Effects of short-term continuous positive airway pressure on myocardial sympathetic nerve function and energetics in patients with heart failure and obstructive sleep apnea: a randomized study.

PubMed

Hall, Allison B; Ziadi, Maria C; Leech, Judith A; Chen, Shin-Yee; Burwash, Ian G; Renaud, Jennifer; deKemp, Robert A; Haddad, Haissam; Mielniczuk, Lisa M; Yoshinaga, Keiichiro; Guo, Ann; Chen, Li; Walter, Olga; Garrard, Linda; DaSilva, Jean N; Floras, John S; Beanlands, Rob S B

2014-09-09

Heart failure with reduced ejection fraction and obstructive sleep apnea (OSA), 2 states of increased metabolic demand and sympathetic nervous system activation, often coexist. Continuous positive airway pressure (CPAP), which alleviates OSA, can improve ventricular function. It is unknown whether this is due to altered oxidative metabolism or presynaptic sympathetic nerve function. We hypothesized that short-term (6-8 weeks) CPAP in patients with OSA and heart failure with reduced ejection fraction would improve myocardial sympathetic nerve function and energetics. Forty-five patients with OSA and heart failure with reduced ejection fraction (left ventricular ejection fraction 35.8±9.7% [mean±SD]) were evaluated with the use of echocardiography and 11C-acetate and 11C-hydroxyephedrine positron emission tomography before and ≈6 to 8 weeks after randomization to receive short-term CPAP (n=22) or no CPAP (n=23). Work metabolic index, an estimate of myocardial efficiency, was calculated as follows: (stroke volume index×heart rate×systolic blood pressure÷Kmono), where Kmono is the monoexponential function fit to the myocardial 11C-acetate time-activity data, reflecting oxidative metabolism. Presynaptic sympathetic nerve function was measured with the use of the 11C-hydroxyephedrine retention index. CPAP significantly increased hydroxyephedrine retention versus no CPAP (Δretention: +0.012 [0.002, 0.021] versus -0.006 [-0.013, 0.005] min(-1); P=0.003). There was no significant change in work metabolic index between groups. However, in those with more severe OSA (apnea-hypopnea index>20 events per hour), CPAP significantly increased both work metabolic index and systolic blood pressure (P<0.05). In patients with heart failure with reduced ejection fraction and OSA, short-term CPAP increased hydroxyephedrine retention, indicating improved myocardial sympathetic nerve function, but overall did not affect energetics. In those with more severe OSA, CPAP may improve cardiac efficiency. Further outcome-based investigation of the consequences of CPAP is warranted. http://www.clinicaltrials.gov. Unique identifier: NCT00756366. © 2014 American Heart Association, Inc.

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.

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

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.

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.

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.

[Course of ejection fraction, regurgitation fraction and ventricular volumes during exertion in chronic aortic insufficiency. Study using technetium 99m gamma-cineangiography].

PubMed

Bassand, J P; Faivre, R; Berthout, P; Cardot, J C; Verdenet, J; Bidet, R; Maurat, J P

1985-06-01

Previous studies have shown that variations of the ejection fraction (EF) during exercise were representative of the contractile state of the left ventricle: an increased EF on effort is considered to be physiological, whilst a decrease would indicate latent LV dysfunction unmasked during exercise. This hypothesis was tested by performing Technetium 99 gamma cineangiography at equilibrium under basal conditions and at maximal effort in 8 healthy subjects and 44 patients with pure, severe aortic regurgitation to measure the ejection and regurgitant fractions and the variations in end systolic and end diastolic LV volume. In the control group the EF increased and end systolic volume decreased significantly on effort whilst the regurgitant fraction and end diastolic volume were unchanged. In the 44 patients with aortic regurgitation no significant variations in EF, end systolic and end diastolic volumes were observed because the individual values were very dispersed. Variations of the EF and end systolic volume were inversely correlated. The regurgitant fraction decreased significantly on effort. Based on the variations of the EF and end systolic volume three different types of response to effort could be identified: in 7 patients, the EF increased on effort and end systolic volume decreased without any significant variation in the end diastolic volume, as in the group of normal control subjects; in 22 patients, a reduction in EF was observed on effort, associated with an increased end systolic volume. These changes indicated latent IV dysfunction inapparent at rest and unmasked by exercise; in a third group of 15 patients, the EF decreased on effort despite a physiological decrease in end systolic volume due to a greater decrease in end diastolic volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxidative stress is associated with increased pulmonary artery systolic pressure in humans.

PubMed

Ghasemzadeh, Nima; Patel, Riyaz S; Eapen, Danny J; Veledar, Emir; Al Kassem, Hatem; Manocha, Pankaj; Khayata, Mohamed; Zafari, A Maziar; Sperling, Laurence; Jones, Dean P; Quyyumi, Arshed A

2014-06-01

Oxidative stress contributes to the development of pulmonary hypertension in experimental models, but this association in humans is unknown. We investigated the relationship between pulmonary artery systolic pressure measured by echocardiography and plasma aminothiol oxidative stress markers, with the hypothesis that oxidative stress will be higher in those with pulmonary hypertension. A group of 347 patients aged 65±12 years from the Emory Cardiovascular Biobank underwent echocardiographic assessment of left ventricular ejection fraction and pulmonary artery systolic pressure. Plasma aminothiols, cysteine, its oxidized form, cystine, glutathione, and its oxidized disulphide were measured and the redox potentials (Eh) of cysteine/cystine and glutathione/oxidized glutathione couples were calculated. Non-normally distributed variables were log transformed (Ln). Univariate predictors of pulmonary artery systolic pressure included age (P<0.001), sex (P=0.002), mitral regurgitation (P<0.001), left ventricular ejection fraction (P<0.001), left atrial size (P<0.001), diabetes mellitus (P=0.03), plasma Ln cystine (β=9.53; P<0.001), Ln glutathione (β=-5.4; P=0.002), and Eh glutathione (β=0.21; P=0.001). A multivariate linear regression model adjusting for all confounding variables demonstrated that Ln cystine (β=6.56; P=0.007), mitral regurgitation (β=4.52; P<0.001), statin use (β=-3.39; P=0.03), left ventricular ejection fraction (β=-0.26; P=0.003), and age (β=0.17; P=0.003) were independent predictors of pulmonary artery systolic pressure. For each 1% increase in plasma cystine, pulmonary artery systolic pressure increased by 16%. This association persisted in the subgroup with preserved left ventricular ejection fraction (≥50%) and no significant mitral regurgitation. Whether treatment of oxidative stress will improve pulmonary hypertension requires further study.

Aspirin Does Not Increase Heart Failure Events in Heart Failure Patients: From the WARCEF Trial.

PubMed

Teerlink, John R; Qian, Min; Bello, Natalie A; Freudenberger, Ronald S; Levin, Bruce; Di Tullio, Marco R; Graham, Susan; Mann, Douglas L; Sacco, Ralph L; Mohr, J P; Lip, Gregory Y H; Labovitz, Arthur J; Lee, Seitetz C; Ponikowski, Piotr; Lok, Dirk J; Anker, Stefan D; Thompson, John L P; Homma, Shunichi

2017-08-01

The aim of this study was to determine whether aspirin increases heart failure (HF) hospitalization or death in patients with HF with reduced ejection fraction receiving an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Because of its cyclooxygenase inhibiting properties, aspirin has been postulated to increase HF events in patients treated with ACE inhibitors or ARBs. However, no large randomized trial has addressed the clinical relevance of this issue. We compared aspirin and warfarin for HF events (hospitalization, death, or both) in the 2,305 patients enrolled in the WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial (98.6% on ACE inhibitor or ARB treatment), using conventional Cox models for time to first event (489 events). In addition, to examine multiple HF hospitalizations, we used 2 extended Cox models, a conditional model and a total time marginal model, in time to recurrent event analyses (1,078 events). After adjustment for baseline covariates, aspirin- and warfarin-treated patients did not differ in time to first HF event (adjusted hazard ratio: 0.87; 95% confidence interval: 0.72 to 1.04; p = 0.117) or first hospitalization alone (adjusted hazard ratio: 0.88; 95% confidence interval: 0.73 to 1.06; p = 0.168). The extended Cox models also found no significant differences in all HF events or in HF hospitalizations alone after adjustment for covariates. Among patients with HF with reduced ejection fraction in the WARCEF trial, there was no significant difference in risk of HF events between the aspirin and warfarin-treated patients. (Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction trial [WARCEF]; NCT00041938). Copyright © 2017 American College of Cardiology Foundation. All rights reserved.

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.

Heart failure treated with low-dose milrinone in a full-term newborn.

PubMed

Sebková, S; Tomek, V; Zemanová, P; Janota, J

2012-01-01

A term newborn with a hypocontractile myocardium complicating persistent pulmonary hypertension of the newborn was successfully treated with a low-dose phosphodiesterase III inhibitor milrinone. Echocardiography diagnosed heart failure with a left ventricular ejection fraction of 35% and a left ventricular shortening fraction of 18% and severe persistent pulmonary hypertension of the newborn with oxygenation index of 28. Milrinone was started at an initial dose of 50 mcg/kg, followed by continuous infusion of 0.20 mcg/kg/min. With lowdose milrinone oxygenation index decreased to 3 within 6 hours, left ventricular ejection fraction and left ventricular shortening fraction increased to 57%, and 30%, respectively. Low doses of milrinone might be promising in the treatment of heart failure and persistent pulmonary hypertension of the newborn in term newborns.

Noninvasive Assessment of Preload Reserve Enhances Risk Stratification of Patients With Heart Failure With Reduced Ejection Fraction.

PubMed

Matsumoto, Kensuke; Onishi, Akira; Yamada, Hirotsugu; Kusunose, Kenya; Suto, Makiko; Hatani, Yutaka; Matsuzoe, Hiroki; Tatsumi, Kazuhiro; Tanaka, Hidekazu; Hirata, Ken-Ichi

2018-05-01

The leg-positive pressure maneuver can safely and noninvasively apply preload stress without increase in total body fluid volume. The purpose of this study was to determine whether preload stress could be useful for risk stratification of patients with heart failure with reduced ejection fraction. For this study, 120 consecutive patients with heart failure with reduced ejection fraction were prospectively recruited. The stroke work index was estimated as product of stroke volume index and mean blood pressure, and the E/e' ratio was calculated to estimate ventricular filling pressure. The echocardiographic parameters were obtained both at rest and during leg-positive pressure stress. During the median follow-up period of 20 months, 30 patients developed adverse cardiovascular events. During preload stress, stroke work index increased significantly (from 3280±1371 to 3857±1581 mm Hg·mL/m 2 ; P <0.001) along with minimal changes in ventricular filling pressure (E/e', from 16±10 to 17±9; P <0.05) in patients without cardiovascular events. However, patients with cardiovascular events showed impairment of Frank-Starling mechanism (stroke work index, from 2863±969 to 2903±1084 mm Hg·mL/m 2 ; P =0.70) and a serious increase in E/e' ratio (from 19±11 to 25±14; P <0.001). Both the patients without contractile reserve and those without diastolic reserve exhibited worse event-free survival than the others ( P <0.001). In a Cox proportional-hazards analysis, the changes in stroke work index (hazard ratio: 0.44 per 500 mm Hg·mL/m 2 increase; P =0.001) and in E/e' (hazard ratio: 2.58 per 5-U increase; P <0.001) were predictors of cardiovascular events. Contractile reserve and diastolic reserve during leg-positive pressure stress are important determinants of cardiovascular outcomes for patients with heart failure with reduced ejection fraction. © 2018 American Heart Association, Inc.

Targeting Endothelial Function to Treat Heart Failure with Preserved Ejection Fraction: The Promise of Exercise Training

PubMed Central

Lemmens, Katrien; Vrints, Christiaan J.

2017-01-01

Although the burden of heart failure with preserved ejection fraction (HFpEF) is increasing, there is no therapy available that improves prognosis. Clinical trials using beta blockers and angiotensin converting enzyme inhibitors, cardiac-targeting drugs that reduce mortality in heart failure with reduced ejection fraction (HFrEF), have had disappointing results in HFpEF patients. A new “whole-systems” approach has been proposed for designing future HFpEF therapies, moving focus from the cardiomyocyte to the endothelium. Indeed, dysfunction of endothelial cells throughout the entire cardiovascular system is suggested as a central mechanism in HFpEF pathophysiology. The objective of this review is to provide an overview of current knowledge regarding endothelial dysfunction in HFpEF. We discuss the molecular and cellular mechanisms leading to endothelial dysfunction and the extent, presence, and prognostic importance of clinical endothelial dysfunction in different vascular beds. We also consider implications towards exercise training, a promising therapy targeting system-wide endothelial dysfunction in HFpEF. PMID:28706575

Evolution of echocardiography in subclinical detection of cancer therapy-related cardiac dysfunction.

PubMed

Moudgil, Rohit; Hassan, Saamir; Palaskas, Nicolas; Lopez-Mattei, Juan; Banchs, Jose; Yusuf, Syed Wamique

2018-05-11

Cancer therapies have resulted in increased survivorship in oncological patients. However, the benefits have been marred by the development of premature cardiovascular disease. The current definition outlines measurement of ejection fraction as a mean to diagnose cancer therapeutic-related cardiac dysfunction (CTRCD); however, up to 58% of the patients do not regain their cardiac function after the CTRCD diagnosis, despite therapeutic interventions. Therefore, there has been a growing interest in the markers for early myocardial changes (ie, changes with normal left ventricular ejection fraction [LVEF]) that may predict the development of subsequent left ventricular ejection fraction reduction or progression to heart failure. This review will highlight the use of diastolic parameters, tissue Doppler imaging (TDI), and speckle tracking echocardiogram (STE) as emerging technologies which can potentially detect cardiac dysfunction thereby stratifying patients for cardioprotective therapies. The goal of this manuscript was to highlight the concepts and discuss the current controversies surrounding these echocardiographic imaging modalities. © 2018 Wiley Periodicals, Inc.

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

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.

Impact of Major Pulmonary Resections on Right Ventricular Function: Early Postoperative Changes.

PubMed

Elrakhawy, Hany M; Alassal, Mohamed A; Shaalan, Ayman M; Awad, Ahmed A; Sayed, Sameh; Saffan, Mohammad M

2018-01-15

Right ventricular (RV) dysfunction after pulmonary resection in the early postoperative period is documented by reduced RV ejection fraction and increased RV end-diastolic volume index. Supraventricular arrhythmia, particularly atrial fibrillation, is common after pulmonary resection. RV assessment can be done by non-invasive methods and/or invasive approaches such as right cardiac catheterization. Incorporation of a rapid response thermistor to pulmonary artery catheter permits continuous measurements of cardiac output, right ventricular ejection fraction, and right ventricular end-diastolic volume. It can also be used for right atrial and right ventricular pacing, and for measuring right-sided pressures, including pulmonary capillary wedge pressure. This study included 178 patients who underwent major pulmonary resections, 36 who underwent pneumonectomy assigned as group (I) and 142 who underwent lobectomy assigned as group (II). The study was conducted at the cardiothoracic surgery department of Benha University hospital in Egypt; patients enrolled were operated on from February 2012 to February 2016. A rapid response thermistor pulmonary artery catheter was inserted via the right internal jugular vein. Preoperatively the following was recorded: central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac output, right ventricular ejection fraction and volumes. The same parameters were collected in fixed time intervals after 3 hours, 6 hours, 12 hours, 24 hours, and 48 hours postoperatively. For group (I): There were no statistically significant changes between the preoperative and postoperative records in the central venous pressure and mean arterial pressure; there were no statistically significant changes in the preoperative and 12, 24, and 48 hour postoperative records for cardiac index; 3 and 6 hours postoperative showed significant changes. There were statistically significant changes between the preoperative and postoperative records for heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, right ventricular ejection fraction and right ventricular end diastolic volume index, in all postoperative records. For group (II): There were no statistically significant changes between the preoperative and all postoperative records for the central venous pressure, mean arterial pressure and cardiac index. There were statistically significant changes between the preoperative and postoperative records for heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, right ventricular ejection fraction and right ventricular end diastolic volume index in all postoperative records. There were statistically significant changes between the two groups in all postoperative records for heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, right ventricular ejection fraction and right ventricular end diastolic volume index. There is right ventricular dysfunction early after major pulmonary resection caused by increased right ventricular afterload. This dysfunction is more present in pneumonectomy than in lobectomy. Heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, right ventricular ejection fraction, and right ventricular end diastolic volume index are significantly affected by pulmonary resection.

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.

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.

Prognostic Nutritional Index and the Risk of Mortality in Patients With Acute Heart Failure.

PubMed

Cheng, Yu-Lun; Sung, Shih-Hsien; Cheng, Hao-Min; Hsu, Pai-Feng; Guo, Chao-Yu; Yu, Wen-Chung; Chen, Chen-Huan

2017-06-25

Nutritional status has been related to clinical outcomes in patients with heart failure. We assessed the association between nutritional status, indexed by prognostic nutritional index (PNI), and survival in patients hospitalized for acute heart failure. A total of 1673 patients (age 76±13 years, 68% men) hospitalized for acute heart failure in a tertiary medical center were analyzed. PNI was calculated as 10×serum albumin (g/dL)+0.005×total lymphocyte count (per mm 3 ). National Death Registry was linked to identify the clinical outcomes of all-cause and cardiovascular death. With increasing tertiles of PNI, age and N-terminal probrain natriuretic peptide decreased, and body mass index, estimated glomerular filtration rate, and hemoglobin increased. During a mean follow-up duration of 31.5 months, a higher PNI tertile was related to better survival free from all-cause and cardiovascular mortality in the total study population and in participants with either reduced or preserved left ventricular ejection fraction. After accounting for age, sex, estimated glomerular filtration rate, left ventricular ejection fraction, serum sodium level, and on-admission systolic blood pressure, PNI was independently associated with cardiovascular death and total mortality (hazard ratio per 1 SD of the natural logarithm of the PNI: 0.76 [95% CI, 0.66-0.87] and 0.79 [95% CI, 0.73-0.87], respectively). In subgroup analyses stratified by age, sex, left ventricular ejection fraction, body mass index, or estimated glomerular filtration rate, PNI was consistently related to mortality. PNI is independently associated with long-term survival in patients hospitalized for acute heart failure with either reduced or preserved left ventricular ejection fraction. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Echocardiographic Parameters and Survival in Chagas Heart Disease with Severe Systolic Dysfunction

PubMed Central

Rassi, Daniela do Carmo; Vieira, Marcelo Luiz Campos; Arruda, Ana Lúcia Martins; Hotta, Viviane Tiemi; Furtado, Rogério Gomes; Rassi, Danilo Teixeira; Rassi, Salvador

2014-01-01

Background Echocardiography provides important information on the cardiac evaluation of patients with heart failure. The identification of echocardiographic parameters in severe Chagas heart disease would help implement treatment and assess prognosis. Objective To correlate echocardiographic parameters with the endpoint cardiovascular mortality in patients with ejection fraction < 35%. Methods Study with retrospective analysis of pre-specified echocardiographic parameters prospectively collected from 60 patients included in the Multicenter Randomized Trial of Cell Therapy in Patients with Heart Diseases (Estudo Multicêntrico Randomizado de Terapia Celular em Cardiopatias) - Chagas heart disease arm. The following parameters were collected: left ventricular systolic and diastolic diameters and volumes; ejection fraction; left atrial diameter; left atrial volume; indexed left atrial volume; systolic pulmonary artery pressure; integral of the aortic flow velocity; myocardial performance index; rate of increase of left ventricular pressure; isovolumic relaxation time; E, A, Em, Am and Sm wave velocities; E wave deceleration time; E/A and E/Em ratios; and mitral regurgitation. Results In the mean 24.18-month follow-up, 27 patients died. The mean ejection fraction was 26.6 ± 5.34%. In the multivariate analysis, the parameters ejection fraction (HR = 1.114; p = 0.3704), indexed left atrial volume (HR = 1.033; p < 0.0001) and E/Em ratio (HR = 0.95; p = 0.1261) were excluded. The indexed left atrial volume was an independent predictor in relation to the endpoint, and values > 70.71 mL/m2 were associated with a significant increase in mortality (log rank p < 0.0001). Conclusion The indexed left atrial volume was the only independent predictor of mortality in this population of Chagasic patients with severe systolic dysfunction. PMID:24553982

Echocardiographic parameters and survival in Chagas heart disease with severe systolic dysfunction.

PubMed

Rassi, Daniela do Carmo; Vieira, Marcelo Luiz Campos; Arruda, Ana Lúcia Martins; Hotta, Viviane Tiemi; Furtado, Rogério Gomes; Rassi, Danilo Teixeira; Rassi, Salvador

2014-03-01

Echocardiography provides important information on the cardiac evaluation of patients with heart failure. The identification of echocardiographic parameters in severe Chagas heart disease would help implement treatment and assess prognosis. To correlate echocardiographic parameters with the endpoint cardiovascular mortality in patients with ejection fraction < 35%. Study with retrospective analysis of pre-specified echocardiographic parameters prospectively collected from 60 patients included in the Multicenter Randomized Trial of Cell Therapy in Patients with Heart Diseases (Estudo Multicêntrico Randomizado de Terapia Celular em Cardiopatias) - Chagas heart disease arm. The following parameters were collected: left ventricular systolic and diastolic diameters and volumes; ejection fraction; left atrial diameter; left atrial volume; indexed left atrial volume; systolic pulmonary artery pressure; integral of the aortic flow velocity; myocardial performance index; rate of increase of left ventricular pressure; isovolumic relaxation time; E, A, Em, Am and Sm wave velocities; E wave deceleration time; E/A and E/Em ratios; and mitral regurgitation. In the mean 24.18-month follow-up, 27 patients died. The mean ejection fraction was 26.6 ± 5.34%. In the multivariate analysis, the parameters ejection fraction (HR = 1.114; p = 0.3704), indexed left atrial volume (HR = 1.033; p < 0.0001) and E/Em ratio (HR = 0.95; p = 0.1261) were excluded. The indexed left atrial volume was an independent predictor in relation to the endpoint, and values > 70.71 mL/m2 were associated with a significant increase in mortality (log rank p < 0.0001). The indexed left atrial volume was the only independent predictor of mortality in this population of Chagasic patients with severe systolic dysfunction.

Frequency of Methamphetamine Use as a Major Contributor Toward the Severity of Cardiomyopathy in Adults ≤50 Years.

PubMed

Neeki, Michael M; Kulczycki, Michael; Toy, Jake; Dong, Fanglong; Lee, Carol; Borger, Rodney; Adigopula, Sasikanth

2016-08-15

Methamphetamine is one of the most commonly abused illegal drugs in the United States. Health care providers are commonly faced with medical illness caused by methamphetamine. This study investigates the impact of methamphetamine use on the severity of cardiomyopathy and heart failure in young adults. This retrospective study analyzed patients seen at Arrowhead Regional Medical Center from 2008 to 2012. Patients were between 18 and 50 years old. All patients had a discharge diagnosis of cardiomyopathy or heart failure. The severity of disease was quantified by left ventricular systolic dysfunction: heart failure with preserved ejection fraction to mildly reduced if ejection fraction was >40% and moderate to severely depressed if ejection fraction was ≤40%. Methamphetamine abuse was determined by a positive urine drug screen or per documented history. Of the 590 patients, 223 (37.8%) had a history of methamphetamine use. More than half the population was men (n = 389, 62.3%); 41% was Hispanic (n = 243), 25.8% was Caucasian (n = 152), and 27.8% was African-American (n = 164); 60.9% were in the age range of 41 to 50 years (n = 359). Patients with a history of methamphetamine use had increased odds (odds ratio = 1.80, 95% confidence interval 1.27 to 2.57) of having a moderately or severely reduced ejection fraction. Additionally, men were more likely (odds ratio 3.13, 95% confidence interval 2.14 to 4.56) to have worse left ventricular systolic dysfunction. In conclusion, methamphetamine use was associated with an increased severity of cardiomyopathy in young adults. Copyright © 2016 Elsevier Inc. All rights reserved.

DNA packaging and ejection forces in bacteriophage

PubMed Central

Kindt, James; Tzlil, Shelly; Ben-Shaul, Avinoam; Gelbart, William M.

2001-01-01

We calculate the forces required to package (or, equivalently, acting to eject) DNA into (from) a bacteriophage capsid, as a function of the loaded (ejected) length, under conditions for which the DNA is either self-repelling or self-attracting. Through computer simulation and analytical theory, we find the loading force to increase more than 10-fold (to tens of piconewtons) during the final third of the loading process; correspondingly, the internal pressure drops 10-fold to a few atmospheres (matching the osmotic pressure in the cell) upon ejection of just a small fraction of the phage genome. We also determine an evolution of the arrangement of packaged DNA from toroidal to spool-like structures. PMID:11707588

Survival Benefits of Invasive Versus Conservative Strategies in Heart Failure in Patients With Reduced Ejection Fraction and Coronary Artery Disease: A Meta-Analysis.

PubMed

Wolff, Georg; Dimitroulis, Dimitrios; Andreotti, Felicita; Kołodziejczak, Michalina; Jung, Christian; Scicchitano, Pietro; Devito, Fiorella; Zito, Annapaola; Occhipinti, Michele; Castiglioni, Battistina; Calveri, Giuseppe; Maisano, Francesco; Ciccone, Marco M; De Servi, Stefano; Navarese, Eliano P

2017-01-01

Heart failure with reduced ejection fraction caused by ischemic heart disease is associated with increased morbidity and mortality. It remains unclear whether revascularization by either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) carries benefits or risks in this group of stable patients compared with medical treatment. We performed a meta-analysis of available studies comparing different methods of revascularization (PCI or CABG) against each other or medical treatment in patients with coronary artery disease and left ventricular ejection fraction ≤40%. The primary outcome was all-cause mortality; myocardial infarction, revascularization, and stroke were also analyzed. Twenty-one studies involving a total of 16 191 patients were included. Compared with medical treatment, there was a significant mortality reduction with CABG (hazard ratio, 0.66; 95% confidence interval, 0.61-0.72; P<0.001) and PCI (hazard ratio, 0.73; 95% confidence interval, 0.62-0.85; P<0.001). When compared with PCI, CABG still showed a survival benefit (hazard ratio, 0.82; 95% confidence interval, 0.75-0.90; P<0.001). The present meta-analysis indicates that revascularization strategies are superior to medical treatment in improving survival in patients with ischemic heart disease and reduced ejection fraction. Between the 2 revascularization strategies, CABG seems more favorable compared with PCI in this particular clinical setting. © 2017 American Heart Association, Inc.

Inappropriate left ventricular mass and poor outcomes in patients with angina pectoris and normal ejection fraction.

PubMed

Huang, Bao-Tao; Peng, Yong; Liu, Wei; Zhang, Chen; Huang, Fang-Yang; Wang, Peng-Ju; Zuo, Zhi-Liang; Liao, Yan-Biao; Chai, Hua; Li, Qiao; Zhao, Zhen-Gang; Luo, Xiao-Lin; Ren, Xin; Huang, Kai-Sen; Meng, Qing-Tao; Chen, Chi; Huang, De-Jia; Chen, Mao

2015-03-01

Although inappropriate left ventricular mass has been associated with clustered cardiac geometric and functional abnormalities, its predictive value in patients with coronary artery disease is still unknown. This study examined the association of inappropriate left ventricular mass with clinical outcomes in patients with angina pectoris and normal ejection fraction. Consecutive patients diagnosed with angina pectoris whose ejection fraction was normal were recruited from 2008 to 2012. Inappropriate left ventricular mass was determined when the ratio of actual left ventricular mass to the predicted one exceeded 150%. The primary endpoint was a composite of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. Clinical outcomes between the inappropriate and appropriate left ventricular mass group were compared before and after propensity matching. Of the total of 1515 participants, 18.3% had inappropriate left ventricular mass. Patients with inappropriate left ventricular mass had a higher composite event rate compared with those with appropriate left ventricular mass (11.2 vs. 6.6%, P=0.010). Multivariate Cox regression analyses showed that inappropriate left ventricular mass was an independent risk factor for adverse events (adjusted hazard ratio, 1.59; 95% confidence interval, 1.03-2.45; P=0.035). The worse outcome in patients with inappropriate left ventricular mass was further validated in a propensity matching cohort and patients with the traditional definition of left ventricular hypertrophy. Inappropriate left ventricular mass was associated with an increased risk of adverse events in patients with angina pectoris and normal ejection fraction.

A porcine model of hypertensive cardiomyopathy: implications for heart failure with preserved ejection fraction.

PubMed

Schwarzl, Michael; Hamdani, Nazha; Seiler, Sebastian; Alogna, Alessio; Manninger, Martin; Reilly, Svetlana; Zirngast, Birgit; Kirsch, Alexander; Steendijk, Paul; Verderber, Jochen; Zweiker, David; Eller, Philipp; Höfler, Gerald; Schauer, Silvia; Eller, Kathrin; Maechler, Heinrich; Pieske, Burkert M; Linke, Wolfgang A; Casadei, Barbara; Post, Heiner

2015-11-01

Heart failure with preserved ejection fraction (HFPEF) evolves with the accumulation of risk factors. Relevant animal models to identify potential therapeutic targets and to test novel therapies for HFPEF are missing. We induced hypertension and hyperlipidemia in landrace pigs (n = 8) by deoxycorticosteroneacetate (DOCA, 100 mg/kg, 90-day-release subcutaneous depot) and a Western diet (WD) containing high amounts of salt, fat, cholesterol, and sugar for 12 wk. Compared with weight-matched controls (n = 8), DOCA/WD-treated pigs showed left ventricular (LV) concentric hypertrophy and left atrial dilatation in the absence of significant changes in LV ejection fraction or symptoms of heart failure at rest. The LV end-diastolic pressure-volume relationship was markedly shifted leftward. During simultaneous right atrial pacing and dobutamine infusion, cardiac output reserve and LV peak inflow velocities were lower in DOCA/WD-treated pigs at higher LV end-diastolic pressures. In LV biopsies, we observed myocyte hypertrophy, a shift toward the stiffer titin isoform N2B, and reduced total titin phosphorylation. LV superoxide production was increased, in part attributable to nitric oxide synthase (NOS) uncoupling, whereas AKT and NOS isoform expression and phosphorylation were unchanged. In conclusion, we developed a large-animal model in which loss of LV capacitance was associated with a titin isoform shift and dysfunctional NOS, in the presence of preserved LV ejection fraction. Our findings identify potential targets for the treatment of HFPEF in a relevant large-animal model. Copyright © 2015 the American Physiological Society.

Impaired Right, Left, or Biventricular Function and Resting Oxygen Saturation Are Associated With Mortality in Eisenmenger Syndrome: A Clinical and Cardiovascular Magnetic Resonance Study.

PubMed

Jensen, Annette S; Broberg, Craig S; Rydman, Riikka; Diller, Gerhard-Paul; Li, Wei; Dimopoulos, Konstantinos; Wort, Stephen J; Pennell, Dudley J; Gatzoulis, Michael A; Babu-Narayan, Sonya V

2015-12-01

Patients with Eisenmenger syndrome (ES) have better survival, despite similar pulmonary vascular pathology, compared with other patients with pulmonary arterial hypertension. Cardiovascular magnetic resonance (CMR) is useful for risk stratification in idiopathic pulmonary arterial hypertension, whereas it has not been evaluated in ES. We studied CMR together with other noninvasive measurements in ES to evaluate its potential role as a noninvasive risk stratification test. Between 2003 and 2005, 48 patients with ES, all with a post-tricuspid shunt, were enrolled in a prospective, longitudinal, single-center study. All patients underwent a standardized baseline assessment with CMR, blood test, echocardiography, and 6-minute walk test and were followed up for mortality until the end of December 2013. Twelve patients (25%) died during follow-up, mostly from heart failure (50%). Impaired ventricular function (right or left ventricular ejection fraction) was associated with increased risk of mortality (lowest quartile: right ventricular ejection fraction, <40%; hazard ratio, 4.4 [95% confidence interval, 1.4-13.5]; P=0.01 and left ventricular ejection fraction, <50%; hazard ratio, 6.6 [95% confidence interval, 2.1-20.8]; P=0.001). Biventricular impairment (lowest quartile left ventricular ejection fraction, <50% and right ventricular ejection fraction, <40%) conveyed an even higher risk of mortality (hazard ratio, 8.0 [95% confidence interval, 2.5-25.1]; P=0.0004). No other CMR or noninvasive measurement besides resting oxygen saturation (hazard ratio, 0.90 [0.83-0.97]/%; P=0.007) was associated with mortality. Impaired right, left, or biventricular systolic function derived from baseline CMR and resting oxygen saturation are associated with mortality in adult patients with ES. CMR is a useful noninvasive tool, which may be incorporated in the risk stratification assessment of ES during lifelong follow-up. © 2015 American Heart Association, Inc.

Spironolactone for heart failure with preserved ejection fraction.

PubMed

Pitt, Bertram; Pfeffer, Marc A; Assmann, Susan F; Boineau, Robin; Anand, Inder S; Claggett, Brian; Clausell, Nadine; Desai, Akshay S; Diaz, Rafael; Fleg, Jerome L; Gordeev, Ivan; Harty, Brian; Heitner, John F; Kenwood, Christopher T; Lewis, Eldrin F; O'Meara, Eileen; Probstfield, Jeffrey L; Shaburishvili, Tamaz; Shah, Sanjiv J; Solomon, Scott D; Sweitzer, Nancy K; Yang, Song; McKinlay, Sonja M

2014-04-10

Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction. In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77 to 1.04; P=0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P=0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 μmol per liter) or higher, or dialysis. In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. (Funded by the National Heart, Lung, and Blood Institute; TOPCAT ClinicalTrials.gov number, NCT00094302.).

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.

One-year mortality outcomes and hospital readmissions of patients admitted with acute heart failure: Data from the Trivandrum Heart Failure Registry in Kerala, India.

PubMed

Harikrishnan, Sivadasanpillai; Sanjay, Ganapathi; Agarwal, Anubha; Kumar, N Pratap; Kumar, K Krishna; Bahuleyan, Charantharayil Gopalan; Vijayaraghavan, Govindan; Viswanathan, Sunitha; Sreedharan, Madhu; Biju, R; Rajalekshmi, N; Nair, Tiny; Suresh, Krishnan; Jeemon, Panniyammakal

2017-07-01

There are sparse data on outcomes of patients with heart failure (HF) from India. The objective was to evaluate hospital readmissions and 1-year mortality outcomes of patients with HF in Kerala, India. We followed 1,205 patients enrolled in the Trivandrum Heart Failure Registry for 1 year. A trained research nurse contacted each participant every 3 months using a structured questionnaire which included hospital readmission and mortality information. The mean (SD) age was 61.2 (13.7) years, and 31% were women. One out of 4 (26%) participants had HF with preserved ejection fraction. Only 25% of patients with HF with reduced ejection fraction received guideline-directed medical therapy at discharge. Cumulative all-cause mortality at 1 year was 30.8% (n = 371), but the greatest risk of mortality was in the first 3 months (18.1%). Most deaths (61%) occurred in patients younger than 70 years. One out of every 3 (30.2%) patients was readmitted at least once over 1 year. The hospital readmission rates were similar between HF with preserved ejection fraction and HF with reduced ejection fraction patients. New York Heart Association functional class IV status and lack of guideline-directed medical treatment after index hospitalization were associated with increased likelihood of readmission. Similarly, older age, lower education status, nonischemic etiology, history of stroke, higher serum creatinine, lack of adherence to guideline-directed medical therapy, and hospital readmissions were associated with increased 1-year mortality. In the Trivandrum Heart Failure Registry, 1 of 3 HF patients died within 1 year of follow-up during their productive life years. Suboptimal adherence to guideline-directed treatment is associated with increased propensity of readmission and death. Quality improvement programs aiming to improve adherence to guideline-based therapy and reducing readmission may result in significant survival benefits in the relatively younger cohort of HF patients in India. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-term echocardiographic and cardioscintigraphic effects of growth hormone treatment in adults with Prader-Willi syndrome.

PubMed

Marzullo, Paolo; Marcassa, Claudio; Minocci, Alessandro; Campini, Riccardo; Eleuteri, Ermanno; Gondoni, Luca Alessandro; Aimaretti, Gianluca; Sartorio, Alessandro; Scacchi, Massimo; Grugni, Graziano

2015-05-01

In Prader-Willi syndrome (PWS), an altered GH secretion has been related to reduced cardiac mass and systolic function compared to controls. The objective was to evaluate the cardiovascular response to a 4-year GH therapy in adult PWS patients. Study participants were nine severely obese PWS adults (three females, six males) and 13 age-, gender-, and body mass index-matched obese controls. In an open-label prospective study, assessment of endocrine parameters and metabolic outcome, whole-body and abdominal fat scans, echocardiography, and radionuclide angiography in unstimulated and dobutamine-stimulated conditions were conducted at baseline and after 1 and 4 years of GH treatment. GH treatment increased IGF-1 (P < .0001), decreased C-reactive protein levels (P < .05), improved visceral fat mass (P < .05), and achieved near-significant changes of fat and fat-free body mass in PWS patients. Left ventricle mass indexed by fat mass increased significantly after 1 and 4 years of GH therapy (P < .05) without evident abnormalities of diastolic function, while a trend toward a reduction of the ejection fraction was documented by echocardiography (P = .054). Radionuclide angiography revealed stable values throughout the study of both the left and right ventricle ejection fractions, although this was accompanied by a statistically nonsignificant reduction of the left ventricle filling rate. A positive association between lean body mass and left ventricle ejection fraction was evident during the study (P < .05). GH therapy increased the cardiac mass of PWS adults without causing overt abnormalities of systolic and diastolic function. Although the association between lean mass and left ventricle ejection fraction during GH therapy corroborates a favorable systemic outcome of long-term GH treatment in adults with PWS, subtle longitudinal modifications of functional parameters advocate appropriate cardiac monitoring in the long-term therapeutic strategy for PWS.

Heart failure.

PubMed

Metra, Marco; Teerlink, John R

2017-10-28

Heart failure is common in adults, accounting for substantial morbidity and mortality worldwide. Its prevalence is increasing because of ageing of the population and improved treatment of acute cardiovascular events, despite the efficacy of many therapies for patients with heart failure with reduced ejection fraction, such as angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), β blockers, and mineralocorticoid receptor antagonists, and advanced device therapies. Combined angiotensin receptor blocker neprilysin inhibitors (ARNIs) have been associated with improvements in hospital admissions and mortality from heart failure compared with enalapril, and guidelines now recommend substitution of ACE inhibitors or ARBs with ARNIs in appropriate patients. Improved safety of left ventricular assist devices means that these are becoming more commonly used in patients with severe symptoms. Antidiabetic therapies might further improve outcomes in patients with heart failure. New drugs with novel mechanisms of action, such as cardiac myosin activators, are under investigation for patients with heart failure with reduced left ventricular ejection fraction. Heart failure with preserved ejection fraction is a heterogeneous disorder that remains incompletely understood and will continue to increase in prevalence with the ageing population. Although some data suggest that spironolactone might improve outcomes in these patients, no therapy has conclusively shown a significant effect. Hopefully, future studies will address these unmet needs for patients with heart failure. Admissions for acute heart failure continue to increase but, to date, no new therapies have improved clinical outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Riser Pattern: Another Determinant of Heart Failure With Preserved Ejection Fraction.

PubMed

Komori, Takahiro; Eguchi, Kazuo; Saito, Toshinobu; Hoshide, Satoshi; Kario, Kazuomi

2016-10-01

Paradoxical increase in blood pressure (BP) during sleep, exceeding those of awake BP, is called the "riser" BP pattern, and known as an abnormal circadian BP rhythm, has been reported to be associated with adverse cardiovascular prognoses. However, the significance of ambulatory BP in heart failure patients with preserved ejection fraction (HFpEF) has never been reported. Here, we tested our hypothesis that abnormal circadian BP rhythm is associated with HFpEF. The authors enrolled 508 patients with hospitalized HF (age 68±13 years; 315 men, 193 women). There were 232 cases of HFpEF and 276 cases of heart failure with reduced ejection fraction (HFrEF). The riser BP pattern was significantly more frequent in the HFpEF (28.9%) group compared with the HFrEF group (19.9%). In a multivariable logistic regression analysis, the riser BP pattern was associated with HFpEF (odds ratio, 1.73; 95% confidence interval, 1.02-2.91; P=.041) independent of the other covariates. In conclusion, the riser BP pattern was associated with HFpEF. ©2016 Wiley Periodicals, Inc.

Heart Failure with Recovered EF and Heart Failure with Mid-Range EF: Current Recommendations and Controversies.

PubMed

Unkovic, Peter; Basuray, Anupam

2018-04-03

This review explores key features and potential management controversies in two emerging populations in heart failure: heart failure with recovered ejection fraction (HF-recovered EF) and heart failure with mid-range ejection fraction (HFmrEF). While HF-recovered EF patients have better outcomes than heart failure with reduced ejection fraction (HFrEF), they continue to have symptoms, persistent biomarker elevations, and abnormal outcomes suggesting a continued disease process. HFmrEF patients appear to have features of HFrEF and heart failure with preserved ejection fraction (HFpEF), but have a high prevalence of ischemic heart disease and may represent a transitory phase between the HFrEF and HFpEF. Management strategies have insufficient data to warrant standardization at this time. HF-recovered EF and HFmrEF represent new populations with unmet needs and expose the pitfalls of an EF basis for heart failure classification.

Mechanisms of decreased left ventricular preload during continuous positive pressure ventilation in ARDS

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

Dhainaut, J.F.; Devaux, J.Y.; Monsallier, J.F.

1986-07-01

Continuous positive pressure ventilation is associated with a reduction in left ventricular preload and cardiac output, but the mechanisms responsible are controversial. The decrease in left ventricular preload may result exclusively from a decreased systemic venous return due to increased pleural pressure, or from an additional effect such as decreased left ventricular compliance. To determine the mechanisms responsible, we studied the changes in cardiac output induced by continuous positive pressure ventilation in eight patients with the adult respiratory distress syndrome. We measured cardiac output by thermodilution, and biventricular ejection fraction by equilibrium gated blood pool scintigraphy. Biventricular end-diastolic volumes weremore » then calculated by dividing stroke volume by ejection fraction. As positive end-expiratory pressure increased from 0 to 20 cm H/sub 2/O, stroke volume and biventricular end-diastolic volumes fell about 25 percent, and biventricular ejection fraction remained unchanged. At 20 cm H/sub 2/O positive end-expiratory pressure, volume expansion for normalizing cardiac output restored biventricular end-diastolic volumes without markedly changing biventricular end-diastolic transmural pressures. The primary cause of the reduction in left ventricular preload with continuous positive pressure ventilation appears to be a fall in venous return and hence in right ventricular stroke volume, without evidence of change in left ventricular diastolic compliance.« less

Role of Myocardial Collagen in Severe Aortic Stenosis With Preserved Ejection Fraction and Symptoms of Heart Failure.

PubMed

Echegaray, Kattalin; Andreu, Ion; Lazkano, Ane; Villanueva, Iñaki; Sáenz, Alberto; Elizalde, María Reyes; Echeverría, Tomás; López, Begoña; Garro, Asier; González, Arantxa; Zubillaga, Elena; Solla, Itziar; Sanz, Iñaki; González, Jesús; Elósegui-Artola, Alberto; Roca-Cusachs, Pere; Díez, Javier; Ravassa, Susana; Querejeta, Ramón

2017-10-01

We investigated the anatomical localization, biomechanical properties, and molecular phenotype of myocardial collagen tissue in 40 patients with severe aortic stenosis with preserved ejection fraction and symptoms of heart failure. Two transmural biopsies were taken from the left ventricular free wall. Mysial and nonmysial regions of the collagen network were analyzed. Myocardial collagen volume fraction (CVF) was measured by picrosirius red staining. Young's elastic modulus (YEM) was measured by atomic force microscopy in decellularized slices to assess stiffness. Collagen types I and III were measured as C I VF and C III VF, respectively, by confocal microscopy in areas with YEM evaluation. Compared with controls, patients exhibited increased mysial and nonmysial CVF and nonmysial:mysial CVF ratio (P < .05). In patients, nonmysial CVF (r = 0.330; P = .046) and the nonmysial:mysial CVF ratio (r = 0.419; P = .012) were directly correlated with the ratio of maximal early transmitral flow velocity in diastole to early mitral annulus velocity in diastole. Both the C I VF:C III VF ratio and YEM were increased (P ≤ .001) in nonmysial regions compared with mysial regions in patients, with a direct correlation (r = 0.895; P < .001) between them. These findings suggest that, in patients with severe aortic stenosis with preserved ejection fraction and symptoms of heart failure, diastolic dysfunction is associated with increased nonmysial deposition of collagen, predominantly type I, resulting in increased extracellular matrix stiffness. Therefore, the characteristics of collagen tissue may contribute to diastolic dysfunction in these patients. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Pressor response to intravenous tyramine is a marker of cardiac, but not vascular, adrenergic function

NASA Technical Reports Server (NTRS)

Meck, Janice V.; Martin, David S.; D'Aunno, Dominick S.; Waters, Wendy W.

2003-01-01

Intravenous injections of the indirect sympathetic amine, tyramine, are used as a test of peripheral adrenergic function. The authors measured the time course of increases in ejection fraction, heart rate, systolic and diastolic pressure, popliteal artery flow, and greater saphenous vein diameter before and after an injection of 4.0 mg/m(2) body surface area of tyramine in normal human subjects. The tyramine caused moderate, significant increases in systolic pressure and significant decreases in total peripheral resistance. The earliest changes were a 30% increase in ejection fraction and a 16% increase in systolic pressure, followed by a 60% increase in popliteal artery flow and a later 11% increase in greater saphenous vein diameter. There were no changes in diastolic pressure or heart rate. These results suggest that pressor responses during tyramine injections are primarily due to an inotropic response that increases cardiac output and pressure and causes a reflex decrease in vascular resistance. Thus, tyramine pressor tests are a measure of cardiac, but not vascular, sympathetic function.

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

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.

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

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.

Factors related to outcome in heart failure with a preserved (or normal) left ventricular ejection fraction.

PubMed

Sanderson, John E

2016-07-01

Heart failure with a preserved ejection faction (HFpEF) is a growing and expensive cause of heart failure (HF) affecting particularly the elderly. It differs in substantial ways in addition to the normal left ventricular ejection fraction, from the more easily recognized form of heart failure with a reduced ejection fraction (HFrEF or 'systolic heart failure') and unlike HFrEF there have been little advances in treatment. In part, this relates to the complexity of the pathophysiology and identifying the correct targets. In HFpEF, there appears to be widespread stiffening of the vasculature and the myocardium affecting ventricular function (both systolic and diastolic), impeding ventricular suction, and thus early diastolic filling leading to breathlessness on exertion and later atrial failure and fibrillation. Left ventricular ejection fraction tends to gradually decline and some evolve into HFrEF. Most patients also have a mixture of several co-morbidities including hypertension, diabetes, obesity, poor renal function, lack of fitness, and often poor social conditions. Therefore, many factors may influence outcome in an individual patient. In this review, the epidemiology, possible causation, pathophysiology, the influence of co-morbidities and some of the many potential predictors of outcome will be considered.

Myosin Activator Omecamtiv Mecarbil Increases Myocardial Oxygen Consumption and Impairs Cardiac Efficiency Mediated by Resting Myosin ATPase Activity.

PubMed

Bakkehaug, Jens Petter; Kildal, Anders Benjamin; Engstad, Erik Torgersen; Boardman, Neoma; Næsheim, Torvind; Rønning, Leif; Aasum, Ellen; Larsen, Terje Steinar; Myrmel, Truls; How, Ole-Jakob

2015-07-01

Omecamtiv mecarbil (OM) is a novel inotropic agent that prolongs systolic ejection time and increases ejection fraction through myosin ATPase activation. We hypothesized that a potentially favorable energetic effect of unloading the left ventricle, and thus reduction of wall stress, could be counteracted by the prolonged contraction time and ATP-consumption. Postischemic left ventricular dysfunction was created by repetitive left coronary occlusions in 7 pigs (7 healthy pigs also included). In both groups, systolic ejection time and ejection fraction increased after OM (0.75 mg/kg loading for 10 minutes, followed by 0.5 mg/kg/min continuous infusion). Cardiac efficiency was assessed by relating myocardial oxygen consumption to the cardiac work indices, stroke work, and pressure-volume area. To circumvent potential neurohumoral reflexes, cardiac efficiency was additionally assessed in ex vivo mouse hearts and isolated myocardial mitochondria. OM impaired cardiac efficiency; there was a 31% and 23% increase in unloaded myocardial oxygen consumption in healthy and postischemic pigs, respectively. Also, the oxygen cost of the contractile function was increased by 63% and 46% in healthy and postischemic pigs, respectively. The increased unloaded myocardial oxygen consumption was confirmed in OM-treated mouse hearts and explained by an increased basal metabolic rate. Adding the myosin ATPase inhibitor, 2,3-butanedione monoxide abolished all surplus myocardial oxygen consumption in the OM-treated hearts. Omecamtiv mecarbil, in a clinically relevant model, led to a significant myocardial oxygen wastage related to both the contractile and noncontractile function. This was mediated by that OM induces a continuous activation in resting myosin ATPase. © 2015 American Heart Association, Inc.

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.

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.

Off-pump coronary artery bypass surgery in severe left ventricular dysfunction.

PubMed

Azarfarin, Rasoul; Pourafkari, Leili; Parvizi, Rezayat; Alizadehasl, Azin; Mahmoodian, Roghaiyeh

2010-02-01

Our aim was to examine hospital outcomes of coronary artery bypass surgery in patients with and without left ventricular dysfunction, with regard to the surgical technique (off- or on-pump). Between March 2007 and March 2008, 689 consecutive patients underwent isolated first-time coronary artery bypass; 127 had ejection fractions < or = 30% (group 1) and 562 had ejection fractions >30% (group 2). Data of preoperative risk profiles and hospital outcomes were collected prospectively. Off-pump operations were performed in 49 (38.6%) patients in group 1 and 196 (34.9%) in group 2. The incidences of infectious, neurologic, and cardiac complications postoperatively were significantly higher in group 1. In multivariate analysis, preoperative ejection fraction < or = 30% was found to be an independent risk factor for postoperative complications and hospital mortality. The subgroup of patients undergoing off-pump surgery in both groups had a significantly lower rate of total complications than those undergoing conventional on-pump operations, but no significant difference in mortality was observed between those undergoing off-pump or conventional surgery in either group. Off-pump surgery helped to limit the increased morbidity rate after coronary bypass in patients with ventricular dysfunction.

New Medications for Heart Failure

PubMed Central

Gordin, Jonathan S.; Fonarow, Gregg C.

2016-01-01

Heart failure is common and results in substantial morbidity and mortality. Current guideline-based therapies for heart failure with reduced ejection fraction, including beta-blockers, angiotensin converting enzyme (ACE) inhibitors, and aldosterone antagonists aim to interrupt deleterious neurohormonal pathways and have shown significant success in reducing morbidity and mortality associated with heart failure. Continued efforts to further improve outcomes in patients with heart failure with reduced ejection fraction have led to the first new-in-class medications approved for heart failure since 2005, ivabradine and sacubitril/valsartan. Ivabradine targets the If channels in the sinoatrial node of the heart, decreasing heart rate. Sacubitril/valsartan combines a neprilysin inhibitor that increases levels of beneficial vasodilatory peptides with an angiotensin receptor antagonist. On a background of previously approved, guideline-directed medical therapies for heart failure, these medications have shown improved clinical outcomes ranging from decreased hospitalizations in a select group of patients to a reduction in all-cause mortality across all pre-specified subgroups. In this review, we will discuss the previously established guideline-directed medical therapies for heart failure with reduced ejection fraction, the translational research that led to the development of these new therapies, and the results from the major clinical trials of ivabradine and sacubitril/valsartan. PMID:27038558

Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management. Position statement on behalf of the Heart Failure Association of the European Society of Cardiology.

PubMed

Gorter, Thomas M; van Veldhuisen, Dirk J; Bauersachs, Johann; Borlaug, Barry A; Celutkiene, Jelena; Coats, Andrew J S; Crespo-Leiro, Marisa G; Guazzi, Marco; Harjola, Veli-Pekka; Heymans, Stephane; Hill, Loreena; Lainscak, Mitja; Lam, Carolyn S P; Lund, Lars H; Lyon, Alexander R; Mebazaa, Alexandre; Mueller, Christian; Paulus, Walter J; Pieske, Burkert; Piepoli, Massimo F; Ruschitzka, Frank; Rutten, Frans H; Seferovic, Petar M; Solomon, Scott D; Shah, Sanjiv J; Triposkiadis, Filippos; Wachter, Rolf; Tschöpe, Carsten; de Boer, Rudolf A

2018-01-01

There is an unmet need for effective treatment strategies to reduce morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Until recently, attention in patients with HFpEF was almost exclusively focused on the left side. However, it is now increasingly recognized that right heart dysfunction is common and contributes importantly to poor prognosis in HFpEF. More insights into the development of right heart dysfunction in HFpEF may aid to our knowledge about this complex disease and may eventually lead to better treatments to improve outcomes in these patients. In this position paper from the Heart Failure Association of the European Society of Cardiology, the Committee on Heart Failure with Preserved Ejection Fraction reviews the prevalence, diagnosis, and pathophysiology of right heart dysfunction and failure in patients with HFpEF. Finally, potential treatment strategies, important knowledge gaps and future directions regarding the right side in HFpEF are discussed. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure: A Phase 1/2 Randomized Controlled Trial (RIMECARD Trial [Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy]).

PubMed

Bartolucci, Jorge; Verdugo, Fernando J; González, Paz L; Larrea, Ricardo E; Abarzua, Ema; Goset, Carlos; Rojo, Pamela; Palma, Ivan; Lamich, Ruben; Pedreros, Pablo A; Valdivia, Gloria; Lopez, Valentina M; Nazzal, Carolina; Alcayaga-Miranda, Francisca; Cuenca, Jimena; Brobeck, Matthew J; Patel, Amit N; Figueroa, Fernando E; Khoury, Maroun

2017-10-27

Umbilical cord-derived mesenchymal stem cells (UC-MSC) are easily accessible and expanded in vitro, possess distinct properties, and improve myocardial remodeling and function in experimental models of cardiovascular disease. Although bone marrow-derived mesenchymal stem cells have been previously assessed for their therapeutic potential in individuals with heart failure and reduced ejection fraction, no clinical trial has evaluated intravenous infusion of UC-MSCs in these patients. Evaluate the safety and efficacy of the intravenous infusion of UC-MSC in patients with chronic stable heart failure and reduced ejection fraction. Patients with heart failure and reduced ejection fraction under optimal medical treatment were randomized to intravenous infusion of allogenic UC-MSCs (Cellistem, Cells for Cells S.A., Santiago, Chile; 1×10 6 cells/kg) or placebo (n=15 per group). UC-MSCs in vitro, compared with bone marrow-derived mesenchymal stem cells, displayed a 55-fold increase in the expression of hepatocyte growth factor, known to be involved in myogenesis, cell migration, and immunoregulation. UC-MSC-treated patients presented no adverse events related to the cell infusion, and none of the patients tested at 0, 15, and 90 days presented alloantibodies to the UC-MSCs (n=7). Only the UC-MSC-treated group exhibited significant improvements in left ventricular ejection fraction at 3, 6, and 12 months of follow-up assessed both through transthoracic echocardiography ( P =0.0167 versus baseline) and cardiac MRI ( P =0.025 versus baseline). Echocardiographic left ventricular ejection fraction change from baseline to month 12 differed significantly between groups (+7.07±6.22% versus +1.85±5.60%; P =0.028). In addition, at all follow-up time points, UC-MSC-treated patients displayed improvements of New York Heart Association functional class ( P =0.0167 versus baseline) and Minnesota Living with Heart Failure Questionnaire ( P <0.05 versus baseline). At study completion, groups did not differ in mortality, heart failure admissions, arrhythmias, or incident malignancy. Intravenous infusion of UC-MSC was safe in this group of patients with stable heart failure and reduced ejection fraction under optimal medical treatment. Improvements in left ventricular function, functional status, and quality of life were observed in patients treated with UC-MSCs. URL: https://www.clinicaltrials.gov/ct2/show/NCT01739777. Unique identifier: NCT01739777. © 2017 The Authors.

Relationship between the prognostic value of ventilatory efficiency and age in patients with heart failure.

PubMed

Kato, Yuko; Suzuki, Shinya; Uejima, Tokuhisa; Semba, Hiroaki; Nagayama, Osamu; Hayama, Etsuko; Arita, Takuto; Yagi, Naoharu; Kano, Hiroto; Matsuno, Shunsuke; Otsuka, Takayuki; Oikawa, Yuji; Kunihara, Takashi; Yajima, Junji; Yamashita, Takeshi

2018-05-01

Background Ventilatory efficiency decreases with age. This study aimed to investigate the prognostic significance and cut-off value of the minute ventilation/carbon dioxide production (VE/VCO 2 ) slope according to age in patients with heart failure. Methods and results We analysed 1501 patients with heart failure from our observational cohort who performed maximal symptom-limited cardiopulmonary exercise testing and separated them into three age groups (≤55 years, 56-70 years and ≥71 years) in total and according to the three ejection fraction categories defined by European Society of Cardiology guidelines. The endpoint was set as heart failure events, hospitalisation for heart failure or death from heart failure. The VE/VCO 2 slope increased with age. During the median follow-up period of 4 years, 141 heart failure (9%) events occurred. In total, univariate Cox analyses showed that the VE/VCO 2 slope (cont.) was significantly related to heart failure events, while on multivariate analysis, the prognostic significance of the VE/VCO 2 slope (cont.) was poor, accompanied by a significant interaction with age ( P < 0.0001). The cut-off value of the VE/VCO 2 slope increased with the increase in age in not only the total but also the sub-ejection fraction categories. Multivariate analyses with a stepwise method adjusted for estimated glomerular filtration rate, peak oxygen consumption, atrial fibrillation and brain natriuretic peptide, showed that the predictive value of the binary VE/VCO 2 slope separated by the cut-off value varied according to age. There was a tendency for the prognostic significance to increase with age irrespective of ejection fraction. Conclusion The prognostic significance and cut-off value of the VE/VCO 2 slope may increase with advancing age.

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

Right Ventricular Structure and Function Are Associated With Incident Atrial Fibrillation: MESA-RV Study (Multi-Ethnic Study of Atherosclerosis-Right Ventricle).

PubMed

Chatterjee, Neal A; Shah, Ravi V; Murthy, Venkatesh L; Praestgaard, Amy; Shah, Sanjiv J; Ventetuolo, Corey E; Barr, R Graham; Kronmal, Richard; Lima, Joao A C; Bluemke, David A; Jerosch-Herold, Michael; Alonso, Alvaro; Kawut, Steven M

2017-01-01

Right ventricular (RV) morphology has been associated with drivers of atrial fibrillation (AF) risk, including left ventricular and pulmonary pathology, systemic inflammation, and neurohormonal activation. The aim of this study was to investigate the association between RV morphology and risk of incident AF. We interpreted cardiac magnetic resonance imaging in 4204 participants free of clinical cardiovascular disease in the MESA (Multi-Ethnic Study of Atherosclerosis). Incident AF was determined using hospital discharge records, study electrocardiograms, and Medicare claims data. The study sample (n=3819) was 61±10 years old and 47% male with 47.2% current/former smokers. After adjustment for demographics and clinical factors, including incident heart failure, higher RV ejection fraction (hazard ratio, 1.16 per SD; 95% confidence interval, 1.03-1.32; P=0.02) and greater RV mass (hazard ratio, 1.25 per SD; 95% confidence interval, 1.08-1.44; P=0.002) were significantly associated with incident AF. After additional adjustment for the respective left ventricular parameter, higher RV ejection fraction remained significantly associated with incident AF (hazard ratio, 1.15 per SD; 95% confidence interval, 1.01-1.32; P=0.04), whereas the association was attenuated for RV mass (hazard ratio, 1.16 per SD; 95% confidence interval, 0.99-1.35; P=0.07). In a subset of patients with available spirometry (n=2540), higher RV ejection fraction and mass remained significantly associated with incident AF after additional adjustment for lung function (P=0.02 for both). Higher RV ejection fraction and greater RV mass were associated with an increased risk of AF in a multiethnic population free of clinical cardiovascular disease at baseline. © 2017 American Heart Association, Inc.

Rationale and design of the Transcatheter Aortic Valve Replacement to UNload the Left ventricle in patients with ADvanced heart failure (TAVR UNLOAD) trial.

PubMed

Spitzer, Ernest; Van Mieghem, Nicolas M; Pibarot, Philippe; Hahn, Rebecca T; Kodali, Susheel; Maurer, Mathew S; Nazif, Tamim M; Rodés-Cabau, Josep; Paradis, Jean-Michel; Kappetein, Arie-Pieter; Ben-Yehuda, Ori; van Es, Gerrit-Anne; Kallel, Faouzi; Anderson, William N; Tijssen, Jan; Leon, Martin B

2016-12-01

Coexistence of moderate aortic stenosis (AS) in patients with heart failure (HF) with reduced ejection fraction is not uncommon. Moderate AS increases afterload, whereas pharmacologic reduction of afterload is a pillar of contemporary HF management. Unloading the left ventricle by reducing the transaortic gradient with transfemoral transcatheter aortic valve replacement (TAVR) may improve clinical outcomes in patients with moderate AS and HF with reduced ejection fraction. The TAVR UNLOAD (NCT02661451) is an international, multicenter, randomized, open-label, clinical trial comparing the efficacy and safety of TAVR with the Edwards SAPIEN 3 Transcatheter Heart Valve in addition to optimal heart failure therapy (OHFT) vs OHFT alone in patients with moderate AS (defined by a mean transaortic gradient ≥20 mm Hg and <40 mm Hg, and an aortic valve area >1.0 cm 2 and ≤1.5 cm 2 at rest or after dobutamine stress echocardiography) and reduced ejection fraction. A total of 600 patients will be randomized in a 1:1 fashion. Clinical follow-up is scheduled at 1, 6, and 12 months, and 2 years after randomization. The primary end point is the hierarchical occurrence of all-cause death, disabling stroke, hospitalizations related to HF, symptomatic aortic valve disease or nondisabling stroke, and the change in the Kansas City Cardiomyopathy Questionnaire at 1 year. Secondary end points capture effects on clinical outcome, biomarkers, echocardiographic parameters, and quality of life. The TAVR UNLOAD trial aims to test the hypothesis that TAVR on top of OHFT improves clinical outcomes in patients with moderate AS and HF with reduced ejection fraction. Copyright © 2016 Elsevier Inc. All rights reserved.

Left Atrial Volume Determinants in Patients with Non-Ischemic Dilated Cardiomyopathy

PubMed Central

Mancuso, Frederico José Neves; Moisés, Valdir Ambrósio; Almeida, Dirceu Rodrigues; Poyares, Dalva; Storti, Luciana Julio; Oliveira, Wércules Antonio; Brito, Flavio Souza; de Paola, Angelo Amato Vincenzo; Carvalho, Antonio Carlos Camargo; Campos, Orlando

2015-01-01

Background Left atrial volume (LAV) is a predictor of prognosis in patients with heart failure. Objective We aimed to evaluate the determinants of LAV in patients with dilated cardiomyopathy (DCM). Methods Ninety patients with DCM and left ventricular (LV) ejection fraction ≤ 0.50 were included. LAV was measured with real-time three-dimensional echocardiography (eco3D). The variables evaluated were heart rate, systolic blood pressure, LV end-diastolic volume and end-systolic volume and ejection fraction (eco3D), mitral inflow E wave, tissue Doppler e´ wave, E/e´ ratio, intraventricular dyssynchrony, 3D dyssynchrony index and mitral regurgitation vena contracta. Pearson´s coefficient was used to identify the correlation of the LAV with the assessed variables. A multiple linear regression model was developed that included LAV as the dependent variable and the variables correlated with it as the predictive variables. Results Mean age was 52 ± 11 years-old, LV ejection fraction: 31.5 ± 8.0% (16-50%) and LAV: 39.2±15.7 ml/m2. The variables that correlated with the LAV were LV end-diastolic volume (r = 0.38; p < 0.01), LV end-systolic volume (r = 0.43; p < 0.001), LV ejection fraction (r = -0.36; p < 0.01), E wave (r = 0.50; p < 0.01), E/e´ ratio (r = 0.51; p < 0.01) and mitral regurgitation (r = 0.53; p < 0.01). A multivariate analysis identified the E/e´ ratio (p = 0.02) and mitral regurgitation (p = 0.02) as the only independent variables associated with LAV increase. Conclusion The LAV is independently determined by LV filling pressures (E/e´ ratio) and mitral regurgitation in DCM. PMID:25993483

Left Atrial Volume Determinants in Patients with Non-Ischemic Dilated Cardiomyopathy.

PubMed

Mancuso, Frederico José Neves; Moisés, Valdir Ambrósio; Almeida, Dirceu Rodrigues; Poyares, Dalva; Storti, Luciana Julio; Oliveira, Wércules Antonio; Brito, Flavio Souza; Paola, Angelo Amato Vincenzo de; Carvalho, Antonio Carlos Camargo; Campos, Orlando

2015-07-01

Left atrial volume (LAV) is a predictor of prognosis in patients with heart failure. We aimed to evaluate the determinants of LAV in patients with dilated cardiomyopathy (DCM). Ninety patients with DCM and left ventricular (LV) ejection fraction ≤ 0.50 were included. LAV was measured with real-time three-dimensional echocardiography (eco3D). The variables evaluated were heart rate, systolic blood pressure, LV end-diastolic volume and end-systolic volume and ejection fraction (eco3D), mitral inflow E wave, tissue Doppler e' wave, E/e' ratio, intraventricular dyssynchrony, 3D dyssynchrony index and mitral regurgitation vena contracta. Pearson's coefficient was used to identify the correlation of the LAV with the assessed variables. A multiple linear regression model was developed that included LAV as the dependent variable and the variables correlated with it as the predictive variables. Mean age was 52 ± 11 years-old, LV ejection fraction: 31.5 ± 8.0% (16-50%) and LAV: 39.2±15.7 ml/m2. The variables that correlated with the LAV were LV end-diastolic volume (r = 0.38; p < 0.01), LV end-systolic volume (r = 0.43; p < 0.001), LV ejection fraction (r = -0.36; p < 0.01), E wave (r = 0.50; p < 0.01), E/e' ratio (r = 0.51; p < 0.01) and mitral regurgitation (r = 0.53; p < 0.01). A multivariate analysis identified the E/e' ratio (p = 0.02) and mitral regurgitation (p = 0.02) as the only independent variables associated with LAV increase. The LAV is independently determined by LV filling pressures (E/e' ratio) and mitral regurgitation in DCM.

Left ventricular ejection fraction in obstructive sleep apnea. Effects of long-term treatment with nasal continuous positive airway pressure.

PubMed

Krieger, J; Grucker, D; Sforza, E; Chambron, J; Kurtz, D

1991-10-01

The effects of treatment with nasal continuous positive airway pressure (CPAP) on left ventricular ejection fraction (LVEF) were assessed in 29 patients with obstructive sleep apnea (OSA) in a prospective study using multiple gated equilibrium radionuclide angiocardiography. All patients were evaluated before CPAP treatment was initiated and were reevaluated after one year (mean +/- SE, 415 +/- 6 days), of home treatment with nasal CPAP. The mean LVEF increased from 59 +/- 1 percent to 63 +/- 1 percent (p less than 0.005). The degree of improvement in LVEF was correlated with baseline LVEF (r = 0.54; p less than 0.003), meaning that the lower the baseline value, the greater the increase with treatment. The changes were not different when subgroups of medicated and unmedicated patients were considered separately. These results show that long-term nasal CPAP treatment results in improved left ventricular function in OSA.

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.

Prevalence and Long-Term Survival After Coronary Artery Bypass Grafting in Women and Men With Heart Failure and Preserved Versus Reduced Ejection Fraction.

PubMed

Sun, Louise Y; Tu, Jack V; Bader Eddeen, Anan; Liu, Peter P

2018-06-16

Heart failure (HF) with reduced ejection fraction (rEF) is a widely regarded prognosticator after coronary artery bypass grafting. HF with preserved ejection fraction (pEF) accounts for up to half of all HF cases and is associated with considerable morbidity and mortality in hospitalized cohorts. However, HFpEF outcomes have not been elucidated in cardiac surgical patients. We investigated the prevalence and outcomes of HFpEF and HFrEF in women and men following coronary artery bypass grafting. We conducted a retrospective cohort study in Ontario, Canada, between October 1, 2008, and March 31, 2015, using Cardiac Care Network and Canadian Institute of Health Information data. HF is captured through a validated population-based database of all Ontarians with physician-diagnosed HF. We defined pEF as ejection fraction ≥50% and rEF as ejection fraction <50%. The primary outcome was all-cause mortality. Analyses were stratified by sex. Mortality rates were calculated using Kaplan-Meier method. The relative hazard of death was assessed using multivariable Cox proportional hazard models. Of 40 083 patients (20.6% women), 55.5% had pEF without HF, 25.7% had rEF without HF, 6.9% had HFpEF, and 12.0% had HFrEF. Age-standardized HFpEF mortality rates at 4±2 years of follow-up were similar in women and men. HFrEF standardized HFpEF mortality rates were higher in women than men. We found a higher prevalence and poorer prognosis of HFpEF in women. A history of HF was a more important prognosticator than ejection fraction. Preoperative screening and extended postoperative follow-up should be focused on women and men with HF rather than on rEF alone. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Gated blood pool tomography for the evaluation of global and regional left ventricular function in comparison to planar techniques and echocardiography.

PubMed

Canclini, S; Terzi, A; Rossini, P; Vignati, A; La Canna, G; Magri, G C; Pizzocaro, C; Giubbini, R

2001-01-01

Multigated radionuclide ventriculography (MUGA) is a simple and reliable tool for the assessment of global systolic and diastolic function and in several studies it is still considered a standard for the assessment of left ventricular ejection fraction. However the evaluation of regional wall motion by MUGA is critical due to two-dimensional imaging and its clinical use is progressively declining in favor of echocardiography. Tomographic MUGA (T-MUGA) is not widely adopted in clinical practice. The aim of this study was to compare T-MUGA to planar MUGA (P-MUGA) for the assessment of global ejection fraction and to transthoracic echocardiography for the evaluation of regional wall motion. A 16-segment model was adopted for the comparison with echo regional wall motion. For each one of the 16 segments the normal range of T-MUGA ejection fraction was quantified and a normal data file was defined; the average value -2.5 SD was used as the lower threshold to identify abnormal segments. In addition, amplitude images from Fourier analysis were quantified and considered abnormal according to three different thresholds (25, 50 and 75% of the maximum). In a study group of 33 consecutive patients the ejection fraction values of T-MUGA highly correlated with those of P-MUGA (r = 0.93). The regional ejection fraction (according to the normal database) and the amplitude analysis (50% threshold) allowed for the correct identification of 203/226 and 167/226 asynergic segments by echocardiography, and of 269/302 and 244/302 normal segments, respectively. Therefore sensitivity, specificity and overall accuracy to detect regional wall motion abnormalities were 90, 89, 89% and 74, 81, 79% for regional ejection fraction and amplitude analysis, respectively. T-MUGA is a reliable tool for regional wall motion evaluation, well correlated with echocardiography, less subjective and able to provide quantitative data.

Heart Failure With Improved Ejection Fraction: Clinical Characteristics, Correlates of Recovery, and Survival: Results From the Valsartan Heart Failure Trial.

PubMed

Florea, Viorel G; Rector, Thomas S; Anand, Inder S; Cohn, Jay N

2016-07-01

Heart failure with recovered or improved ejection fraction (HFiEF) has been proposed as a new category of HF. Whether HFiEF is clinically distinct from HF with persistently reduced ejection fraction remains to be validated. Of the 5010 subjects enrolled in the Valsartan Heart Failure Trial (Val-HeFT), 3519 had a baseline left ventricular EF of <35% and a follow-up echocardiographic assessment of EF at 12 months. Of these, 321 (9.1%) patients who had a 12-month EF of >40% constituted the subgroup with HFiEF. EF improved from 28.7±5.6% to 46.5±5.6% in the subgroup with HFiEF and remained reduced (25.2±6.2% and 27.5±7.1%) in the subgroup with HF with reduced ejection fraction. The group with HFiEF had a less severe hemodynamic, biomarker, and neurohormonal profile, and it was treated with a more intense HF medication regimen. Subjects who had higher blood pressure and those treated with a β-blocker or randomized to valsartan had greater odds of being in the HFiEF group, whereas those with an ischemic pathogenesis, a more dilated left ventricle, and a detectable hs-troponin had lower odds of an improvement in EF. Recovery of the EF to >40% was associated with a better survival compared with persistently reduced EF. Our data support HFiEF as a stratum of HF with reduced ejection fraction with a more favorable outcome, which occurs in a minority of patients with HF with reduced ejection fraction who have a lower prevalence of ischemic heart disease, a less severe hemodynamic, biomarker, and neurohormonal profile, and who are treated with a more intense HF medication regimen. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00336336. © 2016 American Heart Association, Inc.

Observations on obesity patterns in tetralogy of Fallot patients from childhood to adulthood.

PubMed

Briston, David A; Sabanayagam, Aarthi; Zaidi, Ali N

2017-07-01

Obesity is increasingly prevalent, and abnormal body mass index is a risk factor for cardiovascular disease. There are limited data published regarding body mass index and CHD. We tested the hypothesis that body mass index and obesity prevalence are increasing in patients with tetralogy of Fallot over time by analysing time since surgery, age, height, weight, and body mass index among tetralogy of Fallot patients and demographic data from age-matched controls. NYHA class and left ventricular ejection fraction were analysed in adults. Body mass index was categorised into normal, overweight, and obese in this single-centre, retrospective chart review. Data were collected from 137 tetralogy of Fallot patients (71 men:66 women), of whom 40 had body mass index >25 kg/m2. Tetralogy of Fallot patients aged <6 years had lower body mass index (15.9 versus 17.1; p=0.042) until 16-20 years of age (27.4 versus 25.4; p=0.43). For adult tetralogy of Fallot patients, the mean body mass index was 26.5 but not statistically significantly different from the control cohort. Obese adult patients had significantly higher average NYHA class compared with those of normal weight (p=0.03), but no differences in left ventricular ejection fraction by echocardiography (p=0.55) or cardiac MRI (p=0.26) were noted. Lower body mass index was observed initially in tetralogy of Fallot patients, but by late adolescence no significant difference was observed. As adults, tetralogy of Fallot patients with higher body mass index had increased NYHA class but similar left ventricular ejection fraction.

Left ventricular ejection fraction may not be useful as an end point of thrombolytic therapy comparative trials.

PubMed

Califf, R M; Harrelson-Woodlief, L; Topol, E J

1990-11-01

In the era of comparative and adjunctive trials in reperfusion therapy, the need to develop alternative end points for mortality reduction is clear. Left ventricular ejection fraction, which has been commonly used as a surrogate, is problematic due to missing values, technically inadequate studies, and lack of correlation with mortality results in controlled reperfusion trials performed to date. In this paper, we present a composite clinical end point that includes, in order, severity of adverse outcome death, hemorrhagic stroke, nonhemorrhagic stroke, poor ejection fraction (less than 30%), reinfarction, heart failure, and pulmonary edema. Such a composite index may be useful to detect true therapeutic benefit in reperfusion trials without necessitating greater than 20-30,000 patient enrollment.

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

Treatment of dilated cardiomyopathy with carvedilol in children.

PubMed

Erdoğan, Ilkay; Ozer, Sema; Karagöz, Tevfik; Celiker, Alpay; Ozkutlu, Süheyla; Alehan, Dursun

2009-01-01

We performed a study to examine the clinical use of carvedilol, its dosage and its effects on systolic functions in children. Twenty-one patients with dilated cardiomyopathy who were treated with carvedilol adjacent to standard heart failure therapy were enrolled in the study. Echocardiographic assessment was obtained before and during carvedilol therapy, and left ventricular fractional shortening and left ventricular ejection fraction were determined in order to estimate left ventricular function. At a follow-up of six months, left ventricular ejection fraction and fractional shortening significantly improved from 38 +/- 10% to 53 +/- 13% and from 19 +/- 6 % to 27 +/- 8%, respectively, following carvedilol treatment. The results of the present study indicate that carvedilol is well tolerated in children with dilated cardiomyopathy and there is a significant improvement in the clinical status and left ventricular ejection fraction in patients not responding to conventional therapy. Patient selection criteria, optimal timing of carvedilol therapy, its dosage and its long-term effects need to be investigated with multi-institutional trials and large numbers of patients.

Changing the treatment of heart failure with reduced ejection fraction: clinical use of sacubitril-valsartan combination

PubMed Central

Kaplinsky, Edgardo

2016-01-01

Despite significant therapeutic advances, patients with chronic heart failure (HF) remain at high risk of morbidity and mortality. Sacubitril valsartan (previously known as LCZ696) is a new oral agent approved for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. It is described as the first in class angiotensin receptor neprilysin inhibitor (ARNI) since it incorporates the neprilysin inhibitor, sacubitril and the angiotensin II receptor antagonist, valsartan. Neprilysin is an endopeptidase that breaks down several vasoactive peptides including natriuretic peptides (NPs), bradykinin, endothelin and angiotensin II (Ang-II). Therefore, a natural consequence of its inhibition is an increase of plasmatic levels of both, NPs and Ang-II (with opposite biological actions). So, a combined inhibition of these both systems (Sacubitril / valsartan) may enhance the benefits of NPs effects in HF (natriuresis, diuresis, etc) while Ang-II receptor is inhibited (reducing vasoconstriction and aldosterone release). In a large clinical trial (PARADIGM-HF with 8442 patients), this new agent was found to significantly reduce cardiovascular and all cause mortality as well as hospitalizations due to HF (compared to enalapril). This manuscript reviews clinical evidence for sacubitril valsartan, dosing and cautions, future directions and its considered place in the therapy of HF with reduced ejection fraction. PMID:28133468

Association of Smoking, Sleep Apnea, and Plasma Alkalosis With Nocturnal Ventricular Arrhythmias in Men With Systolic Heart Failure

PubMed Central

Shukla, Rakesh; Wexler, Laura

2012-01-01

Background: Excess sudden death due to ventricular tachyarrhythmias remains a major mode of mortality in patients with systolic heart failure. The aim of this study was to determine the association of nocturnal ventricular arrhythmias in patients with low ejection fraction heart failure. We incorporated a large number of known pathophysiologic triggers to identify potential targets for therapy to reduce the persistently high incidence of sudden death in this population despite contemporary treatment. Methods: Eighty-six ambulatory male patients with stable low (≤ 45%) ejection fraction heart failure underwent full-night attendant polysomnography and simultaneous Holter recordings. Patients were divided into groups according to the presence or absence of couplets (paired premature ventricular excitations) and ventricular tachycardia (VT) (at least three consecutive premature ventricular excitations) during sleep. Results: In multiple regression analysis, four variables (current smoking status, increased number of arousals, plasma alkalinity, and old age) were associated with VT and two variables (apnea-hypopnea index and low right ventricular ejection fraction) were associated with couplets during sleep. Conclusions: We speculate that cessation of smoking, effective treatment of sleep apnea, and plasma alkalosis could collectively decrease the incidence of nocturnal ventricular tachyarrhythmias and the consequent risk of sudden death, which remains high despite the use of β blockades. PMID:22172636

Matrix-array 3-dimensional echocardiographic assessment of volumes, mass, and ejection fraction in young pediatric patients with a functional single ventricle: a comparison study with cardiac magnetic resonance.

PubMed

Soriano, Brian D; Hoch, Martin; Ithuralde, Alejandro; Geva, Tal; Powell, Andrew J; Kussman, Barry D; Graham, Dionne A; Tworetzky, Wayne; Marx, Gerald R

2008-04-08

Quantitative assessment of ventricular volumes and mass in pediatric patients with single-ventricle physiology would aid clinical management, but it is difficult to obtain with 2-dimensional echocardiography. The purpose of the present study was to compare matrix-array 3-dimensional echocardiography (3DE) measurements of single-ventricle volumes, mass, and ejection fraction with those measured by cardiac magnetic resonance (CMR) in young patients. Twenty-nine patients (median age, 7 months) with a functional single ventricle undergoing CMR under general anesthesia were prospectively enrolled. The 3DE images were acquired at the conclusion of the CMR. Twenty-seven of 29 3DE data sets (93%) were optimal for 3DE assessment. Two blinded and independent observers performed 3DE measurements of volume, mass, and ejection fraction. The 3DE end-diastolic volume correlated well (r=0.96) but was smaller than CMR by 9% (P<0.01), and 3DE ejection fraction was smaller than CMR by 11% (P<0.01). There was no significant difference in measurements of end-systolic volume and mass. The 3DE interobserver differences for mass and volumes were not significant except for ejection fraction (8% difference; P<0.05). Intraobserver differences were not significant. In young pediatric patients with a functional single ventricle, matrix-array 3DE measurements of mass and volumes compare well with those obtained by CMR. 3DE will provide an important modality for the serial analysis of ventricular size and performance in young patients with functional single ventricles.

Awake craniotomy in a patient with ejection fraction of 10%: considerations of cerebrovascular and cardiovascular physiology.

PubMed

Meng, Lingzhong; Weston, Stephen D; Chang, Edward F; Gelb, Adrian W

2015-05-01

A 37-year-old man with nonischemic 4-chamber dilated cardiomyopathy and low-output cardiac failure (estimated ejection fraction of 10%) underwent awake craniotomy for a low-grade oligodendroglioma resection under monitored anesthesia care. The cerebrovascular and cardiovascular physiologic challenges and our management of this patient are discussed. Published by Elsevier Inc.

Clinical Utility of Exercise Training in Heart Failure with Reduced and Preserved Ejection Fraction

PubMed Central

Asrar Ul Haq, Muhammad; Goh, Cheng Yee; Levinger, Itamar; Wong, Chiew; Hare, David L

2015-01-01

Reduced exercise tolerance is an independent predictor of hospital readmission and mortality in patients with heart failure (HF). Exercise training for HF patients is well established as an adjunct therapy, and there is sufficient evidence to support the favorable role of exercise training programs for HF patients over and above the optimal medical therapy. Some of the documented benefits include improved functional capacity, quality of life (QoL), fatigue, and dyspnea. Major trials to assess exercise training in HF have, however, focused on heart failure with reduced ejection fraction (HFREF). At least half of the patients presenting with HF have heart failure with preserved ejection fraction (HFPEF) and experience similar symptoms of exercise intolerance, dyspnea, and early fatigue, and similar mortality risk and rehospitalization rates. The role of exercise training in the management of HFPEF remains less clear. This article provides a brief overview of pathophysiology of reduced exercise tolerance in HFREF and heart failure with preserved ejection fraction (HFPEF), and summarizes the evidence and mechanisms by which exercise training can improve symptoms and HF. Clinical and practical aspects of exercise training prescription are also discussed. PMID:25698883

Left ventricular systolic function in sickle cell anaemia: an echocardiographic evaluation in adult Nigerian patients.

PubMed

Ejim, Emmanuel; Oguanobi, Nelson

2016-09-01

Reliable diagnostic measures for the evaluation of left ventricular systolic performance in the setting of altered myocardial loading characteristics in sickle cell anaemia remains unresolved. The study was designed to assess left ventricular systolic function in adult sickle cell patients using non-invasive endsystolic stress - end-systolic volume index ratio. A descriptive cross sectional comparative study was done using 52 patients recruited at the adult sickle cell anaemia clinic of the University of Nigeria Teaching Hospital Enugu. An equal number of age and sex-matched healthy volunteers served as controls. All the participants had haematocrit estimation, haemoglobin electrophoresis, as well as echocardiographic evaluation. The mean age of the patients and controls were 23.93 ± 5.28 (range 18-42) and 24.17 ± 4.39 (range 19 -42) years respectively, (t = 0.262; p= .794). No significant difference was seen in estimate of fractional shortening, and ejection fraction. The cardiac out-put, cardiac index and velocity of circumferential shortening were all significantly increased in the cases compared with the controls. The end systolic stress - end systolic volume index ratio (ESS/ESVI) was significantly lower in cases than controls. There were strong positive correlation between the ejection phase indices (ejection fraction and fractional shortening) and end systolic stress and ESS/ESVI. The study findings suggest the presence of left ventricular systolic dysfunction in adult sickle cell anaemia. This is best detected using the loading-pressures independent force-length relationship expressed in ESS/ESVI ratio.

Foundations of Pharmacotherapy for Heart Failure With Reduced Ejection Fraction: Evidence Meets Practice, Part I.

PubMed

Paul, Sara; Page, Robert L

2016-01-01

Pharmacologic treatment for systolic heart failure, otherwise known as heart failure with reduced ejection fraction, has been established through clinical trials and is formulated into guidelines to standardize the diagnosis and treatment. The premise of pharmacologic therapy in heart failure with reduced ejection fraction is aimed primarily at interrupting the neurohormonal cascade that is responsible for altering left ventricular shape and function. This is the first in a series of articles to describe the pharmacologic agents in the guidelines that impact the morbidity and mortality associated with heart failure. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and vasodilators will be presented in the context of the mechanism of action in heart failure, investigational trials that showed beneficial effects, and the practical application for clinical use.

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.

Afterload mismatch in aortic and mitral valve disease: implications for surgical therapy.

PubMed

Ross, J

1985-04-01

In the management of patients with valvular heart disease, an understanding of the effects of altered loading conditions on the left ventricle is important in reaching a proper decision concerning the timing of corrective operation. In acquired valvular aortic stenosis, concentric hypertrophy generally maintains left ventricular chamber size and ejection fraction within normal limits, but in late stage disease function can deteriorate as preload reserve is lost and aortic stenosis progresses. In this setting, even when the ejection fraction is markedly reduced (less than 25%), it can improve to normal after aortic valve replacement, suggesting that afterload mismatch rather than irreversibly depressed myocardial contractility was responsible for left ventricular failure. Therefore, patients with severe aortic stenosis and symptoms should not be denied operation because of impaired cardiac function. In chronic severe aortic and mitral regurgitation, operation is generally recommended when symptoms are present, but whether to recommend operation to prevent irreversible myocardial damage in patients with few or no symptoms has remained controversial. In aortic regurgitation, left ventricular function generally improves postoperatively, even if it is moderately impaired preoperatively, indicating correction of afterload mismatch. Most such patients can be carefully followed by echocardiography. However, in some patients, severe left ventricular dysfunction fails to improve postoperatively. Therefore, when echocardiographic studies in the patient with severe aortic regurgitation show an ejection fraction of less than 40% (fractional shortening less than 25%) plus enlarging left ventricular end-diastolic diameter (approaching 38 mm/m2 body surface area) and end-systolic diameter (approaching 50 mm or 26 mm/m2), confirmation of these findings by cardiac catheterization and consideration of operation are advisable even in patients with minimal symptoms. In chronic mitral regurgitation, maintenance of a normal ejection fraction can mask depressed myocardial contractility. Pre- and postoperative studies in such patients have shown a poor clinical result after mitral valve replacement, associated with a sharp decrease in the ejection fraction after operation. This response appears to reflect unmasking of decreased myocardial contractility by mitral valve replacement, with ejection of the total stroke volume into the high impedance of the aorta (afterload mismatch produced by operation).(ABSTRACT TRUNCATED AT 400 WORDS)

Biomarker Profiles of Acute Heart Failure Patients With a Mid-Range Ejection Fraction.

PubMed

Tromp, Jasper; Khan, Mohsin A F; Mentz, Robert J; O'Connor, Christopher M; Metra, Marco; Dittrich, Howard C; Ponikowski, Piotr; Teerlink, John R; Cotter, Gad; Davison, Beth; Cleland, John G F; Givertz, Michael M; Bloomfield, Daniel M; Van Veldhuisen, Dirk J; Hillege, Hans L; Voors, Adriaan A; van der Meer, Peter

2017-07-01

In this study, the authors used biomarker profiles to characterize differences between patients with acute heart failure with a midrange ejection fraction (HFmrEF) and compare them with patients with a reduced (heart failure with a reduced ejection fraction [HFrEF]) and preserved (heart failure with a preserved ejection fraction [HFpEF]) ejection fraction. Limited data are available on biomarker profiles in acute HFmrEF. A panel of 37 biomarkers from different pathophysiological domains (e.g., myocardial stretch, inflammation, angiogenesis, oxidative stress, hematopoiesis) were measured at admission and after 24 h in 843 acute heart failure patients from the PROTECT trial. HFpEF was defined as left ventricular ejection fraction (LVEF) of ≥50% (n = 108), HFrEF as LVEF of <40% (n = 607), and HFmrEF as LVEF of 40% to 49% (n = 128). Hemoglobin and brain natriuretic peptide levels (300 pg/ml [HFpEF]; 397 pg/ml [HFmrEF]; 521 pg/ml [HFrEF]; p trend  <0.001) showed an upward trend with decreasing LVEF. Network analysis showed that in HFrEF interactions between biomarkers were mostly related to cardiac stretch, whereas in HFpEF, biomarker interactions were mostly related to inflammation. In HFmrEF, biomarker interactions were both related to inflammation and cardiac stretch. In HFpEF and HFmrEF (but not in HFrEF), remodeling markers at admission and changes in levels of inflammatory markers across the first 24 h were predictive for all-cause mortality and rehospitalization at 60 days (p interaction  <0.05). Biomarker profiles in patients with acute HFrEF were mainly related to cardiac stretch and in HFpEF related to inflammation. Patients with HFmrEF showed an intermediate biomarker profile with biomarker interactions between both cardiac stretch and inflammation markers. (PROTECT-1: A Study of the Selective A1 Adenosine Receptor Antagonist KW-3902 for Patients Hospitalized With Acute HF and Volume Overload to Assess Treatment Effect on Congestion and Renal Function; NCT00328692). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Prognostic Value of Right Ventricular Dysfunction in Heart Failure With Reduced Ejection Fraction: Superiority of Longitudinal Strain Over Tricuspid Annular Plane Systolic Excursion.

PubMed

Carluccio, Erberto; Biagioli, Paolo; Alunni, Gianfranco; Murrone, Adriano; Zuchi, Cinzia; Coiro, Stefano; Riccini, Clara; Mengoni, Anna; D'Antonio, Antonella; Ambrosio, Giuseppe

2018-01-01

In heart failure (HF) with reduced ejection fraction, right ventricular (RV) impairment, as defined by reduced tricuspid annular plane systolic excursion, is a predictor of poor outcome. However, peak longitudinal strain of RV free wall (RVFWS) has been recently proposed as a more accurate and sensitive tool to evaluate RV function. Accordingly, we investigated whether RVFWS could help refine prognosis of patients with HF with reduced ejection fraction in whom tricuspid annular plane systolic excursion is still preserved. A total of 200 patients with HF with reduced ejection fraction (age, 66±11 years; ejection fraction, 30±7%) with preserved tricuspid annular plane systolic excursion (>16 mm) underwent RV function assessment using speckle-tracking echocardiography to measure peak RVFWS. After a median follow-up period of 28 months, 62 (31%) patients reached the primary composite end point of all-cause death/HF rehospitalization. Median RVFWS was -19.3% (interquartile range, -23.3% to -15.0%). By lasso-penalized Cox-hazard model, RVFWS was an independent predictor of outcome, along with Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure-HF score, Echo-HF score, and severe mitral regurgitation. The best cutoff value of RVFWS for prediction of outcome was -15.3% (area under the curve, 0.68; P <0.001; sensitivity, 50%; specificity, 80%). In 50 patients (25%), RVFWS was impaired (ie, ≥-15.3%); event rate (per 100 patients per year) was greater in them than in patients with RVFWS <-15.3% (29.5% [95% confidence interval, 20.4-42.7] versus 9.4% [95% confidence interval, 6.7-13.1]; P <0.001). RVFWS yielded a significant net reclassification improvement (0.584 at 3 years; P <0.001), with 68% of nonevents correctly reclassified. In patients with HF with reduced ejection fraction with preserved tricuspid annular plane systolic excursion, RV free-wall strain provides incremental prognostic information and improved risk stratification. © 2018 American Heart Association, Inc.

Dynamic characteristic mechanism of atrial septal defect using real-time three-dimensional echocardiography and evaluation of right ventricular functions.

PubMed

Sharen, Gao-Wa; Zhang, Jun; Qin, Chuan; Lv, Qing

2017-02-01

The dynamic characteristics of the area of the atrial septal defect (ASD) were evaluated using the technique of real-time three-dimensional echocardiography (RT 3DE), the potential factors responsible for the dynamic characteristics of the area of ASD were observed, and the overall and local volume and functions of the patients with ASD were measured. RT 3DE was performed on the 27 normal controls and 28 patients with ASD. Based on the three-dimensional data workstations, the area of ASD was measured at P wave vertex, R wave vertex, T wave starting point, and T wave terminal point and in the T-P section. The right atrial volume in the same time phase of the cardiac cycle and the motion displacement distance of the tricuspid annulus in the corresponding period were measured. The measured value of the area of ASD was analyzed. The changes in the right atrial volume and the motion displacement distance of the tricuspid annulus in the normal control group and the ASD group were compared. The right ventricular ejection fractions in the normal control group and the ASD group were compared using the RT 3DE long-axis eight-plane (LA 8-plane) method. Real-time three-dimensional volume imaging was performed in the normal control group and ASD group (n=30). The right ventricular inflow tract, outflow tract, cardiac apex muscular trabecula dilatation, end-systolic volume, overall dilatation, end-systolic volume, and appropriate local and overall ejection fractions in both two groups were measured with the four-dimensional right ventricular quantitative analysis method (4D RVQ) and compared. The overall right ventricular volume and the ejection fraction measured by the LA 8-plane method and 4D RVQ were subjected to a related analysis. Dynamic changes occurred to the area of ASD in the cardiac cycle. The rules for dynamic changes in the area of ASD and the rules for changes in the right atrial volume in the cardiac cycle were consistent. The maximum value of the changes in the right atrial volume occurred in the end-systolic period when the peak of the curve appeared. The minimum value of the changes occurred in the end-systolic period and was located at the lowest point of the volume variation curve. The area variation curve for ASD and the motion variation curve for the tricuspid annulus in the cardiac cycle were the same. The displacement of the tricuspid annulus exhibited directionality. The measured values of the area of ASD at P wave vertex, R wave vertex, T wave starting point, T wave terminal point and in the T-P section were properly correlated with the right atrial volume (P<0.001). The area of ASD and the motion displacement distance of the tricuspid annulus were negatively correlated (P<0.05). The right atrial volumes in the ASD group in the cardiac cycle in various time phases increased significantly as compared with those in the normal control group (P=0.0001). The motion displacement distance of the tricuspid annulus decreased significantly in the ASD group as compared with that in the normal control group (P=0.043). The right ventricular ejection fraction in the ASD group was lower than that in the normal control group (P=0.032). The ejection fraction of the cardiac apex trabecula of the ASD patients was significantly lower than the ejection fractions of the right ventricular outflow tract and inflow tract and overall ejection fraction. The difference was statistically significant (P=0.005). The right ventricular local and overall dilatation and end-systolic volumes in the ASD group increased significantly as compared with those in the normal control group (P=0.031). The aRVEF and the overall ejection fraction decreased in the ASD group as compared with those in the normal control group (P=0.0005). The dynamic changes in the area of ASD and the motion curves for the right atrial volume and tricuspid annulus have the same dynamic characteristics. RT 3DE can be used to accurately evaluate the local and overall volume and functions of the right ventricle. The local and overall volume loads of the right ventricle in the ASD patients increase significantly as compared with those of the normal people. The right ventricular cardiac apex and the overall systolic function decrease.

Metabolic support for the heart: complementary therapy for heart failure?

PubMed

Heggermont, Ward A; Papageorgiou, Anna-Pia; Heymans, Stephane; van Bilsen, Marc

2016-12-01

The failing heart has an increased metabolic demand and at the same time suffers from impaired energy efficiency, which is a detrimental combination. Therefore, therapies targeting the energy-deprived failing heart and rewiring cardiac metabolism are of great potential, but are lacking in daily clinical practice. Metabolic impairment in heart failure patients has been well characterized for patients with reduced ejection fraction, and is coming of age in patients with 'preserved' ejection fraction. Targeting cardiomyocyte metabolism in heart failure could complement current heart failure treatments that do improve cardiovascular haemodynamics, but not the energetic status of the heart. In this review, we discuss the hallmarks of normal cardiac metabolism, typical metabolic disturbances in heart failure, and past and present therapeutic targets that impact on cardiac metabolism. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

Two-dimensional speckle-tracking strain echocardiography in long-term heart transplant patients: a study comparing deformation parameters and ejection fraction derived from echocardiography and multislice computed tomography.

PubMed

Syeda, Bonni; Höfer, Peter; Pichler, Philipp; Vertesich, Markus; Bergler-Klein, Jutta; Roedler, Susanne; Mahr, Stephane; Goliasch, Georg; Zuckermann, Andreas; Binder, Thomas

2011-07-01

Longitudinal strain determined by speckle tracking is a sensitive parameter to detect systolic left ventricular dysfunction. In this study, we assessed regional and global longitudinal strain values in long-term heart transplants and compared deformation indices with ejection fraction as determined by transthoracic echocardiography (TTE) and multislice computed tomographic coronary angiography (MSCTA). TTE and MSCTA were prospectively performed in 31 transplant patients (10.6 years post-transplantation) and in 42 control subjects. Grey-scale apical views were recorded for speckle tracking (EchoPAC 7.0, GE) of the 16 segments of the left ventricle. The presence of coronary artery disease (CAD) was assessed by MSCTA. Strain analysis was performed in 1168 segments [496 in transplant patients (42.5%), 672 in control subjects (57.7%)]. Global longitudinal peak systolic strain was significantly lower in the transplant recipients than in the healthy population (-13.9 ± 4.2 vs. -17.4 ± 5.8%, P< 0.01). This was still the case after exclusion of the nine transplant patients with CAD (-14.1 ± 4.4 vs. -17.4 ± 5.8%, P=0.03). Transplant patients exhibited significantly lower regional strain values in 9 of the 16 segments. Left ventricular ejection fraction (%) (MSCTA/Simpsons method) was 60.7 ± 10.1%/60.2 ± 6.7% in transplant recipients vs. 64.7 ± 6.4%/63.0 ± 6.2% in the healthy population, P=ns. Even though 'healthy' heart transplants without CAD exhibit normal ejection fraction, deformation indices are reduced in this population when compared with control subjects. Our findings suggests that strain analysis is more sensitive than assessment of ejection fraction for the detection of abnormalities of systolic function.

Usefulness of ambulatory radionuclide monitoring of left ventricular function early after acute myocardial infarction for predicting residual myocardial ischemia

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

Breisblatt, W.M.; Weiland, F.L.; McLain, J.R.

1988-11-15

Ambulatory radionuclide monitoring of left ventricular function was performed with the nuclear Vest device in 35 patients early after acute myocardial infarction. Patients were evaluated during post-infarction treadmill, other activities that included mental stress and cold pressor challenge, and with stress thallium imaging and cardiac catheterization. Of the 35 patients evaluated, 14 had ischemic responses on treadmill testing and 21 had negative responses. By contrast, 20 had redistribution by thallium imaging suggesting ischemia. Vest studies demonstrated 56 responses suggestive of ischemia in 23 patients. Twenty-two occurred during exercise and 13 with mental stress. Seventy-five percent were silent and only 39%more » had associated electrocardiographic changes. Vest responses were compared in patients whose thallium scan was indicative of ischemia (thallium-positive) and those without ischemia (thallium-negative). Ejection fraction was higher in the thallium-positive group (0.52 +/- 0.11), as compared with thallium-negative patients (0.44 +/- 0.1). With exercise, ejection fraction decreased for the thallium-positive patients from 0.52 +/- 0.11 to 0.40 +/- 0.09 at peak exercise. For thallium-negative patients, ejection fraction changes were not significant. During mental stress, ejection fraction decreased from 0.51 +/- 0.11 to 0.45 +/- 0.12 for thallium-positive patients while thallium-negative patients were unchanged. Vest-measured decreases in ejection fraction of greater than or equal to 5 units during exercise were highly sensitive (90%), specific (73%) and predictive (82%) of a positive thallium scan. The same response for mental stress was specific (87%) and predictive (85%) of a positive scan result.« less

Continuous on-line monitoring of left ventricular function with a new nonimaging detector:validation and clinical use in the evaluation of patients post angioplasty.

PubMed

Breisblatt, W M; Schulman, D S; Follansbee, W P

1991-06-01

A new miniaturized nonimaging radionuclide detector (Cardioscint, Oxford, England) was evaluated for the continuous on-line assessment of left ventricular function. This cesium iodide probe can be placed on the patient's chest and can be interfaced to an IBM compatible personal computer conveniently placed at the patient's bedside. This system can provide a beat-to-beat or gated determination of left ventricular ejection fraction and ST segment analysis. In 28 patients this miniaturized probe was correlated against a high resolution gamma camera study. Over a wide range of ejection fraction (31% to 76%) in patients with and without regional wall motion abnormalities, the correlation between the Cardioscint detector and the gamma camera was excellent (r = 0.94, SEE +/- 2.1). This detector system has high temporal (10 msec) resolution, and comparison of peak filling rate (PFR) and time to peak filling (TPFR) also showed close agreement with the gamma camera (PFR, r = 0.94, SEE +/- 0.17; TPFR, r = 0.92, SEE +/- 6.8). In 18 patients on bed rest the long-term stability of this system for measuring ejection fraction and ST segments was verified. During the monitoring period (108 +/- 28 minutes) only minor changes in ejection fraction occurred (coefficient of variation 0.035 +/- 0.016) and ST segment analysis showed no significant change from baseline. To determine whether continuous on-line measurement of ejection fraction would be useful after coronary angioplasty, 12 patients who had undergone a successful procedure were evaluated for 280 +/- 35 minutes with the Cardioscint system.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

Global Longitudinal Strain to Predict Mortality in Patients With Acute Heart Failure.

PubMed

Park, Jin Joo; Park, Jun-Bean; Park, Jae-Hyeong; Cho, Goo-Yeong

2018-05-08

Heart failure (HF) is currently classified according to left ventricular ejection fraction (LVEF); however, the prognostic value of LVEF is controversial. Myocardial strain is a prognostic factor independently of LVEF. The authors sought to evaluate the prognostic value of global longitudinal strain (GLS) in patients with HF. GLS was measured in 4,172 consecutive patients with acute HF. Patients were categorized as either HF with reduced (LVEF <40%), midrange (LVEF 40% to 49%), or preserved ejection fraction (LVEF ≥50%) and were also classified as having mildly (GLS >12.6%), moderately (8.1% < GLS <12.5%), or severely (GLS ≤8.0%) reduced strain. The primary endpoint was 5-year all-cause mortality. Mean GLS was 10.8%, and mean LVEF was 40%. Overall, 1,740 (40.4%) patients had died at 5 years. Patients with reduced ejection fraction had slightly higher mortality than those with midrange or preserved ejection fraction (41%, 38%, and 39%, respectively; log-rank p = 0.031), whereas patients with reduced strain had significantly higher mortality (severely reduced GLS, 49%; moderately reduced GLS, 38%; mildly reduced GLS, 34%; log-rank p < 0.001). In multivariable analysis, each 1% increase in GLS was associated with a 5% decreased risk for mortality (p < 0.001). Patients with moderate (hazard ratio: 1.31; 95% confidence interval: 1.13 to 1.53) and severe GLS reductions (hazard ratio: 1.61; 95% confidence interval: 1.36 to 1.91) had higher mortality, but LVEF was not associated with mortality. In patients with acute HF, GLS has greater prognostic value than LVEF. Therefore, the authors suggest that GLS should be considered as the standard measurement in all patients with HF. This new concept needs validation in further studies. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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.

Effects of angiotensin-neprilysin inhibition compared to angiotensin inhibition on ventricular arrhythmias in reduced ejection fraction patients under continuous remote monitoring of implantable defibrillator devices.

PubMed

de Diego, Carlos; González-Torres, Luis; Núñez, José María; Centurión Inda, Raúl; Martin-Langerwerf, David A; Sangio, Antonio D; Chochowski, Piotr; Casasnovas, Pilar; Blazquéz, Julio C; Almendral, Jesús

2018-03-01

Angiotensin-neprilysin inhibition compared to angiotensin inhibition decreased sudden cardiac death in patients with reduced ejection fraction heart failure (rEFHF). The precise mechanism remains unclear. The purpose of this study was to explore the effect of angiotensin-neprilysin inhibition on ventricular arrhythmias compared to angiotensin inhibition in rEFHF patients with an implantable cardioverter-defibrillator (ICD) and remote monitoring. We prospectively included 120 patients with ICD and (1) New York Heart Association functional class ≥II; (2) left ventricular ejection fraction ≤40%; and (3) remote monitoring. For 9 months, patients received 100% angiotensin inhibition with angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), beta-blockers, and mineraloid antagonist. Subsequently, ACEi or ARB was changed to sacubitril-valsartan in all patients, who were followed for 9 months. Appropriate shocks, nonsustained ventricular tachycardia (NSVT), premature ventricular contraction (PVC) burden, and biventricular pacing percentage were analyzed. Patients were an average age of 69 ± 8 years and had mean left ventricular ejection fraction of 30.4% ± 4% (82% ischemic). Use of beta-blockers (98%), mineraloid antagonist (97%) and antiarrhythmic drugs was similar before and after sacubitril-valsartan. Sacubitril-valsartan significantly decreased NSVT episodes (5.4 ± 0.5 vs 15 ± 1.7 in angiotensin inhibition; P <.002), sustained ventricular tachycardia, and appropriate ICD shocks (0.8% vs 6.7% in angiotensin inhibition; P <.02). PVCs per hour decreased after sacubitril-valsartan (33 ± 12 vs 78 ± 15 in angiotensin inhibition; P <.0003) and was associated with increased biventricular pacing percentage (from 95% ± 6% to 98.8% ± 1.3%; P <.02). Angiotensin-neprilysin inhibition decreased ventricular arrhythmias and appropriate ICD shocks in rEFHF patients under home monitoring compared to angiotensin inhibition. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Cheyne-stokes respiration during wakefulness in patients with chronic heart failure.

PubMed

Grimm, Wolfram; Kesper, Karl; Cassel, Werner; Timmesfeld, Nina; Hildebrandt, Olaf; Koehler, Ulrich

2017-05-01

Cheyne-Stokes respiration (CSR) during sleep has been studied extensively in patients with chronic heart failure (CHF). Prevalence and prognostic significance of CSR during wakefulness in CHF, however, are largely unknown. CSR during wakefulness with an apnea-hypopnea cut-off ≥5/h and moderate to severe CSR with an apnea-hypopnea cutoff ≥15/h were analyzed using polysomnographic recordings in 267 patients with stable CHF with reduced left ventricular (LV) ejection fraction at our institution. Primary endpoint during follow-up was heart transplant-free survival. Fifty of 267 patients (19%) had CSR during wakefulness and 73 of 267 patients (27%) had CSR during sleep. CSR during wakefulness was associated with advanced age, atrial fibrillation, decreased LV ejection fraction, increased LV end-diastolic diameter, brain natriuretic peptide, New York Heart Failure class, and CSR during sleep. During 43 months mean follow-up, 67 patients (25%) died and 4 patients (1%) underwent heart transplantation. Multivariate Cox analysis identified age, male gender, chronic kidney disease, and LV ejection fraction as predictors of reduced transplant-free survival. CSR during wakefulness with an apnea-hypopnea cutoff ≥5/h as well as moderate to severe CSR while awake using an apnea-hypopnea cutoff ≥15/h did not predict reduced transplant-free survival independently from confounding factors. CSR during wakefulness appears to be a marker of heart failure severity.

The safety of sacubitril-valsartan for the treatment of chronic heart failure.

PubMed

Tyler, Jeffrey M; Teerlink, John R

2017-02-01

Sacubitril-valsartan is a combination drug that contains the neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan. In 2015, the US Food and Drug Administration approved sacubitril-valsartan for treatment of heart failure patients with reduced ejection fraction and New York Heart Association class II-IV symptoms following a large, Phase III clinical trial (PARADIGM-HF) that demonstrated a 20% reduction in the combined primary end-point of death from cardiovascular cause or hospitalization for heart failure compared to enalapril. Areas covered: This review discusses the clinical efficacy and safety of angiotensin receptor neprilysin inhibitor sacubitril-valsartan in heart failure with reduced ejection fraction. Expert opinion: Based on the PARADIGM-HF trial, sacubitril-valsartan offers compelling reductions in meaningful clinical endpoints, independent of age or severity of disease. The rate of adverse events was comparable between the enalapril and sacubitril-valsartan groups, although the absolute rates are likely underestimated due to the entry criteria and run-in period. Future trials and post-market surveillance are critical to better understand the risk of angioedema in high risk populations, particularly African-Americans, as well as long-term theoretical risks including the potential for increased cerebral amyloid plaque deposition with possible development of neurocognitive disease. Current trials are underway to evaluate potential benefit in patients with heart failure with preserved ejection fraction.

Correlation of transforming growth factor-β1 and tumour necrosis factor levels with left ventricular function in Chagas disease.

PubMed

Curvo, Eduardo Ov; Ferreira, Roberto R; Madeira, Fabiana S; Alves, Gabriel F; Chambela, Mayara C; Mendes, Veronica G; Sangenis, Luiz Henrique C; Waghabi, Mariana C; Saraiva, Roberto M

2018-02-19

Transforming growth factor β1 (TGF-β1) and tumour necrosis factor (TNF) have been implicated in Chagas disease pathophysiology and may correlate with left ventricular (LV) function. We determined whether TGF-β1 and TNF serum levels correlate with LV systolic and diastolic functions and brain natriuretic peptide (BNP) serum levels in chronic Chagas disease. This cross-sectional study included 152 patients with Chagas disease (43% men; 57 ± 12 years old), classified as 53 patients with indeterminate form and 99 patients with cardiac form (stage A: 24, stage B: 25, stage C: 44, stage D: 6). TGF-β1, TNF, and BNP were determined by enzyme-linked immunosorbent assay ELISA. Echocardiogram was used to determine left atrial and LV diameters, as well as LV ejection fraction and diastolic function. TGF-b1 serum levels were lower in stages B, C, and D, while TNF serum levels were higher in stages C and D of the cardiac form. TGF-β1 presented a weak correlation with LV diastolic function and LV ejection fraction. TNF presented a weak correlation with left atrial and LV diameters and LV ejection fraction. TNF is increased, while TGF-β1 is decreased in the cardiac form of chronic Chagas disease. TNF and TGF-β1 serum levels present a weak correlation with LV systolic and diastolic function in Chagas disease patients.

Effects of increased left ventricular wall thickness on the myocardium in severe aortic stenosis with normal left ventricular ejection fraction: Two- and three-dimensional multilayer speckle tracking echocardiography.

PubMed

Cho, Eun Jeong; Park, Sung-Ji; Kim, Eun Kyoung; Lee, Ga Yeon; Chang, Sung-A; Choi, Jin-Oh; Lee, Sang-Chol; Park, Seung Woo

2017-04-01

The aim of this study was to determine the capability of real time three-dimensional echocardiography (RT3DE) and two-dimensional (2D) multilayer speckle tracking echocardiography (MSTE) for evaluation of early myocardial dysfunction triggered by increased left ventricular (LV) wall thickness in severe aortic stenosis (AS) with normal LV ejection fraction (EF≥55%). Conventional, RT3D STE and 2D MSTE were performed in 45 patients (mean 68.9±9.0 years) with severe AS (aortic valve area <1 cm 2 , aortic velocity Vmax >4 m/s or mean PG >40 mm Hg) and normal left ventricular ejection fraction (LVEF) without overt coronary artery disease and in 18 age-, sex-matched healthy controls. Global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) were calculated using RT3DE and MSTE. The severe AS group had lower 3D GLS, GRS, GAS and 2D epicardium, and mid-wall and endocardium GLS compared to healthy controls. In MSTE analysis, 2D LS and CS values decreased from the endocardial layer toward the epicardial layer. Severe AS patients with increased LV wall thickness had lower 3D GLS and 2D epicardium, and mid-wall and endocardium GLS compared with severe AS patients without LV wall thickening. GLS on RT3D STE was correlated with GLS on 2D MSTE, left ventricular mass index, LVEF, left atrial volume index, and lnNT-proBNP. RT3DE and 2D MSTE can be used to identify subtle contractile dysfunction triggered by increased LV wall thickness in severe AS with normal LVEF. Therefore, RT3D STE and 2D MSTE may provide additional information that can facilitate decision-making regarding severe AS patients with increased LV wall thickness and normal LV function. © 2017, Wiley Periodicals, Inc.

Activation of apoptotic processes during transition from hypertrophy to heart failure in guinea pigs.

PubMed

Sharma, A K; Dhingra, S; Khaper, N; Singal, P K

2007-09-01

Changes in oxidative stress and apoptotic process were studied during the progression of a compensated hypertrophy to a decompensated heart failure in guinea pigs. Banding of the ascending aorta resulted in heart hypertrophy. At 10 wk, ventricle-to-body weight ratio and thickness of the interventricular septum as well as the left ventricular wall were increased significantly. Although fractional shortening and ejection fraction were decreased, there were no signs of heart failure. Furthermore, there was no increase in wet-to-dry weight ratios for the lungs and liver at this stage. However, at 20 wk, heart failure was characterized by a significant depression in heart function as indicated by a decrease in fractional shortening, and ejection fraction and a lesser increase in wall thickness from diastole to systole. Animals also showed clinical signs of heart failure, and the wet-to-dry weight ratios of the lungs and liver were significantly higher. Cardiomyocyte oxidative stress was significantly higher in the 20-wk aortic-banded group. The ratio of Bax to Bcl-xl showed an increase at 10 wk, and there was a further increase at 20 wk. Mitochondrial membrane potential in the aortic-banded animals was significantly decreased at 10 and 20 wk. Cytochrome c levels were higher in the cytosol compared with the mitochondria, leading to a considerable increase in the expression of p17 subunit of caspase-3. At 20 wk, both early and late stages of apoptosis were observed in isolated cardiomyocytes. It is suggested that an increase in oxidative stress initiates mitochondrial death pathway during the hypertrophic stage, leading to apoptosis and heart failure at a later stage.

Unique strain history during ejection in canine left ventricle.

PubMed

Douglas, A S; Rodriguez, E K; O'Dell, W; Hunter, W C

1991-05-01

Understanding the relationship between structure and function in the heart requires a knowledge of the connection between the local behavior of the myocardium (e.g., shortening) and the pumping action of the left ventricle. We asked the question, how do changes in preload and afterload affect the relationship between local myocardial deformation and ventricular volume? To study this, a set of small radiopaque beads was implanted in approximately 1 cm3 of the isolated canine heart left ventricular free wall. Using biplane cineradiography, we tracked the motion of these markers through various cardiac cycles (controlling pre- and afterload) using the relative motion of six markers to quantify the local three dimensional Lagrangian strain. Two different reference states (used to define the strains) were considered. First, we used the configuration of the heart at end diastole for that particular cardiac cycle to define the individual strains (which gave the local "shortening fraction") and the ejection fraction. Second, we used a single reference state for all cardiac cycles i.e., the end-diastolic state at maximum volume, to define absolute strains (which gave local fractional length) and the volume fraction. The individual strain versus ejection fraction trajectories were dependent on preload and afterload. For any one heart, however, each component of absolute strain was more tightly correlated to volume fraction. Around each linear regression, the individual measurements of absolute strain scattered with standard errors that averaged less than 7% of their range. Thus the canine hearts examined had a preferred kinematic (shape) history during ejection, different from the kinematics of filling and independent or pre-or afterload and of stroke volume.

Effects of gonadectomy and hormonal replacement on rat hearts.

PubMed

Scheuer, J; Malhotra, A; Schaible, T F; Capasso, J

1987-07-01

To evaluate the effects of sex hormones on heart function and biochemistry, gonadectomy (GX) was performed in postpubertal male (M) and female (F) rats and compared with sham-operated controls (SH). The groups were MSH; MGX; MGX replaced with testosterone 3 mg/day s.c. (MGX + T), FSH, and FGX replaced with estrogen 2 mg/day (FGX + E), progesterone 0.4 mg/day (FGX + P), estrogen and progesterone (FGX + EP), or testosterone 2 mg/day (FGX + T). Body weight was decreased in MGX and was decreased further in MGX + T. Heart weight was decreased in both MGX and MGX + T. Body weights were increased in FGX and FTX + P and were increased further in FGX + T but were normal in FGX + E and FGX + EP. Heart weights were unchanged in F groups except in FGX + T, where it was increased. Cardiac performance in perfused hearts, as measured by stroke work, ejection fraction, fractional shortening and mean velocity of circumferential fiber shortening, was decreased in MGX but was slightly increased in MGX + T. Papillary muscle studies showed increases in time to peak tension and one-half relaxation in MGX, but these were decreased in MGX + T. Isotonic shortening studies showed decreased velocity of shortening in MGX and increased velocity in MGX + T. Heart function was significantly decreased in FGX and FGX + P compared with FSH but was similar to FSH in FGX + E and FGX + EP. FGX + T had greater stroke work and ejection fraction than FSH and FGX.(ABSTRACT TRUNCATED AT 250 WORDS)

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

Bostroem, P.A.

In order to evaluate the therapeutic effects of metoprolol, nifedipine, and their combination, 11 patients with secondary angina pectoris and with thallium tomographic findings indicating coronary artery disease were studied before and after these three treatment regimes in a single-blind cross-over study. The therapeutic effect was measured by standardized working test and isotope angiocardiography, which enabled evaluation of left ventricular ejection fraction, stroke volume, and phase analysis of left ventricular contraction. Treatment with metoprolol and combination therapy increased work performance. Ejection fraction did not differentiate the treatment regimes, whereas stroke volume was significantly lower at work and heart rate highermore » at rest and at work during nifedipine treatment compared to either metoprolol or combination treatment (p less than 0.05). Cardiac output was significantly reduced during nifedipine and metoprolol treatment during work (p less than 0.05). Phase improved after all therapeutic regimes, but reached significance only during the metoprolol treatment period at rest (p less than 0.05).« less

Temporal Fourier analysis applied to equilibrium radionuclide cineangiography. Importance in the study of global and regional left ventricular wall motion.

PubMed

Cardot, J C; Berthout, P; Verdenet, J; Bidet, A; Faivre, R; Bassand, J P; Bidet, R; Maurat, J P

1982-01-01

Regional and global left ventricular wall motion was assessed in 120 patients using radionuclide cineangiography (RCA) and contrast angiography. Functional imaging procedures based on a temporal Fourier analysis of dynamic image sequences were applied to the study of cardiac contractility. Two images were constructed by taking the phase and amplitude values of the first harmonic in the Fourier transform for each pixel. These two images aided in determining the perimeter of the left ventricle to calculate the global ejection fraction. Regional left ventricular wall motion was studied by analyzing the phase value and by examining the distribution histogram of these values. The accuracy of global ejection fraction calculation was improved by the Fourier technique. This technique increased the sensitivity of RCA for determining segmental abnormalities especially in the left anterior oblique view (LAO).

Spironolactone in cardiovascular disease: an expanding universe?

PubMed

Funder, John W

2017-01-01

Spironolactone has been marketed for over half a century as a 'potassium-sparing diuretic', used primarily in patients with ascites. With the realization that primary aldosteronism is the most common (5-13%) form of secondary hypertension, it has become widely used as a mineralocorticoid receptor antagonist. More recently, in the wake of the RALES trial, spironolactone in addition to standard therapy has been shown to be very beneficial in heart failure with a reduced ejection fraction. Despite the failure of the TOPCAT trial, spironolactone is being increasingly used in diastolic heart failure (i.e. with a preserved ejection fraction). The third currently accepted role for spironolactone is in hypertension resistant to three conventional antihypertensives including a diuretic, where it has been proven to be effective, in contra-distinction to renal artery denervation. Finally, brief consideration will be given to 'areas in waiting' - pulmonary hypertension/fibrosis, cancer - where spironolactone may play very useful roles.

Doppler-derived myocardial performance index in patients with impaired left ventricular relaxation and preserved systolic function.

PubMed

Fernandes, José Maria G; Rivera, Ivan Romero; de Oliveira Romão, Benício; Mendonça, Maria Alayde; Vasconcelos, Miriam Lira Castro; Carvalho, Antônio Carlos; Campos, Orlando; De Paola, Angelo Amato V; Moisés, Valdir A

2009-09-01

The Doppler-derived myocardial performance index (MPI) has been used in the evaluation of left ventricular (LV) function in several diseases. In patients with isolated diastolic dysfunction, the diagnostic utility of this index remains unclear. The aim of this study was to determine the diagnostic utility of MPI in patients with systemic hypertension, impaired LV relaxation, and normal ejection fraction. Thirty hypertensive patients with impaired LV relaxation were compared to 30 control subjects. MPI and its components, isovolumetric relaxation time (IRT), isovolumetric contraction time (ICT), and the ejection time (ET), were measured from LV outflow and mitral inflow Doppler velocity profiles. MPI was higher in patients than in control subjects (0.45 +/- 0.13 vs 0.37 +/- 0.07 P < 0.0029). The increase in MPI was due to the prolongation of IRT without significant change of ICT and ET. MPI cutoff value of > or =0.40 identified impaired LV relaxation with a sensitivity of 63% and specificity of 70% while an IRT >94 ms had a sensitivity of 67% and specificity of 80%. Multivariate analysis identified relative wall thickness, mitral early filling wave velocity (E), and systolic myocardial velocity (Sm) as independent predictors of MPI in patients with hypertension. MPI was increase in patients with hypertension, diastolic dysfunction, and normal ejection fraction but was not superior to IRT to detect impaired LV relaxation.

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.

Predictors of heart failure in patients with stable coronary artery disease: a PEACE study.

PubMed

Lewis, Eldrin F; Solomon, Scott D; Jablonski, Kathleen A; Rice, Madeline Murguia; Clemenza, Francesco; Hsia, Judith; Maggioni, Aldo P; Zabalgoitia, Miguel; Huynh, Thao; Cuddy, Thomas E; Gersh, Bernard J; Rouleau, Jean; Braunwald, Eugene; Pfeffer, Marc A

2009-05-01

Heart failure (HF) is a disease commonly associated with coronary artery disease. Most risk models for HF development have focused on patients with acute myocardial infarction. The Prevention of Events with Angiotensin-Converting Enzyme Inhibition population enabled the development of a risk model to predict HF in patients with stable coronary artery disease and preserved ejection fraction. In the 8290, Prevention of Events with Angiotensin-Converting Enzyme Inhibition patients without preexisting HF, new-onset HF hospitalizations, and fatal HF were assessed over a median follow-up of 4.8 years. Covariates were evaluated and maintained in the Cox regression multivariable model using backward selection if P<0.05. A risk score was developed and converted to an integer-based scoring system. Among the Prevention of Events with Angiotensin-Converting Enzyme Inhibition population (age, 64+/-8; female, 18%; prior myocardial infarction, 55%), there were 268 cases of fatal and nonfatal HF. Twelve characteristics were associated with increased risk of HF along with several baseline medications, including older age, history of hypertension, and diabetes. Randomization to trandolapril independently reduced the risk of HF. There was no interaction between trandolapril treatment and other risk factors for HF. The risk score (range, 0 to 21) demonstrated excellent discriminatory power (c-statistic 0.80). Risk of HF ranged from 1.75% in patients with a risk score of 0% to 33% in patients with risk score >or=16. Among patients with stable coronary artery disease and preserved ejection fraction, traditional and newer factors were independently associated with increased risk of HF. Trandolopril decreased the risk of HF in these patients with preserved ejection fraction.

Heart rate and outcome in heart failure with reduced ejection fraction: Differences between atrial fibrillation and sinus rhythm-A CIBIS II analysis.

PubMed

Mulder, Bart A; Damman, Kevin; Van Veldhuisen, Dirk J; Van Gelder, Isabelle C; Rienstra, Michiel

2017-09-01

Heart rate has been associated with prognosis in patients with heart failure with reduced ejection fraction (HFREF) and sinus rhythm; whether this also holds true in patients with atrial fibrillation (AF) is unknown. To evaluate cardiac rhythm and baseline heart rate and the influence of outcome in patients with HFREF enrolled in the Cardiac Insufficiency Bisoprolol Study II. In total, 2539 patients were stratified according to their baseline heart rhythm (AF or sinus rhythm) and into quartiles of heart rate (≤70 bpm, 71-78 bpm, 79-90 bpm, and >90 bpm). The primary outcome was all-cause mortality. Mean follow-up was 1.3 years. Mean age was 61 years, mean left ventricular ejection fraction was 28%, and 80% were male. A total of 521 (21%) patients had AF at baseline. The risk associated with all-cause mortality for each 5 bpm increase in heart rate in patients with sinus rhythm (hazard ratio [HR]: 1.06, 95% confidence interval [CI]: 1.01-1.11, P = 0.012) was significantly different from those with AF (HR: 1.00, 95% CI: 0.94-1.07, P = 0.90, P for interaction = 0.041). The risk associated with higher heart rate in sinus rhythm was primarily attributable to excess risk in the highest quartile (HR: 1.64, 95% CI: 1.18-2.30, P = 0.003). Allocation to bisoprolol did not modify the interaction between heart rate, rhythm and outcome. In HFREF patients with AF, a higher heart rate is not associated with increased event rates in contrast to HFREF patients with sinus rhythm. © 2017 Wiley Periodicals, Inc.

Effects of an Isolated Complete Right Bundle Branch Block on Mechanical Ventricular Function.

PubMed

Zhang, Qin; Xue, Minghua; Li, Zhan; Wang, Haiyan; Zhu, Lei; Liu, Xinling; Meng, Haiyan; Hou, Yinglong

2015-12-01

The purpose of this study was to investigate the effects of an isolated complete right bundle branch block on mechanical ventricular function. Two groups of participants were enrolled in this study: a block group, consisting of 98 patients with isolated complete right bundle branch blocks without structural heart disease, and a control group, consisting of 92 healthy adults. The diameter, end-diastolic area, end-systolic area, and right ventricular (RV) fractional area change were obtained to evaluate morphologic and systolic function by 2-dimensional sonographic technology. Systolic and diastolic velocities and time interval parameters were measured to assess mechanical ventricular performance using pulsed wave tissue Doppler imaging. Although there was no significant difference in the RV fractional area change between the patients with blocks and controls, the diameter, end-diastolic area, and end-systolic area of the RV were significantly larger in the patients with blocks (P < .05). In the patients with blocks, the peak velocities during systole and early diastole and the ratio of the peak velocities during early and late diastole decreased. The block group had a prolonged pre-ejection period, electromechanical delay time, and isovolumic relaxation time, a decreased ejection time, and an increased pre-ejection period/ejection time ratio, and the myocardial performance index (Tei index) at the basal RV lateral wall was significantly increased. There were no significant differences in any echocardiographic parameters at different sites of the left ventricle. In patients with isolated complete right bundle branch blocks, systolic and diastolic functions are impaired in the RV, and follow-up is needed. © 2015 by the American Institute of Ultrasound in Medicine.

The effect of renin-angiotensin system inhibitors on mortality and heart failure hospitalization in patients with heart failure and preserved ejection fraction: a systematic review and meta-analysis.

PubMed

Shah, Ravi V; Desai, Akshay S; Givertz, Michael M

2010-03-01

Although renin-angiotensin system (RAS) inhibitors have little demonstrable effect on mortality in patients with heart failure and preserved ejection fraction (HF-PEF), some trials have suggested a benefit with regard to reduction in HF hospitalization. Here, we systematically review and evaluate prospective clinical studies of RAS inhibitors enrolling patients with HF-PEF, including the 3 major trials of RAS inhibition (Candesartan in Patients with Chronic Heart Failure and Preserved Left Ventricular Ejection Fraction [CHARM-Preserved], Irbesartan in Patients with Heart Failure and Preserved Ejection Fraction [I-PRESERVE], and Perindopril in Elderly People with Chronic Heart Failure [PEP-CHF]). We also conducted a pooled analysis of 8021 patients in the 3 major randomized trials of RAS inhibition in HF-PEF (CHARM-Preserved, I-PRESERVE, and PEP-CHF) in fixed-effect models, finding no clear benefit with regard to all-cause mortality (odds ratio [OR] 1.03, 95% confidence interval [CI], 0.92-1.15; P=.62), or HF hospitalization (OR 0.90, 95% CI 0.80-1.02; P=.09). Although RAS inhibition may be valuable in the management of comorbidities related to HF-PEF, RAS inhibition in HF-PEF is not associated with consistent reduction in HF hospitalization or mortality in this emerging cohort. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Benefits and Harms of Sacubitril in Adults With Heart Failure and Reduced Left Ventricular Ejection Fraction.

PubMed

Aronow, Wilbert S; Shamliyan, Tatyana A

2017-10-01

The quality of evidence regarding patient-centered outcomes in adults with heart failure (HF) after sacubitril combined with valsartan has not been systematically appraised. We searched 4 databases in February 2017 and graded the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation working group approach. We reviewed 1 meta-analysis and multiple publications of 2 randomized controlled trials (RCT) and 1 unpublished RCT. In adults with HF and reduced ejection fraction, low-quality evidence from 1 RCT of 8,432 patients suggests that sacubitril combined with valsartan reduces all-cause (number needed to treat [NNT] to prevent 1 event [NNTp] = 35) and cardiovascular mortality (NNTp = 32), hospitalization (NNTp = 11), emergency visits (NNTp = 69), and serious adverse effects, leading to treatment discontinuation (NNTp = 63) and improves quality of life when compared with enalapril. In adults with HF and preserved ejection fraction, very low-quality evidence from 1 RCT of 301 patients suggests that there are no differences in mortality, morbidity, or adverse effects between sacubitril combined with valsartan and valsartan alone. In conclusion, in adults with HF and reduced ejection fraction, to reduce cardiovascular mortality and hospitalizations and improve quality of life, clinicians may recommend sacubitril combined with valsartan over angiotensin-converting enzyme inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

On the hypothesis of hyperimpact-induced ejection of asteroid-size bodies from Earth-type planets.

NASA Astrophysics Data System (ADS)

Drobyshevski, E. M.

During the last two decades a number of facts have brought to life a seemingly fantastic idea of ejection of large rocky fragments from planets into space, like for example SNC meteorites or many-km-size fragments of Vesta. The theoretical description of impact processes of this ejection lags behind. Considerable efforts have been spent to show the possibility of ejection of bodies several meters in size from large impact craters on Mars. In general, the possibility of impact self-destruction of inner planets may drastically alter traditional models of the origin of the Solar System. However, non-destructive gasdynamic ejection of large fragments from planets requires a mechanism for fast conversion of shock-wave energy into heat. The extrapolation of data from laboratory impact experiments (≡10 kJ) and nuclear explosions (<1 Mt TNT) in order to describe hyperimpact processes with 105 - 106 Mt TNT energies can hardly be justified, that is why these calculations give relatively small gas production and, consequently, small velocities of fragment ejection from impact craters. It is predicted that at such energies some instabilities may lead to formation of new dissipation channels, that would increase the part of the overheated gas fraction in the hyperimpact ejection products. This would eliminate numerous contradictions in the impact history of planets, asteroids, meteorites etc.

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).

Left atrial ejection force predicts the outcome after catheter ablation for paroxysmal atrial fibrillation.

PubMed

Kishima, Hideyuki; Mine, Takanao; Takahashi, Satoshi; Ashida, Kenki; Ishihara, Masaharu; Masuyama, Tohru

2018-02-01

Left atrium (LA) systolic dysfunction is observed in the early stages of atrial fibrillation (AF) prior to LA anatomical change. We investigated whether LA systolic dysfunction predicts recurrent AF after catheter ablation (CA) in patients with paroxysmal AF. We studied 106 patients who underwent CA for paroxysmal AF. LA systolic function was assessed with the LA emptying volume = Maximum LA volume (LAV max ) - Minimum LA volume (LAV min ), LA emptying fraction = [(LAV max - LAV min )/LAV max ] × 100, and LA ejection force calculated with Manning's method [LA ejection force = (0.5 × ρ × mitral valve area × A 2 )], where ρ is the blood density and A is the late-diastolic mitral inflow velocity. Recurrent AF was detected in 35/106 (33%) during 14.6 ± 9.1 months. Univariate analysis revealed reduced LA ejection force, decreased LA emptying fraction, larger LA diameter, and elevated brain natriuretic peptide as significant variables. On multivariate analysis, reduced LA ejection force and larger LA diameter were independently associated with recurrent AF. Moreover, patients with reduced LA ejection force and larger LA diameter had a higher risk of recurrent AF than preserved LA ejection force (log-rank P = 0.0004). Reduced LA ejection force and larger LA diameter were associated with poor outcome after CA for paroxysmal AF, and could be a new index to predict recurrent AF. © 2017 Wiley Periodicals, Inc.

Natural history and outcome of aortic stenosis diagnosed prenatally.

PubMed Central

Simpson, J. M.; Sharland, G. K.

1997-01-01

OBJECTIVE: To document the growth of the left heart structures and outcome of fetuses with aortic stenosis. DESIGN: Retrospective echocardiographic and clinical study. SETTING: Tertiary centre for fetal cardiology. PATIENTS: 27 consecutive fetuses with aortic stenosis. MAIN OUTCOME MEASURES: Survival of affected fetuses. Measurement of left ventricular end diastolic volume (LVEDV), aortic root diameter, and ejection fraction. RESULTS: Before 25 weeks' gestation, the LVEDV was normal or increased in all cases. In six of eight fetuses studied sequentially, the LVEDV fell across normal centiles. Initial ejection fraction was reduced in 23 fetuses (88%). Before 28 weeks' gestation, the aortic root was normal in all but one case, but after 29 weeks, 11 of 13 fetuses had values below the 50th centile. In two fetuses prenatal aortic valvoplasty was attempted, 10 babies had postnatal interventions, and there were six survivors. Biventricular repair was attempted in eight cases, of whom five survived. A first stage Norwood operation was performed in three babies, of whom one survived. The four fetuses with the highest aortic root z scores had successful biventricular repair. The two fetuses with initially normal ejection fractions survived. Successful biventricular repair was achieved even where the LVEDV was below the 5th centile. CONCLUSIONS: In aortic stenosis diagnosed prenatally, failure of growth of the left ventricle and aortic root often occurs. The outcome of affected fetuses is better than previously reported. Prenatal echocardiography may assist selection of suitable candidates for biventricular versus Norwood repair. Images PMID:9093035

Correlation of transforming growth factor-β1 and tumour necrosis factor levels with left ventricular function in Chagas disease

PubMed Central

Curvo, Eduardo OV; Ferreira, Roberto R; Madeira, Fabiana S; Alves, Gabriel F; Chambela, Mayara C; Mendes, Veronica G; Sangenis, Luiz Henrique C; Waghabi, Mariana C; Saraiva, Roberto M

2018-01-01

BACKGROUND Transforming growth factor β1 (TGF-β1) and tumour necrosis factor (TNF) have been implicated in Chagas disease pathophysiology and may correlate with left ventricular (LV) function. OBJECTIVES We determined whether TGF-β1 and TNF serum levels correlate with LV systolic and diastolic functions and brain natriuretic peptide (BNP) serum levels in chronic Chagas disease. METHODS This cross-sectional study included 152 patients with Chagas disease (43% men; 57 ± 12 years old), classified as 53 patients with indeterminate form and 99 patients with cardiac form (stage A: 24, stage B: 25, stage C: 44, stage D: 6). TGF-β1, TNF, and BNP were determined by enzyme-linked immunosorbent assay ELISA. Echocardiogram was used to determine left atrial and LV diameters, as well as LV ejection fraction and diastolic function. FINDINGS TGF-b1 serum levels were lower in stages B, C, and D, while TNF serum levels were higher in stages C and D of the cardiac form. TGF-β1 presented a weak correlation with LV diastolic function and LV ejection fraction. TNF presented a weak correlation with left atrial and LV diameters and LV ejection fraction. CONCLUSIONS TNF is increased, while TGF-β1 is decreased in the cardiac form of chronic Chagas disease. TNF and TGF-β1 serum levels present a weak correlation with LV systolic and diastolic function in Chagas disease patients. PMID:29513876

Sleep Apnea and Left Atrial Phasic Function in Heart Failure With Reduced Ejection Fraction.

PubMed

Haruki, Nobuhiko; Tsang, Wendy; Thavendiranathan, Paaladinesh; Woo, Anna; Tomlinson, George; Logan, Alexander G; Bradley, T Douglas; Floras, John S

2016-12-01

The study aim was to determine whether phasic left atrial (LA) function of patients with heart failure with reduced ejection fraction differs between those with obstructive sleep apnea (OSA) and central sleep apnea (CSA). Participation in the Adaptive Servo Ventilation for Therapy of Sleep Apnea in Heart Failure (ADVENT-HF) trial requires 2-dimensional echocardiographic documentation of left ventricular ejection fraction ≤ 45% and a polysomnographic apnea hypopnea index (AHI) ≥ 15 events per hour. Of initial enrollees, we identified 132 patients in sinus rhythm (82 with predominantly OSA and 50 with CSA). To determine LA reservoir (expansion index; EI), conduit (passive emptying index; PEI), and booster function (active emptying index), we blindly quantified maximum and minimum LA volume and LA volume before atrial contraction. Each of EI (P = 0.004), PEI (P < 0.001), and active emptying index (P = 0.045) was less in participants with CSA compared with those with OSA, whereas average left ventricular ejection fraction and LA and left ventricular volumes were similar. Multivariable analysis identified an independent relationship between central AHI and LA EI (P = 0.040) and PEI (P = 0.005). In contrast, the obstructive AHI was unrelated to any LA phasic index, and slopes relating central AHI to EI and PEI differed significantly from corresponding relationships with obstructive AHI (P = 0.018; P = 0.006). In these ADVENT-HF patients with heart failure with reduced ejection fraction, all 3 components of LA phasic function (reservoir, conduit, and contractile) were significantly reduced in those with CSA compared with participants with OSA. The severity of CSA, but not OSA associated inversely and independently with LA reservoir and conduit function. Impaired LA phasic function might be consequent to or could exacerbate CSA. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Cardiac cycle-dependent left atrial dynamics: implications for catheter ablation of atrial fibrillation.

PubMed

Patel, Amit R; Fatemi, Omid; Norton, Patrick T; West, J Jason; Helms, Adam S; Kramer, Christopher M; Ferguson, John D

2008-06-01

Left atrial (LA) volume determines prognosis and response to therapy for atrial fibrillation. Integration of electroanatomic maps with three-dimensional images rendered from computed tomography and magnetic resonance imaging (MRI) is used to facilitate atrial fibrillation ablation. The purpose of this study was to measure LA volume changes and regional motion during the cardiac cycle that might affect the accuracy of image integration and to determine their relationship to standard LA volume measurements. MRI was performed in 30 patients with paroxysmal atrial fibrillation. LA time-volume curves were generated and used to divide LA ejection fraction into pumping ejection fraction and conduit ejection fraction and to determine maximum LA volume (LA(max)) and preatrial contraction volume. LA volume was measured using an MRI angiogram and traditional geometric models from echocardiography (area-length model and ellipsoid model). In-plane displacement of the pulmonary veins, anterior left atrium, mitral annulus, and LA appendage was measured. LA(max) was 107 +/- 36 mL and occurred at 42% +/- 5% of the R-R interval. Preatrial contraction volume was 86 +/- 34 mL and occurred at 81% +/- 4% of the R-R interval. LA ejection fraction was 45% +/- 10%, and pumping ejection fraction was 31% +/- 10%. LA volume measurements made from MRI angiogram, area-length model, and ellipsoid model underestimated LA(max) by 21 +/- 25 mL, 16 +/- 26 mL, and 35 +/- 22 mL, respectively. Anterior LA, mitral annulus, and LA appendage were significantly displaced during the cardiac cycle (8.8 +/- 2.0 mm, 13.2 +/- 3.8 mm, and 10.2 +/- 3.4 mm, respectively); the pulmonary veins were not displaced. LA volume changes significantly during the cardiac cycle, and substantial regional variation in LA motion exists. Standard measurements of LA volume significantly underestimate LA(max) compared to the gold standard measure of three-dimensional volumetrics.

Flow-gradient patterns in severe aortic stenosis with preserved ejection fraction: clinical characteristics and predictors of survival.

PubMed

Eleid, Mackram F; Sorajja, Paul; Michelena, Hector I; Malouf, Joseph F; Scott, Christopher G; Pellikka, Patricia A

2013-10-15

Among patients with severe aortic stenosis (AS) and preserved ejection fraction, those with low gradient (LG) and reduced stroke volume may have an adverse prognosis. We investigated the prognostic impact of stroke volume using the recently proposed flow-gradient classification. We examined 1704 consecutive patients with severe AS (aortic valve area <1.0 cm(2)) and preserved ejection fraction (≥50%) using 2-dimensional and Doppler echocardiography. Patients were stratified by stroke volume index (<35 mL/m(2) [low flow, LF] versus ≥35 mL/m(2) [normal flow, NF]) and aortic gradient (<40 mm Hg [LG] versus ≥40 mm Hg [high gradient, HG]) into 4 groups: NF/HG, NF/LG, LF/HG, and LF/LG. NF/LG (n=352, 21%), was associated with favorable survival with medical management (2-year estimate, 82% versus 67% in NF/HG; P<0.0001). LF/LG severe AS (n=53, 3%) was characterized by lower ejection fraction, more prevalent atrial fibrillation and heart failure, reduced arterial compliance, and reduced survival (2-year estimate, 60% versus 82% in NF/HG; P<0.001). In multivariable analysis, the LF/LG pattern was the strongest predictor of mortality (hazard ratio, 3.26; 95% confidence interval, 1.71-6.22; P<0.001 versus NF/LG). Aortic valve replacement was associated with a 69% mortality reduction (hazard ratio, 0.31; 95% confidence interval, 0.25-0.39; P<0.0001) in LF/LG and NF/HG, with no survival benefit associated with aortic valve replacement in NF/LG and LF/HG. NF/LG severe AS with preserved ejection fraction exhibits favorable survival with medical management, and the impact of aortic valve replacement on survival was neutral. LF/LG severe AS is characterized by a high prevalence of atrial fibrillation, heart failure, and reduced survival, and aortic valve replacement was associated with improved survival. These findings have implications for the evaluation and subsequent management of AS severity.

Gender influences sphincter of Oddi response to cholecystokinin in the prairie dog.

PubMed

Tierney, S; Qian, Z; Yung, B; Lipsett, P A; Pitt, H A; Sostre, S; Lillemoe, K D

1995-10-01

Although gallstones and disorders of biliary tract motility are both more common in women than men, sphincter of Oddi motility has not previously been compared between the sexes. In this study, cholescintigraphy (under ketamine and diazepam anesthesia) was used to determine gallbladder emptying rate and ejection fraction in response to cholecystokinin (CCK) in eight male and six female prairie dogs fed a nonlithogenic diet. Ten days later, under alpha-chloralose anesthesia, sphincter of Oddi phasic wave activity was monitored for 10-min intervals before (control), during 20 min of CCK infusion, and for 20 min after infusion. Gallbladder emptying rate and ejection fraction and baseline sphincter of Oddi frequency, amplitude, and motility index (= frequency x amplitude) did not differ significantly between the sexes. Sphincter of Oddi phasic wave frequency was increased during CCK infusion in both males and females, but the change in amplitude was significantly greater in females, than males. We conclude that the increased incidence of biliary tract disease in women may be due to altered sphincter of Oddi hormonal response.

Geographic differences in heart failure trials.

PubMed

Ferreira, João Pedro; Girerd, Nicolas; Rossignol, Patrick; Zannad, Faiez

2015-09-01

Randomized controlled trials (RCTs) are essential to develop advances in heart failure (HF). The need for increasing numbers of patients (without substantial cost increase) and generalization of results led to the disappearance of international boundaries in large RCTs. The significant geographic differences in patients' characteristics, outcomes, and, most importantly, treatment effect observed in HF trials have recently been highlighted. Whether the observed regional discrepancies in HF trials are due to trial-specific issues, patient heterogeneity, structural differences in countries, or a complex interaction between factors are the questions we propose to debate in this review. To do so, we will analyse and review data from HF trials conducted in different world regions, from heart failure with preserved ejection fraction (HF-PEF), heart failure with reduced ejection fraction (HF-REF), and acute heart failure (AHF). Finally, we will suggest objective and actionable measures in order to mitigate regional discrepancies in future trials, particularly in HF-PEF where prognostic modifying treatments are urgently needed and in which trials are more prone to selection bias, due to a larger patient heterogeneity. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Severe Cardiomyopathy after Huffing Dust-Off™

PubMed Central

Cates, Alexis L.; Cook, Matthew D.

2016-01-01

A 34-year-old man was found down in a parking lot after huffing fifteen cans of Dust-Off. Though lucid during the initial hospital evaluation, the patient experienced a generalized seizure followed by a torsades de pointes arrhythmia and was resuscitated. An echocardiogram revealed left and right ventricular dysfunction with an ejection fraction of 25%. This unique outcome of inhalant abuse has scarcely been reported in similar cases. The patient fully recovered and had a normal ejection fraction prior to discharge. PMID:27313914

Echocardiographic Manifestations of Glycogen Storage Disease III: Increase in Wall Thickness and Left Ventricular Mass over Time

PubMed Central

Vertilus, Shawyntee M.; Austin, Stephanie L.; Foster, Kimberly S.; Boyette, Keri E.; Bali, Deeksha; Li, Jennifer S.; Kishnani, Priya S.; Wechsler, Stephanie Burns

2013-01-01

Purpose Glycogen Storage Disease (GSD) type III, glycogen debranching enzyme deficiency, causes accumulation of glycogen in liver, skeletal, and cardiac muscle. Some patients develop increased left ventricular (LV) thickness by echocardiography, but the rate of increase and its significance remain unclear. Methods We evaluated 33 patients with GSD type III, 23 with IIIa and 10 with IIIb, ages 1 month – 55.5 yrs, by echocardiography for wall thickness, LV mass, shortening and ejection fractions, at 1 time point (n = 33) and at 2 time points in patients with more than 1 echocardiogram (13 of the 33). Results Of 23 cross-sectional patients with type IIIa, 12 had elevated LV mass, 11 had elevated wall thickness. One type IIIb patient had elevated LV mass but 4 had elevated wall thickness. For those with multiple observations, 9 of 10 with type IIIa developed increased LV mass over time, with 3 already increased at first measurement. Shortening and ejection fractions were generally normal. Conclusion Elevated LV mass and wall thickness is more common in patients with type IIIa but develops rarely in type IIIb, though ventricular systolic function is preserved. This suggests serial echocardiograms with attention to LV thickness and mass are important for care of these patients. PMID:20526204

Effects of a prostagrandin EP4-receptor agonist ONO-AE1-329 on the left ventricular pressure-volume relationship in the halothane-anesthetized dogs.

PubMed

Honda, Atsushi; Nakamura, Yuji; Ohara, Hiroshi; Cao, Xin; Nomura, Hiroaki; Katagi, Jun; Wada, Takeshi; Izumi-Nakaseko, Hiroko; Ando, Kentaro; Sugiyama, Atsushi

2016-03-15

Cardiac effects of a prostagrandin EP4-receptor agonist ONO-AE1-329 were assessed in the halothane-anesthetized dogs under the monitoring of left ventricular pressure-volume relationship, which were compared with those of clinically recommended doses of dopamine, dobutamine and milrinone (n=4-5 for each treatment). ONO-AE1-329 was intravenously administered in doses of 0.3, 1 and 3 ng/kg/min for 10 min with a pause of 20 min. Dopamine in a dose of 3 µg/kg/min for 10 min, dobutamine in a dose of 1 µg/kg/min for 10 min and milrinone in a dose of 5 µg/kg/min for 10 min followed by 0.5 µg/kg/min for 10 min were intravenously administered. Low dose of ONO-AE1-329 increased the stroke volume. Middle dose of ONO-AE1-329 increased the cardiac output, left ventricular end-diastolic volume, ejection fraction, maximum upstroke/downstroke velocities of the left ventricular pressure and external work, but decreased the end-systolic pressure and internal work besides the change by the low dose. High dose of ONO-AE1-329 increased the heart rate and maximum elastance, but decreased the end-systolic volume besides the changes by the middle dose. Dopamine, dobutamine and milrinone exerted essentially similar cardiac effects to ONO-AE1-329, but they did not significantly change the end-diastolic volume, end-systolic volume, stroke volume, ejection fraction, end-systolic pressure, maximum elastance, external work or internal work. Thus, EP4-receptor stimulation by ONO-AE1-329 may have potential to better promote the passive ventricular filling than the conventional cardiotonic drugs, which could become a candidate of novel therapeutic strategy for the treatment of heart failure with preserved ejection fraction. Copyright © 2016 Elsevier B.V. All rights reserved.

Renin-Angiotensin System Inhibition, Worsening Renal Function, and Outcome in Heart Failure Patients With Reduced and Preserved Ejection Fraction: A Meta-Analysis of Published Study Data.

PubMed

Beldhuis, Iris E; Streng, Koen W; Ter Maaten, Jozine M; Voors, Adriaan A; van der Meer, Peter; Rossignol, Patrick; McMurray, John J V; Damman, Kevin

2017-02-01

Renin-angiotensin aldosterone system (RAAS) inhibitors significantly improve outcome in heart failure (HF) patients with reduced ejection fraction (HFREF), irrespective of the occurrence of worsening renal function (WRF). However, in HF patients with preserved ejection fraction (HFPEF), RAAS inhibitors have not been shown to improve outcome but are still frequently prescribed. Random effect meta-analysis was performed to investigate the relationship between RAAS inhibitor therapy, WRF in both HF phenotypes, and mortality. Studies were selected based on literature search in MEDLNE and included randomized, placebo controlled trials of RAAS inhibitors in chronic HF. The primary outcome consisted of the interaction analysis for the association between RAAS inhibition-induced WRF, HF phenotype and outcome. A total of 8 studies (6 HFREF and 2 HFPEF, including 28 961 patients) were included in our analysis. WRF was more frequent in the RAAS inhibitor group, compared with the placebo group, in both HFREF and HFPEF. In HFREF, WRF induced by RAAS inhibitor therapy was associated with a less increased relative risk of mortality (relative risk, 1.19 (1.08-1.31); P <0.001), compared with WRF induced by placebo (relative risk, 1.48 (1.35-1.62); P <0.001; P for interaction 0.005). In contrast, WRF induced by RAAS inhibitor therapy was strongly associated with worse outcomes in HFPEF (relative risk, 1.78 (1.43-2.21); P <0.001), whereas placebo-induced WRF was not (relative risk, 1.25 (0.88-1.77); P =0.21; P for interaction 0.002). RAAS inhibitors induce renal dysfunction in both HFREF and HFPEF. However, in contrast to patients with HFREF where mortality increase with WRF is small, HFPEF patients with RAAS inhibitor-induced WRF have an increased mortality risk, without experiencing improved outcome with RAAS inhibition. © 2017 American Heart Association, Inc.

Improvement of cardiac function persists long term with medical therapy for left ventricular systolic dysfunction.

PubMed

Chen, David; Chang, Richard; Umakanthan, Branavan; Stoletniy, Liset N; Heywood, J Thomas

2007-09-01

In certain patients with left ventricular (LV) systolic dysfunction, improvements in cardiac function are seen after initiation of medical therapy; however, the long-term stability of ventricular function in such patients is not well described. We retrospectively analyzed 171 patients who had a baseline ejection fraction of 45% or less, a follow-up echocardiogram at 2 to 12 months after initiation of medical therapy, and a final echocardiogram. We found that 48.5% of the patients demonstrated initial improvements in LV function after initiation of medical therapy, and the improvements appear to be sustained (88% of patients) at 44 +/- 21 months follow-up. A nonischemic etiology and younger age were the only independent predictors of change of LV ejection fraction of 10 or more at a mean 8.4 +/- 3.4 months after optimal medical therapy. Our study revealed a trend toward improved long-term survival in individuals with an early improvement in LV ejection fraction with medical therapy, especially in those with sustained improvement.

Ventricular dysfunction in children with obstructive sleep apnea: radionuclide assessment

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

Tal, A.; Leiberman, A.; Margulis, G.

Ventricular function was evaluated using radionuclide ventriculography in 27 children with oropharyngeal obstruction and clinical features of obstructive sleep apnea. Their mean age was 3.5 years (9 months to 7.5 years). Conventional clinical assessment did not detect cardiac involvement in 25 of 27 children; however, reduced right ventricular ejection fraction (less than 35%) was found in 10 (37%) patients (mean: 19.5 +/- 2.3% SE, range: 8-28%). In 18 patients wall motion abnormality was detected. In 11 children in whom radionuclide ventriculography was performed before and after adenotonsillectomy, right ventricular ejection fraction rose from 24.4 +/- 3.6% to 46.7 +/- 3.4%more » (P less than 0.005), and in all cases wall motion showed a definite improvement. In five children, left ventricular ejection fraction rose greater than 10% after removal of oropharyngeal obstruction. It is concluded that right ventricular function may be compromised in children with obstructive sleep apnea secondary to adenotonsillar hypertrophy, even before clinical signs of cardiac involvement are present.« less

Patient Selection in Heart Failure With Preserved Ejection Fraction Clinical Trials

PubMed Central

Kelly, Jacob P.; Mentz, Robert J.; Mebazaa, Alexandre; Voors, Adriaan A.; Butler, Javed; Roessig, Lothar; Fiuzat, Mona; Zannad, Faiez; Pitt, Bertram; O’Connor, Christopher M.; Lam, Carolyn S.P.

2015-01-01

Recent clinical trials in patients with heart failure with preserved ejection fraction (HFpEF) have provided important insights into participant selection strategies. Historically, HFpEF trials have included patients with relatively preserved left ventricular ejection fraction ranging from 40% to 55% and a clinical history of heart failure. Contemporary HFpEF trials have also incorporated inclusion criteria such as hospitalization for HFpEF, altered functional capacity, cardiac structural and functional abnormalities, and abnormalities in neurohormonal status (e.g., elevated natriuretic peptide levels). Careful analyses of the impact of these patient selection criteria on outcomes in prior trials provide valuable lessons for future trial design. We review recent and ongoing HFpEF clinical trials from a patient selection perspective and appraise trial patient selection methodologies in relation to outcomes. This review reflects discussions between clinicians, scientists, trialists, regulators, and regulatory representatives at the 10th Global CardioVascular Clinical Trialists Forum in Paris, France on December 6, 2013. PMID:25908073

Synergistic Utility of Brain Natriuretic Peptide and Left Ventricular Global Longitudinal Strain in Asymptomatic Patients With Significant Primary Mitral Regurgitation and Preserved Systolic Function Undergoing Mitral Valve Surgery.

PubMed

Alashi, Alaa; Mentias, Amgad; Patel, Krishna; Gillinov, A Marc; Sabik, Joseph F; Popović, Zoran B; Mihaljevic, Tomislav; Suri, Rakesh M; Rodriguez, L Leonardo; Svensson, Lars G; Griffin, Brian P; Desai, Milind Y

2016-07-01

In asymptomatic patients with ≥3+ mitral regurgitation and preserved left ventricular (LV) ejection fraction who underwent mitral valve surgery, we sought to discover whether baseline LV global longitudinal strain (LV-GLS) and brain natriuretic peptide provided incremental prognostic utility. Four hundred and forty-eight asymptomatic patients (61±12 years and 69% men) with ≥3+ primary mitral regurgitation and preserved left ventricular ejection fraction, who underwent mitral valve surgery (92% repair) at our center between 2005 and 2008, were studied. Baseline clinical and echocardiographic data (including LV-GLS using Velocity Vector Imaging, Siemens, PA) were recorded. The Society of Thoracic Surgeons score was calculated. The primary outcome was death. Mean Society of Thoracic Surgeons score, left ventricular ejection fraction, mitral effective regurgitant orifice, indexed LV end-diastolic volume, and right ventricular systolic pressure were 4±1%, 62±3%, 0.55±0.2 cm(2), 58±13 cc/m(2), and 37±15 mm Hg, respectively. Forty-five percent of patients had flail. Median log-transformed BNP and LV-GLS were 4.04 (absolute brain natriuretic peptide: 60 pg/dL) and -20.7%. At 7.7±2 years, death occurred in 41 patients (9%; 0% at 30 days). On Cox analysis, a higher Society of Thoracic Surgeons score (hazard ratio 1.55), higher baseline right ventricular systolic pressure (hazard ratio 1.11), more abnormal LV-GLS (hazard ratio 1.17), and higher median log-transformed BNP (hazard ratio 2.26) were associated with worse longer-term survival (all P<0.01). Addition of LV-GLS and median log-transformed BNP to a clinical model (Society of Thoracic Surgeons score and baseline right ventricular systolic pressure) provided incremental prognostic utility (χ(2) for longer-term mortality increased from 31-47 to 61; P<0.001). In asymptomatic patients with significant primary mitral regurgitation and preserved left ventricular ejection fraction who underwent mitral valve surgery, brain natriuretic peptide and LV-GLS provided synergistic risk stratification, independent of established factors. © 2016 American Heart Association, Inc.

Cost-effectiveness Analysis of Sacubitril/Valsartan vs Enalapril in Patients With Heart Failure and Reduced Ejection Fraction.

PubMed

Gaziano, Thomas A; Fonarow, Gregg C; Claggett, Brian; Chan, Wing W; Deschaseaux-Voinet, Celine; Turner, Stuart J; Rouleau, Jean L; Zile, Michael R; McMurray, John J V; Solomon, Scott D

2016-09-01

The angiotensin receptor neprilysin inhibitor sacubitril/valsartan was associated with a reduction in cardiovascular mortality, all-cause mortality, and hospitalizations compared with enalapril. Sacubitril/valsartan has been approved for use in heart failure (HF) with reduced ejection fraction in the United States and cost has been suggested as 1 factor that will influence the use of this agent. To estimate the cost-effectiveness of sacubitril/valsartan vs enalapril in the United States. Data from US adults (mean [SD] age, 63.8 [11.5] years) with HF with reduced ejection fraction and characteristics similar to those in the PARADIGM-HF trial were used as inputs for a 2-state Markov model simulated HF. Risks of all-cause mortality and hospitalization from HF or other reasons were estimated with a 30-year time horizon. Quality of life was based on trial EQ-5D scores. Hospital costs combined Medicare and private insurance reimbursement rates; medication costs included the wholesale acquisition cost for sacubitril/valsartan and enalapril. A discount rate of 3% was used. Sensitivity analyses were performed on key inputs including: hospital costs, mortality benefit, hazard ratio for hospitalization reduction, drug costs, and quality-of-life estimates. Hospitalizations, quality-adjusted life-years (QALYs), costs, and incremental costs per QALY gained. The 2-state Markov model of US adult patients (mean age, 63.8 years) calculated that there would be 220 fewer hospital admissions per 1000 patients with HF treated with sacubitril/valsartan vs enalapril over 30 years. The incremental costs and QALYs gained with sacubitril/valsartan treatment were estimated at $35 512 and 0.78, respectively, compared with enalapril, equating to an incremental cost-effectiveness ratio (ICER) of $45 017 per QALY for the base-case. Sensitivity analyses demonstrated ICERs ranging from $35 357 to $75 301 per QALY. For eligible patients with HF with reduced ejection fraction, the Markov model calculated that sacubitril/valsartan would increase life expectancy at an ICER consistent with other high-value accepted cardiovascular interventions. Sensitivity analyses demonstrated sacubitril/valsartan would remain cost-effective vs enalapril.

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.

Heart failure hospitalization in women with signs and symptoms of ischemia: A report from the women's ischemia syndrome evaluation study.

PubMed

Bakir, May; Nelson, Michael D; Jones, Erika; Li, Quanlin; Wei, Janet; Sharif, Behzad; Minissian, Margo; Shufelt, Chrisandra; Sopko, George; Pepine, Carl J; Merz, C Noel Bairey

2016-11-15

Women with signs and symptoms of ischemia, no obstructive coronary artery disease, and preserved left ventricular ejection fraction enrolled in the National Heart Lung and Blood Institute (NHLBI) sponsored Women's Ischemia Syndrome Evaluation (WISE) study have an unexpectedly high rate of subsequent heart failure (HF) hospitalization. We sought to verify and characterize the HF hospitalizations. A retrospective chart review was performed on 223 women with signs and symptoms of ischemia, undergoing coronary angiography for suspected coronary artery disease followed for 6±2.6years. Data were collected from a single site in the WISE study. At the time of study enrollment, the women were 57±11years of age, all had preserved left ventricular ejection fraction, and 81 (36%) had obstructive CAD (defined as >50% stenosis in at least one epicardial artery). Among the 223 patients, 25 (11%) reported HF hospitalizations, of which 14/25 (56%) had recurrent HF hospitalizations (>2 hospitalizations). Medical records were available in 13/25 (52%) women. Left ventricular ejection fraction was measured in all verified cases and was found to be preserved in 12/13 (92%). HF hospitalization was not related to obstructive CAD. Among women with signs and symptoms of ischemia undergoing coronary angiography for suspected obstructive CAD, HF hospitalization at 6-year follow-up was predominantly characterized by a preserved ejection fraction and not associated with obstructive CAD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effect of inorganic nitrate on exercise capacity in heart failure with preserved ejection fraction.

PubMed

Zamani, Payman; Rawat, Deepa; Shiva-Kumar, Prithvi; Geraci, Salvatore; Bhuva, Rushik; Konda, Prasad; Doulias, Paschalis-Thomas; Ischiropoulos, Harry; Townsend, Raymond R; Margulies, Kenneth B; Cappola, Thomas P; Poole, David C; Chirinos, Julio A

2015-01-27

Inorganic nitrate (NO3(-)), abundant in certain vegetables, is converted to nitrite by bacteria in the oral cavity. Nitrite can be converted to nitric oxide in the setting of hypoxia. We tested the hypothesis that NO3(-) supplementation improves exercise capacity in heart failure with preserved ejection fraction via specific adaptations to exercise. Seventeen subjects participated in this randomized, double-blind, crossover study comparing a single dose of NO3-rich beetroot juice (NO3(-), 12.9 mmol) with an identical nitrate-depleted placebo. Subjects performed supine-cycle maximal-effort cardiopulmonary exercise tests, with measurements of cardiac output and skeletal muscle oxygenation. We also assessed skeletal muscle oxidative function. Study end points included exercise efficiency (total work/total oxygen consumed), peak VO2, total work performed, vasodilatory reserve, forearm mitochondrial oxidative function, and augmentation index (a marker of arterial wave reflections, measured via radial arterial tonometry). Supplementation increased plasma nitric oxide metabolites (median, 326 versus 10 μmol/L; P=0.0003), peak VO2 (12.6±3.7 versus 11.6±3.1 mL O2·min(-1)·kg(-1); P=0.005), and total work performed (55.6±35.3 versus 49.2±28.9 kJ; P=0.04). However, efficiency was unchanged. NO3(-) led to greater reductions in systemic vascular resistance (-42.4±16.6% versus -31.8±20.3%; P=0.03) and increases in cardiac output (121.2±59.9% versus 88.7±53.3%; P=0.006) with exercise. NO3(-) reduced aortic augmentation index (132.2±16.7% versus 141.4±21.9%; P=0.03) and tended to improve mitochondrial oxidative function. NO3(-) increased exercise capacity in heart failure with preserved ejection fraction by targeting peripheral abnormalities. Efficiency did not change as a result of parallel increases in total work and VO2. NO3(-) increased exercise vasodilatory and cardiac output reserves. NO3(-) also reduced arterial wave reflections, which are linked to left ventricular diastolic dysfunction and remodeling. www.clinicaltrials.gov. Unique identifier: NCT01919177. © 2014 American Heart Association, Inc.

Plasma Biomarkers Reflecting Profibrotic Processes in Heart Failure With a Preserved Ejection Fraction: Data From the Prospective Comparison of ARNI With ARB on Management of Heart Failure With Preserved Ejection Fraction Study.

PubMed

Zile, Michael R; Jhund, Pardeep S; Baicu, Catalin F; Claggett, Brian L; Pieske, Burkert; Voors, Adriaan A; Prescott, Margaret F; Shi, Victor; Lefkowitz, Martin; McMurray, John J V; Solomon, Scott D

2016-01-01

Heart failure with preserved ejection fraction is a clinical syndrome that has been associated with changes in the extracellular matrix. The purpose of this study was to determine whether profibrotic biomarkers accurately reflect the presence and severity of disease and underlying pathophysiology and modify response to therapy in patients with heart failure with preserved ejection fraction. Four biomarkers, soluble form of ST2 (an interleukin-1 receptor family member), galectin-3, matrix metalloproteinase-2, and collagen III N-terminal propeptide were measured in the Prospective Comparison of ARNI With ARB on Management of Heart Failure With Preserved Ejection Fraction (PARAMOUNT) trial at baseline, 12 and 36 weeks after randomization to valsartan or LCZ696. We examined the relationship between baseline biomarkers, demographic and echocardiographic characteristics, change in primary (change in N-terminal pro B-type natriuretic peptide) and secondary (change in left atrial volume) end points. The median (interquartile range) value for soluble form of ST2 (33 [24.6-48.1] ng/mL) and galectin 3 (17.8 [14.1-22.8] ng/mL) were higher, and for matrix metalloproteinase-2 (188 [155.5-230.6] ng/mL) lower, than in previously published referent controls; collagen III N-terminal propeptide (5.6 [4.3-6.9] ng/mL) was similar to referent control values. All 4 biomarkers correlated with severity of disease as indicated by N-terminal pro B-type natriuretic peptide, E/E', and left atrial volume. Baseline biomarkers did not modify the response to LCZ696 for lowering N-terminal pro B-type natriuretic peptide; however, left atrial volume reduction varied by baseline level of soluble form of ST2 and galectin 3; patients with values less than the observed median (<33 ng/mL soluble form of ST2 and <17.8 ng/mL galectin 3) had reduction in left atrial volume, those above median did not. Although LCZ696 reduced N-terminal pro B-type natriuretic peptide, levels of the other 4 biomarkers were not affected over time. In patients with heart failure with preserved ejection fraction, biomarkers that reflect collagen homeostasis correlated with the presence and severity of disease and underlying pathophysiology, and may modify the structural response to treatment. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00887588. © 2016 American Heart Association, Inc.

Composition of Coronal Mass Ejections

NASA Technical Reports Server (NTRS)

Zurbuchen, T. H.; Weberg, M.; von Steiger, R.; Mewaldt, R. A.; Lepri, S. T.; Antiochos, S. K.

2016-01-01

We analyze the physical origin of plasmas that are ejected from the solar corona. To address this issue, we perform a comprehensive analysis of the elemental composition of interplanetary coronal mass ejections (ICMEs) using recently released elemental composition data for Fe, Mg, Si, S, C, N, Ne, and He as compared to O and H. We find that ICMEs exhibit a systematic abundance increase of elements with first ionization potential (FIP) less than 10 electronvolts, as well as a significant increase of Ne as compared to quasi-stationary solar wind. ICME plasmas have a stronger FIP effect than slow wind, which indicates either that an FIP process is active during the ICME ejection or that a different type of solar plasma is injected into ICMEs. The observed FIP fractionation is largest during times when the Fe ionic charge states are elevated above Q (sub Fe) is greater than 12.0. For ICMEs with elevated charge states, the FIP effect is enhanced by 70 percent over that of the slow wind. We argue that the compositionally hot parts of ICMEs are active region loops that do not normally have access to the heliosphere through the processes that give rise to solar wind. We also discuss the implications of this result for solar energetic particles accelerated during solar eruptions and for the origin of the slow wind itself.

Composition of Coronal Mass Ejections

NASA Astrophysics Data System (ADS)

Zurbuchen, T. H.; Weberg, M.; von Steiger, R.; Mewaldt, R. A.; Lepri, S. T.; Antiochos, S. K.

2016-07-01

We analyze the physical origin of plasmas that are ejected from the solar corona. To address this issue, we perform a comprehensive analysis of the elemental composition of interplanetary coronal mass ejections (ICMEs) using recently released elemental composition data for Fe, Mg, Si, S, C, N, Ne, and He as compared to O and H. We find that ICMEs exhibit a systematic abundance increase of elements with first ionization potential (FIP) < 10 eV, as well as a significant increase of Ne as compared to quasi-stationary solar wind. ICME plasmas have a stronger FIP effect than slow wind, which indicates either that an FIP process is active during the ICME ejection or that a different type of solar plasma is injected into ICMEs. The observed FIP fractionation is largest during times when the Fe ionic charge states are elevated above Q Fe > 12.0. For ICMEs with elevated charge states, the FIP effect is enhanced by 70% over that of the slow wind. We argue that the compositionally hot parts of ICMEs are active region loops that do not normally have access to the heliosphere through the processes that give rise to solar wind. We also discuss the implications of this result for solar energetic particles accelerated during solar eruptions and for the origin of the slow wind itself.

Plasma lipophilic antioxidants and malondialdehyde in congestive heart failure patients: relationship to disease severity.

PubMed

Polidori, Maria Cristina; Savino, Ketty; Alunni, Gianfranco; Freddio, Michela; Senin, Umberto; Sies, Helmut; Stahl, Wilhelm; Mecocci, Patrizia

2002-01-15

Plasma levels of malondialdehyde (MDA), vitamin A, and of antioxidant micronutrients including vitamin E, lutein, zeaxanthin, beta-cryptoxanthin, lycopene, and alpha- and beta-carotene were measured in 30 patients with class II and III congestive heart failure (CHF) according to the New York Heart Association (NYHA) classification and in 55 controls. Ejection fraction was evaluated by echocardiography in all patients as a measure of the emptying capacity of the heart. Plasma levels of all measured compounds were significantly lower and MDA significantly higher in patients compared to controls (p <.001). Class II NYHA patients showed significantly lower MDA levels and significantly higher levels of vitamin A, vitamin E, lutein, and lycopene than class III patients. Ejection fraction was inversely correlated with MDA levels and directly correlated with vitamin A, vitamin E, lutein, and lycopene levels in patients. The present study supports the concept that an increased consumption of vitamin-rich fruits and vegetables might help in achieving cardiovascular health.

Survival analysis of heart failure patients: A case study.

PubMed

Ahmad, Tanvir; Munir, Assia; Bhatti, Sajjad Haider; Aftab, Muhammad; Raza, Muhammad Ali

2017-01-01

This study was focused on survival analysis of heart failure patients who were admitted to Institute of Cardiology and Allied hospital Faisalabad-Pakistan during April-December (2015). All the patients were aged 40 years or above, having left ventricular systolic dysfunction, belonging to NYHA class III and IV. Cox regression was used to model mortality considering age, ejection fraction, serum creatinine, serum sodium, anemia, platelets, creatinine phosphokinase, blood pressure, gender, diabetes and smoking status as potentially contributing for mortality. Kaplan Meier plot was used to study the general pattern of survival which showed high intensity of mortality in the initial days and then a gradual increase up to the end of study. Martingale residuals were used to assess functional form of variables. Results were validated computing calibration slope and discrimination ability of model via bootstrapping. For graphical prediction of survival probability, a nomogram was constructed. Age, renal dysfunction, blood pressure, ejection fraction and anemia were found as significant risk factors for mortality among heart failure patients.

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

[Catheter ablation of ectopic incessant atrial tachycardia using radiofrequency. Reversion of tachycardiomyopathy].

PubMed

de Paola, A A; Mendonça, A; Balbão, C E; Tavora, M Z; da Silva, R M; Hara, V M; Guiguer Júnior, N; Vattimo, A C; Souza, I A; Portugal, O P

1993-10-01

A 8-year-old female patient with refractory incessant atrial tachycardia, very symptomatic and with left ventricular ejection fraction of 0.25. Electrophysiological study and endocardial mapping localized the site of the origin of atrial tachycardia in the superior right atrium. In this site 2 applications of radiofrequency current (25V, 20 and 50 seconds) resulted in termination of the atrial tachycardia. She was discharged off antiarrhythmic drugs and after 2 months ejection fraction was 0.52. She was completely asymptomatic 6 months after ablation procedure.

Computer-based assessment of left ventricular regional ejection fraction in patients after myocardial infarction

NASA Astrophysics Data System (ADS)

Teo, S.-K.; Su, Y.; Tan, R. S.; Zhong, L.

2014-03-01

After myocardial infarction (MI), the left ventricle (LV) undergoes progressive remodeling which adversely affects heart function and may lead to development of heart failure. There is an escalating need to accurately depict the LV remodeling process for disease surveillance and monitoring of therapeutic efficacy. Current practice of using ejection fraction to quantitate LV function is less than ideal as it obscures regional variation and anomaly. Therefore, we sought to (i) develop a quantitative method to assess LV regional ejection fraction (REF) using a 16-segment method, and (ii) evaluate the effectiveness of REF in discriminating 10 patients 1-3 months after MI and 9 normal control (sex- and agematched) based on cardiac magnetic resonance (CMR) imaging. Late gadolinium enhancement (LGE) CMR scans were also acquired for the MI patients to assess scar extent. We observed that the REF at the basal, mid-cavity and apical regions for the patient group is significantly lower as compared to the control group (P < 0.001 using a 2-tail student t-test). In addition, we correlated the patient REF over these regions with their corresponding LGE score in terms of 4 categories - High LGE, Low LGE, Border and Remote. We observed that the median REF decreases with increasing severity of infarction. The results suggest that REF could potentially be used as a discriminator for MI and employed to measure myocardium homogeneity with respect to degree of infarction. The computational performance per data sample took approximately 25 sec, which demonstrates its clinical potential as a real-time cardiac assessment tool.

Left Ventricular Function Across the Spectrum of Body Mass Index in African Americans: The Jackson Heart Study.

PubMed

Patel, Vivek G; Gupta, Deepak K; Terry, James G; Kabagambe, Edmond K; Wang, Thomas J; Correa, Aldolfo; Griswold, Michael; Taylor, Herman; Carr, John Jeffrey

2017-03-01

This study sought to assess whether body mass index (BMI) was associated with subclinical left ventricular (LV) systolic dysfunction in African-American individuals. Higher BMI is a risk factor for cardiovascular disease, including heart failure. Obesity disproportionately affects African Americans; however, the association between higher BMI and LV function in African Americans is not well understood. Peak systolic circumferential strain (ECC) was measured by tagged cardiac magnetic resonance in 1,652 adult African-American participants of the Jackson Heart Study between 2008 and 2012. We evaluated the association between BMI and ECC in multivariate linear regression and restricted cubic spline analyses adjusted for prevalent cardiovascular disease, conventional cardiovascular risk factors, LV mass, and ejection fraction. In exploratory analyses, we also examined whether inflammation, insulin resistance, or volume of visceral adipose tissue altered the association between BMI and ECC. The proportions of female, nonsmokers, diabetic, and hypertensive participants rose with increase in BMI. In multivariate-adjusted models, higher BMI was associated with worse ECC (β = 0.052; 95% confidence interval: 0.028 to 0.075), even in the setting of preserved LV ejection fraction. Higher BMI was also associated with worse ECC when accounting for markers of inflammation (C-reactive protein, E-selection, and P-selectin), insulin resistance, and volume of visceral adipose tissue. Higher BMI is significantly associated with subclinical LV dysfunction in African Americans, even in the setting of preserved LV ejection fraction. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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

[Baseline characteristics and changes in treatment after a period of optimization of the patients included in the study EFICAR].

PubMed

Gómez-Marcos, Manuel A; Agudo-Conde, Cristina; Torcal, Jesús; Echevarria, Pilar; Domingo, Mar; Arietaleanizbeascoa, María; Sanz-Guinea, Aitor; de la Torre, Maria M; Ramírez, Jose I; García-Ortiz, Luis

2016-03-01

To describe the baseline date and drugs therapy changes during treatment optimization in patients with heart failure with depressed systolic function included in the EFICAR study. Multicenter randomized clinical trial. Seven Health Centers. 150 patients (ICFSD) age 68±10 years, 77% male. Sociodemographic variables, comorbidities (Charlson index), functional capacity and quality of life. Drug therapy optimization was performed. The main etiology was ischemic heart disease (45%), with 89% in functional class II. The Charlson index was 2.03±1.05. The ejection fraction mean was 37%±8, 19% with ejection fraction <30%. With the stress test 6.3±1.6 mean was reached, with the 6 minutes test 446±78 meters and the chair test 13.7±4.4 seconds. The overall quality of life with ejection fraction was 22.8±18.7 and with the Short Form-36 Health Survey, physical health 43.3±8.4 and mental health 50.1±10.6. After optimizing the treatment, the percentage of patients on drugs therapy and the dose of angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists and beta-blockers were not changed. The majority of the subjects are in functional class II, with functional capacity and quality of life decreased and comorbidity index high. A protocolized drug therapy adjustment did not increase the dose or number of patients with effective drugs for heart failure with depressed systolic function. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

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.

Investigation of a continuous heating/cooling technique for cardiac output measurement.

PubMed

Ehlers, K C; Mylrea, K C; Calkins, J M

1987-01-01

Cardiac output is frequently measured to assess patient hemodynamic status in the operating room and intensive care unit. Current research for measuring cardiac output includes continuous sinusoidal heating and synchronous detection of thermal signals. This technique is limited by maximum heating element temperatures and background thermal noise. A continuous heating and cooling technique was investigated in vitro to determine if greater thermal signal magnitudes could be obtained. A fast responding thermistor was employed to measure consecutive ejected temperature plateaus in the thermal signal. A flow bath and mechanical ventricle were used to simulate the cardiovascular system. A thermoelectric module was used to apply heating and cooling energy to the flow stream. Trials encompassing a range of input power, input frequency, and flow rate were conducted. By alternating heating and cooling, thermal signal magnitude can be increased when compared to continuous heating alone. However, the increase was not sufficient to allow for recording in all patients over the expected normal range of cardiac output. Consecutive ejected temperature plateaus were also measured on the thermal signal and ejection fraction calculations were made.

Iron Charge Distribution as an Identifier of Interplanetary Coronal Mass Ejections

NASA Technical Reports Server (NTRS)

Lepri, S. T.; Zurbuchen, T. H.; Fisk, L. A.; Richardson, I. G.; Cane, H. V.; Gloeckler, G.

2001-01-01

We present solar wind Fe charge state data measured on the Advanced Composition Explorer (ACE) from early 1998 to the middle of 2000. Average Fe charge states in the solar wind are typically around 9 to 11. However, deviations from these average charge states occur, including intervals with a large fraction of Fe(sup greater or = 16+) which are consistently associated with interplanetary coronal mass ejections (ICMEs). By studying the Fe charge state distribution we are able to extract coronal electron temperatures often exceeding 2 x 10(exp 6) kelvins. We also discuss the temporal trends of these events, indicating the more frequent appearance of periods with high Fe charge states as solar activity increases.

Fatty-acid oxidation and calcium homeostasis are involved in the rescue of bupivacaine-induced cardiotoxicity by lipid emulsion in rats.

PubMed

Partownavid, Parisa; Umar, Soban; Li, Jingyuan; Rahman, Siamak; Eghbali, Mansoureh

2012-08-01

Lipid emulsion 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 lipid emulsion in rats. We also compared the mitochondrial function and calcium threshold for triggering of mitochondrial permeability transition pore opening in bupivacaine-induced cardiac arrest before and after resuscitation with lipid emulsion. Prospective, randomized animal study. University research laboratory. Adult male Sprague-Dawley rats. Asystole was achieved with a single dose of bupivacaine (10 mg/kg over 20 secs, intravenously) and 20% lipid emulsion infusion (5 mL/kg bolus, and 0.5 mL/kg/min maintenance), and cardiac massage started immediately. The rats in CVT-4325 (CVT) group were pretreated with a single dose of fatty-acid oxidation inhibitor CVT (0.5, 0.25, 0.125, or 0.0625 mg/kg bolus intravenously) 5 mins prior to inducing asystole by bupivacaine overdose. Heart rate, ejection fraction, fractional shortening, the threshold for opening of mitochondrial permeability transition pore, oxygen consumption, and membrane potential were measured. The values are mean ± SEM. Administration of bupivacaine resulted in asystole. Lipid Emulsion infusion improved the cardiac function gradually as the ejection fraction was fully recovered within 5 mins (ejection fraction=64±4% and fractional shortening=36±3%, n=6) and heart rate increased to 239±9 beats/min (71% recovery, n=6) within 10 mins. Lipid emulsion was only able to rescue rats pretreated with low dose of CVT (0.0625 mg/kg; heart rate~181±11 beats/min at 10 mins, recovery of 56%; ejection fraction=50±1%; fractional shortening=26±0.6% at 5 mins, n=3), but was unable to resuscitate rats pretreated with higher doses of CVT (0.5, 0.25, or 0.125 mg/kg). The calcium-retention capacity in response to Ca²⁺ overload was significantly higher in cardiac mitochondria isolated from rats resuscitated with 20% lipid emulsion compared to the group that did not receive Lipid Emulsion after bupivacaine overdose (330±42 nmol/mg vs. 180±8.2 nmol/mg of mitochondrial protein, p<.05, n=3 in each group). The mitochondrial oxidative rate and membrane potential were similar in the bupivacaine group before and after resuscitation with lipid emulsion infusion. Fatty-acid oxidation is required for successful rescue of bupivacaine-induced cardiotoxicity by lipid emulsion. This rescue action is associated with inhibition of mitochondrial permeability transition pore opening.

Plasma bilirubin values on admission and ventricular remodeling after a first anterior ST-segment elevation acute myocardial infarction.

PubMed

Miranda, Berta; Barrabés, José A; Figueras, Jaume; Pineda, Victor; Rodríguez-Palomares, José; Lidón, Rosa-Maria; Sambola, Antonia; Bañeras, Jordi; Otaegui, Imanol; García-Dorado, David

2016-01-01

Bilirubin may elicit cardiovascular protection and heme oxygenase-1 overexpression attenuated post-infarction ventricular remodeling in experimental animals, but the association between bilirubin levels and post-infarction remodeling is unknown. In 145 patients with a first anterior ST-segment elevation acute myocardial infarction (STEMI), we assessed whether plasma bilirubin on admission predicted adverse remodeling (left ventricular end-diastolic volume [LVEDV] increase ≥20% between discharge and 6 months, estimated by magnetic resonance imaging). Patients' baseline characteristics and management were comparable among bilirubin tertiles. LVEDV increased at 6 months (P < 0.001) with respect to the initial exam, but the magnitude of this increase was similar across increasing bilirubin tertiles (10.8 [30.2], 10.1 [22.9], and 12.7 [24.3]%, P = 0.500). Median (25-75 percentile) bilirubin values in patients with and without adverse remodeling were 0.75 (0.60-0.93) and 0.73 (0.60-0.92) mg/dL (P = 0.693). Absence of final TIMI flow grade 3 (odds ratio 3.92, 95% CI 1.12-13.66) and a history of hypertension (2.04, 0.93-4.50), but not admission bilirubin, were independently associated with adverse remodeling. Bilirubin also did not predict the increase in ejection fraction at 6 months. Admission bilirubin values are not related to LVEDV or ejection fraction progression after a first anterior STEMI and do not predict adverse ventricular remodeling. Key messages Bilirubin levels are inversely related to cardiovascular disease, and overexpression of heme oxygenase-1 (the enzyme that determines bilirubin production) has prevented post-infarction ventricular remodeling in experimental animals, but the association between bilirubin levels and the progression of ventricular volumes and function in patients with acute myocardial infarction remained unexplored. In this cohort of patients with a first acute anterior ST-segment elevation myocardial infarction receiving contemporary management, bilirubin levels on admission were not predictive of the changes in left ventricular volumes or ejection fraction at 6 months measured by serial cardiac magnetic resonance imaging. The data are contrary to a significant protective effect of bilirubin against post-infarction ventricular remodeling.

AT1-receptor blockade, but not renin inhibition, reduces aneurysm growth and cardiac failure in fibulin-4 mice.

PubMed

Te Riet, Luuk; van Deel, Elza D; van Thiel, Bibi S; Moltzer, Els; van Vliet, Nicole; Ridwan, Yanto; van Veghel, Richard; van Heijningen, Paula M; Robertus, Jan Lukas; Garrelds, Ingrid M; Vermeij, Marcel; van der Pluijm, Ingrid; Danser, A H Jan; Essers, Jeroen

2016-04-01

Increasing evidence supports a role for the angiotensin II-AT1-receptor axis in aneurysm development. Here, we studied whether counteracting this axis via stimulation of AT2 receptors is beneficial. Such stimulation occurs naturally during AT1-receptor blockade with losartan, but not during renin inhibition with aliskiren. Aneurysmal homozygous fibulin-4 mice, displaying a four-fold reduced fibulin-4 expression, were treated with placebo, losartan, aliskiren, or the β-blocker propranolol from day 35 to 100. Their phenotype includes cystic media degeneration, aortic regurgitation, left ventricular dilation, reduced ejection fraction, and fractional shortening. Although losartan and aliskiren reduced hemodynamic stress and increased renin similarly, only losartan increased survival. Propranolol had no effect. No drug rescued elastic fiber fragmentation in established aneurysms, although losartan did reduce aneurysm size. Losartan also increased ejection fraction, decreased LV diameter, and reduced cardiac pSmad2 signaling. None of these effects were seen with aliskiren or propranolol. Longitudinal micro-CT measurements, a novel method in which each mouse serves as its own control, revealed that losartan reduced LV growth more than aneurysm growth, presumably because the heart profits both from the local (cardiac) effects of losartan and its effects on aortic root remodeling. Losartan, but not aliskiren or propranolol, improved survival in fibulin-4 mice. This most likely relates to its capacity to improve structure and function of both aorta and heart. The absence of this effect during aliskiren treatment, despite a similar degree of blood pressure reduction and renin-angiotensin system blockade, suggests that it might be because of AT2-receptor stimulation.

Implications of the interstellar object 1I/'Oumuamua for planetary dynamics and planetesimal formation

NASA Astrophysics Data System (ADS)

Raymond, Sean N.; Armitage, Philip J.; Veras, Dimitri; Quintana, Elisa V.; Barclay, Thomas

2018-05-01

'Oumuamua, the first bona fide interstellar planetesimal, was discovered passing through our Solar system on a hyperbolic orbit. This object was likely dynamically ejected from an extrasolar planetary system after a series of close encounters with gas giant planets. To account for 'Oumuamua's detection, simple arguments suggest that ˜1 M⊕ of planetesimals are ejected per solar mass of Galactic stars. However, that value assumes mono-sized planetesimals. If the planetesimal mass distribution is instead top-heavy, the inferred mass in interstellar planetesimals increases to an implausibly high value. The tension between theoretical expectations for the planetesimal mass function and the observation of 'Oumuamua can be relieved if a small fraction ({˜ } 0.1-1 {per cent}) of planetesimals are tidally disrupted on the pathway to ejection into 'Oumuamua-sized fragments. Using a large suite of simulations of giant planet dynamics including planetesimals, we confirm that 0.1-1 per cent of planetesimals pass within the tidal disruption radius of a gas giant on their pathway to ejection. 'Oumuamua may thus represent a surviving fragment of a disrupted planetesimal. Finally, we argue that an asteroidal composition is dynamically disfavoured for 'Oumuamua, as asteroidal planetesimals are both less abundant and ejected at a lower efficiency than cometary planetesimals.

Association between sleep-disordered breathing and arterial stiffness in heart failure patients with reduced or preserved ejection fraction.

PubMed

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

2018-06-01

Sleep-disordered breathing (SDB) is associated with arterial stiffness, which may be one of the factors that lead to heart failure (HF). We examined the relationship between pulse wave velocity (PWV) and SDB in patients who have HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). We measured the apnoea-hypopnoea index (AHI) by polysomnography, echocardiographic parameters, and PWV in 221 HF patients. Age, blood pressure, and PWV were higher in HFpEF (ejection fraction > 50%, n = 70) patients than in HFrEF (ejection fraction < 50%, n = 151) patients. All HF patients were divided into three groups according to AHI: none-to-mild SDB group (AHI < 15 times/h, n = 77), moderate SDB group (15 < AHI < 30 times/h, n = 59), and severe SDB group (AHI > 30 times/h, n = 85). Although blood pressure and echocardiographic parameters did not differ among the three groups, PWV was significantly higher in the severe SDB group than in the none-to-mild and moderate SDB groups (P = 0.002). When the HFrEF and HFpEF patients were analysed separately, PWV was significantly higher in the severe SDB group than in the none-to-mild and moderate SDB groups in patients with HFpEF (P = 0.002), but not in those with HFrEF (P = 0.068). In the multiple regression analysis to determine PWV, the presence of severe SDB was found to be an independent predictor of high PWV in HFpEF (β = 0.234, P = 0.005), but not in HFrEF patients. Severe SDB is associated with elevated arterial stiffness and may be related to the pathophysiology of HF, especially in HFpEF patients. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Submaximal oxygen uptake kinetics, functional mobility, and physical activity in older adults with heart failure and reduced ejection fraction

PubMed Central

Hummel, Scott L; Herald, John; Alpert, Craig; Gretebeck, Kimberlee A; Champoux, Wendy S; Dengel, Donald R; Vaitkevicius, Peter V; Alexander, Neil B

2016-01-01

Background Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure (HF). We examined relationships between maximal oxygen uptake, submaximal oxygen kinetics, functional mobility, and physical activity in older adults with HF and reduced ejection fraction. Methods Older adults with HF and reduced ejection fraction (n = 25, age 75 ± 7 years) were compared to 25 healthy age- and gender-matched controls. Assessments included a maximal treadmill test for peak oxygen uptake (VO2peak), oxygen uptake kinetics at onset of and on recovery from a submaximal treadmill test, functional mobility testing [Get Up and Go (GUG), Comfortable Gait Speed (CGS), Unipedal Stance (US)], and self-reported physical activity (PA). Results Compared to controls, HF had worse performance on GUG, CGS, and US, greater delays in submaximal oxygen uptake kinetics, and lower PA. In controls, VO2peak was more strongly associated with functional mobility and PA than submaximal oxygen uptake kinetics. In HF patients, submaximal oxygen uptake kinetics were similarly associated with GUG and CGS as VO2peak, but weakly associated with PA. Conclusions Based on their mobility performance, older HF patients with reduced ejection fraction are at risk for adverse functional outcomes. In this population, submaximal oxygen uptake measures may be equivalent to VO2 peak in predicting functional mobility, and in addition to being more feasible, may provide better insight into how aerobic function relates to mobility in older adults with HF. PMID:27594875

Submaximal oxygen uptake kinetics, functional mobility, and physical activity in older adults with heart failure and reduced ejection fraction.

PubMed

Hummel, Scott L; Herald, John; Alpert, Craig; Gretebeck, Kimberlee A; Champoux, Wendy S; Dengel, Donald R; Vaitkevicius, Peter V; Alexander, Neil B

2016-07-01

Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure (HF). We examined relationships between maximal oxygen uptake, submaximal oxygen kinetics, functional mobility, and physical activity in older adults with HF and reduced ejection fraction. Older adults with HF and reduced ejection fraction (n = 25, age 75 ± 7 years) were compared to 25 healthy age- and gender-matched controls. Assessments included a maximal treadmill test for peak oxygen uptake (VO2peak), oxygen uptake kinetics at onset of and on recovery from a submaximal treadmill test, functional mobility testing [Get Up and Go (GUG), Comfortable Gait Speed (CGS), Unipedal Stance (US)], and self-reported physical activity (PA). Compared to controls, HF had worse performance on GUG, CGS, and US, greater delays in submaximal oxygen uptake kinetics, and lower PA. In controls, VO2peak was more strongly associated with functional mobility and PA than submaximal oxygen uptake kinetics. In HF patients, submaximal oxygen uptake kinetics were similarly associated with GUG and CGS as VO2peak, but weakly associated with PA. Based on their mobility performance, older HF patients with reduced ejection fraction are at risk for adverse functional outcomes. In this population, submaximal oxygen uptake measures may be equivalent to VO2 peak in predicting functional mobility, and in addition to being more feasible, may provide better insight into how aerobic function relates to mobility in older adults with HF.

Comparison of the clinical utility of atrial and B type natriuretic peptide measurement for the diagnosis of systolic dysfunction in a low‐risk population

PubMed Central

Galasko, Gavin; Collinson, Paul O; Barnes, Sophie C; Gaze, David; Lahiri, Arjivit; Senior, Roxy

2007-01-01

Background Measurement of B type natriuretic peptide and its N terminal prohormone (NTproBNP) can now be performed routinely by automated high‐throughput immunoassays. The study compared measurement of NTproBNP with measurement of N terminal pro‐atrial natriuretic peptide (NTproANP) for detection of ventricular systolic dysfunction in primary care. Methods 734 subjects aged >45 years (349 men and 385 women, median age 58 years, range 45–89, interquartile range 51–67 years) from seven representative general practices attended for echocardiography with determination of ejection fraction and completed a questionnaire. Blood samples were collected into gel serum separation tubes (Becton–Dickinson, Franklin Lakes, New Jersey, USA), the serum separated and aliquots stored frozen at −70°C until analyses. Samples were analysed for NTproBNP (Roche Diagnostics, Lewes, UK; coefficient of variation (CV) 3.2–2.4%) and for NTproANP (Biomedica, Vienna, Austria; CV 5.6–10.1%). Echocardiography was used as the diagnostic “gold standard”, with ventricular systolic dysfunction defined as abnormal when there was an ejection fraction of ⩽40%. Patients were dichotomised by ejection fraction from 50% to 30%, and receiver operating characteristic curves constructed and the area under the curve (AUC) compared. Results At 40% ejection fraction, NTproANP and NTproBNP showed AUCs of, respectively, 0.738 (0.601–0.875) and 0.973 (0.958–0.989), p<0.004. Conclusion NTproBNP is superior to NTproANP for detection of systolic dysfunction. PMID:17513518

Changes in left ventricular ejection fraction and coronary flow reserve after coronary microembolization

PubMed Central

Ma, Jianying; Qian, Juying; Zeng, Xin; Sun, Aijun; Chang, Shufu; Chen, Zhangwei; Zou, Yunzeng

2012-01-01

Introduction Although coronary microembolization (CME) is a frequent phenomenon in patients undergoing percutaneous coronary intervention, few data are available on the changes in left ventricular ejection fraction (LVEF) and coronary flow reserve (CFR) after CME. Material and methods In this study, six miniature swine of either sex (body weight 21-25 kg) were used to prepare a CME model. After coronary angiography, 1.2 × 105 microspheres (42 µm) were selectively infused into the left anterior descending artery via an infusion catheter. Left ventricular ejection fraction was evaluated using transthoracic echocardiography; myocardial blood flow was measured using coloured microspheres; and CFR and coronary pressure were measured using Doppler and a pressure wire. Results Left ventricular ejection fraction was 0.77 ±0.08 at baseline, 0.69 ±0.08 at 2 h, 0.68 ±0.08 at 6 h, and 0.76 ±0.06 at 1 week (2 h vs. baseline p < 0.05; 6 h vs. baseline p < 0.01). After CME, left ventricular end systolic volume (LVESV) and end diastolic volume (LVEDV) were significant larger 1 week later (p < 0.01 for both), while CFR was significantly reduced at 6 h (1.24 ±0.10 at 6 h vs. 1.77 ±0.30 at baseline, p < 0.01) and myocardial blood flow remained unchanged. Serum ET-1 level was significantly higher only at 6 h after CME (6 h vs. baseline p < 0.05). Conclusions Reduction of CFR and LVEF is significant at 6 h after CME and recovers 1 week later with left ventricular dilation. PMID:22457677

Does quantitative left ventricular regional wall motion change after fibrous tissue resection in endomyocardial fibrosis?

PubMed

Salemi, Vera Maria Cury; Fernandes, Fabio; Sirvente, Raquel; Nastari, Luciano; Rosa, Leonardo Vieira; Ferreira, Cristiano A; Pena, José Luiz Barros; Picard, Michael H; Mady, Charles

2009-01-01

We compared left ventricular regional wall motion, the global left ventricular ejection fraction, and the New York Heart Association functional class pre- and postoperatively. Endomyocardial fibrosis is characterized by fibrous tissue deposition in the endomyocardium of the apex and/or inflow tract of one or both ventricles. Although left ventricular global systolic function is preserved, patients exhibit wall motion abnormalities in the apical and inferoapical regions. Fibrous tissue resection in New York Heart Association FC III and IV endomyocardial fibrosis patients has been shown to decrease morbidity and mortality. We prospectively studied 30 patients (20 female, 30+/-10 years) before and 5+/-8 months after surgery. The left ventricular ejection fraction was determined using the area-length method. Regional left ventricular motion was measured by the centerline method. Five left ventricular segments were analyzed pre- and postoperatively. Abnormality was expressed in units of standard deviation from the mean motion in a normal reference population. Left ventricular wall motion in the five regions did not differ between pre- and postoperative measurements. Additionally, the left ventricular ejection fraction did not change after surgery (0.45+/-0.13% x 0.43+/-0.12% pre- and postoperatively, respectively). The New York Heart Association functional class improved to class I in 40% and class II in 43% of patients postoperatively (p<0.05). Although endomyocardial fibrosis patients have improved clinical symptoms after surgery, the global left ventricular ejection fraction and regional wall motion in these patients do not change. This finding suggests that other explanations, such as improvements in diastolic function, may be operational.

LCZ696 (Valsartan/Sacubitril)--A Possible New Treatment for Hypertension and Heart Failure.

PubMed

Andersen, Mathilde Borring; Simonsen, Ulf; Wehland, Markus; Pietsch, Jessica; Grimm, Daniela

2016-01-01

The aim of this MiniReview was to introduce the newly invented dual-acting drug valsartan/sacubitril (LCZ696), which combines an angiotensin receptor blocker (valsartan) with sacubitril, a specific inhibitor of the neutral endopeptidase (NEP) that degrades vasoactive peptides, including natriuretic peptides ANP and BNP, but also glucagon, enkephalins and bradykinin, among others. The MiniReview presents the data of four available trials NCT01193101, NCT00549770, NCT00887588 and NCT01035255 and provides the current knowledge about LCZ696 effects in patients with hypertension and heart failure. Presently, patients suffering from hypertension and heart failure are treated with ACE inhibitors or angiotensin receptor antagonists often in combination with other drugs. These current medications lead to a reduction in blood pressure in hypertensive patients and a decreased mortality and morbidity in patients with heart failure with reduced ejection fraction, but not in patients with heart failure with preserved ejection fraction. LCZ696 had been tested to utilize the beneficial properties of natriuretic peptides in combination with angiotensin receptor antagonism. It induces even greater blood pressure reductions and decreased mortality and morbidity in patients with heart failure with reduced ejection fraction, while patients with heart failure with preserved ejection fraction show lowered blood pressure and decreased NT-pro-BNP levels. Although long-term studies remain to be performed, these initial data suggest that there is a potential clinical benefit of LCZ696 in the treatment of hypertension and heart failure. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Isosorbide Dinitrate, With or Without Hydralazine, Does Not Reduce Wave Reflections, Left Ventricular Hypertrophy, or Myocardial Fibrosis in Patients With Heart Failure With Preserved Ejection Fraction.

PubMed

Zamani, Payman; Akers, Scott; Soto-Calderon, Haideliza; Beraun, Melissa; Koppula, Maheswara R; Varakantam, Swapna; Rawat, Deepa; Shiva-Kumar, Prithvi; Haines, Philip G; Chittams, Jesse; Townsend, Raymond R; Witschey, Walter R; Segers, Patrick; Chirinos, Julio A

2017-02-20

Wave reflections, which are increased in patients with heart failure with preserved ejection fraction, impair diastolic function and promote pathologic myocardial remodeling. Organic nitrates reduce wave reflections acutely, but whether this is sustained chronically or affected by hydralazine coadministration is unknown. We randomized 44 patients with heart failure with preserved ejection fraction in a double-blinded fashion to isosorbide dinitrate (ISDN; n=13), ISDN+hydralazine (ISDN+hydral; n=15), or placebo (n=16) for 6 months. The primary end point was the change in reflection magnitude (RM; assessed with arterial tonometry and Doppler echocardiography). Secondary end points included change in left ventricular mass and fibrosis, measured with cardiac magnetic resonance imaging, and the 6-minute walk distance. ISDN reduced aortic characteristic impedance (mean baseline=0.15 [95% CI, 0.14-0.17], 3 months=0.11 [95% CI, 0.10-0.13], 6 months=0.10 [95% CI, 0.08-0.12] mm Hg/mL per second; P =0.003) and forward wave amplitude (P f , mean baseline=54.8 [95% CI, 47.6-62.0], 3 months=42.2 [95% CI, 33.2-51.3]; 6 months=37.0 [95% CI, 27.2-46.8] mm Hg, P =0.04), but had no effect on RM ( P =0.64), left ventricular mass ( P =0.33), or fibrosis ( P =0.63). ISDN+hydral increased RM (mean baseline=0.39 [95% CI, 0.35-0.43]; 3 months=0.31 [95% CI, 0.25-0.36]; 6 months=0.44 [95% CI, 0.37-0.51], P =0.03), reduced 6-minute walk distance (mean baseline=343.3 [95% CI, 319.2-367.4]; 6 months=277.0 [95% CI, 242.7-311.4] meters, P =0.022), and increased native myocardial T1 (mean baseline=1016.2 [95% CI, 1002.7-1029.7]; 6 months=1054.5 [95% CI, 1036.5-1072.3], P =0.021). A high proportion of patients experienced adverse events with active therapy (ISDN=61.5%, ISDN+hydral=60.0%; placebo=12.5%; P =0.007). ISDN, with or without hydralazine, does not exert beneficial effects on RM, left ventricular remodeling, or submaximal exercise and is poorly tolerated. ISDN+hydral appears to have deleterious effects on RM, myocardial remodeling, and submaximal exercise. Our findings do not support the routine use of these vasodilators in patients with heart failure with preserved ejection fraction. URL: www.clinicaltrials.gov. Unique identifier: NCT01516346. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

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/.

Haemodynamic dose-response effects of intravenous nisoldipine in coronary artery disease.

PubMed Central

Silke, B; Frais, M A; Muller, P; Verma, S P; Reynolds, G; Taylor, S H

1985-01-01

The circulatory consequences of slow-calcium channel blockade with a new dihydropyridine nisoldipine were evaluated at rest and during exercise-induced angina in 16 patients with angiographically proven coronary artery disease. In 10 patients resting cardiac stroke output (thermodilution) and pulmonary artery occluded pressure were determined following four intravenous nisoldipine injections (cumulative dosage of 1, 2, 4 and 8 micrograms kg-1). The exercise effects of nisoldipine were evaluated by comparing the effects of the 8 micrograms kg-1 cumulative dosage with a control exercise period at the same workload. At rest nisoldipine reduced systemic vascular resistance and mean arterial pressure, and increased heart rate, cardiac and stroke volume indices. During 4 min supine-bicycle exercise nisoldipine reduced systemic mean arterial pressure and vascular resistance; this resulted in augmented cardiac and stroke volume indices at an unchanged pulmonary artery occluded pressure. In six additional patients rest and exercise ejection fractions were measured using a nonimaging nuclear probe. Nisoldipine (4 micrograms kg-1) resulted in a small trend to increase left ventricular rest and exercise ejection fraction. These data demonstrated improved rest and exercise cardiac performance following nisoldipine in patients with severe coronary artery disease. PMID:4091998

Murine Models of Heart Failure with Preserved Ejection Fraction: a “Fishing Expedition”

PubMed Central

Valero-Muñoz, Maria; Backman, Warren; Sam, Flora

2017-01-01

Summary Heart failure with preserved ejection fraction (HFpEF) is characterized by signs and symptoms of HF in the presence of a normal left ventricular (LV) ejection fraction (EF). Despite accounting for up to 50% of all clinical presentations of HF, the mechanisms implicated in HFpEF are poorly understood, thus precluding effective therapy. The pathophysiological heterogeneity in the HFpEF phenotype also contributes to this disease and likely to the absence of evidence-based therapies. Limited access to human samples and imperfect animal models that completely recapitulate the human HFpEF phenotype have impeded our understanding of the mechanistic underpinnings that exist in this disease. Aging and comorbidities such as atrial fibrillation, hypertension, diabetes and obesity, pulmonary hypertension and renal dysfunction are highly associated with HFpEF. Yet, the relationship and contribution between them remains ill-defined. This review discusses some of the distinctive clinical features of HFpEF in association with these comorbidities and highlights the advantages and disadvantage of commonly used murine models, used to study the HFpEF phenotype. PMID:29333506

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.

Pulmonary Hypertension in Heart Failure Patients: Pathophysiology and Prognostic Implications.

PubMed

Guazzi, Marco; Labate, Valentina

2016-12-01

Pulmonary hypertension (PH) due to left heart disease (LHD), i.e., group 2 PH, is the most common reason for increased pressures in the pulmonary circuit. Although recent guidelines incorporate congenital heart disease in this classification, left-sided heart diseases of diastolic and systolic origin including valvular etiology are the vast majority. In these patients, an increased left-sided filling pressure triggers a multistage hemodynamic evolution that ends into right ventricular failure through an initial passive increase in pulmonary artery pressure complicated over time by pulmonary vasoconstriction, endothelial dysfunction, and remodeling of the small-resistance pulmonary arteries. Regardless of the underlying left heart pathology, when present, PH-LHD is associated with more severe symptoms, worse exercise tolerance, and outcome, especially when right ventricular dysfunction and failure are part of the picture. Compared with group 1 and other forms of pulmonary arterial hypertension, PH-LHD is more often seen in elderly patients with a higher prevalence of cardiovascular comorbidities and most, if not all, of the features of metabolic syndrome, especially in case of HF preserved ejection fraction. In this review, we provide an update on current knowledge and some potential challenges about the pathophysiology and established prognostic implications of group 2 PH in patients with HF of either preserved or reduced ejection fraction.

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.

Impact of sleep-disordered breathing in patients with acute myocardial infarction: a retrospective analysis.

PubMed

Gessner, Verena; Bitter, Thomas; Horstkotte, Dieter; Oldenburg, Olaf; Fox, Henrik

2017-10-01

Sleep-disordered breathing (SDB) is associated with an increased risk of cardiovascular events. Previous studies showed that severe SDB has a negative impact on myocardial salvage and progression of left ventricular dysfunction after acute myocardial infarction (AMI). This study investigated the frequency of SDB and the effects of SDB on left ventricular function after AMI. This retrospective study enrolled all patients with AMI who had undergone cardiorespiratory polygraphy for SDB diagnosis. The apnea-hypopnea index was used as a standard metric of SDB severity. SDB was classified as mild (apnea-hypopnea index >5 to <15 per h), moderate (≥15 to <30 per h) or severe (apnea-hypopnea index ≥30 per h). According to the majority of events, SDB was classified as predominant obstructive sleep apnea, central sleep apnea or mixed sleep apnea (mixed SDB). A total of 223 patients with AMI (112 with ST elevation and 111 without ST elevation; 63.2 ± 11.2 years, 82% male, left ventricular ejection fraction 49 ± 12%) were enrolled. SDB was present in 85.6%, and was moderate-to-severe in 63.2%; 40.8% had obstructive sleep apnea, 41.7% had central sleep apnea and 3.1% had mixed SDB. Left ventricular ejection fraction was lower in patients with AMI with severe SDB (45 ± 14%) versus those without SDB (57 ± 7%; P < 0.005). In addition, lower left ventricular ejection fraction (≤45%) was associated with increased frequency (apnea-hypopnea index ≥5 per h in 96%) and severity (apnea-hypopnea index ≥30 per h in 48%) of SDB in general and a higher percentage of central sleep apnea (57%) in particular. SDB is highly frequent in patients with AMI. SDB severity appeared to be linked to impaired left ventricular function, especially in patients with central sleep apnea. © 2017 European Sleep Research Society.

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

Outcome and Impact of Aortic Valve Replacement in Patients With Preserved LVEF and Low-Gradient Aortic Stenosis.

PubMed

Dayan, Victor; Vignolo, Gustavo; Magne, Julien; Clavel, Marie-Annick; Mohty, Dania; Pibarot, Philippe

2015-12-15

Low mean transvalvular gradient (<40 mm Hg) and small aortic valve area (<1.0 cm(2)) in patients with aortic stenosis (AS) and preserved left ventricular ejection fraction raises uncertainty about the actual severity of the stenosis and survival benefit of aortic valve replacement (AVR). This study analyzed studies of mortality and survival impact of AVR in patients with low-gradient (LG) AS and preserved left ventricular ejection fraction, including paradoxical low-flow (i.e., stroke volume index <35 ml/m(2)), low-gradient (LF-LG) and normal-flow, low-gradient (NF-LG), and those with high-gradient (≥ 40 mm Hg) AS or moderate AS. Studies published between 2005 and 2015 were analyzed. Primary outcome was the survival benefit associated with AVR. Secondary outcome was overall mortality regardless of treatment. Eighteen studies were included in the analysis. Patients with LF-LG AS have increased mortality compared with patients with moderate AS (hazard ratio [HR]: 1.68; 95% confidence interval [CI]: 1.31 to 2.17), NF-LG (HR: 1.80; 95% CI: 1.29 to 2.51), and high-gradient (HR: 1.67; 95% CI: 1.16 to 2.39) AS. AVR was associated with reduced mortality in patients with LF-LG (HR: 0.44; 95% CI: 0.25 to 0.77). Similar benefit occurred with AVR in patients with NF-LG (HR: 0.48; 95% CI: 0.28 to 0.83). Compared with patients with high-gradient AS, those with LF-LG were less likely to be referred to AVR (odds ratio: 0.32; 95% CI: 0.21 to 0.49). Patients with paradoxical LF-LG AS and NF-LG AS have increased risk of mortality compared with other subtypes of AS with preserved left ventricular ejection fraction, and improved outcome with AVR. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Cost-Effectiveness of Implantable Pulmonary Artery Pressure Monitoring in Chronic Heart Failure.

PubMed

Sandhu, Alexander T; Goldhaber-Fiebert, Jeremy D; Owens, Douglas K; Turakhia, Mintu P; Kaiser, Daniel W; Heidenreich, Paul A

2016-05-01

This study aimed to evaluate the cost-effectiveness of the CardioMEMS (CardioMEMS Heart Failure System, St Jude Medical Inc, Atlanta, Georgia) device in patients with chronic heart failure. The CardioMEMS device, an implantable pulmonary artery pressure monitor, was shown to reduce hospitalizations for heart failure and improve quality of life in the CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) trial. We developed a Markov model to determine the hospitalization, survival, quality of life, cost, and incremental cost-effectiveness ratio of CardioMEMS implantation compared with usual care among a CHAMPION trial cohort of patients with heart failure. We obtained event rates and utilities from published trial data; we used costs from literature estimates and Medicare reimbursement data. We performed subgroup analyses of preserved and reduced ejection fraction and an exploratory analysis in a lower-risk cohort on the basis of the CHARM (Candesartan in Heart failure: Reduction in Mortality and Morbidity) trials. CardioMEMS reduced lifetime hospitalizations (2.18 vs. 3.12), increased quality-adjusted life-years (QALYs) (2.74 vs. 2.46), and increased costs ($176,648 vs. $156,569), thus yielding a cost of $71,462 per QALY gained and $48,054 per life-year gained. The cost per QALY gained was $82,301 in patients with reduced ejection fraction and $47,768 in those with preserved ejection fraction. In the lower-risk CHARM cohort, the device would need to reduce hospitalizations for heart failure by 41% to cost <$100,000 per QALY gained. The cost-effectiveness was most sensitive to the device's durability. In populations similar to that of the CHAMPION trial, the CardioMEMS device is cost-effective if the trial effectiveness is sustained over long periods. Post-marketing surveillance data on durability will further clarify its value. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Multicenter Automatic Defibrillator Implantation Trial-Subcutaneous Implantable Cardioverter Defibrillator (MADIT S-ICD): Design and clinical protocol.

PubMed

Kutyifa, Valentina; Beck, Christopher; Brown, Mary W; Cannom, David; Daubert, James; Estes, Mark; Greenberg, Henry; Goldenberg, Ilan; Hammes, Stephen; Huang, David; Klein, Helmut; Knops, Reinoud; Kosiborod, Mikhail; Poole, Jeanne; Schuger, Claudio; Singh, Jagmeet P; Solomon, Scott; Wilber, David; Zareba, Wojciech; Moss, Arthur J

2017-07-01

Patients with diabetes mellitus, prior myocardial infarction, older age, and a relatively preserved left ventricular ejection fraction remain at risk for sudden cardiac death that is potentially amenable by the subcutaneous implantable cardioverter defibrillator with a good risk-benefit profile. The launched MADIT S-ICD study is designed to test the hypothesis that post-myocardial infarction diabetes patients with relatively preserved ejection fraction of 36%-50% will have a survival benefit from a subcutaneous implantable cardioverter defibrillator. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

The Fraction of Interplanetary Coronal Mass Ejections That Are Magnetic Clouds: Evidence for a Solar Cycle Variation

NASA Technical Reports Server (NTRS)

Richardson, I. G.; Cane, H. V.

2004-01-01

"Magnetic clouds" (MCs) are a subset of interplanetary coronal mass ejections (ICMEs) characterized by enhanced magnetic fields with an organized rotation in direction, and low plasma beta. Though intensely studied, MCs only constitute a fraction of all the ICMEs that are detected in the solar wind. A comprehensive survey of ICMEs in the near- Earth solar wind during the ascending, maximum and early declining phases of solar cycle 23 in 1996 - 2003 shows that the MC fraction varies with the phase of the solar cycle, from approximately 100% (though with low statistics) at solar minimum to approximately 15% at solar maximum. A similar trend is evident in near-Earth observations during solar cycles 20 - 21, while Helios 1/2 spacecraft observations at 0.3 - 1.0 AU show a weaker trend and larger MC fraction.

Percutaneous coronary intervention in patients with severe aortic stenosis: implications for transcatheter aortic valve replacement.

PubMed

Goel, Sachin S; Agarwal, Shikhar; Tuzcu, E Murat; Ellis, Stephen G; Svensson, Lars G; Zaman, Tarique; Bajaj, Navkaranbir; Joseph, Lee; Patel, Neil S; Aksoy, Olcay; Stewart, William J; Griffin, Brian P; Kapadia, Samir R

2012-02-28

With the availability of transcatheter aortic valve replacement, management of coronary artery disease in patients with severe aortic stenosis (AS) is posing challenges. Outcomes of percutaneous coronary intervention (PCI) in patients with severe AS and coronary artery disease remain unknown. We sought to compare the short-term outcomes of PCI in patients with and without AS. From our PCI database, we identified 254 patients with severe AS who underwent PCI between 1998 and 2008. Using propensity matching, we found 508 patients without AS who underwent PCI in the same period. The primary end point of 30-day mortality after PCI was similar in patients with and without severe AS (4.3% [11 of 254] versus 4.7% [24 of 508]; hazard ratio, 0.93; 95% confidence interval, 0.51-1.69; P=0.2). Patients with low ejection fraction (≤30%) and severe AS had a higher 30-day post-PCI mortality compared with those with an ejection fraction >30% (5.4% [7 of 45] versus 1.2% [4 of 209]; P<0.001). In addition, AS patients with high Society of Thoracic Surgeons score (≥10) had a higher 30-day post-PCI mortality than those with a Society of Thoracic Surgeons score <10 (10.4% [10 of 96] versus 0%; P<0.001). PCI can be performed in patients with severe symptomatic AS and coronary artery disease without an increased risk of short-term mortality compared with propensity-matched patients without AS. Patients with ejection fraction ≤30% and Society of Thoracic Surgeons score ≥10% are at a highest risk of 30-day mortality after PCI. This finding has significant implications in the management of severe coronary artery disease in high-risk severe symptomatic AS patients being considered for transcatheter aortic valve replacement.

Effect of valsartan on systemic right ventricular function: a double-blind, randomized, placebo-controlled pilot trial.

PubMed

van der Bom, Teun; Winter, Michiel M; Bouma, Berto J; Groenink, Maarten; Vliegen, Hubert W; Pieper, Petronella G; van Dijk, Arie P J; Sieswerda, Gertjan T; Roos-Hesselink, Jolien W; Zwinderman, Aeilko H; Mulder, Barbara J M

2013-01-22

The role of angiotensin II receptor blockers in patients with a systemic right ventricle has not been elucidated. We conducted a multicenter, double-blind, parallel, randomized controlled trial of angiotensin II receptor blocker valsartan 160 mg twice daily compared with placebo in patients with a systemic right ventricle caused by congenitally or surgically corrected transposition of the great arteries. The primary end point was change in right ventricular ejection fraction during 3-year follow-up, determined by cardiovascular magnetic resonance imaging or, in patients with contraindication for magnetic resonance imaging, multirow detector computed tomography. Secondary end points were change in right ventricular volumes and mass, Vo(2)peak, and quality of life. Primary analyses were performed on an intention-to-treat basis. A total of 88 patients (valsartan, n=44; placebo, n=44) were enrolled in the trial. No serious adverse effects occurred in either group. There was no significant effect of 3-year valsartan therapy on systemic right ventricular ejection fraction (treatment effect, 1.3%; 95% confidence interval, -1.3% to 3.9%; P=0.34), maximum exercise capacity, or quality of life. There was a larger increase in right ventricular end-diastolic volume (15 mL; 95% confidence interval, 3-28 mL; P<0.01) and mass (8 g; 95% confidence interval, 2-14 g; P=0.01) in the placebo group than in the valsartan group. There was no significant treatment effect of valsartan on right ventricular ejection fraction, exercise capacity, or quality of life. Valsartan was associated with a similar frequency of significant clinical events as placebo. Small but significant differences between valsartan and placebo were present for change in right ventricular volumes and mass. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN52352170.

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

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

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

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

Papillary Muscle Repositioning as a Subvalvular Apparatus Preservation Technique in Mitral Stenosis Patients with Normal Left Ventricular Systolic Function

PubMed Central

Lafci, Gokhan; Cagli, Kerim; Korkmaz, Kemal; Turak, Osman; Uzun, Alper; Yalcinkaya, Adnan; Diken, Adem; Gunertem, Eren; Cagli, Kumral

2014-01-01

Subvalvular apparatus preservation is an important concept in mitral valve replacement (MVR) surgery that is performed to remedy mitral regurgitation. In this study, we sought to determine the effects of papillary muscle repositioning (PMR) on clinical outcomes and echocardiographic left ventricular function in rheumatic mitral stenosis patients who had normal left ventricular systolic function. We prospectively assigned 115 patients who were scheduled for MVR surgery with mechanical prosthesis to either PMR or MVR-only groups. Functional class and echocardiographic variables were evaluated at baseline and at early and late postoperative follow-up examinations. All values were compared between the 2 groups. The PMR group consisted of 48 patients and the MVR-only group of 67 patients. The 2 groups’ baseline characteristics and surgery-related factors (including perioperative mortality) were similar. During the 18-month follow-up, all echocardiographic variables showed a consistent improvement in the PMR group; the mean left ventricular ejection fraction deteriorated significantly in the MVR-only group. Comparison during follow-up of the magnitude of longitudinal changes revealed that decreases in left ventricular end-diastolic and end-systolic diameters and in left ventricular sphericity indices, and increases in left ventricular ejection fractions, were significantly higher in the PMR group than in the MVR-only group. This study suggests that, in patients with rheumatic mitral stenosis and preserved left ventricular systolic function, the addition of papillary muscle repositioning to valve replacement with a mechanical prosthesis improves left ventricular dimensions, ejection fraction, and sphericity index at the 18-month follow-up with no substantial undesirable effect on the surgery-related factors. PMID:24512397

Cardiac Rotational Mechanics As a Predictor of Myocardial Recovery in Heart Failure Patients Undergoing Chronic Mechanical Circulatory Support: A Pilot Study.

PubMed

Bonios, Michael J; Koliopoulou, Antigone; Wever-Pinzon, Omar; Taleb, Iosif; Stehlik, Josef; Xu, Weining; Wever-Pinzon, James; Catino, Anna; Kfoury, Abdallah G; Horne, Benjamin D; Nativi-Nicolau, Jose; Adamopoulos, Stamatis N; Fang, James C; Selzman, Craig H; Bax, Jeroen J; Drakos, Stavros G

2018-04-01

Impaired qualitative and quantitative left ventricular (LV) rotational mechanics predict cardiac remodeling progression and prognosis after myocardial infarction. We investigated whether cardiac rotational mechanics can predict cardiac recovery in chronic advanced cardiomyopathy patients. Sixty-three patients with advanced and chronic dilated cardiomyopathy undergoing implantation of LV assist device (LVAD) were prospectively investigated using speckle tracking echocardiography. Acute heart failure patients were prospectively excluded. We evaluated LV rotational mechanics (apical and basal LV twist, LV torsion) and deformational mechanics (circumferential and longitudinal strain) before LVAD implantation. Cardiac recovery post-LVAD implantation was defined as (1) final resulting LV ejection fraction ≥40%, (2) relative LV ejection fraction increase ≥50%, (iii) relative LV end-systolic volume decrease ≥50% (all 3 required). Twelve patients fulfilled the criteria for cardiac recovery (Rec Group). The Rec Group had significantly less impaired pre-LVAD peak LV torsion compared with the Non-Rec Group. Notably, both groups had similarly reduced pre-LVAD LV ejection fraction. By receiver operating characteristic curve analysis, pre-LVAD peak LV torsion of 0.35 degrees/cm had a 92% sensitivity and a 73% specificity in predicting cardiac recovery. Peak LV torsion before LVAD implantation was found to be an independent predictor of cardiac recovery after LVAD implantation (odds ratio, 0.65 per 0.1 degrees/cm [0.49-0.87]; P =0.014). LV rotational mechanics seem to be useful in selecting patients prone to cardiac recovery after mechanical unloading induced by LVADs. Future studies should investigate the utility of these markers in predicting durable cardiac recovery after the explantation of the cardiac assist device. © 2018 American Heart Association, Inc.

Impact of Preeclampsia on Clinical and Functional Outcomes in Women With Peripartum Cardiomyopathy.

PubMed

Lindley, Kathryn J; Conner, Shayna N; Cahill, Alison G; Novak, Eric; Mann, Douglas L

2017-06-01

Preeclampsia is a risk factor for the development of peripartum cardiomyopathy (PPCM), but it is unknown whether preeclampsia impacts clinical or left ventricular (LV) functional outcomes. This study sought to assess clinical and functional outcomes in women with PPCM complicated by preeclampsia. This retrospective cohort study included women diagnosed with PPCM delivering at Barnes-Jewish Hospital between 2004 to 2014. The primary outcome was one-year event-free survival rate for the combined end point of death and hospital readmission. The secondary outcome was recovery of LV ejection fraction. Seventeen of 39 women (44%) with PPCM had preeclampsia. The groups had similar mean LV ejection fraction at diagnosis (29.6 with versus 27.3 without preeclampsia; P =0.5). Women with preeclampsia had smaller mean LV end-diastolic diameters (5.2 versus 6.0 cm; P =0.001), greater relative wall thickness (0.41 versus 0.35 mm Hg; P =0.009), and lower incidence of eccentric remodeling (12% versus 48%; P =0.03). Clinical follow-up was available for 32 women; 5 died of cardiovascular complications within 1 year of diagnosis (4/15 with versus 1/17 without preeclampsia; P =0.16). In time to event analysis, patients with preeclampsia had worse event-free survival during 1-year follow-up ( P =0.047). Echocardiographic follow-up was available in 10 survivors with and 16 without preeclampsia. LV ejection fraction recovered in 80% of survivors with versus 25% without preeclampsia ( P =0.014). PPCM with concomitant preeclampsia is associated with increased morbidity and mortality and different patterns of LV remodeling and recovery of LV function when compared with patients with PPCM that is not complicated by preeclampsia. © 2017 American Heart Association, Inc.

Left ventricular ejection time is an independent predictor of incident heart failure in a community-based cohort.

PubMed

Biering-Sørensen, Tor; Querejeta Roca, Gabriela; Hegde, Sheila M; Shah, Amil M; Claggett, Brian; Mosley, Thomas H; Butler, Kenneth R; Solomon, Scott D

2017-09-04

Systolic time intervals change in the progress of cardiac dysfunction. The usefulness of left ventricular ejection time (LVET) to predict cardiovascular morbidity, however, is unknown. We studied middle-aged African-Americans from one of four cohorts of the Atherosclerosis Risk in Communities study (Jackson cohort, n=1980) who underwent echocardiography between 1993 and 1995. Left ventricular ejection time was measured by pulsed-wave Doppler of the left ventricular outflow tract and related to outcomes. A shorter LVET was associated with younger age, male sex, higher diastolic blood pressure, higher proportion of diabetes, higher heart rate, higher blood glucose levels and worse fractional shortening. During a median follow-up of 17.6 years, 384 (19%) had incident heart failure (HF), 158 (8%) had a myocardial infarction, and 587 (30%) died. In univariable analysis, a lower LVET was significantly associated with increased risk of all events (P<0.05 for all). However, after multivariable adjustment for age, sex, hypertension, diabetes, body mass index, heart rate, systolic and diastolic blood pressure, fractional shortening and left atrial diameter, LVET remained an independent predictor only of incident HF [hazard ratio 1.07 (1.02-1.14), P=0.010 per 10 ms decrease]. In addition, LVET provided incremental prognostic information to the known risk factors included in the Framingham risk score, in regard to predicting all outcomes except for myocardial infarction. Left ventricular ejection time is an independent predictor of incident HF in a community-based cohort and provides incremental prognostic information on the risk of future HF and death when added to known risk prediction models. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Impairment of left ventricular function during coronary angioplastic occlusion evaluated with a nonimaging scintillation probe.

PubMed

Hartmann, A; Maul, F D; Zimny, M; Klepzig, H; Vallbracht, C; Kneissl, H G; Schräder, R; Hör, G; Kaltenbach, M

1991-09-01

Impairment of left ventricular function during controlled myocardial ischemia induced by coronary angioplasty has been reported from angiographic and echocardiographic studies. Ejection fraction, peak ejection, peak filling rates, and end-systolic and end-diastolic volumes were investigated before, during and after coronary occlusion on-line with a nonimaging scintillation probe. The study consisted of 18 patients (mean age 59 +/- 10 years) with coronary artery stenosis of greater than 70%. During balloon inflation of 60 seconds' duration, coronary occlusion pressure was 31.6 +/- 12 mm Hg. There was no significant change in heart rate. Delay between first and second dilatation was 109 +/- 63 seconds. Ejection fraction decreased from 53 +/- 16 to 40 +/- 12% (first dilatation, p less than 0.01) and to 39 +/- 14% (second dilatation, p less than 0.01) and recovered to 51 +/- 16% 5 minutes after the second dilatation. Peak ejection rate was significantly reduced during the first and second balloon inflations. Peak filling rate decreased from 2.5 +/- 0.8 to 2.0 +/- 0.7 end-diastolic volume.s-1 (first dilatation, p less than 0.01) and to 1.8 +/- 0.7 end-diastolic volume.s-1 (second dilatation, p less than 0.01) and remained reduced at 2.2 +/- 0.7 end-diastolic volume.s-1 (p = not significant) at 5 minutes after the second dilatation. End-systolic and end-diastolic volumes increased significantly during the first and second dilatations and returned to normal after dilatation. It is concluded that short, controlled myocardial ischemia during coronary angioplasty leads to a decrease in systolic and diastolic left ventricular function. Sequential dilatations do not further decrease function if a sufficient interval is kept.

Swapping Rocks: Ejection and Exchange of Surface Material Among the Terrestrial Planets

NASA Astrophysics Data System (ADS)

Melosh, H. J.; Tonks, W. B.

1993-07-01

The discovery of meteorites originating from both the Moon and Mars has led to the realization that major impacts can eject material from planetary-sized objects. Although there is not yet any direct proof, there appears to be no reason why such impacts cannot eject material from the surfaces of Earth and Venus as well. Because of this possibility, and in view of the implications of such exchange for biological evolution, we examined the orbital evolution and ultimate fate of ejecta from each of the terrestrial planets. This work employed an Opik-type orbital evolution model in which both planets and ejected particles follow elliptical orbits about the Sun, with uniformly precessing arguments of perihelion and ascending nodes. An encounter takes place when the particle passes within the sphere of influence of the planet. When this occurs, the encounter is treated as a two-body scattering event, with a randomly chosen impact parameter within the sphere of influence. If the impact parameter is less than the planet's radius, an impact is scored. Otherwise, the scattered particle either takes up a new Keplerian orbit or is ejected from the solar system. We incorporated several different space erosion models and examined the full matrix of possible outcomes of ejection from each planet in random directions with velocities at great distance from the planet of 0.5, 2.5, and 5.0 km/s. Each run analyzed the evolution of 5000 particles to achieve sufficient statistical resolution. Both the ultimate fate and median transit times of particles was recorded. The results show very little dependence on velocity of ejection. Mercury ejecta is nearly all reaccreted by Mercury or eroded in space--very little ever evolves to cross the orbits of the other planets (a few percent impact Venus). The median time between ejection and reimpact is about 30 m.y. for all erosion models. Venus ejecta is mostly reaccreted by Venus, but a significant fraction (about 30%) falls on the Earth with a median transit time of 12 m.y. Of the remainder, a few percent strike Mars and a larger fraction (about 20%) are ejected from the solar system by Jupiter. Earth ejecta is also mainly reaccreted by the Earth, but about 30% strike Venus within 15 m.y. and 5% strike Mars within 150 m.y. Again, about 20% of Earth ejecta is thrown out of the solar system by Jupiter. Mars ejecta is more equitably distributed: Nearly equal fractions fall on Earth and Venus, slightly more are accreted to Mars, and a few percent strike Mercury. About 20% of Mars ejecta is thrown out of the solar system by Jupiter. The larger terrestrial planets, Venus and Earth, thus readily exchange ejecta. Mars ejecta largely falls on Venus and Earth, but Mars only receives a small fraction of their ejecta. A substantial fraction of ejecta from all the terrestrial planets (except Mercury) is thrown out of the solar system by Jupiter, a fact that may have some implications for the panspermia mechanism of spreading life through the galaxy. From the standpoint of collecting meteorites on Earth, in addition to martian and lunar meteorites, we should expect someday to find meteorites from Earth itself (Earth rocks that have spent a median time of 5 m.y. in space before falling again on the Earth) and from Venus.

Supplementary Administration of Everolimus Reduces Cardiac Systolic Function in Kidney Transplant Recipients.

PubMed

Tsujimura, Kazuma; Ota, Morihito; Chinen, Kiyoshi; Nagayama, Kiyomitsu; Oroku, Masato; Nishihira, Morikuni; Shiohira, Yoshiki; Abe, Masami; Iseki, Kunitoshi; Ishida, Hideki; Tanabe, Kazunari

2017-05-26

BACKGROUND The effect of everolimus, one of the mammalian targets of rapamycin inhibitors, on cardiac function was evaluated in kidney transplant recipients. MATERIAL AND METHODS Seventy-six participants who underwent kidney transplant between March 2009 and May 2016 were retrospectively reviewed. To standardize everolimus administration, the following criteria were used: (1) the recipient did not have a donor-specific antigen before kidney transplantation; (2) the recipient did not have proteinuria and uncontrollable hyperlipidemia after kidney transplantation; and (3) acute rejection was not observed on protocol biopsy 3 months after kidney transplantation. According to these criteria, everolimus administration for maintenance immunosuppression after kidney transplantation was included. Cardiac function was compared between the treatment group (n=30) and non-treatment group (n=46). RESULTS The mean observation periods of the treatment and non-treatment groups were 41.3±12.6 and 43.9±19.8 months, respectively (p=0.573). The mean ejection fraction and fractional shortening of the treatment and non-treatment groups after kidney transplant were 66.5±7.9% vs. 69.6±5.5% (p=0.024) and 37.1±6.2% vs. 39.3±4.7% (p=0.045), respectively. In the treatment group, the mean ejection fraction and fractional shortening before and after kidney transplantation did not differ significantly (p=0.604 and 0.606, respectively). In the non-treatment group, the mean ejection fraction and fractional shortening before and after kidney transplantation differed significantly (p=0.004 and 0.006, respectively). CONCLUSIONS Supplementary administration of everolimus after kidney transplantation can reduce cardiac systolic function.

Pharmacokinetics and Pharmacodynamics of Inorganic Nitrate in Heart Failure With Preserved Ejection Fraction.

PubMed

Zamani, Payman; Tan, Victor; Soto-Calderon, Haideliza; Beraun, Melissa; Brandimarto, Jeffrey A; Trieu, Lien; Varakantam, Swapna; Doulias, Paschalis-Thomas; Townsend, Raymond R; Chittams, Jesse; Margulies, Kenneth B; Cappola, Thomas P; Poole, David C; Ischiropoulos, Harry; Chirinos, Julio A

2017-03-31

Nitrate-rich beetroot juice has been shown to improve exercise capacity in heart failure with preserved ejection fraction, but studies using pharmacological preparations of inorganic nitrate are lacking. To determine (1) the dose-response effect of potassium nitrate (KNO 3 ) on exercise capacity; (2) the population-specific pharmacokinetic and safety profile of KNO 3 in heart failure with preserved ejection fraction. We randomized 12 subjects with heart failure with preserved ejection fraction to oral KNO 3 (n=9) or potassium chloride (n=3). Subjects received 6 mmol twice daily during week 1, followed by 6 mmol thrice daily during week 2. Supine cycle ergometry was performed at baseline (visit 1) and after each week (visits 2 and 3). Quality of life was assessed with the Kansas City Cardiomyopathy Questionnaire. The primary efficacy outcome, peak O 2 -uptake, did not significantly improve ( P =0.13). Exploratory outcomes included exercise duration and quality of life. Exercise duration increased significantly with KNO 3 (visit 1: 9.87, 95% confidence interval [CI] 9.31-10.43 minutes; visit 2: 10.73, 95% CI 10.13-11.33 minute; visit 3: 11.61, 95% CI 11.05-12.17 minutes; P =0.002). Improvements in the Kansas City Cardiomyopathy Questionnaire total symptom (visit 1: 58.0, 95% CI 52.5-63.5; visit 2: 66.8, 95% CI 61.3-72.3; visit 3: 70.8, 95% CI 65.3-76.3; P =0.016) and functional status scores (visit 1: 62.2, 95% CI 58.5-66.0; visit 2: 68.6, 95% CI 64.9-72.3; visit 3: 71.1, 95% CI 67.3-74.8; P =0.01) were seen after KNO 3 . Pronounced elevations in trough levels of nitric oxide metabolites occurred with KNO 3 (visit 2: 199.5, 95% CI 98.7-300.2 μmol/L; visit 3: 471.8, 95% CI 377.8-565.8 μmol/L) versus baseline (visit 1: 38.0, 95% CI 0.00-132.0 μmol/L; P <0.001). KNO 3 did not lead to clinically significant hypotension or methemoglobinemia. After 6 mmol of KNO 3 , systolic blood pressure was reduced by a maximum of 17.9 (95% CI -28.3 to -7.6) mm Hg 3.75 hours later. Peak nitric oxide metabolites concentrations were 259.3 (95% CI 176.2-342.4) μmol/L 3.5 hours after ingestion, and the median half-life was 73.0 (interquartile range 33.4-232.0) minutes. KNO 3 is potentially well tolerated and improves exercise duration and quality of life in heart failure with preserved ejection fraction. This study reinforces the efficacy of KNO 3 and suggests that larger randomized trials are warranted. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02256345. © 2016 American Heart Association, Inc.

Accuracy of tissue Doppler echocardiography in the diagnosis of new-onset congestive heart failure in patients with levels of B-type natriuretic peptide in the midrange and normal left ventricular ejection fraction.

PubMed

Arques, Stephane; Roux, Emmanuel; Sbragia, Pascal; Pieri, Bertrand; Gelisse, Richard; Ambrosi, Pierre; Luccioni, Roger

2006-09-01

Based on the hypothesis that it reflects left ventricular (LV) diastolic pressures, B-type natriuretic peptide (BNP) is largely utilized as first-line diagnostic complement in the emergency diagnosis of congestive heart failure (HF). The incremental diagnostic value of tissue Doppler echocardiography, a reliable noninvasive estimate of LV filling pressures, has been reported in patients with preserved LV ejection fraction and discrepancy between BNP levels and the clinical judgment, however, its clinical validity in such patients in the presence of BNP concentrations in the midrange, which may reflect intermediate, nondiagnostic levels of LV filling pressures, is unknown. 34 patients without history of HF, presenting with acute dyspnea at rest, BNP levels of 100-400 pg/ml and normal LV ejection fraction were prospectively enrolled (17 with congestive HF and 17 with noncardiac cause). Tissue Doppler echocardiography was performed within 3 hours after admission. Unlike BNP (P = 0.78), Boston criteria (P = 0.0129), radiographic pulmonary edema (P = 0.0036) and average E/Ea ratio (P = 0.0032) were predictive of congestive HF by logistic regression analysis. In this clinical setting, radiographic pulmonary edema had a positive predictive value of 80% in the diagnosis of congestive HF. In patients without evidence of radiographic pulmonary edema, average E/Ea > 10 was a powerful predictor of congestive HF (area under the ROC curve of 0.886, P < 0.001, sensitivity 100% and specificity 78.6%). By better reflecting LV filling pressures, bedside tissue Doppler echocardiography accurately differentiates congestive HF from noncardiac cause in dyspneic patients with intermediate, nondiagnostic BNP levels and normal LV ejection fraction.

Real-world heart failure management in 10,910 patients with chronic heart failure in the Netherlands : Design and rationale of the Chronic Heart failure ESC guideline-based Cardiology practice Quality project (CHECK-HF) registry.

PubMed

Brugts, J J; Linssen, G C M; Hoes, A W; Brunner-La Rocca, H P

2018-05-01

Data from patient registries give insight into the management of patients with heart failure (HF), but actual data from unselected real-world HF patients are scarce. Therefore, we performed a cross sectional study of current HF care in the period 2013-2016 among more than 10,000 unselected HF patients at HF outpatient clinics in the Netherlands. In 34 participating centres, all 10,910 patients with chronic HF treated at cardiology centres were included in the CHECK-HF registry. Of these, most (96%) were managed at a specific HF outpatient clinic. Heart failure was typically diagnosed according to the ESC guidelines 2012, based on signs, symptoms and structural and/or functional cardiac abnormalities. Information on diagnostics, treatment and co-morbidities were recorded, with specific focus on drug therapy and devices. In our cohort, the mean age was 73 years (SD 12) and 60% were male. Frequent co-morbidities reported in the patient records were diabetes mellitus 30%, hypertension 43%, COPD 19%, and renal insufficiency 58%. In 47% of the patients, ischaemia was the origin of HF. In our registry, the prevalence of HF with preserved ejection fraction was 21%. The CHECK-HF registry will provide insight into the current, real world management of patient with chronic HF, including HF with reduced ejection fraction, preserved ejection fraction and mid-range ejection fraction, that will help define ways to improve quality of care. Drug and device therapy and guideline adherence as well as interactions with age, gender and co-morbidities will receive specific attention.

THE EFFECT OF RIGHT VENTRICULAR PACEMAKER LEAD POSITION ON FUNCTIONAL STATUS IN PATIENTS WITH PRESERVED LEFT VENTRICULAR EJECTION FRACTION.

PubMed

Mitov, Vladimir M; Perisic, Zoran; Jolic, Aleksandar; Kostic, Tomislav; Aleksic, Aleksandar; Aleksic, Zeljka

2016-07-01

The study was aimed at assessing the difference between the right ventricle apex versus the right ventricular outflow tract lead position in functional capacity in the patients with the preserved left ventricular ejection fraction after 12 months of pacemaker stimulation. This was a prospective, randomized, follow-up study, which lasted for 12 months. The study sample included 132 consecutive patients who were implanted with permanent anti-bradicardiac pacemaker. Regarding the right ventricular lead position the patients were divided into two groups: the right ventricle apex group consisting of 61 patients with right ventricular apex lead position. The right ventricular outflow tract group included 71 patients with right ventricular outflow tract lead position. Functional capacity was assessed by Minnesota Living With Heart Failure score, New York Heart Association class and Six Minute Walk Test. Left ventricular ejection fraction was assessed by echocardiography. Minnesota Living With Heart Failure score and New York Heart Association class had a statistically significant improvement in both study groups. The patients from right ventricle apex group walked 20.95% (p=O.03) more in comparison to starting values. The patients from right ventricular outflow tract group walked only 13.63% (p=0.09) longer distance than the startingoneConclusion. Analysis of tests of functional status New York Heart Association class and Minnesota Living With Heart Failure questionnaire showed an even improvement in the right ventricle apex and right ventricular outflow tract groups. Analysis of 6 minute walk test showed that only the patients with the preserved left ventricular ejection fraction from the right ventricle apex group had a significant improvement after 12 months of pacemaker stimulation..

Thirty Years of Evidence on the Efficacy of Drug Treatments for Chronic Heart Failure With Reduced Ejection Fraction

PubMed Central

Earley, Amy; Voors, Adriaan A.; Senni, Michele; McMurray, John J.V.; Deschaseaux, Celine; Cope, Shannon

2017-01-01

Background— Treatments that reduce mortality and morbidity in patients with heart failure with reduced ejection fraction, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), β-blockers (BB), mineralocorticoid receptor antagonists (MRA), and angiotensin receptor–neprilysin inhibitors (ARNI), have not been studied in a head-to-head fashion. This network meta-analysis aimed to compare the efficacy of these drugs and their combinations regarding all-cause mortality in patients with heart failure with reduced ejection fraction. Methods and Results— A systematic literature review identified 57 randomized controlled trials published between 1987 and 2015, which were compared in terms of study and patient characteristics, baseline risk, outcome definitions, and the observed treatment effects. Despite differences identified in terms of study duration, New York Heart Association class, ejection fraction, and use of background digoxin, a network meta-analysis was considered feasible and all trials were analyzed simultaneously. The random-effects network meta-analysis suggested that the combination of ACEI+BB+MRA was associated with a 56% reduction in mortality versus placebo (hazard ratio 0.44, 95% credible interval 0.26–0.66); ARNI+BB+MRA was associated with the greatest reduction in all-cause mortality versus placebo (hazard ratio 0.37, 95% credible interval 0.19–0.65). A sensitivity analysis that did not account for background therapy suggested that ARNI monotherapy is more efficacious than ACEI or ARB monotherapy. Conclusions— The network meta-analysis showed that treatment with ACEI, ARB, BB, MRA, and ARNI and their combinations were better than the treatment with placebo in reducing all-cause mortality, with the exception of ARB monotherapy and ARB plus ACEI. The combination of ARNI+BB+MRA resulted in the greatest mortality reduction. PMID:28087688

Usefulness of the troponin-ejection fraction product to differentiate stress cardiomyopathy from ST-segment elevation myocardial infarction.

PubMed

Nascimento, Francisco O; Yang, Solomon; Larrauri-Reyes, Maiteder; Pineda, Andres M; Cornielle, Vertilio; Santana, Orlando; Heimowitz, Todd B; Stone, Gregg W; Beohar, Nirat

2014-02-01

The presentation of stress cardiomyopathy (SC) with nonobstructive coronary artery disease mimics that of ST-segment elevation myocardial infarction (STEMI) due to coronary occlusion. No single parameter has been successful in differentiating the 2 entities. We thus sought to develop a noninvasive clinical tool to discriminate between these 2 conditions. We retrospectively reviewed 59 consecutive cases of SC at our institution from July 2005 through June 2011 and compared those with 60 consecutives cases of angiographically confirmed STEMI treated with primary percutaneous coronary intervention in the same period. All patients underwent acute echocardiography, and the peak troponin I level was determined. The troponin-ejection fraction product (TEFP) was derived by multiplying the peak troponin I level and the echocardiographically derived left ventricular ejection fraction. Comparing the SC and STEMI groups, the mean left ventricular ejection fraction at the time of presentation was 30 ± 9% versus 44 ± 11%, respectively (p <0.001), and the peak troponin I was 7.6 ± 18 versus 102.2 ± 110.3 ng/dl, respectively (p <0.001). The mean TEFP was thus 182 ± 380 and 4,088 ± 4,244 for the SC and STEMI groups, respectively (p <0.001). Receiver operating characteristic curve analysis showed that a TEFP value ≥250 had a sensitivity of 95%, a specificity of 87%, a negative predictive value of 94%, a positive predictive value of 88%, and an overall accuracy of 91% to differentiate a true STEMI from SC (C-statistic 0.91 ± 0.02, p <0.001). In conclusion, for patients not undergoing emergent angiography, the TEFP may be used with high accuracy to differentiate SC with nonobstructive coronary artery disease from true STEMI due to coronary occlusion. Copyright © 2014 Elsevier Inc. All rights reserved.

Mid-range Ejection Fraction Does Not Permit Risk Stratification Among Patients Hospitalized for Heart Failure.

PubMed

Gómez-Otero, Inés; Ferrero-Gregori, Andreu; Varela Román, Alfonso; Seijas Amigo, José; Pascual-Figal, Domingo A; Delgado Jiménez, Juan; Álvarez-García, Jesús; Fernández-Avilés, Francisco; Worner Diz, Fernando; Alonso-Pulpón, Luis; Cinca, Juan; Gónzalez-Juanatey, José Ramón

2017-05-01

European Society of Cardiology heart failure guidelines include a new patient category with mid-range (40%-49%) left ventricular ejection fraction (HFmrEF). HFmrEF patient characteristics and prognosis are poorly defined. The aim of this study was to analyze the HFmrEF category in a cohort of hospitalized heart failure patients (REDINSCOR II Registry). A prospective observational study was conducted with 1420 patients classified according to ejection fraction as follows: HFrEF, < 40%; HFmrEF, 40%-49%; and HFpEF, ≥ 50%. Baseline patient characteristics were examined, and outcome measures were mortality and readmission for heart failure at 1-, 6-, and 12-month follow-up. Propensity score matching was used to compare the HFmrEF group with the other ejection fraction groups. Among the study participants, 583 (41%) had HFrEF, 227 (16%) HFmrEF, and 610 (43%) HFpEF. HFmrEF patients had a clinical profile similar to that of HFpEF patients in terms of age, blood pressure, and atrial fibrillation prevalence, but shared with HFrEF patients a higher proportion of male participants and ischemic etiology, and use of class I drugs targeting HFrEF. All other features were intermediate, and comorbidities were similar among the 3 groups. There were no significant differences in all-cause mortality, cause of death, or heart failure readmission. The similar outcomes were confirmed in the propensity score matched cohorts. The HFmrEF patient group has characteristics between the HFrEF and HFpEF groups, with more similarities to the HFpEF group. No between-group differences were observed in total mortality, cause of death, or heart failure readmission. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Rationale, Design, and Methodology of the APOLLON trial: A comPrehensive, ObservationaL registry of heart faiLure with midrange and preserved ejectiON fraction.

PubMed

Özlek, Bülent; Özlek, Eda; Çelik, Oğuzhan; Çil, Cem; Doğan, Volkan; Tekinalp, Mehmet; Zencirkıran Ağuş, Hicaz; Kahraman, Serkan; Ösken, Altuğ; Rencüzoğulları, İbrahim; Tanık, Veysel Ozan; Bekar, Lütfü; Çakır, Mustafa Ozan; Kaya, Bedri Caner; Tibilli, Hakan; Çelik, Yunus; Başaran, Özcan; Mert, Kadir Uğur; Sevinç, Samet; Demirci, Erkan; Dondurmacı, Engin; Biteker, Murat

2018-05-01

Although almost half of chronic heart failure (HF) patients have mid-range (HFmrEF) and preserved left-ventricular ejection fraction (HFpEF), no studies have been carried out with these patients in our country. This study aims to determine the demographic characteristics and current status of the clinical background of HFmrEF and HFpEF patients in a multicenter trial. A comPrehensive, ObservationaL registry of heart faiLure with mid range and preserved ejectiON fraction (APOLLON) trial will be an observational, multicenter, and noninterventional study conducted in Turkey. The study population will include 1065 patients from 12 sites in Turkey. All data will be collected at one point in time and the current clinical practice will be evaluated (ClinicalTrials.gov number NCT03026114). We will enroll all consecutive patients admitted to the cardiology clinics who were at least 18 years of age and had New York Heart Association class II, III, or IV HF, elevated brain natriuretic peptide levels within the last 30 days, and an left ventricular ejection fraction (LVEF) of at least 40%. Patients fulfilling the exclusion criteria will not be included in the study. Patients will be stratified into two categories according to LVEF: mid-range EF (HFmrEF, LVEF 40%-49%) and preserved EF (HFpEF, LVEF ≥50%). Regional quota sampling will be performed to ensure that the sample was representative of the Turkish population. Demographic, lifestyle, medical, and therapeutic data will be collected by this specific survey. The APOLLON trial will be the largest and most comprehensive study in Turkey evaluating HF patients with a LVEF ≥40% and will also be the first study to specifically analyze the recently designated HFmrEF category.

Impact of Obstructive Sleep Apnoea on Heart Failure with Preserved Ejection Fraction.

PubMed

Arikawa, Takuo; Toyoda, Shigeru; Haruyama, Akiko; Amano, Hirohisa; Inami, Shu; Otani, Naoyuki; Sakuma, Masashi; Taguchi, Isao; Abe, Shichiro; Node, Koichi; Inoue, Teruo

2016-05-01

The impact of obstructive sleep apnoea on heart failure with preserved ejection fraction is unknown. Fifty-eight patients who had heart failure with a left ventricular ejection fraction; ≥50% underwent a sleep study. Brain natriuretic peptide (BNP) levels were determined at enrolment and at one, six, 12 and 36 months after enrolment. Obstructive sleep apnoea was found in 39 patients (67%), and they were all subsequently treated with continuous positive airway pressure. Echocardiography at admission showed that E/E' tended to be higher in the 39 patients with, than in the 19 patients without, obstructive sleep apnoea (15.0±3.6 vs 12.1±1.9, respectively, P=0.05). The median BNP levels at enrolment were similar in patients with and without obstructive sleep apnoea [median (interquartile range): 444 (233-752) vs 316 (218-703) pg/ml]. Although BNP levels decreased over time in both groups, the reduction was less pronounced in patients with obstructive sleep apnoea (P<0.05). Consequently, BNP levels were higher in patients with sleep apnoea at six months, [221 (137-324) vs 76 (38-96) pg/ml, P<0.05], 12 months [123 (98-197) vs 52 (38-76) pg/ml, P<0.05] and 36 months [115 (64-174) vs 56 (25-74) pg/ml, P<0.05]. Obstructive sleep apnoea, even when treated appropriately, may worsen long-term cardiac function and outcomes in patients who have heart failure with preserved ejection fraction. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Autonomic regulation therapy to enhance myocardial function in heart failure patients: the ANTHEM‐HFpEF study

PubMed Central

DiCarlo, Lorenzo A.; Libbus, Imad; Kumar, H. Uday; Mittal, Sanjay; Premchand, Rajendra K.; Amurthur, Badri; KenKnight, Bruce H.; Ardell, Jeffrey L.

2017-01-01

Abstract Background Approximately half of the patients presenting with new‐onset heart failure (HF) have HF with preserved left ventricular ejection fraction (HFpEF) and HF with mid‐range left ventricular ejection fraction (HFmrEF). These patients have neurohormonal activation like that of HF with reduced ejection fraction; however, beta‐blockers and angiotensin‐converting enzyme inhibitors have not been shown to improve their outcomes, and current treatment for these patients is symptom based and empiric. Sympathoinhibition using parasympathetic stimulation has been shown to improve central and peripheral aspects of the cardiac nervous system, reflex control, induce myocyte cardioprotection, and can lead to regression of left ventricular hypertrophy. Beneficial effects of autonomic regulation therapy (ART) using vagus nerve stimulation (VNS) have also been observed in several animal models of HFpEF, suggesting a potential role for ART in patients with this disease. Methods The Autonomic Neural Regulation Therapy to Enhance Myocardial Function in Patients with Heart Failure and Preserved Ejection Fraction (ANTHEM‐HFpEF) study is designed to evaluate the feasibility, tolerability, and safety of ART using right cervical VNS in patients with chronic, stable HFpEF and HFmrEF. Patients with symptomatic HF and HFpEF or HFmrEF fulfilling the enrolment criteria will receive chronic ART with a subcutaneous VNS system attached to the right cervical vagus nerve. Safety parameters will be continuously monitored, and cardiac function and HF symptoms will be assessed every 3 months during a post‐titration follow‐up period of at least 12 months. Conclusions The ANTHEM‐HFpEF study is likely to provide valuable information intended to expand our understanding of the potential role of ART in patients with chronic symptomatic HFpEF and HFmrEF. PMID:29283224

Exercise for Preventing Hospitalization and Readmission in Adults with Congestive Heart Failure.

PubMed

Aronow, Wilbert S; Shamliyan, Tatyana A

2018-05-04

We critically appraised all available evidence regarding exercise interventions for improving patient survival and reducing hospital admissions in adults with chronic heart failure (HF). We searched 4 databases up to April 2018 and graded the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group approach. We reviewed 7 meta-analyses and the publications of 48 randomized, controlled trials (RCT). In HF with reduced ejection fraction, low-quality evidence suggests that exercise prevents all-cause hospitalizations (RR 0.77; 95% CI 0.63;0.93; 1328 patients in 15 RCTs) and hospitalizations due to HF (RR 0.57; 95% CI 0.37;0.88; 1073 patients in 13 RCTs) and improves quality of life (standardized mean difference [SMD] -0.37; 95% CI -0.60;-0.14; 1270 patients in 25 RCTs) but has no effect on mortality. In HF with preserved ejection fraction, low-quality evidence suggests that exercise improves peak oxygen uptake (mean difference [MD] 2.36; 95% CI 1.16;3.57; 171 patients in 3 RCTs) and quality of life (MD -4.65; 95% CI -8.46;-0.83; 203 patients in 4 RCTs). In patients after heart transplantation, low-quality evidence suggests that exercise improves peak oxygen uptake (SMD 0.68; 95% CI 0.43;0.93; 284 patients in 9 RCTs) but does not improve quality of life. In order to reduce hospitalization and improve quality of life for adults with HF and reduced ejection fraction, clinicians should recommend exercise interventions. For adults with HF and preserved ejection fraction and in those undergoing heart transplantation, clinicians may recommend exercise interventions in order to improve peak oxygen uptake.

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.

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.

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

[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.

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.

The management of patients with aortic regurgitation and severe left ventricular dysfunction: a systematic review.

PubMed

Badar, Athar A; Brunton, Alan P T; Mahmood, Ammad H; Dobbin, Stephen; Pozzi, Andrea; McMinn, Jenna F; Sinclair, Andrew J E; Gardner, Roy S; Petrie, Mark C; Curry, Phil A; Al-Attar, Nawwar H K; Pettit, Stephen J

2015-01-01

A systematic search of Medline, EMBASE and CINAHL electronic databases was performed. Original research articles reporting all-cause mortality following surgery in patients with aortic regurgitation and severe left ventricular systolic dysfunction (LVSD) were identified. Nine of the 10 eligible studies were observational, single-center, retrospective analyses. Survival ranged from 86 to 100% at 30 days; 81 to 100% at 1 year and 68 to 84% at 5 years. Three studies described an improvement in mean left ventricular ejection fraction (LVEF) following aortic valve replacement (AVR) of 5-14%; a fourth study reported an increase in mean left ventricular ejection fraction (LVEF) of 9% in patients undergoing isolated AVR but not when AVR was combined with coronary artery bypass graft and/or mitral valve surgery. Three studies demonstrated improvements in functional New York Heart Association (NYHA) class following AVR. Additional studies are needed to clarify the benefits of AVR in patients with more extreme degrees of left ventricular systolic dysfunction (LVSD) and the potential roles of cardiac transplantation and transaortic valve implantation.

The left ventricle in aortic stenosis--imaging assessment and clinical implications.

PubMed

Călin, Andreea; Roşca, Monica; Beladan, Carmen Cristiana; Enache, Roxana; Mateescu, Anca Doina; Ginghină, Carmen; Popescu, Bogdan Alexandru

2015-04-29

Aortic stenosis has an increasing prevalence in the context of aging population. In these patients non-invasive imaging allows not only the grading of valve stenosis severity, but also the assessment of left ventricular function. These two goals play a key role in clinical decision-making. Although left ventricular ejection fraction is currently the only left ventricular function parameter that guides intervention, current imaging techniques are able to detect early changes in LV structure and function even in asymptomatic patients with significant aortic stenosis and preserved ejection fraction. Moreover, new imaging parameters emerged as predictors of disease progression in patients with aortic stenosis. Although proper standardization and confirmatory data from large prospective studies are needed, these novel parameters have the potential of becoming useful tools in guiding intervention in asymptomatic patients with aortic stenosis and stratify risk in symptomatic patients undergoing aortic valve replacement.This review focuses on the mechanisms of transition from compensatory left ventricular hypertrophy to left ventricular dysfunction and heart failure in aortic stenosis and the role of non-invasive imaging assessment of the left ventricular geometry and function in these patients.

Heart Failure with Preserved Ejection Fraction - Concept, Pathophysiology, Diagnosis and Challenges for Treatment.

PubMed

Miljkovik, Lidija Veterovska; Spiroska, Vera

2015-09-15

Heart failure (HF) with preserved left ventricular (LV) ejection fraction (HFpEF) occurs in 40 to 60% of the patients with HF, with a prognosis which is similar to HF with reduced ejection fraction (HFrEF). HFpEF pathophysiology is different from that of HFrEF, and has been characterized with diastolic dysfunction. Diastolic dysfunction has been defined with elevated left ventricular stiffness, prolonged iso-volumetric LV relaxation, slow LV filing and elevated LV end-diastolic pressure. Arterial hypertension occurs in majority cases with HFpEF worldwide. Patients are mostly older and obese. Diabetes mellitus and atrial fibrillation appear proportionally in a high frequency of patients with HFpEF. The HFpEF diagnosis is based on existence of symptoms and signs of heart failure, normal or approximately normal ejection and diagnosing of LV diastolic dysfunction by means of heart catheterization or Doppler echocardiography and/or elevated concentration of plasma natriuretic peptide. The present recommendations for HFpEF treatment include blood pressure control, heart chamber frequency control when atrial fibrillation exists, in some situations even coronary revascularization and an attempt for sinus rhythm reestablishment. Up to now, it is considered that no medication or a group of medications improve the survival of HFpEF patients. Due to these causes and the bad prognosis of the disorder, rigorous control is recommended of the previously mentioned precipitating factors for this disorder. This paper presents a universal review of the most important parameters which determine this disorder.

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.

The sympathetic/parasympathetic imbalance in heart failure with reduced ejection fraction

PubMed Central

Floras, John S.; Ponikowski, Piotr

2015-01-01

Cardiovascular autonomic imbalance, a cardinal phenotype of human heart failure, has adverse implications for symptoms during wakefulness and sleep; for cardiac, renal, and immune function; for exercise capacity; and for lifespan and mode of death. The objectives of this Clinical Review are to summarize current knowledge concerning mechanisms for disturbed parasympathetic and sympathetic circulatory control in heart failure with reduced ejection fraction and its clinical and prognostic implications; to demonstrate the patient-specific nature of abnormalities underlying this common phenotype; and to illustrate how such variation provides opportunities to improve or restore normal sympathetic/parasympathetic balance through personalized drug or device therapy. PMID:25975657

Foundations of Pharmacotherapy for Heart Failure With Reduced Ejection Fraction: Evidence Meets Practice, Part II.

PubMed

McIlvennan, Colleen K; Page, Robert L

Pharmacologic treatment for systolic heart failure, otherwise known as heart failure with reduced ejection fraction, has been established through clinical trials and is formulated into guidelines to standardize the diagnosis and treatment. Since the introduction of angiotensin-converting enzyme inhibitors and vasodilators in the 1980s, many guideline-recommended therapies have emerged over the past 20 years targeting specific neurohormones, aldosterone, and catecholamines to treat heart failure. Part 2 of this series will describe β-blockers, digoxin, and aldosterone antagonists in the context of the mechanism of action in heart failure, investigational trials that showed beneficial effects, and the practical applications for clinical use.

Exercise physiology in heart failure and preserved ejection fraction.

PubMed

Haykowsky, Mark J; Kitzman, Dalane W

2014-07-01

Recent advances in the pathophysiology of exercise intolerance in patients with heart failure with preserved ejection fraction (HFPEF) suggest that noncardiac peripheral factors contribute to the reduced peak V(o2) (peak exercise oxygen uptake) and to its improvement after endurance exercise training. A greater understanding of the peripheral skeletal muscle vascular adaptations that occur with physical conditioning may allow for tailored exercise rehabilitation programs. The identification of specific mechanisms that improve whole body and peripheral skeletal muscle oxygen uptake could establish potential therapeutic targets for medical therapies and a means to follow therapeutic response. Copyright © 2014 Elsevier Inc. All rights reserved.

Transient Cardiomyopathy and Quadriplegia Induced by Ephedrine Decongestant.

PubMed

Snipelisky, David F; Kurklinsky, Andrew K; Chirila, Razvan

2015-12-01

Ephedrine decongestant products are widely used. Common side effects include palpitations, nervousness, and headache. More severe adverse reactions include cardiomyopathy and vasospasm. We report the case of an otherwise healthy 37-year-old woman who presented with acute-onset quadriplegia and heart failure. She had a normal chest radiograph on admission, but developed marked pulmonary edema and bilateral effusions the next day. Echocardiography revealed a left ventricular ejection fraction of 0.18 and no obvious intrinsic pathologic condition such as foramen narrowing on spinal imaging. Laboratory screening was positive for methamphetamines in the urine, and the patient admitted to having used, over the past several weeks, multiple ephedrine-containing products for allergy-symptom relief. She was ultimately diagnosed with an acute catecholamine-induced cardiomyopathy and spinal artery vasospasm consequential to excessive use of decongestants. Her symptoms resolved completely with supportive care and appropriate heart-failure management. An echocardiogram 2 weeks after admission showed improvement of the left ventricular ejection fraction to 0.33. Ten months after the event, the patient was entirely asymptomatic and showed further improvement of her ejection fraction to 0.45. To our knowledge, ours is the first report of spinal artery vasospasm resulting in quadriplegia in a human being after ephedrine ingestion.

Riser Pattern Is a Novel Predictor of Adverse Events in Heart Failure Patients With Preserved Ejection Fraction.

PubMed

Komori, Takahiro; Eguchi, Kazuo; Saito, Toshinobu; Hoshide, Satoshi; Kario, Kazuomi

2017-01-25

The cardiovascular prognosis of heart failure with preserved ejection fraction (HFpEF) has been shown to be similar to that of heart failure with reduced ejection fraction (HFrEF). It is unknown which factors predict cardiovascular outcome in HFpEF. We tested the hypothesis that the abnormal pattern of circadian blood pressure (BP) rhythm known as the riser BP pattern is associated with adverse outcomes in HFpEF.Methods and Results:We performed a prospective, observational cohort study of hospitalized HF patients who underwent ambulatory BP monitoring (ABPM). Five hundred and sixteen hospitalized HF patients (age, 69±13 years; male, n=321 [62%]; female, n=195 [38%]) were followed up for a median 20.9 months. The composite outcome consisting of all-cause mortality and cardiovascular events was observed in 220 patients. On Kaplan-Meier analysis, the riser BP pattern subgroup had a significantly higher incidence of the composite outcome than the other subgroups of HFpEF patients (HR, 3.01; 95% CI: 1.54-6.08, P<0.01), but not the HFrEF patients. The riser BP pattern was found to be a novel predictor of cardiovascular outcome in HFpEF patients.

Outcome of Heart Failure with Preserved Ejection Fraction: A Multicentre Spanish Registry

PubMed Central

Castillo, Juan C; Anguita1, Manuel P; Jiménez, Manuel

2009-01-01

Background: Studies on clinical features, treatment and prognosis of patients with congestive heart failure (CHF) and preserved left ventricular ejection fraction (LVEF) are few and their results frequently conflicting. Aims: To investigate the characteristics and long term prognosis of patients with CHF and preserved (≥ 45%) LVEF. Methods and Results: We conducted a prospective multicentre study with 4720 patients attended in 62 heart failure clinics from 1999 to 2003 in Spain (BADAPIC registry). LVEF was preserved in 30% patients. Age, female gender, prevalence of atrial fibrillation, hypertension and non-ischaemic cardiopathy were all significantly greater in patients with preserved LVEF. Mean follow-up was 40±12 months. Mortality and other cardiovascular complication rates during follow up were similar in both groups. On multivariate analysis ejection fraction was not an independent predictor for mortality. Survival at one and five years was similar in both groups (79% and 59% for patients with preserved LVEF and 78% and 57% for those with reduced LVEF, respectively). Conclusions: In the BADAPIC registry, a high percentage of heart failure patients had preserved LVEF. Although clinical differences were seen between groups, morbidity and mortality were similar in both groups. PMID:21037850

Off-pump surgery: a choice in unstable angina.

PubMed

Kohli, Vijay; Goel, Mukesh; Sharma, Vijay Kumar; Mishra, Yugal; Malhotra, Rajneesh; Mehta, Yatin; Trehan, Naresh

2003-12-01

The benefit and safety of off-pump coronary artery bypass surgery in patients with unstable angina was assessed retrospectively. From February 1996 to October 2001, 5,306 patients underwent multivessel off-pump coronary artery bypass, of whom 920 (17%) had unstable angina. In these 920 patients, ejection fractions ranged from 15% to 70%, 203 (22%) had an ejection fraction of 20%-35%, and 11 (1%) had an ejection fraction < 20%. Triple-vessel disease was present in 625 patients. Preoperative intraaortic balloon pump support was used in 28 patients. Operative approaches included mid sternotomy (86%), lower partial sternotomy (9%), and left anterior thoracotomy (2%). The number of grafts ranged from 1 to 5 with a mean of 2.43 +/- 0.86, and 92.3% of patients received a left internal mammary artery graft. Twenty-two patients need intraoperative intraaortic balloon pumping. Ten patients (1%) suffered perioperative myocardial infarction. The mean hospital stay was 7.8 +/- 4.3 days. Hospital mortality was 2/920 (0.22%). Intraaortic balloon pumping was helpful in these cases of unstable angina refractory to medical therapy. Off-pump coronary artery surgery was found to be safe and beneficial in these patients.

Left atrial function in heart failure with impaired and preserved ejection fraction.

PubMed

Fang, Fang; Lee, Alex Pui-Wai; Yu, Cheuk-Man

2014-09-01

Left atrial structural and functional changes in heart failure are relatively ignored parts of cardiac assessment. This review illustrates the pathophysiological and functional changes in left atrium in heart failure as well as their prognostic value. Heart failure can be divided into those with systolic dysfunction and heart failure with preserved ejection fraction (HFPEF). Left atrial enlargement and dysfunction commonly occur in systolic heart failure, in particular, in idiopathic dilated cardiomyopathy. Atrial enlargement and dysfunction also carry important prognostic value in systolic heart failure, independently of known parameters such as left ventricular ejection fraction. In HFPEF, there is evidence of left atrial enlargement, impaired atrial compliance, and reduction of atrial pump function. This occurs not only at rest but also during exercise, indicating significant impairment of atrial contractile reserve. Furthermore, atrial dyssynchrony is common in HFPEF. These factors further contribute to the development of new onset or progression of atrial arrhythmias, in particular, atrial fibrillation. Left atrial function is an integral part of cardiac function and its structural and functional changes in heart failure are common. As changes of left atrial structure and function have different clinical implications in systolic heart failure and HFPEF, routine assessment is warranted.

Plasma Biomarkers Reflecting Profibrotic Processes in Heart Failure With a Preserved Ejection Fraction

PubMed Central

Zile, Michael R.; Jhund, Pardeep S.; Baicu, Catalin F.; Claggett, Brian L.; Pieske, Burkert; Voors, Adriaan A.; Prescott, Margaret F.; Shi, Victor; Lefkowitz, Martin; McMurray, John J.V.; Solomon, Scott D.

2017-01-01

Background Heart failure with preserved ejection fraction is a clinical syndrome that has been associated with changes in the extracellular matrix. The purpose of this study was to determine whether profibrotic biomarkers accurately reflect the presence and severity of disease and underlying pathophysiology and modify response to therapy in patients with heart failure with preserved ejection fraction. Methods and Results Four biomarkers, soluble form of ST2 (an interleukin-1 receptor family member), galectin-3, matrix metalloproteinase-2, and collagen III N-terminal propeptide were measured in the Prospective Comparison of ARNI With ARB on Management of Heart Failure With Preserved Ejection Fraction (PARAMOUNT) trial at baseline, 12 and 36 weeks after randomization to valsartan or LCZ696. We examined the relationship between baseline biomarkers, demographic and echocardiographic characteristics, change in primary (change in N-terminal pro B-type natriuretic peptide) and secondary (change in left atrial volume) end points. The median (interquartile range) value for soluble form of ST2 (33 [24.6–48.1] ng/mL) and galectin 3 (17.8 [14.1–22.8] ng/mL) were higher, and for matrix metalloproteinase-2 (188 [155.5–230.6] ng/mL) lower, than in previously published referent controls; collagen III N-terminal propeptide (5.6 [4.3–6.9] ng/mL) was similar to referent control values. All 4 biomarkers correlated with severity of disease as indicated by N-terminal pro B-type natriuretic peptide, E/E′, and left atrial volume. Baseline biomarkers did not modify the response to LCZ696 for lowering N-terminal pro B-type natriuretic peptide; however, left atrial volume reduction varied by baseline level of soluble form of ST2 and galectin 3; patients with values less than the observed median (<33 ng/mL soluble form of ST2 and <17.8 ng/mL galectin 3) had reduction in left atrial volume, those above median did not. Although LCZ696 reduced N-terminal pro B-type natriuretic peptide, levels of the other 4 biomarkers were not affected over time. Conclusions In patients with heart failure with preserved ejection fraction, biomarkers that reflect collagen homeostasis correlated with the presence and severity of disease and underlying pathophysiology, and may modify the structural response to treatment. PMID:26754625

Adaptive servo ventilation for central sleep apnoea in heart failure: SERVE-HF on-treatment analysis.

PubMed

Woehrle, Holger; Cowie, Martin R; Eulenburg, Christine; Suling, Anna; Angermann, Christiane; d'Ortho, Marie-Pia; Erdmann, Erland; Levy, Patrick; Simonds, Anita K; Somers, Virend K; Zannad, Faiez; Teschler, Helmut; Wegscheider, Karl

2017-08-01

This on-treatment analysis was conducted to facilitate understanding of mechanisms underlying the increased risk of all-cause and cardiovascular mortality in heart failure patients with reduced ejection fraction and predominant central sleep apnoea randomised to adaptive servo ventilation versus the control group in the SERVE-HF trial.Time-dependent on-treatment analyses were conducted (unadjusted and adjusted for predictive covariates). A comprehensive, time-dependent model was developed to correct for asymmetric selection effects (to minimise bias).The comprehensive model showed increased cardiovascular death hazard ratios during adaptive servo ventilation usage periods, slightly lower than those in the SERVE-HF intention-to-treat analysis. Self-selection bias was evident. Patients randomised to adaptive servo ventilation who crossed over to the control group were at higher risk of cardiovascular death than controls, while control patients with crossover to adaptive servo ventilation showed a trend towards lower risk of cardiovascular death than patients randomised to adaptive servo ventilation. Cardiovascular risk did not increase as nightly adaptive servo ventilation usage increased.On-treatment analysis showed similar results to the SERVE-HF intention-to-treat analysis, with an increased risk of cardiovascular death in heart failure with reduced ejection fraction patients with predominant central sleep apnoea treated with adaptive servo ventilation. Bias is inevitable and needs to be taken into account in any kind of on-treatment analysis in positive airway pressure studies. Copyright ©ERS 2017.

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.

Hemodynamic responses to external counterbalancing of auto-positive end-expiratory pressure in mechanically ventilated patients with chronic obstructive pulmonary disease.

PubMed

Baigorri, F; de Monte, A; Blanch, L; Fernández, R; Vallés, J; Mestre, J; Saura, P; Artigas, A

1994-11-01

To study the effect of positive end-expiratory pressure (PEEP) on right ventricular hemodynamics and ejection fraction in patients with chronic obstructive pulmonary disease and positive alveolar pressure throughout expiration by dynamic hyperinflation (auto-PEEP). Open, prospective, controlled trial. General intensive care unit of a community hospital. Ten patients sedated and paralyzed with an acute exacerbation of chronic obstructive pulmonary disease undergoing mechanical ventilation. Insertion of a pulmonary artery catheter modified with a rapid response thermistor and a radial arterial catheter. PEEP was then increased from 0 (PEEP 0) to auto-PEEP level (PEEP = auto-PEEP) and 5 cm H2O above that (PEEP = auto-PEEP +5). At each level of PEEP, airway pressures, flow and volume, hemodynamic variables (including right ventricular ejection fraction by thermodilution technique), and blood gas analyses were recorded. The mean auto-PEEP was 6.6 +/- 2.8 cm H2O and the total PEEP reached was 12.2 +/- 2.4 cm H2O. The degree of lung inflation induced by PEEP averaged 145 +/- 87 mL with PEEP = auto-PEEP and 495 +/- 133 mL with PEEP = auto-PEEP + 5. The PEEP = auto-PEEP caused a right ventricular end-diastolic pressure increase, but there was no other significant hemodynamic change. With PEEP = auto-PEEP + 5, there was a significant increase in intravascular pressures; this amount of PEEP reduced cardiac output (from 4.40 +/- 1.38 L/min at PEEP 0 to 4.13 +/- 1.48 L/min; p < .05). The cardiac output reduction induced by PEEP = auto-PEEP + 5 was > 10% in only five cases and this group of patients had significantly lower right ventricular volumes than the group with less cardiac output variation (right ventricular end-diastolic volume: 64 +/- 9 vs. 96 +/- 26 mL/m2; right ventricular end-systolic volume: 38 +/- 6 vs. 65 +/- 21 mL/m2; p < .05) without significant difference in the other variables that were measured. Neither right ventricular ejection fraction nor right ventricle volumes changed as PEEP increased, but there were marked interpatient differences and also pronounced changes in volume between stages in individual patients. In the study conditions, PEEP application up to values approaching auto-PEEP did not result in the impairment of right ventricular hemodynamics, while higher levels reduced cardiac output in selected patients.

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

Increase in cardiac myosin heavy-chain (MyHC) alpha protein isoform in hibernating ground squirrels, with echocardiographic visualization of ventricular wall hypertrophy and prolonged contraction

PubMed Central

Nelson, O. Lynne; Rourke, Bryan C.

2013-01-01

SUMMARY Deep hibernators such as golden-mantled ground squirrels (Callospermophilus lateralis) have multiple challenges to cardiac function during low temperature torpor and subsequent arousals. As heart rates fall from over 300 beats min−1 to less than 10, chamber dilation and reduced cardiac output could lead to congestive myopathy. We performed echocardiography on a cohort of individuals prior to and after several months of hibernation. The left ventricular chamber exhibited eccentric and concentric hypertrophy during hibernation and thus calculated ventricular mass was ~30% greater. Ventricular ejection fraction was mildly reduced during hibernation but stroke volumes were greater due to the eccentric hypertrophy and dramatically increased diastolic filling volumes. Globally, the systolic phase in hibernation was ~9.5 times longer, and the diastolic phase was 28× longer. Left atrial ejection generally was not observed during hibernation. Atrial ejection returned weakly during early arousal. Strain echocardiography assessed the velocity and total movement distance of contraction and relaxation for regional ventricular segments in active and early arousal states. Myocardial systolic strain during early arousal was significantly greater than the active state, indicating greater total contractile movement. This mirrored the increased ventricular ejection fraction noted with early arousal. However, strain rates were slower during early arousal than during the active period, particularly systolic strain, which was 33% of active, compared with the rate of diastolic strain, which was 67% of active. As heart rate rose during the arousal period, myocardial velocities and strain rates also increased; this was matched closely by cardiac output. Curiously, though heart rates were only 26% of active heart rates during early arousal, the cardiac output was nearly 40% of the active state, suggesting an efficient pumping system. We further analyzed proportions of cardiac myosin heavy-chain (MyHC) isoforms in a separate cohort of squirrels over 5 months, including time points before hibernation, during hibernation and just prior to emergence. Hibernating individuals were maintained in both a 4°C cold room and a 20°C warm room. Measured by SDS-PAGE, relative percentages of cardiac MyHC alpha were increased during hibernation, at both hibernacula temperatures. A potential increase in contractile speed, and power, from more abundant MyHC alpha may aid force generation at low temperature and at low heart rates. Unlike many models of cardiomyopathies where the alpha isoform is replaced by the beta isoform in order to reduce oxygen consumption, ground squirrels demonstrate a potential cardioprotective mechanism to maintain cardiac output during torpor. PMID:24072796

Therapeutic options of Angiotensin Receptor Neprilysin inhibitors (ARNis) in chronic heart failure with reduced ejection fraction: Beyond RAAS and sympathetic nervous system inhibition.

PubMed

Volterrani, Maurizio; Iellamo, Ferdinando; Senni, Michele; Piepoli, Massimo F

2017-01-01

In heart failure, in addition to the renin-angiotensin-aldosterone system and sympathetic nervous system, the natriuretic peptide (NP) system plays a fundamental role among compensating mechanisms. The NPs undergo rapid enzymatic degradation that limits their vasorelaxant, natriuretic, and diuretic actions. Degradation of NPs is partially due to the action of neprilysin, which is a membrane-bound endopeptidase found in many tissues. This article summarizes recent findings on a new natriuretic peptide-enhancing drug and their implication for future pharmacological treatment of patients suffering from heart failure with reduced ejection fraction. Copyright © 2016. Published by Elsevier Ireland Ltd.

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.

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

Production of Star-Grazing and Star-Impacting Planetestimals via Orbital Migration of Extrasolar Planets

NASA Technical Reports Server (NTRS)

Quillen, A. C.; Holman, M.

2000-01-01

During the orbital migration of a giant extrasolar planet via ejection of planetesimals (as studied by Murray et al. in 1998), inner mean-motion resonances can be strong enough to cause planetesimals to graze or impact the star. We integrate numerically the motions of particles which pass through the 3:1 or 4:1 mean-motion resonances of a migrating Jupiter-mass planet. We find that many particles can be trapped in the 3:1 or 4:1 resonances and pumped to high enough eccentricities that they impact the star. This implies that for a planet migrating a substantial fraction of its semimajor axis, a fraction of its mass in planetesimals could impact the star. This process may be capable of enriching the metallicity of the star at a time when the star is no longer fully convective. Upon close approaches to the star, the surfaces of these planetesimals will be sublimated. Orbital migration should cause continuing production of evaporating bodies, suggesting that this process should be detectable with searches for transient absorption lines in young stars. The remainder of the particles will not impact the star but can be ejected subsequently by the planet as it migrates further inward. This allows the planet to migrate a substantial fraction of its initial semimajor axis by ejecting planetesimals.

The role of arterial hypertension in development heart failure with preserved ejection fraction: just a risk factor or something more?

PubMed

Tadic, Marijana; Cuspidi, Cesare; Frydas, Athanasios; Grassi, Guido

2018-04-04

Heart failure with preserved ejection fraction (HFpEF) is an entity that still raises many questions. The agreement about definition, pathophysiology, and therapeutic approach is still missing. Arterial hypertension is present in majority of patients with HFpEF, and it is still not clear if it represent a risk factor or "sine qua non" condition for HFpEF development. The underlying mechanisms of hypertension and HFpEF involve the same biohumoral systems: renin-angiotensin-aldosterone, sympathetic nervous system, and oxidative stress. However, not all hypertensive patients have HFpEF. The predisposition of some hypertensive patients to develop HFpEF needs to be resolved. Large randomized controlled trials did not prove the usefulness of renin-angiotensin-aldosterone inhibitors, diuretics, calcium channel blockers, and beta-blockers in HFpEF patients. The majority of studies did not succeed to demonstrate the reduction of cardiovascular and all-cause mortality in HFpEF individuals. One of the major limitations in these investigations was the inconsistency of HFpEF definition, which mainly refers to left ventricular ejection fraction (LVEF) cut-off that ranged from 40 to 50% in different studies. This review article provides the available data about pathophysiology and mechanisms that connect hypertension and HFpEF, investigations and therapy used in both conditions.

Transient Cardiomyopathy and Quadriplegia Induced by Ephedrine Decongestant

PubMed Central

Kurklinsky, Andrew K.; Chirila, Razvan

2015-01-01

Ephedrine decongestant products are widely used. Common side effects include palpitations, nervousness, and headache. More severe adverse reactions include cardiomyopathy and vasospasm. We report the case of an otherwise healthy 37-year-old woman who presented with acute-onset quadriplegia and heart failure. She had a normal chest radiograph on admission, but developed marked pulmonary edema and bilateral effusions the next day. Echocardiography revealed a left ventricular ejection fraction of 0.18 and no obvious intrinsic pathologic condition such as foramen narrowing on spinal imaging. Laboratory screening was positive for methamphetamines in the urine, and the patient admitted to having used, over the past several weeks, multiple ephedrine-containing products for allergy-symptom relief. She was ultimately diagnosed with an acute catecholamine-induced cardiomyopathy and spinal artery vasospasm consequential to excessive use of decongestants. Her symptoms resolved completely with supportive care and appropriate heart-failure management. An echocardiogram 2 weeks after admission showed improvement of the left ventricular ejection fraction to 0.33. Ten months after the event, the patient was entirely asymptomatic and showed further improvement of her ejection fraction to 0.45. To our knowledge, ours is the first report of spinal artery vasospasm resulting in quadriplegia in a human being after ephedrine ingestion. PMID:26664316

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.

Early risk of mortality after coronary artery revascularization in patients with left ventricular dysfunction and potential role of the wearable cardioverter defibrillator.

PubMed

Zishiri, Edwin T; Williams, Sarah; Cronin, Edmond M; Blackstone, Eugene H; Ellis, Stephen G; Roselli, Eric E; Smedira, Nicholas G; Gillinov, A Marc; Glad, Jo Ann; Tchou, Patrick J; Szymkiewicz, Steven J; Chung, Mina K

2013-02-01

Implantation of implantable cardioverter defibrillator for prevention of sudden cardiac death is deferred for 90 days after coronary revascularization, but mortality may be highest early after cardiac procedures in patients with ventricular dysfunction. We determined mortality risk in postrevascularization patients with left ventricular ejection fraction ≤35% and compared survival with those discharged with a wearable cardioverter defibrillator (WCD). Hospital survivors after surgical (coronary artery bypass graft surgery) or percutaneous (percutaneous coronary intervention [PCI]) revascularization with left ventricular ejection fraction ≤35% were included from Cleveland Clinic and national WCD registries. Kaplan-Meier, Cox proportional hazards, propensity score-matched survival, and hazard function analyses were performed. Early mortality hazard was higher among 4149 patients discharged without a defibrillator compared with 809 with WCDs (90-day mortality post-coronary artery bypass graft surgery 7% versus 3%, P=0.03; post-PCI 10% versus 2%, P<0.0001). WCD use was associated with adjusted lower risks of long-term mortality in the total cohort (39%, P<0.0001) and both post-coronary artery bypass graft surgery (38%, P=0.048) and post-PCI (57%, P<0.0001) cohorts (mean follow-up, 3.2 years). In propensity-matched analyses, WCD use remained associated with lower mortality (58% post-coronary artery bypass graft surgery, P=0.002; 67% post-PCI, P<0.0001). Mortality differences were not attributable solely to therapies for ventricular arrhythmia. Only 1.3% of the WCD group had a documented appropriate therapy. Patients with left ventricular ejection fraction ≤35% have higher early compared to late mortality after coronary revascularization, particularly after PCI. As early hazard seemed less marked in WCD users, prospective studies in this high-risk population are indicated to confirm whether WCD use as a bridge to left ventricular ejection fraction improvement or implantable cardioverter defibrillator implantation can improve outcomes after coronary revascularization.

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.

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

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.

Race and Beta-Blocker Survival Benefit in Patients With Heart Failure: An Investigation of Self-Reported Race and Proportion of African Genetic Ancestry.

PubMed

Luzum, Jasmine A; Peterson, Edward; Li, Jia; She, Ruicong; Gui, Hongsheng; Liu, Bin; Spertus, John A; Pinto, Yigal M; Williams, L Keoki; Sabbah, Hani N; Lanfear, David E

2018-05-08

It remains unclear whether beta-blockade is similarly effective in black patients with heart failure and reduced ejection fraction as in white patients, but self-reported race is a complex social construct with both biological and environmental components. The objective of this study was to compare the reduction in mortality associated with beta-blocker exposure in heart failure and reduced ejection fraction patients by both self-reported race and by proportion African genetic ancestry. Insured patients with heart failure and reduced ejection fraction (n=1122) were included in a prospective registry at Henry Ford Health System. This included 575 self-reported blacks (129 deaths, 22%) and 547 self-reported whites (126 deaths, 23%) followed for a median 3.0 years. Beta-blocker exposure (BBexp) was calculated from pharmacy claims, and the proportion of African genetic ancestry was determined from genome-wide array data. Time-dependent Cox proportional hazards regression was used to separately test the association of BBexp with all-cause mortality by self-reported race or by proportion of African genetic ancestry. Both sets of models were evaluated unadjusted and then adjusted for baseline risk factors and beta-blocker propensity score. BBexp effect estimates were protective and of similar magnitude both by self-reported race and by African genetic ancestry (adjusted hazard ratio=0.56 in blacks and adjusted hazard ratio=0.48 in whites). The tests for interactions with BBexp for both self-reported race and for African genetic ancestry were not statistically significant in any model ( P >0.1 for all). Among black and white patients with heart failure and reduced ejection fraction, reduction in all-cause mortality associated with BBexp was similar, regardless of self-reported race or proportion African genetic ancestry. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

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.

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.

Prognostic Significance of Baseline Serum Sodium in Heart Failure With Preserved Ejection Fraction.

PubMed

Patel, Yash R; Kurgansky, Katherine E; Imran, Tasnim F; Orkaby, Ariela R; McLean, Robert R; Ho, Yuk-Lam; Cho, Kelly; Gaziano, J Michael; Djousse, Luc; Gagnon, David R; Joseph, Jacob

2018-06-13

The purpose of this study was to evaluate the relationship between serum sodium at the time of diagnosis and long term clinical outcomes in a large national cohort of patients with heart failure with preserved ejection fraction. We studied 25 440 patients with heart failure with preserved ejection fraction treated at Veterans Affairs medical centers across the United States between 2002 and 2012. Serum sodium at the time of heart failure diagnosis was analyzed as a continuous variable and in categories as follows: low (115.00-134.99 mmol/L), low-normal (135.00-137.99 mmol/L), referent group (138.00-140.99 mmol/L), high normal (141.00-143.99 mmol/L), and high (144.00-160.00 mmol/L). Multivariable Cox regression and negative binomial regression were performed to estimate hazard ratios (95% confidence interval [CI]) and incidence density ratios (95% CI) for the associations of serum sodium with mortality and hospitalizations (heart failure and all-cause), respectively. The average age of patients was 70.8 years, 96.2% were male, and 14% were black. Compared with the referent group, low, low-normal, and high sodium values were associated with 36% (95% CI, 28%-44%), 6% (95% CI, 1%-12%), and 9% (95% CI, 1%-17%) higher risk of all-cause mortality, respectively. Low and low-normal serum sodium were associated with 48% (95% CI, 10%-100%) and 38% (95% CI, 8%-77%) higher risk of number of days of heart failure hospitalizations per year, and with 44% (95% CI, 32%-56%) and 18% (95% CI, 10%-27%) higher risk of number of days of all-cause hospitalizations per year, respectively. Both elevated and reduced serum sodium, including values currently considered within normal range, are associated with adverse outcomes in patients with heart failure with preserved ejection fraction. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Right ventricular dysfunction affects survival after surgical left ventricular restoration.

PubMed

Couperus, Lotte E; Delgado, Victoria; Palmen, Meindert; van Vessem, Marieke E; Braun, Jerry; Fiocco, Marta; Tops, Laurens F; Verwey, Harriëtte F; Klautz, Robert J M; Schalij, Martin J; Beeres, Saskia L M A

2017-04-01

Several clinical and left ventricular parameters have been associated with prognosis after surgical left ventricular restoration in patients with ischemic heart failure. The aim of this study was to determine the prognostic value of right ventricular function. A total of 139 patients with ischemic heart failure (62 ± 10 years; 79% were male; left ventricular ejection fraction 27% ± 7%) underwent surgical left ventricular restoration. Biventricular function was assessed with echocardiography before surgery. The independent association between all-cause mortality and right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain was assessed. The additive effect of multiple impaired right ventricular parameters on mortality also was assessed. Baseline right ventricular fractional area change was 42% ± 9%, tricuspid annular plane systolic excursion was 18 ± 3 mm, and right ventricular longitudinal peak systolic strain was -24% ± 7%. Within 30 days after surgery, 15 patients died. Right ventricular fractional area change (hazard ratio, 0.93; 95% confidence interval, 0.88-0.98; P < .01), tricuspid annular plane systolic excursion (hazard ratio, 0.80; 95% confidence interval, 0.66-0.96; P = .02), and right ventricular longitudinal peak systolic strain (hazard ratio, 1.15; 95% confidence interval, 1.05-1.26; P < .01) were independently associated with 30-day mortality, after adjusting for left ventricular ejection fraction and aortic crossclamping time. Right ventricular function was impaired in 21%, 20%, and 27% of patients on the basis of right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain, respectively. Any echocardiographic parameter of right ventricular dysfunction was present in 39% of patients. The coexistence of several impaired right ventricular parameters per patient was independently associated with increased 30-day mortality (hazard ratio, 2.83; 95% confidence interval, 1.64-4.87, P < .01 per additional impaired parameter). Baseline right ventricular systolic dysfunction is independently associated with increased mortality in patients with ischemic heart failure undergoing surgical left ventricular restoration. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Cytoskeletal role in the transition from compensated to decompensated hypertrophy during adult canine left ventricular pressure overloading

NASA Technical Reports Server (NTRS)

Tagawa, H.; Koide, M.; Sato, H.; Zile, M. R.; Carabello, B. A.; Cooper, G. 4th

1998-01-01

Increased microtubule density causes cardiocyte contractile dysfunction in right ventricular (RV) pressure-overload hypertrophy, and these linked phenotypic and contractile abnormalities persist and progress during the transition to failure. Although more severe in cells from failing than hypertrophied RVs, the mechanical defects are normalized in each case by microtubule depolymerization. To define the role of increased microtubule density in left ventricular (LV) pressure-overload hypertrophy and failure, in a given LV we examined ventricular mechanics, sarcomere mechanics, and free tubulin and microtubule levels in control dogs and in dogs with aortic stenosis both with LV hypertrophy alone and with initially compensated hypertrophy that had progressed to LV muscle failure. In comparing initial values with those at study 8 weeks later, dogs with hypertrophy alone had a very substantial increase in LV mass but preservation of a normal ejection fraction and mean systolic wall stress. Dogs with hypertrophy and associated failure had a substantial but lesser increase in LV mass and a reduction in ejection fraction, as well as a marked increase in mean systolic wall stress. Cardiocyte contractile function was equivalent, and unaffected by microtubule depolymerization, in cells from control LVs and those with compensated hypertrophy. In contrast, cardiocyte contractile function in cells from failing LVs was quite depressed but was normalized by microtubule depolymerization. Microtubules were increased only in failing LVs. These contractile and cytoskeletal changes, when assayed longitudinally in a given dog by biopsy, appeared in failing ventricles only when wall stress began to increase and function began to decrease. Thus, the microtubule-based cardiocyte contractile dysfunction characteristic of pressure-hypertrophied myocardium, originally described in the RV, obtains equally in the LV but is shown here to have a specific association with increased wall stress.

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

Relationship between plasma levels of cardiac natriuretic peptides and soluble Fas: plasma soluble Fas as a prognostic predictor in patients with congestive heart failure.

PubMed

Tsutamoto, T; Wada, A; Maeda, K; Mabuchi, N; Hayashi, M; Tsutsui, T; Ohnishi, M; Fujii, M; Matsumoto, T; Yamamoto, T; Takayama, T; Kinoshita, M

2001-12-01

Cardiac natriuretic peptides may induce apoptosis in myocytes; however, the relationship between plasma levels of cardiac natriuretic peptides and those of soluble Fas (sFas) and tumor necrosis factor (TNF)-alpha remains unknown in patients with congestive heart failure (CHF). We measured plasma levels of sFas and TNF-alpha and those of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), norepinephrine, and endothelin 1 in 96 patients with CHF (ejection fraction < 45%). The patients were monitored for 3 years. Plasma levels of sFas and TNF-alpha increased with the severity of CHF. There was no significant correlation between sFas plasma levels and those of ANP and BNP. Cox proportional hazard analysis showed that high levels of sFas (P = .009) and BNP (P < .0001) and a low ejection fraction (P = .019) were independent significant prognostic predictors. There is no significant correlation between cardiac natriuretic peptide and sFas levels in plasma. Plasma sFas is a useful prognostic marker independent of neurohumoral factors, suggesting that immune activation and/or apoptosis play a significant role in the pathogenesis of CHF.

B-type natriuretic peptide testing for detection of heart failure.

PubMed

Saul, Lauren; Shatzer, Melanie

2003-01-01

The incidence of heart failure (HF) is on the increase with the aging population. Heart failure can manifest as either systolic or diastolic dysfunction. Systolic dysfunction causes impaired ventricular contractility with an ejection fraction of less than 45%. In contrast, diastolic dysfunction is evidenced by impaired ventricular relaxation and an ejection fraction greater than 45%. The diagnosis of HF is challenging with patients who present with acute dyspnea and a history of chronic obstructive pulmonary disease or pneumonia. The pathophysiology of HF and the resulting compensatory mechanisms involve a complex neuroendocrine response that includes a release of natriuretic peptides including B-type natriuretic peptides (BNPs). Elevation of BNP is in response to ventricular wall stress and volume overload from HF. BNP promotes natriuresis, diuresis, and vasodilitation and therefore counteracts some of the deleterious effects of the neuroendocrine response in HF Recently, a new laboratory test for BNP has been developed to assist in rapid identification of patients with HF. Research studies have shown that BNP testing assists in differentiating between cardiac and pulmonary causes of acute dyspnea and could be used to evaluate effectiveness of therapy and as a predictor for length of stay and readmission.

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

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

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.

Predictors of Increased Left Ventricular Filling Pressure in Dialysis Patients with Preserved Left Ventricular Ejection Fraction

PubMed Central

Bajraktari, Gani; Berbatovci-Ukimeraj, Mimoza; Hajdari, Ali; Ibraimi, Lavdim; Daullxhiu, Irfan; Elezi, Ymer; Ndrepepa, Gjin

2009-01-01

Aim To study the left and right ventricular function and to assess the predictors of increased left ventricular (LV) filling pressure in dialysis patients with preserved LV ejection fraction. Methods This study included 63 consecutive patients (age 57 ± 14 years, 57% women) with end-stage renal failure. Echocardiography, including tissue Doppler measurements, was performed in all patients. Based on the median value of the ratio of transmitral early diastolic velocity to early myocardial velocity (E/E’ ratio), patients were divided into 2 groups: the group with high filling pressure (E/E’>10.16) and the group with low filling pressure (E/E’≤10.16). Results Compared with patients with low filling pressure, the group of patients with high filling pressure included a higher proportion of diabetic patients (41% vs 13%, P = 0.022) and had greater LV mass index (211 ± 77 vs 172 ± 71 g/m3, P = 0.04), lower LV lateral long axis amplitude (1.4 ± 0.3 vs 1.6 ± 0.3 cm, P = 0.01), higher E wave (84 ± 19 vs 64 ± 18cm/s, P < 0.001), lower systolic myocardial velocity (S’:8.6 ± 1.5 vs 7.0 ± 1.3 cm/s, P < 0.001), and lower diastolic myocardial velocities (E’: 6.3 ± 1.9 vs 9.5 ± 2.9 cm/s, P < 0.001; A’: 8.4 ± 1.9 vs 9.7 ± 2.5 cm/s, P = 0.018). Multivariate analysis identified LV systolic myocardial velocity – S’ wave (adjusted odds ratio, 1.909; 95% confidence interval, 1.060-3.439; P = 0.031) and age (1.053; 1.001-1.108; P = 0.048) as the only independent predictors of high LV filling pressure in dialysis patients. Conclusions In dialysis patients with preserved left ventricular ejection fraction, reduced systolic myocardial velocity and elderly age are independent predictors of increased left ventricular filling pressure. PMID:20017222

Efficacy and safety of out-of-hospital intravenous metoprolol administration in anterior ST-segment elevation acute myocardial infarction: insights from the METOCARD-CNIC trial.

PubMed

Mateos, Alonso; García-Lunar, Inés; García-Ruiz, José M; Pizarro, Gonzalo; Fernández-Jiménez, Rodrigo; Huertas, Pilar; García-Álvarez, Ana; Fernández-Friera, Leticia; Bravo, Jesús; Flores-Arias, José; Barreiro, María V; Chayán-Zas, Luisa; Corral, Ervigio; Fuster, Valentín; Sánchez-Brunete, Vicente; Ibáñez, Borja

2015-03-01

We seek to examine the efficacy and safety of prereperfusion emergency medical services (EMS)-administered intravenous metoprolol in anterior ST-segment elevation myocardial infarction patients undergoing eventual primary angioplasty. This is a prespecified subgroup analysis of the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction trial population, who all eventually received oral metoprolol within 12 to 24 hours. We studied patients receiving intravenous metoprolol by EMS and compared them with others treated by EMS but not receiving intravenous metoprolol. Outcomes included infarct size and left ventricular ejection fraction on cardiac magnetic resonance imaging at 1 week, and safety by measuring the incidence of the predefined combined endpoint (composite of death, malignant ventricular arrhythmias, advanced atrioventricular block, cardiogenic shock, or reinfarction) within the first 24 hours. From the total population of the trial (N=270), 147 patients (54%) were recruited during out-of-hospital assistance and transferred to the primary angioplasty center (74 intravenous metoprolol and 73 controls). Infarct size was smaller in patients receiving intravenous metoprolol compared with controls (23.4 [SD 15.0] versus 34.0 [SD 23.7] g; adjusted difference -11.4; 95% confidence interval [CI] -18.6 to -4.3). Left ventricular ejection fraction was higher in the intravenous metoprolol group (48.1% [SD 8.4%] versus 43.1% [SD 10.2%]; adjusted difference 5.0; 95% CI 1.6 to 8.4). Metoprolol administration did not increase the incidence of the prespecified safety combined endpoint: 6.8% versus 17.8% in controls (risk difference -11.1; 95% CI -21.5 to -0.6). Out-of-hospital administration of intravenous metoprolol by EMS within 4.5 hours of symptom onset in our subjects reduced infarct size and improved left ventricular ejection fraction with no excess of adverse events during the first 24 hours. Copyright © 2014 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

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.

Effects of extracorporeal cardiopulmonary resuscitation on neurological and cardiac outcome after ischaemic refractory cardiac arrest.

PubMed

Cesana, Francesca; Avalli, Leonello; Garatti, Laura; Coppo, Anna; Righetti, Stefano; Calchera, Ivan; Scanziani, Elisabetta; Cozzolino, Paolo; Malafronte, Cristina; Mauro, Andrea; Soffici, Federica; Sulmina, Endrit; Bozzon, Veronica; Maggioni, Elena; Foti, Giuseppe; Achilli, Felice

2017-10-01

Extracorporeal cardiopulmonary resuscitation is increasingly recognised as a rescue therapy for refractory cardiac arrest, nevertheless data are scanty about its effects on neurologic and cardiac outcome. The aim of this study is to compare clinical outcome in patients with cardiac arrest of ischaemic origin (i.e. critical coronary plaque during angiography) and return of spontaneous circulation during conventional cardiopulmonary resuscitation vs refractory cardiac arrest patients needing extracorporeal cardiopulmonary resuscitation. Moreover, we tried to identify predictors of survival after successful cardiopulmonary resuscitation. We enrolled 148 patients with ischaemic cardiac arrest admitted to our hospital from 2011-2015. We compared clinical characteristics, cardiac arrest features, neurological and echocardiographic data obtained after return of spontaneous circulation (within 24 h, 15 days and six months). Patients in the extracorporeal cardiopulmonary resuscitation group ( n=63, 43%) were younger (59±9 vs 63±8 year-old, p=0.02) with lower incidence of atherosclerosis risk factors than those with conventional cardiopulmonary resuscitation. In the extracorporeal cardiopulmonary resuscitation group, left ventricular ejection fraction was lower than conventional cardiopulmonary resuscitation at early echocardiography (19±16% vs 37±11 p<0.01). Survivors in both groups showed similar left ventricular ejection fraction 15 days and 4-6 months after cardiac arrest (46±8% vs 49±10, 47±11% vs 45±13%, p not significant for both), despite a major extent and duration of cardiac ischaemia in extracorporeal cardiopulmonary resuscitation patients. At multivariate analysis, the total cardiac arrest time was the only independent predictor of survival. Extracorporeal cardiopulmonary resuscitation patients are younger and have less comorbidities than conventional cardiopulmonary resuscitation, but they have worse survival and lower early left ventricular ejection fraction. Survivors after extracorporeal cardiopulmonary resuscitation have a neurological outcome and recovery of heart function comparable to subjects with return of spontaneous circulation. Total cardiac arrest time is the only predictor of survival after cardiopulmonary resuscitation in both groups.

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.

Myocarditis in children and detection of viruses in myocardial tissue: implications for immunosuppressive therapy.

PubMed

Camargo, Paulo Roberto; Okay, Thelma Suely; Yamamoto, Lídia; Del Negro, Gilda Maria Bárbaro; Lopes, Antonio Augusto

2011-04-14

There is scarce information on the potential benefits of immunosuppression in children with myocarditis and viral genomes in myocardium. We investigated the occurrence of myocarditis in children with a preliminary diagnosis of dilated cardiomyopathy, the frequency of cardiotropic viruses in the myocardium, and the response to immunosuppression. Thirty patients (nine months to 12 years) with left ventricular ejection fraction of 22.8 ± 4.1% were subjected to right cardiac catheterization and endomyocardial biopsy. Specimens were analyzed for the presence of inflammatory elements (Dallas criteria) and viral genome (polymerase chain reaction). Patients with active myocarditis received immunosuppressants (azatioprine and prednisone) and were re-catheterized nine months later. A historical control group of nine patients with myocarditis who did not receive immunosuppressants was included. Active myocarditis was diagnosed in ten patients (five with viral genomes detected). Immunosuppression resulted in a significant increase in left ventricular ejection fraction from 25.2 ± 2.8% to 45.7 ± 8.6% (versus 20.0 ± 4.0% to 22.0 ± 9.0% in historical controls, p<0.01) and cardiac index from 3.28 ± 0.51 L/min/m(2) to 4.40 ± 0.49 L/min/m(2) (versus 3.50 ± 0.40 L/min/m(2) to 3.70 ± 0.50 L/min/m(2) in controls, p<0.01), regardless of the presence of viral genomes (p=0.98 and p=0.22, respectively for the two variables). No relevant clinical events were observed. Non-inflammatory cardiomyopathy was diagnosed in 20 patients (seven with viral genomes). While on conventional therapy, there were four deaths and three assignments to transplantation, and no improvement of left ventricular ejection fraction in the remaining ones (22.5 ± 3.6% to 27.5 ± 10.6%). Children with chronic myocarditis seem to benefit from immunosuppressive therapy, regardless of the presence of viral genome in the myocardium. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

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.

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.

Reliability, construct validity and determinants of 6-minute walk test performance in patients with chronic heart failure.

PubMed

Uszko-Lencer, Nicole H M K; Mesquita, Rafael; Janssen, Eefje; Werter, Christ; Brunner-La Rocca, Hans-Peter; Pitta, Fabio; Wouters, Emiel F M; Spruit, Martijn A

2017-08-01

In-depth analyses of the measurement properties of the 6-minute walk test (6MWT) in patients with chronic heart failure (CHF) are lacking. We investigated the reliability, construct validity, and determinants of the distance covered in the 6MWT (6MWD) in CHF patients. 337 patients were studied (median age 65years, 70% male, ejection fraction 35%). Participants performed two 6MWTs on subsequent days. Demographics, anthropometrics, clinical data, ejection fraction, maximal exercise capacity, body composition, lung function, and symptoms of anxiety and depression were also assessed. Construct validity was assessed in terms of convergent, discriminant and known-groups validity. Stepwise linear regression was used. 6MWT was reliable (ICC=0.90, P<0.0001). The learning effect was 31m (95%CI 27, 35m). Older age (≥65years), lower lung diffusing capacity (<80% predicted) and higher NYHA class (NYHA III) were associated with a lower likelihood of a meaningful increase in the second test (OR 0.45-0.56, P<0.05 for all). The best 6MWD had moderate-to-good correlations with peak exercise capacity (r s =0.54-0.69) and no-to-fair correlations with body composition, lung function, ejection fraction, and symptoms of anxiety and depression (r s =0.04-0.49). Patients with higher NYHA classes had lower 6MWD. 6MWD was independently associated with maximal power output during maximal exercise, estimated glomerular filtration rate and age (51.7% of the variability). 6MWT was found to be reliable and valid in patients with mild-to-moderate CHF. Maximal exercise capacity, renal function and age were significant determinants of the best 6MWD. These findings strengthen the clinical utility of the 6MWT in CHF. Copyright © 2017 Elsevier B.V. All rights reserved.

Novel All-Extremity High-Intensity Interval Training Improves Aerobic Fitness, Cardiac Function and Insulin Resistance in Healthy Older Adults

PubMed Central

Hwang, Chueh-Lung; Yoo, Jeung-Ki; Kim, Han-Kyul; Hwang, Moon-Hyon; Handberg, Eileen M.; Petersen, John W.; Christou, Demetra D.

2016-01-01

Aging is associated with decreased aerobic fitness and cardiac remodeling leading to increased risk for cardiovascular disease. High-intensity interval training (HIIT) on the treadmill has been reported to be more effective in ameliorating these risk factors compared with moderate-intensity continuous training (MICT) in patients with cardiometabolic disease. In older adults, however, weight-bearing activities are frequently limited due to musculoskeletal and balance problems. The purpose of this study was to examine the feasibility and safety of non-weight-bearing all-extremity HIIT in older adults. In addition, we tested the hypothesis that all-extremity HIIT will be more effective in improving aerobic fitness, cardiac function, and metabolic risk factors compared with all-extremity MICT. Fifty-one healthy sedentary older adults (age: 65±1 years) were randomized to HIIT (n=17), MICT (n=18) or non-exercise control (CONT; n=16). HIIT (4×4 minutes 90% of peak heart rate; HRpeak) and isocaloric MICT (70% of HRpeak) were performed on a non-weight-bearing all-extremity ergometer, 4x/week for 8 weeks under supervision. All-extremity HIIT was feasible in older adults and resulted in no adverse events. Aerobic fitness (peak oxygen consumption; VO2peak) and ejection fraction (echocardiography) improved by 11% (P<0.0001) and 4% (P=0.001) respectively in HIIT, while no changes were observed in MICT and CONT (P≥0.1). Greater improvements in ejection fraction were associated with greater improvements in VO2peak (r=0.57; P<0.0001). Insulin resistance (homeostatic model assessment) decreased only in HIIT by 26% (P=0.016). Diastolic function, body composition, glucose and lipids were unaffected (P≥0.1). In conclusion, all-extremity HIIT is feasible and safe in older adults. HIIT, but not MICT, improved aerobic fitness, ejection fraction, and insulin resistance. PMID:27346646

Novel all-extremity high-intensity interval training improves aerobic fitness, cardiac function and insulin resistance in healthy older adults.

PubMed

Hwang, Chueh-Lung; Yoo, Jeung-Ki; Kim, Han-Kyul; Hwang, Moon-Hyon; Handberg, Eileen M; Petersen, John W; Christou, Demetra D

2016-09-01

Aging is associated with decreased aerobic fitness and cardiac remodeling leading to increased risk for cardiovascular disease. High-intensity interval training (HIIT) on the treadmill has been reported to be more effective in ameliorating these risk factors compared with moderate-intensity continuous training (MICT) in patients with cardiometabolic disease. In older adults, however, weight-bearing activities are frequently limited due to musculoskeletal and balance problems. The purpose of this study was to examine the feasibility and safety of non-weight-bearing all-extremity HIIT in older adults. In addition, we tested the hypothesis that all-extremity HIIT will be more effective in improving aerobic fitness, cardiac function, and metabolic risk factors compared with all-extremity MICT. Fifty-one healthy sedentary older adults (age: 65±1years) were randomized to HIIT (n=17), MICT (n=18) or non-exercise control (CONT; n=16). HIIT (4×4min 90% of peak heart rate; HRpeak) and isocaloric MICT (70% of HRpeak) were performed on a non-weight-bearing all-extremity ergometer, 4×/week for 8weeks under supervision. All-extremity HIIT was feasible in older adults and resulted in no adverse events. Aerobic fitness (peak oxygen consumption; VO2peak) and ejection fraction (echocardiography) improved by 11% (P<0.0001) and 4% (P=0.001), respectively in HIIT, while no changes were observed in MICT and CONT (P≥0.1). Greater improvements in ejection fraction were associated with greater improvements in VO2peak (r=0.57; P<0.0001). Insulin resistance (homeostatic model assessment) decreased only in HIIT by 26% (P=0.016). Diastolic function, body composition, glucose and lipids were unaffected (P≥0.1). In conclusion, all-extremity HIIT is feasible and safe in older adults. HIIT, but not MICT, improved aerobic fitness, ejection fraction, and insulin resistance. Copyright © 2016 Elsevier Inc. All rights reserved.

Beneficial effects of exercise training in heart failure are lost in male diabetic rats.

PubMed

Boudia, Dalila; Domergue, Valérie; Mateo, Philippe; Fazal, Loubina; Prud'homme, Mathilde; Prigent, Héloïse; Delcayre, Claude; Cohen-Solal, Alain; Garnier, Anne; Ventura-Clapier, Renée; Samuel, Jane-Lise

2017-12-01

Exercise training has been demonstrated to have beneficial effects in patients with heart failure (HF) or diabetes. However, it is unknown whether diabetic patients with HF will benefit from exercise training. Male Wistar rats were fed either a standard (Sham, n = 53) or high-fat, high-sucrose diet ( n = 66) for 6 mo. After 2 mo of diet, the rats were already diabetic. Rats were then randomly subjected to either myocardial infarction by coronary artery ligation (MI) or sham operation. Two months later, heart failure was documented by echocardiography and animals were randomly subjected to exercise training with treadmill for an additional 8 wk or remained sedentary. At the end, rats were euthanized and tissues were assayed by RT-PCR, immunoblotting, spectrophotometry, and immunohistology. MI induced a similar decrease in ejection fraction in diabetic and lean animals but a higher premature mortality in the diabetic group. Exercise for 8 wk resulted in a higher working power developed by MI animals with diabetes and improved glycaemia but not ejection fraction or pathological phenotype. In contrast, exercise improved the ejection fraction and increased adaptive hypertrophy after MI in the lean group. Trained diabetic rats with MI were nevertheless able to develop cardiomyocyte hypertrophy but without angiogenic responses. Exercise improved stress markers and cardiac energy metabolism in lean but not diabetic-MI rats. Hence, following HF, the benefits of exercise training on cardiac function are blunted in diabetic animals. In conclusion, exercise training only improved the myocardial profile of infarcted lean rats fed the standard diet. NEW & NOTEWORTHY Exercise training is beneficial in patients with heart failure (HF) or diabetes. However, less is known of the possible benefit of exercise training for HF patients with diabetes. Using a rat model where both diabetes and MI had been induced, we showed that 2 mo after MI, 8 wk of exercise training failed to improve cardiac function and metabolism in diabetic animals in contrast to lean animals.

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.

Correlation between increased urinary sodium excretion and decreased left ventricular diastolic function in patients with type 2 diabetes mellitus.

PubMed

Kagiyama, Shuntaro; Koga, Tokushi; Kaseda, Shigeru; Ishihara, Shiro; Kawazoe, Nobuyuki; Sadoshima, Seizo; Matsumura, Kiyoshi; Takata, Yutaka; Tsuchihashi, Takuya; Iida, Mitsuo

2009-10-01

Increased salt intake may induce hypertension, lead to cardiac hypertrophy, and exacerbate heart failure. When elderly patients develop heart failure, diastolic dysfunction is often observed, although the ejection fraction has decreased. Diabetes mellitus (DM) is an established risk factor for heart failure. However, little is known about the relationship between cardiac function and urinary sodium excretion (U-Na) in patients with DM. We measured 24-hour U-Na; cardiac function was evaluated directly during coronary catheterization in type 2 DM (n = 46) or non-DM (n = 55) patients with preserved cardiac systolic function (ejection fraction > or = 60%). Cardiac diastolic and systolic function was evaluated as - dp/dt and + dp/dt, respectively. The average of U-Na was 166.6 +/- 61.2 mEq/24 hour (mean +/- SD). In all patients, stepwise multivariate regression analysis revealed that - dp/dt had a negative correlation with serum B-type natriuretic peptide (BNP; beta = - 0.23, P = .021) and U-Na (beta = - 0.24, P = .013). On the other hand, + dp/dt negatively correlated with BNP (beta = - 0.30, P < .001), but did not relate to U-Na. In the DM-patients, stepwise multivariate regression analysis showed that - dp/dt still had a negative correlation with U-Na (beta = - 0.33, P = .025). The results indicated that increased urinary sodium excretion is associated with an impairment of cardiac diastolic function, especially in patients with DM, suggesting that a reduction of salt intake may improve cardiac diastolic function.

Diabetes mellitus is associated with adverse structural and functional cardiac remodelling in chronic heart failure with reduced ejection fraction.

PubMed

Walker, Andrew Mn; Patel, Peysh A; Rajwani, Adil; Groves, David; Denby, Christine; Kearney, Lorraine; Sapsford, Robert J; Witte, Klaus K; Kearney, Mark T; Cubbon, Richard M

2016-09-01

Diabetes mellitus is associated with an increased risk of death and hospitalisation in patients with chronic heart failure. Better understanding of potential underlying mechanisms may aid the development of diabetes mellitus-specific chronic heart failure therapeutic strategies. Prospective observational cohort study of 628 patients with chronic heart failure associated with left ventricular systolic dysfunction receiving contemporary evidence-based therapy. Indices of cardiac structure and function, along with symptoms and biochemical parameters, were compared in patients with and without diabetes mellitus at study recruitment and 1 year later. Patients with diabetes mellitus (24.2%) experienced higher rates of all-cause [hazard ratio, 2.3 (95% confidence interval, 1.8-3.0)] and chronic heart failure-specific mortality and hospitalisation despite comparable pharmacological and device-based therapies. At study recruitment, patients with diabetes mellitus were more symptomatic, required greater diuretic doses and more frequently had radiologic evidence of pulmonary oedema, despite higher left ventricular ejection fraction. They also exhibited echocardiographic evidence of increased left ventricular wall thickness and pulmonary arterial pressure. Diabetes mellitus was associated with reduced indices of heart rate variability and increased heart rate turbulence. During follow-up, patients with diabetes mellitus experienced less beneficial left ventricular remodelling and greater deterioration in renal function. Diabetes mellitus is associated with features of adverse structural and functional cardiac remodelling in patients with chronic heart failure. © The Author(s) 2016.

Regional myocardial extraction of a radioiodinated branched chain fatty acid during right ventricular pressure overload due to acute pulmonary hypertension

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

Hurford, W.; Lowenstein, E.; Zapol, W.

1985-05-01

To determine whether branched chain fatty acid extraction is reduced during right ventricular (RV) dysfunction due to acute pulmonary artery hypertension, studies were done in 6 anesthetized dogs. Regional branched chain fatty acid extraction was measured by comparing the myocardial uptake of I-125 labeled 15-(p-(iodophenyl))-3-methylpentadecanoic acid (I-PDA) to myocardial blood flow. Acute pulmonary hypertension was induced by incremental intravenous injection of 100 micron diameter glass beads into six pentobarbital anesthetized, mechanically ventilated dogs. Myocardial blood flow was measured by radiolabeled microspheres both under baseline conditions and during pulmonary hypertension. Mean RV pressure rose from 12 +- 2 (mean +- SEM)more » to 30 +-3mmHg resulting in a 225 +- 16% increase in RV stroke work. RV ejection fraction, as assessed by gated blood pool scans fell from 39 +- 2 to 18 +- 2%. Left ventricular (LV) pressures, stroke work and ejection fraction were unchanged. Myocardial blood flow increased 132 + 59% in the RV free wall and 67 +- 22% in the RV septum. LV blood flow was unchanged. Despite increased RV work and myocardial blood flow, no differences were noted in the branched chain fatty acid extraction ratios among LV or RV free walls or septum. The authors conclude that early RV dysfunction associated with pulmonary artery hypertension is not due to inadequate myocardial blood flow or branched chain fatty acid extraction.« less

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

The impact of coronary artery disease and left ventricular ejection fraction on the prognosis of patients with peripheral artery disease.

PubMed

Tsujimura, Takuya; Iida, Osamu; Ishihara, Takayuki; Fujita, Masashi; Masuda, Masaharu; Okamoto, Shin; Nanto, Kiyonori; Kanda, Takashi; Sunaga, Akihiro; Takahara, Mitsuyoshi; Uematsu, Masaaki

2017-11-01

The impact of the severity of coronary artery disease (CAD) and left ventricular ejection fraction (LVEF) on the prognosis of patients with peripheral artery disease (PAD) has not been systematically studied. We retrospectively analysed 622 patients with PAD (intermittent claudication (IC): n = 446; critical limb ischaemia (CLI): n = 176). The association of SYNTAX score and LVEF with mortality was analysed using the Cox proportional hazard model. In patients with IC, a high SYNTAX score was significantly associated with mortality, whereas reduced LVEF was significantly associated with mortality in patients with CLI. The prognostic impact of CAD and LVEF appears different between patients with IC and CLI. © 2017 Royal Australasian College of Physicians.

Heart Failure in Women

PubMed Central

Bozkurt, Biykem; Khalaf, Shaden

2017-01-01

Heart failure is an important cause of morbidity and mortality in women, and they tend to develop it at an older age compared to men. Heart failure with preserved ejection fraction is more common in women than in men and accounts for at least half the cases of heart failure in women. When comparing men and women who have heart failure and a low left ventricular ejection fraction, the women are more symptomatic and have a similarly poor outcome. Overall recommendations for guideline-directed medical therapies show no differences in treatment approaches between men and women. Overall, women are generally underrepresented in clinical trials for heart failure. Further studies are needed to shed light into different mechanisms, causes, and targeted therapies of heart failure in women. PMID:29744014

Restrictive Cardiomyopathy Associated With Long-Term Use of Hydroxychloroquine for Systemic Lupus Erythematosus.

PubMed

Sabato, Leah A; Mendes, Lisa A; Cox, Zachary L

2017-10-01

Hydroxychloroquine (HQ) is commonly prescribed for autoimmune diseases such as systemic lupus erythematosus. We report a case of a 75-year-old female presenting with de novo decompensated heart failure and restrictive cardiomyopathy (left ventricular ejection fraction: 40%-45%) after treatment with HQ for more than 11 years. Hydroxychloroquine was discontinued, and follow-up echocardiogram 57 days after discontinuation showed normalization of her left ventricular ejection fraction. A score of 7 on the Naranjo Adverse Drug Reaction Probability Scale indicates that HQ is a probable cause of this patient's cardiomyopathy. An adverse drug effect due to HQ should be considered in treated patients who present with restrictive cardiomyopathy. Discontinuation may allow for partial or complete reversal of the cardiomyopathy.

Determination of right ventricular ejection fraction in children with cystic fibrosis

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

Piepsz, A.; Ham, H.R.; Millet, E.

1987-01-01

The radionuclide right ventricular ejection fraction (RVEF) determined by means of Krypton-81m represents a simple, noninvasive, and accurate procedure to quantify the right ventricular contractility. This procedure was applied to 25 young patients with cystic fibrosis. The RVEF tended to decrease with the progression of the lung disease, as assessed by the clinical S-K score, the degree of the defects on lung scintigraphy, the PaO/sub 2/, and the lung function tests. However, the decrease of RVEF in patients with marked lung function tests. However, the decrease of RVEF in patients with marked lung involvement was moderate, and terminal lung diseasemore » was sometimes associated with normal right heart contractility.« less

High-sugar intake does not exacerbate metabolic abnormalities or cardiac dysfunction in genetic cardiomyopathy.

PubMed

Hecker, Peter A; Galvao, Tatiana F; O'Shea, Karen M; Brown, Bethany H; Henderson, Reney; Riggle, Heather; Gupte, Sachin A; Stanley, William C

2012-05-01

A high-sugar intake increases heart disease risk in humans. In animals, sugar intake accelerates heart failure development by increased reactive oxygen species (ROS). Glucose-6-phosphate dehydrogenase (G6PD) can fuel ROS production by providing reduced nicotinamide adenine dinucleotide phosphate (NADPH) for superoxide generation by NADPH oxidase. Conversely, G6PD also facilitates ROS scavenging using the glutathione pathway. We hypothesized that a high-sugar intake would increase flux through G6PD to increase myocardial NADPH and ROS and accelerate cardiac dysfunction and death. Six-week-old TO-2 hamsters, a non-hypertensive model of genetic cardiomyopathy caused by a δ-sarcoglycan mutation, were fed a long-term diet of high starch or high sugar (57% of energy from sucrose plus fructose). After 24 wk, the δ-sarcoglycan-deficient animals displayed expected decreases in survival and cardiac function associated with cardiomyopathy (ejection fraction: control 68.7 ± 4.5%, TO-2 starch 46.1 ± 3.7%, P < 0.05 for TO-2 starch versus control; TO-2 sugar 58.0 ± 4.2%, NS, versus TO-2 starch or control; median survival: TO-2 starch 278 d, TO-2 sugar 318 d, P = 0.133). Although the high-sugar intake was expected to exacerbate cardiomyopathy, surprisingly, there was no further decrease in ejection fraction or survival with high sugar compared with starch in cardiomyopathic animals. Cardiomyopathic animals had systemic and cardiac metabolic abnormalities (increased serum lipids and glucose and decreased myocardial oxidative enzymes) that were unaffected by diet. The high-sugar intake increased myocardial superoxide, but NADPH and lipid peroxidation were unaffected. A sugar-enriched diet did not exacerbate ventricular function, metabolic abnormalities, or survival in heart failure despite an increase in superoxide production. Copyright © 2012 Elsevier Inc. All rights reserved.

Effect of Sleep-Disordered Breathing on Appropriate Implantable Cardioverter-defibrillator Therapy in Patients With Heart Failure

PubMed Central

Kwon, Younghoon; Koene, Ryan J.; Kwon, Osung; Kealhofer, Jessica V.; Adabag, Selcuk; Duval, Sue

2017-01-01

Background Patients with heart failure and reduced ejection fraction are at increased risk of malignant ventricular arrhythmias. Implantable cardioverter-defibrillator (ICD) is recommended to prevent sudden cardiac death in some of these patients. Sleep-disordered breathing (SDB) is highly prevalent in this population and may impact arrhythmogenicity. We performed a systematic review and meta-analysis of prospective studies that assessed the impact of SDB on ICD therapy. Methods and Results Relevant prospective studies were identified in the Ovid MEDLINE, EMBASE, and Google Scholar databases. Weighted risk ratios of the association between SDB and appropriate ICD therapies were estimated using random effects meta-analysis. Nine prospective cohort studies (n=1274) were included in this analysis. SDB was present in 52% of the participants. SDB was associated with a 55% higher risk of appropriate ICD therapies (45% versus 28%; risk ratio, 1.55; 95% confidence interval, 1.32–1.83). In a subgroup analysis based on the subtypes of SDB, the risk was higher in both central (risk ratio, 1.50; 95% confidence interval, 1.11–2.02) and obstructive (risk ratio, 1.43; 95% confidence interval, 1.01–2.03) sleep apnea. Conclusions SDB is associated with an increased risk of appropriate ICD therapy in patients with heart failure and reduced ejection fraction. PMID:28213507

Sinomenine prevents the development of cardiomyopathy in diabetic rats by inhibiting inflammatory responses and blocking activation of NF-κB.

PubMed

Jiang, Cheng; Tong, Yun-Long; Zhang, Dan; Liu, Li-Zhi; Wang, Ju-Fei

2017-01-01

Diabetic cardiomyopathy is a severe complication of diabetes mellitus (DM). The goal of current work was to study the effects of sinomenine on streptozotocin-induced cardiomyopathy in rats. DM in rats was induced by intraperitoneal injection of streptozotocin. Cardiac function was evaluated by measuring left ventricle end-diastolic diameter, left ventricle end-systolic diameter and ejection fraction. Cardiac inflammation was evaluated by the degree of infiltration of T lymphocytes and the levels of pro-inflammatory cytokines. Sinomenine attenuated diabetic symptoms without affecting plasma glucose. Cardiac dysfunction in the sinomenine-treated diabetic rats was significantly improved, as reflected by decreased levels of left ventricle end-diastolic diameter, left ventricle end systolic diameter and an increased level of ejection fraction. Sinomenine observably reduced cardiomyocyte hypertrophy in DM rats. Moreover, sinomenine reduced infiltration of CD3+ and CD68+ positive cells and decreased the levels of tumor necrosis factor-α, interlukin-1 and interlukin-6. Finally, sinomenine-treated rats showed a reduced expression of NF-κB and an increased expression of IκB in the myocardium compared with the myocardium of untreated diabetic rats. Our results indicate sinomenine significantly improves cardiac function in diabetic rats, which may be attributed to the deactivation of NF-κB and the blockade of inflammatory cytokine-mediated immune reactions.

Transient myocardial tissue and function changes during a marathon in less fit marathon runners.

PubMed

Gaudreault, Valerie; Tizon-Marcos, Helena; Poirier, Paul; Pibarot, Philippe; Gilbert, Philippe; Amyot, Marc; Rodés-Cabau, Josep; Després, Jean-Pierre; Bertrand, Olivier; Larose, Eric

2013-10-01

Although regular physical activity improves health, strenuous exercise might transiently increase cardiac risk. Training and fitness might provide protection. We prospectively studied 20 recreational marathon runners without known cardiovascular disease or symptoms: at peak training before, immediately after, and 3 months after a 42.2-km marathon. Changes in global/segmental myocardial function, edema, resting perfusion, and fibrosis were measured. At peak training, runners exercised 8.1 ± 2.3 hours and 62 ± 18 km per week with mean maximal oxygen consumption (VO2max) of 53.2 ± 8.3 mL/kg/min. In response to the marathon, global left ventricular and right ventricular ejection fraction decreased in half of the runners; these runners had poorer peak training distance, training time, and fitness level. Change in global left ventricular ejection fraction was associated with VO2max. Overall, 36% of segments developed edema, 53% decreased function, and 59% decreased perfusion. Significant agreement was observed between segment decreasing function, decreasing perfusion, and developing edema. Myocardial changes were reversible at 3 months. Completing a marathon leads to localized myocardial edema, diminished perfusion, and decreased function occurring more extensively in less trained and fit runners. Although reversible, these changes might contribute to the transient increase in cardiac risk reported during sustained vigorous exercise. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Decrease of total antioxidant capacity during coronary artery bypass surgery.

PubMed

Kunt, Alper Sami; Selek, Sahbettin; Celik, Hakim; Demir, Deniz; Erel, Ozcan; Andac, Mehmet Halit

2006-09-01

Cardiac surgery induces an oxidative stress, which may lead to impairment of cardiac function. In this study, we aimed to measure the changes of oxidative and antioxidative status of patients undergoing coronary artery bypass surgery (CABG). We studied 79 patients who underwent CABG with and without cardiopulmonary bypass (CPB). Of the 79 patients, 39 had CPB and 40 did not. Blood samples were drawn before, during, and after the surgery. Antioxidant status was evaluated by measuring total antioxidant capacity (TAC), and oxidative status was evaluated by measuring total peroxide (TP) levels and oxidative stress index (OSI). TP and OSI levels increased, while TAC decreased progressively after the beginning of surgery, for all patients. There were negative correlations between TAC levels and aortic cross-clamping period and anastomosis time ( r = -0.553, p < 0.001 and r = -0.500, p < 0.001, respectively). In addition, there was a positive correlation between TAC and ejection fraction (r = 0.647, p < 0.001). During CABG, oxidant and OSI levels significantly increase and TAC significantly decreases. This situation is influenced by long CPB and anastomosis time, and also by low ventricular ejection fraction. We concluded that the patients who undergo CABG are exposed to potent oxidative stress that impairs their TAC. We speculate that supplementation with antioxidant vitamins such as vitamins C and E may be beneficial for patients undergoing CABG.

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

Development and intra-institutional and inter-institutional validation of a comprehensive new hepatobiliary software: Part 1--Liver and gallbladder function.

PubMed

Krishnamurthy, Gerbail T; Krishnamurthy, Shakuntala; Gambhir, Sanjiv Sam; Rodrigues, Cesar; Rosenberg, Jarrett; Schiepers, Christiaan; Buxton-Thomas, Muriel

2009-12-01

To develop a software tool for quantification of liver and gallbladder function, and to assess the repeatability and reproducibility of measurements made with it. The software tool developed with the JAVA programming language uses the JAVA2 Standard Edition framework. After manual selection of the regions of interest on a 99mTc hepatic iminodiacetic acid study, the program calculates differential hepatic bile flow, basal duodeno-gastric bile reflux (B-DGBR), hepatic extraction fraction (HEF) of both the lobes with deconvolutional analysis and excretion half-time with nonlinear least squares fit. Gallbladder ejection fraction, ejection period (EP), ejection rate (ER), and postcholecystokinin (CCK) DGBR are calculated after stimulation with CCK-8. To assess intra-observer repeatability and intra-observer reproducibility, measurements from 10 normal participants were analyzed twice by three nuclear medicine technologists at the primary center. To assess inter-site reproducibility, measurements from a superset of 24 normal participants were also assessed once by three observers at the primary center and single observer at three other sites. For the 24 control participants, mean+/-SD of hepatic bile flow into gallbladder was 63.87+/-28.7%, HEF of the right lobe 100+/-0%, left lobe 99.43+2.63%, excretion half-time of the right lobe 21.50+6.98 min, left lobe 28.3+/-11.3 min. Basal DGBR was 1.2+/-1.0%. Gallbladder ejection fraction was 80+/-11%, EP 15.0+/-3.0 min, ER 5.8+/-1.6%/min, and DGBR-CCK 1.3+/-2.3%. Left and right lobe HEF was virtually identical across readers. All measures showed high repeatability except for gallbladder bile flow, basal DGBR, and EP, which exhibited marginal repeatability. Ejection fraction exhibited high reproducibility. There was high concordance among the three primary center observers except for basal DGBR, EP, and ER. Concordance between the primary site and one of the other sites was high, one was fair, and one was poor. New United States Food and Drug Administration-approved personal computer-based Krishnamurthy Hepato-Biliary Software for quantification of the liver and gallbladder function shows promise for consistently repeatable and reproducible results both within and between institutions, and may help to promote universal standardization of data acquisition and analysis in nuclear hepatology.

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

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.

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.

Increased passive stiffness promotes diastolic dysfunction despite improved Ca2+ handling during left ventricular concentric hypertrophy

PubMed Central

Røe, Åsmund T.; Aronsen, Jan Magnus; Skårdal, Kristine; Hamdani, Nazha; Linke, Wolfgang A.; Danielsen, Håvard E.; Sejersted, Ole M.; Sjaastad, Ivar; Louch, William E.

2017-01-01

Abstract Aims Concentric hypertrophy following pressure-overload is linked to preserved systolic function but impaired diastolic function, and is an important substrate for heart failure with preserved ejection fraction. While increased passive stiffness of the myocardium is a suggested mechanism underlying diastolic dysfunction in these hearts, the contribution of active diastolic Ca2+ cycling in cardiomyocytes remains unclear. In this study, we sought to dissect contributions of passive and active mechanisms to diastolic dysfunction in the concentrically hypertrophied heart following pressure-overload. Methods and results Rats were subjected to aortic banding (AB), and experiments were performed 6 weeks after surgery using sham-operated rats as controls. In vivo ejection fraction and fractional shortening were normal, confirming preservation of systolic function. Left ventricular concentric hypertrophy and diastolic dysfunction following AB were indicated by thickening of the ventricular wall, reduced peak early diastolic tissue velocity, and higher E/e’ values. Slowed relaxation was also observed in left ventricular muscle strips isolated from AB hearts, during both isometric and isotonic stimulation, and accompanied by increases in passive tension, viscosity, and extracellular collagen. An altered titin phosphorylation profile was observed with hypophosphorylation of the phosphosites S4080 and S3991 sites within the N2Bus, and S12884 within the PEVK region. Increased titin-based stiffness was confirmed by salt-extraction experiments. In contrast, isolated, unloaded cardiomyocytes exhibited accelerated relaxation in AB compared to sham, and less contracture at high pacing frequencies. Parallel enhancement of diastolic Ca2+ handling was observed, with augmented NCX and SERCA2 activity and lowered resting cytosolic [Ca2+]. Conclusion In the hypertrophied heart with preserved systolic function, in vivo diastolic dysfunction develops as cardiac fibrosis and alterations in titin phosphorylation compromise left ventricular compliance, and despite compensatory changes in cardiomyocyte Ca2+ homeostasis. PMID:28472418

A moderately precise dynamical age for the Homunculus of Eta Carinae based on 13 years of HST imaging

NASA Astrophysics Data System (ADS)

Smith, Nathan

2017-11-01

The Hubble Space Telescope archive contains a large collection of images of η Carinae, and this paper analyses those most suitable for measuring its expanding Homunculus Nebula. Multiple intensity tracings through the Homunculus reveal the fractional increase in the overall size of the nebula; this avoids registration uncertainty, mitigates brightness fluctuations, and is independent of previous methods. Combining a 13 yr baseline of Wide Field Planetary Camera 2 images in the F631N filter, with a 4 yr baseline of Advanced Camera for Surveys/High Resolution Channel images in the F550M filter, yields an ejection date (assuming linear motion) of 1847.1 (±0.8 yr). This result improves the precision, but is in excellent agreement with the previous study by Morse et al., that used a shorter time baseline and a different analysis method. This more precise date is inconsistent with ejection during a periastron passage of the eccentric binary. Ejection occurred well into the main plateau of the Great Eruption, and not during the brief peaks in 1843 and 1838. The age uncertainty is dominated by a real spread in ages of various knots, and by some irregular brightness fluctuations. Several knots appear to have been ejected decades before or after the mean date, implying a complicated history of mass-loss episodes outside the main bright phase of the eruption. The extended history of mass ejection may have been largely erased by the passage of a shock through clumpy ejecta, as most material was swept into a thin shell with nearly uniform apparent age.

PubMed Central

RUSSO, VINCENZO; RAGO, ANNA; DI MEO, FEDERICA; CIOPPA, NADIA DELLA; PAPA, ANDREA ANTONIO; RUSSO, MARIA GIOVANNA

2014-01-01

The occurrence of ventricular fibrillation, induced by bipolar electrocautery during elective dual chamber pacemaker implantation, is reported in a patient affected by Myotonic Distrophy type 1 with normal left ventricular ejection fraction PMID:25873784

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.

Changes in Right Ventricular Shape and Deformation Following Coronary Artery Bypass Surgery-Insights from Echocardiography with Strain Rate and Magnetic Resonance Imaging.

PubMed

Rösner, Assami; Avenarius, Derk; Malm, Siri; Iqbal, Amjid; Schirmer, Henrik; Bijnens, Bart; Myrmel, Truls

2015-12-01

This study was designed to assess whether altered RV geometry and deformation parameters persisted well into the recovery period after presumably uncomplicated coronary artery bypass grafting (CABG). It was our hypothesis that the altered geometry of and load in the RV following pericardial opening would change both regional and global deformation indices for an extensive period postoperatively. Fifty-seven patients scheduled for CABG underwent preoperative and 8-10 months postoperative magnetic resonance imaging (MRI) for RV volume measurements, and resting echocardiography with assessment of geometry and RV mechanical function determined by tissue Doppler imaging (TDI) based longitudinal strain. Both MRI and echocardiography revealed postoperative dilatation of the RV apex, shortened longitudinal RV length but unchanged RV ejection fraction. Echocardiography parameters associated with filling of the right atrium showed signs of constraint with a reduced systolic filling fraction and increased right atrial size. Right ventricular segmental strain (-20 ± 13% vs. -29 ± 20% preoperatively; mean ±SD, P < 0.0001) was reduced postoperatively in parallel with TAPSE (1.3 ± 0.3 cm vs. 2.2 ± 0.4 cm; P < 0.0001). Post-CABG longitudinal motion of the RV lateral wall is reduced after uneventful CABG despite preserved RV ejection fraction and stroke volume. The discrepancy in various RV systolic performance indicators results from increased sphericity of the RV following opening the pericardium during surgery. Therefore, longitudinal functional parameters may underestimate RV systolic function for at least 8-10 months post-CABG. Changes in deformation parameters should thus always be interpreted in relation to changes in geometry. © 2015, Wiley Periodicals, Inc.

Rationale and design of the Karolinska-Rennes (KaRen) prospective study of dyssynchrony in heart failure with preserved ejection fraction.

PubMed

Donal, Erwan; Lund, Lars H; Linde, Cecilia; Edner, Magnus; Lafitte, Stéphane; Persson, Hans; Bauer, Fabrice; Ohrvik, John; Ennezat, Pierre-Vladimir; Hage, Camilla; Löfman, Ida; Juilliere, Yves; Logeart, Damien; Derumeaux, Geneviève; Gueret, Pascal; Daubert, Jean-Claude

2009-02-01

Heart failure with preserved ejection fraction (HFPEF) is common but not well understood. Electrical dyssynchrony in systolic heart failure is harmful. Little is known about the prevalence and the prognostic impact of dyssynchrony in HFPEF. We have designed a prospective, multicenter, international, observational study to characterize HFPEF and to determine whether electrical or mechanical dyssynchrony affects prognosis. Patients presenting with acute heart failure (HF) will be screened so as to identify 400 patients with HFPEF. Inclusion criteria will be: acute presentation with Framingham criteria for HF, left ventricular ejection fraction>or=45%, brain natriuretic peptide (BNP)>100 pg/mL or NT-proBNP>300 pg/mL. Once stabilized, 4-8 weeks after the index presentation, patients will return and undergo questionnaires, serology, ECG, and Doppler echocardiography. Thereafter, patients will be followed for mortality and HF hospitalization every 6 months for at least 18 months. Sub-studies will focus on echocardiographic changes from the acute presentation to the stable condition and on exercise echocardiography, cardiopulmonary exercise testing, and serological markers. KaRen aims to characterize electrical and mechanical dyssynchrony and to assess its prognostic impact in HFPEF. The results might improve our understanding of HFPEF and generate answers to the question whether dyssynchrony could be a target for therapy in HFPEF.

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.

Cognitive Function in Ambulatory Patients with Systolic Heart Failure: Insights from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial

PubMed Central

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

2014-01-01

We sought to determine whether cognitive function in stable outpatients with heart failure (HF) is affected by HF severity. A retrospective, cross-sectional analysis was performed using data from 2, 043 outpatients with systolic HF and without prior stroke enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial. Multivariable regression analysis was used to assess the relationship between cognitive function measured using the Mini-Mental Status Exam (MMSE) and markers of HF severity (left ventricular ejection fraction [LVEF], New York Heart Association [NYHA] functional class, and 6-minute walk distance). The mean (SD) for the MMSE was 28.6 (2.0), with 64 (3.1%) of the 2,043 patients meeting the cut-off of MMSE <24 that indicates need for further evaluation of cognitive impairment. After adjustment for demographic and clinical covariates, 6-minute walk distance (β-coefficient 0.002, p<0.0001), but not LVEF or NYHA functional class, was independently associated with the MMSE as a continuous measure. Age, education, smoking status, body mass index, and hemoglobin level were also independently associated with the MMSE. In conclusion, six-minute walk distance, but not LVEF or NYHA functional class, was an important predictor of cognitive function in ambulatory patients with systolic heart failure. PMID:25426862

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.

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.

Genesis Solar Wind Interstream, Coronal Hole and Coronal Mass Ejection Samples: Update on Availability and Condition

NASA Technical Reports Server (NTRS)

Allton, J. H.; Gonzalez, C. P.; Allums, K. K.

2017-01-01

Recent refinement of analysis of ACE/SWICS data (Advanced Composition Explorer/Solar Wind Ion Composition Spectrometer) and of onboard data for Genesis Discovery Mission of 3 regimes of solar wind at Earth-Sun L1 make it an appropriate time to update the availability and condition of Genesis samples specifically collected in these three regimes and currently curated at Johnson Space Center. ACE/SWICS spacecraft data indicate that solar wind flow types emanating from the interstream regions, from coronal holes and from coronal mass ejections are elementally and isotopically fractionated in different ways from the solar photosphere, and that correction of solar wind values to photosphere values is non-trivial. Returned Genesis solar wind samples captured very different kinds of information about these three regimes than spacecraft data. Samples were collected from 11/30/2001 to 4/1/2004 on the declining phase of solar cycle 23. Meshik, et al is an example of precision attainable. Earlier high precision laboratory analyses of noble gases collected in the interstream, coronal hole and coronal mass ejection regimes speak to degree of fractionation in solar wind formation and models that laboratory data support. The current availability and condition of samples captured on collector plates during interstream slow solar wind, coronal hole high speed solar wind and coronal mass ejections are de-scribed here for potential users of these samples.

Effects of Dexmedotomidine in the Coronary Artery Bypass Graft (CABG) Patient: A Pilot Study

DTIC Science & Technology

2006-04-14

diabetes, gross obesity, ejection fraction of< 30%, drug overdose , and any other condition or factor that the investigator felt might increase risk to the...addition of DEX to a post-op pain relief regimen has decreased the amount of morphine administered, as well as fentanyl .4’ 15’ 16 Studies have also...and pre-operative fentanyl . British Journal of Anaesthesia. 1992;68:126-131. 7. Jalonen, J., Hynynen, M., Kuitunen, A., Heikkila, H., Perttila, J

υ-driven winds from the remnant of binary neutron star mergers

NASA Astrophysics Data System (ADS)

Perego, A.

2018-01-01

We present a 3D hydrodynamic study of the neutrino-driven winds that emerge from the remnant of a neutron star merger, represented by a thick accretion disc orbiting around a massive neutron star. This strong baryonic wind is blown out by neutrino absorption on free baryons inside the disc. It expands within a few tens of ms along the original binary rotation axis. If the central object survives for at least 200ms, the mass ejected in the wind can reach 5% of the initial mass of the accretion disc. Due to the intense neutrino irradiation, matter ejected in the wind increases its electron fraction between 0.3 and 0.4, producing weak r-process nucleosynthesis yields. We predict a distinct UV/optical transient associated with the wind ejecta that peaks from a few hours to a few days after the merger.

Digoxin test

MedlinePlus

Heart failure - digoxin test ... Mann DL. Management of patients with heart failure with reduced ejection fraction. In: Mann DL, Zipes DP, Libby P, Bonow RO, Braunwald E, eds. Braunwald's Heart Disease: A Textbook of ...

The evolving approach to the evaluation of low-gradient aortic stenosis.

PubMed

Cutting, William B; Bavry, Anthony A

2018-04-07

Severe aortic stenosis (AS) is typically identified by a low valve area (≤1.0 cm 2 ) and high mean gradient (≥40 mm Hg). A subset of patients are found to have a less than severe mean gradient (<40 mm Hg) despite a low valve area. These latter types can present as either low ejection fraction with low-gradient AS (stage D2) or normal ejection fraction with low-gradient AS (stage D3). Determining the true severity of disease within these categories has proved difficult. In this review we illustrate both traditional and novel techniques that can be used for further valvular assessment. We also propose a simple algorithm that can be used to evaluate low-gradient AS. Published by Elsevier Inc.

Modeling UV Radiation Feedback from Massive Stars. II. Dispersal of Star-forming Giant Molecular Clouds by Photoionization and Radiation Pressure

NASA Astrophysics Data System (ADS)

Kim, Jeong-Gyu; Kim, Woong-Tae; Ostriker, Eve C.

2018-05-01

UV radiation feedback from young massive stars plays a key role in the evolution of giant molecular clouds (GMCs) by photoevaporating and ejecting the surrounding gas. We conduct a suite of radiation hydrodynamic simulations of star cluster formation in marginally bound, turbulent GMCs, focusing on the effects of photoionization and radiation pressure on regulating the net star formation efficiency (SFE) and cloud lifetime. We find that the net SFE depends primarily on the initial gas surface density, Σ0, such that the SFE increases from 4% to 51% as Σ0 increases from 13 to 1300 {M}ȯ {pc}}-2. Cloud destruction occurs within 2–10 Myr after the onset of radiation feedback, or within 0.6–4.1 freefall times (increasing with Σ0). Photoevaporation dominates the mass loss in massive, low surface density clouds, but because most photons are absorbed in an ionization-bounded Strömgren volume, the photoevaporated gas fraction is proportional to the square root of the SFE. The measured momentum injection due to thermal and radiation pressure forces is proportional to {{{Σ }}}0-0.74, and the ejection of neutrals substantially contributes to the disruption of low mass and/or high surface density clouds. We present semi-analytic models for cloud dispersal mediated by photoevaporation and by dynamical mass ejection, and show that the predicted net SFE and mass loss efficiencies are consistent with the results of our numerical simulations.

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.

Allogeneic Cardiospheres Delivered via Percutaneous Transendocardial Injection Increase Viable Myocardium, Decrease Scar Size, and Attenuate Cardiac Dilatation in Porcine Ischemic Cardiomyopathy

PubMed Central

Tseliou, Eleni; Cheng, Ke; Luthringer, Daniel J.; Ho, Chak-Sum; Takayama, Kentaro; Minamino, Naoto; Dawkins, James F.; Chowdhury, Supurna; Duong, Doan Trang; Seinfeld, Jeffrey; Middleton, Ryan C.; Dharmakumar, Rohan; Li, Debiao; Marbán, Linda; Makkar, Raj R.; Marbán, Eduardo

2014-01-01

Background Epicardial injection of heart-derived cell products is safe and effective post-myocardial infarction (MI), but clinically-translatable transendocardial injection has never been evaluated. We sought to assess the feasibility, safety and efficacy of percutaneous transendocardial injection of heart-derived cells in porcine chronic ischemic cardiomyopathy. Methods and Results We studied a total of 89 minipigs; 63 completed the specified protocols. After NOGA-guided transendocardial injection, we quantified engraftment of escalating doses of allogeneic cardiospheres or cardiosphere-derived cells in minipigs (n = 22) post-MI. Next, a dose-ranging, blinded, randomized, placebo-controlled (“dose optimization”) study of transendocardial injection of the better-engrafting product was performed in infarcted minipigs (n = 16). Finally, the superior product and dose (150 million cardiospheres) were tested in a blinded, randomized, placebo-controlled (“pivotal”) study (n = 22). Contrast-enhanced cardiac MRI revealed that all cardiosphere doses preserved systolic function and attenuated remodeling. The maximum feasible dose (150 million cells) was most effective in reducing scar size, increasing viable myocardium and improving ejection fraction. In the pivotal study, eight weeks post-injection, histopathology demonstrated no excess inflammation, and no myocyte hypertrophy, in treated minipigs versus controls. No alloreactive donor-specific antibodies developed over time. MRI showed reduced scar size, increased viable mass, and attenuation of cardiac dilatation with no effect on ejection fraction in the treated group compared to placebo. Conclusions Dose-optimized injection of allogeneic cardiospheres is safe, decreases scar size, increases viable myocardium, and attenuates cardiac dilatation in porcine chronic ischemic cardiomyopathy. The decreases in scar size, mirrored by increases in viable myocardium, are consistent with therapeutic regeneration. PMID:25460005

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.

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.

Mediterranean diet score and left ventricular structure and function: the Multi-Ethnic Study of Atherosclerosis12

PubMed Central

Levitan, Emily B; Ahmed, Ali; Arnett, Donna K; Polak, Joseph F; Hundley, W Gregory; Bluemke, David A; Heckbert, Susan R; Jacobs, David R; Nettleton, Jennifer A

2016-01-01

Background: Data are limited on the relation between dietary patterns and left ventricular (LV) structure and function. Objective: We examined cross-sectional associations of a diet-score assessment of a Mediterranean dietary pattern with LV mass, volume, mass-to-volume ratio, stroke volume, and ejection fraction. Design: We measured LV variables with the use of cardiac MRI in 4497 participants in the Multi-Ethnic Study of Atherosclerosis study who were aged 45–84 y and without clinical cardiovascular disease. We calculated a Mediterranean diet score from intakes of fruit, vegetables, nuts, legumes, whole grains, fish, red meat, the monounsaturated fat:saturated fat ratio, and alcohol that were self-reported with the use of a food-frequency questionnaire. We used linear regression with adjustment for body size, physical activity, and cardiovascular disease risk factors to model associations and assess the shape of these associations (linear or quadratic). Results: The Mediterranean diet score had a slight U-shaped association with LV mass (adjusted means: 146, 145, 146, and 147 g across quartiles of diet score, respectively; P-quadratic trend = 0.04). The score was linearly associated with LV volume, stroke volume, and ejection fraction: for each +1-U difference in score, LV volume was 0.4 mL higher (95% CI: 0.0, 0.8 mL higher), the stroke volume was 0.5 mL higher (95% CI: 0.2, 0.8 mL higher), and the ejection fraction was 0.2 percentage points higher (95% CI: 0.1, 0.3 percentage points higher). The score was not associated with the mass-to-volume ratio. Conclusions: A higher Mediterranean diet score is cross-sectionally associated with a higher LV mass, which is balanced by a higher LV volume as well as a higher ejection fraction and stroke volume. Participants in this healthy, multiethnic sample whose dietary patterns most closely conformed to a Mediterranean-type pattern had a modestly better LV structure and function than did participants with less–Mediterranean-like dietary patterns. This trial was registered at clinicaltrials.gov as NCT00005487. PMID:27488238

Mediterranean diet score and left ventricular structure and function: the Multi-Ethnic Study of Atherosclerosis.

PubMed

Levitan, Emily B; Ahmed, Ali; Arnett, Donna K; Polak, Joseph F; Hundley, W Gregory; Bluemke, David A; Heckbert, Susan R; Jacobs, David R; Nettleton, Jennifer A

2016-09-01

Data are limited on the relation between dietary patterns and left ventricular (LV) structure and function. We examined cross-sectional associations of a diet-score assessment of a Mediterranean dietary pattern with LV mass, volume, mass-to-volume ratio, stroke volume, and ejection fraction. We measured LV variables with the use of cardiac MRI in 4497 participants in the Multi-Ethnic Study of Atherosclerosis study who were aged 45-84 y and without clinical cardiovascular disease. We calculated a Mediterranean diet score from intakes of fruit, vegetables, nuts, legumes, whole grains, fish, red meat, the monounsaturated fat:saturated fat ratio, and alcohol that were self-reported with the use of a food-frequency questionnaire. We used linear regression with adjustment for body size, physical activity, and cardiovascular disease risk factors to model associations and assess the shape of these associations (linear or quadratic). The Mediterranean diet score had a slight U-shaped association with LV mass (adjusted means: 146, 145, 146, and 147 g across quartiles of diet score, respectively; P-quadratic trend = 0.04). The score was linearly associated with LV volume, stroke volume, and ejection fraction: for each +1-U difference in score, LV volume was 0.4 mL higher (95% CI: 0.0, 0.8 mL higher), the stroke volume was 0.5 mL higher (95% CI: 0.2, 0.8 mL higher), and the ejection fraction was 0.2 percentage points higher (95% CI: 0.1, 0.3 percentage points higher). The score was not associated with the mass-to-volume ratio. A higher Mediterranean diet score is cross-sectionally associated with a higher LV mass, which is balanced by a higher LV volume as well as a higher ejection fraction and stroke volume. Participants in this healthy, multiethnic sample whose dietary patterns most closely conformed to a Mediterranean-type pattern had a modestly better LV structure and function than did participants with less-Mediterranean-like dietary patterns. This trial was registered at clinicaltrials.gov as NCT00005487. © 2016 American Society for Nutrition.

Mortality associated with heart failure with preserved vs. reduced ejection fraction in a prospective international multi-ethnic cohort study.

PubMed

Lam, Carolyn S P; Gamble, Greg D; Ling, Lieng H; Sim, David; Leong, Kui Toh Gerard; Yeo, Poh Shuan Daniel; Ong, Hean Yee; Jaufeerally, Fazlur; Ng, Tze P; Cameron, Vicky A; Poppe, Katrina; Lund, Mayanna; Devlin, Gerry; Troughton, Richard; Richards, A Mark; Doughty, Robert N

2018-05-21

Whether prevalence and mortality of patients with heart failure with preserved or mid-range (40-49%) ejection fraction (HFpEF and HFmREF) are similar to those of heart failure with reduced ejection fraction (HFrEF), as reported in some epidemiologic studies, remains highly controversial. We determined and compared characteristics and outcomes for patients with HFpEF, HFmREF, and HFrEF in a prospective, international, multi-ethnic population. Prospective multi-centre longitudinal study in New Zealand (NZ) and Singapore. Patients with HF were assessed at baseline and followed over 2 years. The primary outcome was death from any cause. Secondary outcome was death and HF hospitalization. Cox proportional hazards models were used to compare outcomes for patients with HFpEF, HFmrEF, and HFrEF. Of 2039 patients enrolled, 28% had HFpEF, 13% HFmrEF, and 59% HFrEF. Compared with HFrEF, patients with HFpEF were older (62 vs. 72 years), more commonly female (17% vs. 48%), and more likely to have a history of hypertension (61% vs. 78%) but less likely to have coronary artery disease (55% vs. 41%). During 2 years of follow-up, 343 (17%) patients died. Adjusting for age, sex, and clinical risk factors, patients with HFpEF had a lower risk of death compared with those with HFrEF (hazard ratio 0.62, 95% confidence interval 0.46-0.85). Plasma (NT-proBNP) was similarly related to mortality in both HFpEF, HFmrEF, and HFrEF independent of the co-variates listed and of ejection fraction. Results were similar for the composite endpoint of death or HF and were consistent between Singapore and NZ. These prospective multinational data showed that the prevalence of HFpEF within the HF population was lower than HFrEF. Death rate was comparable in HFpEF and HFmrEF and lower than in HFrEF. Plasma levels of NT-proBNP were independently and similarly predictive of death in the three HF phenotypes. Australian New Zealand Clinical Trial Registry (ACTRN12610000374066).

Eligibility of sacubitril-valsartan in a real-world heart failure population: a community-based single-centre study.

PubMed

Norberg, Helena; Bergdahl, Ellinor; Lindmark, Krister

2018-04-01

This study aims to investigate the eligibility of the Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor (ARNI) with ACE inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) study to a real-world heart failure population. Medical records of all heart failure patients living within the catchment area of Umeå University Hospital were reviewed. This district consists of around 150 000 people. Out of 2029 patients with a diagnosis of heart failure, 1924 (95%) had at least one echocardiography performed, and 401 patients had an ejection fraction of ≤35% at their latest examination. The major PARADIGM-HF criteria were applied, and 95 patients fulfilled all enrolment criteria and thus were eligible for sacubitril-valsartan. This corresponds to 5% of the overall heart failure population and 24% of the population with ejection fraction ≤ 35%. The eligible patients were significantly older (73.2 ± 10.3 vs. 63.8 ± 11.5 years), had higher blood pressure (128 ± 17 vs. 122 ± 15 mmHg), had higher heart rate (77 ± 17 vs. 72 ± 12 b.p.m.), and had more atrial fibrillation (51.6% vs. 36.2%) than did the PARADIGM-HF population. Only 24% of our real-world heart failure and reduced ejection fraction population was eligible for sacubitril-valsartan, and the real-world heart failure and reduced ejection fraction patients were significantly older than the PARADIGM-HF population. The lack of data on a majority of the patients that we see in clinical practice is a real problem, and we are limited to extrapolation of results on a slightly different population. This is difficult to address, but perhaps registry-based randomized clinical trials will help to solve this issue. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

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.

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.

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.

The Influence of Different Operating Conditions on the Blood Damage of a Pulsatile Ventricular Assist Device.

PubMed

Xu, Zihao; Yang, Ming; Wang, Xianghui; Wang, Zhong

2015-01-01

Because of pulsatile blood flow's benefit for myocardial recovery, perfusion of coronary arteries and end organs, pulsatile ventricular assist devices (VADs) are still widely used as paracorporeal mechanical circulatory support devices in clinical applications, especially in pediatric heart failure patients. However, severe blood damage limits the VAD's service period. Besides optimizing the VAD geometry to reduce blood damage, the blood damage may also be decreased by changing the operating conditions. In this article, a pulsatile VAD was used to investigate the influence of operating conditions on its blood damage, including hemolysis, platelet activation, and platelet deposition. Three motion profiles of pusher plate (sine, cosine, and polynomial), three stroke volumes (ejection fractions) (56 ml [70%], 42 ml [52.5%], and 28 ml [35%]), three pulsatile rates (75, 100, and 150 bpm), and two assist modes (copulsation and counterpulsation) were implemented respectively in VAD fluid-structure interaction simulations to calculate blood damage. The blood damage indices indicate that cosine motion profile, higher ejection fraction, higher pulsatile rate, and counterpulsation can decrease platelet deposition whereas increase hemolysis and platelet activation, and vice versa. The results suggest that different operating conditions have different effects on pulsatile VAD's blood damage and may be beneficial to choose suitable operating condition to reduce blood damage in clinical applications.

Heart failure in patients with kidney disease and iron deficiency; the role of iron therapy.

PubMed

Cases Amenós, Aleix; Ojeda López, Raquel; Portolés Pérez, José María

Chronic kidney disease and anaemia are common in heart failure (HF) and are associated with a worse prognosis in these patients. Iron deficiency is also common in patients with HF and increases the risk of morbidity and mortality, regardless of the presence or absence of anaemia. While the treatment of anaemia with erythropoiesis-stimulating agents in patients with HF have failed to show a benefit in terms of morbidity and mortality, treatment with IV iron in patients with HF and reduced ejection fraction and iron deficiency is associated with clinical improvement. In a posthoc analysis of a clinical trial, iron therapy improved kidney function in patients with HF and iron deficiency. In fact, the European Society of Cardiology's recent clinical guidelines on HF suggest that in symptomatic patients with reduced ejection fraction and iron deficiency, treatment with IV ferric carboxymaltose should be considered to improve symptoms, the ability to exercise and quality of life. Iron plays a key role in oxygen storage (myoglobin) and in energy metabolism, and there are pathophysiological bases that explain the beneficial effect of IV iron therapy in patients with HF. All these aspects are reviewed in this article. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Right heart chamber geometry and tricuspid annulus morphology in patients undergoing mitral valve repair with and without tricuspid valve annuloplasty.

PubMed

Tamborini, Gloria; Fusini, Laura; Muratori, Manuela; Gripari, Paola; Ghulam Ali, Sarah; Fiorentini, Cesare; Pepi, Mauro

2016-06-01

According to current recommendations, patients could benefit from tricuspid valve (TV) annuloplasty at the time mitral valve (MV) surgery if tricuspid regurgitation is severe or if tricuspid annulus (TA) dilatation is present. Therefore, an accurate pre-operative echocardiographic study is mandatory for left but also for right cardiac structures. Aims of this study are to assess right atrial (RA), right ventricular (RV) and TA geometry and function in patients undergoing MV repair without or with TV annuloplasty. We studied 103 patients undergoing MV surgery without (G1: 54 cases) or with (G2: 49 cases) concomitant TV annuloplasty and 40 healthy subjects (NL) as controls. RA, RV and TA were evaluated by three-dimensional (3D) transthoracic echocardiography. Comparing the pathological to the NL group, TA parameters and 3D right chamber volumes were significantly larger. RA and RV ejection fraction and TA% reduction were lower in pathological versus NL, and in G2 versus G1. In pathological patients, TA area positively correlated to systolic pulmonary pressure and negatively with RV and RA ejection fraction. Patients undergoing MV surgery and TV annuloplasty had an increased TA dimensions and a more advanced remodeling of right heart chambers probably reflecting an advanced stage of the disease.

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.

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.

Randomized placebo controlled blinded study to assess valsartan efficacy in preventing left ventricle remodeling in patients with dual chamber pacemaker--Rationale and design of the trial.

PubMed

Tomasik, Andrzej; Jacheć, Wojciech; Wojciechowska, Celina; Kawecki, Damian; Białkowska, Beata; Romuk, Ewa; Gabrysiak, Artur; Birkner, Ewa; Kalarus, Zbigniew; Nowalany-Kozielska, Ewa

2015-05-01

Dual chamber pacing is known to have detrimental effect on cardiac performance and heart failure occurring eventually is associated with increased mortality. Experimental studies of pacing in dogs have shown contractile dyssynchrony leading to diffuse alterations in extracellular matrix. In parallel, studies on experimental ischemia/reperfusion injury have shown efficacy of valsartan to inhibit activity of matrix metalloproteinase-9, to increase the activity of tissue inhibitor of matrix metalloproteinase-3 and preserve global contractility and left ventricle ejection fraction. To present rationale and design of randomized blinded trial aimed to assess whether 12 month long administration of valsartan will prevent left ventricle remodeling in patients with preserved left ventricle ejection fraction (LVEF ≥ 40%) and first implantation of dual chamber pacemaker. A total of 100 eligible patients will be randomized into three parallel arms: placebo, valsartan 80 mg/daily and valsartan 160 mg/daily added to previously used drugs. The primary endpoint will be assessment of valsartan efficacy to prevent left ventricle remodeling during 12 month follow-up. We assess patients' functional capacity, blood plasma activity of matrix metalloproteinases and their tissue inhibitors, NT-proBNP, tumor necrosis factor alpha, and Troponin T. Left ventricle function and remodeling is assessed echocardiographically: M-mode, B-mode, tissue Doppler imaging. If valsartan proves effective, it will be an attractive measure to improve long term prognosis in aging population and increasing number of pacemaker recipients. ClinicalTrials.org (NCT01805804). Copyright © 2015 Elsevier Inc. All rights reserved.

Left ventricular ejection fraction and left atrium diameter related to new-onset atrial fibrillation following acute myocardial infarction: a systematic review and meta-analysis.

PubMed

Zeng, Rui-Xiang; Chen, Mao-Sheng; Lian, Bao-Tao; Liao, Peng-Da; Zhang, Min-Zhou

2017-10-06

New-onset atrial fibrillation (NOAF) occurs frequently in patients with acute myocardial infarction (AMI), and is associated with increased subsequent cardiovascular mortality. However, only a few studies directly evaluated the relationship of left ventricular ejection fraction (LVEF) or left atrium diameter (LAD) and NOAF following AMI. MEDLINE ® , EMBASE ® and the Cochrane Library were carried out to find studies until January 2017. Pooled mean difference (MD) and 95% confidence interval (CI) were calculated to evaluate the value of LVEF and LAD in the prediction of NOAF after AMI. We performed sensitivity analyses to explore the potential sources of heterogeneity. Statistical analyses were carried out using the Revman 5.3. We included 10 qualifying studies comprising a total of 708 patients with NOAF and 6785 controls. Overall, decreased LVEF and increased LAD levels had a significant positive association with NOAF in patients with AMI. The MD in the LVEF levels between the patients with and those without NOAF was -4.91 units (95% Cl: -5.70 to -4.12), test for overall effect z-score = 12.18 ( p < 0.00001, I 2 = 35%). Moreover, in a subgroup analysis, the MD for LAD and NOAF was 2.55 units (95% Cl: 1.91 to 3.19), test for overall effect z-score = 7.80 ( p < 0.00001, I 2 = 57%). Our meta-analysis demonstrated that both decreased LVEF and increased LAD levels were associated with greater risk of NOAF following AMI.

A Systematic Review Concerning the Relation between the Sympathetic Nervous System and Heart Failure with Preserved Left Ventricular Ejection Fraction

PubMed Central

Verloop, Willemien L.; Beeftink, Martine M. A.; Santema, Bernadet T.; Bots, Michiel L.; Blankestijn, Peter J.; Cramer, Maarten J.; Doevendans, Pieter A.; Voskuil, Michiel

2015-01-01

Background Heart failure with preserved left ventricular ejection fraction (HFPEF) affects about half of all patients diagnosed with heart failure. The pathophysiological aspect of this complex disease state has been extensively explored, yet it is still not fully understood. Since the sympathetic nervous system is related to the development of systolic HF, we hypothesized that an increased sympathetic nerve activation (SNA) is also related to the development of HFPEF. This review summarizes the available literature regarding the relation between HFPEF and SNA. Methods and Results Electronic databases and reference lists through April 2014 were searched resulting in 7722 unique articles. Three authors independently evaluated citation titles and abstracts, resulting in 77 articles reporting about the role of the sympathetic nervous system and HFPEF. Of these 77 articles, 15 were included for critical appraisal: 6 animal and 9 human studies. Based on the critical appraisal, we selected 9 articles (3 animal, 6 human) for further analysis. In all the animal studies, isoproterenol was administered to mimic an increased sympathetic activity. In human studies, different modalities for assessment of sympathetic activity were used. The studies selected for further evaluation reported a clear relation between HFPEF and SNA. Conclusion Current literature confirms a relation between increased SNA and HFPEF. However, current literature is not able to distinguish whether enhanced SNA results in HFPEF, or HFPEF results in enhanced SNA. The most likely setting is a vicious circle in which HFPEF and SNA sustain each other. PMID:25658630

Left ventricular dysfunction after closure of large patent ductus arteriosus.

PubMed

Galal, M Omar; Amin, Mohamed; Hussein, Arif; Kouatli, Amjad; Al-Ata, Jameel; Jamjoom, Ahmed

2005-03-01

Changes in left ventricular dimensions and performance were studied in 43 patients after transcatheter occlusion or surgical ligation of patent ductus arteriosus. The patients were assigned to 2 groups based on their ductal diameter: >/= 3.1 mm to group A (n = 27) and

DDD versus VVIR versus VVI mode in patients with indication to dual-chamber stimulation: a prospective, randomized, controlled, single-blind study.

PubMed

Moro, Eugenio; Caprioglio, Francesco; Berton, Giuseppe; Marcon, Carlo; Riva, Umberto; Corbucci, Giorgio; Delise, Pietro

2005-09-01

The aim of this study was to compare VVI, VVIR and DDD modes in patients with indication to dual-chamber stimulation, depending on left ventricular function. Two groups of patients were implanted with a DDD pacemaker: Group I with ejection fraction > 40% and Group II with ejection fraction < 40%. Patients with a history of atrial arrhythmia or retrograde conduction were excluded. At follow-up (1 month each) quality of life (QoL), patient preference and echo parameters were collected. At hospital discharge all patients were programmed in DDD for 1 month and then randomized to VVI or VVIR mode. At the end of the period in VVI or VVIR mode each patient underwent a control period in DDD and then was programmed in VVIR or VVI mode. Seventeen patients out of 23 preferred DDD mode and 6 did not perceive any subjective difference among DDD, VVI and VVIR modes (4/9 in Group I and 2/14 in Group II, p = 0.0017). QoL was significantly different between the two groups and at each follow-up showed the best values in DDD. The correlation between QoL and Tei index was 0.62 in Group I (p < 0.001) and 0.35 in Group II (p = 0.001). Neither ejection fraction nor fractional shortening showed any significant difference during the three phases of the study. Most patients preferred the DDD mode. The Tei index showed a good correlation with QoL and both QoL and Tei index significantly improved with DDD mode as compared to VVI and VVIR.

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.

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

Massie, B.; Kramer, B.L.; Topic, N.

Although the resting hemodynamic effects of captopril in congestive heart failure are known, little information is available about the hemodynamic response to captopril during exercise or about changes in noninvasive measurements of the size and function of both ventricles. In this study, 14 stable New York Heart Association class III patients were given 25 mg of oral captopril. Rest and exercise hemodynamic measurements and blood pool scintigrams were performed simultaneously before and 90 minutes after captopril. The radionuclide studies were analyzed for left and right ventricular end-diastolic volumes, end-systolic volumes, ejection fractions and pulmonary blood volume. The primary beneficial responsesmore » at rest were decreases in left and right ventricular end-diastolic volumes from 388 +/- 81 to 350 +/- 77 ml and from 52 +/- 26 to 43 +/- 20 volume units, respectively, and in their corresponding filling pressures, from 24 +/- 10 to 17 +/- 9 mm Hg and 10 +/- 5 to 6 +/- 5 mm Hg. Although stroke volume did not increase significantly, both left and right ventricular ejection fractions increased slightly, from 19 +/- 6% to 22+/- 5% and from 25 +/- 9% to 29 +/- 11%, respectively. During exercise, similar changes were noted in both hemodynamic and radionuclide indexes. This, in patients with moderate symptomatic limitation from chronic heart failure, captopril predominantly reduces ventricular volume and filling pressure, with a less significant effect on cardiac output. These effects persist during exercise, when systemic vascular resistance is already very low. Radionuclide techniques are valuable in assessing the drug effect in these subjects, particularly when ventricular volumes are also measured.« less

Spironolactone in patients with heart failure and preserved ejection fraction.

PubMed

Sánchez-Sánchez, C; Mendoza-Ruiz de Zuazu, H F; Formiga, F; Manzano, L; Ceresuela, L M; Carrera-Izquierdo, M; González Franco, Á; Epelde-Gonzalo, F; Cerqueiro-González, J M; Montero-Pérez-Barquero, M

2015-01-01

Aldosterone inhibitors have been shown to be beneficial for patients with systolic heart failure. However, the evidence from patients with heart failure and preserved ejection fraction (HFPEF) is limited. We evaluated the role of spironolactone in the prognosis of a cohort of patients with HFPEF. We analyzed the outcomes of patients hospitalized for HFPEF in 52 departments of internal medicine of the Spanish RICA registry according to those who did and did not take spironolactone. We recorded the posthospital mortality rate and readmissions at 1 year and performed a multivariate survival analysis. We included 1212 patients with HFPEF, with a mean age of 79 years (standard deviation, 7.9), (64.1% women), the majority of whom had hypertensive heart disease (50.7%). The patients treated with spironolactone, compared with those who were not treated with this diuretic, had a more advanced functional class, a higher number of readmissions (44.3 vs. 29.1%; p<0.001) and a higher rate in the combined variable of readmissions/mortality (39.0 vs. 29.0%; p=0.001). In the multivariate analysis, the administration of spironolactone was associated with an increase in readmissions (RR, 1.4; 95% CI, 1.16-1.78; p=0.001). For patients with HFPEF, the administration of spironolactone was associated with an increase in all-cause readmission, perhaps due to the higher rate of hyperpotassemia. Copyright © 2015. Published by Elsevier España, S.L.U.

Mass selectivity of dipolar resonant excitation in a linear quadrupole ion trap.

PubMed

Douglas, D J; Konenkov, N V

2014-03-15

For mass analysis, linear quadrupole ion traps operate with dipolar excitation of ions for either axial or radial ejection. There have been comparatively few computer simulations of this process. We introduce a new concept, the excitation contour, S(q), the fraction of the excited ions that reach the trap electrodes when trapped at q values near that corresponding to the excitation frequency. Ion trajectory calculations are used to calculate S(q). Ions are given Gaussian distributions of initial positions in x and y, and thermal initial velocity distributions. To model gas damping, a drag force is added to the equations of motion. The effects of the initial conditions, ejection Mathieu parameter q, scan speed, excitation voltage and collisional damping, are modeled. We find that, with no buffer gas, the mass resolution is mostly determined by the excitation time and is given by R~dβ/dq qn, where β(q) determines the oscillation frequency, and n is the number of cycles of the trapping radio frequency during the excitation or ejection time. The highest resolution at a given scan speed is reached with the lowest excitation amplitude that gives ejection. The addition of a buffer gas can increase the mass resolution. The simulation results are in broad agreement with experiments. The excitation contour, S(q), introduced here, is a useful tool for studying the ejection process. The excitation strength, excitation time and buffer gas pressure interact in a complex way but, when set properly, a mass resolution R0.5 of at least 10,000 can be obtained at a mass-to-charge ratio of 609. Copyright © 2014 John Wiley & Sons, Ltd.

Patients with a hypertensive response to exercise have impaired left ventricular diastolic function.

PubMed

Takamura, Takeshi; Onishi, Katsuya; Sugimoto, Tadafumi; Kurita, Tairo; Fujimoto, Naoki; Dohi, Kaoru; Tanigawa, Takashi; Isaka, Naoki; Nobori, Tsutomu; Ito, Masaaki

2008-02-01

An exaggerated increase in systolic blood pressure prolongs myocardial relaxation and increases left ventricular (LV) chamber stiffness, resulting in an increase in LV filling pressure. We hypothesize that patients with a marked hypertensive response to exercise (HRE) have LV diastolic dysfunction leading to exercise intolerance, even in the absence of resting hypertension. We recruited 129 subjects (age 63+/-9 years, 64% male) with a preserved ejection fraction and a negative stress test. HRE was evaluated at the end of a 6-min exercise test using the modified Bruce protocol. Patients were categorized into three groups: a group without HRE and without resting hypertension (control group; n=30), a group with HRE but without resting hypertension (HRE group; n=25), and a group with both HRE and resting hypertension (HTN group; n=74). Conventional Doppler and tissue Doppler imaging were performed at rest. After 6-min exercise tests, systolic blood pressure increased in the HRE and HTN groups, compared with the control group (226+/-17 mmHg, 226+/-17 mmHg, and 180+/-15 mmHg, respectively, p<0.001). There were no significant differences in LV ejection fraction, LV end-diastolic diameter, and early mitral inflow velocity among the three groups. However, early diastolic mitral annular velocity (E') was significantly lower and the ratio of early diastolic mitral inflow velocity (E) to E' (E/E') was significantly higher in patients of the HRE and HTN groups compared to controls (E': 5.9+/-1.6 cm/s, 5.9+/-1.7 cm/s, 8.0+/-1.9 cm/s, respectively, p<0.05). In conclusion, irrespective of the presence of resting hypertension, patients with hypertensive response to exercise had impaired LV longitudinal diastolic function and exercise intolerance.

Effect of Adjuvant Chemotherapy on Left Ventricular Remodeling in Women with Newly Diagnosed Primary Breast Cancer: A Pilot Prospective Longitudinal Cardiac Magnetic Resonance Imaging Study.

PubMed

Avelar, Erick; Truong, Quynh A; Inyangetor, David; Marfatia, Ravi; Yang, Clifford; Kaloudis, Electra; Tannenbaum, Susan; Rosito, Guido; Litwin, Sheldon

2017-11-01

The aim of this study was to assess the left ventricular (LV) remodeling response to chemotherapy in low-cardiac-risk women with newly diagnosed nonmetastatic breast cancer. Cardiotoxic effects of chemotherapy are an increasing concern. To effectively interpret cardiac imaging studies performed for screening purposes in patients undergoing cancer therapy it is necessary to understand the normal changes in structure and function that may occur. Twenty women without preexisting cardiovascular disease, of a mean age of 50 years, newly diagnosed with nonmetastatic breast cancer and treated with anthracycline or trastuzumab, were prospectively enrolled and evaluated at four time points (at baseline, during chemotherapy, 2 weeks after chemotherapy, and 6 months after chemotherapy) using cardiac magnetic resonance imaging, blood samples, and a clinical questionnaire. Over a 6-month period, the left ventricular ejection fraction (%) decreased (64.15±5.30 to 60.41±5.77, P<0.002) and the LV end-diastolic (mm) and end-systolic (mm) volumes increased (124.73±20.25 to 132.21±19.33, P<0.04 and 45.16±11.88 to 52.57±11.65, P<0.00, respectively). The LV mass (g) did not change (73.06±11.51 to 69.21±15.3, P=0.08), but the LV mass to LVEDV ratio (g/mm) decreased (0.594±0.098 to 0.530±0.124, P<0.04). In low-cardiac-risk women with nonmetastatic breast cancer, the increased LV volume and a mildly decreased left ventricular ejection fraction during and after chemotherapy do not seem to be associated with laboratory or clinical evidence of increased risk for heart failure.

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.

Resveratrol improves exercise performance and skeletal muscle oxidative capacity in heart failure.

PubMed

Sung, Miranda M; Byrne, Nikole J; Robertson, Ian M; Kim, Ty T; Samokhvalov, Victor; Levasseur, Jody; Soltys, Carrie-Lynn; Fung, David; Tyreman, Neil; Denou, Emmanuel; Jones, Kelvin E; Seubert, John M; Schertzer, Jonathan D; Dyck, Jason R B

2017-04-01

We investigated whether treatment of mice with established pressure overload-induced heart failure (HF) with the naturally occurring polyphenol resveratrol could improve functional symptoms of clinical HF such as fatigue and exercise intolerance. C57Bl/6N mice were subjected to either sham or transverse aortic constriction surgery to induce HF. Three weeks postsurgery, a cohort of mice with established HF (%ejection fraction <45) was administered resveratrol (~450 mg·kg -1 ·day -1 ) or vehicle for 2 wk. Although the percent ejection fraction was similar between both groups of HF mice, those mice treated with resveratrol had increased total physical activity levels and exercise capacity. Resveratrol treatment was associated with altered gut microbiota composition, increased skeletal muscle insulin sensitivity, a switch toward greater whole body glucose utilization, and increased basal metabolic rates. Although muscle mass and strength were not different between groups, mice with HF had significant declines in basal and ADP-stimulated O 2 consumption in isolated skeletal muscle fibers compared with sham mice, which was completely normalized by resveratrol treatment. Overall, resveratrol treatment of mice with established HF enhances exercise performance, which is associated with alterations in whole body and skeletal muscle energy metabolism. Thus, our preclinical data suggest that resveratrol supplementation may effectively improve fatigue and exercise intolerance in HF patients. NEW & NOTEWORTHY Resveratrol treatment of mice with heart failure leads to enhanced exercise performance that is associated with altered gut microbiota composition, increased whole body glucose utilization, and enhanced skeletal muscle metabolism and function. Together, these preclinical data suggest that resveratrol supplementation may effectively improve fatigue and exercise intolerance in heart failure via these mechanisms. Copyright © 2017 the American Physiological Society.

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.

Determination of left ventricular volume, ejection fraction, and myocardial mass by real-time three-dimensional echocardiography

NASA Technical Reports Server (NTRS)

Qin, J. X.; Shiota, T.; Thomas, J. D.

2000-01-01

Reconstructed three-dimensional (3-D) echocardiography is an accurate and reproducible method of assessing left ventricular (LV) functions. However, it has limitations for clinical study due to the requirement of complex computer and echocardiographic analysis systems, electrocardiographic/respiratory gating, and prolonged imaging times. Real-time 3-D echocardiography has a major advantage of conveniently visualizing the entire cardiac anatomy in three dimensions and of potentially accurately quantifying LV volumes, ejection fractions, and myocardial mass in patients even in the presence of an LV aneurysm. Although the image quality of the current real-time 3-D echocardiographic methods is not optimal, its widespread clinical application is possible because of the convenient and fast image acquisition. We review real-time 3-D echocardiographic image acquisition and quantitative analysis for the evaluation of LV function and LV mass.

Determination of left ventricular volume, ejection fraction, and myocardial mass by real-time three-dimensional echocardiography.

PubMed

Qin, J X; Shiota, T; Thomas, J D

2000-11-01

Reconstructed three-dimensional (3-D) echocardiography is an accurate and reproducible method of assessing left ventricular (LV) functions. However, it has limitations for clinical study due to the requirement of complex computer and echocardiographic analysis systems, electrocardiographic/respiratory gating, and prolonged imaging times. Real-time 3-D echocardiography has a major advantage of conveniently visualizing the entire cardiac anatomy in three dimensions and of potentially accurately quantifying LV volumes, ejection fractions, and myocardial mass in patients even in the presence of an LV aneurysm. Although the image quality of the current real-time 3-D echocardiographic methods is not optimal, its widespread clinical application is possible because of the convenient and fast image acquisition. We review real-time 3-D echocardiographic image acquisition and quantitative analysis for the evaluation of LV function and LV mass.

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.

Echocardiographic dimensions and function in adults with primary growth hormone resistance (Laron syndrome).

PubMed

Feinberg, M S; Scheinowitz, M; Laron, Z

2000-01-15

Patients with primary growth hormone (GH) resistance-Laron Syndrome (LS)-have no GH signal transmission, and thus, no generation of circulating insulin-like growth factor-I (IGF-I), and should serve as a unique model to explore the controversies concerning the longterm effect of GH/IGF-I deficiency on cardiac dimension and function. We assessed 8 patients with LS (4 men, 4 women) with a mean (+/- SD) age of 38+/-7 years (range 22 to 45), and 8 aged-matched controls (4 men, 4 women) with a mean age of 38+/-9 years (range 18 to 47) by echocardiography at rest, following exercise, and during dobutamine administration. Left ventricular (LV) septum, posterior wall, and end-diastolic diameter were significantly reduced in untreated patients with LS compared with the control group (p<0.05 for all). Systolic Doppler-derived parameters, including LV stroke volume, stroke index, cardiac output, and cardiac index, were significantly lower (p<0.05 for all) than in the control subjects, whereas LV diastolic Doppler parameters, including mitral valve waves E, A, E/A ratio, and E deceleration time, were similar in both groups. LV ejection fraction at rest as well as the stress-induced increment of the LV ejection fraction were similar in both groups. Our results show that untreated patients with long-term IGF-I deficiency have reduced cardiac dimensions and output but normal LV ejection fraction at rest and LV contractile reserve following stress.

Cardiac magnetic resonance analysis of right ventricular function: comparison of quantification in the short-axis and 4-chamber planes.

PubMed

Souto Bayarri, M; Masip Capdevila, L; Remuiñan Pereira, C; Suárez-Cuenca, J J; Martínez Monzonís, A; Couto Pérez, M I; Carreira Villamor, J M

2015-01-01

To compare the methods of right ventricle segmentation in the short-axis and 4-chamber planes in cardiac magnetic resonance imaging and to correlate the findings with those of the tricuspid annular plane systolic excursion (TAPSE) method in echocardiography. We used a 1.5T MRI scanner to study 26 patients with diverse cardiovascular diseases. In all MRI studies, we obtained cine-mode images from the base to the apex in both the short-axis and 4-chamber planes using steady-state free precession sequences and 6mm thick slices. In all patients, we quantified the end-diastolic volume, end-systolic volume, and the ejection fraction of the right ventricle. On the same day as the cardiac magnetic resonance imaging study, 14 patients also underwent echocardiography with TAPSE calculation of right ventricular function. No statistically significant differences were found in the volumes and function of the right ventricle calculated using the 2 segmentation methods. The correlation between the volume estimations by the two segmentation methods was excellent (r=0,95); the correlation for the ejection fraction was slightly lower (r=0,8). The correlation between the cardiac magnetic resonance imaging estimate of right ventricular ejection fraction and TAPSE was very low (r=0,2, P<.01). Both ventricular segmentation methods quantify right ventricular function adequately. The correlation with the echocardiographic method is low. Copyright © 2012 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

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.

Electrocardiograph-gated single photon emission computed tomography radionuclide angiography presents good interstudy reproducibility for the quantification of global systolic right ventricular function.

PubMed

Daou, Doumit; Coaguila, Carlos; Vilain, Didier

2007-05-01

Electrocardiograph-gated single photon emission computed tomography (SPECT) radionuclide angiography provides accurate measurement of right ventricular ejection fraction and end-diastolic and end-systolic volumes. In this study, we report the interstudy precision and reliability of SPECT radionuclide angiography for the measurement of global systolic right ventricular function using two, three-dimensional volume processing methods (SPECT-QBS, SPECT-35%). These were compared with equilibrium planar radionuclide angiography. Ten patients with chronic coronary artery disease having two SPECT and planar radionuclide angiography acquisitions were included. For the right ventricular ejection fraction, end-diastolic volume and end-systolic volume, the interstudy precision and reliability were better with SPECT-35% than with SPECT-QBS. The sample sizes needed to objectify a change in right ventricular volumes or ejection fraction were lower with SPECT-35% than with SPECT-QBS. The interstudy precision and reliability of SPECT-35% and SPECT-QBS for the right ventricle were better than those of equilibrium planar radionuclide angiography, but poorer than those previously reported for the left ventricle with SPECT radionuclide angiography on the same population. SPECT-35% and SPECT-QBS present good interstudy precision and reliability for right ventricular function, with the results favouring the use of SPECT-35%. The results are better than those of equilibrium planar radionuclide angiography, but poorer than those previously reported for the left ventricle with SPECT radionuclide angiography. They need to be confirmed in a larger population.

Hearts and Minds: Real-Life Cardiotoxicity With Clozapine in Psychosis.

PubMed

Joy, George; Whiskey, Eromona; Bolstridge, Mark; Porras-Segovia, Alejandro; McDonagh, Theresa A; Plymen, Carla M; Shergill, Sukhi S

2017-12-01

Schizophrenia has a 1% prevalence in the population; 30% of these patients are treatment refractory. Clozapine is the only drug licensed to treat treatment refractory psychosis, but concerns about potential adverse effects result in only a proportion of eligible patients being treated. Although a well-documented neutropenia risk is mitigated by routine blood testing, cardiac toxicity is a commonly cited reason to discontinue clozapine treatment. However, there is little data on the real-life cardiac outcomes in those receiving clozapine treatment. Retrospective review of electrocardiogram, echocardiogram, and clinical outcomes in 39 inpatients with treatment-refractory schizophrenia, treated with clozapine and other antipsychotic medication, referred for cardiology opinion. Commonest reasons for referral were development of left ventricular (LV) impairment or sinus tachycardia with normal LV function. Patients were reviewed by a range of cardiologists, receiving varied interventions.Median LV ejection fraction in the clozapine group was normal (52%). Serial echocardiograms demonstrated that clozapine-treated patients with LV impairment had no change in LV ejection fraction over a 4-month follow-up. Left ventricular ejection fraction did not differ between patients treated with clozapine and other antipsychotics. However, over an 11-year follow-up period, 48% of patients had discontinued clozapine treatment. This naturalistic study demonstrates that clozapine is not associated with significant cardiac mortality or morbidity. There is a real need for multidisciplinary working between specialist cardiologists and psychiatrists caring for these complex patients to facilitate optimal long-term physical and mental health outcomes.

Hypertension and Organ Damage in Women.

PubMed

Muiesan, Maria Lorenza; Paini, Anna; Aggiusti, Carlo; Bertacchini, Fabio; Rosei, Claudia Agabiti; Salvetti, Massimo

2018-06-26

An adequate cardiovascular (CV) prevention strategy in women should consider the acknowledgement of sex-specific risk factors, such as hypertension in pregnancy, the concomitant presence of autoimmune diseases and the benefit of evaluating subclinical organ damage and treating hypertension. In accordance to current guidelines, the diagnostic approach does not differ between men and women, although the cardiac response to pressure overload may suggest greater sensitivity in women, and may vary according to age, ethnic background and obesity, that potentiates the effect of hypertension on left ventricular (LV) hypertrophy. Several studies have observed peculiar abnormalities in LV systolic and diastolic function according to gender. The possible mechanisms that influence a different cardiac adaptation to chronic pressure overload in men and women are not fully understood, although hormonal status, and in particular the lack of estrogen effects after menopause may contribute to the cardiovascular adaptation response to increased afterload. The increase in LV mass in response to chronic pressure overload is associated with higher LV ejection fraction in women than in men and LV torsion is maintained with aging in women but not in men. Interstitial fibrosis may reduce circumferential shortening and early diastolic strain rate, in the presence of a preserved ejection fraction in women, favoring the development of heart failure with preserved ejection fraction. Changes in aortic stiffness with aging may influence cardiac structural and functional changes. Isolated systolic hypertension reflects an increase in aortic stiffness, is frequent in women and may be associated to a greater development of concentric LVH. The regression of hypertensive LVH is more difficult in women, and residual hypertrophy is more common in women than in men despite effective antihypertensive treatment and blood pressure control. Carotid atherosclerosis has been extensively investigated in men and women, showing that women usually develop carotid plaques after menopause, with smaller and less unstable plaques; however large and/or a hypoechogenic plaques are more strictly related to cerebrovascular events in women than in men. More advanced abnormalities in the subcutaneous microcirculation have been recently observed, and well translate in the evidence of more prevalent coronary microcirculation involvement in women ischemic heart disease. The prevalence of albuminuria and of reduced estimated glomerular filtration rate (eGFR < 60 ml/min/1.73) are respectively lower and higher in postmenopausal women than in men. Experimental data suggest the possible involvement of renin-angiotensin-aldosterone system and of T regulatory lymphocytes to this regard.

Redistribution of Lunar Polar Water to Mid-latitudes and its Role in Forming an OH veneer - Revisited

NASA Technical Reports Server (NTRS)

Farrell, W. M.; Killen, R. M.; Hurley, D. M.; Hodges, R. R.; Halekas, J. S.; Delory, G. T.

2012-01-01

We suggest that energization processes like ion sputtering and impact vaporization can eject/release polar water molecules residing within lunar cold trapped regions with sufficient velocity to allow their redistribution to mid-latitudes. We consider the possibility that these polar-ejected molecules can be an additional (but not dominant) contribution to the water/OH veneer observed as a 3 micron absorption feature at mid-latitudes by Chandrayaan-I, Cassini, and EPOXI. Taking the conservative case that polar water is ejected only from the floor of polar craters with an 0.1 % icy regolith then overall source rates are near 10(exp 18) H20s/s. This outflow amounts to approx 10(exp -7) kg/s of water to be ejected from each pole and is a water source rate that is 10(exp .5 lower than the overall exospheric source rate for all species. Hence, the out-flowing polar water is a perturbation in the overall exosphere composition & dynamics. This polar water 'fountain' model may not fully account for the relatively high concentrations in the mid-latitude water veneer observed in the IR (approx 10-1000 ppm). However, it may account for some part of the veneer. We note that the polar water fountain source rates scale linearly with ice concentration, and larger mass fractions of polar crater water should provide correspondingly larger fractions of water emission out of the poles which then 'spills' on to mid-latitude surfaces.

Differential right ventricular regional function and the effect of pulmonary hypertension: three-dimensional echo study.

PubMed

Calcutteea, Avin; Chung, Robin; Lindqvist, Per; Hodson, Margaret; Henein, Michael Y

2011-06-01

The right ventricle is multicompartmental in orientation. To assess the normal differential function of the right ventricular (RV) inflow, apical and outflow compartments, also their inter-relations and the response to pulmonary arterial hypertension (PAH). 45 people were studied--16 controls and 29 patients with left-sided heart failure, 15 without (group 1) and 14 with (group 2) secondary PAH, using two-dimensional (2D) and 3D echocardiography in addition to conventional Doppler techniques. There was a strong correlation between RV inlet diameter (2D) and end-diastolic volume (3D) (r=0.69, p<0.001) and between tricuspid annular plane systolic excursion and RV ejection fraction (3D) (r=0.71, p<0.001). In controls and patients, the apical ejection fraction was less than the inflow and outflow (controls: p<0.01 and p<0.01, group 1: p<0.05 and p<0.01 and group 2: p<0.05 and p<0.01, respectively). Ejection fraction was reduced in patients (inflow: p<0.001 for both, apical: p<0.01 for both and outflow tract: p<0.05 for both). In controls, the inflow compartment reached the minimum volume 20 ms before the outflow and apex but in group 2 it was simultaneous. Isovolumic contraction and relaxation times were prolonged in patients (Group 1: p=0.02 and p<0.01 and Group 2: p=0.01 for both). Peak RV ejection time correlated with the rate of outflow volume fall in controls but with the apex in group 2 (r=0.6, p<0.05). The right ventricle has distinct features for the inflow, apical and outflow tract compartments, with different extent of contribution to the overall systolic function. In PAH, the right ventricle becomes one dyssynchronous compartment, which itself may have perpetual effect on overall cardiac dysfunction.

Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure.

PubMed

Cowie, Martin R; Woehrle, Holger; Wegscheider, Karl; Angermann, Christiane; d'Ortho, Marie-Pia; Erdmann, Erland; Levy, Patrick; Simonds, Anita K; Somers, Virend K; Zannad, Faiez; Teschler, Helmut

2015-09-17

Central sleep apnea is associated with poor prognosis and death in patients with heart failure. Adaptive servo-ventilation is a therapy that uses a noninvasive ventilator to treat central sleep apnea by delivering servo-controlled inspiratory pressure support on top of expiratory positive airway pressure. We investigated the effects of adaptive servo-ventilation in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea. We randomly assigned 1325 patients with a left ventricular ejection fraction of 45% or less, an apnea-hypopnea index (AHI) of 15 or more events (occurrences of apnea or hypopnea) per hour, and a predominance of central events to receive guideline-based medical treatment with adaptive servo-ventilation or guideline-based medical treatment alone (control). The primary end point in the time-to-event analysis was the first event of death from any cause, lifesaving cardiovascular intervention (cardiac transplantation, implantation of a ventricular assist device, resuscitation after sudden cardiac arrest, or appropriate lifesaving shock), or unplanned hospitalization for worsening heart failure. In the adaptive servo-ventilation group, the mean AHI at 12 months was 6.6 events per hour. The incidence of the primary end point did not differ significantly between the adaptive servo-ventilation group and the control group (54.1% and 50.8%, respectively; hazard ratio, 1.13; 95% confidence interval [CI], 0.97 to 1.31; P=0.10). All-cause mortality and cardiovascular mortality were significantly higher in the adaptive servo-ventilation group than in the control group (hazard ratio for death from any cause, 1.28; 95% CI, 1.06 to 1.55; P=0.01; and hazard ratio for cardiovascular death, 1.34; 95% CI, 1.09 to 1.65; P=0.006). Adaptive servo-ventilation had no significant effect on the primary end point in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea, but all-cause and cardiovascular mortality were both increased with this therapy. (Funded by ResMed and others; SERVE-HF ClinicalTrials.gov number, NCT00733343.).

Cardiovascular Outcomes With Minute Ventilation-Targeted Adaptive Servo-Ventilation Therapy in Heart Failure: The CAT-HF Trial.

PubMed

O'Connor, Christopher M; Whellan, David J; Fiuzat, Mona; Punjabi, Naresh M; Tasissa, Gudaye; Anstrom, Kevin J; Benjafield, Adam V; Woehrle, Holger; Blase, Amy B; Lindenfeld, JoAnn; Oldenberg, Olaf

2017-03-28

Sleep apnea is common in hospitalized heart failure (HF) patients and is associated with increased morbidity and mortality. The CAT-HF (Cardiovascular Improvements With MV-ASV Therapy in Heart Failure) trial investigated whether minute ventilation (MV) adaptive servo-ventilation (ASV) improved cardiovascular outcomes in hospitalized HF patients with moderate-to-severe sleep apnea. Eligible patients hospitalized with HF and moderate-to-severe sleep apnea were randomized to ASV plus optimized medical therapy (OMT) or OMT alone (control). The primary endpoint was a composite global rank score (hierarchy of death, cardiovascular hospitalizations, and percent changes in 6-min walk distance) at 6 months. 126 of 215 planned patients were randomized; enrollment was stopped early following release of the SERVE-HF (Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure) trial results. Average device usage was 2.7 h/night. Mean number of events measured by the apnea-hypopnea index decreased from 35.7/h to 2.1/h at 6 months in the ASV group versus 35.1/h to 19.0/h in the control group (p < 0.0001). The primary endpoint did not differ significantly between the ASV and control groups (p = 0.92 Wilcoxon). Changes in composite endpoint components were not significantly different between ASV and control. There was no significant interaction between treatment and ejection fraction (p = 0.10 Cox model); however, pre-specified subgroup analysis suggested a positive effect of ASV in patients with HF with preserved ejection fraction (p = 0.036). In hospitalized HF patients with moderate-to-severe sleep apnea, adding ASV to OMT did not improve 6-month cardiovascular outcomes. Study power was limited for detection of safety signals and identifying differential effects of ASV in patients with HF with preserved ejection fraction, but additional studies are warranted in this population. (Cardiovascular Improvements With MV ASV Therapy in Heart Failure [CAT-HF]; NCT01953874). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

High-Intensity Interval Training in Patients With Heart Failure With Reduced Ejection Fraction

PubMed Central

Halle, Martin; Conraads, Viviane; Støylen, Asbjørn; Dalen, Håvard; Delagardelle, Charles; Larsen, Alf-Inge; Hole, Torstein; Mezzani, Alessandro; Van Craenenbroeck, Emeline M.; Videm, Vibeke; Beckers, Paul; Christle, Jeffrey W.; Winzer, Ephraim; Mangner, Norman; Woitek, Felix; Höllriegel, Robert; Pressler, Axel; Monk-Hansen, Tea; Snoer, Martin; Feiereisen, Patrick; Valborgland, Torstein; Kjekshus, John; Hambrecht, Rainer; Gielen, Stephan; Karlsen, Trine; Prescott, Eva; Linke, Axel

2017-01-01

Background: Small studies have suggested that high-intensity interval training (HIIT) is superior to moderate continuous training (MCT) in reversing cardiac remodeling and increasing aerobic capacity in patients with heart failure with reduced ejection fraction. The present multicenter trial compared 12 weeks of supervised interventions of HIIT, MCT, or a recommendation of regular exercise (RRE). Methods: Two hundred sixty-one patients with left ventricular ejection fraction ≤35% and New York Heart Association class II to III were randomly assigned to HIIT at 90% to 95% of maximal heart rate, MCT at 60% to 70% of maximal heart rate, or RRE. Thereafter, patients were encouraged to continue exercising on their own. Clinical assessments were performed at baseline, after the intervention, and at follow-up after 52 weeks. Primary end point was a between-group comparison of change in left ventricular end-diastolic diameter from baseline to 12 weeks. Results: Groups did not differ in age (median, 60 years), sex (19% women), ischemic pathogenesis (59%), or medication. Change in left ventricular end-diastolic diameter from baseline to 12 weeks was not different between HIIT and MCT (P=0.45); left ventricular end-diastolic diameter changes compared with RRE were −2.8 mm (−5.2 to −0.4 mm; P=0.02) in HIIT and −1.2 mm (−3.6 to 1.2 mm; P=0.34) in MCT. There was also no difference between HIIT and MCT in peak oxygen uptake (P=0.70), but both were superior to RRE. However, none of these changes was maintained at follow-up after 52 weeks. Serious adverse events were not statistically different during supervised intervention or at follow-up at 52 weeks (HIIT, 39%; MCT, 25%; RRE, 34%; P=0.16). Training records showed that 51% of patients exercised below prescribed target during supervised HIIT and 80% above target in MCT. Conclusions: HIIT was not superior to MCT in changing left ventricular remodeling or aerobic capacity, and its feasibility remains unresolved in patients with heart failure. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00917046. PMID:28082387

High-Intensity Interval Training in Patients With Heart Failure With Reduced Ejection Fraction.

PubMed

Ellingsen, Øyvind; Halle, Martin; Conraads, Viviane; Støylen, Asbjørn; Dalen, Håvard; Delagardelle, Charles; Larsen, Alf-Inge; Hole, Torstein; Mezzani, Alessandro; Van Craenenbroeck, Emeline M; Videm, Vibeke; Beckers, Paul; Christle, Jeffrey W; Winzer, Ephraim; Mangner, Norman; Woitek, Felix; Höllriegel, Robert; Pressler, Axel; Monk-Hansen, Tea; Snoer, Martin; Feiereisen, Patrick; Valborgland, Torstein; Kjekshus, John; Hambrecht, Rainer; Gielen, Stephan; Karlsen, Trine; Prescott, Eva; Linke, Axel

2017-02-28

Small studies have suggested that high-intensity interval training (HIIT) is superior to moderate continuous training (MCT) in reversing cardiac remodeling and increasing aerobic capacity in patients with heart failure with reduced ejection fraction. The present multicenter trial compared 12 weeks of supervised interventions of HIIT, MCT, or a recommendation of regular exercise (RRE). Two hundred sixty-one patients with left ventricular ejection fraction ≤35% and New York Heart Association class II to III were randomly assigned to HIIT at 90% to 95% of maximal heart rate, MCT at 60% to 70% of maximal heart rate, or RRE. Thereafter, patients were encouraged to continue exercising on their own. Clinical assessments were performed at baseline, after the intervention, and at follow-up after 52 weeks. Primary end point was a between-group comparison of change in left ventricular end-diastolic diameter from baseline to 12 weeks. Groups did not differ in age (median, 60 years), sex (19% women), ischemic pathogenesis (59%), or medication. Change in left ventricular end-diastolic diameter from baseline to 12 weeks was not different between HIIT and MCT ( P =0.45); left ventricular end-diastolic diameter changes compared with RRE were -2.8 mm (-5.2 to -0.4 mm; P =0.02) in HIIT and -1.2 mm (-3.6 to 1.2 mm; P =0.34) in MCT. There was also no difference between HIIT and MCT in peak oxygen uptake ( P =0.70), but both were superior to RRE. However, none of these changes was maintained at follow-up after 52 weeks. Serious adverse events were not statistically different during supervised intervention or at follow-up at 52 weeks (HIIT, 39%; MCT, 25%; RRE, 34%; P =0.16). Training records showed that 51% of patients exercised below prescribed target during supervised HIIT and 80% above target in MCT. HIIT was not superior to MCT in changing left ventricular remodeling or aerobic capacity, and its feasibility remains unresolved in patients with heart failure. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00917046. © 2017 The Authors.

Quercetin protects against inflammation, MMP‑2 activation and apoptosis induction in rat model of cardiopulmonary resuscitation through modulating Bmi‑1 expression.

PubMed

Wang, Dawei; Lou, Xiaoqian; Jiang, Xiao-Ming; Yang, Chenxi; Liu, Xiao-Liang; Zhang, Nan

2018-05-08

With extensive pharmacological actions, quercetin has anti‑oxidant, free radical scavenging, anti‑tumor, anti‑inflammatory, anti‑bacterial and anti‑viral activity. Quercetin also reduces blood glucose and reduces high blood pressure, and has immunoregulation and cardiovascular protection functions. Additionally, it has been reported that it can reduce depression. The current study evaluated whether quercetin protects against inflammation, matrix metalloproteinase‑2 (MMP‑2) activation and apoptosis induction in a rat model of cardiopulmonary resuscitation (CPR), and whether Bmi‑1 expression was involved in the effects. In CPR model rats, treatment with quercetin significantly recovered left ventricular ejection fraction, left ventricular fractional shortening, ejection fraction (%), and left ventricle weight/body weight. Treatment with quercetin significantly inhibited ROS generation, inflammation and MMP‑2 protein expression in the rat model CPR. Finally, quercetin significantly suppressed caspase‑3 activity and activated Bmi‑1 protein expression in the rat model of CPR. The results demonstrated that quercetin protects against inflammation, MMP‑2 activation and apoptosis induction in a rat model of CPR, and that this may be mediated by modulating Bmi‑1 expression.

Ejection of rocky and icy material from binary star systems: implications for the origin and composition of 1I/`Oumuamua

NASA Astrophysics Data System (ADS)

Jackson, Alan P.; Tamayo, Daniel; Hammond, Noah; Ali-Dib, Mohamad; Rein, Hanno

2018-06-01

In single-star systems like our own Solar system, comets dominate the mass budget of bodies ejected into interstellar space, since they form further away and are less tightly bound. However, 1I/`Oumuamua, the first interstellar object detected, appears asteroidal in its spectra and lack of detectable activity. We argue that the galactic budget of interstellar objects like 1I/`Oumuamua should be dominated by planetesimal material ejected during planet formation in circumbinary systems, rather than in single-star systems or widely separated binaries. We further show that in circumbinary systems, rocky bodies should be ejected in comparable numbers to icy ones. This suggests that a substantial fraction of interstellar objects discovered in future should display an active coma. We find that the rocky population, of which 1I/`Oumuamua seems to be a member, should be predominantly sourced from A-type and late B-star binaries.

Three-Dimensional Structure and Energy Balance of a Coronal Mass Ejection

NASA Technical Reports Server (NTRS)

Lee, J.-Y.; Raymond, J. C.; Ko, Y.-K.; Kim, K.-S.

2009-01-01

UVCS observed Doppler-shifted material of a partial halo coronal mass ejection (CME) on 2001 December 13. The observed ratio of [O VJ/O V] is a reliable density diagnostic important for assessing the state of the plasma. Earlier UVCS observations of CMEs found evidence that the ejected plasma is heated long after the eruption. This paper investigated the heating rates, which represent a significant fraction of the CME energy budget. The parameterized heating and radiative and adiabatic cooling have been used to evaluate the temperature evolution of the CME material with a time-dependent ionization state model. Continuous heating is required to match the UVCS observations. To match the O VI bright knots, a higher heating rate is required such that the heating energy is greater than the kinetic energy.

Exploratory assessment of left ventricular strain–volume loops in severe aortic valve diseases

PubMed Central

Hulshof, Hugo G.; van Dijk, Arie P.; George, Keith P.; Hopman, Maria T. E.; Thijssen, Dick H. J.

2017-01-01

Key points Severe aortic valve diseases are common cardiac abnormalities that are associated with poor long‐term survival.Before any reduction in left ventricular (LV) function, the left ventricle undergoes structural remodelling under the influence of changing haemodynamic conditions.In this study, we combined temporal changes in LV structure (volume) with alterations in LV functional characteristics (strain, ԑ) into a ԑ–volume loop, in order to provide novel insight into the haemodynamic cardiac consequences of aortic valve diseases in those with preserved LV ejection fraction.We showed that our novel ԑ–volume loop and the specific loop characteristics provide additional insight into the functional and mechanical haemodynamic consequences of severe aortic valve diseases (with preserved LV ejection fraction).Finally, we showed that the ԑ–volume loop characteristics provide discriminative capacity compared with conventional measures of LV function. Abstract The purpose of this study was to examine left ventricular (LV) strain (ԑ)–volume loops to provide novel insight into the haemodynamic cardiac consequences of aortic valve stenosis (AS) and aortic valve regurgitation (AR). Twenty‐seven participants were retrospectively recruited: AR (n = 7), AS (n = 10) and control subjects (n = 10). Standard transthoracic echocardiography was used to obtain apical four‐chamber images to construct ԑ–volume relationships, which were assessed using the following parameters: early systolic ԑ (ԑ_ES); slope of ԑ–volume relationship during systole (Sslope); end‐systolic peak ԑ (peak ԑ); and diastolic uncoupling (systolic ԑ–diastolic ԑ at same volume) during early diastole (UNCOUP_ED) and late diastole (UNCOUP_LD). Receiver operating characteristic curves were used to determine the ability to detect impaired LV function. Although LV ejection fraction was comparable between groups, longitudinal peak ԑ was reduced compared with control subjects. In contrast, ԑ_ES and Sslope were lower in both pathologies compared with control subejcts (P < 0.01), but also different between AS and AR (P < 0.05). UNCOUP_ED and UNCOUP_LD were significantly higher in both patient groups compared with control subjects (P < 0.05). Receiver operating characteristic curves revealed that loop characteristics (AUC = 0.99, 1.00 and 1.00; all P < 0.01) were better able then peak ԑ (AUC = 0.75, 0.89 and 0.76; P = 0.06, <0.01 and 0.08, respectively) and LV ejection fraction (AUC = 0.56, 0.69 and 0.69; all P > 0.05) to distinguish AS vs control, AR vs control and AS vs AR groups, respectively. Temporal changes in ԑ–volume characteristics provide novel insight into the haemodynamic cardiac impact of AS and AR. Contrary to traditional measures (i.e. ejection fraction, peak ԑ), these novel measures successfully distinguish between the haemodynamic cardiac impact of AS and AR. PMID:28117492

Exploratory assessment of left ventricular strain-volume loops in severe aortic valve diseases.

PubMed

Hulshof, Hugo G; van Dijk, Arie P; George, Keith P; Hopman, Maria T E; Thijssen, Dick H J; Oxborough, David L

2017-06-15

Severe aortic valve diseases are common cardiac abnormalities that are associated with poor long-term survival. Before any reduction in left ventricular (LV) function, the left ventricle undergoes structural remodelling under the influence of changing haemodynamic conditions. In this study, we combined temporal changes in LV structure (volume) with alterations in LV functional characteristics (strain, ԑ) into a ԑ-volume loop, in order to provide novel insight into the haemodynamic cardiac consequences of aortic valve diseases in those with preserved LV ejection fraction. We showed that our novel ԑ-volume loop and the specific loop characteristics provide additional insight into the functional and mechanical haemodynamic consequences of severe aortic valve diseases (with preserved LV ejection fraction). Finally, we showed that the ԑ-volume loop characteristics provide discriminative capacity compared with conventional measures of LV function. The purpose of this study was to examine left ventricular (LV) strain (ԑ)-volume loops to provide novel insight into the haemodynamic cardiac consequences of aortic valve stenosis (AS) and aortic valve regurgitation (AR). Twenty-seven participants were retrospectively recruited: AR (n = 7), AS (n = 10) and control subjects (n = 10). Standard transthoracic echocardiography was used to obtain apical four-chamber images to construct ԑ-volume relationships, which were assessed using the following parameters: early systolic ԑ (ԑ_ES); slope of ԑ-volume relationship during systole (Sslope); end-systolic peak ԑ (peak ԑ); and diastolic uncoupling (systolic ԑ-diastolic ԑ at same volume) during early diastole (UNCOUP_ED) and late diastole (UNCOUP_LD). Receiver operating characteristic curves were used to determine the ability to detect impaired LV function. Although LV ejection fraction was comparable between groups, longitudinal peak ԑ was reduced compared with control subjects. In contrast, ԑ_ES and Sslope were lower in both pathologies compared with control subejcts (P < 0.01), but also different between AS and AR (P < 0.05). UNCOUP_ED and UNCOUP_LD were significantly higher in both patient groups compared with control subjects (P < 0.05). Receiver operating characteristic curves revealed that loop characteristics (AUC = 0.99, 1.00 and 1.00; all P < 0.01) were better able then peak ԑ (AUC = 0.75, 0.89 and 0.76; P = 0.06, <0.01 and 0.08, respectively) and LV ejection fraction (AUC = 0.56, 0.69 and 0.69; all P > 0.05) to distinguish AS vs control, AR vs control and AS vs AR groups, respectively. Temporal changes in ԑ-volume characteristics provide novel insight into the haemodynamic cardiac impact of AS and AR. Contrary to traditional measures (i.e. ejection fraction, peak ԑ), these novel measures successfully distinguish between the haemodynamic cardiac impact of AS and AR. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Saxagliptin and Tadalafil Differentially Alter Cyclic Guanosine Monophosphate (cGMP) Signaling and Left Ventricular Function in Aortic-Banded Mini-Swine.

PubMed

Hiemstra, Jessica A; Lee, Dong I; Chakir, Khalid; Gutiérrez-Aguilar, Manuel; Marshall, Kurt D; Zgoda, Pamela J; Cruz Rivera, Noelany; Dozier, Daniel G; Ferguson, Brian S; Heublein, Denise M; Burnett, John C; Scherf, Carolin; Ivey, Jan R; Minervini, Gianmaria; McDonald, Kerry S; Baines, Christopher P; Krenz, Maike; Domeier, Timothy L; Emter, Craig A

2016-04-20

Cyclic guanosine monophosphate-protein kinase G-phosphodiesterase 5 signaling may be disturbed in heart failure (HF) with preserved ejection fraction, contributing to cardiac remodeling and dysfunction. The purpose of this study was to manipulate cyclic guanosine monophosphate signaling using the dipeptidyl-peptidase 4 inhibitor saxagliptin and phosphodiesterase 5 inhibitor tadalafil. We hypothesized that preservation of cyclic guanosine monophosphate cGMP signaling would attenuate pathological cardiac remodeling and improve left ventricular (LV) function. We assessed LV hypertrophy and function at the organ and cellular level in aortic-banded pigs. Concentric hypertrophy was equal in all groups, but LV collagen deposition was increased in only HF animals. Prevention of fibrotic remodeling by saxagliptin and tadalafil was correlated with neuropeptide Y plasma levels. Saxagliptin better preserved integrated LV systolic and diastolic function by maintaining normal LV chamber volumes and contractility (end-systolic pressure-volume relationship, preload recruitable SW) while preventing changes to early/late diastolic longitudinal strain rate. Function was similar to the HF group in tadalafil-treated animals including increased LV contractility, reduced chamber volume, and decreased longitudinal, circumferential, and radial mechanics. Saxagliptin and tadalafil prevented a negative cardiomyocyte shortening-frequency relationship observed in HF animals. Saxagliptin increased phosphodiesterase 5 activity while tadalafil increased cyclic guanosine monophosphate levels; however, neither drug increased downstream PKG activity. Early mitochondrial dysfunction, evident as decreased calcium-retention capacity and Complex II-dependent respiratory control, was present in both HF and tadalafil-treated animals. Both saxagliptin and tadalafil prevented increased LV collagen deposition in a manner related to the attenuation of increased plasma neuropeptide Y levels. Saxagliptin appears superior for treating heart failure with preserved ejection fraction, considering its comprehensive effects on integrated LV systolic and diastolic function. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Ex vivo biomechanical characterization of syringe-needle ejections for intracerebral cell delivery.

PubMed

Wahlberg, Brendon; Ghuman, Harmanvir; Liu, Jessie R; Modo, Michel

2018-06-15

Intracerebral implantation of cell suspensions is finding its clinical translation with encouraging results in patients with stroke. However, the survival of cells in the brain remains poor. Although the biological potential of neural stem cells (NSCs) is widely documented, the biomechanical effects of delivering cells through a syringe-needle remain poorly understood. We here detailed the biomechanical forces (pressure, shear stress) that cells are exposed to during ejection through different sized needles (20G, 26G, 32G) and syringes (10, 50, 250 µL) at relevant flow rates (1, 5, 10 µL/min). A comparison of 3 vehicles, Phosphate Buffered Saline (PBS), Hypothermosol (HTS), and Pluronic, indicated that less viscous vehicles are favorable for suspension with a high cell volume fraction to minimize sedimentation. Higher suspension viscosity was associated with greater shear stress. Higher flow rates with viscous vehicle, such as HTS reduced viability by ~10% and also produced more apoptotic cells (28%). At 5 µL/min ejection using a 26G needle increased neuronal differentiation for PBS and HTS suspensions. These results reveal the biological impact of biomechanical forces in the cell delivery process. Appropriate engineering strategies can be considered to mitigate these effects to ensure the efficacious translation of this promising therapy.

Epinephrine and left atrial and left ventricular diastolic function decrease in normal subjects.

PubMed

Fuenmayor, Abdel J; Solórzano, Moisés I; Gómez, Luisangelly

2016-10-01

We assessed the effect of epinephrine over left atrial and left ventricular diastolic function in subjects without structural heart disease. Twenty-seven, 34.6±17.2year-old patients without structural heart disease were included. Intravenous epinephrine (50 to 100ng/kg/min) was infused. Left atrial and ventricular functions were evaluated by means of echocardiography before and during the epinephrine infusion. No complications were observed. Significant increases in heart rate and systolic blood pressure were recorded. Both left atrial (minimal and maximal) volumes increased but increase in the minimal volume was more pronounced, and the ejection fraction diminished. Left atrial expansion index decreased and the fraction of left ventricular inflow volume resulting from atrial contraction increased. Two patients displayed abnormal left ventricular diastolic function. During epinephrine infusion, E/A and e' decreased, and isovolumetric relaxation time increased. In this group of young adults without structural heart disease, epinephrine infusion was safe, did not produce any complications, and induced a small but significant decrease in left atrial function and left ventricular diastolic function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Mass resolution of linear quadrupole ion traps with round rods.

PubMed

Douglas, D J; Konenkov, N V

2014-11-15

Auxiliary dipole excitation is widely used to eject ions from linear radio-frequency quadrupole ion traps for mass analysis. Linear quadrupoles are often constructed with round rod electrodes. The higher multipoles introduced to the electric potential by round rods might be expected to change the ion ejection process. We have therefore investigated the optimum ratio of rod radius, r, to field radius, r0, for excitation and ejection of ions. Trajectory calculations are used to determine the excitation contour, S(q), the fraction of ions ejected when trapped at q values close to the ejection (or excitation) q. Initial conditions are randomly selected from Gaussian distributions of the x and y coordinates and a thermal distribution of velocities. The N = 6 (12 pole) and N = 10 (20 pole) multipoles are added to the quadrupole potential. Peak shapes and resolution were calculated for ratios r/r0 from 1.09 to 1.20 with an excitation time of 1000 cycles of the trapping radio-frequency. Ratios r/r0 in the range 1.140 to 1.160 give the highest resolution and peaks with little tailing. Ratios outside this range give lower resolution and peaks with tails on either the low-mass side or the high-mass side of the peaks. This contrasts with the optimum ratio of 1.126-1.130 for a quadrupole mass filter operated conventionally at the tip of the first stability region. With the optimum geometry the resolution is 2.7 times greater than with an ideal quadrupole field. Adding only a 2.0% hexapole field to a quadrupole field increases the resolution by a factor of 1.6 compared with an ideal quadrupole field. Addition of a 2.0% octopole lowers resolution and degrades peak shape. With the optimum value of r/r0 , the resolution increases with the ejection time (measured in cycles of the trapping rf, n) approximately as R0.5 = 6.64n, in contrast to a pure quadrupole field where R0.5 = 1.94n. Adding weak nonlinear fields to a quadrupole field can improve the resolution with mass-selective ejection of ions by up to a factor of 2.7. The optimum ratio r/r0 is 1.14 to 1.16, which differs from the optimum ratio for a mass filter of 1.128-1.130. Copyright © 2014 John Wiley & Sons, Ltd.

Cardiovascular effects of fenoterol under conditions of hypoxaemia.

PubMed Central

Bremner, P; Burgess, C D; Crane, J; McHaffie, D; Galletly, D; Pearce, N; Woodman, K; Beasley, R

1992-01-01

BACKGROUND: The reason for the association of increased risk of death with fenoterol in patients with asthma in New Zealand is unknown but may relate to its cardiovascular effects. Most deaths from asthma occur outside hospital, where hypoxaemia is likely to be a complicating factor. The cardiovascular effects of fenoterol have been investigated therefore under conditions of normoxaemia and hypoxaemia. METHOD: Eight healthy men were studied on two occasions. Measurements of heart rate, blood pressure, total electromechanical systole (QS2I), electrocardiographic QTc interval, cardiac index, stroke volume, and ejection fraction were made under conditions of normoxaemia and hypoxaemia (arterial oxygen saturation 90%) before and after administration of 800 micrograms of fenoterol by a metered dose inhaler. The order in which treatments were applied was according to a Latin square design. RESULTS: Before inhalation of fenoterol hypoxaemia was associated with a significant increase in heart rate (8 beats/min) and QTc interval (15.6 ms). Under conditions of normoxaemia fenoterol caused a significant increase in heart rate (14.3 beats/min), systolic blood pressure (7.7 mm Hg), stroke volume (27.7 ml), cardiac index (1.6 1/min/m2), ejection fraction (11.48), and QTc interval (32.9 ms) and a fall in QS2I (-23.2 ms) and diastolic blood pressure (-8.4 mm Hg). Under conditions of hypoxaemia the changes after inhalation of fenoterol were similar to those recorded during normoxaemia; thus the effects of hypoxaemia and fenoterol were additive (heart rate 21.9 beats/min, QTc 43.5 ms with fenoterol and hypoxaemia). CONCLUSION: The chronotropic and electrophysiological effects of fenoterol were enhanced by conditions of hypoxaemia. PMID:1481183

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

Optimising the dichotomy limit for left ventricular ejection fraction in selecting patients for defibrillator therapy after myocardial infarction.

PubMed

Yap, Yee Guan; Duong, Trinh; Bland, J Martin; Malik, Marek; Torp-Pedersen, Christian; Køber, Lars; Gallagher, Mark M; Camm, A John

2007-07-01

The selection of patients for prophylactic implantable cardioverter-defibrilator (ICD) treatment after myocardial infarction (MI) remains controversial. To determine the optimum left ventricular ejection fraction (LVEF) dichotomy limit for ICD treatment in patients with a history of MI. Data from the placebo arms of four randomised trials were pooled to create a cohort of 2828 patients (2206 men, mean (SD) age 65 (11) years) with reduced left ventricular function after MI. The median LVEF was 33% (range 6-40%). LVEF significantly predicted mortality. Each 10% reduction in LVEF <40% conferred a 42% increase in all-cause mortality, a 39% increase in arrhythmic cardiac mortality and a 49% increase in non-arrhythmic cardiac mortality over the 2-year period of follow-up (p<0.001 for all modes of mortality). As the LVEF progressively decreased from < or =40% to < or =10%, the data show a U-shaped relationship between the dichotomy limit for LVEF used and the number of patients who must be treated to prevent one arrhythmic death in 2 years. At an LVEF of 16-20%, more patients are likely to die from arrhythmic than non-arrhythmic cardiac deaths, whereas in those with LVEF < or =10% all deaths were non-arrhythmic. However, the total number of deaths substantially decreased with lower LVEF. A trade-off exists between the sensitivity and positive predictive accuracy across a range of LVEF, and no single dichotomy limit is completely satisfactory. In patients with LVEF < or =10% ICD treatment was not beneficial as all patients in this subgroup died from non-arrhythmic causes. The use of a single dichotomy limit for LVEF alone is not sufficient in selecting patients for ICD treatment in the primary prevention of cardiac arrest.

Cardiovascular outcomes after pharmacologic stress myocardial perfusion imaging.

PubMed

Lee, Douglas S; Husain, Mansoor; Wang, Xuesong; Austin, Peter C; Iwanochko, Robert M

2016-04-01

While pharmacologic stress single photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) is used for noninvasive evaluation of patients who are unable to perform treadmill exercise, its impact on net reclassification improvement (NRI) of prognosis is unknown. We evaluated the prognostic value of pharmacologic stress MPI for prediction of cardiovascular death or non-fatal myocardial infarction (MI) within 1 year at a single-center, university-based laboratory. We examined continuous and categorical NRI of pharmacologic SPECT-MPI for prediction of outcomes beyond clinical factors alone. Six thousand two hundred forty patients (median age 66 years [IQR 56-74], 3466 men) were studied and followed for 5963 person-years. SPECT-MPI variables associated with increased risk of cardiovascular death or non-fatal MI included summed stress score, stress ST-shift, and post-stress resting left ventricular ejection fraction ≤50%. Compared to a clinical model which included age, sex, cardiovascular disease, risk factors, and medications, model χ(2) (210.5 vs. 281.9, P < .001) and c-statistic (0.74 vs. 0.78, P < .001) were significantly increased by addition of SPECT-MPI predictors (summed stress score, stress ST-shift and stress resting left ventricular ejection fraction). SPECT-MPI predictors increased continuous NRI by 49.4% (P < .001), reclassifying 66.5% of patients as lower risk and 32.8% as higher risk of cardiovascular death or non-fatal MI. Addition of MPI predictors to clinical factors using risk categories, defined as <1%, 1% to 3%, and >3% annualized risk of cardiovascular death or non-fatal MI, yielded a 15.0% improvement in NRI (95% CI 7.6%-27.6%, P < .001). Pharmacologic stress MPI substantially improved net reclassification of cardiovascular death or MI risk beyond that afforded by clinical factors. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Right Ventricular Volumes and Systolic Function by Cardiac Magnetic Resonance and the Impact of Sex, Age, and Obesity in a Longitudinally Followed Cohort Free of Pulmonary and Cardiovascular Disease: The Framingham Heart Study.

PubMed

Foppa, Murilo; Arora, Garima; Gona, Philimon; Ashrafi, Arman; Salton, Carol J; Yeon, Susan B; Blease, Susan J; Levy, Daniel; O'Donnell, Christopher J; Manning, Warren J; Chuang, Michael L

2016-03-01

Cardiac magnetic resonance is uniquely well suited for noninvasive imaging of the right ventricle. We sought to define normal cardiac magnetic resonance reference values and to identify the main determinants of right ventricular (RV) volumes and systolic function using a modern imaging sequence in a community-dwelling, longitudinally followed cohort free of clinical cardiovascular and pulmonary disease. The Framingham Heart Study Offspring cohort has been followed since 1971. We scanned 1794 Offspring cohort members using steady-state free precession cardiac magnetic resonance and identified a reference group of 1336 adults (64±9 years, 576 men) free of prevalent cardiovascular and pulmonary disease. RV trabeculations and papillary muscles were considered cavity volume. Men had greater RV volumes and cardiac output before and after indexation to body size (all P<0.001). Women had higher RV ejection fraction than men (68±6% versus 64±7%; P<0.0001). RV volumes and cardiac output decreased with advancing age. There was an increase in raw and height-indexed RV measurements with increasing body mass index, but this trend was weakly inverted after indexation of RV volumes to body surface area. Sex, age, height, body mass index, and heart rate account for most of the variability in RV volumes and function in this community-dwelling population. We report sex-specific normative values for RV measurements among principally middle-aged and older adults. RV ejection fraction is greater in women. RV volumes increase with body size, are greater in men, and are smaller in older people. Body surface area seems to be appropriate for indexation of cardiac magnetic resonance-derived RV volumes. © 2016 American Heart Association, Inc.

Biventricular Heart Remodeling After Percutaneous or Surgical Pulmonary Valve Implantation: Evaluation by Cardiac Magnetic Resonance.

PubMed

Secchi, Francesco; Resta, Elda C; Cannaò, Paola M; Pluchinotta, Francesca; Piazza, Luciane; Butera, Gianfranco; Carminati, Mario; Sardanelli, Francesco

2017-11-01

The aim of this study was to evaluate the impact of percutaneous pulmonary valve implantation (PPVI) and surgical pulmonary valve replacement (SPVR) on biventricular and pulmonary valve function using cardiac magnetic resonance. Thirty-five patients aged 20±8 years (mean±SD) underwent PPVI, whereas 16 patients aged 30±11 years underwent SPVR. Cardiac magnetic resonance examinations were performed before and after the procedures with an average follow-up interval of 10 months. Cine steady-state free precession sequences for cardiac function and phase-contrast sequences for pulmonary flow were performed. The right ventricle (RV) and left ventricle (LV) functions were evaluated using a dedicated software. The RV end-diastolic volume index (mL/m) decreased significantly after PPVI and SPVR, from 74 to 64 (P=0.030) and from 137 to 83 (P=0.001), respectively. The RV ejection fraction increased significantly after SPVR, from 47% to 53% (P=0.038). The LV end-diastolic volume index increased significantly after PPVI, from 66 to 76 mL/m (P<0.001). The LV stroke volume index increased significantly after PPVI, from 34 to 43 mL/m (P=0.004). The analysis of bivariate correlations showed that in patients undergoing SPVR the RV changes after the procedure were positively correlated to LV changes in terms of end-systolic volume index (r=0587; P=0.017) and ejection fraction (r=0.681; P=0.004). A RV volumetric reduction and a positive effect on ventricular-ventricular interaction were observed after both PPVI and SPVR. After PPVI, a positive volumetric LV remodeling was found. No LV remodeling was found after SPVR. After both procedures, the replaced pulmonary valve functioned well.

Longitudinal Assessment of Vascular Function With Sunitinib in Patients With Metastatic Renal Cell Carcinoma.

PubMed

Catino, Anna B; Hubbard, Rebecca A; Chirinos, Julio A; Townsend, Ray; Keefe, Stephen; Haas, Naomi B; Puzanov, Igor; Fang, James C; Agarwal, Neeraj; Hyman, David; Smith, Amanda M; Gordon, Mary; Plappert, Theodore; Englefield, Virginia; Narayan, Vivek; Ewer, Steven; ElAmm, Chantal; Lenihan, Daniel; Ky, Bonnie

2018-03-01

Sunitinib, used widely in metastatic renal cell carcinoma, can result in hypertension, left ventricular dysfunction, and heart failure. However, the relationships between vascular function and cardiac dysfunction with sunitinib are poorly understood. In a multicenter prospective study of 84 metastatic renal cell carcinoma patients, echocardiography, arterial tonometry, and BNP (B-type natriuretic peptide) measures were performed at baseline and at 3.5, 15, and 33 weeks after sunitinib initiation, correlating with sunitinib cycles 1, 3, and 6. Mean change in vascular function parameters and 95% confidence intervals were calculated. Linear regression models were used to estimate associations between vascular function and left ventricular ejection fraction, longitudinal strain, diastolic function (E/e'), and BNP. After 3.5 weeks of sunitinib, mean systolic blood pressure increased by 9.5 mm Hg (95% confidence interval, 2.0-17.1; P =0.02) and diastolic blood pressure by 7.2 mm Hg (95% confidence interval, 4.3-10.0; P <0.001) across all participants. Sunitinib resulted in increases in large artery stiffness (carotid-femoral pulse wave velocity) and resistive load (total peripheral resistance and arterial elastance; all P <0.05) and changes in pulsatile load (total arterial compliance and wave reflection). There were no statistically significant associations between vascular function and systolic dysfunction (left ventricular ejection fraction and longitudinal strain). However, baseline total peripheral resistance, arterial elastance, and aortic impedance were associated with worsening diastolic function and filling pressures over time. In patients with metastatic renal cell carcinoma, sunitinib resulted in early, significant increases in blood pressure, arterial stiffness, and resistive and pulsatile load within 3.5 weeks of treatment. Baseline vascular function parameters were associated with worsening diastolic but not systolic function. © 2018 American Heart Association, Inc.

Effects of passive heating on central blood volume and ventricular dimensions in humans

PubMed Central

Crandall, C G; Wilson, T E; Marving, J; Vogelsang, T W; Kjaer, A; Hesse, B; Secher, N H

2008-01-01

Mixed findings regarding the effects of whole-body heat stress on central blood volume have been reported. This study evaluated the hypothesis that heat stress reduces central blood volume and alters blood volume distribution. Ten healthy experimental and seven healthy time control (i.e. non-heat stressed) subjects participated in this protocol. Changes in regional blood volume during heat stress and time control were estimated using technetium-99m labelled autologous red blood cells and gamma camera imaging. Whole-body heating increased internal temperature (≥ 1.0°C), cutaneous vascular conductance (approximately fivefold), and heart rate (52 ± 2 to 93 ± 4 beats min−1), while reducing central venous pressure (5.5 ± 07 to 0.2 ± 0.6 mmHg) accompanied by minor decreases in mean arterial pressure (all P < 0.05). The heat stress reduced the blood volume of the heart (18 ± 2%), heart plus central vasculature (17 ± 2%), thorax (14 ± 2%), inferior vena cava (23 ± 2%) and liver (23 ± 2%) (all P≤ 0.005 relative to time control subjects). Radionuclide multiple-gated acquisition assessment revealed that heat stress did not significantly change left ventricular end-diastolic volume, while ventricular end-systolic volume was reduced by 24 ± 6% of pre-heat stress levels (P < 0.001 relative to time control subjects). Thus, heat stress increased left ventricular ejection fraction from 60 ± 1% to 68 ± 2% (P= 0.02). We conclude that heat stress shifts blood volume from thoracic and splanchnic regions presumably to aid in heat dissipation, while simultaneously increasing heart rate and ejection fraction. PMID:17962331

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.

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

Exercise-induced myocardial ischemia in patients with coronary artery disease: lack of evidence for platelet activation or fibrin formation in peripheral venous blood.

PubMed

Marcella, J J; Nichols, A B; Johnson, L L; Owen, J; Reison, D S; Kaplan, K L; Cannon, P J

1983-05-01

The hypothesis that exercise-induced myocardial ischemia is associated with abnormal platelet activation and fibrin formation or dissolution was tested in patients with coronary artery disease undergoing upright bicycle stress testing. In vivo platelet activation was assessed by radioimmunoassay of platelet factor 4, beta-thrombo-globulin and thromboxane B2. In vivo fibrin formation was assessed by radioimmunoassay of fibrinopeptide A, and fibrinolysis was assessed by radioimmunoassay of thrombin-increasable fibrinopeptide B which reflects plasmin cleavage of fibrin I. Peripheral venous concentrations of these substances were measured in 10 normal subjects and 13 patients with coronary artery disease at rest and during symptom-limited peak exercise. Platelet factor 4, beta-thromboglobulin and thromboxane B2 concentrations were correlated with rest and exercise catecholamine concentrations to determine if exercise-induced elevation of norepinephrine and epinephrine enhances platelet activation. Left ventricular end-diastolic and end-systolic volumes, ejection fraction and segmental wall motion were measured at rest and during peak exercise by first pass radionuclide angiography. All patients with coronary artery disease had documented exercise-induced myocardial ischemia manifested by angina pectoris, ischemic electrocardiographic changes, left ventricular segmental dyssynergy and a reduction in ejection fraction. Rest and peak exercise plasma concentrations were not significantly different for platelet factor 4, beta-thromboglobulin, thromboxane B2, fibrinopeptide A and thrombin-increasable fibrinopeptide B. Peripheral venous concentrations of norepinephrine and epinephrine increased significantly (p less than 0.001) in both groups of patients. The elevated catecholamine levels did not lead to detectable platelet activation. This study demonstrates that enhanced platelet activation, thromboxane release and fibrin formation or dissolution are not detectable in peripheral venous blood of patients with coronary disease during exercise-induced myocardial ischemia.

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.

Ventriculogram segmentation using boosted decision trees

NASA Astrophysics Data System (ADS)

McDonald, John A.; Sheehan, Florence H.

2004-05-01

Left ventricular status, reflected in ejection fraction or end systolic volume, is a powerful prognostic indicator in heart disease. Quantitative analysis of these and other parameters from ventriculograms (cine xrays of the left ventricle) is infrequently performed due to the labor required for manual segmentation. None of the many methods developed for automated segmentation has achieved clinical acceptance. We present a method for semi-automatic segmentation of ventriculograms based on a very accurate two-stage boosted decision-tree pixel classifier. The classifier determines which pixels are inside the ventricle at key ED (end-diastole) and ES (end-systole) frames. The test misclassification rate is about 1%. The classifier is semi-automatic, requiring a user to select 3 points in each frame: the endpoints of the aortic valve and the apex. The first classifier stage is 2 boosted decision-trees, trained using features such as gray-level statistics (e.g. median brightness) and image geometry (e.g. coordinates relative to user supplied 3 points). Second stage classifiers are trained using the same features as the first, plus the output of the first stage. Border pixels are determined from the segmented images using dilation and erosion. A curve is then fit to the border pixels, minimizing a penalty function that trades off fidelity to the border pixels with smoothness. ED and ES volumes, and ejection fraction are estimated from border curves using standard area-length formulas. On independent test data, the differences between automatic and manual volumes (and ejection fractions) are similar in size to the differences between two human observers.

New strategies for heart failure with preserved ejection fraction: the importance of targeted therapies for heart failure phenotypes

PubMed Central

Senni, Michele; Paulus, Walter J.; Gavazzi, Antonello; Fraser, Alan G.; Díez, Javier; Solomon, Scott D.; Smiseth, Otto A.; Guazzi, Marco; Lam, Carolyn S. P.; Maggioni, Aldo P.; Tschöpe, Carsten; Metra, Marco; Hummel, Scott L.; Edelmann, Frank; Ambrosio, Giuseppe; Stewart Coats, Andrew J.; Filippatos, Gerasimos S.; Gheorghiade, Mihai; Anker, Stefan D.; Levy, Daniel; Pfeffer, Marc A.; Stough, Wendy Gattis; Pieske, Burkert M.

2014-01-01

The management of heart failure with reduced ejection fraction (HF-REF) has improved significantly over the last two decades. In contrast, little or no progress has been made in identifying evidence-based, effective treatments for heart failure with preserved ejection fraction (HF-PEF). Despite the high prevalence, mortality, and cost of HF-PEF, large phase III international clinical trials investigating interventions to improve outcomes in HF-PEF have yielded disappointing results. Therefore, treatment of HF-PEF remains largely empiric, and almost no acknowledged standards exist. There is no single explanation for the negative results of past HF-PEF trials. Potential contributors include an incomplete understanding of HF-PEF pathophysiology, the heterogeneity of the patient population, inadequate diagnostic criteria, recruitment of patients without true heart failure or at early stages of the syndrome, poor matching of therapeutic mechanisms and primary pathophysiological processes, suboptimal study designs, or inadequate statistical power. Many novel agents are in various stages of research and development for potential use in patients with HF-PEF. To maximize the likelihood of identifying effective therapeutics for HF-PEF, lessons learned from the past decade of research should be applied to the design, conduct, and interpretation of future trials. This paper represents a synthesis of a workshop held in Bergamo, Italy, and it examines new and emerging therapies in the context of specific, targeted HF-PEF phenotypes where positive clinical benefit may be detected in clinical trials. Specific considerations related to patient and endpoint selection for future clinical trials design are also discussed. PMID:25104786

Takotsubo cardiomyopathy associated with Miller-Fisher syndrome.

PubMed

Gill, Dalvir; Liu, Kan

2017-07-01

51-year-old female who presented with progressive paresthesia, numbness of the lower extremities, double vision, and trouble walking. Physical exam was remarkable for areflexia, and ptosis. Her initial EKG showed nonspecific ST segment changes and her Troponin T was elevated to 0.41ng/mL which peaked at 0.66ng/mL. Echocardiogram showed a depressed left ventricular ejection fraction to 35% with severely hypokinetic anterior wall and left ventricular apex was severely hypokinetic. EMG nerve conduction study showed severely decreased conduction velocity and prolonged distal latency in all nerves consistent with demyelinating disease. She was treated with 5days of intravenous immunoglobulin therapy to which she showed significant improvement in strength in her lower extremities. Echocardiogram repeated 4days later showing an improved left ventricular ejection fraction of 55% and no left ventricular wall motion abnormalities. Takotsubo cardiomyopathy is a rare complication of Miller-Fisher syndrome and literature review did not reveal any cases. Miller-Fisher syndrome is an autoimmune process that affects the peripheral nervous system causing autonomic dysfunction which may involve the heart. Due to significant autonomic dysfunction in Miller-Fisher syndrome, it could lead to arrhythmias, blood pressure changes, acute coronary syndrome and myocarditis, Takotsubo cardiomyopathy can be difficult to distinguish. The treatment of Takotsubo cardiomyopathy is supportive with beta-blockers and angiotensin-converting enzyme inhibitors are recommended until left ventricle ejection fraction improvement. Takotsubo cardiomyopathy is a rare complication during the acute phase of Miller-Fisher syndrome and must be distinguished from autonomic dysfunction as both diagnoses have different approaches to treatment. Published by Elsevier Inc.

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.

Computer-based assessment of right ventricular regional ejection fraction in patients with repaired Tetralogy of Fallot

NASA Astrophysics Data System (ADS)

Teo, S.-K.; Wong, S. T.; Tan, M. L.; Su, Y.; Zhong, L.; Tan, Ru-San

2015-03-01

After surgical repair for Tetralogy of Fallot (TOF), most patients experience long-term complications as the right ventricle (RV) undergoes progressive remodeling that eventually affect heart functions. Thus, post-repair surgery is required to prevent further deterioration of RV functions that may result in malignant ventricular arrhythmias and mortality. The timing of such post-repair surgery therefore depends crucially on the quantitative assessment of the RV functions. Current clinical indices for such functional assessment measure global properties such as RV volumes and ejection fraction. However, these indices are less than ideal as regional variations and anomalies are obscured. Therefore, we sought to (i) develop a quantitative method to assess RV regional function using regional ejection fraction (REF) based on a 13-segment model, and (ii) evaluate the effectiveness of REF in discriminating 6 repaired TOF patients and 6 normal control based on cardiac magnetic resonance (CMR) imaging. We observed that the REF for the individual segments in the patient group is significantly lower compared to the control group (P < 0.05 using a 2-tail student t-test). In addition, we also observed that the aggregated REF at the basal, mid-cavity and apical regions for the patient group is significantly lower compared to the control group (P < 0.001 using a 2-tail student t-test). The results suggest that REF could potentially be used as a quantitative index for assessing RV regional functions. The computational time per data set is approximately 60 seconds, which demonstrates our method's clinical potential as a real-time cardiac assessment tool.

Uso de recursos y costos de hospitalizaciones por insufi ciencia card í aca: un estudio retrospective multic é ntrico en Argentina.

PubMed

Augustovski, Federico; Caporale, Joaquín; Fosco, Matías; Alcaraz, Andrea; Diez, Mirta; Thierer, Jorge; Peradejordi, Margarita; Pichon Riviere, Andrés

2017-12-01

Heart failure has a great impact on health budget, mainly due to the cost of hospitalizations. Our aim was to describe health resource use and costs of heart failure admissions in three important institutions in Argentina. Multi-center retrospective cohort study, with descriptive and analytical analysis by subgroups of ejection fraction, blood pressure and renal function at admission. Generalized linear models were used to assess the association of independent variables to main outcomes. We included 301 subjects; age 75.3±11.8 years; 37% women; 57% with depressed ejection fraction; 46% of coronary etiology. Blood pressure at admission was 129.8±29.7 mmHg; renal function 57.9±26.2 ml/min/1.73 m 2 . Overall mortality was 7%. Average length of stay was 7.82±7.06 days (median 5.69), and was significantly longer in patients with renal impairment (8.9 vs. 8.18; p=0.03) and shorter in those with high initial blood pressure (6.08±4.03; p=0.009). Mean cost per patient was AR$68,861±96,066 (US$=8,071; 1US$=AR$8.532); 71% attributable to hospital stay, 20% to interventional procedures and 6.7% to diagnostic studies. Variables independently associated with higher costs were depressed ejection fraction, presence of valvular disease, and impaired renal function. Resource use and costs associated to hospitalizations for heart failure is high, and the highest proportion is attributable to the costs related to hospital stay. Copyright © 2017. Published by Elsevier Inc.

Warfarin versus aspirin in patients with reduced cardiac ejection fraction (WARCEF): rationale, objectives, and design.

PubMed

Pullicino, Patrick; Thompson, John L P; Barton, Bruce; Levin, Bruce; Graham, Susan; Freudenberger, Ronald S

2006-02-01

Warfarin is widely prescribed for patients with heart failure without level 1 evidence, and an adequately powered randomized study is needed. The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction study is a National Institutes of Health-funded, randomized, double-blind clinical trial with a target enrollment of 2860 patients. It is designed to test with 90% power the 2-sided primary null hypothesis of no difference between warfarin (International Normalized Ratio 2.5-3) and aspirin (325 mg) in 3- to 5-year event-free survival for the composite endpoint of death, or stroke (ischemic or hemorrhagic) among patients with cardiac ejection fraction < or =35% who do not have atrial fibrillation or mechanical prosthetic heart valves. Secondary analyses will compare warfarin and aspirin for reduction of all-cause mortality, ischemic stroke, and myocardial infarction (MI), balanced against the risk of intracerebral hemorrhage, among women and African Americans; and compare warfarin and aspirin for prevention of stroke alone. Randomization is stratified by site, New York Heart Association (NYHA) heart class (I vs II-IV), and stroke or transient ischemic attack (TIA) within 1 year before randomization versus no stroke or TIA in that period. NYHA class I patients will not exceed 20%, and the study has a target of 20% (or more) patients with stroke or TIA within 12 months. Randomized patients receive active warfarin plus placebo or active aspirin plus placebo, double-blind. The results should help guide the selection of optimum antithrombotic therapy for patients with left ventricular dysfunction.

Patient-specific CFD models for intraventricular flow analysis from 3D ultrasound imaging: Comparison of three clinical cases.

PubMed

Bavo, A M; Pouch, A M; Degroote, J; Vierendeels, J; Gorman, J H; Gorman, R C; Segers, P

2017-01-04

As the intracardiac flow field is affected by changes in shape and motility of the heart, intraventricular flow features can provide diagnostic indications. Ventricular flow patterns differ depending on the cardiac condition and the exploration of different clinical cases can provide insights into how flow fields alter in different pathologies. In this study, we applied a patient-specific computational fluid dynamics model of the left ventricle and mitral valve, with prescribed moving boundaries based on transesophageal ultrasound images for three cardiac pathologies, to verify the abnormal flow patterns in impaired hearts. One case (P1) had normal ejection fraction but low stroke volume and cardiac output, P2 showed low stroke volume and reduced ejection fraction, P3 had a dilated ventricle and reduced ejection fraction. The shape of the ventricle and mitral valve, together with the pathology influence the flow field in the left ventricle, leading to distinct flow features. Of particular interest is the pattern of the vortex formation and evolution, influenced by the valvular orifice and the ventricular shape. The base-to-apex pressure difference of maximum 2mmHg is consistent with reported data. We used a CFD model with prescribed boundary motion to describe the intraventricular flow field in three patients with impaired diastolic function. The calculated intraventricular flow dynamics are consistent with the diagnostic patient records and highlight the differences between the different cases. The integration of clinical images and computational techniques, therefore, allows for a deeper investigation intraventricular hemodynamics in patho-physiology. Copyright © 2016 Elsevier Ltd. All rights reserved.

Peak oxygen uptake and left ventricular ejection fraction, but not depressive symptoms, are associated with cognitive impairment in patients with chronic heart failure.

PubMed

Steinberg, Gerrit; Lossnitzer, Nicole; Schellberg, Dieter; Mueller-Tasch, Thomas; Krueger, Carsten; Haass, Markus; Ladwig, Karl Heinz; Herzog, Wolfgang; Juenger, Jana

2011-01-01

The aim of the present study was to assess cognitive impairment in patients with chronic heart failure (CHF) and its associations with depressive symptoms and somatic indicators of illness severity, which is a matter of controversy. Fifty-five patients with CHF (mean age 55.3 ± 7.8 years; 80% male; New York Heart Association functional class I-III) underwent assessment with an expanded neuropsychological test battery (eg, memory, complex attention, mental flexibility, psychomotor speed) to evaluate objective and subjective cognitive impairment. Depressive symptoms were assessed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID) and a self-report inventory (Hospital Anxiety and Depression Scale [HADS]). A comprehensive clinical dataset, including left ventricular ejection fraction, peak oxygen uptake, and a 6-minute walk test, was obtained for all patients. Neuropsychological functioning revealed impairment in 56% of patients in at least one measure of our neuropsychological test battery. However, the Mini Mental State Examination (MMSE) could only detect cognitive impairment in 1.8% of all patients, 24% had HADS scores indicating depressive symptoms, and 11.1% met SCID criteria for a depressive disorder. No significant association was found between depressive symptoms and cognitive impairment. Left ventricular ejection fraction was related to subjective cognitive impairment, and peak oxygen uptake was related to objective cognitive impairment. Cognitive functioning was substantially reduced in patients with CHF and should therefore be diagnosed and treated in routine clinical practice. Caution is advised when the MMSE is used to identify cognitive impairment in patients with CHF.

Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition

PubMed Central

Hubers, Scott A.; Brown, Nancy J.

2016-01-01

Heart failure affects approximately 5.7 million people in the United States alone. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and aldosterone antagonists have improved mortality in patients with heart failure and reduced ejection fraction, but mortality remains high. In July 2015, the FDA approved the first of a new class of drugs for the treatment of heart failure; valsartan/sacubitril (formerly known as LCZ696 and currently marketed by Novartis as Entresto) combines the angiotensin receptor blocker valsartan and the neprilysin inhibitor prodrug sacubitril in a 1:1 ratio in a sodium supramolecular complex. Sacubitril is converted by esterases to LBQ657, which inhibits neprilysin, the enzyme responsible for the degradation of the natriuretic peptides and many other vasoactive peptides. Thus, this combined angiotensin receptor antagonist and neprilysin inhibitor addresses two of the pathophysiologic mechanisms of heart failure - activation of the renin-angiotensin-aldosterone system and decreased sensitivity to natriuretic peptides. In the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial, valsartan/sacubitril significantly reduced mortality and hospitalization for heart failure, as well as blood pressure, compared to enalapril in patients with heart failure, reduced ejection fraction, and an elevated circulating level of brain natriuretic peptide or N-terminal pro-brain natriuretic peptide. Ongoing clinical trials are evaluating the role of valsartan/sacubitril in the treatment of heart failure with preserved ejection fraction and hypertension. We review here the mechanisms of action of valsartan/sacubitril, the pharmacologic properties of the drug, and its efficacy and safety in the treatment of heart failure and hypertension. PMID:26976916

Greater nighttime blood pressure variability is associated with left atrial enlargement in atrial fibrillation patients with preserved ejection fraction.

PubMed

Norioka, Naoki; Iwata, Shinichi; Ito, Asahiro; Tamura, Soichiro; Kawai, Yu; Nonin, Shinichi; Ishikawa, Sera; Doi, Atsushi; Hanatani, Akihisa; Yoshiyama, Minoru

2018-06-13

Left atrial enlargement is an independent risk factor for ischemic stroke in patients with atrial fibrillation. Little is known regarding the association between nighttime blood pressure variability and left atrial enlargement in patients with atrial fibrillation and preserved ejection fraction. The study population consisted of 140 consecutive patients with atrial fibrillation (mean age 64 ± 10 years) with preserved ejection fraction (≥50%). Nighttime blood pressure was measured at hourly intervals, using a home blood pressure monitoring device. Nighttime blood pressure variability was expressed as the standard deviation of all readings. Left atrial volume index was measured using the modified Simpson's biplane method with transthoracic echocardiography. Multiple regression analysis indicated that nighttime mean systolic/diastolic blood pressure and its variability remained independently associated with left atrial enlargement after adjustment for age, sex, anti-hypertensive medication class, and left ventricular mass index (P < 0.01). When patients were divided into four groups according to nighttime blood pressure and its variability, the group with higher nighttime blood pressure and its variability had significantly larger left atrial volume than the group with lower nighttime blood pressure and its variability (46.6 ml/m 2 vs. 35.0 ml/m 2 , P < 0.0001). Higher nighttime blood pressure and its variability are associated with left atrial enlargement. The combination of nighttime blood pressure and its variability has additional predictive value for left atrial enlargement. Intensive intervention for these high-risk patients may avoid or delay progression of left atrial enlargement and reduce the risk of stroke.

Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis

PubMed Central

Zheng, Sean Lee; Chan, Fiona T; Nabeebaccus, Adam A; Shah, Ajay M; McDonagh, Theresa; Okonko, Darlington O; Ayis, Salma

2018-01-01

Background Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality. Methods We systematically searched Medline, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) assessing pharmacological treatments in patients with heart failure with left ventricular (LV) ejection fraction≥40% from January 1996 to May 2016. The primary efficacy outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure hospitalisation, exercise capacity (6-min walk distance, exercise duration, VO2 max), quality of life and biomarkers (B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide). Random-effects models were used to estimate pooled relative risks (RR) for the binary outcomes, and weighted mean differences for continuous outcomes, with 95% CI. Results We included data from 25 RCTs comprising data for 18101 patients. All-cause mortality was reduced with beta-blocker therapy compared with placebo (RR: 0.78, 95%CI 0.65 to 0.94, p=0.008). There was no effect seen with ACE inhibitors, aldosterone receptor blockers, mineralocorticoid receptor antagonists and other drug classes, compared with placebo. Similar results were observed for cardiovascular mortality. No single drug class reduced heart failure hospitalisation compared with placebo. Conclusion The efficacy of treatments in patients with heart failure and an LV ejection fraction≥40% differ depending on the type of therapy, with beta-blockers demonstrating reductions in all-cause and cardiovascular mortality. Further trials are warranted to confirm treatment effects of beta-blockers in this patient group. PMID:28780577

Role of cardiopulmonary exercise testing in clinical stratification in heart failure. A position paper from the Committee on Exercise Physiology and Training of the Heart Failure Association of the European Society of Cardiology.

PubMed

Corrà, Ugo; Agostoni, Pier Giuseppe; Anker, Stefan D; Coats, Andrew J S; Crespo Leiro, Maria G; de Boer, Rudolph A; Hairola, Veli-Pekka; Hill, Loreena; Lainscak, Mitja; Lund, Lars H; Metra, Marco; Ponikowski, Piotr; Riley, Jillian; Seferović, Petar M; Piepoli, Massimo F

2018-01-01

Traditionally, the main indication for cardiopulmonary exercise testing (CPET) in heart failure (HF) was for the selection of candidates to heart transplantation: CPET was mainly performed in middle-aged male patients with HF and reduced left ventricular ejection fraction. Today, CPET is used in broader patients' populations, including women, elderly, patients with co-morbidities, those with preserved ejection fraction, or left ventricular assistance device recipients, i.e. individuals with different responses to incremental exercise and markedly different prognosis. Moreover, the diagnostic and prognostic utility of symptom-limited CPET parameters derived from submaximal tests is more and more considered, since many patients are unable to achieve maximal aerobic power. Repeated tests are also being used for risk stratification and evaluation of intervention, so that these data are now available. Finally, patients, physicians and healthcare decision makers are increasingly considering how treatments might impact morbidity and quality of life rather than focusing more exclusively on hard endpoints (such as mortality) as was often the case in the past. Innovative prognostic flowcharts, with CPET at their core, that help optimize risk stratification and the selection of management options in HF patients, have been developed. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

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.

Long-Term Effects of Spironolactone in Peritoneal Dialysis Patients

PubMed Central

Mizuno, Masashi; Suzuki, Yasuhiro; Tamai, Hirofumi; Hiramatsu, Takeyuki; Ohashi, Hiroshige; Ito, Isao; Kasuga, Hirotake; Horie, Masanobu; Maruyama, Shoichi; Yuzawa, Yukio; Matsubara, Tatsuaki; Matsuo, Seiichi

2014-01-01

ESRD treated with dialysis is associated with increased left ventricular hypertrophy, which, in turn, is related to high mortality. Mineralocorticoid receptor antagonists improve survival in patients with chronic heart failure; however, the effects in patients undergoing dialysis remain uncertain. We conducted a multicenter, open-label, prospective, randomized trial with 158 patients receiving angiotensin-converting enzyme inhibitor or angiotensin type 1 receptor antagonist and undergoing peritoneal dialysis with and without (control group) spironolactone for 2 years. As a primary endpoint, rate of change in left ventricular mass index assessed by echocardiography improved significantly at 6 (P=0.03), 18 (P=0.004), and 24 (P=0.01) months in patients taking spironolactone compared with the control group. Rate of change in left ventricular ejection fraction improved significantly at 24 weeks with spironolactone compared with nontreatment (P=0.02). The benefits of spironolactone were clear in patients with reduced residual renal function. As secondary endpoints, renal Kt/V and dialysate-to-plasma creatinine ratio did not differ significantly between groups during the observation period. No serious adverse effects, such as hyperkalemia, occurred. In this trial, spironolactone prevented cardiac hypertrophy and decreases in left ventricular ejection fraction in patients undergoing peritoneal dialysis, without significant adverse effects. Further studies, including those to determine relative effectiveness in women and men and to evaluate additional secondary endpoints, should confirm these data in a larger cohort. PMID:24335969

Sleep disordered breathing in cardiac surgery patients: The NU-SLEEP trial.

PubMed

Sezai, Akira; Akahoshi, Toshiki; Osaka, Shunji; Yaoita, Hiroko; Arimoto, Munehito; Hata, Hiroaki; Tanaka, Masashi; Sekino, Hisakuni; Akashiba, Tsuneto

2017-01-15

Sleep disordered breathing (SDB) is associated with lifestyle-related diseases and its treatment influence the prognosis of cardiac disease, but little investigation of SDB has been conducted in cardiac surgery patients. A prospective study was performed in 1005 patients undergoing cardiac surgery. The primary endpoint was the severity of SDB determined from the apnea/hypopnea index. The secondary endpoints were patient background factors, cardiovascular risk factors, ejection fraction, atrial and brain natriuretic peptides, oxidative stress and inflammatory markers, and postoperative atrial fibrillation. While 227 patients (22.6%) did not have SDB, there were 361 patients (35.9%) with mild SDB, 260 patients (25.9%) with moderate SDB, and 157 patients (15.6%) with severe SDB. Patients with severe SDB had a lower ejection fraction and higher levels of atrial and brain natriuretic peptides than the other groups. Postoperative atrial fibrillation occurred in 28 patients without SDB (13.6%), 43 patients with mild SDB (13.5%), 74 patients with moderate SDB (31.9%), and 73 patients with severe SDB (52.5%), being significantly more frequent in the severe group than the other groups. SDB was frequent in cardiac surgery patients. Activation of the renin-angiotensin-aldosterone system, postoperative atrial fibrillation atrial, and cardiac dysfunction were associated with severe SDB. Markers of inflammation and oxidative stress also increased as SDB became more severe. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

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

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.

Sex Differences in the Biology and Pathology of the Aging Heart.

PubMed

Keller, Kaitlyn M; Howlett, Susan E

2016-09-01

The knowledge that advanced age is a major risk factor for cardiovascular disease (CVD) has stimulated interest in cardiac aging. Understanding how the heart remodels with age can help us appreciate why older individuals are more likely to acquire heart disease. Growing evidence in both humans and animals shows that the heart exhibits distinct structural and functional changes as a consequence of age. These changes occur even in the absence of overt cardiovascular disease and are often maladaptive. For example, atrial hypertrophy and fibrosis may increase susceptibility to atrial fibrillation in older adults. Age-dependent increases in left ventricular fibrosis, stiffness, and wall thickness promote diastolic dysfunction, predisposing to heart failure with preserved ejection fraction. The influence of age on the heart is evident at rest but is even more prominent during exercise. There is also evidence for sex-specific variation in age-associated remodelling. For instance, there is some evidence that the number of ventricular myocytes declines with age through apoptosis in men but not in women. This helps explain why older men are more likely than women to experience heart failure with reduced ejection fraction. Emerging evidence from preclinical studies suggests that frailty rather than chronological age promotes adverse cardiac remodelling. Mechanisms implicated in cardiac aging include impaired calcium handling, excessive activation of the ß-adrenergic and renin-angiotensin systems, and mitochondrial dysfunction. Further research into cardiac aging in both sexes is needed, because it may be possible to modify disease treatment if the substrate upon which the disease first develops is better understood. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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.

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

Massie, B.; Kramer, B.L.; Topic, N.

Although the resting hemodynamic effects of captopril in congestive heart failure are known, little information is available about the hemodynamic response to captopril during exercise or about changes in noninvasive measurements of the size and function of both ventricles. In this study, 14 stable New York Heart Association class III patients were given 25 mg of oral captopril. Rest and exercise hemodynamic measurements and blood pool scintigrams were performed simultaneously before and 90 minutes after captopril. The radionuclide studies were analyzed for left and right ventricular end-diastolic volumes, end-systolic volumes, ejection fractions and pulmonary blood volume. The primary beneficial responsesmore » at rest were decreases in left and right ventricular end-diastolic volumes from 388 + 81 to 350 + 77 ml (p < 0.01) and from 52 + 26 to 43 + 20 volume units (p < 0.01), respectively, and in their corresponding filling pressures, from 24 + 10 to 17 + 9 mm Hg and 10 + 5 to and + 5 mm Hg (both p < 0.01). Altough stroke volume did not increase significantly, both left and right ventricular ejection fractions increased slightly, from 19 + 6% to 22 + 5% and from 25 + 9% to 29 + 11%, respectively (both p < 0.01). During exercise, similar changes were noted in both hemodynamic and radionuclide indexes. Thus, in patients with moderate symptomatic limitation from chronic heart failure, captopril predominantly reduces ventricular volume and filling pressure, with a less significant effect on cardiac output. These effects persist during exercise, when systemic vascular resistance is already very low. Radionuclide techniques are valuable in assessing the drug effect in these subjects, particularly when ventricular volumes are also measured.« less

Cardiovascular effects of 3,4-methylenedioxymethamphetamine. A double-blind, placebo-controlled trial.

PubMed

Lester, S J; Baggott, M; Welm, S; Schiller, N B; Jones, R T; Foster, E; Mendelson, J

2000-12-19

The psychoactive stimulant 3, 4-methylenedioxymethamphetamine (MDMA), also known as "ecstasy," is widely used in nonmedical settings. Little is known about its cardiovascular effects. To evaluate the acute cardiovascular effects of MDMA by using transthoracic two-dimensional and Doppler echocardiography. Four-session, ascending-dose, double-blind, placebo-controlled trial. Urban hospital. Eight healthy adults who self-reported MDMA use. Echocardiographic effects of dobutamine (5, 20, and 40 microg/kg of body weight per minute) were measured in a preliminary session. Oral MDMA (0.5 and 1.5 mg/kg of body weight) or placebo was administered 1 hour before echocardiographic measurements in three weekly sessions. Heart rate and blood pressure were measured at regular intervals before and after MDMA administration. Echocardiographic measures of stroke volume, ejection fraction, cardiac output, and meridional wall stress were obtained 1 hour after MDMA administration and during dobutamine infusions. At a dose of 1.5 mg/kg, MDMA increased mean heart rate (by 28 beats/min), systolic blood pressure (by 25 mm Hg), diastolic blood pressure (by 7 mm Hg), and cardiac output (by 2 L/min). The effects of MDMA were similar to those of dobutamine, 20 and 40 microg/kg per minute. Inotropism, measured by using meridional wall stress corrected for ejection fraction, decreased after administration of dobutamine, 40 microg/kg per minute, but did not change after either dose of MDMA. Modest oral doses of MDMA increase heart rate, blood pressure, and myocardial oxygen consumption in a magnitude similar to dobutamine, 20 to 40 microg/kg per minute. In contrast to dobutamine, MDMA has no measurable inotropic effects.

Effect of L-Carnitine Supplementation on Reverse Remodeling in Patients with Ischemic Heart Disease Undergoing Coronary Artery Bypass Grafting: A Randomized, Placebo-Controlled Trial.

PubMed

da Silva Guimarães, Sheila; de Souza Cruz, Wanise; da Silva, Licinio; Maciel, Gabrielle; Huguenin, Ana Beatriz; de Carvalho, Monicque; Costa, Bárbara; da Silva, Geisiane; da Costa, Carlos; D'Ippolito, João Alvaro; Colafranceschi, Alexandre; Scalco, Fernanda; Boaventura, Gilson

2017-01-01

During cardiac failure, cardiomyocytes have difficulty in using the substrates to produce energy. L-carnitine is a necessary nutrient for the transport of fatty acids that are required for generating energy. Coronary artery graft surgery reduces the plasma levels of L-carnitine and increases the oxidative stress. This study demonstrates the effect of L-carnitine supplementation on the reverse remodeling of patients undergoing coronary artery bypass graft. Patients with ischemic heart failure who underwent coronary graft surgery were randomized to group A - supplemented with L-carnitine or group B controls. Left ventricular ejection fraction, left ventricular systolic and diastolic diameters were assessed preoperatively, 60 and 180 days after surgery. Our study included 28 patients (26 [93.0%] males) with a mean age ± SD of 58.1 ± 10.5 years. The parameters for the evaluation of reverse remodeling did not improve after 60 and 180 days of coronary artery bypass grafting in comparison between groups (p > 0.05). Evaluation within the L-carnitine group showed a 37.1% increase in left ventricle ejection fraction (p = 0.002) and 14.3% (p = 0.006) and 3.3% (p > 0.05) reduction in systolic and diastolic diameters, respectively. L-carnitine supplementation at a dose of 50 mg/kg combined with artery bypass surgery did not demonstrate any additional benefit in reverse remodeling. However, evaluation within the L-carnitine group may indicate a clinical benefit of L-carnitine supplementation. © 2017 S. Karger AG, Basel.

Risk Related to Pre-Diabetes Mellitus and Diabetes Mellitus in Heart Failure With Reduced Ejection Fraction: Insights From Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial.

PubMed

Kristensen, Søren L; Preiss, David; Jhund, Pardeep S; Squire, Iain; Cardoso, José Silva; Merkely, Bela; Martinez, Felipe; Starling, Randall C; Desai, Akshay S; Lefkowitz, Martin P; Rizkala, Adel R; Rouleau, Jean L; Shi, Victor C; Solomon, Scott D; Swedberg, Karl; Zile, Michael R; McMurray, John J V; Packer, Milton

2016-01-01

The prevalence of pre-diabetes mellitus and its consequences in patients with heart failure and reduced ejection fraction are not known. We investigated these in the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. We examined clinical outcomes in 8399 patients with heart failure and reduced ejection fraction according to history of diabetes mellitus and glycemic status (baseline hemoglobin A1c [HbA1c]: < 6.0% [< 42 mmol/mol], 6.0%-6.4% [42-47 mmol/mol; pre-diabetes mellitus], and ≥ 6.5% [≥ 48 mmol/mol; diabetes mellitus]), in Cox regression models adjusted for known predictors of poor outcome. Patients with a history of diabetes mellitus (n = 2907 [35%]) had a higher risk of the primary composite outcome of heart failure hospitalization or cardiovascular mortality compared with those without a history of diabetes mellitus: adjusted hazard ratio, 1.38; 95% confidence interval, 1.25 to 1.52; P < 0.001. HbA1c measurement showed that an additional 1106 (13% of total) patients had undiagnosed diabetes mellitus and 2103 (25%) had pre-diabetes mellitus. The hazard ratio for patients with undiagnosed diabetes mellitus (HbA1c, > 6.5%) and known diabetes mellitus compared with those with HbA1c < 6.0% was 1.39 (1.17-1.64); P < 0.001 and 1.64 (1.43-1.87); P < 0.001, respectively. Patients with pre-diabetes mellitus were also at higher risk (hazard ratio, 1.27 [1.10-1.47]; P < 0.001) compared with those with HbA1c < 6.0%. The benefit of LCZ696 (sacubitril/valsartan) compared with enalapril was consistent across the range of HbA1c in the trial. In patients with heart failure and reduced ejection fraction, dysglycemia is common and pre-diabetes mellitus is associated with a higher risk of adverse cardiovascular outcomes (compared with patients with no diabetes mellitus and HbA1c < 6.0%). LCZ696 was beneficial compared with enalapril, irrespective of glycemic status. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255. © 2016 The Authors.

Is the 6-minute walk test a reliable substitute for peak oxygen uptake in patients with dilated cardiomyopathy?

PubMed

Zugck, C; Krüger, C; Dürr, S; Gerber, S H; Haunstetter, A; Hornig, K; Kübler, W; Haass, M

2000-04-01

The 6-min walk test may serve as a more simple clinical tool to assess functional capacity in congestive heart failure than determination of peak oxygen uptake by cardiopulmonary exercise testing. The purpose of the study was to prospectively examine whether the distance ambulated during a 6-min walk test (i) correlates with peak oxygen uptake, (ii) allows peak oxygen uptake to be predicted, and (iii) provides prognostic information similar to peak oxygen uptake in patients with dilated cardiomyopathy and left ventricular ejection fraction < or = 35%. In 113 patients (age: 54+/-12 years, NYHA: 2.2+/-0.8) with dilated cardiomyopathy (left ventricular ejection fraction 19+/-7%) a 6-min walk test and cardiopulmonary exercise testing were performed. The 6-min walk test and peak oxygen uptake were closely correlated at the initial visit (r=0.68, n=113), as well as after 263+/-114 (r=0.71, n=28) and 381+/-170 days (r=0.74, n=14). During serial exercise testing the 6-min walk test allowed peak oxygen uptake to be reliably predicted (r=0.76 between calculated and real peak oxygen uptake). After 528+/-234 days, 42 patients were hospitalized due to worsening heart failure and/or died from cardiovascular causes. Compared to clinically stable patients, these 42 patients walked a shorter distance (423+/-104 vs 501+/-95 m, P<0.001) and had a lower peak oxygen uptake (12.7+/-4.0 vs 17.4 + 5.6 ml x min(-1) x kg(-1), P<0.001). By univariate analysis the 6-min walk test outperformed other prognostic parameters such as left ventricular ejection fraction, cardiac index and plasma norepinephrine concentration and conferred a prognostic power similar to peak oxygen uptake. This predictive value could be further improved in a multivariate model, by combining the 6-min walk test with independent variables, such as left ventricular ejection fraction or cardiac index. The 6-min walk test correlated with peak oxygen uptake when tested serially over the course of the disease. Although both tests define two distinct domains of functional capacity, the 6-min walk test provides prognostic information very similar to peak oxygen uptake in congestive heart failure patients with dilated cardiomyopathy.

Risk Related to Pre–Diabetes Mellitus and Diabetes Mellitus in Heart Failure With Reduced Ejection Fraction

PubMed Central

Kristensen, Søren L.; Preiss, David; Jhund, Pardeep S.; Squire, Iain; Cardoso, José Silva; Merkely, Bela; Martinez, Felipe; Starling, Randall C.; Desai, Akshay S.; Lefkowitz, Martin P.; Rizkala, Adel R.; Rouleau, Jean L.; Shi, Victor C.; Solomon, Scott D.; Swedberg, Karl; Zile, Michael R.; Packer, Milton

2016-01-01

Background— The prevalence of pre–diabetes mellitus and its consequences in patients with heart failure and reduced ejection fraction are not known. We investigated these in the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. Methods and Results— We examined clinical outcomes in 8399 patients with heart failure and reduced ejection fraction according to history of diabetes mellitus and glycemic status (baseline hemoglobin A1c [HbA1c]: <6.0% [<42 mmol/mol], 6.0%–6.4% [42–47 mmol/mol; pre–diabetes mellitus], and ≥6.5% [≥48 mmol/mol; diabetes mellitus]), in Cox regression models adjusted for known predictors of poor outcome. Patients with a history of diabetes mellitus (n=2907 [35%]) had a higher risk of the primary composite outcome of heart failure hospitalization or cardiovascular mortality compared with those without a history of diabetes mellitus: adjusted hazard ratio, 1.38; 95% confidence interval, 1.25 to 1.52; P<0.001. HbA1c measurement showed that an additional 1106 (13% of total) patients had undiagnosed diabetes mellitus and 2103 (25%) had pre–diabetes mellitus. The hazard ratio for patients with undiagnosed diabetes mellitus (HbA1c, >6.5%) and known diabetes mellitus compared with those with HbA1c<6.0% was 1.39 (1.17–1.64); P<0.001 and 1.64 (1.43–1.87); P<0.001, respectively. Patients with pre–diabetes mellitus were also at higher risk (hazard ratio, 1.27 [1.10–1.47]; P<0.001) compared with those with HbA1c<6.0%. The benefit of LCZ696 (sacubitril/valsartan) compared with enalapril was consistent across the range of HbA1c in the trial. Conclusions— In patients with heart failure and reduced ejection fraction, dysglycemia is common and pre–diabetes mellitus is associated with a higher risk of adverse cardiovascular outcomes (compared with patients with no diabetes mellitus and HbA1c <6.0%). LCZ696 was beneficial compared with enalapril, irrespective of glycemic status. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255. PMID:26754626

A New Parameter for Cardiac Efficiency Analysis

NASA Astrophysics Data System (ADS)

Borazjani, Iman; Rajan, Navaneetha Krishnan; Song, Zeying; Hoffmann, Kenneth; MacMahon, Eileen; Belohlavek, Marek

2014-11-01

Detecting and evaluating a heart with suboptimal pumping efficiency is a significant clinical goal. However, the routine parameters such as ejection fraction, quantified with current non-invasive techniques are not predictive of heart disease prognosis. Furthermore, they only represent left-ventricular (LV) ejection function and not the efficiency, which might be affected before apparent changes in the function. We propose a new parameter, called the hemodynamic efficiency (H-efficiency) and defined as the ratio of the useful to total power, for cardiac efficiency analysis. Our results indicate that the change in the shape/motion of the LV will change the pumping efficiency of the LV even if the ejection fraction is kept constant at 55% (normal value), i.e., H-efficiency can be used for suboptimal cardiac performance diagnosis. To apply H-efficiency on a patient-specific basis, we are developing a system that combines echocardiography (echo) and computational fluid dynamics (CFD) to provide the 3D pressure and velocity field to directly calculate the H-efficiency parameter. Because the method is based on clinically used 2D echo, which has faster acquisition time and lower cost relative to other imaging techniques, it can have a significant impact on a large number of patients. This work is partly supported by the American Heart Association.

THE PROPERTIES OF DYNAMICALLY EJECTED RUNAWAY AND HYPER-RUNAWAY STARS

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

Perets, Hagai B.; Subr, Ladislav

2012-06-01

Runaway stars are stars observed to have large peculiar velocities. Two mechanisms are thought to contribute to the ejection of runaway stars, both of which involve binarity (or higher multiplicity). In the binary supernova scenario, a runaway star receives its velocity when its binary massive companion explodes as a supernova (SN). In the alternative dynamical ejection scenario, runaway stars are formed through gravitational interactions between stars and binaries in dense, compact clusters or cluster cores. Here we study the ejection scenario. We make use of extensive N-body simulations of massive clusters, as well as analytic arguments, in order to characterizemore » the expected ejection velocity distribution of runaway stars. We find that the ejection velocity distribution of the fastest runaways (v {approx}> 80 km s{sup -1}) depends on the binary distribution in the cluster, consistent with our analytic toy model, whereas the distribution of lower velocity runaways appears independent of the binaries' properties. For a realistic log constant distribution of binary separations, we find the velocity distribution to follow a simple power law: {Gamma}(v){proportional_to}v{sup -8/3} for the high-velocity runaways and v{sup -3/2} for the low-velocity ones. We calculate the total expected ejection rates of runaway stars from our simulated massive clusters and explore their mass function and their binarity. The mass function of runaway stars is biased toward high masses and strongly depends on their velocity. The binarity of runaways is a decreasing function of their ejection velocity, with no binaries expected to be ejected with v > 150 km s{sup -1}. We also find that hyper-runaways with velocities of hundreds of km s{sup -1} can be dynamically ejected from stellar clusters, but only at very low rates, which cannot account for a significant fraction of the observed population of hyper-velocity stars in the Galactic halo.« less

LA-ICP-MS depth profile analysis of apatite: Protocol and implications for (U-Th)/He thermochronometry

NASA Astrophysics Data System (ADS)

Johnstone, Samuel; Hourigan, Jeremy; Gallagher, Christopher

2013-05-01

Heterogeneous concentrations of α-producing nuclides in apatite have been recognized through a variety of methods. The presence of zonation in apatite complicates both traditional α-ejection corrections and diffusive models, both of which operate under the assumption of homogeneous concentrations. In this work we develop a method for measuring radial concentration profiles of 238U and 232Th in apatite by laser ablation ICP-MS depth profiling. We then focus on one application of this method, removing bias introduced by applying inappropriate α-ejection corrections. Formal treatment of laser ablation ICP-MS depth profile calibration for apatite includes construction and calibration of matrix-matched standards and quantification of rates of elemental fractionation. From this we conclude that matrix-matched standards provide more robust monitors of fractionation rate and concentrations than doped silicate glass standards. We apply laser ablation ICP-MS depth profiling to apatites from three unknown populations and small, intact crystals of Durango fluorapatite. Accurate and reproducible Durango apatite dates suggest that prolonged exposure to laser drilling does not impact cooling ages. Intracrystalline concentrations vary by at least a factor of 2 in the majority of the samples analyzed, but concentration variation only exceeds 5x in 5 grains and 10x in 1 out of the 63 grains analyzed. Modeling of synthetic concentration profiles suggests that for concentration variations of 2x and 10x individual homogeneous versus zonation dependent α-ejection corrections could lead to age bias of >5% and >20%, respectively. However, models based on measured concentration profiles only generated biases exceeding 5% in 13 of the 63 cases modeled. Application of zonation dependent α-ejection corrections did not significantly reduce the age dispersion present in any of the populations studied. This suggests that factors beyond homogeneous α-ejection corrections are the dominant source of overdispersion in apatite (U-Th)/He cooling ages.

Interplanetary Coronal Mass Ejections During 1996 - 2007

NASA Technical Reports Server (NTRS)

Richardson, I. G.; Cane, H. V.

2007-01-01

Interplanetary coronal mass ejections, the interplanetary counterparts of coronal mass ejections at the Sun, are the major drivers of interplanetary shocks in the heliosphere, and are associated with modulations of the galactic cosmic ray intensity, both short term (Forbush decreases caused by the passage of the shock, post-shock sheath, and ICME), and possibly with longer term modulation. Using several in-situ signatures of ICMEs, including plasma temperature, and composition, magnetic fields, and cosmic ray modulations, made by near-Earth spacecraft, we have compiled a "comprehensive" list of ICMEs passing the Earth since 1996, encompassing solar cycle 23. We summarize the properties of these ICMEs, such as their occurrence rate, speeds and other parameters, the fraction of ICMEs that are classic magnetic clouds, and their association with solar energetic particle events, halo CMEs, interplanetary shocks, geomagnetic storms, shocks and cosmic ray decreases.

Ventricular fibrillation induced by coagulating mode bipolar electrocautery during pacemaker implantation in Myotonic Dystrophy type 1 patient.

PubMed

Russo, Vincenzo; Rago, Anna; DI Meo, Federica; Cioppa, Nadia Della; Papa, Andrea Antonio; Russo, Maria Giovanna; Nigro, Gerardo

2014-12-01

The occurrence of ventricular fibrillation, induced by bipolar electrocautery during elective dual chamber pacemaker implantation, is reported in a patient affected by Myotonic Distrophy type 1 with normal left ventricular ejection fraction.

Implantation of the Medtronic Harmony Transcatheter Pulmonary Valve Improves Right Ventricular Size and Function in an Ovine Model of Postoperative Chronic Pulmonary Insufficiency.

PubMed

Schoonbeek, Rosanne C; Takebayashi, Satoshi; Aoki, Chikashi; Shimaoka, Toru; Harris, Matthew A; Fu, Gregory L; Kim, Timothy S; Dori, Yoav; McGarvey, Jeremy; Litt, Harold; Bouma, Wobbe; Zsido, Gerald; Glatz, Andrew C; Rome, Jonathan J; Gorman, Robert C; Gorman, Joseph H; Gillespie, Matthew J

2016-10-01

Pulmonary insufficiency is the nexus of late morbidity and mortality after transannular patch repair of tetralogy of Fallot. This study aimed to establish the feasibility of implantation of the novel Medtronic Harmony transcatheter pulmonary valve (hTPV) and to assess its effect on pulmonary insufficiency and ventricular function in an ovine model of chronic postoperative pulmonary insufficiency. Thirteen sheep underwent baseline cardiac magnetic resonance imaging, surgical pulmonary valvectomy, and transannular patch repair. One month after transannular patch repair, the hTPV was implanted, followed by serial magnetic resonance imaging and computed tomography imaging at 1, 5, and 8 month(s). hTPV implantation was successful in 11 animals (85%). There were 2 procedural deaths related to ventricular fibrillation. Seven animals survived the entire follow-up protocol, 5 with functioning hTPV devices. Two animals had occlusion of hTPV with aneurysm of main pulmonary artery. A strong decline in pulmonary regurgitant fraction was observed after hTPV implantation (40.5% versus 8.3%; P=0.011). Right ventricular end diastolic volume increased by 49.4% after transannular patch repair (62.3-93.1 mL/m 2 ; P=0.028) but was reversed to baseline values after hTPV implantation (to 65.1 mL/m 2 at 8 months, P=0.045). Both right ventricular ejection fraction and left ventricular ejection fraction were preserved after hTPV implantation. hTPV implantation is feasible, significantly reduces pulmonary regurgitant fraction, facilitates right ventricular volume improvements, and preserves biventricular function in an ovine model of chronic pulmonary insufficiency. This percutaneous strategy could potentially offer an alternative for standard surgical pulmonary valve replacement in dilated right ventricular outflow tracts, permitting lower risk, nonsurgical pulmonary valve replacement in previously prohibitive anatomies. © 2016 American Heart Association, Inc.

Space-time evolution of ejected plasma for the triggering of gas switch

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

Liu, Shanhong, E-mail: liushanhong108098@163.com; Liu, Xuandong; Shen, Xi

2016-06-15

Ejected plasma has been widely applied to the discharge process of gas spark switches as a trigger technology, and the development process of ejected plasma has a direct and important effect on the discharge characteristics of gas switches. In this paper, both the injection characteristics and space-time evolution of ejected plasma for the triggering of gas spark switch with different stored energies, pulse polarities, and pressures are studied. The discharge characteristics and breakdown process of a gas switch ignited by ejected plasma under different working coefficients are also discussed briefly. The results show that stored energy has significant influence onmore » the characteristics of ejected plasma. With the increase of stored energy, the propulsion mode of ejected plasma in the axial direction transforms from “plasmoid” to “plasma flow,” and the distribution of the ejected plasma goes through “cloud,” “core-cloud,” and “branch” in sequence. The velocity of ejected plasma under negative pulse polarity is obviously higher than that under positive pulse polarity, especially at the very beginning time. The radial dimensions of ejected plasma under two kinds of pulse polarities follow the similar varying pattern over time, which increase first and then decrease, assuming an inverted “U”-shaped curve. With the increase of pressure, the velocity of ejected plasma significantly decreases and the “branch” channels droop earlier. Applying the ejected plasma to the triggering of a gas switch, the switch can be triggered reliably in a much wide working coefficient range of 10%–90%. With the increase of working coefficient, the breakdown process of the switch translates from slow working mode to fast working mode, and the delay time reduces from tens of μs to hundreds of ns.« less

Longitudinal and transverse right ventricular function in pulmonary hypertension: cardiovascular magnetic resonance imaging study from the ASPIRE registry

PubMed Central

Rajaram, Smitha; Capener, Dave; Elliot, Charlie; Condliffe, Robin; Wild, Jim M.; Kiely, David G.

2015-01-01

Abstract Right ventricular (RV) function is a strong predictor of outcome in cardiovascular diseases. Two components of RV function, longitudinal and transverse motion, have been investigated in pulmonary hypertension (PH). However, their individual clinical significance remains uncertain. The aim of this study was to determine the factors associated with transverse and longitudinal RV motion in patients with PH. In 149 treatment-naive patients with PH and 16 patients with suspected PH found to have mean pulmonary arterial pressure of <20 mmHg, cardiovascular magnetic resonance imaging was performed within 24 hours of right heart catheterization. In patients with PH, fractional longitudinal motion (fractional tricuspid annulus to apex distance [f-TAAD]) was significantly greater than fractional transverse motion (fractional septum to free wall distance [f-SFD]; P = 0.002). In patients without PH, no significant difference between f-SFD and f-TAAD was identified (P = 0.442). Longitudinal RV motion was singularly associated with RV ejection fraction independent of age, invasive hemodynamics, and cardiac magnetic resonance measurements (P = 0.024). In contrast, transverse RV motion was independently associated with left ventricular eccentricity (P = 0.036) in addition to RV ejection fraction (P = 0.014). In conclusion, RV motion is significantly greater in the longitudinal direction in patients with PH, whereas patients without PH have equal contributions of transverse and longitudinal motion. Longitudinal RV motion is primarily associated with global RV pump function in PH. Transverse RV motion not only reflects global pump function but is independently influenced by ventricular interaction in patients with PH. PMID:26401257

Longitudinal and transverse right ventricular function in pulmonary hypertension: cardiovascular magnetic resonance imaging study from the ASPIRE registry.

PubMed

Swift, Andrew J; Rajaram, Smitha; Capener, Dave; Elliot, Charlie; Condliffe, Robin; Wild, Jim M; Kiely, David G

2015-09-01

Right ventricular (RV) function is a strong predictor of outcome in cardiovascular diseases. Two components of RV function, longitudinal and transverse motion, have been investigated in pulmonary hypertension (PH). However, their individual clinical significance remains uncertain. The aim of this study was to determine the factors associated with transverse and longitudinal RV motion in patients with PH. In 149 treatment-naive patients with PH and 16 patients with suspected PH found to have mean pulmonary arterial pressure of <20 mmHg, cardiovascular magnetic resonance imaging was performed within 24 hours of right heart catheterization. In patients with PH, fractional longitudinal motion (fractional tricuspid annulus to apex distance [f-TAAD]) was significantly greater than fractional transverse motion (fractional septum to free wall distance [f-SFD]; P = 0.002). In patients without PH, no significant difference between f-SFD and f-TAAD was identified (P = 0.442). Longitudinal RV motion was singularly associated with RV ejection fraction independent of age, invasive hemodynamics, and cardiac magnetic resonance measurements (P = 0.024). In contrast, transverse RV motion was independently associated with left ventricular eccentricity (P = 0.036) in addition to RV ejection fraction (P = 0.014). In conclusion, RV motion is significantly greater in the longitudinal direction in patients with PH, whereas patients without PH have equal contributions of transverse and longitudinal motion. Longitudinal RV motion is primarily associated with global RV pump function in PH. Transverse RV motion not only reflects global pump function but is independently influenced by ventricular interaction in patients with PH.

Cardiac function adaptations in hibernating grizzly bears (Ursus arctos horribilis).

PubMed

Nelson, O Lynne; Robbins, Charles T

2010-03-01

Research on the cardiovascular physiology of hibernating mammals may provide insight into evolutionary adaptations; however, anesthesia used to handle wild animals may affect the cardiovascular parameters of interest. To overcome these potential biases, we investigated the functional cardiac phenotype of the hibernating grizzly bear (Ursus arctos horribilis) during the active, transitional and hibernating phases over a 4 year period in conscious rather than anesthetized bears. The bears were captive born and serially studied from the age of 5 months to 4 years. Heart rate was significantly different from active (82.6 +/- 7.7 beats/min) to hibernating states (17.8 +/- 2.8 beats/min). There was no difference from the active to the hibernating state in diastolic and stroke volume parameters or in left atrial area. Left ventricular volume:mass was significantly increased during hibernation indicating decreased ventricular mass. Ejection fraction of the left ventricle was not different between active and hibernating states. In contrast, total left atrial emptying fraction was significantly reduced during hibernation (17.8 +/- 2.8%) as compared to the active state (40.8 +/- 1.9%). Reduced atrial chamber function was also supported by reduced atrial contraction blood flow velocities and atrial contraction ejection fraction during hibernation; 7.1 +/- 2.8% as compared to 20.7 +/- 3% during the active state. Changes in the diastolic cardiac filling cycle, especially atrial chamber contribution to ventricular filling, appear to be the most prominent macroscopic functional change during hibernation. Thus, we propose that these changes in atrial chamber function constitute a major adaptation during hibernation which allows the myocardium to conserve energy, avoid chamber dilation and remain healthy during a period of extremely low heart rates. These findings will aid in rational approaches to identifying underlying molecular mechanisms.

Lung Deflation and Cardiovascular Structure and Function in Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial.

PubMed

Stone, Ian S; Barnes, Neil C; James, Wai-Yee; Midwinter, Dawn; Boubertakh, Redha; Follows, Richard; John, Leonette; Petersen, Steffen E

2016-04-01

Patients with chronic obstructive pulmonary disease develop increased cardiovascular morbidity with structural alterations. To investigate through a double-blind, placebo-controlled, crossover study the effect of lung deflation on cardiovascular structure and function using cardiac magnetic resonance. Forty-five hyperinflated patients with chronic obstructive pulmonary disease were randomized (1:1) to 7 (maximum 14) days inhaled corticosteroid/long-acting β2-agonist fluticasone furoate/vilanterol 100/25 μg or placebo (7-day minimum washout). Primary outcome was change from baseline in right ventricular end-diastolic volume index versus placebo. There was a 5.8 ml/m(2) (95% confidence interval, 2.74-8.91; P < 0.001) increase in change from baseline right ventricular end-diastolic volume index and a 429 ml (P < 0.001) reduction in residual volume with fluticasone furoate/vilanterol versus placebo. Left ventricular end-diastolic and left atrial end-systolic volumes increased by 3.63 ml/m(2) (P = 0.002) and 2.33 ml/m(2) (P = 0.002). In post hoc analysis, right ventricular stroke volume increased by 4.87 ml/m(2) (P = 0.003); right ventricular ejection fraction was unchanged. Left ventricular adaptation was similar; left atrial ejection fraction improved by +3.17% (P < 0.001). Intrinsic myocardial function was unchanged. Pulmonary artery pulsatility increased in two of three locations (main +2.9%, P = 0.001; left +2.67%, P = 0.030). Fluticasone furoate/vilanterol safety profile was similar to placebo. Pharmacologic treatment of chronic obstructive pulmonary disease has consistent beneficial and plausible effects on cardiac function and pulmonary vasculature that may contribute to favorable effects of inhaled therapies. Future studies should investigate the effect of prolonged lung deflation on intrinsic myocardial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01691885).

Comparison of stroke work between repaired tetralogy of Fallot and normal right ventricular physiologies.

PubMed

Lee, Namheon; Das, Ashish; Banerjee, Rupak K; Gottliebson, William M

2013-01-01

Adult patients who underwent tetralogy of Fallot repair surgery (rTOF) confront life-threatening ailments due to right ventricular (RV) myocardial dysfunction. Pulmonary valve replacement (PVR) needs to be performed to restore the deteriorating RV function. Determination of correct timing to perform PVR in an rTOF patient remains subjective, due to the unavailability of quantifiable clinical diagnostic parameters. The objective of this study is to evaluate the possibility of using RV body surface area (BSA)-indexed stroke work (SW(I)) to quantify RV inefficiency in TOF patients. We hypothesized that RV SW(I) required to push blood to the lungs in rTOF patients is significantly higher than that of normal subjects. Seven patients with rTOF pathophysiology and eight controls with normal RV physiology were registered for this study. Right ventricular volume and pressure were measured using cardiac magnetic resonance imaging and catheterization, respectively. Statistical analysis was performed to quantify the difference in SW(I) between the RV of the rTOF and control groups. Right ventricular SW(I) in rTOF patients (0.176 ± 0.055 J/m(2)) was significantly higher by 93.4% (P = 0.0026) than that of controls (0.091 ± 0.030 J/m(2)). Further, rTOF patients were found to have significantly higher (P < 0.05) BSA normalized RV end-systolic volume, end-systolic pressure, and regurgitation fraction than control subjects. Ejection fraction and peak ejection rate of rTOF patients were significantly lower (P < 0.05) than those of controls. Patients with rTOF pathophysiology had significantly higher RV SW(I) compared with subjects with normal RV physiology. Therefore, RV SW(I) may be useful to quantify RV inefficiency in rTOF patients along with currently used clinical end points such as RV volume, pressure, regurgitation fraction, and ejection fraction.

Comparison of Characteristics and Outcomes of Asymptomatic Versus Symptomatic Left Ventricular Dysfunction in Subjects 65 Years Old or Older (from the Cardiovascular Health Study)

PubMed Central

Pandhi, Jay; Gottdiener, John S.; Bartz, Traci M.; Kop, Willem J.; Mehra, Mandeep R.

2014-01-01

Although asymptomatic left ventricular (LV) systolic dysfunction (ALVSD) is common, its phenotype and prognosis for incident heart failure (HF) and mortality are insufficiently understood. Echocardiography was done in 5,649 participants in the Cardiovascular Health Study (age 73.0 ± 5.6 years, 57.6% women). The clinical characteristics and cardiovascular risk factors of the participants with ALVSD were compared to those with normal LV function (ejection fraction ≥55%) and with symptomatic LV systolic dysfunction (SLVSD; ejection fraction <55% and a history of HF). Cox proportional hazards models were used to estimate the risk of incident HF and mortality in those with ALVSD. Also, comparisons were made among the LV ejection fraction subgroups using previously validated cutoff values (<45% and 45% to 55%), adjusting for the demographic and cardiovascular disease risk factors. Those with ALVSD (7.3%) were more likely to have cardiovascular risk factors than those in the reference group (without LV dysfunction or symptomatic HF) but less likely than those with SLVSD. The HF rate was 24 occurrences per 1,000 person-years in the reference group and 57 occurrences per 1,000 person-years in those with ALVSD. The HF rate was 45 occurrences per 1,000 person-years for those with ALVSD and mildly impaired LV dysfunction and 93 occurrences per 1,000 person-years for those with ALVSD and moderate to severe LV dysfunction. The mortality rate was 51 deaths per 1,000 person-years in the reference group, 90 deaths per 1,000 person-years in the ALVSD group, and 156 deaths per 1,000 person-years in the SLVSD group. Adjusting for covariates, compared to the reference group, ALVSD was associated with an increased risk of incident HF (hazard ratio 1.60,95% confidence interval 1.35 to 1.91), cardiovascular mortality (hazard ratio 2.13, 95% confidence interval 1.81 to 2.51), and all-cause mortality (hazard ratio 1.46, 95% confidence interval 1.29 to 1.64). In conclusion, subjects with ALVSD are characterized by a greater prevalence of cardiovascular risk factors and co-morbidities than those with normal LV function and without HF. However, the prevalence is lower than in those with SLVSD. Patients with ALVSD are at an increased risk of HF and mortality, particularly those with greater severity of LV impairment. PMID:21575752

Comparison of characteristics and outcomes of asymptomatic versus symptomatic left ventricular dysfunction in subjects 65 years old or older (from the Cardiovascular Health Study).

PubMed

Pandhi, Jay; Gottdiener, John S; Bartz, Traci M; Kop, Willem J; Mehra, Mandeep R

2011-06-01

Although asymptomatic left ventricular (LV) systolic dysfunction (ALVSD) is common, its phenotype and prognosis for incident heart failure (HF) and mortality are insufficiently understood. Echocardiography was done in 5,649 participants in the Cardiovascular Health Study (age 73.0 ± 5.6 years, 57.6% women). The clinical characteristics and cardiovascular risk factors of the participants with ALVSD were compared to those with normal LV function (ejection fraction ≥55%) and with symptomatic LV systolic dysfunction (SLVSD; ejection fraction <55% and a history of HF). Cox proportional hazards models were used to estimate the risk of incident HF and mortality in those with ALVSD. Also, comparisons were made among the LV ejection fraction subgroups using previously validated cutoff values (<45% and 45% to 55%), adjusting for the demographic and cardiovascular disease risk factors. Those with ALVSD (7.3%) were more likely to have cardiovascular risk factors than those in the reference group (without LV dysfunction or symptomatic HF) but less likely than those with SLVSD. The HF rate was 24 occurrences per 1,000 person-years in the reference group and 57 occurrences per 1,000 person-years in those with ALVSD. The HF rate was 45 occurrences per 1,000 person-years for those with ALVSD and mildly impaired LV dysfunction and 93 occurrences per 1,000 person-years for those with ALVSD and moderate to severe LV dysfunction. The mortality rate was 51 deaths per 1,000 person-years in the reference group, 90 deaths per 1,000 person-years in the ALVSD group, and 156 deaths per 1,000 person-years in the SLVSD group. Adjusting for covariates, compared to the reference group, ALVSD was associated with an increased risk of incident HF (hazard ratio 1.60, 95% confidence interval 1.35 to 1.91), cardiovascular mortality (hazard ratio 2.13, 95% confidence interval 1.81 to 2.51), and all-cause mortality (hazard ratio 1.46, 95% confidence interval 1.29 to 1.64). In conclusion, subjects with ALVSD are characterized by a greater prevalence of cardiovascular risk factors and co-morbidities than those with normal LV function and without HF. However, the prevalence is lower than in those with SLVSD. Patients with ALVSD are at an increased risk of HF and mortality, particularly those with greater severity of LV impairment. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

Usefulness of Speckle-Tracking Imaging for Right Ventricular Assessment after Acute Myocardial Infarction: A Magnetic Resonance Imaging/Echocardiographic Comparison within the Relation between Aldosterone and Cardiac Remodeling after Myocardial Infarction Study.

PubMed

Lemarié, Jérémie; Huttin, Olivier; Girerd, Nicolas; Mandry, Damien; Juillière, Yves; Moulin, Frédéric; Lemoine, Simon; Beaumont, Marine; Marie, Pierre-Yves; Selton-Suty, Christine

2015-07-01

Right ventricular (RV) dysfunction after acute myocardial infarction (AMI) is frequent and associated with poor prognosis. The complex anatomy of the right ventricle makes its echocardiographic assessment challenging. Quantification of RV deformation by speckle-tracking echocardiography is a widely available and reproducible technique that readily provides an integrated analysis of all segments of the right ventricle. The aim of this study was to investigate the accuracy of conventional echocardiographic parameters and speckle-tracking echocardiographic strain parameters in assessing RV function after AMI, in comparison with cardiac magnetic resonance imaging (CMR). A total of 135 patients admitted for AMI (73 anterior, 62 inferior) were prospectively studied. Right ventricular function was assessed by echocardiography and CMR within 2 to 4 days of hospital admission. Right ventricular dysfunction was defined as CMR RV ejection fraction < 50%. Right ventricular global peak longitudinal systolic strain (GLPSS) was calculated by averaging the strain values of the septal, lateral, and inferior walls. Right ventricular dysfunction was documented in 20 patients. Right ventricular GLPSS was the best echographic correlate of CMR RV ejection fraction (r = -0.459, P < .0001) and possessed good diagnostic value for RV dysfunction (area under the receiver operating characteristic curve [AUROC], 0.724; 95% CI, 0.590-0.857), which was comparable with that of RV fractional area change (AUROC, 0.756; 95% CI, 0.647-0.866). In patients with inferior myocardial infarctions, the AUROCs for RV GLPSS (0.822) and inferolateral strain (0.877) were greater than that observed for RV fractional area change (0.760) Other conventional echocardiographic parameters performed poorly (all AUROCs < 0.700). After AMI, RV GLPSS is the best correlate of CMR RV ejection fraction. In patients with inferior AMIs, RV GLPSS displays even higher diagnostic value than conventional echocardiographic parameters. Copyright © 2015 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Asteroid Deflection: How, Where and When?

NASA Astrophysics Data System (ADS)

Fargion, D.

2008-10-01

To deflect impact-trajectory of massive and spinning km^3 asteroid by a few terrestrial radiuses one need a large momentum exchange. The dragging of huge spinning bodies in space by external engine seems difficult or impossible. Our solution is based on the landing of multi screw-rockets, powered by mini-nuclear engines, on the body, that dig a small fraction of the soil surface to use as an exhaust propeller, ejecting it vertically in phase among themselves. Such a mass ejection increases the momentum exchange, their number redundancy guarantees the stability of the system. The slow landing (below ≃ 40 cm s^{-1}) of each engine-unity at those very low gravity field, may be achieved by safe rolling and bouncing along the surface. The engine array tuned activity, overcomes the asteroid angular velocity. Coherent turning of the jet heads increases the deflection efficiency. A procession along its surface may compensate at best the asteroid spin. A small skin-mass (about 2×10^4 tons) may be ejected by mini-nuclear engines. Such prototypes may also build first safe galleries for humans on the Moon. Conclusive deflecting tests might be performed on remote asteroids. The incoming asteroid 99942 Apophis (just 2% of km^3) may be deflected safely a few Earth radiuses. Its encounter maybe not just a hazard but an opportunity, learning how to land, to dig, to build and also to nest safe human station inside. Asteroids amplified deflections by gravity swing may be driven into longest planetary journeys, beginning i.e. with the preliminary landing of future missions on Mars' moon-asteroid Phobos or Deimos.

Usefulness of bedside tissue Doppler echocardiography and B-type natriuretic peptide (BNP) in differentiating congestive heart failure from noncardiac cause of acute dyspnea in elderly patients with a normal left ventricular ejection fraction and permanent, nonvalvular atrial fibrillation: insights from a prospective, monocenter study.

PubMed

Arques, Stephane; Roux, Emmanuel; Sbragia, Pascal; Pieri, Bertrand; Gelisse, Richard; Luccioni, Roger; Ambrosi, Pierre

2007-05-01

The incremental role of bedside tissue Doppler echocardiography and B-type natriuretic peptide (BNP) over the clinical judgment has been recently reported in the emergency diagnosis of congestive heart failure with a normal left ventricular ejection fraction (HFNEF). However, how well does this diagnostic strategy be applicable in the setting of atrial fibrillation is unknown. To investigate the usefulness of bedside tissue Doppler echocardiography and BNP in the emergency diagnosis of HFNEF in elderly patients with permanent, nonvalvular atrial fibrillation. Forty-one consecutive elderly patients with an ejection fraction > or =50% (mean age 84 years; 22 with HFNEF and 19 with noncardiac cause), hospitalized for acute dyspnea at rest, were prospectively enrolled; bedside septal E/Ea and BNP were obtained at admission. By multivariable logistic regression analysis including the clinical judgment of heart failure, E/Ea and BNP, E/Ea (P = 0.014) and BNP (P = 0.018) provided independent diagnostic information. Optimal cutoffs were 13 for E/Ea (area under the ROC curve of 0.846, P < 0.0001; sensitivity 81.8%, specificity 89.5%) and 253 pg/ml for BNP (area under the ROC curve of 0.928, P < 0.0001; sensitivity 86.4%, specificity 89.5%). The concordance between the clinical judgment and BNP concentration at the cutoff of 253 pg/ml correctly classified 24 of 25 patients; E/Ea at the cutoff of 13 correctly classified 14 of the 16 patients with discrepancy. Bedside tissue Doppler echocardiography and BNP provide useful additional diagnostic information over the clinical judgment for the emergency diagnosis of HFNEF in elderly patients with permanent, nonvalvular atrial fibrillation.

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 clinical benefit of cardiac resynchronization therapy optimization using a device-based hemodynamic sensor in a patient with dilated cardiomyopathy: a case report.

PubMed

Volpicelli, Mario; Covino, Gregorio; Capogrosso, Paolo

2015-12-19

Results on the evolution of the clinical status of patients undergoing cardiac resynchronization therapy with a defibrillator after automatic optimization of their cardiac resynchronization therapy are scarce. We observed a rapid and important change in the clinical status of our non-responding patient following activation of a sensor capable of weekly atrioventricular and interventricular delays' optimization. A 78-year-old Caucasian man presented with dilated cardiomyopathy, left bundle branch block, a left ventricular ejection fraction of 35 %, New York Heart Association class III/IV heart failure, and paroxysmal atrial fibrillation. Our patient was implanted with a cardiac resynchronization device with a defibrillator and the SonRtip atrial lead. Right ventricular and left ventricular leads were also implanted. Because of the recurrence of atrial fibrillation, the automatic optimization was set off at discharge. Consequently, the device did not optimize atrioventricular and interventricular delays (programming at discharge: 125 ms for the atrioventricular delay and 0 ms for the interventriculardelay). Our patient was treated with an anti-arrhythmic drug. Five months after implantation, his clinical status remained impaired (left ventricular ejection fraction = 30 %). The SonR signal amplitude had also decreased from 0.52 g to 0.29 g. Nevertheless, because our patient was no longer presenting with atrial fibrillation, the anti-arrhythmic treatment was stopped and the SonR optimization system was activated. After 2 months of automatic cardiac resynchronization therapy with defibrillator optimization, our patient's clinical status had significantly improved (left ventricular ejection fraction = 60 %, New York Heart Association class II) and the SonR signal amplitude had doubled shortly after the first weekly automatic optimization. In this non-responding patient, device-based automatic cardiac resynchronization therapy optimization was shown to significantly improve his clinical status.

Gallbladder filling and emptying during cholesterol gallstone formation in the prairie dog. A cholescintigraphic study

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

Pellegrini, C.A.; Ryan, T.; Broderick, W.

1986-01-01

We studied gallbladder bile flow before, during, and after cholesterol gallstone formation in the prairie dog using infusion cholescintigraphy with /sup 99m/Tc-diethyl iminodiacetic acid. In 18 fasting animals partitioning of bile between gallbladder and intestine was determined every 15 min for 140 min, and gallbladder response to cholecystokinin (5 U/kg X h) was calculated from the gallbladder ejection fraction. Ten prairie dogs were then placed on a 0.4% cholesterol diet and 8 on a regular diet, and the studies were repeated 1, 2, and 6 wk later. The proportion of hepatic bile that entered the gallbladder relative to the intestinemore » varied from one 15-min period to the next, and averaged 28.2% +/- 5.1% at 140 min. Partial spontaneous gallbladder emptying (ejection fraction 11.5% +/- 5.6%) was intermittently observed. Neither the number nor the ejection fraction of spontaneous gallbladder contractions changed during gallstone formation. By contrast, the percent of gallbladder emptying in response to cholecystokinin decreased from 72.1% +/- 5% to 25.9% +/- 9.3% (p less than 0.025) in the first week and was 14.3% +/- 5.5% at 6 wk (p less than 0.01 from prediet values, not significant from first week). Gallbladder filling decreased from 28.2% +/- 5.1% to 6.7% +/- 3% (p less than 0.01), but this change was only observed after 6 wk, when gallstones had formed. This study shows that bile flow into the gallbladder during fasting is not constant; the gallbladder contracts intermittently; gallbladder emptying in response to exogenous cholecystokinin is altered very early during gallstone formation; and gallbladder filling remains unaffected until later stages, when gallstones have formed.« less

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.

Relationship between right and left ventricular function in candidates for implantable cardioverter defibrillator with low left ventricular ejection fraction.

PubMed

Jimenez-Juan, Laura; Karur, Gauri R; Connelly, Kim A; Deva, Djeven; Yan, Raymond T; Wald, Rachel M; Singh, Sheldon; Leung, General; Oikonomou, Anastasia; Dorian, Paul; Angaran, Paul; Yan, Andrew T

2017-04-01

Indications for the primary prevention of sudden death using an implantable cardioverter defibrillator (ICD) are based predominantly on left ventricular ejection fraction (LVEF). However, right ventricular ejection fraction (RVEF) is also a known prognostic factor in a variety of structural heart diseases that predispose to sudden cardiac death. We sought to investigate the relationship between right and left ventricular parameters (function and volume) measured by cardiovascular magnetic resonance (CMR) among a broad spectrum of patients considered for an ICD. In this retrospective, single tertiary-care center study, consecutive patients considered for ICD implantation who were referred for LVEF assessment by CMR were included. Right and left ventricular function and volumes were measured. In total, 102 patients (age 62±14 years; 23% women) had a mean LVEF of 28±11% and RVEF of 44±12%. The left ventricular and right ventricular end diastolic volume index was 140±42 mL/m 2 and 81±27 mL/m 2 , respectively. Eighty-six (84%) patients had a LVEF <35%, and 63 (62%) patients had right ventricular systolic dysfunction. Although there was a significant and moderate correlation between LVEF and RVEF ( r =0.40, p <0.001), 32 of 86 patients (37%) with LVEF <35% had preserved RVEF, while 9 of 16 patients (56%) with LVEF ≥35% had right ventricular systolic dysfunction (Kappa=0.041). Among patients being considered for an ICD, there is a positive but moderate correlation between LVEF and RVEF. A considerable proportion of patients who qualify for an ICD based on low LVEF have preserved RVEF, and vice versa.

Do we overestimate left ventricular ejection fraction by two-dimensional echocardiography in patients with left bundle branch block?

PubMed

Cabuk, Ali K; Cabuk, Gizem; Sayin, Ahmet; Karamanlioglu, Murat; Kilicaslan, Barış; Ekmekci, Cenk; Solmaz, Hatice; Aslanturk, Omer F; Ozdogan, Oner

2018-02-01

Left bundle branch block (LBBB) causes a dyssynchronized contraction of left ventricle. This is a kind of regional wall-motion abnormality and measuring left ventricular ejection fraction (LVEF) by two-dimensional (2D) echocardiography could be less reliable in this particular condition. Our aim was to evaluate the role of dyssynchrony index (SDI), measured by three-dimensional (3D) echocardiography, in assessment of LVEF and left ventricular volumes accurately in patients with LBBB. In this case-control study, we included 52 of 64 enrolled participants (twelve participants with poor image quality were excluded) with LBBB and normal LVEF or nonischemic cardiomyopathy. Left ventricular ejection fraction (LVEF) and left ventricular volumes were assessed by 2D (modified Simpson's rule) and 3D (four beats full volume analysis) echocardiography and the impact of SDI on results were evaluated. In patients with SDI ≥6%, LVEF measurements were significantly different (46.00% [29.50-52.50] vs 37.60% [24.70-45.15], P < .001) between 2D and 3D echocardiography, respectively. In patients with SDI < 6%, there were no significant differences between two modalities in terms of LVEF measurements (54.50% [49.00-59.00] vs 54.25% [40.00-58.25], P = .193). LV diastolic volumes were not significantly different while systolic volumes were underestimated by 2D echocardiography, and this finding was more pronounced when SDI ≥ 6%. In patients with LBBB and high SDI (≥6%), LVEF values were overestimated and systolic volumes were underestimated by 2D echocardiography compared to 3D echocardiography. © 2017 Wiley Periodicals, Inc.

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

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.

Off-pump coronary artery bypass surgery in selected patients is superior to the conventional approach for patients with severely depressed left ventricular function

PubMed Central

Caputti, Guido Marco; Palma, José Honório; Gaia, Diego Felipe; Buffolo, Enio

2011-01-01

OBJECTIVES: Patients with coronary artery disease and left ventricular dysfunction have high mortality when kept in clinical treatment. Coronary artery bypass grafting can improve survival and the quality of life. Recently, revascularization without cardiopulmonary bypass has been presented as a viable alternative. The aim of this study is to compare patients with left ventricular ejection fractions of less than 20% who underwent coronary artery bypass graft with or without cardiopulmonary bypass. METHODS: From January 2001 to December 2005, 217 nonrandomized, consecutive, and nonselected patients with an ejection fraction less than or equal to 20% underwent coronary artery bypass graft surgery with (112) or without (off-pump) (105) the use of cardiopulmonary bypass. We studied demographic, operative, and postoperative data. RESULTS: There were no demographic differences between groups. The outcome variables showed similar graft numbers in both groups. Mortality was 12.5% in the cardiopulmonary bypass group and 3.8% in the off-pump group. Postoperative complications were statistically different (cardiopulmonary bypass versus off-pump): total length of hospital stay (days)—11.3 vs. 7.2, length of ICU stay (days)—3.7 vs. 2.1, pulmonary complications—10.7% vs. 2.8%, intubation time (hours)—22 vs. 10, postoperative bleeding (mL)—654 vs. 440, acute renal failure—8.9% vs. 1.9% and left-ventricle ejection fraction before discharge—22% vs. 29%. CONCLUSION: Coronary artery bypass grafting without cardiopulmonary bypass in selected patients with severe left ventricular dysfunction is valid and safe and promotes less mortality and morbidity compared with conventional operations. PMID:22189729

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.

Factors associated with atrial fibrillation in rheumatic mitral stenosis.

PubMed

Pourafkari, Leili; Ghaffari, Samad; Bancroft, George R; Tajlil, Arezou; Nader, Nader D

2015-01-01

Atrial fibrillation is a complication of mitral valve stenosis that causes several adverse neurologic outcomes. Our objective was to establish a mathematical model to predict the risk of atrial fibrillation in patients with mitral stenosis. Of 819 patients with mitral stenosis who were screened, 603 were enrolled in the study and grouped according to whether they were in sinus rhythm or atrial fibrillation. Demographic, echocardiographic, and hemodynamic data were recorded. Logistic regression models were constructed to identify the relative risks for each contributing factor and calculate the probability of developing atrial fibrillation. Receiver operating characteristic curves were plotted. Two hundred (33%) patients had atrial fibrillation; this group was older, in a higher functional class, more likely to have suffered previous thromboembolic events, and had significantly larger left atrial diameters, lower ejection fractions, and lower left atrial appendage emptying flow velocity. The factors independently associated with atrial fibrillation were left atrial strain (odds ratio = 7.53 [4.47-12.69], p < 0.001), right atrial pressure (odds ratio = 1.09 [1.02-1.17], p = 0.01), age (odds ratio = 1.14 [1.05-1.25], p = 0.002), and ejection fraction (odds ratio = 0.92 [0.87-0.97], p = 0.003). The area under the curve for the combined receiver operating characteristic for this model was 0.90 ± 0.12. Age, right atrial pressure, ejection fraction, and left atrial strain can be used to construct a mathematical model to predict the development of atrial fibrillation in rheumatic mitral stenosis. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Symptom-limited exercise testing causes sustained diastolic dysfunction in patients with coronary disease and low effort tolerance.

PubMed

Fragasso, G; Benti, R; Sciammarella, M; Rossetti, E; Savi, A; Gerundini, P; Chierchia, S L

1991-05-01

Exercise stress testing is routinely used for the noninvasive assessment of coronary artery disease and is considered a safe procedure. However, the provocation of severe ischemia might potentially cause delayed recovery of myocardial function. To investigate the possibility that maximal exercise testing could induce prolonged impairment of left ventricular function, 15 patients with angiographically proved coronary disease and 9 age-matched control subjects with atypical chest pain and normal coronary arteries were studied. Radionuclide ventriculography was performed at rest, at peak exercise, during recovery and 2 and 7 days after exercise. Ejection fraction, peak filling and peak emptying rates and left ventricular wall motion were analyzed. All control subjects had a normal exercise test at maximal work loads and improved left ventricular function on exercise. Patients developed 1 mm ST depression at 217 +/- 161 s at a work load of 70 +/- 30 W and a rate-pressure product of 18,530 +/- 4,465 mm Hg x beats/min. Although exercise was discontinued when angina or equivalent symptoms occurred, in all patients diagnostic ST depression (greater than or equal to 1 mm) developed much earlier than symptoms. Predictably, at peak exercise patients showed a decrease in ejection fraction and peak emptying and filling rates. Ejection fraction and peak emptying rate normalized within the recovery period, whereas peak filling rate remained depressed throughout recovery (p less than 0.002) and was still reduced 2 days after exercise (p less than 0.02). In conclusion, in patients with severe impairement of coronary flow reserve, maximal exercise may cause sustained impairement of diastolic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Gender related differences in clinical profile and outcome of patients with heart failure. Results of the RICA Registry.

PubMed

Conde-Martel, A; Arkuch, M E; Formiga, F; Manzano-Espinosa, L; Aramburu-Bodas, O; González-Franco, Á; Dávila-Ramos, M F; Suárez-Pedreira, I; Herrero-Domingo, A; Montero-Pérez-Barquero, M

2015-10-01

To analyze the differential clinical characteristics according to gender of patients with heart failure in terms of etiology, comorbidity, triggers, treatment, hospital stay and overall mortality at one year. We employed data from the RICA registry, a multicenter prospective cohort of patients hospitalized in internal medicine departments for heart failure, with a follow-up of one year. We analyzed the differences between the gender in terms of the etiology of the heart disease, comorbidity, triggers, left ventricle ejection fraction, functional state, mental condition, treatment, length of stay and mortality at 1 year. A total of 1772 patients (47.2% men) were included. The women were older than the men (p<.001) and had a higher prevalence of hypertension, obesity, chronic kidney disease, atrial fibrillation and preserved left ventricle ejection fraction (p<.001). The men's medical history had a predominance of myocardial infarction, chronic obstructive pulmonary disease, peripheral arteriopathy (p<.001) and anemia (p=.02). In the women, a hypertensive etiology was predominant, followed by valvular. The main triggers were hypertension and atrial fibrillation. Treatment with beta-blockers, ACEIs and/or ARBs did not differ by sex. The women had poorer functional capacity (p<.001), according to the Barthel index. After adjusting for age and other prognostic factors, the mortality at one year was lower among the women (RR: 0.69; 95% CI 0.53-0.89; p=.004). HF in women occurs at a later age and with different comorbidities. The hypertensive and valvular etiology is predominant, with preserved left ventricle ejection fraction, and the age-adjusted mortality is lower than in men. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Optimizing risk stratification in heart failure and the selection of candidates for heart transplantation.

PubMed

Pereira-da-Silva, Tiago; M Soares, Rui; Papoila, Ana Luísa; Pinto, Iola; Feliciano, Joana; Almeida-Morais, Luís; Abreu, Ana; Cruz Ferreira, Rui

2018-02-01

Selecting patients for heart transplantation is challenging. We aimed to identify the most important risk predictors in heart failure and an approach to optimize the selection of candidates for heart transplantation. Ambulatory patients followed in our center with symptomatic heart failure and left ventricular ejection fraction ≤40% prospectively underwent a comprehensive baseline assessment including clinical, laboratory, electrocardiographic, echocardiographic, and cardiopulmonary exercise testing parameters. All patients were followed for 60 months. The combined endpoint was cardiac death, urgent heart transplantation or need for mechanical circulatory support, up to 36 months. In the 263 enrolled patients (75% male, age 54±12 years), 54 events occurred. The independent predictors of adverse outcome were ventilatory efficiency (VE/VCO 2 ) slope (HR 1.14, 95% CI 1.11-1.18), creatinine level (HR 2.23, 95% CI 1.14-4.36), and left ventricular ejection fraction (HR 0.96, 95% CI 0.93-0.99). VE/VCO 2 slope was the most accurate risk predictor at any follow-up time analyzed (up to 60 months). The threshold of 39.0 yielded high specificity (97%), discriminated a worse or better prognosis than that reported for post-heart transplantation, and outperformed peak oxygen consumption thresholds of 10.0 or 12.0 ml/kg/min. For low-risk patients (VE/VCO 2 slope <39.0), sodium and creatinine levels and variations in end-tidal carbon dioxide partial pressure on exercise identified those with excellent prognosis. VE/VCO 2 slope was the most accurate parameter for risk stratification in patients with heart failure and reduced ejection fraction. Those with VE/VCO 2 slope ≥39.0 may benefit from heart transplantation. Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

[Type B natriuretic peptide in the diagnosis of heart failure with preserved systolic function].

PubMed

Castro, A; Dias, P; Pereira, M; Pimenta, J; Friões, F; Rodrigues, R; Ferreira, A; Bettencourt, P

2001-11-01

Heart failure (HF) with preserved left ventricular systolic function (LVSF) is observed in up to 50% patients with HF. There is no consensus on non-invasive diagnosis of this entity. Evaluation of B-type natriuretic peptide (BNP) in the diagnosis of HF with preserved left ventricular systolic function. Prospective study. One hundred and seventy-six consecutive patients with suspected HF were evaluated. Patients were classified as having HF with preserved LVSF, if they had symptoms and signs of HF, an ejection fraction greater than 40% and an abnormal Doppler pattern of the mitral inflow or atrial fibrilation and no other causes for the symptoms. All patients had a 12-lead EKG, chest roentgenogram, simple spirometry, M-mode and 2D echocardiogram with pulsed Doppler study of transmitral inflow and determination of plasma BNP levels. Of the 176 patients, 65 had ejection fraction greater than 40%. Of these patients 46 were classified as having HF with preserved LVSF and 19 as not having HF. Patients with HF and preserved LVSF were older, had a higher systolic blood pressure (SBP), less pathologic Q waves on ECG and higher left ventricular ejection fraction and plasma BNP than patients without HF. Multivariate analysis revealed that BNP and SBP were independently associated with the diagnosis of HF. The accuracy of BNP in the diagnosis of HF with preserved LVSF evaluated by the area under the receiver operating characteristic curve was 0.94. These results suggest that the measurement of BNP levels can help clinicians in the diagnosis of HF with preserved LVSF. Whether BNP levels might be used in clinical practice as a test for the diagnosis of HF with preserved LVSF is a question that merits further studies.

Renal dysfunction in patients with heart failure with preserved versus reduced ejection fraction: impact of the new Chronic Kidney Disease-Epidemiology Collaboration Group formula.

PubMed

McAlister, Finlay A; Ezekowitz, Justin; Tarantini, Luigi; Squire, Iain; Komajda, Michel; Bayes-Genis, Antoni; Gotsman, Israel; Whalley, Gillian; Earle, Nikki; Poppe, Katrina K; Doughty, Robert N

2012-05-01

Prior studies in heart failure (HF) have used the Modification of Diet in Renal Disease (MDRD) equation to calculate estimated glomerular filtration rate (eGFR). The Chronic Kidney Disease-Epidemiology Collaboration Group (CKD-EPI) equation provides a more-accurate eGFR than the MDRD when compared against the radionuclide gold standard. The prevalence and prognostic import of renal dysfunction in HF if the CKD-EPI equation is used rather than the MDRD is uncertain. We used individual patient data from 25 prospective studies to stratify patients with HF by eGFR using the CKD-EPI and the MDRD equations and examined survival across eGFR strata. In 20 754 patients (15 962 with HF with reduced ejection fraction [HF-REF] and 4792 with HF with preserved ejection fraction [HF-PEF]; mean age, 68 years; deaths per 1000 patient-years, 151; 95% CI, 146-155), 10 589 (51%) and 11 422 (55%) had an eGFR <60 mL/min using the MDRD and CKD-EPI equations, respectively. Use of the CKD-EPI equation resulted in 3760 (18%) patients being reclassified into different eGFR risk strata; 3089 (82%) were placed in a lower eGFR category and exhibited higher all-cause mortality rates (net reclassification improvement with CKD-EPI, 3.7%; 95% CI, 1.5%-5.9%). Reduced eGFR was a stronger predictor of all-cause mortality in HF-REF than in HF-PEF. Use of the CKD-EPI rather than the MDRD equation to calculate eGFR leads to higher estimates of renal dysfunction in HF and a more-accurate categorization of mortality risk. Renal function is more closely related to outcomes in HF-REF than in HF-PEF.

Systolic Strain Abnormalities to Predict Hospital Readmission in Patients With Heart Failure and Normal Ejection Fraction

PubMed Central

Borer, Steven M.; Kokkirala, Aravind; O'Sullivan, David M.; Silverman, David I.

2011-01-01

Background Despite intensive investigation, the pathogenesis of heart failure with normal ejection fraction (HFNEF) remains unclear. We hypothesized that subtle abnormalities of systolic function might play a role, and that abnormal systolic strain and strain rate would provide a marker for adverse outcomes. Methods Patients of new CHF and left ventricular ejection fraction > 50% were included. Exclusion criteria were recent myocardial infarction, severe valvular heart disease, severe left ventricular hypertrophy (septum >1.8 cm), or a technically insufficient echocardiogram. Average peak systolic strain and strain rate were measured using an off-line grey scale imaging technique. Systolic strain and strain rate for readmitted patients were compared with those who remained readmission-free. Results One hundred consecutive patients with a 1st admission for HFNEF from January 1, 2004 through December 31, 2007, inclusive, were analyzed. Fifty two patients were readmitted with a primary diagnosis of heart failure. Systolic strain and strain rates were reduced in both study groups compared to controls. However, systolic strain did not differ significantly between the two groups (-11.7% for those readmitted compared with -12.9% for those free from readmission, P = 0.198) and systolic strain rates also were similar (-1.05 s-1 versus -1.09 s-1, P = 0.545). E/e’ was significantly higher in readmitted patients compared with those who remained free from readmission (14.5 versus 11.0, P = 0.013). E/e’ (OR 1.189, 95% CI 1.026-1.378; P = 0.021) was found to be an independent predictor for HFNEF readmission. Conclusions Among patients with new onset HFNEF, SS and SR rates are reduced compared with patients free of HFNEF, but do not predict hospital readmission. Elevated E/e’ is a predictor of readmission in these patients. PMID:28352395

Peak oxygen uptake and left ventricular ejection fraction, but not depressive symptoms, are associated with cognitive impairment in patients with chronic heart failure

PubMed Central

Steinberg, Gerrit; Lossnitzer, Nicole; Schellberg, Dieter; Mueller-Tasch, Thomas; Krueger, Carsten; Haass, Markus; Ladwig, Karl Heinz; Herzog, Wolfgang; Juenger, Jana

2011-01-01

Background The aim of the present study was to assess cognitive impairment in patients with chronic heart failure (CHF) and its associations with depressive symptoms and somatic indicators of illness severity, which is a matter of controversy. Methods and results Fifty-five patients with CHF (mean age 55.3 ± 7.8 years; 80% male; New York Heart Association functional class I–III) underwent assessment with an expanded neuropsychological test battery (eg, memory, complex attention, mental flexibility, psychomotor speed) to evaluate objective and subjective cognitive impairment. Depressive symptoms were assessed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID) and a self-report inventory (Hospital Anxiety and Depression Scale [HADS]). A comprehensive clinical dataset, including left ventricular ejection fraction, peak oxygen uptake, and a 6-minute walk test, was obtained for all patients. Neuropsychological functioning revealed impairment in 56% of patients in at least one measure of our neuropsychological test battery. However, the Mini Mental State Examination (MMSE) could only detect cognitive impairment in 1.8% of all patients, 24% had HADS scores indicating depressive symptoms, and 11.1% met SCID criteria for a depressive disorder. No significant association was found between depressive symptoms and cognitive impairment. Left ventricular ejection fraction was related to subjective cognitive impairment, and peak oxygen uptake was related to objective cognitive impairment. Conclusion Cognitive functioning was substantially reduced in patients with CHF and should therefore be diagnosed and treated in routine clinical practice. Caution is advised when the MMSE is used to identify cognitive impairment in patients with CHF. PMID:22267941

[Clinical characteristics and medium-term prognosis of patients with heart failure and preserved systolic function. Do they differ in systolic dysfunction?].

PubMed

Ojeda, Soledad; Anguita, Manuel; Muñoz, Juan F; Rodríguez, Marcos T; Mesa, Dolores; Franco, Manuel; Ureña, Isabel; Vallés, Federico

2003-11-01

To assess the prevalence, clinical profile and medium-term prognosis in patients with heart failure and preserved systolic ventricular function compared to those with systolic dysfunction. 153 patients were included, 62 with preserved systolic ventricular function (left ventricular ejection fraction > or = 45%) and 91 with impaired systolic ventricular function (left ventricular ejection fraction < 45%). The mean follow-up period was 25 10 months. Mean age was similar (66 10 vs. 65 10; p = 0.54). There was a higher proportion of women among patients with preserved systolic function (53% vs. 28%; p < 0.01). Ischemic and idiopathic cardiomyopathy were the most common causes of heart failure in patients with systolic dysfunction, whereas valvular disease and hypertensive cardiopathy were the most common in patients with preserved systolic function. Angiotensin-converting enzyme inhibitors and beta-blockers were more often prescribed in patients with impaired systolic ventricular function (86% vs. 52%; p < 0.01 and 33% vs. 11%; p < 0.01, respectively). There were no differences between the groups in terms of mortality rate (37% vs. 29%), readmission rate for other causes (29% vs. 23%), readmission rate for heart failure (45% vs. 45%), cumulative survival (51% vs. 62%) and the likelihood of not being readmitted for heart failure (50% vs. 52%). In the multivariate analysis, left ventricular ejection fraction was not a predictor of death or readmission because of heart failure. In a large proportion of patients with heart failure, systolic ventricular function is preserved. Despite the clinical differences between patients with preserved and impaired systolic ventricular function, the medium-term prognosis was similar in both groups.

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.

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

Significance of left ventricular diastolic function on outcomes after surgical ventricular restoration.

PubMed

Marui, Akira; Nishina, Takeshi; Saji, Yoshiaki; Yamazaki, Kazuhiro; Shimamoto, Takeshi; Ikeda, Tadashi; Sakata, Ryuzo

2010-05-01

Surgical ventricular restoration (SVR) has been introduced to restore the dilated left ventricular (LV) chamber and improve LV systolic function; however, SVR has also been reported to detrimentally affect LV diastolic properties. We sought to investigate the impact of preoperative LV diastolic function on outcomes after SVR in patients with heart failure. Sixty-seven patients (60 +/- 14 years) with LV systolic dysfunction (LV ejection fraction, 0.27 +/- 0.10) underwent SVR. They were evaluated by echocardiography preoperatively, and early (

Liposome encapsulated berberine treatment attenuates cardiac dysfunction after myocardial infarction.

PubMed

Allijn, Iris E; Czarny, Bertrand M S; Wang, Xiaoyuan; Chong, Suet Yen; Weiler, Marek; da Silva, Acarilia Eduardo; Metselaar, Josbert M; Lam, Carolyn Su Ping; Pastorin, Giorgia; de Kleijn, Dominique P V; Storm, Gert; Wang, Jiong-Wei; Schiffelers, Raymond M

2017-02-10

Inflammation is a known mediator of adverse ventricular remodeling after myocardial infarction (MI) that may lead to reduction of ejection fraction and subsequent heart failure. Berberine is a isoquinoline quarternary alkaloid from plants that has been associated with anti-inflammatory, anti-oxidative, and cardioprotective properties. Its poor solubility in aqueous buffers and its short half-life in the circulation upon injection, however, have been hampering the extensive usage of this natural product. We hypothesized that encapsulation of berberine into long circulating liposomes could improve its therapeutic availability and efficacy by protecting cardiac function against MI in vivo. Berberine-loaded liposomes were prepared by ethanol injection and characterized. They contained 0.3mg/mL of the drug and were 0.11μm in diameter. Subsequently they were tested for IL-6 secretion inhibition in RAW 264.7 macrophages and for cardiac function protection against adverse remodeling after MI in C57BL/6J mice. In vitro, free berberine significantly inhibited IL-6 secretion (IC 50 =10.4μM), whereas encapsulated berberine did not as it was not released from the formulation in the time frame of the in vitro study. In vivo, berberine-loaded liposomes significantly preserved the cardiac ejection fraction at day 28 after MI by 64% as compared to control liposomes and free berberine. In conclusion, liposomal encapsulation enhanced the solubility of berberine in buffer and preserves ejection fraction after MI. This shows that delivery of berberine-loaded liposomes significantly improves its therapeutic availability and identifies berberine-loaded liposomes as potential treatment of adverse remodeling after MI. Copyright © 2017 Elsevier B.V. All rights reserved.

True Anemia-Red Blood Cell Volume Deficit-in Heart Failure: A Systematic Review.

PubMed

Montero, David; Lundby, Carsten; Ruschitzka, Frank; Flammer, Andreas J

2017-05-01

Anemia in heart failure (HF) is commonly diagnosed according to hemoglobin concentration [Hb], hence may be the result of hemodilution or true red blood cell volume (RBCV) deficit. Whether true (nonhemodilutional) anemia in HF can or cannot be generally inferred by [Hb] measurements and clinical correlates remains unclear. The purpose of this study was to systematically review the literature and investigate the status and correlates of RBCV in patients with HF. MEDLINE, Scopus, and Web of Science were searched since their inceptions until April 2016 for articles directly reporting or allowing the calculation of intravascular volumes (RBCV, plasma volume) in patients with HF according to the International Council for Standardization in Hematology. Eighteen studies were included after systematic review, comprising a total of 368 patients with HF (limits for mean age=49-80 years, sex=0%-92% females, left ventricular ejection fraction=26%-61%). Mean RBCV was reduced (limits=67%-88% of normal) in all studies including HF patients with anemia (low [Hb]) (7 studies, n=127), whereas only 2 of 10 studies in nonanemic patients with HF presented lower than normal mean RBCV (90% and 96%). In metaregression analyses, RBCV was positively associated with [Hb] ( B =6.10, SE=1.44) and negatively associated with age ( B =-1.14, SE=0.23), % females ( B =-0.38, SE=0.04), left ventricular ejection fraction ( B =-0.81, SE=0.20), and body mass index ( B =-3.55, SE=0.46; P <0.001). Presence or absence of true anemia in patients with HF as determined by RBCV status mainly concurs with diagnosis based on [Hb] and presents negative relationships with age, female sex, left ventricular ejection fraction, and body mass index. © 2017 American Heart Association, Inc.

3D heart motion from single-plane angiography of the coronary vasculature: a model-based approach

NASA Astrophysics Data System (ADS)

Sherknies, Denis; Meunier, Jean; Tardif, Jean-Claude

2004-05-01

In order to complete a thorough examination of a patient heart muscle, physicians practice two common invasive procedures: the ventriculography, which allows the determination of the ejection fraction, and the coronarography, giving among other things, information on stenosis of arteries. We propose a method that allows the determination of a contraction index similar to ejection fraction, using only single-plane coronarography. Our method first reconstructs in 3D, selected points on the angiogram, using a 3D model devised from data published by Dodge ea. ['88, '92]. We then follow the point displacements through a complete heart contraction cycle. The objective function, minimizing the RMS distances between the angiogram and the model, relies on affine transformations, i.e. translation, rotation and isotropic scaling. We validate our method on simulated projections using cases from Dodge data. In order to avoid any bias, a leave-one-out strategy was used, which excludes the reference case when constructing the 3D coronary heart model. The simulated projections are created by transforming the reference case, with scaling, translation and rotation transformations, and by adding random 3D noise for each frame in the contraction cycle. Comparing the true scaling parameters to the reconstructed sequence, our method is quite robust (R2=96.6%, P<1%), even when noise error level is as high as 1 cm. Using 10 clinical cases we then proceeded to reconstruct the contraction sequence for a complete cardiac cycle starting at end-diastole. A simple heart contraction mathematical model permitted us to link the measured ejection fraction of the different cases to the maximum heart contraction amplitude (R2=57%, P<1%) determined by our method.

In vivo cardiac cellular reprogramming efficacy is enhanced by angiogenic preconditioning of the infarcted myocardium with vascular endothelial growth factor.

PubMed

Mathison, Megumi; Gersch, Robert P; Nasser, Ahmed; Lilo, Sarit; Korman, Mallory; Fourman, Mitchell; Hackett, Neil; Shroyer, Kenneth; Yang, Jianchang; Ma, Yupo; Crystal, Ronald G; Rosengart, Todd K

2012-12-01

In situ cellular reprogramming offers the possibility of regenerating functional cardiomyocytes directly from scar fibroblasts, obviating the challenges of cell implantation. We hypothesized that pretreating scar with gene transfer of the angiogenic vascular endothelial growth factor (VEGF) would enhance the efficacy of this strategy. Gata4, Mef2c, and Tbx5 (GMT) administration via lentiviral transduction was demonstrated to transdifferentiate rat fibroblasts into (induced) cardiomyocytes in vitro by cardiomyocyte marker studies. Fisher 344 rats underwent coronary ligation and intramyocardial administration of an adenovirus encoding all 3 major isoforms of VEGF (AdVEGF-All6A(+)) or an AdNull control vector (n=12/group). Lentivirus encoding GMT or a GFP control was administered to each animal 3 weeks later, followed by histologic and echocardiographic analyses. GMT administration reduced the extent of fibrosis by half compared with GFP controls (12 ± 2% vs 24 ± 3%, P<0.01) and reduced the number of myofibroblasts detected in the infarct zone by 4-fold. GMT-treated animals also demonstrated greater density of cardiomyocyte-specific marker beta myosin heavy chain 7(+) cells compared with animals receiving GFP with or without VEGF (P<0.01). Ejection fraction was significantly improved after GMT vs GFP administration (12 ± 3% vs -7 ± 3%, P<0.01). Eight (73%) GFP animals but no GMT animals demonstrated decreased ejection fraction during this interval (P<0.01). Also, improvement in ejection fraction was 4-fold greater in GMT/VEGF vs GMT/null animals (17 ± 2% vs 4 ± 1%, P<0.05). VEGF administration to infarcted myocardium enhances the efficacy of GMT-mediated cellular reprogramming in improving myocardial function and reducing the extent of myocardial fibrosis compared with the use of GMT or VEGF alone.

Role of Three-Dimensional Speckle Tracking Echocardiography in the Quantification of Myocardial Iron Overload in Patients with Beta-Thalassemia Major.

PubMed

Li, Shu-Juan; Hwang, Yu-Yan; Ha, Shau-Yin; Chan, Godfrey C F; Mok, Amanda S P; Wong, Sophia J; Cheung, Yiu-Fai

2016-09-01

The new three-dimensional speckle tracking echocardiography (3DSTE) may enable comprehensive quantification of global left ventricular (LV) myocardial mechanics. Twenty-four patients aged 29.3 ± 5.2 years and 22 controls were studied. 3DSTE was performed to assess LV 3D global strain, twist and torsion, ejection fraction, and systolic dyssynchrony index (SDI). The LV SDI was calculated as % of SD of times-to-peak strain of 16 segments/RR interval. The global performance index (GPI) was calculated as (global 3D strain·torsion)/SDI. Area under the receiver operating characteristic curve (AUC) was calculated to determine the capability of 3DSTE parameters to discriminate between patients with (cardiac magnetic resonance T2* <20 ms) and those without myocardial iron overload. Compared with controls, patients had significantly lower LV global 3D strain (P < 0.001), twist (P = 0.01), torsion (P = 0.04), and ejection fraction (P < 0.001) and greater SDI (P < 0.001). The GPI was lower in patients than controls (P < 0.001). T2* value correlated positively with global 3D strain (r = 0.74, P < 0.001) and GPI (r = 0.63, P = 0.001), and negatively with SDI (r = -0.44, P = 0.03). The AUCs of GPI, global 3D strain, ejection fraction, torsion, and 1/SDI were 0.94, 0.90, 0.87, 0.82, and 0.70, respectively. The GPI cutoff of 2.7°/cm had a sensitivity of 94.9% and a specificity of 88.9% of differentiating patients with from those without myocardial iron overload. The LV composite index of strain, torsion, and dyssynchrony derived from 3DSTE enables sensitive detection of myocardial iron overload in patients with thalassemia. © 2016, Wiley Periodicals, Inc.

Cost-Effectiveness of Sacubitril-Valsartan in Patients With Heart Failure With Reduced Ejection Fraction.

PubMed

Sandhu, Alexander T; Ollendorf, Daniel A; Chapman, Richard H; Pearson, Steven D; Heidenreich, Paul A

2016-11-15

Sacubitril-valsartan therapy reduces cardiovascular mortality compared with enalapril therapy in patients with heart failure with reduced ejection fraction. To evaluate the cost-effectiveness of sacubitril-valsartan versus angiotensin-converting enzyme inhibitor therapy in patients with chronic heart failure. Markov decision model. Clinical trials, observational analyses, reimbursement data from the Centers for Medicare & Medicaid Services, drug pricing databases, and Centers for Disease Control and Prevention life tables. Patients at an average age of 64 years, New York Heart Association (NYHA) class II to IV heart failure, and left ventricular ejection fraction of 0.40 or less. Lifetime. Societal. Treatment with sacubitril-valsartan or lisinopril. Life-years, quality-adjusted life-years (QALYs), costs, heart failure hospitalizations, and incremental cost-effectiveness ratios. The sacubitril-valsartan group experienced 0.08 fewer heart failure hospitalization, 0.69 additional life-year, 0.62 additional QALY, and $29 203 in incremental costs, equating to a cost per QALY gained of $47 053. The cost per QALY gained was $44 531 in patients with NYHA class II heart failure and $58 194 in those with class III or IV heart failure. Sacubitril-valsartan treatment was most sensitive to the duration of improved outcomes, with a cost per QALY gained of $120 623 if the duration was limited to the length of the trial (median, 27 months). No variations in other parameters caused the cost to exceed $100 000 per QALY gained. The benefit of sacubitril-valsartan is based on a single clinical trial. Treatment with sacubitril-valsartan provides reasonable value in reducing cardiovascular mortality and morbidity in patients with NYHA class II to IV heart failure. U.S. Department of Veterans Affairs and Institute for Clinical and Economic Review.

Baseline characteristics and treatment of patients in Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF)

PubMed Central

McMurray, John J V; Packer, Milton; Desai, Akshay S; Gong, Jianjian; Lefkowitz, Martin; Rizkala, Adel R; Rouleau, Jean L; Shi, Victor C; Solomon, Scott D; Swedberg, Karl; Zile, Michael R

2014-01-01

Aim To describe the baseline characteristics and treatment of the patients randomized in the PARADIGM-HF (Prospective comparison of ARNi with ACEi to Determine Impact on Global Mortality and morbidity in Heart Failure) trial, testing the hypothesis that the strategy of simultaneously blocking the renin–angiotensin–aldosterone system and augmenting natriuretic peptides with LCZ696 200 mg b.i.d. is superior to enalapril 10 mg b.i.d. in reducing mortality and morbidity in patients with heart failure and reduced ejection fraction. Methods Key demographic, clinical and laboratory findings, along with baseline treatment, are reported and compared with those of patients in the treatment arm of the Studies Of Left Ventricular Dysfunction (SOLVD-T) and more contemporary drug and device trials in heart failure and reduced ejection fraction. Results The mean age of the 8442 patients in PARADIGM-HF is 64 (SD 11) years and 78% are male, which is similar to SOLVD-T and more recent trials. Despite extensive background therapy with beta-blockers (93% patients) and mineralocorticoid receptor antagonists (60%), patients in PARADIGM-HF have persisting symptoms and signs, reduced health related quality of life, a low LVEF (mean 29 ± SD 6%) and elevated N-terminal-proB type-natriuretic peptide levels (median 1608 inter-quartile range 886–3221 pg/mL). Conclusion PARADIGM-HF will determine whether LCZ696 is more beneficial than enalapril when added to other disease-modifying therapies and if further augmentation of endogenous natriuretic peptides will reduce morbidity and mortality in heart failure and reduced ejection fraction. PMID:24828035

The impact of anabolic androgenic steroids abuse and type of training on left ventricular remodeling and function in competitive athletes.

PubMed

Ilić, Ivan; Djordjević, Vitomir; Stanković, Ivan; Vlahović-Stipac, Alja; Putniković, Biljana; Babić, Rade; Nesković, Aleksandar N

2014-04-01

Long-term intensive training is associated with distinctive cardiac adaptations which are known as athlete's heart. The aim of this study was to determine whether the use of anabolic androgenic steroids (AAS) could affect echocardiographic parameters of left ventricular (LV) morphology and function in elite strength and endurance athletes. A total of 20 elite strength athletes (10 AAS users and 10 non-users) were compared to 12 steroid-free endurance athletes. All the subjects underwent comprehensive standard echocardiography and tissue Doppler imaging. After being indexed for body surface area, both left atrium (LA) and LV end-diastolic diameter (LVEDD) were significantly higher in the endurance than strength athletes, regardless of AAS use (p < 0.05, for both). A significant correlation was found between LA diameter and LVEDD in the steroid-free endurance athletes, showing that 75% of LA size variability depends on variability of LVEDD (p < 0.001). No significant differences in ejection fraction and cardiac output were observed among the groups, although mildly reduced LV ejection fraction was seen only in the AAS users. The AAS-using strength athletes had higher A-peak velocity when compared to steroid-free athletes, regardless of training type (p < 0.05 for both). Both AAS-using and AAS-free strength athletes had lower e' peak velocity and higher E/e' ratio than endurance athletes (p < 0.05, for all). There is no evidence that LV ejection fraction in elite athletes is altered by either type of training or AAS misuse. Long-term endurance training is associated with preferable effects on LV diastolic function compared to strength training, particularly when the latter is combined with AAS abuse.

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.

Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis.

PubMed

Zheng, Sean Lee; Chan, Fiona T; Nabeebaccus, Adam A; Shah, Ajay M; McDonagh, Theresa; Okonko, Darlington O; Ayis, Salma

2018-03-01

Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality. We systematically searched Medline, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) assessing pharmacological treatments in patients with heart failure with left ventricular (LV) ejection fraction≥40% from January 1996 to May 2016. The primary efficacy outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure hospitalisation, exercise capacity (6-min walk distance, exercise duration, VO 2 max), quality of life and biomarkers (B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide). Random-effects models were used to estimate pooled relative risks (RR) for the binary outcomes, and weighted mean differences for continuous outcomes, with 95% CI. We included data from 25 RCTs comprising data for 18101 patients. All-cause mortality was reduced with beta-blocker therapy compared with placebo (RR: 0.78, 95%CI 0.65 to 0.94, p=0.008). There was no effect seen with ACE inhibitors, aldosterone receptor blockers, mineralocorticoid receptor antagonists and other drug classes, compared with placebo. Similar results were observed for cardiovascular mortality. No single drug class reduced heart failure hospitalisation compared with placebo. The efficacy of treatments in patients with heart failure and an LV ejection fraction≥40% differ depending on the type of therapy, with beta-blockers demonstrating reductions in all-cause and cardiovascular mortality. Further trials are warranted to confirm treatment effects of beta-blockers in this patient group. © 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.

Mass Ejection from the Remnant of a Binary Neutron Star Merger: Viscous-radiation Hydrodynamics Study

NASA Astrophysics Data System (ADS)

Fujibayashi, Sho; Kiuchi, Kenta; Nishimura, Nobuya; Sekiguchi, Yuichiro; Shibata, Masaru

2018-06-01

We perform long-term general relativistic neutrino radiation hydrodynamics simulations (in axisymmetry) for a massive neutron star (MNS) surrounded by a torus, which is a canonical remnant formed after the binary neutron star merger. We take into account the effects of viscosity, which is likely to arise in the merger remnant due to magnetohydrodynamical turbulence. The viscous effect plays key roles for the mass ejection from the remnant in two phases of the evolution. In the first t ≲ 10 ms, a differential rotation state of the MNS is changed to a rigidly rotating state. A shock wave caused by the variation of its quasi-equilibrium state induces significant mass ejection of mass ∼(0.5–2.0) × {10}-2 {M}ȯ for the α-viscosity parameter of 0.01–0.04. For the longer-term evolution with ∼0.1–10 s, a significant fraction of the torus material is ejected. We find that the total mass of the viscosity-driven ejecta (≳ {10}-2 {M}ȯ ) could dominate over that of the dynamical ejecta (≲ {10}-2 {M}ȯ ). The electron fraction, Y e , of the ejecta is always high enough (Y e ≳ 0.25) that this post-merger ejecta is lanthanide-poor; hence, the opacity of the ejecta is likely to be ∼10–100 times lower than that of the dynamical ejecta. This indicates that the electromagnetic signal from the ejecta would be rapidly evolving, bright, and blue if it is observed from a small viewing angle (≲45°) for which the effect of the dynamical ejecta is minor.

CARBONYLATION OF MYOSIN HEAVY CHAINS IN RAT HEARTS DURING DIABETES

PubMed Central

Shao, Chun-Hong; Rozanski, George J.; Nagai, Ryoji; Stockdale, Frank E.; Patel, Kaushik P.; Wang, Mu; Singh, Jaipaul; Mayhan, William G.; Bidasee, Keshore R.

2010-01-01

Cardiac inotropy progressively declines during diabetes mellitus. To date, the molecular mechanisms underlying this defect remain incompletely characterized. This study tests the hypothesis that ventricular myosin heavy chains (MHC) undergo carbonylation by reactive carbonyl species (RCS) during diabetes and these modifications contribute to the inotropic decline. Male Sprague-Dawley rats were injected with streptozotocin (STZ). Fourteen days later animals were divided into two groups: one group was treated with the RCS blocker aminoguanidine for six weeks, while the other group received no treatment. After eight weeks of diabetes, cardiac ejection fraction, fractional shortening, left ventricular pressure development (+dP/dt) and myocyte shortening were decreased by 9%, 16%, 34% and 18%, respectively. Ca2+- and Mg2+-actomyosin ATPase activities and peak actomyosin syneresis were also reduced by 35%, 28%, and 72%. MHC-α to MHC-β ratio was 12:88. Mass spectrometry and Western blots revealed the presence of carbonyl adducts on MHC-α and MHC-β. Aminoguandine treatment did not alter MHC composition, but it blunted formation of carbonyl adducts and decreases in actomyosin Ca2+-sensitive ATPase activity, syneresis, myocyte shortening, cardiac ejection fraction, fractional shortening and +dP/dt induced by diabetes. From these new data it can be concluded that in addition to isozyme switching, modification of MHC by RCS also contributes to the inotropic decline seen during diabetes. PMID:20359464

A DIPOLE ON THE SKY: PREDICTIONS FOR HYPERVELOCITY STARS FROM THE LARGE MAGELLANIC CLOUD

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

Boubert, Douglas; Evans, N. Wyn, E-mail: d.boubert@ast.cam.ac.uk, E-mail: nwe@ast.cam.ac.uk

2016-07-01

We predict the distribution of hypervelocity stars (HVSs) ejected from the Large Magellanic Cloud (LMC), under the assumption that the dwarf galaxy hosts a central massive black hole (MBH). For the majority of stars ejected from the LMC, the orbital velocity of the LMC has contributed a significant fraction of their galactic rest-frame velocity, leading to a dipole density distribution on the sky. We quantify the dipole using spherical harmonic analysis and contrast with the monopole expected for HVSs ejected from the Galactic center (GC). There is a tendril in the density distribution that leads the LMC, which is coincidentmore » with the well-known and unexplained clustering of HVSs in the constellations of Leo and Sextans. Our model is falsifiable since it predicts that Gaia will reveal a large density of HVSs in the southern hemisphere.« less

Chronic mitral regurgitation and Doppler estimation of left ventricular filling pressures in patients with heart failure

NASA Technical Reports Server (NTRS)

Temporelli, P. L.; Scapellato, F.; Corra, U.; Eleuteri, E.; Firstenberg, M. S.; Thomas, J. D.; Giannuzzi, P.

2001-01-01

Previous studies relating Doppler parameters and pulmonary capillary wedge pressures (PCWP) typically exclude patients with severe mitral regurgitation (MR). We evaluated the effects of varying degrees of chronic MR on the Doppler estimation of PCWP. PCWP and mitral Doppler profiles were obtained in 88 patients (mean age 55 +/- 8 years) with severe left ventricular (LV) dysfunction (mean ejection fraction 23% +/- 5%). Patients were classified by severity of MR. Patients with severe MR had greater left atrial areas, LV end-diastolic volumes, and mean PCWPs and lower ejection fractions (each P <.01). In patients with mild MR, multiple echocardiographic parameters correlated with PCWP; however, with worsening MR, only deceleration time strongly related to PCWP. From stepwise multivariate analysis, deceleration time was the best independent predictor of PCWP overall, and it was the only predictor in patients with moderate or severe MR. Doppler-derived early mitral deceleration time reliably predicts PCWP in patients with severe LV dysfunction irrespective of degree of MR.

[Aortic Valve Replacement after Balloon Valvuloplasty for Aortic Valve Stenosis in a Dialysis Patient with Cardiogenic Shock;Report of a Case].

PubMed

Takamatsu, Masanori; Hirotani, Takashi; Ohtsubo, Satoshi; Saito, Sumikatsu; Takeuchi, Shigeyuki; Hasegawa, Tasuku; Endo, Ayaka; Yamasaki, Yu; Hayashida, Kentaro

2015-06-01

A 67-year-old man on chronic hemodialysis was admitted with worsening congestive heart failure due to critical aortic stenosis. Echocardiography showed severe aortic stenosis with a valve area of 0.67 cm2 and an ejection fraction of 0.31. Cardiac catheterization revealed severe pulmonary hypertension with pulmonary artery pressures of 62/32 mmHg. In the middle of cardiac catheterization, the systolic pressure declined to 60 mmHg due to cardiogenic shock. Dopamine hydrochloride and dobutamine hydrochloride infusions were necessary to maintain a systolic pressure greater than 80 mmHg. Balloon aortic valvuloplasty was urgently performed. The patient's symptoms rapidly resolved except for angina on exertion. One month later, elective aortic valve replacement was performed. The postoperative course was uneventful and the he was discharged on the 60th postoperative day. A follow-up echocardiogram 6 months postoperatively revealed normal prosthetic valve function and an ejection fraction of 0.6.

Hemorrhagic Tamponade as Initial Manifestation of Systemic Lupus with Subsequent Refractory and Progressive Lupus Myocarditis Resulting in Cardiomyopathy and Mitral Regurgitation.

PubMed

Marijanovich, Nicole; Halalau, Alexandra

2018-01-01

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a wide range of clinical and serological manifestations. Cardiac disease among patients with SLE is common and can involve the pericardium, myocardium, valves, conduction system, and coronary arteries. We are reporting a case of SLE in a young woman that is unique is unique in that initial symptoms consisted of pericarditis and hemorrhagic tamponade which remained progressive and resistant to aggressive immunosuppressive treatment and led to severe cardiomyopathy (ejection fraction of 25%) and severe (+4) mitral regurgitation. Her immunosuppressive treatment included hydroxychloroquine, high-dose steroids, intravenous immunoglobulins, azathioprine, and mycophenolate mofetil. Her disease progression was felt to be due to underlying uncontrolled SLE because the complement levels remained persistently low throughout the entire course and PET Myocardial Perfusion and Viability study showed stable persistent active inflammation. Eventually, she was treated with cyclophosphamide which led to improvement in ejection fraction to 55% with only mild mitral regurgitation.

Hemorrhagic Tamponade as Initial Manifestation of Systemic Lupus with Subsequent Refractory and Progressive Lupus Myocarditis Resulting in Cardiomyopathy and Mitral Regurgitation

PubMed Central

Marijanovich, Nicole

2018-01-01

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a wide range of clinical and serological manifestations. Cardiac disease among patients with SLE is common and can involve the pericardium, myocardium, valves, conduction system, and coronary arteries. We are reporting a case of SLE in a young woman that is unique is unique in that initial symptoms consisted of pericarditis and hemorrhagic tamponade which remained progressive and resistant to aggressive immunosuppressive treatment and led to severe cardiomyopathy (ejection fraction of 25%) and severe (+4) mitral regurgitation. Her immunosuppressive treatment included hydroxychloroquine, high-dose steroids, intravenous immunoglobulins, azathioprine, and mycophenolate mofetil. Her disease progression was felt to be due to underlying uncontrolled SLE because the complement levels remained persistently low throughout the entire course and PET Myocardial Perfusion and Viability study showed stable persistent active inflammation. Eventually, she was treated with cyclophosphamide which led to improvement in ejection fraction to 55% with only mild mitral regurgitation. PMID:29610699

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.

Compression therapy in mixed ulcers increases venous output and arterial perfusion.

PubMed

Mosti, Giovanni; Iabichella, Maria Letizia; Partsch, Hugo

2012-01-01

This study was conducted to define bandage pressures that are safe and effective in treating leg ulcers of mixed arterial-venous etiology. In 25 patients with mixed-etiology leg ulcers who received inelastic bandages applied with pressures from 20 to 30, 31 to 40, and 41 to 50 mm Hg, the following measurements were performed before and after bandage application to ensure patient safety throughout the investigation: laser Doppler fluxmetry (LDF) close to the ulcer under the bandage and at the great toe, transcutaneous oxygen pressure (TcPo(2)) on the dorsum of the foot, and toe pressure. Ejection fraction (EF) of the venous pump was performed to assess efficacy on venous hemodynamics. LDF values under the bandages increased by 33% (95% confidence interval [CI], 17-48; P < .01), 28% (95% CI, 12-45; P < .05), and 10% (95% CI, -7 to 28), respectively, under the three pressure ranges applied. At toe level, a significant decrease in flux of -20% (95% CI, -48 to 9; P < .05) was seen when bandage pressure >41 mm Hg. Toe pressure values and TcPo(2) showed a moderate increase, excluding a restriction to arterial perfusion induced by the bandages. Inelastic bandages were highly efficient in improving venous pumping function, increasing the reduced ejection fraction by 72% (95% CI, 50%-95%; P < .001) under pressure of 21 to 30 mm Hg and by 103% (95% CI, 70%-128%; P < .001) at 31 to 40 mm Hg. In patients with mixed ulceration, an ankle-brachial pressure index >0.5 and an absolute ankle pressure of >60 mm Hg, inelastic compression of up to 40 mm Hg does not impede arterial perfusion but may lead to a normalization of the highly reduced venous pumping function. Such bandages are therefore recommended in combination with walking exercises as the basic conservative management for patients with mixed leg ulcers. Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Intravenously Delivered Mesenchymal Stem Cells: Systemic Anti-Inflammatory Effects Improve Left Ventricular Dysfunction in Acute Myocardial Infarction and Ischemic Cardiomyopathy.

PubMed

Luger, Dror; Lipinski, Michael J; Westman, Peter C; Glover, David K; Dimastromatteo, Julien; Frias, Juan C; Albelda, M Teresa; Sikora, Sergey; Kharazi, Alex; Vertelov, Grigory; Waksman, Ron; Epstein, Stephen E

2017-05-12

Virtually all mesenchymal stem cell (MSC) studies assume that therapeutic effects accrue from local myocardial effects of engrafted MSCs. Because few intravenously administered MSCs engraft in the myocardium, studies have mainly utilized direct myocardial delivery. We adopted a different paradigm. To test whether intravenously administered MSCs reduce left ventricular (LV) dysfunction both post-acute myocardial infarction and in ischemic cardiomyopathy and that these effects are caused, at least partly, by systemic anti-inflammatory activities. Mice underwent 45 minutes of left anterior descending artery occlusion. Human MSCs, grown chronically at 5% O 2 , were administered intravenously. LV function was assessed by serial echocardiography, 2,3,5-triphenyltetrazolium chloride staining determined infarct size, and fluorescence-activated cell sorting assessed cell composition. Fluorescent and radiolabeled MSCs (1×10 6 ) were injected 24 hours post-myocardial infarction and homed to regions of myocardial injury; however, the myocardium contained only a small proportion of total MSCs. Mice received 2×10 6 MSCs or saline intravenously 24 hours post-myocardial infarction (n=16 per group). At day 21, we harvested blood and spleens for fluorescence-activated cell sorting and hearts for 2,3,5-triphenyltetrazolium chloride staining. Adverse LV remodeling and deteriorating LV ejection fraction occurred in control mice with large infarcts (≥25% LV). Intravenous MSCs eliminated the progressive deterioration in LV end-diastolic volume and LV end-systolic volume. MSCs significantly decreased natural killer cells in the heart and spleen and neutrophils in the heart. Specific natural killer cell depletion 24 hours pre-acute myocardial infarction significantly improved infarct size, LV ejection fraction, and adverse LV remodeling, changes associated with decreased neutrophils in the heart. In an ischemic cardiomyopathy model, mice 4 weeks post-myocardial infarction were randomized to tail-vein injection of 2×10 6 MSCs, with injection repeated at week 3 (n=16) versus PBS control (n=16). MSCs significantly increased LV ejection fraction and decreased LV end-systolic volume. Intravenously administered MSCs for acute myocardial infarction attenuate the progressive deterioration in LV function and adverse remodeling in mice with large infarcts, and in ischemic cardiomyopathy, they improve LV function, effects apparently modulated in part by systemic anti-inflammatory activities. © 2017 American Heart Association, Inc.

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.

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.

Left Ventricular Reverse Remodeling With Biventricular Versus Right Ventricular Pacing in Patients With Atrioventricular Block and Heart Failure in the BLOCK HF Trial.

PubMed

St John Sutton, Martin; Plappert, Ted; Adamson, Philip B; Li, Pei; Christman, Shelly A; Chung, Eugene S; Curtis, Anne B

2015-05-01

Biventricular pacing in heart failure (HF) improves survival, relieves symptoms, and attenuates left ventricular (LV) remodeling. However, little is known about biventricular pacing in HF patients with atrioventricular block because they are typically excluded from biventricular trials. The Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) trial randomized patients with atrioventricular block, New York Heart Association symptom classes I to III HF, and LV ejection fraction ≤50% to biventricular or right ventricular pacing. Doppler echocardiograms were obtained at randomization (after 30 to 60 days of right ventricular pacing postimplant) and every 6 months through 24 months. Data analysis comparing changes in 10 prespecified echo parameters over time was conducted using a Bayesian design. LV end systolic volume index was also evaluated as a predictor of mortality/morbidity. Of 691 randomized subjects, 624 had paired Doppler echocardiogram data for ≥1 analyses at 6, 12, 18, or 24 months. Biventricular pacing significantly reduced LV volume indices and intraventricular mechanical delay, and improved LV ejection fraction, consistent with LV reverse remodeling. These parameters showed little change with right ventricular pacing alone, indicating no systematic reverse remodeling with right ventricular pacing. LV end systolic volume index was predictive of mortality/morbidity; the estimated risk increased up to 1% for every 1 mL/m(2) increase in LV end systolic volume index. LV end systolic volume index is a significant predictor of mortality/morbidity in this population. Cardiac structure and function are improved with biventricular pacing for patients with atrioventricular block and LV systolic dysfunction. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00267098. © 2015 American Heart Association, Inc.

The ratio of (18)F-FDG activity uptake between the right and left ventricle in patients with pulmonary hypertension correlates with the right ventricular function.

PubMed

Yang, Tao; Wang, Lei; Xiong, Chang-Ming; He, Jian-Guo; Zhang, Yan; Gu, Qing; Zhao, Zhi-Hui; Ni, Xin-Hai; Fang, Wei; Liu, Zhi-Hong

2014-05-01

It is known that patients with pulmonary hypertension (PH) can have elevated F-FDG uptake in the right ventricle (RV) on PET imaging. This study was designed to assess possible relationship between FDG uptake of ventricles and the function/hemodynamics of the RV in patients with PH. Thirty-eight patients with PH underwent FDG PET imaging in both fasting and glucose-loading conditions. The standard uptake value (SUVs) corrected for partial volume effect in both RV and left ventricle (LV) were measured. The ratio of FDG uptake between RV to LV (SUVR/L) was calculated. Right heart catheterization and cardiac magnetic resonance (CMR) were performed in all patients within 1 week. The FDG uptake levels by the ventricles were compared with the result form the right heart catheterization and CMR. The SUV of RV (SUVR) and SUV of LV were significantly higher in glucose-loading condition than in fasting condition. In both fasting and glucose-loading conditions, SUVR and SUVR/L showed reverse correlation with right ventricular ejection fraction derived from CMR. In addition, in both fasting and glucose-loading conditions, SUVR and SUVR/L showed positive correlations with pulmonary vascular resistance. However, only SUVR/L in glucose-loading condition could independently predict right ventricular ejection fraction after adjusted for age, body mass index, sex, mean right atrial pressure, mean pulmonary arterial pressure, and pulmonary vascular resistance (P = 0.048). The FDG uptake of RV increases with decreased right ventricular function in patients with PH. Increased FDG uptake ratio between RV and LV might be useful to assess the right ventricular function.

Enhancement of organ regeneration in animal models by a stem cell-stimulating plant mixture.

PubMed

Kiss, István; Tibold, Antal; Halmosi, Róbert; Bartha, Eva; Koltai, Katalin; Orsós, Zsuzsanna; Bujdosó, László; Ember, István

2010-06-01

Adult stem cells play an important role in the regeneration of damaged organs. Attempts have already been made to enhance stem cell production by cytokines, in order to increase the improvement of cardiac functions after myocardial infarction. In our present study we investigated the possibility whether instead of cytokine injection dietary stimulation of stem cell production accelerates the organ regeneration in animals. A dietary supplement, Olimpiq StemXCell (Crystal Institute Ltd., Eger, Hungary), containing plant extracts (previously proved to increase the number of circulating CD34(+) cells) was consumed in human equivalent doses by the experimental animals. In the first experiment carbon tetrachloride was applied to CBA/Ca mice, to induce liver damage, and liver weights between StemXCell-fed and control animals were compared 10 days after the treatment. In the second model experimental diabetes was induced in F344 rats by alloxan. Blood sugar levels were measured for 5 weeks in the control and StemXCell-fed groups. The third part of the study investigated the effect of StemXCell on cardiac functions. Eight weeks after causing a myocardial infarction in Wistar rats by isoproterenol, left ventricular ejection fraction was determined as a functional parameter of myocardial regeneration. In all three animal models StemXCell consumption statistically significantly improved the organ regeneration (relative liver weights, 4.78 +/-0.06 g/100 g vs. 4.97 +/- 0.07 g/100 g; blood sugar levels at week 5, 16 +/- 1.30 mmol/L vs. 10.2 +/- 0.92 mmol/L; ejection fraction, 57.5 +/- 2.23 vs. 68.2 +/- 4.94; controls vs. treated animals, respectively). Our study confirms the hypothesis that dietary enhancement of stem cell production may protect against organ injuries and helps in the regeneration.

The overloaded right heart and ventricular interdependence.

PubMed

Naeije, Robert; Badagliacca, Roberto

2017-10-01

The right and the left ventricle are interdependent as both structures are nested within the pericardium, have the septum in common and are encircled with common myocardial fibres. Therefore, right ventricular volume or pressure overloading affects left ventricular function, and this in turn may affect the right ventricle. In normal subjects at rest, right ventricular function has negligible interaction with left ventricular function. However, the right ventricle contributes significantly to the normal cardiac output response to exercise. In patients with right ventricular volume overload without pulmonary hypertension, left ventricular diastolic compliance is decreased and ejection fraction depressed but without intrinsic alteration in contractility. In patients with right ventricular pressure overload, left ventricular compliance is decreased with initial preservation of left ventricular ejection fraction, but with eventual left ventricular atrophic remodelling and altered systolic function. Breathing affects ventricular interdependence, in healthy subjects during exercise and in patients with lung diseases and altered respiratory system mechanics. Inspiration increases right ventricular volumes and decreases left ventricular volumes. Expiration decreases both right and left ventricular volumes. The presence of an intact pericardium enhances ventricular diastolic interdependence but has negligible effect on ventricular systolic interdependence. On the other hand, systolic interdependence is enhanced by a stiff right ventricular free wall, and decreased by a stiff septum. Recent imaging studies have shown that both diastolic and systolic ventricular interactions are negatively affected by right ventricular regional inhomogeneity and prolongation of contraction, which occur along with an increase in pulmonary artery pressure. The clinical relevance of these observations is being explored. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Effect of Age, Estrogen Status, and Late-Life GPER Activation on Cardiac Structure and Function in the Fischer344×Brown Norway Female Rat.

PubMed

Alencar, Allan K; da Silva, Jaqueline S; Lin, Marina; Silva, Ananssa M; Sun, Xuming; Ferrario, Carlos M; Cheng, Cheping; Sudo, Roberto T; Zapata-Sudo, Gisele; Wang, Hao; Groban, Leanne

2017-02-01

Age-associated changes in cardiac structure and function, together with estrogen loss, contribute to the progression of heart failure with preserved ejection fraction in older women. To investigate the effects of aging and estrogen loss on the development of its precursor, asymptomatic left ventricular diastolic dysfunction, echocardiograms were performed in 10 middle-aged (20 months) and 30 old-aged (30 months) female Fischer344×Brown-Norway rats, 4 and 8 weeks after ovariectomy (OVX) and sham procedures (gonads left intact). The cardioprotective potential of administering chronic G1, the selective agonist to the new G-protein-coupled estrogen receptor (GPER), was further evaluated in old rats (Old-OVX+G1) versus age-matched, vehicle-treated OVX and gonadal intact rats. Advanced age and estrogen loss led to decreases in myocardial relaxation and elevations in filling pressure, in part, due to reductions in phosphorylated phospholamban and increases in cardiac collagen deposition. Eight weeks of G-protein-coupled estrogen receptor activation in Old-OVX+G1 rats reversed the adverse effects of age and estrogen loss on myocardial relaxation through increases in sarcoplasmic reticulum Ca 2+ ATPase expression and reductions in interstitial fibrosis. These findings may explain the preponderance of heart failure with preserved ejection fraction in older postmenopausal women and provide a promising, late-life therapeutic target to reverse or halt the progression of left ventricular diastolic dysfunction. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Comparison of Causes of Death After Heart Transplantation in Patients With Left Ventricular Ejection Fractions ≤35% Versus >35.

PubMed

Birati, Edo Y; Mathelier, Hansie; Molina, Maria; Hanff, Thomas C; Mazurek, Jeremy A; Atluri, Pavan; Acker, Michael A; Rame, J Eduardo; Margulies, Kenneth B; Goldberg, Lee R; Jessup, Mariell

2016-04-15

Sudden cardiac death (SCD) is a common cause of death in the general population, occurring in 300,000 to 350,000 people in the United States alone. Currently, there are no data supporting implantable cardioverter-defibrillator therapy in patients who underwent orthotopic heart transplant (OHT) with low left ventricular ejection fraction (LVEF). In this retrospective study, we included all patients who underwent primary OHT at our institution from 2007 to 2013. We compared the cause of death in patients who underwent OHT and evaluated the correlation of the cause of death and the patients' LVEF. Our objectives were to determine whether patients who underwent OHT with LVEF <35% are at increased risk for SCD compared with those who underwent OHT with normal LVEF. To summarize our results, a total of 345 patients were included in our study (mean age 50 ± 14 years, 68% men). The mean follow-up was 1,260 ± 698 days. Forty patients (11.5%) died >6 months after OHT. Surviving patients had higher LVEF compared with deceased patients (64 ± 7% and 50 ± 24%, respectively, p ≤0.001). In all, 10 (25%) of the deceased patients died suddenly, 9 (23%) from sepsis, and 8 (20%) from malignancy. Of the 11 deceased patients with LVEF ≤35%, 2 patients (18%) died suddenly compared with 9 SCDs among the 29 deceased patients (31%) with LVEF >35% (p = 0.54). In conclusion, patients who underwent OHT who died were more likely to have LVEF <35%, and a quarter of the deceased patients who underwent OHT died suddenly. A reduced LVEF was not associated with an increased risk of SCD. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Effects of omega-3 fatty acids on resting heart rate, heart rate recovery after exercise, and heart rate variability in men with healed myocardial infarctions and depressed ejection fractions.

PubMed

O'Keefe, James H; Abuissa, Hussam; Sastre, Antonio; Steinhaus, David M; Harris, William S

2006-04-15

We explored possible mechanisms by which recommended intakes of omega-3 fatty acids may decrease the risk for sudden cardiac death in patients with documented coronary heart disease. The cardioprotective effects of omega-3 fatty acids have been documented in epidemiologic and randomized controlled trials. These fatty acids are presumed to decrease susceptibility to fatal arrhythmias, but whether this is mediated by classic risk factors or direct cardiac mechanisms is not known. Eighteen white men with a history of myocardial infarction and ejection fractions <40% were randomized to placebo or omega-3 fatty acids (585 mg of docosahexaenoic acid and 225 mg of eicosapentaenoic acid) for two 4-month periods in a crossover design. At the end of each period, heart rate (HR), HR variability, and rate of HR recovery after exercise were determined, as were effects on arterial compliance, blood pressure, cardiac function, and fasting serum levels of lipids and inflammatory markers. Omega-3 fatty acids decreased HR at rest from 73 +/- 13 to 68 +/- 13 beats/min (p <0.0001) and improved 1-minute HR recovery after exercise (-27 +/- 10 to -32 +/- 12 beats/min, p <0.01). HR variability in the high-frequency band increased (p <0.02), but no change was noted in overall HR variability. There were no significant effects on blood pressure, arterial compliance, lipids, or inflammatory markers. These changes are consistent with an increase in vagal activity and may in part explain the observed decrease in risk for sudden cardiac death seen with omega-3 fatty acid supplementation.

Relationship between angina pectoris and outcomes in patients with heart failure and reduced ejection fraction: an analysis of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA).

PubMed

Badar, Athar A; Perez-Moreno, Ana Cristina; Jhund, Pardeep S; Wong, Chih M; Hawkins, Nathaniel M; Cleland, John G F; van Veldhuisen, Dirk J; Wikstrand, John; Kjekshus, John; Wedel, Hans; Watkins, Stuart; Gardner, Roy S; Petrie, Mark C; McMurray, John J V

2014-12-21

Angina pectoris is common in patients with heart failure and reduced ejection fraction (HF-REF) but its relationship with outcomes has not been well defined. This relationship was investigated further in a retrospective analysis of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). Four thousand, eight hundred and seventy-eight patients were divided into three categories: no history of angina and no chest pain at baseline (Group A; n = 1240), past history of angina but no chest pain at baseline (Group B; n = 1353) and both a history of angina and chest pain at baseline (Group C; n = 2285). Outcomes were examined using Kaplan-Meier and Cox regression survival analysis. Compared with Group A, Group C had a higher risk of non-fatal myocardial infarction or unstable angina (HR: 2.36, 1.54-3.61; P < 0.001), this composite plus coronary revascularization (HR: 2.54, 1.76-3.68; P < 0.001), as well as HF hospitalization (HR: 1.35, 1.13-1.63; P = 0.001), over a median follow-up period of 33 months. There was no difference in cardiovascular or all-cause mortality. Group B had a smaller increase in risk of coronary events but not of heart failure hospitalization. Patients with HF-REF and ongoing angina are at an increased risk of acute coronary syndrome and HF hospitalization. Whether these patients would benefit from more aggressive medical therapy or percutaneous revascularization is not known and merits further investigation. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

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

Prognostic value of coronary collaterals in patients with acute coronary syndromes.

PubMed

Kurtul, Alparslan; Ozturk, Selcuk

2017-08-01

The presence of good coronary collateral circulation (CCC) can protect and preserve myocardium from ischemia, increase myocardial contractility, and reduce adverse clinical events. However, its impact on mortality is still a topic of debate, particularly in acute coronary syndrome (ACS). The aim of this study was to investigate the association of CCC with cardiac risk factors and in-hospital mortality in patients hospitalized with a diagnosis of ACS. The study population included 2286 patients with ACS who underwent coronary angiography and were found to have at least 90% significant lesion in at least one major coronary artery. The CCC was graded according to the Rentrop classification. The patients were classified into a poor CCC group (Rentrop grades 0-1, n=1859) or a good CCC group (Rentrop grades 2-3, n=427). Patients with good CCC had more high-risk patient characteristics such as older age, higher rate of Killip class of at least 2 at admission, lower left ventricular ejection fraction, and impaired renal functions compared with the patients with poor CCC. In multivariate analysis, the presence of good CCC [odds ratio (OR): 2.000; 95% confidence interval: 1.116-3.585; P=0.020], left ventricular ejection fraction less than 40% (OR: 2.381; P=0.003), Killip class of at least 2 at admission (OR: 3.609; P<0.001), age of at least 65 years (OR: 2.975; P=0.003), and hemoglobin (OR: 0.797; P=0.003) were independent predictors of in-hospital mortality. In contrast to previous studies, our study did not confirm a beneficial role of good CCC in patients with ACS; the presence of good CCC was even independently associated with increased in-hospital mortality in the multivariate analysis.

Risk factors for gallbladder contractility after cholecystolithotomy in elderly high-risk surgical patients

PubMed Central

Wang, Tao; Luo, Hao; Yan, Hong-tao; Zhang, Guo-hu; Liu, Wei-hui; Tang, Li-jun

2017-01-01

Objective Cholecystolithiasis is a common disease in the elderly patient. The routine therapy is open or laparoscopic cholecystectomy. In the previous study, we designed a minimally invasive cholecystolithotomy based on percutaneous cholecystostomy combined with a choledochoscope (PCCLC) under local anesthesia. Methods To investigate the effect of PCCLC on the gallbladder contractility function, PCCLC and laparoscope combined with a choledochoscope were compared in this study. Results The preoperational age and American Society of Anesthesiologists (ASA) scores, as well as postoperational lithotrity rate and common biliary duct stone rate in the PCCLC group, were significantly higher than the choledochoscope group. However, the pre- and postoperational gallbladder ejection fraction was not significantly different. Univariable and multivariable logistic regression analyses indicated that the preoperational thickness of gallbladder wall (odds ratio [OR]: 0.540; 95% confidence interval [CI]: 0.317–0.920; P=0.023) and lithotrity (OR: 0.150; 95% CI: 0.023–0.965; P=0.046) were risk factors for postoperational gallbladder ejection fraction. The area under receiver operating characteristics curve was 0.714 (P=0.016; 95% CI: 0.553–0.854). Conclusion PCCLC strategy should be carried out cautiously. First, restricted by the diameter of the drainage tube, the PCCLC should be used only for small gallstones in high-risk surgical patients. Second, the usage of lithotrity should be strictly limited to avoid undermining the gallbladder contractility and increasing the risk of secondary common bile duct stones. PMID:28138229

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.

Implications of gallbladder cholesterolosis and cholesterol polyps?

PubMed

Dairi, Saif; Demeusy, Andrew; Sill, Anne M; Patel, Shirali T; Kowdley, Gopal C; Cunningham, Steven C

2016-02-01

The clinical significance of cholesterolosis has not been well established but there are some provocative, if not robust, studies of the role it may play in the pathophysiology of pancreatitis and biliary dyskinesia, as well as hypercholesterolemia. Our aim was to take advantage of a very large cholecystectomy (CCY) database to support or refute these potentially important reported associations. A retrospective review of 6868 patients who underwent CCY from 2001-2013 was performed. Comparisons were made using the student t-test for continuous and chi-square analysis for categorical, variables. Among patients for whom the CCY was the primary operation, 1053 (18%) had cholesterolosis and 4596 did not. Compared to those without cholesterolosis, those with cholesterolosis were no more likely to have elevated cholesterol levels (P = 0.64) nor low gallbladder ejection fraction (P = 0.2). To evaluate cholesterolosis as a cause of pancreatitis, all patients with gallstones were eliminated, leaving 639 patients. Among these, not only was cholesterolosis not associated with more pancreatitis, but rather there was not a single patient with or without cholesterolosis who had pancreatitis. Despite prior reports of associations between cholesterolosis and elevated serum cholesterol, depressed ejection fraction, and increased risk of pancreatitis, careful analysis of this current, larger data set does not support these associations. Any patient with stones or sludge, or with biliary dyskinesia, and appropriate symptoms, should be considered for CCY, with or without suspected cholesterolosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Determination of right ventricular ejection fraction in children with cystic fibrosis, using krypton-81m

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

Piepsz, A.; Ham, H.R.; Millet, E.

1984-01-01

The diagnosis of cor pulmonale and incipient heart failure remains difficult to assess in cystic fibrosis (CF) on the basis of the clinical as well as the biological parameters. The measurement of the right ventricular ejection fraction has been facilitated these last years by the introduction of the radionuclide methods. Methodological difficulties are however encountered when Tc-99m RBC are used, and are mainly related to heart chambers superposition (equilibrium method) or the low count density (first pass method). Few papers have been published on RVEF in cystic fibrosis and the results are somewhat contradictory. The authors have recently introduced amore » new method for the determination of RVEF, using equilibrium study during continuous injection of Kr-81m in glucose solution. This method offers several advantages related to an increased accuracy and a favorable dosimetry. In 25 patients aged 2 to 23 years with CF, one or more RVEF studies were performed. The severity of the disease was evaluated on the basis of the clinical Schwachman score, the lung function tests, the ventilation scan and the pa02. RVEF tended to decrease with the progression of the lung disease, although, owing to the spread of the results, no RVEF could be predicted on the basis of the other parameters. The decrease of RVEF in patients with advanced lung disease was moderate and terminal lung disease was sometimes associated with normal right heart contractility.« less

Sacubitril/Valsartan: The Newest Addition to the Toolbox for Guideline-Directed Medical Therapy of Heart Failure.

PubMed

Rodgers, Jo E

2017-06-01

Sacubitril/valsartan combines a neprilysin inhibitor with an angiotensin receptor blocker. As an inhibitor of neprilysin, an enzyme that degrades biologically active natriuretic peptides, this first-in-class therapy increases levels of circulating natriuretic peptides, resulting in natriuretic, diuretic, and vasodilatory effects. In patients with chronic New York Heart Association class II-IV heart failure with reduced ejection fraction, the PARADIGM-HF trial demonstrated that sacubitril/valsartan significantly reduced the primary endpoint of cardiovascular mortality and heart failure hospitalization, compared with enalapril. The rate of all-cause mortality was also significantly reduced. Subsequently, the American College of Cardiology/American Heart Association/Heart Failure Society of America recently updated guideline recommendations for Stage C patients with heart failure with reduced ejection fraction to recommend angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril/valsartan in conjunction with other evidence-based therapies to reduce morbidity and mortality. Several analyses have suggested the cost-effectiveness of this new therapy. To ensure tolerability, initiating the lower dosage form of sacubitril/valsartan is warranted in patients with severe renal impairment, moderate hepatic impairment, and low blood pressure, and close monitoring is warranted in such patients. A 36-hour washout period is recommended when switching patients from an angiotensin-converting enzyme inhibitor to sacubitril/valsartan. Similarly, sacubitril/valsartan is contraindicated in patients receiving concomitant angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and those with a history of angioedema. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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

Factors Associated with Delayed Ejection in Mishaps Between 1993 and 2013.

PubMed

Miles, John E

2015-09-01

The purpose of this investigation was to identify factors associated with Air Force aviators delaying ejection during in-flight emergencies. The investigator reviewed all reports within the Air Force Safety Automated System describing mishaps that resulted in the destruction of Air Force ejection-seat equipped aircraft between 1993 and 2013. Crewmembers were classified as either timely or delayed ejectors based on altitude at onset of emergency, altitude at ejection, and a determination regarding whether or not the aircraft was controlled during the mishap sequence. Univariate analysis and multivariate logistic regression were used to explore the association between delayed ejection and multiple potential risk factors. In total, 366 crewmembers were involved in in-flight emergencies in ejection-seat-equipped aircraft that resulted in the loss of the aircraft; 201 (54.9%) of these crewmembers delayed ejection until their aircraft had descended below recommended minimum ejection altitudes. Multivariate analysis indicated that independent risk factors for delayed ejection included increased crewmember flight hours and a mechanical or human-factors related cause of the emergency versus bird strike or midair collision. This investigation provided quantitative assessments of factors associated with aviators delaying ejection during in-flight emergencies. Increased odds of delay among crewmembers with greater than 1500 total flight hours suggests that complacency and overconfidence may adversely influence the ejection decision to at least as great a degree as inexperience. Increased odds of delay during mechanical and human factors mishaps confirms previously reported hypotheses and reaffirms the importance of targeting these areas to reduce aviator injuries and fatalities.

Jet behaviors and ejection mode recognition of electrohydrodynamic direct-write

NASA Astrophysics Data System (ADS)

Zheng, Jianyi; Zhang, Kai; Jiang, Jiaxin; Wang, Xiang; Li, Wenwang; Liu, Yifang; Liu, Juan; Zheng, Gaofeng

2018-01-01

By introducing image recognition and micro-current testing, jet behavior research was conducted, in which the real-time recognition of ejection mode was realized. To study the factors influencing ejection modes and the current variation trends under different modes, an Electrohydrodynamic Direct-Write (EDW) system with functions of current detection and ejection mode recognition was firstly built. Then a program was developed to recognize the jet modes. As the voltage applied to the metal tip increased, four jet ejection modes in EDW occurred: droplet ejection mode, Taylor cone ejection mode, retractive ejection mode and forked ejection mode. In this work, the corresponding relationship between the ejection modes and the effect on fiber deposition as well as current was studied. The real-time identification of ejection mode and detection of electrospinning current was realized. The results in this paper are contributed to enhancing the ejection stability, providing a good technical basis to produce continuous uniform nanofibers controllably.

Interleukin-1 Blockade With Canakinumab to Improve Exercise Capacity in Patients With Chronic Systolic Heart Failure and Elevated High Sensitivity C-reactive Protein (Hs-CRP)

ClinicalTrials.gov

2017-09-14

Prior Acute Myocardial Infarction; Evidence of Systemic Inflammation (C Reactive Protein Plasma >2 mg/l); Reduced Left Ventricle Ejection Fraction (<50%); Symptoms of Heart Failure (NYHA Class II-III)

Cardiovascular Ultrasound of Neonatal Long Evans Rats Exposed Prenatally to Trichloroacetic Acid: Effects on Heart Rate, Ejection Fraction, and Cardiac Output

EPA Science Inventory

This abstract describes the use of a relatively new technology, cardiovascular ultrasound (echocardiography) for evaluating developmental toxicity affecting heart development. The abstract describes the effects of two known cardiac teratogens, trichloroacetic acid and dimethadio...

Body mass and atherogenic dyslipidemia as major determinants of blood levels of B-type natriuretic peptides in Arab subjects with acute coronary syndromes.

PubMed

Akanji, Abayomi O; Suresh, Cheriyil G; Al-Radwan, Reem; Fatania, Hasmukh R

2009-12-01

The plasma B-type natriuretic peptide (BNP) level is elevated in cardiac ischemia and may be useful in assessing prognosis in acute coronary syndromes (ACS). This study aimed to: (1) establish BNP levels and its determinants in a healthy Gulf Arab population and in a group of patients with acute myocardial infarction and (2) investigate associations between BNP levels and markers of myocardial damage (ejection fractions, cardiac troponin I [cTnI] levels) and inflammation (serum C-reactive protein [CRP]). We studied 2 groups of Arab subjects: (1) Healthy control (HC), 142 healthy control subjects; (2) Coronary heart disease (CHD), 257 patients with proven acute myocardial infarction within 1 day of admission. Each subject was assessed clinically, and ejection fractions (left ventricular ejection fraction [LVEF]) were determined by echocardiography in those with CHD. Fasting blood samples were processed for full blood counts and serum glucose, urea, creatinine, uric acid, and lipids (total cholesterol [TC], triglycerides [TG], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein [LDL], and apolipoprotein B [apoB]), cTnI, BNP, and high-sensitivity (hs) CRP levels. The results were compared between groups, and the associations of BNP with other parameters were explored. In comparison to HC, the CHD group had a greater waist-hip ratio (WHR) (P < 0.01), worse atherogenic profile, worse renal function, and higher values for CRP and BNP (all P < 0.001). There were no significant differences in values for BNP related to age, diabetes, hypertension, WHR, and hematocrit, although there was a consistent trend in both HC and CHD groups toward a negative relationship of BNP with body mass, TG, and apoB levels, and a positive relationship with HDL, independent only for HDL and apoB on multiple logistic regression. No correlations could be established with cTnI, CRP, and LVEF. The patterns of cross-correlations did not differ significantly with diabetic status. In an Arab population with CHD, blood levels of BNP are higher than in a healthy control population and appear correlated to body mass and atherogenic lipids but not CRP, troponin, or ejection fraction. BNP levels did not appear to be influenced by the classical CHD risk factors of diabetes, hypertension, cigarette smoking, hematocrit, or WHR. The independent link with atherogenic dyslipidemia suggests that BNP is important in atherogenesis and may not be just an index of cardiac contractile dysfunction.

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.

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%.

Stroke in Heart Failure in Sinus Rhythm: The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction Trial

PubMed Central

Pullicino, Patrick M.; Thompson, John L.P.; Sacco, Ralph L.; Sanford, Alexandra R.; Qian, Min; Teerlink, John R.; Haddad, Haissam; Diek, Monika; Freudenberger, Ronald S.; Labovitz, Arthur J.; Di Tullio, Marco R.; Lok, Dirk J.; Ponikowski, Piotr; Anker, Stefan D.; Graham, Susan; Mann, Douglas L.; Mohr, J.P.; Homma, Shunichi

2014-01-01

Background The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial found no difference between warfarin and aspirin in patients with low ejection fraction in sinus rhythm for the primary outcome: first to occur of 84 incident ischemic strokes (IIS), 7 intracerebral hemorrhages or 531 deaths. Prespecified secondary analysis showed a 48% hazard ratio reduction (p = 0.005) for warfarin in IIS. Cardioembolism is likely the main pathogenesis of stroke in heart failure. We examined the IIS benefit for warfarin in more detail in post hoc secondary analyses. Methods We subtyped IIS into definite, possible and noncardioembolic using the Stroke Prevention in Atrial Fibrillation method. Statistical tests, stratified by prior ischemic stroke or transient ischemic attack, were the conditional binomial for independent Poisson variables for rates, the Cochran-Mantel-Haenszel test for stroke subtype and the van Elteren test for modified Rankin Score (mRS) and National Institute of Health Stroke Scale (NIHSS) distributions, and an exact test for proportions. Results Twenty-nine of 1,142 warfarin and 55 of 1,163 aspirin patients had IIS. The warfarin IIS rate (0.727/100 patient-years, PY) was lower than for aspirin (1.36/100 PY, p = 0.003). Definite cardioembolic IIS was less frequent on warfarin than aspirin (0.22 vs. 0.55/100 PY, p = 0.012). Possible cardioembolic IIS tended to be less frequent on warfarin than aspirin (0.37 vs. 0.67/100 PY, p = 0.063) but noncardioembolic IIS showed no difference: 5 (0.12/100 PY) versus 6 (0.15/100 PY, p = 0.768). Among patients experiencing IIS, there were no differences by treatment arm in fatal IIS, baseline mRS, mRS 90 days after IIS, and change from baseline to post-IIS mRS. The warfarin arm showed a trend to a lower proportion of severe nonfatal IIS [mRS 3–5; 3/23 (13.0%) vs. 16/48 (33.3%), p = 0.086]. There was no difference in NIHSS at the time of stroke (p = 0.825) or in post-IIS mRS (p = 0.948) between cardioembolic, possible cardioembolic and noncardioembolic stroke including both warfarin and aspirin groups. Conclusions The observed benefits in the reduction of IIS for warfarin compared to aspirin are most significant for cardioembolic IIS among patients with low ejection fraction in sinus rhythm. This is supported by trends to lower frequencies of severe IIS and possible cardioembolic IIS in patients on warfarin compared to aspirin. PMID:23921215

Stroke in heart failure in sinus rhythm: the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial.

PubMed

Pullicino, Patrick M; Thompson, John L P; Sacco, Ralph L; Sanford, Alexandra R; Qian, Min; Teerlink, John R; Haddad, Haissam; Diek, Monika; Freudenberger, Ronald S; Labovitz, Arthur J; Di Tullio, Marco R; Lok, Dirk J; Ponikowski, Piotr; Anker, Stefan D; Graham, Susan; Mann, Douglas L; Mohr, J P; Homma, Shunichi

2013-01-01

The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial found no difference between warfarin and aspirin in patients with low ejection fraction in sinus rhythm for the primary outcome: first to occur of 84 incident ischemic strokes (IIS), 7 intracerebral hemorrhages or 531 deaths. Prespecified secondary analysis showed a 48% hazard ratio reduction (p = 0.005) for warfarin in IIS. Cardioembolism is likely the main pathogenesis of stroke in heart failure. We examined the IIS benefit for warfarin in more detail in post hoc secondary analyses. We subtyped IIS into definite, possible and noncardioembolic using the Stroke Prevention in Atrial Fibrillation method. Statistical tests, stratified by prior ischemic stroke or transient ischemic attack, were the conditional binomial for independent Poisson variables for rates, the Cochran-Mantel-Haenszel test for stroke subtype and the van Elteren test for modified Rankin Score (mRS) and National Institute of Health Stroke Scale (NIHSS) distributions, and an exact test for proportions. Twenty-nine of 1,142 warfarin and 55 of 1,163 aspirin patients had IIS. The warfarin IIS rate (0.727/100 patient-years, PY) was lower than for aspirin (1.36/100 PY, p = 0.003). Definite cardioembolic IIS was less frequent on warfarin than aspirin (0.22 vs. 0.55/100 PY, p = 0.012). Possible cardioembolic IIS tended to be less frequent on warfarin than aspirin (0.37 vs. 0.67/100 PY, p = 0.063) but noncardioembolic IIS showed no difference: 5 (0.12/100 PY) versus 6 (0.15/100 PY, p = 0.768). Among patients experiencing IIS, there were no differences by treatment arm in fatal IIS, baseline mRS, mRS 90 days after IIS, and change from baseline to post-IIS mRS. The warfarin arm showed a trend to a lower proportion of severe nonfatal IIS [mRS 3-5; 3/23 (13.0%) vs. 16/48 (33.3%), p = 0.086]. There was no difference in NIHSS at the time of stroke (p = 0.825) or in post-IIS mRS (p = 0.948) between cardioembolic, possible cardioembolic and noncardioembolic stroke including both warfarin and aspirin groups. The observed benefits in the reduction of IIS for warfarin compared to aspirin are most significant for cardioembolic IIS among patients with low ejection fraction in sinus rhythm. This is supported by trends to lower frequencies of severe IIS and possible cardioembolic IIS in patients on warfarin compared to aspirin. Copyright © 2013 S. Karger AG, Basel.

Effect of Levosimendan on Low Cardiac Output Syndrome in Patients With Low Ejection Fraction Undergoing Coronary Artery Bypass Grafting With Cardiopulmonary Bypass

PubMed Central

Caruba, Thibaut; Grosjean, Sandrine; Amour, Julien; Ouattara, Alexandre; Villacorta, Judith; Miguet, Bertrand; Guinet, Patrick; Lévy, François; Squara, Pierre; Aït Hamou, Nora; Carillon, Aude; Boyer, Julie; Boughenou, Marie-Fazia; Rosier, Sebastien; Robin, Emmanuel; Radutoiu, Mihail; Durand, Michel; Guidon, Catherine; Desebbe, Olivier; Charles-Nelson, Anaïs; Menasché, Philippe; Rozec, Bertrand; Girard, Claude; Fellahi, Jean-Luc; Pirracchio, Romain; Chatellier, Gilles

2017-01-01

Importance Low cardiac output syndrome after cardiac surgery is associated with high morbidity and mortality in patients with impaired left ventricular function. Objective To assess the ability of preoperative levosimendan to prevent postoperative low cardiac output syndrome. Design, Setting, and Participants Randomized, double-blind, placebo-controlled trial conducted in 13 French cardiac surgical centers. Patients with a left ventricular ejection fraction less than or equal to 40% and scheduled for isolated or combined coronary artery bypass grafting with cardiopulmonary bypass were enrolled from June 2013 until May 2015 and followed during 6 months (last follow-up, November 30, 2015). Interventions Patients were assigned to a 24-hour infusion of levosimendan 0.1 µg/kg/min (n = 167) or placebo (n = 168) initiated after anesthetic induction. Main Outcomes and Measures Composite end point reflecting low cardiac output syndrome with need for a catecholamine infusion 48 hours after study drug initiation, need for a left ventricular mechanical assist device or failure to wean from it at 96 hours after study drug initiation when the device was inserted preoperatively, or need for renal replacement therapy at any time postoperatively. It was hypothesized that levosimendan would reduce the incidence of this composite end point by 15% in comparison with placebo. Results Among 336 randomized patients (mean age, 68 years; 16% women), 333 completed the trial. The primary end point occurred in 87 patients (52%) in the levosimendan group and 101 patients (61%) in the placebo group (absolute risk difference taking into account center effect, −7% [95% CI, −17% to 3%]; P = .15). Predefined subgroup analyses found no interaction with ejection fraction less than 30%, type of surgery, and preoperative use of β-blockers, intra-aortic balloon pump, or catecholamines. The prevalence of hypotension (57% vs 48%), atrial fibrillation (50% vs 40%), and other adverse events did not significantly differ between levosimendan and placebo. Conclusions and Relevance Among patients with low ejection fraction who were undergoing coronary artery bypass grafting with cardiopulmonary bypass, levosimendan compared with placebo did not result in a significant difference in the composite end point of prolonged catecholamine infusion, use of left ventricular mechanical assist device, or renal replacement therapy. These findings do not support the use of levosimendan for this indication. Trial Registration EudraCT Number: 2012-000232-25; clinicaltrials.gov Identifier: NCT02184819 PMID:28787507

Hemodynamic changes during weaning: can we assess and predict cardiac-related weaning failure by transthoracic echocardiography?

PubMed Central

2010-01-01

Cardiac-related failure of weaning from mechanical ventilation is an important reason for prolonged mechanical ventilation, intensive care unit treatment, and increased morbidity and mortality. When transthoracic echocardiography (TTE) is routinely performed before a weaning trial, patients at high risk of cardiac-related failure can be detected by low left ventricular (LV) ejection fraction, diastolic dysfunction, and elevated LV filling pressure. During the weaning trial, a further increase of LV filling pressure and progression of diastolic failure can be observed by repeated TTE. Owing to certain limitations concerning patients and methodology, TTE cannot be employed in every patient and invasive hemodynamic monitoring is still mandatory in selected patients with repetitive weaning failure. PMID:20619005

Hemodynamic changes during weaning: can we assess and predict cardiac-related weaning failure by transthoracic echocardiography?

PubMed

Voga, Gorazd

2010-01-01

Cardiac-related failure of weaning from mechanical ventilation is an important reason for prolonged mechanical ventilation, intensive care unit treatment, and increased morbidity and mortality. When transthoracic echocardiography (TTE) is routinely performed before a weaning trial, patients at high risk of cardiac-related failure can be detected by low left ventricular (LV) ejection fraction, diastolic dysfunction, and elevated LV filling pressure. During the weaning trial, a further increase of LV filling pressure and progression of diastolic failure can be observed by repeated TTE. Owing to certain limitations concerning patients and methodology, TTE cannot be employed in every patient and invasive hemodynamic monitoring is still mandatory in selected patients with repetitive weaning failure.

Postural effects on the noninvasive baselines of ventricular performance

NASA Technical Reports Server (NTRS)

Lance, V. Q.; Spodick, D. H.

1977-01-01

The effects of posture on time-based noninvasive measurements were determined utilizing the sequence supine-sitting-standing in a formal protocol in which observer biases were eliminated by blinding the measurement and calculation phases. Compared to the supine posture, the sitting and standing postures produced significant increases in heart rate, isovolumic contraction time, pre-ejection period and pre-ejection period/left-ventricular ejection time and significant decreases in ejection time and ejection time index. The response patterns are consistent with the hemodynamic correlates cited in the literature which show increased adrenergic activity and decreased venous return in the sitting and standing postures, the effect on venous return being dominant.

The velocity and composition of supernova ejecta

NASA Technical Reports Server (NTRS)

Colgate, S. A.

1971-01-01

In case of the Gum nebula, a pulsar - a presumed neutron star - is believed to be a relic of the supernova explosion. Regardless of the mechanism of the explosion, the velocity distribution and composition of the ejected matter will be roughly the same. The reimploding mass fraction is presumed to be neutron rich. The final composition is thought to be roughly 1/3 iron and 2/3 silicon, with many small fractions of elements from helium to iron. The termination of helium shell burning occurs because the shell is expanded and cooled by radiation stress. The mass fraction of the helium burning shell was calculated.

Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction).

PubMed

Schroten, Nicolas F; Damman, Kevin; Hemmelder, Marc H; Voors, Adriaan A; Navis, Gerjan; Gaillard, Carlo A J M; van Veldhuisen, Dirk J; Van Gilst, Wiek H; Hillege, Hans L

2015-05-01

We examined the effect of the renin inhibitor, aliskiren, on renal blood flow (RBF) in patients with heart failure with reduced ejection fraction (HFREF) and decreased glomerular filtration rate (GFR). Renal blood flow is the main determinant of GFR in HFREF patients. Both reduced GFR and RBF are associated with increased mortality. Aliskiren can provide additional renin-angiotensin-aldosterone system inhibition and increases RBF in healthy individuals. Patients with left ventricular ejection fraction ≤45% and estimated GFR 30 to 75 mL/min per 1.73 m(2) on optimal medical therapy were randomized 2:1 to receive aliskiren 300 mg once daily or placebo. Renal blood flow and GFR were measured using radioactive-labeled (125)I-iothalamate and (131)I-hippuran at baseline and 26 weeks. After 41 patients were included, the trial was halted based on an interim safety analysis showing futility. Mean age was 68 ± 9 years, 82% male, GFR (49 ± 16 mL/min per 1.73 m(2)), RBF (294 ± 77 mL/min per 1.73 m(2)), and NT-proBNP 999 (435-2040) pg/mL. There was a nonsignificant change in RBF after 26 weeks in the aliskiren group compared with placebo (-7.1 ± 30 vs +14 ± 54 mL/min per 1.73 m(2); P = .16). However, GFR decreased significantly in the aliskiren group compared with placebo (-2.8 ± 6.0 vs +4.4 ± 9.6 mL/min per 1.73 m(2); P = .01) as did filtration fraction (-2.2 ± 3.3 vs +1.1 ± 3.1%; P = .01). There were no significant differences in plasma aldosterone, NT-proBNP, urinary tubular markers, or adverse events. Plasma renin activity was markedly reduced in the aliskiren group versus placebo throughout the treatment phase (P = .007). Adding aliskiren on top of optimal HFREF medical therapy did not improve RBF and was associated with a reduction of GFR and filtration fraction. Copyright © 2015 Mosby, Inc. All rights reserved.

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

Genda, H.; Kobayashi, H.; Kokubo, E., E-mail: genda@elsi.jp

In our solar system, Mars-sized protoplanets frequently collided with each other during the last stage of terrestrial planet formation, called the giant impact stage. Giant impacts eject a large amount of material from the colliding protoplanets into the terrestrial planet region, which may form debris disks with observable infrared excesses. Indeed, tens of warm debris disks around young solar-type stars have been observed. Here we quantitatively estimate the total mass of ejected materials during the giant impact stages. We found that ∼0.4 times the Earth’s mass is ejected in total throughout the giant impact stage. Ejected materials are ground down bymore » collisional cascade until micron-sized grains are blown out by radiation pressure. The depletion timescale of these ejected materials is determined primarily by the mass of the largest body among them. We conducted high-resolution simulations of giant impacts to accurately obtain the mass of the largest ejected body. We then calculated the evolution of the debris disks produced by a series of giant impacts and depleted by collisional cascades to obtain the infrared excess evolution of the debris disks. We found that the infrared excess is almost always higher than the stellar infrared flux throughout the giant impact stage (∼100 Myr) and is sometimes ∼10 times higher immediately after a giant impact. Therefore, giant impact stages would explain the infrared excess from most observed warm debris disks. The observed fraction of stars with warm debris disks indicates that the formation probability of our solar-system-like terrestrial planets is approximately 10%.« less

Searching for Biosignatures in Exoplanetary Impact Ejecta

NASA Astrophysics Data System (ADS)

Cataldi, Gianni; Brandeker, Alexis; Thébault, Philippe; Singer, Kelsi; Ahmed, Engy; de Vries, Bernard L.; Neubeck, Anna; Olofsson, Göran

2017-08-01

With the number of confirmed rocky exoplanets increasing steadily, their characterization and the search for exoplanetary biospheres are becoming increasingly urgent issues in astrobiology. To date, most efforts have concentrated on the study of exoplanetary atmospheres. Instead, we aim to investigate the possibility of characterizing an exoplanet (in terms of habitability, geology, presence of life, etc.) by studying material ejected from the surface during an impact event. For a number of impact scenarios, we estimate the escaping mass and assess its subsequent collisional evolution in a circumstellar orbit, assuming a Sun-like host star. We calculate the fractional luminosity of the dust as a function of time after the impact event and study its detectability with current and future instrumentation. We consider the possibility to constrain the dust composition, giving information on the geology or the presence of a biosphere. As examples, we investigate whether calcite, silica, or ejected microorganisms could be detected. For a 20 km diameter impactor, we find that the dust mass escaping the exoplanet is roughly comparable to the zodiacal dust, depending on the exoplanet's size. The collisional evolution is best modeled by considering two independent dust populations, a spalled population consisting of nonmelted ejecta evolving on timescales of millions of years, and dust recondensed from melt or vapor evolving on much shorter timescales. While the presence of dust can potentially be inferred with current telescopes, studying its composition requires advanced instrumentation not yet available. The direct detection of biological matter turns out to be extremely challenging. Despite considerable difficulties (small dust masses, noise such as exozodiacal dust, etc.), studying dusty material ejected from an exoplanetary surface might become an interesting complement to atmospheric studies in the future.

Searching for Biosignatures in Exoplanetary Impact Ejecta.

PubMed

Cataldi, Gianni; Brandeker, Alexis; Thébault, Philippe; Singer, Kelsi; Ahmed, Engy; de Vries, Bernard L; Neubeck, Anna; Olofsson, Göran

2017-08-01

With the number of confirmed rocky exoplanets increasing steadily, their characterization and the search for exoplanetary biospheres are becoming increasingly urgent issues in astrobiology. To date, most efforts have concentrated on the study of exoplanetary atmospheres. Instead, we aim to investigate the possibility of characterizing an exoplanet (in terms of habitability, geology, presence of life, etc.) by studying material ejected from the surface during an impact event. For a number of impact scenarios, we estimate the escaping mass and assess its subsequent collisional evolution in a circumstellar orbit, assuming a Sun-like host star. We calculate the fractional luminosity of the dust as a function of time after the impact event and study its detectability with current and future instrumentation. We consider the possibility to constrain the dust composition, giving information on the geology or the presence of a biosphere. As examples, we investigate whether calcite, silica, or ejected microorganisms could be detected. For a 20 km diameter impactor, we find that the dust mass escaping the exoplanet is roughly comparable to the zodiacal dust, depending on the exoplanet's size. The collisional evolution is best modeled by considering two independent dust populations, a spalled population consisting of nonmelted ejecta evolving on timescales of millions of years, and dust recondensed from melt or vapor evolving on much shorter timescales. While the presence of dust can potentially be inferred with current telescopes, studying its composition requires advanced instrumentation not yet available. The direct detection of biological matter turns out to be extremely challenging. Despite considerable difficulties (small dust masses, noise such as exozodiacal dust, etc.), studying dusty material ejected from an exoplanetary surface might become an interesting complement to atmospheric studies in the future. Key Words: Biosignatures-Exoplanets-Impacts-Interplanetary dust-Remote sensing. Astrobiology 17, 721-746.

N-terminal B-type natriuretic peptide concentrations are similarly increased by 30 minutes of moderate and brisk walking in patients with coronary artery disease.

PubMed

Scharhag, Jürgen; Herrmann, Markus; Weissinger, Melanie; Herrmann, Wolfgang; Kindermann, Wilfried

2007-04-01

Elevated concentrations of B-type natriuretic peptide (BNP) and N-terminal pro- BNP (NT-proBNP) reflect elevated myocardial wall stress due to volume or pressure overload in cardiac disease. Recently, exercise-induced elevations of (NT-pro)BNP in coronary artery disease (CAD) patients have been reported to result from exercise-induced ischemia associated regional wall abnormalities. Therefore, the study aimed to examine NT-proBNP concentrations in patients with CAD after moderate and brisk walking (MW, BW). We hypothesized that BW induces higher increases than MW. In randomized order 14 patients with stable CAD (12 male symbol/2 female symbol; 63 +/- 9 years; LV ejection fraction: 59+/-9%) of a out-patient rehabilitation group performed MW with 4.5 +/- 0.6 km/h (mean heart rate: 80 +/- 11/min) or BWat their allowed upper exercise heart rate of 102+/-9/min with a speed of 6.2 +/- 0.6 km/h for 30 min on a tartan track on two separate days. Blood samples were taken before, immediately, 1 h, 3 h and 1 day after exercise to determine NT-proBNP and cardiac troponin T (cTnT). Echocardiographic LV function was determined before and 1 h after exercise. Median concentrations of NT-proBNP significantly increased from 222 to 295 ng/l (MW) and from 222 to 296 ng/l (BW) without a difference between both modalities. cTnT remained below the detection limit of 0.01 microg/l. LV functions remained unchanged. A cutoff level of 250 ng/l distinguished CAD patients with elevated exercise-induced increases in NT-proBNP and a diminished LV ejection fraction at rest. BW and MW induce similar increases in NT-proBNP in CAD patients without myocardial damage, which have to be considered when NT-proBNP is determined. Derived from the exercise- induced increase in NTproBNP, the myocardial strain in BW is not elevated in comparison to MW.

Manganese-Enhanced Magnetic Resonance Imaging Enables In Vivo Confirmation of Peri-Infarct Restoration Following Stem Cell Therapy in a Porcine Ischemia-Reperfusion Model.

PubMed

Dash, Rajesh; Kim, Paul J; Matsuura, Yuka; Ikeno, Fumiaki; Metzler, Scott; Huang, Ngan F; Lyons, Jennifer K; Nguyen, Patricia K; Ge, Xiaohu; Foo, Cheryl Wong Po; McConnell, Michael V; Wu, Joseph C; Yeung, Alan C; Harnish, Phillip; Yang, Phillip C

2015-07-27

The exact mechanism of stem cell therapy in augmenting the function of ischemic cardiomyopathy is unclear. In this study, we hypothesized that increased viability of the peri-infarct region (PIR) produces restorative benefits after stem cell engraftment. A novel multimodality imaging approach simultaneously assessed myocardial viability (manganese-enhanced magnetic resonance imaging [MEMRI]), myocardial scar (delayed gadolinium enhancement MRI), and transplanted stem cell engraftment (positron emission tomography reporter gene) in the injured porcine hearts. Twelve adult swine underwent ischemia-reperfusion injury. Digital subtraction of MEMRI-negative myocardium (intrainfarct region) from delayed gadolinium enhancement MRI-positive myocardium (PIR and intrainfarct region) clearly delineated the PIR in which the MEMRI-positive signal reflected PIR viability. Human amniotic mesenchymal stem cells (hAMSCs) represent a unique population of immunomodulatory mesodermal stem cells that restored the murine PIR. Immediately following hAMSC delivery, MEMRI demonstrated an increased PIR viability signal compared with control. Direct PIR viability remained higher in hAMSC-treated hearts for >6 weeks. Increased PIR viability correlated with improved regional contractility, left ventricular ejection fraction, infarct size, and hAMSC engraftment, as confirmed by immunocytochemistry. Increased MEMRI and positron emission tomography reporter gene signal in the intrainfarct region and the PIR correlated with sustained functional augmentation (global and regional) within the hAMSC group (mean change, left ventricular ejection fraction: hAMSC 85±60%, control 8±10%; P<0.05) and reduced chamber dilatation (left ventricular end-diastole volume increase: hAMSC 24±8%, control 110±30%; P<0.05). The positron emission tomography reporter gene signal of hAMSC engraftment correlates with the improved MEMRI signal in the PIR. The increased MEMRI signal represents PIR viability and the restorative potential of the injured heart. This in vivo multimodality imaging platform represents a novel, real-time method of tracking PIR viability and stem cell engraftment while providing a mechanistic explanation of the therapeutic efficacy of cardiovascular stem cells. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.