMed

Suzuki, Satoshi; Yoshihisa, Akiomi; Yamaki, Takayoshi; Sugimoto, Koichi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Abe, Yukihiko; Saito, Tomiyoshi; Ohwada, Takayuki; Suzuki, Hitoshi; Saitoh, Shu-ichi; Kubota, Isao; Takeishi, Yasuchika

2015-01-01

Diuresis is a major therapy for the reduction of congestive symptoms in acute decompensated heart failure (ADHF) patients. Carperitide has natriuretic and vasodilatory effects, and tolvaptan produces water excretion without electrolyte excretion. We previously reported the usefulness of tolvaptan compared to carperitide in ADHF patients with fluid volume retention. The purpose of this study was to examine whether the efficacy of tolvaptan was altered in ADHF patients with reduced left ventricular systolic function and in those with hypotension. A total of 109 hospitalized ADHF patients were randomly assigned to either a tolvaptan or a carperitide treatment group. Baseline clinical characteristics were not different between the two groups. We divided these patients based on the left ventricular ejection fraction (EF) by echocardiography, and blood pressure (BP) at the time of admission. Daily urine volume between the tolvaptan and carperitide groups in patients with preserved EF (≥ 50%) was not different, however, in those with reduced EF (< 50%), the urine volume was significantly higher in the tolvaptan group than in the carperitide group (day 2, 3, 4, P < 0.05 for all). Daily urine volume did not differ between these two groups in the high blood pressure group (BP ≥ 140 mmHg), but was significantly higher in the tolvaptan group than in the carperitide group (day 1, P = 0.021; day 3, P = 0.017) in the low blood pressure group (BP < 140 mmHg). The present study reveals that tolvaptan is more effective than carperitide, especially in ADHF patients with reduced left ventricular systolic function and without hypertension.

Echocardiographic assessment of the incidence of mechanical complications during the early phase of myocardial infarction in the reperfusion era: a French multicentre prospective registry.

PubMed

Gueret, P; Khalife, K; Jobic, Y; Fillipi, E; Isaaz, K; Tassan-Mangina, S; Baixas, C; Motreff, P; Meune, C

2008-01-01

Since the early reports on the incidence of mechanical complications of acute myocardial infarction (AMI) assessed by echocardiography published in the 1980s, the management of patients with AMI has changed considerably, in particular with the progressive development of early revascularisation. The aim of this multicentre study was to assess the incidence of mechanical complications of AMI in the reperfusion era. Nine-hundred and eight consecutive patients were included. Echocardiography was performed on admission and at discharge. Seventy-eight percent of patients were revascularised at the acute phase. The following incidence rates of mechanical complications were observed: mitral regurgitation 28%, secondary to left ventricular (LV) remodelling (43%) or papillary muscle dysfunction (57%); pericardial effusion 6.6%, more frequent after anterior AMI and associated with a lower ejection fraction (EF); LV thrombus 2.4%, mainly after anterior AMI and associated with a lower EF (38+/-10% vs. 48+/-12%; p<0.001); early infarct expansion 4%; septal rupture 0.6%; and acute free wall rupture 0.8%. The following factors were independently associated with the occurrence of mechanical complications by multivariate logistic regression analysis: lack of early revascularisation (OR 3.48, 95%CI 1.36-8.95; p<0.001), LV-EF<50% (OR 1.95, 95%CI 1.42-2.67; p<0.001), Killip class>II (OR 1.91, 95%CI 1.27-2.87; p<0.002) and age > or =70 years (OR 1.42, 95%CI 1.03-1.97; p<0.03). This study demonstrates the favourable prognostic influence of early revascularisation as shown by the low incidence of mechanical complications after AMI, and underlines the persistent relationship between the development of these complications and depressed LV function.

National experience with long-term use of the wearable cardioverter defibrillator in patients with cardiomyopathy.

PubMed

Lamichhane, Madhab; Gardiner, Joseph C; Bianco, Nicole R; Szymkiewicz, Steven J; Thakur, Ranjan K

2017-01-01

The wearable cardioverter defibrillator (WCD) is generally used for short periods of sudden cardiac death (SCD) risk; circumstances may occasionally result in prolonged use (over 1 year). The aim of this study was to determine the benefits and risks of prolonged use in patients with systolic heart failure (HF). ZOLL's post-market US database included adult patients (≥18 years) with ischemic and/or non-ischemic cardiomyopathy (ICM, NICM) and at least 1 year of use. Cox-regression was used to identify factors associated with survival with WCD use, and reasons for stopping use were entered as time-dependent factors. Among 220 patients, age (mean ± SD) 55.4 ± 14.8 years, WCD use 451.4 ± 289.9 days, and 67.3 % were male and their left ventricle ejection fraction (EF) averaged 20.9 ± 7.2 %. Eighty-nine (40.5 %) were continuing WCD use at the last follow-up. Thirty-six (16.4 %) and 56 (25.5 %) patients discontinued WCD use because of EF recovery and implantable cardioverter (ICD) implantation, respectively. Nine patients (4.1 %) received appropriate shock therapy for 13 episodes of sustained ventricular tachyarrhythmia with 12 (92.3 %) successful shocks. One patient died of refractory ventricular fibrillation. One patient died from sinus bradycardia transitioning to asystole. Eight patients (3.6 %) had nine episodes of non-fatal inappropriate shocks. Long-term use of the WCD is safe and effective. Recovery of EF was seen in significant number of patients even after 1 year of WCD use.

The Wearable Cardioverter Defibrillator in Nonischemic Cardiomyopathy: A US National Database Analysis.

PubMed

Salehi, Negar; Nasiri, Mojdeh; Bianco, Nicole R; Opreanu, Madalina; Singh, Vini; Satija, Vaibhav; Jhand, Aravdeep S; Karapetyan, Lilit; Safadi, Abdul Rahman; Surapaneni, Phani; Thakur, Ranjan K

2016-10-01

The wearable cardioverter defibrillator (WCD) is often used in patients at risk of sudden cardiac death (SCD) who are not yet candidates for an implantable cardioverter defibrillator (ICD). Newly diagnosed cardiomyopathy may be reversible, and a WCD may protect patients during the initial period of risk. We evaluate the benefit and compliance of the WCD in patients with nonischemic cardiomyopathy (NICM). We reviewed a national database of patients with NICM who used WCDs and who self-reported a history of excess alcohol use, although other causes of cardiomyopathy could not be excluded. The database contained demographic data, initial ejection fraction (EF), reason for WCD prescription, compliance and use data, any detected arrhythmias, therapies, and reason for discontinuing WCD. Statistical analyses were performed using SAS, version 9.3 (SAS Institute, Cary, NC). Of the 127 patients, 88% were men with a mean age of 52.6 ± 11.0 years. The mean initial EF was 19.9% ± 7.4%. Patients wore the WCD for a median of 51 days and a median daily use of 18.0 hours per day. The most common reasons for discontinuing the WCD were improvement in EF (33%) or ICD implantation (23.6%). Seven patients (5.5%) had 9 sustained ventricular arrhythmia events, which were successfully treated with 100% conversion. There were 11 deaths (8.6%) during 100 days of follow-up. No deaths resulted from WCD shock failure or undersensing. NICM may have a significant risk of ventricular arrhythmias and death in the first few months. The WCD delivered appropriate therapy in 5.5% of patients. This study suggests that a WCD may be effective temporary prophylaxis for prevention of SCD in patients with newly diagnosed NICM. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

TRPV2 knockout mice demonstrate an improved cardiac performance following myocardial infarction due to attenuated activity of peri-infarct macrophages.

PubMed

Entin-Meer, Michal; Cohen, Lena; Hertzberg-Bigelman, Einat; Levy, Ran; Ben-Shoshan, Jeremy; Keren, Gad

2017-01-01

We have recently shown that the expression of the transient receptor potential vanilloid 2 channel, TRPV2, is upregulated in the peri-infarct zone 3-5 days following an acute myocardial infarction (AMI). Further analysis has demonstrated that invading monocytes maturing to macrophages merely harbor the documented elevated expression of this channel. Assess cardiac function in TRPV2-KO mice compared to TRPV2-WT following AMI and analyze the potential involvement of TRPV2-expressing macrophages in the recovery process. TRPV2-KO or WT mice were induced with AMI by ligation of the left anterior descending artery (LAD). In another set of experiments, TRPV2-KO mice induced with AMI, were intravenously (IV) injected with WT or TRPV2-KO peritoneal macrophages in order to directly assess the potential contribution of TRPV2-expressing macrophages to cardiac healing. Cardiac parameters were obtained by echocardiography 1 day and 30 days post infarction. The relative changes in the ejection fraction (EF) and additional cardiac parameters between baseline (day 1) and day 30 were calculated and statistical significance was determined (SPSS). The in vivo study showed that while EF was significantly decreased in the WT animals between baseline and day 30, EF was only slightly and insignificantly reduced in the KO animals. Likewise LVESD and LVESA were significantly modified exclusively in the WT animals. Moreover, intravenous administration of peritoneal WT macrophages, but not KO macrophages, significantly reduced survival of post-MI TRPV2-KO mice. The data suggest that knockout of the TRPV2 channel may attenuate macrophage-dependent pro-inflammatory processes and result in better cardiac recovery. TRPV2 may thus represent a novel therapeutic target for treatment of patients undergoing an acute MI.

Enantiomer fractions of chlordane components in sediment from U.S. Geological Survey sites in lakes and rivers

USGS Publications Warehouse

Ulrich, E.M.; Foreman, W.T.; Van Metre, P.C.; Wilson, J.T.; Rounds, S.A.

2009-01-01

Spatial, temporal, and sediment-type trends in enantiomer signatures were evaluated for cis- and trans-chlordane (CC, TC) in archived core, suspended, and surficial-sediment samples from six lake, reservoir, and river sites across the United States. The enantiomer fractions (EFs) measured in these samples are in good agreement with those reported for sediment, soil, and air samples in previous studies. The chlordane EFs were generally close to the racemic value of 0.5, with CC values ranging from 0.493 to 0.527 (usually >0.5) and TC values from 0.463 to 0.53 (usually <0.5). EF changes with core depth were detected for TC and CC in some cores, with the most non-racemic values near the top of the core. Surficial and suspended sediments generally have EF values similar to the top core layers but are often more non-racemic, indicating that enantioselective degradation is occurring before soils are eroded and deposited into bottom sediments. We hypothesize that rapid losses (desorption or degradation) from suspended sediments of the more bioavailable chlordane fraction during transport and initial deposition could explain the apparent shift to more racemic EF values in surficial and top core sediments. Near racemic CC and TC in the core profiles suggest minimal alteration of chlordane from biotic degradation, unless it is via non-enantioselective processes. EF values for the heptachlor degradate, heptachlor epoxide (HEPX), determined in surficial sediments from one location only were always non-racemic (EF ??? 0.66), were indicative of substantial biotic processing, and followed reported EF trends.

Non-selective His bundle pacing with a biphasic waveform: enhancing septal resynchronization.

PubMed

Ortega, Daniel F; Barja, Luis D; Logarzo, Emilio; Mangani, Nicolas; Paolucci, Analia; Bonomini, Maria P

2018-05-01

His bundle pacing has shown to prevent detrimental effects from right ventricular apical pacing (RVA) and proved to resynchronize many conduction disturbances cases. However, the extent of His bundle pacing resynchronization is limited. An optimized stimulation waveform could expand this limit when implemented in His bundle pacing sets. In this work, we temporarily implemented RVA and Non-selective His bundle pacing with a biphasic anodal-first waveform (AF-nHB) and compared their effects against sinus rhythm (SR). Fifteen patients referred for electrophysiologic study with conduction disturbances, cardiomyopathy and ejection fraction below 35% were enrolled for the study. The following acute parameters were measured: QRS duration, left ventricular activation (RLVT), time of isovolumic contraction (IVCT), ejection fraction (EF), and dP/dtmax. QRS duration and RLVT decreased markedly under AF-nHB (SR: 169 ± 34 ms vs. nHB: 116 ± 31 ms, P < 0.0005) while RVA significantly increased QRS duration (SR: 169 ms vs. RVA: 198 ms, P < 0.05) and did not change RLVT (P = NS). Consistently, IVCT moderately decreased under AF-nHB (SR: 238 ms vs. RVA: 184 ms, P < 0.05 vs. SR) and dP/dtmax showed a 93.35 [mmHg] average increase under AF-nHB against SR. Also, T-wave inversions were observed during AF-nHB immediately after SR and RVA pacing suggesting the occurrence of cardiac memory. AF-nHB corrected bundle branch blocks in patients with severe conduction disturbances, even in those with dilated cardiomiopathy, outstanding from RVA. Also, the occurrence of cardiac memory during AF-nHB turned up as an observational finding of this study.

Rheumatoid Arthritis is Independently Associated with Increased Left Ventricular Mass but not Reduced Ejection Fraction

PubMed Central

Rudominer, Rebecca L.; Roman, Mary J.; Devereux, Richard B.; Paget, Stephen A.; Schwartz, Joseph E.; Lockshin, Michael D.; Crow, Mary K.; Sammaritano, Lisa; Levine, Daniel M.; Salmon, Jane E.

2008-01-01

Background Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with premature atherosclerosis, vascular stiffening, and heart failure. Whether RA is associated with underlying structural and functional abnormalities of the left ventricle (LV) is poorly understood. Methods and Results 89 patients with RA without clinical cardiovascular disease and 89 healthy matched controls underwent echocardiography, carotid ultrasonography, and radial tonometry to measure arterial stiffness. RA patients and controls were similar in body size, hypertension and diabetes status, and cholesterol. LV diastolic diameter (4.92 vs. 4.64 cm, p <0.001), mass (136.9 vs. 121.7 g, p = 0.001 or 36.5 vs. 32.9 g/m 2.7, p = 0.01), ejection fraction (EF) (71% vs. 67%, p <0.001), and prevalence of LV hypertrophy (LVH) (18% vs. 6.7%, p = 0.023) were all higher among RA patients. In multivariate analysis, presence of RA (p = 0.004) was an independent correlate of LV mass. Furthermore, RA was independently associated with the presence of LVH (OR 4.14, [95% CI 1.24-13.80; p=0.021]). Among RA patients, age at diagnosis and disease duration were independently related to LV mass. RA patients with LVH were older and had higher systolic pressure, damage index score, C-reactive protein, homocysteine and arterial stiffness index compared to those without LVH. Conclusion RA is associated with increased LV mass. Disease duration is independently related to increased LV mass, suggesting a pathophysiological link between chronic inflammation and LVH. In contrast, LV systolic function is preserved in RA patients indicating that systolic dysfunction is not an intrinsic feature of RA. PMID:19116901

Role of cardioprotective therapy for prevention of cardiotoxicity with chemotherapy: a systematic review and meta-analysis.

PubMed

Kalam, Kashif; Marwick, Thomas H

2013-09-01

Cardiotoxicity is a well-recognised complication of chemotherapy with anthracycline and/or trastuzumab, and its prevention remains an important challenge in cancer survivorship. Several successful preventative strategies have been identified in animal trials. We sought to assemble the clinical evidence that prophylactic pharmacological interventions could prevent left ventricular (LV) dysfunction and heart failure in patients undergoing chemotherapy. We undertook a systemic review of the evidence from randomised trials and observational studies where a prophylactic intervention was compared with a control arm in patients with a normal ejection fraction and no past history of heart failure. The primary outcome was development of heart failure (HF), a drop in ejection fraction (EF) or both. A random-effects model was used to combine relative risks (RR) and 95% confidence intervals (CIs), and a meta-regression was undertaken to assess the impact of potential covariates. Data were collated from 14 published articles (n=2015 paediatric and adult patients) comprising 12 randomised controlled trials and two observational studies. The most studied chemotherapeutic agents were anthracyclines, and prophylactic agents included dexrazoxane, statins, beta-blocker and angiotensin antagonists. There were 304 cardiac events in the control arm compared to 83 in the prophylaxis arm (RR=0.31 [95% CI: 0.25-0.39], p<0.00001). Cardiac events were reduced with dexrazoxane (RR=0.35 [95% CI 0.27-0.45], p<0.00001), beta-blockade (RR=0.31 [95% CI 0.16-0.63], p=0.001), statin (RR=0.31 [95% CI 0.13-0.77], p=0.01) and angiotensin antagonists (RR=0.11 [95% CI 0.04-0.29], p<0.0001). Prophylactic treatment with dexrazoxane, beta-blocker, statin or angiotensin antagonists appear to have similar efficacy for reducing cardiotoxicity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Serum levels of NT- pro ANP, BNP, NT-pro BNP and function of the left atrium in patients with heart failure and preserved ejection fraction after myocardial infarction

NASA Astrophysics Data System (ADS)

Shurupov, V.; Suslova, T.; Ryabov, V.

2015-11-01

The objective of our study was to evaluate the levels of natriuretic peptides in patients (pts) with heart failure with preserved ejection fraction (HFpEF) in 12 month after ST elevation myocardial infarction (STEMI) with a focus on the function of left atrium (LA) and left ventricular (LV) filling pressure. 55 pts were included in the study. 6-minute walk test was performed. Echo exam was performed by the diagnostic system VIVID 7. BNP in whole blood was determined using the Triage ® Meter BNP test. The serum levels of NT-pro BNP, NT-pro ANP («Biomedica», Austria) were determined in blood samples by enzyme-linked immune-sorbent assay (ELISA). LA volume index were differences (16.03±3.39 ml/m2; 25.36±8.26 ml/m2; 29.41±9.46 ml/m2 accordingly I, II, III class) depending on severity of HF. Well as E/E' ratio were differences (7.5±1.4; 9.8±5.1; 13.5±7.6 accordingly I, II, III class) depending on severity of HF. The LA volume index correlated with levels of NT-pro ANP (R=0.29; p=0.04), levels of NT-pro BNP (R=0.37; p=0.01), levels of BNP (R=0.51; p=0.0001). The LV filling pressure correlated with levels of NT-pro ANP (R=0.45; p=0.002), levels of NT-pro BNP (R=0.49; p=0.001), levels of BNP (R=0.37; p=0.01).

Efficient determination of vehicle emission factors by fuel use category using on-road measurements: downward trends on Los Angeles freight corridor I-710

PubMed Central

Hudda, N.; Fruin, S.; Delfino, R. J.; Sioutas, C.

2013-01-01

To evaluate the success of vehicle emissions regulations, trends in both fleet-wide average emissions as well as high-emitter emissions are needed, but it is challenging to capture the full spread of vehicle emission factors (EFs) with chassis dynamometer or tunnel studies, and remote sensing studies cannot evaluate particulate compounds. We developed an alternative method that links real-time on-road pollutant measurements from a mobile platform with real-time traffic data, and allows efficient calculation of both the average and the spread of EFs for light-duty gasoline-powered vehicles (LDG) and heavy-duty diesel-powered vehicles (HDD). This is the first study in California to report EFs under a full range of real-world driving conditions on multiple freeways. Fleet average LDG EFs were in agreement with most recent studies and an order of magnitude lower than observed HDD EFs. HDD EFs reflected the relatively rapid decreases in diesel emissions that have recently occurred in Los Angeles/California, and on I-710, a primary route used for goods movement and a focus of additional truck fleet turnover incentives, HDD EFs were often lower than on other freeways. When freeway emission rates (ER) were quantified as the product of EF and vehicle miles traveled (VMT) per time per mile of freeway, despite a twoto three-fold difference in HDD fractions between freeways, ERs were found to be generally similar in magnitude. Higher LDG VMT on low HDD fraction freeways largely offset the difference. Therefore, the conventional assumption that free ways with the highest HDD fractions are significantly worse sources of total emissions in Los Angeles may no longer be true. PMID:24244208

Efficient determination of vehicle emission factors by fuel use category using on-road measurements: downward trends on Los Angeles freight corridor I-710.

PubMed

Hudda, N; Fruin, S; Delfino, R J; Sioutas, C

2013-01-11

To evaluate the success of vehicle emissions regulations, trends in both fleet-wide average emissions as well as high-emitter emissions are needed, but it is challenging to capture the full spread of vehicle emission factors (EFs) with chassis dynamometer or tunnel studies, and remote sensing studies cannot evaluate particulate compounds. We developed an alternative method that links real-time on-road pollutant measurements from a mobile platform with real-time traffic data, and allows efficient calculation of both the average and the spread of EFs for light-duty gasoline-powered vehicles (LDG) and heavy-duty diesel-powered vehicles (HDD). This is the first study in California to report EFs under a full range of real-world driving conditions on multiple freeways. Fleet average LDG EFs were in agreement with most recent studies and an order of magnitude lower than observed HDD EFs. HDD EFs reflected the relatively rapid decreases in diesel emissions that have recently occurred in Los Angeles/California, and on I-710, a primary route used for goods movement and a focus of additional truck fleet turnover incentives, HDD EFs were often lower than on other freeways. When freeway emission rates (ER) were quantified as the product of EF and vehicle miles traveled (VMT) per time per mile of freeway, despite a twoto three-fold difference in HDD fractions between freeways, ERs were found to be generally similar in magnitude. Higher LDG VMT on low HDD fraction freeways largely offset the difference. Therefore, the conventional assumption that free ways with the highest HDD fractions are significantly worse sources of total emissions in Los Angeles may no longer be true.

Effectiveness and cost-effectiveness of serum B-type natriuretic peptide testing and monitoring in patients with heart failure in primary and secondary care: an evidence synthesis, cohort study and cost-effectiveness model.

PubMed Central

Pufulete, Maria; Maishman, Rachel; Dabner, Lucy; Mohiuddin, Syed; Hollingworth, William; Rogers, Chris A; Higgins, Julian; Dayer, Mark; Macleod, John; Purdy, Sarah; McDonagh, Theresa; Nightingale, Angus; Williams, Rachael; Reeves, Barnaby C

2017-01-01

BACKGROUND Heart failure (HF) affects around 500,000 people in the UK. HF medications are frequently underprescribed and B-type natriuretic peptide (BNP)-guided therapy may help to optimise treatment. OBJECTIVE To evaluate the clinical effectiveness and cost-effectiveness of BNP-guided therapy compared with symptom-guided therapy in HF patients. DESIGN Systematic review, cohort study and cost-effectiveness model. SETTING A literature review and usual care in the NHS. PARTICIPANTS (a) HF patients in randomised controlled trials (RCTs) of BNP-guided therapy; and (b) patients having usual care for HF in the NHS. INTERVENTIONS Systematic review: BNP-guided therapy or symptom-guided therapy in primary or secondary care. Cohort study: BNP monitored (≥ 6 months' follow-up and three or more BNP tests and two or more tests per year), BNP tested (≥ 1 tests but not BNP monitored) or never tested. Cost-effectiveness model: BNP-guided therapy in specialist clinics. MAIN OUTCOME MEASURES Mortality, hospital admission (all cause and HF related) and adverse events; and quality-adjusted life-years (QALYs) for the cost-effectiveness model. DATA SOURCES Systematic review: Individual participant or aggregate data from eligible RCTs. Cohort study: The Clinical Practice Research Datalink, Hospital Episode Statistics and National Heart Failure Audit (NHFA). REVIEW METHODS A systematic literature search (five databases, trial registries, grey literature and reference lists of publications) for published and unpublished RCTs. RESULTS Five RCTs contributed individual participant data (IPD) and eight RCTs contributed aggregate data (1536 participants were randomised to BNP-guided therapy and 1538 participants were randomised to symptom-guided therapy). For all-cause mortality, the hazard ratio (HR) for BNP-guided therapy was 0.87 [95% confidence interval (CI) 0.73 to 1.04]. Patients who were aged < 75 years or who had heart failure with a reduced ejection fraction (HFrEF) received the most benefit [interactions (p = 0.03): < 75 years vs. ≥ 75 years: HR 0.70 (95% CI 0.53 to 0.92) vs. 1.07 (95% CI 0.84 to 1.37); HFrEF vs. heart failure with a preserved ejection fraction (HFpEF): HR 0.83 (95% CI 0.68 to 1.01) vs. 1.33 (95% CI 0.83 to 2.11)]. In the cohort study, incident HF patients (1 April 2005-31 March 2013) were never tested (n = 13,632), BNP tested (n = 3392) or BNP monitored (n = 71). Median survival was 5 years; all-cause mortality was 141.5 out of 1000 person-years (95% CI 138.5 to 144.6 person-years). All-cause mortality and hospital admission rate were highest in the BNP-monitored group, and median survival among 130,433 NHFA patients (1 January 2007-1 March 2013) was 2.2 years. The admission rate was 1.1 patients per year (interquartile range 0.5-3.5 patients). In the cost-effectiveness model, in patients aged < 75 years with HFrEF or HFpEF, BNP-guided therapy improves median survival (7.98 vs. 6.46 years) with a small QALY gain (5.68 vs. 5.02) but higher lifetime costs (£64,777 vs. £58,139). BNP-guided therapy is cost-effective at a threshold of £20,000 per QALY. LIMITATIONS The limitations of the trial were a lack of IPD for most RCTs and heterogeneous interventions; the inability to identify BNP monitoring confidently, to determine medication doses or to distinguish between HFrEF and HFpEF; the use of a simplified two-state Markov model; a focus on health service costs and a paucity of data on HFpEF patients aged < 75 years and HFrEF patients aged ≥ 75 years. CONCLUSIONS The efficacy of BNP-guided therapy in specialist HF clinics is uncertain. If efficacious, it would be cost-effective for patients aged < 75 years with HFrEF. The evidence reviewed may not apply in the UK because care is delivered differently. FUTURE WORK Identify an optimal BNP-monitoring strategy and how to optimise HF management in accordance with guidelines; update the IPD meta-analysis to include the Guiding Evidence Based Therapy Using Biomarker Intensified Treatment (GUIDE-IT) RCT; collect routine long-term outcome data for completed and ongoing RCTs. TRIAL REGISTRATION Current Controlled Trials ISRCTN37248047 and PROSPERO CRD42013005335. FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 40. See the NIHR Journals Library website for further project information. The British Heart Foundation paid for Chris A Rogers' and Maria Pufulete's time contributing to the study. Syed Mohiuddin's time is supported by the NIHR Collaboration for Leadership in Applied Health Research and Care West at University Hospitals Bristol NHS Foundation Trust. Rachel Maishman contributed to the study when she was in receipt of a NIHR Methodology Research Fellowship. PMID:28774374

Effectiveness and cost-effectiveness of serum B-type natriuretic peptide testing and monitoring in patients with heart failure in primary and secondary care: an evidence synthesis, cohort study and cost-effectiveness model.

PubMed

Pufulete, Maria; Maishman, Rachel; Dabner, Lucy; Mohiuddin, Syed; Hollingworth, William; Rogers, Chris A; Higgins, Julian; Dayer, Mark; Macleod, John; Purdy, Sarah; McDonagh, Theresa; Nightingale, Angus; Williams, Rachael; Reeves, Barnaby C

2017-08-01

Heart failure (HF) affects around 500,000 people in the UK. HF medications are frequently underprescribed and B-type natriuretic peptide (BNP)-guided therapy may help to optimise treatment. To evaluate the clinical effectiveness and cost-effectiveness of BNP-guided therapy compared with symptom-guided therapy in HF patients. Systematic review, cohort study and cost-effectiveness model. A literature review and usual care in the NHS. (a) HF patients in randomised controlled trials (RCTs) of BNP-guided therapy; and (b) patients having usual care for HF in the NHS. Systematic review : BNP-guided therapy or symptom-guided therapy in primary or secondary care. Cohort study : BNP monitored (≥ 6 months' follow-up and three or more BNP tests and two or more tests per year), BNP tested (≥ 1 tests but not BNP monitored) or never tested. Cost-effectiveness model : BNP-guided therapy in specialist clinics. Mortality, hospital admission (all cause and HF related) and adverse events; and quality-adjusted life-years (QALYs) for the cost-effectiveness model. Systematic review : Individual participant or aggregate data from eligible RCTs. Cohort study : The Clinical Practice Research Datalink, Hospital Episode Statistics and National Heart Failure Audit (NHFA). A systematic literature search (five databases, trial registries, grey literature and reference lists of publications) for published and unpublished RCTs. Five RCTs contributed individual participant data (IPD) and eight RCTs contributed aggregate data (1536 participants were randomised to BNP-guided therapy and 1538 participants were randomised to symptom-guided therapy). For all-cause mortality, the hazard ratio (HR) for BNP-guided therapy was 0.87 [95% confidence interval (CI) 0.73 to 1.04]. Patients who were aged < 75 years or who had heart failure with a reduced ejection fraction (HFrEF) received the most benefit [interactions ( p  = 0.03): < 75 years vs. ≥ 75 years: HR 0.70 (95% CI 0.53 to 0.92) vs. 1.07 (95% CI 0.84 to 1.37); HFrEF vs. heart failure with a preserved ejection fraction (HFpEF): HR 0.83 (95% CI 0.68 to 1.01) vs. 1.33 (95% CI 0.83 to 2.11)]. In the cohort study, incident HF patients (1 April 2005-31 March 2013) were never tested ( n  = 13,632), BNP tested ( n  = 3392) or BNP monitored ( n  = 71). Median survival was 5 years; all-cause mortality was 141.5 out of 1000 person-years (95% CI 138.5 to 144.6 person-years). All-cause mortality and hospital admission rate were highest in the BNP-monitored group, and median survival among 130,433 NHFA patients (1 January 2007-1 March 2013) was 2.2 years. The admission rate was 1.1 patients per year (interquartile range 0.5-3.5 patients). In the cost-effectiveness model, in patients aged < 75 years with HFrEF or HFpEF, BNP-guided therapy improves median survival (7.98 vs. 6.46 years) with a small QALY gain (5.68 vs. 5.02) but higher lifetime costs (£64,777 vs. £58,139). BNP-guided therapy is cost-effective at a threshold of £20,000 per QALY. The limitations of the trial were a lack of IPD for most RCTs and heterogeneous interventions; the inability to identify BNP monitoring confidently, to determine medication doses or to distinguish between HFrEF and HFpEF; the use of a simplified two-state Markov model; a focus on health service costs and a paucity of data on HFpEF patients aged < 75 years and HFrEF patients aged ≥ 75 years. The efficacy of BNP-guided therapy in specialist HF clinics is uncertain. If efficacious, it would be cost-effective for patients aged < 75 years with HFrEF. The evidence reviewed may not apply in the UK because care is delivered differently. Identify an optimal BNP-monitoring strategy and how to optimise HF management in accordance with guidelines; update the IPD meta-analysis to include the Guiding Evidence Based Therapy Using Biomarker Intensified Treatment (GUIDE-IT) RCT; collect routine long-term outcome data for completed and ongoing RCTs. Current Controlled Trials ISRCTN37248047 and PROSPERO CRD42013005335. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 21, No. 40. See the NIHR Journals Library website for further project information. The British Heart Foundation paid for Chris A Rogers' and Maria Pufulete's time contributing to the study. Syed Mohiuddin's time is supported by the NIHR Collaboration for Leadership in Applied Health Research and Care West at University Hospitals Bristol NHS Foundation Trust. Rachel Maishman contributed to the study when she was in receipt of a NIHR Methodology Research Fellowship.

A portable cadmium telluride multidetector probe for cardiac function monitoring

NASA Astrophysics Data System (ADS)

Arntz, Y.; Chambron, J.; Dumitresco, B.; Eclancher, B.; Prat, V.

1999-06-01

A new nuclear stethoscope based on a matrix of small CdTe semiconductor detectors has been developed for studying the cardiac performance by gamma ventriculography at the equilibrium, in rest and stress conditions, in the early and recovery phases of the coronary disease and to follow the long-term therapy. The light-weight probe consists of an array of 64 detectors 5×5×2 mm grouped in 16 independent units in a lead shielded aluminum box including 16 preamplifiers. The probe is connected to an electronic box containing DC power supply, 16 channel amplifiers, discriminators and counters, two analog-triggering ECG channels, and interface to a PC. The left ventricle activity is, preferentially, detected by using a low-resolution matching convergent collimator. A physical evaluation of the probe has been performed, both with static tests and dynamically with a hydraulic home-built model of beating heart ventricle paced by a rhythm simulator. The sum of the 16 detectors activity provided a radiocardiogram (RCG) which well depicted the filling and ejection of the cardiac beats, allowing to compare the clinically relevant parameters of the cardiac performance, proportional variables of the stroke volume (SV), ejection fraction (EF) and ventricular flow-rate with the known absolute values programmed on the model. The portable system is now in operation for clinical assessment of cardiac patients.

Fatty Acid Oxidation and Calcium Homeostasis are Involved in the Rescue of Bupivacaine Induced Cardiotoxicity by Lipid Emulsion in Rats

PubMed Central

Partownavid, Parisa; Umar, Soban; Li, Jingyuan; Rahman, Siamak; Eghbali, Mansoureh

2012-01-01

OBJECTIVES Lipid Emulsion (LE) has been shown to be effective in resuscitating bupivacaine-induced cardiac arrest but its mechanism of action is not clear. Here we investigated whether fatty acid oxidation is required for rescue of bupivacaine induced cardiotoxicity by LE in rats. We also compared the mitochondrial function and calcium threshold for triggering of mitochondrial permeability transition pore (mPTP) opening in bupivacaine-induced cardiac arrest before and after resuscitation with LE. DESIGN Prospective, randomized, animal study. SETTING University Research Laboratory. SUBJECTS Adult male Sprague-Dawley rats. INTERVENTIONS Asystole was achieved with a single dose of bupivacaine (10mg/kg over 20seconds, i.v.) and 20% LE infusion (5ml/kg bolus, and 0.5ml/kg/min maintenance) with cardiac massage started immediately. The rats in CVT group were pretreated with a single dose of fatty acid oxidation inhibitor CVT (0.5, 0.25, 0.125 or 0.0625mg/kg bolus i.v.) 5min prior to inducing asystole by bupivacaine overdose. Heart rate (HR), ejection fraction (EF), fractional shortening (FS), the threshold for opening of mPTP, oxygen consumption and membrane potential were measured. The values are Mean±SEM. MEASUREMENTS AND MAIN RESULTS Administration of bupivacaine resulted in asystole. ILP infusion improved the cardiac function gradually as the EF was fully recovered within 5min (EF=64±4% and FS=36±3%, n=6) and heart rate increased to 239±9 beats/min (71% recovery, n=6) within 10min. LE was only able to rescue rats pretreated with low dose of CVT (0.0625mg/kg) (HR=~181±11 beats/min at 10 min, recovery of 56%; EF=50±1%; FS=26±0.6% at 5min, n=3) but was unable to resuscitate rats pretreated with higher doses of CVT (0.5, 0.25 or 0.125mg/kg). The calcium retention capacity in response to Ca2+ overload was significantly higher in cardiac mitochondria isolated from rats resuscitated with 20% LE compared to the group that did not receive ILP after bupivacaine-overdose (330±42 vs. 180±8.2 nmol/mg-mitochondrial protein, p<0.05, n=3 in each group). The mitochondrial oxidative rate and membrane potential were similar in bupivacaine group before and after resuscitation with LE infusion. CONCLUSIONS Fatty acid oxidation is required for successful rescue of bupivacaine induced cardiotoxicity by LE. This rescue action is associated with inhibition of mitochondrial permeability transition pore opening. PMID:22647409

Multiformity of elongation factor eEF-2 isolated from rat liver cells.

PubMed

Gajko, A; Gałasiński, W; Gindzieński, A

1994-07-29

Two fractions of eEF-2 (M(r) approx. 100,000 and M(r) approx. 65,000) were isolated from post-ribosomal supernatant of the rat liver cells. Only eEF-2, with mol. weight of about 100,000 Da, can be phosphorylated, but only eEF-2, with mol. weight of about 65,000 Da, was isolated from the active polyribosomes. The existence of two eEF-2 forms with different properties in the rat liver cells is striking and uncovers new aspects for the cellular function of this protein.

Copula based prediction models: an application to an aortic regurgitation study

PubMed Central

Kumar, Pranesh; Shoukri, Mohamed M

2007-01-01

Background: An important issue in prediction modeling of multivariate data is the measure of dependence structure. The use of Pearson's correlation as a dependence measure has several pitfalls and hence application of regression prediction models based on this correlation may not be an appropriate methodology. As an alternative, a copula based methodology for prediction modeling and an algorithm to simulate data are proposed. Methods: The method consists of introducing copulas as an alternative to the correlation coefficient commonly used as a measure of dependence. An algorithm based on the marginal distributions of random variables is applied to construct the Archimedean copulas. Monte Carlo simulations are carried out to replicate datasets, estimate prediction model parameters and validate them using Lin's concordance measure. Results: We have carried out a correlation-based regression analysis on data from 20 patients aged 17–82 years on pre-operative and post-operative ejection fractions after surgery and estimated the prediction model: Post-operative ejection fraction = - 0.0658 + 0.8403 (Pre-operative ejection fraction); p = 0.0008; 95% confidence interval of the slope coefficient (0.3998, 1.2808). From the exploratory data analysis, it is noted that both the pre-operative and post-operative ejection fractions measurements have slight departures from symmetry and are skewed to the left. It is also noted that the measurements tend to be widely spread and have shorter tails compared to normal distribution. Therefore predictions made from the correlation-based model corresponding to the pre-operative ejection fraction measurements in the lower range may not be accurate. Further it is found that the best approximated marginal distributions of pre-operative and post-operative ejection fractions (using q-q plots) are gamma distributions. The copula based prediction model is estimated as: Post -operative ejection fraction = - 0.0933 + 0.8907 × (Pre-operative ejection fraction); p = 0.00008 ; 95% confidence interval for slope coefficient (0.4810, 1.3003). For both models differences in the predicted post-operative ejection fractions in the lower range of pre-operative ejection measurements are considerably different and prediction errors due to copula model are smaller. To validate the copula methodology we have re-sampled with replacement fifty independent bootstrap samples and have estimated concordance statistics 0.7722 (p = 0.0224) for the copula model and 0.7237 (p = 0.0604) for the correlation model. The predicted and observed measurements are concordant for both models. The estimates of accuracy components are 0.9233 and 0.8654 for copula and correlation models respectively. Conclusion: Copula-based prediction modeling is demonstrated to be an appropriate alternative to the conventional correlation-based prediction modeling since the correlation-based prediction models are not appropriate to model the dependence in populations with asymmetrical tails. Proposed copula-based prediction model has been validated using the independent bootstrap samples. PMID:17573974

Hemodynamic-GUIDEd Management of Heart Failure

ClinicalTrials.gov

2018-03-29

Heart Failure; Heart Failure, Systolic; Heart Failure, Diastolic; Heart Failure NYHA Class II; Heart Failure NYHA Class III; Heart Failure NYHA Class IV; Heart Failure，Congestive; Heart Failure With Reduced Ejection Fraction; Heart Failure With Normal Ejection Fraction; Heart Failure; With Decompensation

Clinical benefit of cardiac resynchronization therapy with a defibrillator in patients with an ejection fraction > 35% estimated by cardiac magnetic resonance.

PubMed

Fabregat-Andrés, Oscar; García-González, Pilar; Valle-Muñoz, Alfonso; Estornell-Erill, Jordi; Pérez-Boscá, Leandro; Palanca-Gil, Victor; Payá-Serrano, Rafael; Quesada-Dorador, Aurelio; Morell, Salvador; Ridocci-Soriano, Francisco

2014-02-01

Cardiac resynchronization therapy with a defibrillator prolongs survival and improves quality of life in advanced heart failure. Traditionally, patients with ejection fraction > 35 estimated by echocardiography have been excluded. We assessed the prognostic impact of this therapy in a group of patients with severely depressed systolic function as assessed by echocardiography but with an ejection fraction > 35% as assessed by cardiac magnetic resonance. We analyzed consecutive patients admitted for decompensated heart failure between 2004 and 2011. The patients were in functional class II-IV, with a QRS ≥ to 120 ms, ejection fraction ≤ 35% estimated by echocardiography, and a cardiac magnetic resonance study. We included all patients (n=103) who underwent device implantation for primary prevention. Ventricular arrhythmia, all-cause mortality and readmission for heart failure were considered major cardiac events. The patients were divided into 2 groups according to systolic function assessed by magnetic resonance. The 2 groups showed similar improvements in functional class and ejection fraction at 6 months. We found a nonsignificant trend toward a higher risk of all-cause mortality in patients with systolic function ≤ 35% at long-term follow-up. The presence of a pattern of necrosis identified patients with a worse prognosis for ventricular arrhythmias and mortality in both groups. We conclude that cardiac resynchronization therapy with a defibrillator leads to a similar clinical benefit in patients with an ejection fraction ≤ 35% or > 35% estimated by cardiac magnetic resonance. Analysis of the pattern of late gadolinium enhancement provides additional information on arrhythmic risk and long-term prognosis. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Value of normal electrocardiographic findings in predicting resting left ventricular function in patients with chest pain and suspected coronary artery disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Keefe, J.H. Jr.; Zinsmeister, A.R.; Gibbons, R.J.

1989-06-01

Characterization of left ventricular function is important in managing patients with coronary artery disease. Although many methods are available to assess left ventricular function, most are either expensive, invasive, or both. In this study, we examined the ability of normal or near-normal resting electrocardiographic findings to predict resting left ventricular ejection fraction, measured by resting radionuclide angiography, in 874 patients with chest pain and suspected coronary artery disease. A retrospective review was undertaken of 4,410 Mayo Clinic patients who underwent rest and exercise radionuclide ventriculography for the evaluation of chest pain and known or suspected coronary artery disease; of these,more » 874 patients met the inclusion criteria for the current study. A 15-lead electrocardiogram, which was interpreted by the cardiologist or cardiology trainee working in the laboratory, was obtained at the same evaluation as the radionuclide study. In 590 patients with no previous history of a myocardial infarction and entirely normal resting electrocardiographic results without nonspecific ST-T wave abnormalities, the mean left ventricular ejection fraction was 0.63 +/- 0.004, and 559 patients (95%) had a normal resting ejection fraction (defined as 0.50 or more). Both nonspecific ST-T wave abnormalities (p less than 0.001) and, to a lesser degree, a history of myocardial infarction (p = 0.06) were independent predictors of an abnormal resting ejection fraction. In 185 patients with nonspecific ST-T wave abnormalities and no history of myocardial infarction, the mean left ventricular ejection fraction was 0.61 +/- 0.009, and 85% had a normal resting ejection fraction.« less

Anti-inflammatory activity of bioaccessible fraction from Eryngium foetidum leaves.

PubMed

Dawilai, Suwitcha; Muangnoi, Chawanphat; Praengamthanachoti, Phawachaya; Tuntipopipat, Siriporn

2013-01-01

Eryngium foetidum (EF) has long been used as a medicinal plant and culinary spice in tropical regions. Phytochemicals in its leaves have been proposed to be responsible for the anti-inflammatory and antioxidant activities. The present study used in vitro digestion coupled with Caco-2 cells to assess such activities. Caco-2 cells were incubated with aqueous fraction from simulated digestion (bioaccessible fraction) of EF leaves with/without bile extract prior to stimulation with interleukin-1 beta (IL-1β). Monocyte chemoattractant protein-1 (MCP-1) and IL-8 in culture media and the intracellular reactive oxygen species (ROS) were measured. Approximately 24% β-carotene and 35% lutein of leaves were present in the aqueous fraction. The transfer of caffeic and chlorogenic acids to the aqueous fraction was 76%-81%, while that of kaempferol was 48%. Prior incubation of Caco-2 cells with the bioaccessible fraction suppressed IL-1β activated IL-8 and MCP-1 by 33%, but the fraction lacking mixed micelles decreased IL-8 and MCP-1 levels only by 11%. The pretreatment of Caco-2 cells with the bioaccessible fraction of EF reduced ROS by 34%; the fraction lacking mixed micelles decreased ROS by 28%. These data suggest that bioactive compounds partitioning in mixed micelles play a significant role to suppress the proinflammatory insult but with a modest antioxidant effect.

Anti-Inflammatory Activity of Bioaccessible Fraction from Eryngium foetidum Leaves

PubMed Central

Dawilai, Suwitcha; Muangnoi, Chawanphat; Praengamthanachoti, Phawachaya; Tuntipopipat, Siriporn

2013-01-01

Eryngium foetidum (EF) has long been used as a medicinal plant and culinary spice in tropical regions. Phytochemicals in its leaves have been proposed to be responsible for the anti-inflammatory and antioxidant activities. The present study used in vitro digestion coupled with Caco-2 cells to assess such activities. Caco-2 cells were incubated with aqueous fraction from simulated digestion (bioaccessible fraction) of EF leaves with/without bile extract prior to stimulation with interleukin-1 beta (IL-1β). Monocyte chemoattractant protein-1 (MCP-1) and IL-8 in culture media and the intracellular reactive oxygen species (ROS) were measured. Approximately 24% β-carotene and 35% lutein of leaves were present in the aqueous fraction. The transfer of caffeic and chlorogenic acids to the aqueous fraction was 76%–81%, while that of kaempferol was 48%. Prior incubation of Caco-2 cells with the bioaccessible fraction suppressed IL-1β activated IL-8 and MCP-1 by 33%, but the fraction lacking mixed micelles decreased IL-8 and MCP-1 levels only by 11%. The pretreatment of Caco-2 cells with the bioaccessible fraction of EF reduced ROS by 34%; the fraction lacking mixed micelles decreased ROS by 28%. These data suggest that bioactive compounds partitioning in mixed micelles play a significant role to suppress the proinflammatory insult but with a modest antioxidant effect. PMID:24151629

Expression of epicardial adipose tissue thermogenic genes in patients with reduced and preserved ejection fraction heart failure.

PubMed

Pérez-Belmonte, Luis M; Moreno-Santos, Inmaculada; Gómez-Doblas, Juan J; García-Pinilla, José M; Morcillo-Hidalgo, Luis; Garrido-Sánchez, Lourdes; Santiago-Fernández, Concepción; Crespo-Leiro, María G; Carrasco-Chinchilla, Fernando; Sánchez-Fernández, Pedro L; de Teresa-Galván, Eduardo; Jiménez-Navarro, Manuel

2017-01-01

Epicardial adipose tissue has been proposed to participate in the pathogenesis of heart failure. The aim of our study was to assess the expression of thermogenic genes (Uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), and PR-domain-missing 16 (PRDM16) in epicardial adipose tissue in patients with heart failure, stablishing the difference according to left ventricular ejection fraction (reduced or preserved). Among the 75 patients in our study, 42.7% (n=32) had reduced left ventricular ejection fraction. UCP1, PGC1α and PRDM16 mRNA in EAT were significantly lower in patients with reduced left ventricular ejection fraction. Multiple regression analysis showed that age, male gender, body max index, presence of obesity, type-2-diabetes mellitus, hypertension and coronary artery disease and left ventricular ejection fraction were associated with the expression levels of UCP1, PGC1α and PRDM16 mRNA. Thermogenic genes expressions in epicardial adipose tissue (UCP1: OR 0.617, 95%CI 0.103-0.989, p=0.042; PGC1α: OR 0.416, 95%CI 0.171-0.912, p=0.031; PRDM16: OR 0.643, 95%CI 0.116-0.997, p=0.044) were showed as protective factors against the presence of heart failure with reduced left ventricular ejection fraction, and age (OR 1.643, 95%CI 1.001-3.143, p=0.026), presence of coronary artery disease (OR 6.743, 95%CI 1.932-15.301, p<0.001) and type-2-diabetes mellitus (OR 4.031, 95%CI 1.099-7.231, p<0.001) were associated as risk factors. The adequate expression of thermogenic genes has been shown as possible protective factors against heart failure with reduced ejection fraction, suggesting that a loss of functional epicardial adipose tissue brown-like features would participate in a deleterious manner on heart metabolism. Thermogenic genes could represent a future novel therapeutic target in heart failure.

Diabetes Mellitus-Induced Microvascular Destabilization in the Myocardium.

PubMed

Hinkel, Rabea; Howe, Andrea; Renner, Simone; Ng, Judy; Lee, Seungmin; Klett, Katharina; Kaczmarek, Veronika; Moretti, Alessandra; Laugwitz, Karl-Ludwig; Skroblin, Philipp; Mayr, Manuel; Milting, Hendrik; Dendorfer, Andreas; Reichart, Bruno; Wolf, Eckhard; Kupatt, Christian

2017-01-17

Diabetes mellitus causes microcirculatory rarefaction and may impair the responsiveness of ischemic myocardium to proangiogenic factors. This study sought to determine whether microvascular destabilization affects organ function and therapeutic neovascularization in diabetes mellitus. The authors obtained myocardial samples from patients with end-stage heart failure at time of transplant, with or without diabetes mellitus. Diabetic (db) and wild-type (wt) pigs were used to analyze myocardial vascularization and function. Chronic ischemia was induced percutaneously (day 0) in the circumflex artery. At day 28, recombinant adeno-associated virus (rAAV) (5 × 10 12 viral particles encoding vascular endothelial growth factor-A [VEGF-A] or thymosin beta 4 [Tβ4]) was applied regionally. CD31+ capillaries per high power field (c/hpf) and NG2+ pericyte coverage were analyzed. Global myocardial function (ejection fraction [EF] and left ventricular end-diastolic pressure) was assessed at days 28 and 56. Diabetic human myocardial explants revealed capillary rarefaction and pericyte loss compared to nondiabetic explants. Hyperglycemia in db pigs, even without ischemia, induced capillary rarefaction in the myocardium (163 ± 14 c/hpf in db vs. 234 ± 8 c/hpf in wt hearts; p < 0.005), concomitant with a distinct loss of EF (44.9% vs. 53.4% in nondiabetic controls; p < 0.05). Capillary density further decreased in chronic ischemic hearts, as did EF (both p < 0.05). Treatment with rAAV.Tβ4 enhanced capillary density and maturation in db hearts less efficiently than in wt hearts, similar to collateral growth. rAAV.VEGF-A, though stimulating angiogenesis, induced neither pericyte recruitment nor collateral growth. As a result, rAAV.Tβ4 but not rAAV.VEGF-A improved EF in db hearts (34.5 ± 1.4%), but less so than in wt hearts (44.8 ± 1.5%). Diabetes mellitus destabilized microvascular vessels of the heart, affecting the amplitude of therapeutic neovascularization via rAAV.Tβ4 in a translational large animal model of hibernating myocardium. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Right ventricular volumes and function in thalassemia major patients in the absence of myocardial iron overload

PubMed Central

2010-01-01

Aim We aimed to define reference ranges for right ventricular (RV) volumes, ejection fraction (EF) in thalassemia major patients (TM) without myocardial iron overload. Methods and results RV volumes, EF and mass were measured in 80 TM patients who had no myocardial iron overload (myocardial T2* > 20 ms by cardiovascular magnetic resonance). All patients were receiving deferoxamine chelation and none had evidence of pulmonary hypertension or other cardiovascular comorbidity. Forty age and sex matched healthy non-anemic volunteers acted as controls. The mean RV EF was higher in TM patients than controls (males 66.2 ± 4.1% vs 61.6 ± 6%, p = 0.0009; females 66.3 ± 5.1% vs 62.6 ± 6.4%, p = 0.017), which yielded a raised lower threshold of normality for RV EF in TM patients (males 58.0% vs 50.0% and females 56.4% vs 50.1%). RV end-diastolic volume index was higher in male TM patients (mean 98.1 ± 17.3 mL vs 88.4 ± 11.2 mL/m2, p = 0.027), with a higher upper limit (132 vs 110 mL/m2) but this difference was of borderline significance for females (mean 86.5 ± 13.6 mL vs 80.3 ± 12.8 mL/m2, p = 0.09, with upper limit of 113 vs 105 mL/m2). The cardiac index was raised in TM patients (males 4.8 ± 1.0 L/min vs 3.4 ± 0.7 L/min, p < 0.0001; females 4.5 ± 0.8 L/min vs 3.2 ± 0.8 L/min, p < 0.0001). No differences in RV mass index were identified. Conclusion The normal ranges for functional RV parameters in TM patients with no evidence of myocardial iron overload differ from healthy non-anemic controls. The new reference RV ranges are important for determining the functional effects of myocardial iron overload in TM patients. PMID:20416084

Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, Eugene; Corbett, James R.; Moran, Jean M.

Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses tomore » the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was −0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF.« less

Determinants and clinical outcome of uptitration of ACE-inhibitors and beta-blockers in patients with heart failure: a prospective European study.

PubMed

Ouwerkerk, W; Voors, A A; Anker, S D; Cleland, J G; Dickstein, K; Filippatos, G; van der Harst, P; Hillege, H L; Lang, C C; Ter Maaten, J M; Ng, L L; Ponikowski, P; Samani, N J; van Veldhuisen, D J; Zannad, F; Metra, M; Zwinderman, A H

2017-06-21

Despite clear guidelines recommendations, most patients with heart failure and reduced ejection-fraction (HFrEF) do not attain guideline-recommended target doses. We aimed to investigate characteristics and for treatment-indication-bias corrected clinical outcome of patients with HFrEF that did not reach recommended treatment doses of ACE-inhibitors/Angiotensin receptor blockers (ARBs) and/or beta-blockers. BIOSTAT-CHF was specifically designed to study uptitration of ACE-inhibitors/ARBs and/or beta-blockers in 2516 heart failure patients from 69 centres in 11 European countries who were selected if they were suboptimally treated while initiation or uptitration was anticipated and encouraged. Patients who died during the uptitration period (n = 151) and patients with a LVEF > 40% (n = 242) were excluded. Median follow up was 21 months. We studied 2100 HFrEF patients (76% male; mean age 68 ±12), of which 22% achieved the recommended treatment dose for ACE-inhibitor/ARB and 12% of beta-blocker. There were marked differences between European countries. Reaching <50% of the recommended ACE-inhibitor/ARB and beta-blocker dose was associated with an increased risk of death and/or heart failure hospitalization. Patients reaching 50-99% of the recommended ACE-inhibitor/ARB and/or beta-blocker dose had comparable risk of death and/or heart failure hospitalization to those reaching ≥100%. Patients not reaching recommended dose because of symptoms, side effects and non-cardiac organ dysfunction had the highest mortality rate (for ACE-inhibitor/ARB: HR 1.72; 95% CI 1.43-2.01; for beta-blocker: HR 1.70; 95% CI 1.36-2.05). Patients with HFrEF who were treated with less than 50% of recommended dose of ACE-inhibitors/ARBs and beta-blockers seemed to have a greater risk of death and/or heart failure hospitalization compared with patients reaching ≥100%. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Rationale and design of the comParIson Of sacubitril/valsartaN versus Enalapril on Effect on nt-pRo-bnp in patients stabilized from an acute Heart Failure episode (PIONEER-HF) trial.

PubMed

Velazquez, Eric J; Morrow, David A; DeVore, Adam D; Ambrosy, Andrew P; Duffy, Carol I; McCague, Kevin; Hernandez, Adrian F; Rocha, Ricardo A; Braunwald, Eugene

2018-04-01

The objective is to assess the safety, tolerability, and efficacy of sacubitril/valsartan compared with enalapril in patients with heart failure (HF) with a reduced ejection fraction (EF) stabilized during hospitalization for acute decompensated HF. Sacubitril/valsartan, a first-in-class angiotensin receptor-neprilysin inhibitor, improves survival among ambulatory HF patients with a reduced EF. However, there is very limited experience with the in-hospital initiation of sacubitril/valsartan in patients who have been stabilized following hospitalization for acute decompensated HF. PIONEER-HF is a 12-week, prospective, multicenter, double-blind, randomized controlled trial enrolling a planned 882 patients at more than 100 participating sites in the United States. Medically stable patients >18 years of age with an EF <40% and an amino terminal-pro b-type natriuretic peptide >1600 pg/mL or b-type natriuretic peptide >400 pg/mL are eligible for participation no earlier than 24 hours and up to 10 days from initial presentation while still hospitalized. Patients are randomly assigned 1:1 to in-hospital initiation of sacubitril/valsartan titrated to 97/103 mg by mouth twice daily versus enalapril titrated to 10 mg by mouth twice daily for 8 weeks. All patients receive open-label treatment with sacubitril/valsartan for the remaining 4 weeks of the study. The primary efficacy end point is the time-averaged proportional change in amino terminal-pro b-type natriuretic peptide from baseline through weeks 4 and 8. Secondary and exploratory end points include serum and urinary biomarkers as well as clinical outcomes. Safety end points include the incidence of angioedema, hypotension, renal insufficiency, and hyperkalemia. The PIONEER-HF trial will inform clinical practice by providing evidence on the safety, tolerability, and efficacy of in-hospital initiation of sacubitril/valsartan among patients who have been stabilized following an admission for acute decompensated HF with a reduced EF. Copyright © 2018 Elsevier Inc. All rights reserved.

Do implantable cardioverter defibrillators improve survival in patients with severe left ventricular systolic dysfunction after coronary artery bypass graft surgery?

PubMed

Fazal, Iftikhar A; Bates, Matthew G D; Matthews, Iain G; Turley, Andrew J

2011-06-01

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether implantable cardioverter defibrillators (ICD) improve survival in patients with severe left ventricular systolic dysfunction (LVSD) after coronary artery bypass graft (CABG) surgery. ICDs are designed to terminate potentially fatal cardiac tachyarrhythmias. A right ventricular lead is mandatory for detection, pacing and defibrillation capabilities. Dual chamber ICDs have an additional right atrial lead and are used for patients with conventional atrioventricular pacing indications. More sophisticated, biventricular devices exist to provide cardiac resynchronisation therapy (CRT) in addition to defibrillation (CRT-D). ICDs have been extensively investigated in patients with LVSD post myocardial infarction and in patients with non-ischaemic cardiomyopathy for both secondary prevention (history of ventricular arrhythmias) and primary prevention (deemed high risk for ventricular arrhythmias). This best evidence topic aims to review the evidence and its applicability to patients post CABG. Nine hundred and sixteen papers were identified using the search method outlined. Eight randomised controlled trials, two meta-analyses, and one non-randomised trial, in addition to international guidelines presented the best evidence to answer the clinical question. The current evidence base and guidelines suggest that ICDs should be considered for all patients with LVSD [ejection fraction (EF) ≤30-40%] receiving optimal pharmacological management, who are ≥40 days post MI [four weeks for National Institute for Health and Clinical Excellence (NICE)] and in New York Heart Association (NYHA) class I-III. UK NICE guidelines require in addition; non-sustained ventricular tachycardia (NSVT) on a Holter monitor and inducible ventricular tachycardia at electrophysiological study for EF between 30 and 35%; or a QRS >120 ms if EF <30%. The North American guidelines recommend EF <30% as a threshold for those with NYHA class I symptoms. The evidence is applicable to patients post CABG, provided all the other criteria are met. European Society of Cardiology (ESC) guidelines recommend waiting at least three months (consensus opinion) after revascularisation prior to assessment for an ICD, to allow time for potential recovery of ventricular function.

Remote Monitoring in Heart Failure: the Current State.

PubMed

Mohan, Rajeev C; Heywood, J Thomas; Small, Roy S

2017-03-01

The treatment of congestive heart failure is an expensive undertaking with much of this cost occurring as a result of hospitalization. It is not surprising that many remote monitoring strategies have been developed to help patients maintain clinical stability by avoiding congestion. Most of these have failed. It seems very unlikely that these failures were the result of any one underlying false assumption but rather from the fact that heart failure is a progressive, deadly disease and that human behavior is hard to modify. One lesson that does stand out from the myriad of methods to detect congestion is that surrogates of congestion, such as weight and impedance, are not reliable or actionable enough to influence outcomes. Too many factors influence these surrogates to successfully and confidently use them to affect HF hospitalization. Surrogates are often attractive because they can be inexpensively measured and followed. They are, however, indirect estimations of congestion, and due to the lack specificity, the time and expense expended affecting the surrogate do not provide enough benefit to warrant its use. We know that high filling pressures cause transudation of fluid into tissues and that pulmonary edema and peripheral edema drive patients to seek medical assistance. Direct measurement of these filling pressures appears to be the sole remote monitoring modality that shows a benefit in altering the course of the disease in these patients. Congestive heart failure is such a serious problem and the consequences of hospitalization so onerous in terms of patient well-being and costs to society that actual hemodynamic monitoring, despite its costs, is beneficial in carefully selected high-risk patients. Those patients who benefit are ones with a prior hospitalization and ongoing New York Heart Association (NYHA) class III symptoms. Patients with NYHA class I and II symptoms do not require hemodynamic monitoring because they largely have normal hemodynamics. Those with NYHA class IV symptoms do not benefit because their hemodynamics are so deranged that they cannot be substantially altered except by mechanical circulatory support or heart transplantation. Finally, hemodynamic monitoring offers substantial hope to those patients with normal ejection fraction (EF) heart failure, a large group for whom medical therapy has largely been a failure. These patients have not benefited from the neurohormonal revolution that improved the lives of their brothers and sisters with reduced ejection fractions. Hemodynamic stabilization improves the condition of both but more so of the normal EF cohort. This is an important observation that will help us design future trials for the 50% of heart failure patients with normal systolic function.

Increase in electrocardiographic R-waves after revascularization in patients with acute myocardial infarction.

PubMed

Isobe, Satoshi; Takada, Yasuo; Ando, Akitada; Ohshima, Satoru; Yamada, Kiyoyasu; Nanasato, Mamoru; Unno, Kazumasa; Ogawa, Takuo; Kondo, Takahisa; Izawa, Hideo; Inden, Yasuya; Hirai, Makoto; Murohara, Toyoaki

2006-11-01

The physiological mechanism of the increase in the electrocardiographic (ECG) R-wave voltage after revascularization in patients with acute myocardial infarction (MI) needs to be elucidated. One hundred and thirty-eight MI patients (83: anterior MI, 45: inferior MI, 10: lateral MI) underwent ECG and echocardiography in both the acute and subacute phases after emergency revascularization, as well as a resting thallium-201/iodine-123 15-p-iodophenyl-3-(R,S)-methyl pentadecanoic acid myocardial scintigraphy in the acute phase. The total sum of the R-wave voltage (SigmaR) was calculated over multiple leads on ECG for each infarcted lesion. Scintigraphic defect on each tracer was expressed as the percentage (%) defect of the total left ventricular (LV) myocardium. The % defect-discordance on both images in the acute phase and the % increase in SigmaR and the absolute increase in LV ejection fraction from the acute to the subacute phase (DeltaEF) were also calculated. The SigmaR in the subacute phase was significantly greater than that in the acute phase (p<0.0001). The % increase in SigmaR significantly correlated with the DeltaEF (r=0.57, p<0.0001). The % increase in SigmaR also correlated with the % defect-discordance (r=0.68, p<0.0001). The increase in the ECG R-wave voltage reflects not only the improvement in myocardial perfusion but also the presence of salvaged myocardium after revascularization in acute MI patients.

Critical Questions about PARADIGM-HF and the Future

PubMed Central

Chen, Chen-Huan

2016-01-01

Cardiovascular (CV) diseases in general and heart failure (HF) in particular are major contributors to death and morbidity and are also recognized as important drivers of health care expenditure. The PARADIGM-HF trial was a pivotal trial designed to compare the long-term effects of LCZ696 with enalapril in patients with symptomatic HF with reduced ejection fraction (HFrEF). This review article presents an in-depth view of the PARADIGM-HF trial and the implications of the results in the management of patients with HF and is based on peer reviewed manuscripts, editorials, perspectives and opinions written about the PARADIGM-HF trial. The article presents the key safety and efficacy results of the trial with specific emphasis on the clinical implications of these findings. The review highlights the highly statistically significant, 20% reduction in the primary composite endpoint of cardiovascular death or HF hospitalization, and a 16% reduction in the risk of death from any cause. It also provides an overview of the design, clinical findings, limitations and special areas of clinical interest. The review discusses the future of LCZ696 and additional trials that seek to answer questions in other sub-populations of patients with HF. The article reiterates what has been concluded by many experts in the field of HF- the introduction of LCZ696 into routine clinical care, while dependent on the regulatory approvals in various countries as well as acceptance by physicians, payers and patients, will change the treatment landscape for patients with HFrEF. PMID:27471351

Effect of milrinone on short term outcome of patients with myocardial dysfunction undergoing off-pump coronary artery bypass graft: a randomized clinical trial.

PubMed

Hadadzadeh, Mehdi; Hosseini, Seyed Habib; Mostafavi Pour Manshadi, Seyed Mohammad Yousof; Naderi, Nafiseh; Emami Meybodi, Mahmood

2013-01-01

Myocardial dysfunction is a major complication in cardiac surgery that needs inotropic support. This study evaluates the effect of milrinone on patients with low ventricular ejection fraction undergoing off- pump coronary artery bypass graft (OPCAB). The present study is designed to evaluate the effect of milrinone on myocardial dysfunction. Eighty patients with low ventricular ejection fraction (<35%), candidate for elective OPCAB, were enrolled in this study. They were randomly assigned to two groups. One group received milrinone (50 μg/kg) intravenously and another group received a saline as placebo followed by 24 hours infusion of each agent (0.5 μg/kg/min). Short outcome of patients such as hemodynamic parameters and left ventricular ejection fraction were variables evaluated. Serum levels of creatine phosphokinase, the MB isoenzyme of creatine kinase, occurrence of arrhythmias and mean duration of mechanical ventilation were significantly lower in milrinone group (P<0.05). The mean post operative left ventricular ejection fraction was significantly higher in milrinone group (P=0.031). There were no statistical significant differences between the two groups in terms of intra-aortic balloon pump, inotropic support requirement, myocardial ischemia, myocardial infarction, duration of inotropic support, duration of intensive care unit stay, mortality and morbidity rate. Administration of milrinone in patients undergoing OPCAB with low ventricular ejection fraction is useful and effective.

Long Term Osmotic Mini Pump Treatment with Alpha-MSH Improves Myocardial Function in Zucker Diabetic Fatty Rats.

PubMed

Szokol, Miklos; Priksz, Daniel; Bombicz, Mariann; Varga, Balazs; Kovacs, Arpad; Fulop, Gabor Aron; Csipo, Tamas; Posa, Aniko; Toth, Attila; Papp, Zoltan; Szilvassy, Zoltan; Juhasz, Bela

2017-10-12

The present investigation evaluates the cardiovascular effects of the anorexigenic mediator alpha-melanocyte stimulating hormone (MSH), in a rat model of type 2 diabetes. Osmotic mini pumps delivering MSH or vehicle, for 6 weeks, were surgically implanted in Zucker Diabetic Fatty (ZDF) rats. Serum parameters, blood pressure, and weight gain were monitored along with oral glucose tolerance (OGTT). Echocardiography was conducted and, following sacrifice, the effects of treatment on ischemia/reperfusion cardiac injury were assessed using the isolated working heart method. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was measured to evaluate levels of oxidative stress, and force measurements were performed on isolated cardiomyocytes to determine calcium sensitivity, active tension and myofilament co-operation. Vascular status was also evaluated on isolated arterioles using a contractile force measurement setup. The echocardiographic parameters ejection fraction (EF), fractional shortening (FS), isovolumetric relaxation time (IVRT), mitral annular plane systolic excursion (MAPSE), and Tei-index were significantly better in the MSH-treated group compared to ZDF controls. Isolated working heart aortic and coronary flow was increased in treated rats, and higher Hill coefficient indicated better myofilament co-operation in the MSH-treated group. We conclude that MSH improves global heart functions in ZDF rats, but these effects are not related to the vascular status.

A study on the reactivity characteristics of dissolved effluent organic matter (EfOM) from municipal wastewater treatment plant during ozonation.

PubMed

Jin, Pengkang; Jin, Xin; Bjerkelund, Viggo A; Østerhus, Stein W; Wang, Xiaochang C; Yang, Lei

2016-01-01

The reactivity of dissolved effluent organic matter (EfOM) in the process of ozonation was examined. Under different ozone dosages (0.42 ± 0.09, 0.98 ± 0.11 and 2.24 ± 0.17 mgO3/mg DOC), the EfOM before and after ozonation could be classified into four fractions according to their hydrophobicities. By ozonation, the hydrophobic fractions, especially hydrophobic acid (HOA) and hydrophobic neutral (HON), were found to undergo a process of transformation into hydrophilic fractions (HI), of which the HOA were first transformed into HON, and then the majority of the HON fraction was later converted to HI by further ozonation. It was noticeable that after ozonation, the fluorescence intensity in the humic-like and protein-like regions decreased as indicated by the excitation and emission matrix (EEM) spectra for the hydrophobic fractions. By coupling the EEM spectra with the molecular size analysis using high performance size exclusion chromatography (HPSEC), the difference between the characteristic distributions of the humic-like and protein-like fluorophores were further revealed. It could thus be extrapolated that ozone might have preferentially reacted with the protein-like hydrophobic fraction with molecular weight (MW) less than 100 kDa. Moreover, by X-ray photoelectron spectroscopy (XPS) analysis, it was identified that with increasing ozone dosage (from 0 to 2.24 ± 0.17 mgO3/mg DOC), the aromaticity of HON decreased dramatically, while aliphatics and ketones increased especially at the low ozone dose (0.42 ± 0.09 mgO3/mg DOC). Of the EfOM fractions, the HON fraction would have a higher content of electron enriched aromatics which could preferentially react with ozone rather than the HOA fraction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effective removal of effluent organic matter (EfOM) from bio-treated coking wastewater by a recyclable aminated hyper-cross-linked polymer.

PubMed

Yang, Wenlan; Li, Xuchun; Pan, Bingcai; Lv, Lu; Zhang, Weiming

2013-09-01

Effluent organic matter (EfOM) is a complex matrix of organic substance mainly from bio-treated sewage effluent and is considered as the main constraint to further advanced treatment. Here a recyclable aminated hyper-cross-linked polymeric adsorbent (NDA-802) featured with aminated functional groups, large specific surface area, and sufficient micropore region was synthesized for effective removal of EfOM from the bio-treated coking wastewater (BTCW), and its removal characteristics was investigated. It was found that hydrophobic fraction was the main constituent (64.8% of DOC) in EfOM of BTCW, and the hydrophobic-neutral fraction had the highest SUVA level (7.06 L mg(-1) m(-1)), which were significantly different from that in the domestic wastewater. Column adsorption experiments showed that NDA-802 exhibited much higher removal efficiency of EfOM than other polymeric adsorbents D-301, XAD-4, and XAD-7, and the efficiency could be readily sustained according to continuous 28-cycle batch adsorption-regeneration experiments. Moreover, dissolved organic matter (DOM) fractionation and excitation-emission matrix (EEM) fluorescence spectroscopy study indicated that NDA-802 showed attractive adsorption preference as well as high removal efficiency of hydrophobic and aromatic compounds. Possibly ascribed to the presence of functional aminated groups, relatively large specific surface area and micropore region of the unique polymer, NDA-802 possesses high and sustained efficiency for the removal of EfOM, and provides a potential alternative for the advanced treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Studies of elongation factor Tu in Streptococcus faecium (ATCC 9790)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bourbeau, P.P.

1986-01-01

It has been known for over twenty years that elongation factor Tu (Ef-Tu) is one of the proteins involved in protein synthesis in bacteria. Several years ago, it was proposed that Ef-Tu may, in addition, have other structural functions in bacterial. The author's research has examined the function of Ef-Tu in Streptococcus faecium. Using an antibiotic kirromycin, which specifically inhibits Ef-Tu function, the effects upon a number of cellular parameters were determined. Inhibition of both protein and RNA synthesis was found to be similar to the effect of chloramphenicol. Using the residual division technique for the determination of cell cyclemore » events with both heterogeneous and sucrose gradient fractionated cell populations, a kirromycin sensitive event was detected between 8 min. (Td = 30 min.) and 19 min. (Td = 175 min.) later in the cell cycle than the chloramphenical sensitive event. This suggests that kirromycin is inhibiting a terminal cell cycle event which is in addition to the inhibition of protein synthesis. Purification of Ef-Tu was performed using two different methods: ion exchange and molecular exclusion chromatography; and GDP affinity chromatography. Various schemes were employed to try and obtain optimum cellular fractionation, allowing for both proper separation of ribosomes from the other cellular fractions and retention of enzymatic activity by Ef-Tu as determined by a /sup 3/H-GDP binding assay. Analysis of the cell cycle of S. faecium using the residual division technique was also performed. In addition, certain cell wall antibiotics were used to determine if other cell cycle events could be determined using the residual division technique.« less

Determination of Cardiac Output and Ejection Fraction with the Dual Cardiac Probe

PubMed Central

Cardenas, Carlos G.; Depuey, E. Gordon; Thompson, Wayne L.; Garcia, Efrain; Burdine, John A.

1983-01-01

Cardiac output and left ventricular ejection fraction were determined noninvasively at the bedside in 26 patients by using a dual scintillation probe. The probe is a nonimaging detector that records a high frequency time-activity curve of the passage of an intravenously injected radioactive bolus through the heart. Results were correlated with ejection fraction measured by biplane cineangiography (r = 0.80) and cardiac output determined by green dye dilution (R = 0.86). It is concluded that the dual probe provides an accurate noninvasive means of measuring these parameters, and that it may be particularly applicable to serial measurements in patients in the intensive care unit. Images PMID:15227151

The effects of acute oral antioxidants on diving-induced alterations in human cardiovascular function

PubMed Central

Obad, Ante; Palada, Ivan; Valic, Zoran; Ivančev, Vladimir; Baković, Darija; Wisløff, Ulrik; Brubakk, Alf O; Dujić, Željko

2007-01-01

Diving-induced acute alterations in cardiovascular function such as arterial endothelial dysfunction, increased pulmonary artery pressure (PAP) and reduced heart function have been recently reported. We tested the effects of acute antioxidants on arterial endothelial function, PAP and heart function before and after a field dive. Vitamins C (2 g) and E (400 IU) were given to subjects 2 h before a second dive (protocol 1) and in a placebo-controlled crossover study design (protocol 2). Seven experienced divers performed open sea dives to 30 msw with standard decompression in a non-randomized protocol, and six of them participated in a randomized trial. Before and after the dives ventricular volumes and function and pulmonary and brachial artery function were assessed by ultrasound. The control dive resulted in a significant reduction in flow-mediated dilatation (FMD) and heart function with increased mean PAP. Twenty-four hours after the control dive FMD was still reduced 37% below baseline (8.1 versus 5.1%, P = 0.005), while right ventricle ejection fraction (RV-EF), left ventricle EF and endocardial fractional shortening were reduced much less (∼2–3%). At the same time RV end-systolic volume was increased by 9% and mean PAP by 5%. Acute antioxidants significantly attenuated only the reduction in FMD post-dive (P < 0.001), while changes in pulmonary artery and heart function were unaffected by antioxidant ingestion. These findings were confirmed by repeating the experiments in a randomized study design. FMD returned to baseline values 72 h after the dive with pre-dive placebo, whereas for most cardiovascular parameters this occurred earlier (24–48 h). Right ventricular dysfunction and increased PAP lasted longer. Acute antioxidants attenuated arterial endothelial dysfunction after diving, while reduction in heart and pulmonary artery function were unchanged. Cardiovascular changes after diving are not fully reversed up to 3 days after a dive, suggesting longer lasting negative effects. PMID:17110413

Caffeoylxanthiazonoside exerts cardioprotective effects during chronic heart failure via inhibition of inflammatory responses in cardiac cells

PubMed Central

Yang, Bin; Wang, Fei; Cao, Huili; Liu, Guifang; Zhang, Yuean; Yan, Ping; Li, Bao

2017-01-01

Caffeoylxanthiazonoside (CYT) is an active constituent isolated from the fruit of the Xanthium strumarium L plant. The aim of the present study was to investigate the cardioprotective effects of oral administration of CYT on chronic heart failure (CHF) and its underlying mechanisms. A rat model of CHF was first established, and cardiac function indices, including the heart/body weight index, left heart/body weight index, fractional shortening (FS), ejection fraction (EF), cardiac output (CO) and heart rate (HR), were subsequently determined by cardiac ultrasound. Serum levels of lactate dehydrogenase (LDH) and creatine kinase (CK), and the levels of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in heart tissues and cardiac microvascular endothelial cells (CMECs) were determined using ELISA. In addition, the protein expression levels of nuclear factor-κB (NF-κB) signaling pathway members were determined by western blotting in CMECs. The results demonstrated that oral administration of 10, 20, 40 mg/kg CYT significantly reduced cardiac hypertrophy and reversed FS, EF, CO and HR when compared with CHF model rats. In addition, CYT administration significantly decreased the levels of TNF-α, IL-6 and IL-1β in heart tissues, as well as serum LDH and CK levels. Furthermore, exposure of CMECs to 20, 40 and 80 µg/ml CYT significantly decreased the production of TNF-α, IL-1β and IL-6. The protein expression levels of cytoplasmic NF-κB p65 and IκB were upregulated, while nuclear NF-κB p65 was downregulated following treatment of CMECs with 20, 40 and 80 µg/ml CYT when compared with untreated CHF model controls. In conclusion, the results of the current study suggest that CYT demonstrates cardioprotective effects in CHF model rats by suppressing the expression of pro-inflammatory cytokines and the NF-κB signaling pathway. PMID:29104638

Caffeoylxanthiazonoside exerts cardioprotective effects during chronic heart failure via inhibition of inflammatory responses in cardiac cells.

PubMed

Yang, Bin; Wang, Fei; Cao, Huili; Liu, Guifang; Zhang, Yuean; Yan, Ping; Li, Bao

2017-11-01

Caffeoylxanthiazonoside (CYT) is an active constituent isolated from the fruit of the Xanthium strumarium L plant. The aim of the present study was to investigate the cardioprotective effects of oral administration of CYT on chronic heart failure (CHF) and its underlying mechanisms. A rat model of CHF was first established, and cardiac function indices, including the heart/body weight index, left heart/body weight index, fractional shortening (FS), ejection fraction (EF), cardiac output (CO) and heart rate (HR), were subsequently determined by cardiac ultrasound. Serum levels of lactate dehydrogenase (LDH) and creatine kinase (CK), and the levels of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in heart tissues and cardiac microvascular endothelial cells (CMECs) were determined using ELISA. In addition, the protein expression levels of nuclear factor-κB (NF-κB) signaling pathway members were determined by western blotting in CMECs. The results demonstrated that oral administration of 10, 20, 40 mg/kg CYT significantly reduced cardiac hypertrophy and reversed FS, EF, CO and HR when compared with CHF model rats. In addition, CYT administration significantly decreased the levels of TNF-α, IL-6 and IL-1β in heart tissues, as well as serum LDH and CK levels. Furthermore, exposure of CMECs to 20, 40 and 80 µg/ml CYT significantly decreased the production of TNF-α, IL-1β and IL-6. The protein expression levels of cytoplasmic NF-κB p65 and IκB were upregulated, while nuclear NF-κB p65 was downregulated following treatment of CMECs with 20, 40 and 80 µg/ml CYT when compared with untreated CHF model controls. In conclusion, the results of the current study suggest that CYT demonstrates cardioprotective effects in CHF model rats by suppressing the expression of pro-inflammatory cytokines and the NF-κB signaling pathway.

Blood pressure, left ventricular geometry, and systolic function in children exposed to inorganic arsenic.

PubMed

Osorio-Yáñez, Citlalli; Ayllon-Vergara, Julio C; Arreola-Mendoza, Laura; Aguilar-Madrid, Guadalupe; Hernández-Castellanos, Erika; Sánchez-Peña, Luz C; Del Razo, Luz M

2015-06-01

Inorganic arsenic (iAs) is a ubiquitous element present in the groundwater worldwide. Cardiovascular effects related to iAs exposure have been studied extensively in adult populations. Few epidemiological studies have been focused on iAs exposure-related cardiovascular disease in children. In this study we investigated the association between iAs exposure, blood pressure (BP), and functional and anatomical echocardiographic parameters in children. A cross-sectional study of 161 children between 3 and 8 years was conducted in Central Mexico. The total concentration of arsenic (As) species in urine (U-tAs) was determined by hydride generation-cryotrapping-atomic absorption spectrometry and lifetime iAs exposure was estimated by multiplying As concentrations measured in drinking water by the duration of water consumption in years (LAsE). BP was measured by standard protocols, and M-mode echocardiographic parameters were determined by ultrasonography. U-tAs concentration and LAsE were significantly associated with diastolic (DBP) and systolic blood pressure (SBP) in multivariable linear regression models: DBP and SBP were 0.013 (95% CI: 0.002, 0.024) and 0.021 (95% CI: 0.004, 0.037) mmHg higher in association with each 1-ng/mL increase in U-tAs (p < 0.025), respectively. Left ventricular mass (LVM) was significantly associated with LAsE [5.5 g higher (95% CI: 0.65, 10.26) in children with LAsE > 620 compared with < 382 μg/L-year; p = 0.03] in an adjusted multivariable model. The systolic function parameters left ventricular ejection fraction (EF) and shortening fraction were 3.67% (95% CI: -7.14, -0.20) and 3.41% (95% CI: -6.44, -0.37) lower, respectively, in children with U-tAs > 70 ng/mL compared with < 35 ng/mL. Early-life exposure to iAs was significantly associated with higher BP and LVM and with lower EF in our study population of Mexican children.

Echocardiographic Assessment of Cardiac Function by Conventional and Speckle-Tracking Echocardiography in Dogs with Patent Ductus Arteriosus.

PubMed

Spalla, I; Locatelli, C; Zanaboni, A M; Brambilla, P; Bussadori, C

2016-05-01

Patent ductus arteriosus (PDA) is one of the most common congenital heart defects in dogs. Advanced echocardiographic techniques such as speckle-tracking echocardiography (STE) have not been extensively used to evaluate cardiac function in affected dogs. Advanced echocardiographic techniques are more sensitive than standard echocardiographic techniques in analyzing systolic function in dogs with PDA. Forty-four client-owned dogs: 34 dogs with PDA (preoperative evaluation) and 10 healthy sex- and weight-matched controls. Prospective study. Dogs were recruited over a 2-year period. Complete echocardiographic evaluation was performed, including conventional (end-diastolic volumes indexed to body surface area in B and M-mode [EDVIB /M ], end-systolic volumes indexed to body surface area in B and M-mode [ESVIB /M ], allometric scaling in diastole and systole [AlloD/S], pulmonary flow to systemic flow [Qp/Qs], ejection fraction [EF] and fractional shortening [FS]) and speckle-tracking echocardiography ([STE]: global longitudinal, radial and circumferential strain [S] and strain rate [SR]). Dogs with PDA had significantly different EDVIB /M , ESVIB /M , AlloD/S, Qp/Qs and all STE-derived parameters (global longitudinal S and SR, global circumferential S and SR, global radial S and SR)compared to healthy dogs. No correlation was found between standard techniques (EDVIB /M , ESVIB /M , AlloD/S, Qp/Qs) and STE-derived parameters (global longitudinal, circumferential and radial S and SR). Conventional parameters routinely used to assess systolic function (EF and FS) were not different between the groups; STE-derived parameters identified subtle changes in cardiac systolic function and contractility between the 2 groups of dogs. Based on these findings, STE may be a more appropriate tool to assess cardiac contractility in dogs with PDA. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

The effects of acute oral antioxidants on diving-induced alterations in human cardiovascular function.

PubMed

Obad, Ante; Palada, Ivan; Valic, Zoran; Ivancev, Vladimir; Baković, Darija; Wisløff, Ulrik; Brubakk, Alf O; Dujić, Zeljko

2007-02-01

Diving-induced acute alterations in cardiovascular function such as arterial endothelial dysfunction, increased pulmonary artery pressure (PAP) and reduced heart function have been recently reported. We tested the effects of acute antioxidants on arterial endothelial function, PAP and heart function before and after a field dive. Vitamins C (2 g) and E (400 IU) were given to subjects 2 h before a second dive (protocol 1) and in a placebo-controlled crossover study design (protocol 2). Seven experienced divers performed open sea dives to 30 msw with standard decompression in a non-randomized protocol, and six of them participated in a randomized trial. Before and after the dives ventricular volumes and function and pulmonary and brachial artery function were assessed by ultrasound. The control dive resulted in a significant reduction in flow-mediated dilatation (FMD) and heart function with increased mean PAP. Twenty-four hours after the control dive FMD was still reduced 37% below baseline (8.1 versus 5.1%, P = 0.005), while right ventricle ejection fraction (RV-EF), left ventricle EF and endocardial fractional shortening were reduced much less (approximately 2-3%). At the same time RV end-systolic volume was increased by 9% and mean PAP by 5%. Acute antioxidants significantly attenuated only the reduction in FMD post-dive (P < 0.001), while changes in pulmonary artery and heart function were unaffected by antioxidant ingestion. These findings were confirmed by repeating the experiments in a randomized study design. FMD returned to baseline values 72 h after the dive with pre-dive placebo, whereas for most cardiovascular parameters this occurred earlier (24-48 h). Right ventricular dysfunction and increased PAP lasted longer. Acute antioxidants attenuated arterial endothelial dysfunction after diving, while reduction in heart and pulmonary artery function were unchanged. Cardiovascular changes after diving are not fully reversed up to 3 days after a dive, suggesting longer lasting negative effects.

Comparison of LVEF assessed by 2D echocardiography, gated blood pool SPECT, 99mTc tetrofosmin gated SPECT, and 18F-FDG gated PET with ERNV in patients with CAD and severe LV dysfunction.

PubMed

Raja, Senthil; Mittal, Bhagwant R; Santhosh, Sampath; Bhattacharya, Anish; Rohit, Manoj K

2014-11-01

Left ventricular ejection fraction (LVEF) is the single most important predictor of prognosis in patients with coronary artery disease (CAD) and left ventricular (LV) dysfunction. Equilibrium radionuclide ventriculography (ERNV) is considered the most reliable technique for assessing LVEF. Most of these patients undergo two dimensional (2D) echocardiography and myocardial viability study using gated myocardial perfusion imaging (MPI) or gated F-fluorodeoxyglucose (F-FDG) PET. However, the accuracy of LVEF assessed by these methods is not clear. This study has been designed to assess the correlation and agreement between the LVEF measured by 2D echocardiography, gated blood pool single photon emission computed tomography (SPECT), Tc tetrofosmin gated SPECT, and F-FDG gated PET with ERNV in CAD patients with severe LV dysfunction. Patients with CAD and severe LV dysfunction [ejection fraction (EF) <35 assessed by 2D echocardiography] were prospectively included in the study. These patients underwent ERNV along with gated blood pool SPECT, Tc tetrofosmin gated SPECT, and F-FDG gated PET as per the standard protocol for myocardial viability assessment and LVEF calculation. Spearman's coefficient of correlation (r) was calculated for the different sets of values with significance level kept at a P-value less than 0.05. Bland-Altman plots were inspected to visually assess the between-agreement measurements from different methods. Forty-one patients were prospectively included. LVEF calculated by various radionuclide methods showed good correlation with ERNV as follows: gated blood pool SPECT, r=0.92; MPI gated SPECT, r=0.85; and F-FDG gated PET, r=0.76. However, the correlation between 2D echocardiography and ERNV was poor (r=0.520). The Bland-Altman plot for LVEF measured by all radionuclide methods showed good agreement with ERNV. However, agreement between 2D echocardiography and ERNV is poor, as most of the values in this plot gave a negative difference for low EF and a positive difference for high EF. The mean difference between various techniques [2D echocardiography (a), gated blood pool SPECT (b), MPI gated SPECT (c), F-FDG gated PET (d)] and ERNV (e) was as follows: (a)-(e), 3.3; (b)-(e), 5; (c)-(e), 1.1; and (d)-(e), 2.9. The best possible correlation and agreement was found between MPI gated SPECT and ERNV. This study showed good correlation and agreement between MPI gated SPECT and F-FDG gated PET with ERNV for LVEF calculation in CAD patients with severe LV dysfunction. Thus, subjecting patients who undergo viability assessment by MPI gated SPECT or F-FDG gated PET to a separate procedure like ERNV for LVEF assessment may not be warranted. As the gated blood pool SPECT also showed good correlation and agreement with ERNV for LVEF assessment in CAD patients with severe LV dysfunction, with better characteristics than ERNV, it can be routinely used whenever accurate LVEF assessment is needed.

Quantification of the relative contribution of the different right ventricular wall motion components to right ventricular ejection fraction: the ReVISION method.

PubMed

Lakatos, Bálint; Tősér, Zoltán; Tokodi, Márton; Doronina, Alexandra; Kosztin, Annamária; Muraru, Denisa; Badano, Luigi P; Kovács, Attila; Merkely, Béla

2017-03-27

Three major mechanisms contribute to right ventricular (RV) pump function: (i) shortening of the longitudinal axis with traction of the tricuspid annulus towards the apex; (ii) inward movement of the RV free wall; (iii) bulging of the interventricular septum into the RV and stretching the free wall over the septum. The relative contribution of the aforementioned mechanisms to RV pump function may change in different pathological conditions.Our aim was to develop a custom method to separately assess the extent of longitudinal, radial and anteroposterior displacement of the RV walls and to quantify their relative contribution to global RV ejection fraction using 3D data sets obtained by echocardiography.Accordingly, we decomposed the movement of the exported RV beutel wall in a vertex based manner. The volumes of the beutels accounting for the RV wall motion in only one direction (either longitudinal, radial, or anteroposterior) were calculated at each time frame using the signed tetrahedron method. Then, the relative contribution of the RV wall motion along the three different directions to global RV ejection fraction was calculated either as the ratio of the given direction's ejection fraction to global ejection fraction and as the frame-by-frame RV volume change (∆V/∆t) along the three motion directions.The ReVISION (Right VentrIcular Separate wall motIon quantificatiON) method may contribute to a better understanding of the pathophysiology of RV mechanical adaptations to different loading conditions and diseases.