New-Onset Heart Failure and Mortality in Hospital Survivors of Sepsis-Related Left Ventricular Dysfunction.

PubMed

Vallabhajosyula, Saraschandra; Jentzer, Jacob C; Geske, Jeffrey B; Kumar, Mukesh; Sakhuja, Ankit; Singhal, Akhil; Poterucha, Joseph T; Kashani, Kianoush; Murphy, Joseph G; Gajic, Ognjen; Kashyap, Rahul

2018-02-01

The association between new-onset left ventricular (LV) dysfunction during sepsis with long-term heart failure outcomes is lesser understood. Retrospective cohort study of all adult patients with severe sepsis and septic shock between 2007 and 2014 who underwent echocardiography within 72 h of admission to the intensive care unit. Patients with prior heart failure, LV dysfunction, and structural heart disease were excluded. LV systolic dysfunction was defined as LV ejection fraction <50% and LV diastolic dysfunction as ≥grade II. Primary composite outcome included new hospitalization for acute decompensated heart failure and all-cause mortality at 2-year follow-up. Secondary outcomes included persistent LV dysfunction, and hospital mortality and length of stay. During this 8-year period, 434 patients with 206 (48%) patients having LV dysfunction were included. The two groups had similar baseline characteristics, but those with LV dysfunction had worse function as demonstrated by worse LV ejection fraction, cardiac index, and LV diastolic dysfunction. In the 331 hospital survivors, new-onset acute decompensated heart failure hospitalization did not differ between the two cohorts (15% vs. 11%). The primary composite outcome was comparable at 2-year follow-up between the groups with and without LV dysfunction (P = 0.24). Persistent LV dysfunction was noted in 28% hospital survivors on follow-up echocardiography. Other secondary outcomes were similar between the two groups. In patients with severe sepsis and septic shock, the presence of new-onset LV dysfunction did not increase the risk of long-term adverse heart failure outcomes.

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.

Copeptin in patients with heart failure and preserved ejection fraction: a report from the prospective KaRen-study

PubMed Central

Hage, Camilla; Lund, Lars H; Donal, Erwan; Daubert, Jean-Claude; Linde, Cecilia; Mellbin, Linda

2015-01-01

Introduction Underlying mechanisms of heart failure (HF) with preserved ejection fraction (HFPEF) remain unknown. We explored copeptin, a biomarker of the arginine vasopressin system, hypothesising that copeptin in HFPEF is elevated, associated with diastolic dysfunction and N-terminal pro-brain natriuretic peptide (NT-proBNP) and predictive of HF hospitalisation and mortality. Methods and analysis In a prospective observational substudy of the The Karolinska Rennes (KaRen) 86 patients with symptoms of acute HF and ejection fraction (EF) ≥45% were enrolled. After 4–8 weeks, blood sampling and echocardiography was performed. Plasma-copeptin was analysed in 86 patients and 62 healthy controls. Patients were followed in median 579 days (quartile 1; quartile 3 (Q1;Q3) 276;1178) regarding the composite end point all-cause mortality or HF hospitalisation. Ethics and dissemination The patients with HFPEF had higher copeptin levels, median 13.56 pmol/L (Q1;Q3 8.56;20.55) than controls 5.98 pmol/L (4.15;9.42; p<0.001). Diastolic dysfunction, assessable in 75/86 patients, was present in 45 and absent in 30 patients. Copeptin did not differ regarding diastolic dysfunction and did not correlate with cardiac function but with NT-proBNP (r=0.223; p value=0.040). In univariate Cox regression analysis log copeptin predicted the composite end point (HR 1.56 (95% CI 1.03 to 2.38; p value=0.037)) but not after adjusting for NT-proBNP (HR 1.39 (95% CI 0.91 to 2.12; p value=0.125)). Conclusions In the present patients with HFPEF, copeptin is elevated, correlates with NT-proBNP but not markers of diastolic dysfunction, and has prognostic implications, however blunted after adjustment for NT-proBNP. The HFPEF pathophysiology may be better reflected by markers of neurohormonal activation than by diastolic dysfunction. Trial registration number ClinicalTrials.gov NCT00774709. PMID:26568833

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.

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.

Cardiac Structure and Function in Cushing's Syndrome: A Cardiac Magnetic Resonance Imaging Study

PubMed Central

Roux, Charles; Salenave, Sylvie; Kachenoura, Nadjia; Raissouni, Zainab; Macron, Laurent; Guignat, Laurence; Jublanc, Christel; Azarine, Arshid; Brailly, Sylvie; Young, Jacques; Mousseaux, Elie; Chanson, Philippe

2014-01-01

Background: Patients with Cushing's syndrome have left ventricular (LV) hypertrophy and dysfunction on echocardiography, but echo-based measurements may have limited accuracy in obese patients. No data are available on right ventricular (RV) and left atrial (LA) size and function in these patients. Objectives: The objective of the study was to evaluate LV, RV, and LA structure and function in patients with Cushing's syndrome by means of cardiac magnetic resonance, currently the reference modality in assessment of cardiac geometry and function. Methods: Eighteen patients with active Cushing's syndrome and 18 volunteers matched for age, sex, and body mass index were studied by cardiac magnetic resonance. The imaging was repeated in the patients 6 months (range 2–12 mo) after the treatment of hypercortisolism. Results: Compared with controls, patients with Cushing's syndrome had lower LV, RV, and LA ejection fractions (P < .001 for all) and increased end-diastolic LV segmental thickness (P < .001). Treatment of hypercortisolism was associated with an improvement in ventricular and atrial systolic performance, as reflected by a 15% increase in the LV ejection fraction (P = .029), a 45% increase in the LA ejection fraction (P < .001), and an 11% increase in the RV ejection fraction (P = NS). After treatment, the LV mass index and end-diastolic LV mass to volume ratio decreased by 17% (P < .001) and 10% (P = .002), respectively. None of the patients had late gadolinium myocardial enhancement. Conclusion: Cushing's syndrome is associated with subclinical biventricular and LA systolic dysfunctions that are reversible after treatment. Despite skeletal muscle atrophy, Cushing's syndrome patients have an increased LV mass, reversible upon correction of hypercortisolism. PMID:25093618

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.

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.

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.

Cardiomyocyte Functional Etiology in Heart Failure With Preserved Ejection Fraction Is Distinctive-A New Preclinical Model.

PubMed

Curl, Claire L; Danes, Vennetia R; Bell, James R; Raaijmakers, Antonia J A; Ip, Wendy T K; Chandramouli, Chanchal; Harding, Tristan W; Porrello, Enzo R; Erickson, Jeffrey R; Charchar, Fadi J; Kompa, Andrew R; Edgley, Amanda J; Crossman, David J; Soeller, Christian; Mellor, Kimberley M; Kalman, Jonathan M; Harrap, Stephen B; Delbridge, Lea M D

2018-06-01

Among the growing numbers of patients with heart failure, up to one half have heart failure with preserved ejection fraction (HFpEF). The lack of effective treatments for HFpEF is a substantial and escalating unmet clinical need-and the lack of HFpEF-specific animal models represents a major preclinical barrier in advancing understanding of HFpEF. As established treatments for heart failure with reduced ejection fraction (HFrEF) have proven ineffective for HFpEF, the contention that the intrinsic cardiomyocyte phenotype is distinct in these 2 conditions requires consideration. Our goal was to validate and characterize a new rodent model of HFpEF, undertaking longitudinal investigations to delineate the associated cardiac and cardiomyocyte pathophysiology. The selectively inbred Hypertrophic Heart Rat (HHR) strain exhibits adult cardiac enlargement (without hypertension) and premature death (40% mortality at 50 weeks) compared to its control strain, the normal heart rat. Hypertrophy was characterized in vivo by maintained systolic parameters (ejection fraction at 85%-90% control) with marked diastolic dysfunction (increased E/E'). Surprisingly, HHR cardiomyocytes were hypercontractile, exhibiting high Ca 2+ operational levels and markedly increased L-type Ca 2+ channel current. In HHR, prominent regions of reparative fibrosis in the left ventricle free wall adjacent to the interventricular septum were observed. Thus, the cardiomyocyte remodeling process in the etiology of this HFpEF model contrasts dramatically with the suppressed Ca 2+ cycling state that typifies heart failure with reduced ejection fraction. These findings may explain clinical observations, that treatments considered appropriate for heart failure with reduced ejection fraction are of little benefit for HFpEF-and suggest a basis for new therapeutic strategies. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

[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)

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.

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

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

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

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.

[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.

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.

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.

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.

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.

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

PubMed

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

2014-12-21

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

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.

Combined circumferential and longitudinal left ventricular systolic dysfunction in patients with asymptomatic aortic stenosis.

PubMed

Cioffi, Giovanni; Mazzone, Carmine; Barbati, Giulia; Rossi, Andrea; Nistri, Stefano; Ognibeni, Federica; Tarantini, Luigi; Di Lenarda, Andrea; Faggiano, Pompilio; Pulignano, Giovanni; Stefenelli, Carlo; de Simone, Giovanni; Devereux, Richard B

2015-07-01

Early detection of left ventricular (LV) systolic dysfunction is pivotal in the management of patients with aortic stenosis (AS). LV circumferential and/or longitudinal shortening may be impaired in these patients despite LV ejection fraction is preserved. We focused on prevalence and factors associated with combined impairment of circumferential and longitudinal shortening (C&L) in asymptomatic AS patients. Echocardiographic and clinical data from 200 patients with asymptomatic AS of any degree without history of heart failure and normal LV ejection fraction were analyzed. C&L were evaluated by mid-wall shortening (MS) and tissue Doppler mitral annular peak systolic velocity (S'), and classified low if <16.5% and if <8.5 cm/sec, respectively (10th percentiles of controls). Combined C&L dysfunction was detected in 72 patients (36%). The variables associated with this condition were higher LV mass (OR 1.02 [CI 1.01-1.04], P = 0.03), concentric LV geometry (OR 4.30 [CI 1.79-10.34], P = 0.001), increasing pulmonary artery wedge pressure (by E/e' ratio; OR 1.11 [CI 1.04-1.19], P = 0.001). The relation of MS and peak S' was linear and slightly significant in the whole population (r = 0.23; F statistic=0.001), absent in patients with C&L dysfunction (r = 0.04; F = ns), negative (linear model) in the subgroup of patients without C&L dysfunction (r = -0.22; F = 0.02). C&L dysfunction is present in more than one-third of patients with asymptomatic AS and is associated with concentric LV geometry and higher degree of diastolic dysfunction. The relation between MS and peak S' largely varies in the subgroups with different C&L function. © 2014, Wiley Periodicals, Inc.

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

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.

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.

The BEAUTIFUL study: randomized trial of ivabradine in patients with stable coronary artery disease and left ventricular systolic dysfunction - baseline characteristics of the study population.

PubMed

Ferrari, R; Ford, I; Fox, K; Steg, P G; Tendera, M

2008-01-01

Ivabradine is a selective heart rate-lowering agent that acts by inhibiting the pacemaker current If in sinoatrial node cells. Patients with coronary artery disease and left ventricular dysfunction are at high risk of death and cardiac events, and the BEAUTIFUL study was designed to evaluate the effects of ivabradine on outcome in such patients receiving optimal medical therapy. This report describes the study population at baseline. BEAUTIFUL is an international, multicentre, randomized, double-blind trial to compare ivabradine with placebo in reducing mortality and cardiovascular events in patients with stable coronary artery disease and left ventricular systolic dysfunction (ejection fraction <40%). A total of 10,917 patients were randomized. At baseline, their mean age was 65 years, 83% were male, 98% Caucasian, 88% had previous myocardial infarction, 37% had diabetes, and 40% had metabolic syndrome. Mean ejection fraction was 32% and resting heart rate was 71.6 bpm. Concomitant medications included beta-blockers (87%), renin-angiotensin system agents (89%), antithrombotic agents (94%), and lipid-lowering agents (76%). Main results from BEAUTIFUL are expected in 2008, and should show whether ivabradine, on top of optimal medical treatment, reduces mortality and cardiovascular events in this population of high-risk patients. (c) 2007 S. Karger AG, Basel

Estimation of cardiac left ventricular ejection fraction in transfusional cardiac iron overload by R2* magnetic resonance.

PubMed

Sakuta, Juri; Ito, Yoshikazu; Kimura, Yukihiko; Park, Jinho; Tokuuye, Koichi; Ohyashiki, Kazuma

2010-12-01

Cardiac dysfunction due to transfusional iron overload is one of the most critical complications for patients with transfusion-dependent hematological disorders. Clinical parameters such as total red blood cell (RBC) transfusion units and serum ferritin level are usually considered as indicators for initiation of iron chelation therapy. We used MRI-T2*, MRI-R2* values, and left ventricular ejection fraction in 19 adult patients with blood transfusion-dependent hematological disorders without consecutive oral iron chelation therapy, and propose possible formulae of cardiac function using known parameters, such as total RBC transfusion units and serum ferritin levels. We found a positive correlation in all patients between both R2* values (reciprocal values of T2*) and serum ferritin levels (r = 0.81) and also total RBC transfusion volume (r = 0.90), but not when we analyzed subgroups of patients whose T2* values were over 30 ms (0.52). From the formulae of the R2*, we concluded that approximately 50 Japanese units or 2,900 pmol/L ferritin might be the cutoff value indicating possible future cardiac dysfunction.

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.

Attenuating the defibrillation dosage decreases postresuscitation myocardial dysfunction in a swine model of pediatric ventricular fibrillation

PubMed Central

Berg, Marc D.; Banville, Isabelle L.; Chapman, Fred W.; Walker, Robert G.; Gaballa, Mohammed A.; Hilwig, Ronald W.; Samson, Ricardo A.; Kern, Karl B.; Berg, Robert A.

2009-01-01

Objective The optimal biphasic defibrillation dose for children is unknown. Postresuscitation myocardial dysfunction is common and may be worsened by higher defibrillation doses. Adult-dose automated external defibrillators are commonly available; pediatric doses can be delivered by attenuating the adult defibrillation dose through a pediatric pads/cable system. The objective was to investigate whether unattenuated (adult) dose biphasic defibrillation results in greater postresuscitation myocardial dysfunction and damage than attenuated (pediatric) defibrillation. Design Laboratory animal experiment. Setting University animal laboratory. Subjects Domestic swine weighing 19 ± 3.6 kg. Interventions Fifty-two piglets were randomized to receive biphasic defibrillation using either adult-dose shocks of 200, 300, and 360 J or pediatric-dose shocks of ~50, 75, and 85 J after 7 mins of untreated ventricular fibrillation. Contrast left ventriculograms were obtained at baseline and then at 1, 2, 3, and 4 hrs postresuscitation. Postresuscitation left ventricular ejection fraction and cardiac troponins were evaluated. Measurements and Main Results By design, piglets in the adult-dose group received shocks with more energy (261 ± 65 J vs. 72 ± 12 J, p < .001) and higher peak current (37 ± 8 A vs. 13 ± 2 A, p < .001) at the largest defibrillation dose needed. In both groups, left ventricular ejection fraction was reduced significantly at 1, 2, and 4 hrs from baseline and improved during the 4 hrs postresuscitation. The decrease in left ventricular ejection fraction from baseline was greater after adult-dose defibrillation. Plasma cardiac troponin levels were elevated 4 hrs postresuscitation in 11 of 19 adult-dose piglets vs. four of 20 pediatric-dose piglets (p = .02). Conclusions Unattenuated adult-dose defibrillation results in a greater frequency of myocardial damage and worse postresuscitation myocardial function than pediatric doses in a swine model of prolonged out-of-hospital pediatric ventricular fibrillation cardiac arrest. These data support the use of pediatric attenuating electrodes with adult biphasic automated external defibrillators to defibrillate children. PMID:18496405

Prevalence and Prognostic Significance of Right Ventricular Systolic Dysfunction in Patients Undergoing Transcatheter Aortic Valve Implantation.

PubMed

Lindsay, Alistair C; Harron, Katie; Jabbour, Richard J; Kanyal, Ritesh; Snow, Thomas M; Sawhney, Paramvir; Alpendurada, Francisco; Roughton, Michael; Pennell, Dudley J; Duncan, Alison; Di Mario, Carlo; Davies, Simon W; Mohiaddin, Raad H; Moat, Neil E

2016-07-01

Cardiovascular magnetic resonance (CMR) can provide important structural information in patients undergoing transcatheter aortic valve implantation. Although CMR is considered the standard of reference for measuring ventricular volumes and mass, the relationship between CMR findings of right ventricular (RV) function and outcomes after transcatheter aortic valve implantation has not previously been reported. A total of 190 patients underwent 1.5 Tesla CMR before transcatheter aortic valve implantation. Steady-state free precession sequences were used for aortic valve planimetry and to assess ventricular volumes and mass. Semiautomated image analysis was performed by 2 specialist reviewers blinded to patient treatment. Patient follow-up was obtained from the Office of National Statistics mortality database. The median age was 81.0 (interquartile range, 74.9-85.5) years; 50.0% were women. Impaired RV function (RV ejection fraction ≤50%) was present in 45 (23.7%) patients. Patients with RV dysfunction had poorer left ventricular ejection fractions (42% versus 69%), higher indexed left ventricular end-systolic volumes (96 versus 40 mL), and greater indexed left ventricular mass (101 versus 85 g/m(2); P<0.01 for all) than those with normal RV function. Median follow-up was 850 days; 21 of 45 (46.7%) patients with RV dysfunction died, compared with 43 of 145 (29.7%) patients with normal RV function (P=0.035). After adjustment for significant baseline variables, both RV ejection fraction ≤50% (hazard ratio, 2.12; P=0.017) and indexed aortic valve area (hazard ratio, 4.16; P=0.025) were independently associated with survival. RV function, measured on preprocedural CMR, is an independent predictor of mortality after transcatheter aortic valve implantation. CMR assessment of RV function may be important in the risk stratification of patients undergoing transcatheter aortic valve implantation. © 2016 American Heart Association, Inc.

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.

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.

Pharmacological heart rate lowering in patients with a preserved ejection fraction-review of a failing concept.

PubMed

Meyer, Markus; Rambod, Mehdi; LeWinter, Martin

2018-07-01

Epidemiological studies have demonstrated that high resting heart rates are associated with increased mortality. Clinical studies in patients with heart failure and reduced ejection fraction have shown that heart rate lowering with beta-blockers and ivabradine improves survival. It is therefore often assumed that heart rate lowering is beneficial in other patients as well. Here, we critically appraise the effects of pharmacological heart rate lowering in patients with both normal and reduced ejection fraction with an emphasis on the effects of pharmacological heart rate lowering in hypertension and heart failure. Emerging evidence from recent clinical trials and meta-analyses suggest that pharmacological heart rate lowering is not beneficial in patients with a normal or preserved ejection fraction. This has just begun to be reflected in some but not all guideline recommendations. The detrimental effects of pharmacological heart rate lowering are due to an increase in central blood pressures, higher left ventricular systolic and diastolic pressures, and increased ventricular wall stress. Therefore, we propose that heart rate lowering per se reproduces the hemodynamic effects of diastolic dysfunction and imposes an increased arterial load on the left ventricle, which combine to increase the risk of heart failure and atrial fibrillation. Pharmacologic heart rate lowering is clearly beneficial in patients with a dilated cardiomyopathy but not in patients with normal chamber dimensions and normal systolic function. These conflicting effects can be explained based on a model that considers the hemodynamic and ventricular structural effects of heart rate changes.

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.

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.

Dynamic phantom for radionuclide cardiology

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

Nickles, R.J.

1979-06-01

A flow-based phantom has been developed to verify analysis routines most frequently employed in clinical radionuclide cardiology. Ejection-fraction studies by first-pass or equilibrium techniques are simulated, as well as assessment of shunts and cardiac output. This hydraulic phantom, with its valve-selectable dysfunctions, offers a greater role in training than in quality control, as originally intended.

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

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.

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)

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.

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

PubMed

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

2017-08-01

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

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.

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

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

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 (

Correlation of left ventricular systolic dysfunction determined by low ejection fraction and 30-day mortality in patients with severe sepsis and septic shock: a systematic review and meta-analysis.

PubMed

Sevilla Berrios, Ronaldo A; O'Horo, John C; Velagapudi, Venu; Pulido, Juan N

2014-08-01

The prognostic implications of myocardial dysfunction in patients with sepsis and its association with mortality are controversial. Several tools have been proposed to evaluate cardiac function in these patients, but their usefulness beyond guiding therapy is unclear. We review the value of echocardiographic estimate of left ventricular ejection fraction (LVEF) in the setting of severe sepsis and/or septic shock and its correlation with 30-day mortality. We conducted a systematic review and meta-analysis to evaluate the prognostic functionality of newly diagnosed LV systolic dysfunction by transthoracic echocardiography on critical ill patients admitted to the intensive care unit with severe sepsis or septic shock. A search of EMBASE and PubMed, Ovide MEDLINE, and Cochrane CENTRAL medical databases yielded 7 studies meeting inclusion criteria reporting on a total of 585 patients. The pooled sensitivity of depressed LVEF for mortality was 52% (95% confidence interval [CI], 29%-73%), and pooled specificity was 63% (95% CI, 53%-71%). Summary receiver operating characteristic curve showed an area under the curve of 0.62 (95% CI, 0.58-0.67). The overall mortality diagnostic odd ratio for septic patients with LV systolic dysfunction was 1.92 (95% CI, 1.27-2.899). Statistical heterogeneity of studies was moderate. The presence of new LV systolic dysfunction associated with sepsis and defined as low LVEF is neither a sensitive nor a specific predictor of mortality. These findings are limited because of the heterogeneity and underpower of the studies. Further research into this method is warranted. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

Evaluation of Trastuzumab-induced early cardiac dysfunction using two-dimensional Strain Echocardiography.

PubMed

Emren, Sadik Volkan; Tuluce, Selcen Yakar; Levent, Fatih; Tuluce, Kamil; Kalkan, Toygar; Yildiz, Yasar; Alacacioğlu, Ahmet; Kucukzeybek, Yüksel; Akyol, Murat; Salman, Tarık

2015-12-01

Trastuzumab, a chemotherapeutic agent used in the treatment of breast cancer. has been shown to induce subclinical left ventricular (LV) dysfunction during a three to six month period as evidenced by strain echocardiographic examination without any change occurring in the ejection fraction of LV. The present study evaluated the presence of subclinical LV dysfunction using strain echocardiography 1 day and 7 days after the initiation of trastuzumab therapy. The patients with breast cancer receiving adjuvant trastuzumab therapy underwent 2-dimensional, tissue Doppler, and strain echocardiographic examination at baseline and 1 day and 7 days after therapy. LV global longitudinal strain (GLS), global circumferential strain (GCS) values, and other echocardiographic parameters were calculated. A total of 40 females, mean age 50+/-10 years, were evaluated. Of these patients, 97% received anthracycline and 73% received radiotherapy before the initiation of trastuzumab therapy. No change was observed in any of the echocardiographic parameters 1 day after the initiation of trastuzumab therapy (p>0.05). The LV ejection fraction, tissue Doppler parameters, and GCS values did not show any changes 7 days after the initiation of therapy, whereas significant decreases were observed in GLS value (19.2+/-4.0% vs. 17.2+/-3.4, p=0.001) and systolic annular velocity of the lateral LV wall (S' velocity) (10.5+/-3.2 vs. 8.6+/-2.2, p=0.002). Trastuzumab therapy is associated with subclinical LV dysfunction as early as 7 days after initiation of the therapy as evidenced by the decreases in GLS value of LV and systolic annular velocity of the lateral LV wall.

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.

Age-related changes in intraventricular kinetic energy: a physiological or pathological adaptation?

PubMed

Wong, James; Chabiniok, Radomir; deVecchi, Adelaide; Dedieu, Nathalie; Sammut, Eva; Schaeffter, Tobias; Razavi, Reza

2016-03-15

Aging has important deleterious effects on the cardiovascular system. We sought to compare intraventricular kinetic energy (KE) in healthy subjects of varying ages with subjects with ventricular dysfunction to understand if changes in energetic momentum may predispose individuals to heart failure. Four-dimensional flow MRI was acquired in 35 healthy subjects (age: 1-67 yr) and 10 patients with left ventricular (LV) dysfunction (age: 28-79 yr). Healthy subjects were divided into age quartiles (1st quartile: <16 yr, 2nd quartile: 17-32 yr, 3rd quartile: 33-48 yr, and 4th quartile: 49-64 yr). KE was measured in the LV throughout the cardiac cycle and indexed to ventricular volume. In healthy subjects, two large peaks corresponding to systole and early diastole occurred during the cardiac cycle. A third smaller peak was seen during late diastole in eight adults. Systolic KE (P = 0.182) and ejection fraction (P = 0.921) were preserved through all age groups. Older adults showed a lower early peak diastolic KE compared with children (P < 0.0001) and young adults (P = 0.025). Subjects with LV dysfunction had reduced ejection fraction (P < 0.001) and compared with older healthy adults exhibited a similar early peak diastolic KE (P = 0.142) but with the addition of an elevated KE in diastasis (P = 0.029). In healthy individuals, peak diastolic KE progressively decreases with age, whereas systolic peaks remain constant. Peak diastolic KE in the oldest subjects is comparable to those with LV dysfunction. Unique age-related changes in ventricular diastolic energetics might be physiological or herald subclinical pathology. Copyright © 2016 the American Physiological Society.

Age-related changes in intraventricular kinetic energy: a physiological or pathological adaptation?

PubMed Central

Wong, James; Chabiniok, Radomir; deVecchi, Adelaide; Dedieu, Nathalie; Sammut, Eva; Schaeffter, Tobias

2016-01-01

Aging has important deleterious effects on the cardiovascular system. We sought to compare intraventricular kinetic energy (KE) in healthy subjects of varying ages with subjects with ventricular dysfunction to understand if changes in energetic momentum may predispose individuals to heart failure. Four-dimensional flow MRI was acquired in 35 healthy subjects (age: 1–67 yr) and 10 patients with left ventricular (LV) dysfunction (age: 28–79 yr). Healthy subjects were divided into age quartiles (1st quartile: <16 yr, 2nd quartile: 17–32 yr, 3rd quartile: 33–48 yr, and 4th quartile: 49–64 yr). KE was measured in the LV throughout the cardiac cycle and indexed to ventricular volume. In healthy subjects, two large peaks corresponding to systole and early diastole occurred during the cardiac cycle. A third smaller peak was seen during late diastole in eight adults. Systolic KE (P = 0.182) and ejection fraction (P = 0.921) were preserved through all age groups. Older adults showed a lower early peak diastolic KE compared with children (P < 0.0001) and young adults (P = 0.025). Subjects with LV dysfunction had reduced ejection fraction (P < 0.001) and compared with older healthy adults exhibited a similar early peak diastolic KE (P = 0.142) but with the addition of an elevated KE in diastasis (P = 0.029). In healthy individuals, peak diastolic KE progressively decreases with age, whereas systolic peaks remain constant. Peak diastolic KE in the oldest subjects is comparable to those with LV dysfunction. Unique age-related changes in ventricular diastolic energetics might be physiological or herald subclinical pathology. PMID:26747496

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.

Coronary artery disease detection - limitations of stress testing in left ventricular dysfunction

PubMed Central

Bomb, Ritin; Kumar, Senthil; Chockalingam, Anand

2017-01-01

Incidental diagnosis of left ventricular systolic dysfunction (LVD) is common in clinical practice. The prevalence of asymptomatic LVD (Ejection Fraction, EF < 50%) is 6.0% in men and 0.8% in women and is twice as common as symptomatic LVD. The timely and definitive exclusion of an ischemic etiology is central to optimizing care and reducing mortality in LVD. Advances in cardiovascular imaging provide many options for imaging of patients with left ventricular dysfunction. Clinician experience, patient endurance, imaging modality characteristics, cost and safety determine the choice of testing. In this review, we have compared the diagnostic utility of established tests - nuclear and echocardiographic stress testing with newer techniques like coronary computerized tomography and cardiac magnetic resonance imaging and highlight their inherent limitations in patients with underlying left ventricular dysfunction. PMID:28515848

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.

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

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

PubMed

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

2015-03-01

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

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

PubMed

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

2017-10-05

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

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.

Effect of 10-Week Supervised Moderate-Intensity Intermittent vs. Continuous Aerobic Exercise Programs on Vascular Adhesion Molecules in Patients with Heart Failure.

PubMed

Aksoy, Sibel; Findikoglu, Gulin; Ardic, Fusun; Rota, Simin; Dursunoglu, Dursun

2015-10-01

Abnormal expression of cellular adhesion molecules may be related to endothelial dysfunction, a key feature in chronic heart failure. This study compares the effects of 10-wk supervised moderate-intensity continuous aerobic exercise (CAE) and intermittent aerobic exercise (IAE) programs on markers of endothelial damage, disease severity, functional and metabolic status, and quality-of-life in chronic heart failure patients. Fifty-seven patients between 41 and 81 yrs with New York Heart Association class II-III chronic heart failure and with a left ventricular ejection fraction of 35%-55% were randomized into three groups: nonexercising control, CAE, and IAE, which exercised three times a week for 10 wks. Endothelial damage was assessed by serum markers of vascular cell adhesion molecule-1, serum intercellular adhesion molecule-1, and nitric oxide; disease severity was measured by left ventricular ejection fraction and N-terminal probrain natriuretic peptide; metabolic status was evaluated by body composition analysis and lipid profile levels; functional status was evaluated by cardiorespiratory exercise stress test and 6-min walking distance; quality-of-life was assessed with Left Ventricular Dysfunction-36 and Short-Form 36 questionnaires at the baseline and at the end of the 10th week. Significant decreases in serum vascular cell adhesion molecule-1 or serum intercellular adhesion molecule-1 in IAE and CAE groups after training were found, respectively. Resting systolic and diastolic blood pressure, peak systolic and diastolic blood pressure, 6-min walking distance, and the mental health and vitality components of Short-Form 36 improved in the CAE group, whereas left ventricular ejection fraction and 6-min walking distance improved in the IAE group compared with the control group. Both moderate-intensity CAE and IAE programs significantly reduced serum markers of adhesion molecules and prevented the change in VO2 in patients with chronic heart failure.

Very high rate programming in primary prevention patients with reduced ejection fraction implanted with a defibrillator: Results from a large multicenter controlled study.

PubMed

Clementy, Nicolas; Challal, Farid; Marijon, Eloi; Boveda, Serge; Defaye, Pascal; Leclercq, Christophe; Deharo, Jean-Claude; Sadoul, Nicolas; Klug, Didier; Piot, Olivier; Gras, Daniel; Bordachar, Pierre; Algalarrondo, Vincent; Fauchier, Laurent; Babuty, Dominique

2017-02-01

Programming implantable cardioverter-defibrillators (ICDs) with a high-rate therapy strategy has proven to be effective in reducing shocks and is associated with a reduced mortality. We sought to determine the impact of a very high rate cutoff programming strategy on outcomes in patients with a primary indication for an ICD due to reduced left ventricular ejection fraction. Using data from the multicenter French DAI-PP registry, this cohort-controlled study compared outcomes in 500 patients programmed with a very high rate cutoff (VH-RATE group: monitor zone 170-219 beats/min; ventricular fibrillation zone ≥220 beats/min with 13 ± 4 detection intervals) with 1500 matched control patients programmed with 1 or 2 therapy zone. All ICDs were implanted for primary prevention in patients with systolic dysfunction. Risks of events were compared after propensity score matching of sex, age, ejection fraction, New York Heart Association class, cardiomyopathy, atrial fibrillation, and type of device. After a mean follow-up of 3.6 ± 2.3 years, VH-RATE programming was associated with a reduction of appropriate therapy risk (hazard ratio [HR] 0.40; 95% confidence interval [CI] 0.31-0.51; P < .0001) and inappropriate shock (HR 0.42; 95% CI 0.27-0.63; P < .0001). It was also associated with a decreased risk of sudden cardiac death (HR 0.43; 95% CI 0.17-0.99; P = .04) as compared with patients programmed with 2 therapy zones. There was no significant difference in overall survival between the groups. In patients implanted with an ICD in primary prevention with left ventricular dysfunction, very high rate cutoff programming (single therapy zone ≥220 beats/min) was associated with a 60% reduction of appropriate therapies as well as inappropriate shocks, without affecting mortality. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Cardiac macrophages promote diastolic dysfunction.

PubMed

Hulsmans, Maarten; Sager, Hendrik B; Roh, Jason D; Valero-Muñoz, María; Houstis, Nicholas E; Iwamoto, Yoshiko; Sun, Yuan; Wilson, Richard M; Wojtkiewicz, Gregory; Tricot, Benoit; Osborne, Michael T; Hung, Judy; Vinegoni, Claudio; Naxerova, Kamila; Sosnovik, David E; Zile, Michael R; Bradshaw, Amy D; Liao, Ronglih; Tawakol, Ahmed; Weissleder, Ralph; Rosenzweig, Anthony; Swirski, Filip K; Sam, Flora; Nahrendorf, Matthias

2018-02-05

Macrophages populate the healthy myocardium and, depending on their phenotype, may contribute to tissue homeostasis or disease. Their origin and role in diastolic dysfunction, a hallmark of cardiac aging and heart failure with preserved ejection fraction, remain unclear. Here we show that cardiac macrophages expand in humans and mice with diastolic dysfunction, which in mice was induced by either hypertension or advanced age. A higher murine myocardial macrophage density results from monocyte recruitment and increased hematopoiesis in bone marrow and spleen. In humans, we observed a parallel constellation of hematopoietic activation: circulating myeloid cells are more frequent, and splenic 18 F-FDG PET/CT imaging signal correlates with echocardiographic indices of diastolic dysfunction. While diastolic dysfunction develops, cardiac macrophages produce IL-10, activate fibroblasts, and stimulate collagen deposition, leading to impaired myocardial relaxation and increased myocardial stiffness. Deletion of IL-10 in macrophages improves diastolic function. These data imply expansion and phenotypic changes of cardiac macrophages as therapeutic targets for cardiac fibrosis leading to diastolic dysfunction. © 2018 Hulsmans et al.

Air pollution and heart failure: Relationship with the ejection fraction

PubMed Central

Dominguez-Rodriguez, Alberto; Abreu-Afonso, Javier; Rodríguez, Sergio; Juarez-Prera, Ruben A; Arroyo-Ucar, Eduardo; Gonzalez, Yenny; Abreu-Gonzalez, Pedro; Avanzas, Pablo

2013-01-01

AIM: To study whether the concentrations of particulate matter in ambient air are associated with hospital admission due to heart failure in patients with heart failure with preserved ejection fraction and reduced ejection fraction. METHODS: We studied 353 consecutive patients admitted into a tertiary care hospital with a diagnosis of heart failure. Patients with ejection fraction of ≥ 45% were classified as having heart failure with preserved ejection fraction and those with an ejection fraction of < 45% were classified as having heart failure with reduced ejection fraction. We determined the average concentrations of different sizes of particulate matter (< 10, < 2.5, and < 1 μm) and the concentrations of gaseous pollutants (carbon monoxide, sulphur dioxide, nitrogen dioxide and ozone) from 1 d up to 7 d prior to admission. RESULTS: The heart failure with preserved ejection fraction population was exposed to higher nitrogen dioxide concentrations compared to the heart failure with reduced ejection fraction population (12.95 ± 8.22 μg/m3 vs 4.50 ± 2.34 μg/m3, P < 0.0001). Multivariate analysis showed that nitrogen dioxide was a significant predictor of heart failure with preserved ejection fraction (odds ratio ranging from (1.403, 95%CI: 1.003-2.007, P = 0.04) to (1.669, 95%CI: 1.043-2.671, P = 0.03). CONCLUSION: This study demonstrates that short-term nitrogen dioxide exposure is independently associated with admission in the heart failure with preserved ejection fraction population. PMID:23538391

Histone deacetylase activity governs diastolic dysfunction through a nongenomic mechanism

PubMed Central

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

2018-01-01

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

[VIABILITY OF MYOCAROIUM AS RISK FACTOR FOR MORTALITY IN EARLY AND LATE PERIOD AFTER BYPASS SURGERY OF CORONARY ARTERIES IN PATIENTS WITH CORONARY HEART DISEASE AND SEVERE LEFT VENTRICULAR DYSFUNCTION].

PubMed

Todurov, B M; Zelenchuk, V; Kuzmich, I M; Ivanyuk, N B; Nikolaichuk, M V

2015-06-01

In coronary heart disease and low ejection fraction of the left ventricle (LV) in patients after coronary artery bypass surgery tend mortality and complication rate higher than preserved LV systolic function. Significant preoperative predictors of early mortality and remote in these patients, and the incidence of complications in the early postoperative period were reveald.

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.

Chagas' heart disease: gender differences in myocardial damage assessed by cardiovascular magnetic resonance.

PubMed

Assunção, Antonildes N; Jerosch-Herold, Michael; Melo, Rodrigo L; Mauricio, Alejandra V; Rocha, Liliane; Torreão, Jorge A; Fernandes, Fabio; Ianni, Barbara M; Mady, Charles; Ramires, José A F; Kalil-Filho, Roberto; Rochitte, Carlos E

2016-11-28

Since a male-related higher cardiovascular morbidity and mortality in patients with Chagas' heart disease has been reported, we aimed to investigate gender differences in myocardial damage assessed by cardiovascular magnetic resonance (CMR). Retrospectively, 62 seropositive Chagas' heart disease patients referred to CMR (1.5 T) and with low probability of having significant coronary artery disease were included in this analysis. Amongst both sexes, there was a strong negative correlation between LV ejection fraction and myocardial fibrosis (male r = 0.64, female r = 0.73, both P < 0.001), with males showing significantly greater myocardial fibrosis (P = 0.002) and lower LV ejection fraction (P < 0.001) than females. After adjustment for potential confounders, gender remained associated with myocardial dysfunction, and 53% of the effect was mediated by myocardial fibrosis (P for mediation = 0.004). Also, the transmural pattern was more prevalent among male patients (23.7 vs. 9.9%, P < 0.001) as well as the myocardial heterogeneity or gray zone (2.2 vs. 1.3 g, P = 0.003). We observed gender-related differences in myocardial damage assessed by CMR in patients with Chagas' heart disease. As myocardial fibrosis and myocardial dysfunction are associated to cardiovascular outcomes, our findings might help to understand the poorer prognosis observed in males in Chagas' disease.

[Interest of tricuspid annular displacement (TAD) in evaluation of right ventricular ejection fraction].

PubMed

Hugues, T; Ducreux, D; Bertora, D; Berthier, F; Lemoigne, F; Padovani, B; Gibelin, P

2010-04-01

The ultrasound assessment of RV structure and function is often sub-optimal. The range of excursions of the mitral or tricuspid annulus measured in millimetre by 2D or TM-mode in centimetre per second by DTI-mode echocardiography has been shown to reflect the systolic function of both ventricles. We studied a new technique based on a tissue tracking algorithm that is ultrasound beam angle independent for automated detection of tricuspid annular displacement (TAD) (QLAB, Philips Medical Imaging). Twenty-six patients (pts) referred for magnetic resonance imaging (MRI) and 44 control subjects underwent a complete transthoracic echocardiography. MRI of the right ventricular ejection fraction (RVEF) was correlated by linear regression with TAD. Sixteen pts (61.5%) exhibited right ventricular systolic dysfunction (MRI RVEF<40%). The MRI RVEF was positively correlated with TAD (R(2)=0,65; p<0,0001). A value of TAD <14mm predicted right ventricular dysfunction with a sensitivity of 87.5% and a specificity of 90%. Most of (90%) healthy subjects exhibited TAD values exceeding this cut-off point (mean: 16.9+/-1.64mm; range: 13.3 to 24.8mm). Negative correlation was found between TAD and age (R(2)=0,36; p<0,0001). Our study is the first to correlate TAD with MRI RVEF. TAD is a simple, rapid, and non-invasive tool for right ventricular systolic function assessment.

Noninvasive iPhone Measurement of Left Ventricular Ejection Fraction Using Intrinsic Frequency Methodology.

PubMed

Pahlevan, Niema M; Rinderknecht, Derek G; Tavallali, Peyman; Razavi, Marianne; Tran, Thao T; Fong, Michael W; Kloner, Robert A; Csete, Marie; Gharib, Morteza

2017-07-01

The study is based on previously reported mathematical analysis of arterial waveform that extracts hidden oscillations in the waveform that we called intrinsic frequencies. The goal of this clinical study was to compare the accuracy of left ventricular ejection fraction derived from intrinsic frequencies noninvasively versus left ventricular ejection fraction obtained with cardiac MRI, the most accurate method for left ventricular ejection fraction measurement. After informed consent, in one visit, subjects underwent cardiac MRI examination and noninvasive capture of a carotid waveform using an iPhone camera (The waveform is captured using a custom app that constructs the waveform from skin displacement images during the cardiac cycle.). The waveform was analyzed using intrinsic frequency algorithm. Outpatient MRI facility. Adults able to undergo MRI were referred by local physicians or self-referred in response to local advertisement and included patients with heart failure with reduced ejection fraction diagnosed by a cardiologist. Standard cardiac MRI sequences were used, with periodic breath holding for image stabilization. To minimize motion artifact, the iPhone camera was held in a cradle over the carotid artery during iPhone measurements. Regardless of neck morphology, carotid waveforms were captured in all subjects, within seconds to minutes. Seventy-two patients were studied, ranging in age from 20 to 92 years old. The main endpoint of analysis was left ventricular ejection fraction; overall, the correlation between ejection fraction-iPhone and ejection fraction-MRI was 0.74 (r = 0.74; p < 0.0001; ejection fraction-MRI = 0.93 × [ejection fraction-iPhone] + 1.9). Analysis of carotid waveforms using intrinsic frequency methods can be used to document left ventricular ejection fraction with accuracy comparable with that of MRI. The measurements require no training to perform or interpret, no calibration, and can be repeated at the bedside to generate almost continuous analysis of left ventricular ejection fraction without arterial cannulation.

The effect of right ventricle pacemaker lead position on diastolic function in patients with preserved left ventricle ejection fraction.

PubMed

Mitov, Vladimir; Perisić, Zoran; Jolić, Aleksandar; Adamović, Dragana; Zastranović, Lale; Aleksić, Aleksandar; Kostić, Tomislav; Božinović, Nenad; Aleksić, Zeljka; Soldatović, Ivan

2013-01-01

Our aim was to analyze any changes during diastole in patients with normal left ventricular ejection fraction (LVEF), after pacemaker stimulation from the right ventricular outflow tract (RVOT) and right ventricular apex (RVA) lead position. This was a prospective, randomized, follow up study, which lasted for 12 months. Our research included 132 consecutive patients who were implanted with a permanent antibradycardiac pacemaker. Regarding the right ventricle lead position the patients were divided into two groups: The RVOT group--71 patients, with right ventricle outflow tract lead position and the RVA group--61 patients, with right ventricle apex lead position. We measured LVEF and diastolic parameters: peak filling ratio and time to peak filling ratio obtained by radionuclide ventriculography (RNV). The LVEF and various diastolic parameters and left atrial diameter were obtained by echocardiography. Based on the values of deceleration time of early diastolic filling (DTE), and other diastolic parameters like left atrial diameter, all the patients were classified into three degrees of diastolic dysfunction. Our results showed that there was no group difference in distribution of gender, age, body mass index (BMI), VVI to DDD pacemakers implantation ratio, RNV parameters (LVEF, peak filling rate (PFR), time to PFR (TPFR)) and echocardiography parameters: LVEF and parameters of diastolic dysfunction. After 12 months of pacemaker stimulation, LVEF by RNV remained the same in the RVOT group 51.31±15.80% (P=0.75), and also in the RVA group 53.83±6.57%, (P=0.19). In the RVOT group the PFR was highly lower and this finding was significant (P=0.01), while TPFR was also significantly lower (P=0.03). By dividing the patients according to the degree of diastolic dysfunction we found that most patients in both groups at enrollment had a second degree diastolic dysfunction. In both groups diastolic dysfunction increased, the number of patients with third degree diastolic dysfunction increased, and the number of patients with second degree diastolic dysfunction decreased, however, the worsening of diastolic function was significant only in the RVOT group. In conclusion, pacemaker stimulation from RVOT, but not in RVA, leads to progression of diastolic dysfunction in patients with preserved LVEF. This negative effect of pacemaker stimulation from RVOT on diastolic parameters was confirmed by two independent methods, RNV and echocardiography.

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.

Predictors of transient left ventricular dysfunction following transcatheter patent ductus arteriosus closure in pediatric age.

PubMed

Agha, Hala Mounir; Hamza, Hala S; Kotby, Alyaa; Ganzoury, Mona E L; Soliman, Nanies

2017-10-01

To evaluate the left ventricular function before and after transcatheter percutaneous patent ductus arteriosus (PDA) closure, and to identify the predictors of myocardial dysfunction post-PDA closure if present. Transcatheter PDA closure; conventional, Doppler, and tissue Doppler imaging; and speckle tracking echocardiography. To determine the feasibility and reliability of tissue Doppler and myocardial deformation imaging for evaluating myocardial function in children undergoing transcatheter PDA closure. Forty-two children diagnosed with hemodynamically significant PDA underwent percutaneous PDA closure. Conventional, Doppler, and tissue Doppler imaging, and speckle-derived strain rate echocardiography were performed at preclosure and at 48 hours, 1 month, and 6 months postclosure. Tissue Doppler velocities of the lateral and septal mitral valve annuli were obtained. Global and regional longitudinal peak systolic strain values were determined using two-dimensional speckle tracking echocardiography. The median age of the patients was 2 years and body weight was 15 kg, with the mean PDA diameter of 3.11 ± 0.99 mm. M-mode measurements (left ventricular end diastolic diameter, left atrium diameter to aortic annulus ratio, ejection fraction, and shortening fraction) reduced significantly early after PDA closure ( p  < 0.001). After 1 month, left ventricular end diastolic diameter and left atrium diameter to aortic annulus ratio continued to decrease, while ejection fraction and fractional shortening improved significantly. All tissue Doppler velocities showed a significant decrease at 48 hours with significant prolongation of global myocardial function ( p  < 0.001) and then were normalized within 1 month postclosure. Similarly, global longitudinal strain significantly decreased at 48 hours postclosure ( p  < 0.001), which also recovered at 1 month follow-up. Preclosure global longitudinal strain showed a good correlation with the postclosure prolongation of the myocardial performance index. Transcatheter PDA closure causes a significant decrease in left ventricular performance early after PDA closure, which recovers completely within 1 month. Preclosure global longitudinal strain can be a predictor of postclosure myocardial dysfunction.

An evaluation of the use of new Doppler methods for detecting longitudinal function abnormalities in a pacing-induced heart failure model

NASA Technical Reports Server (NTRS)

Tabata, Tomotsugu; Cardon, Lisa A.; Armstrong, Guy P.; Fukamach, Kiyotaka; Takagaki, Masami; Ochiai, Yoshie; McCarthy, Patrick M.; Thomas, James D.

2003-01-01

BACKGROUND: Doppler tissue echocardiography and color M-mode Doppler flow propagation velocity have proven useful in evaluating cross-sections of patients with left ventricular (LV) dysfunction, but experience with serial changes is limited. Purpose and methods: We tested their use by evaluating the temporal changes of LV function in a pacing-induced congestive heart failure model. Rapid ventricular pacing was initiated and maintained in 20 dogs for 4 weeks. Echocardiography was performed at baseline and weekly during brief pacing cessation. RESULTS: With rapid pacing, LV volume significantly increased and ejection fraction (57%-28%), stroke volume (37-18 mL), and mitral annulus systolic velocity (16.1-6.6 cm/s) by Doppler tissue echocardiography significantly decreased, with ejection fraction and mitral annulus systolic velocity closely correlated (r = 0.706, P <.0001). In contrast to the mitral inflow velocities, mitral annulus early diastolic velocity decreased steadily (12.3-7.3 cm/s) resulting in a dramatic decrease in mitral annulus early/late (1.22-0.57) diastolic velocity with no tendency toward pseudonormalization. The color M-mode Doppler flow propagation velocity also showed significant steady decrease (57-24 cm/s) throughout the pacing period. Multiple regression analysis chose mitral annulus systolic velocity (r = 0.895, P <.0001) and propagation velocity (r = 0.782, P <.0001) for the most important factor predicting LV systolic and diastolic function, respectively. CONCLUSIONS: Doppler tissue echocardiography and color M-mode Doppler flow could evaluate the serial deterioration in LV dysfunction throughout the pacing period. These were more useful in quantifying progressive LV dysfunction than conventional ehocardiographic techniques, and were probably relatively independent of preload. These techniques could be suitable for longitudinal evaluation in addition to the cross-sectional study.

Global longitudinal strain in patients with suspected heart failure and a normal ejection fraction: does it improve diagnosis and risk stratification?

PubMed

Pellicori, Pierpaolo; Kallvikbacka-Bennett, Anna; Khaleva, Olga; Carubelli, Valentina; Costanzo, Pierluigi; Castiello, Teresa; Wong, Kenneth; Zhang, Jufen; Cleland, John G F; Clark, Andrew L

2014-01-01

Many patients have clinical, structural or bio-marker evidence of heart failure (HF) but a normal left ventricular ejection fraction (LVEF; HeFNEF). Measurement of global longitudinal strain (GLS) may add diagnostic and prognostic information. Patients with symptoms suggesting heart failure and LVEF ≥50% were studied: 76 had no substantial cardiac dysfunction (left atrial diameter (LAD) <40 mm and amino-terminal pro-brain natriuretic peptide (NTproBNP) <400 ng/l); 99 had "possible HeFNEF" (LAD ≥40 mm or NTproBNP ≥400 ng/l); and 138 had "definite HeFNEF" (LAD ≥40 mm and NTproBNP ≥400 ng/L). Mean LVEF was 58% in each subgroup. Patients with definite HeFNEF were older, more likely to have atrial fibrillation, had more symptoms and signs of fluid retention, were more likely to have right ventricular dysfunction and had higher pulmonary pressures than other groups. Mean GLS (SD) was less negative in patients with definite HeFNEF (-13.6 (3.0)% vs. possible HeFNEF: -15.2 (3.1)% vs. no substantial cardiac dysfunction: -15.9 (2.4)%; p < 0.001). GLS was -19.1 (2.1)% in 20 controls. During a median follow up of 647 days, cardiovascular death or an unplanned hospitalisation for heart failure occurred in 62 patients. In univariable analysis, GLS but not LVEF predicted events. However, in a multi-variable analysis, only urea, NTproBNP, left atrial volume, inferior vena cava diameter and atrial fibrillation independently predicted adverse outcome. GLS is abnormal in patients who have other evidence of HeFNEF, is associated with a worse prognosis in this population but is not a powerful independent predictor of outcome.

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.

Systolic versus diastolic heart failure in community practice: clinical features, outcomes, and the use of angiotensin-converting enzyme inhibitors.

PubMed

Philbin, E F; Rocco, T A; Lindenmuth, N W; Ulrich, K; Jenkins, P L

2000-12-01

Among patients with heart failure, there is controversy about whether there are clinical features and laboratory tests that can differentiate patients who have low ejection fractions from those with normal ejection fractions. The usefulness of angiotensin-converting enzyme (ACE) inhibitors among heart failure patients who have normal left ventricular ejection fractions is also not known. From a registry of 2,906 unselected consecutive patients with heart failure who were admitted to 10 acute-care community hospitals during 1995 and 1997, we identified 1291 who had a quantitative measurement of their left ventricular ejection fraction. Patients were separated into three groups based on ejection fraction: < or =0.39 (n = 741, 57%), 0.40 to 0.49 (n = 238, 18%), and > or =0.50 (n = 312, 24%). In-hospital mortality, prescription of ACE inhibitors at discharge, subsequent rehospitalization, quality of life, and survival were measured; survivors were observed for at least 6 months after hospitalization. The mean (+/- SD) age of the sample was 75+/-11 years; the majority (55%) of patients were women. In multivariate models, age >75 years, female sex, weight >72.7 kg, and a valvular etiology for heart failure were associated with an increased probability of having an ejection fraction > or =0.50; a prior history of heart failure, an ischemic or idiopathic cause of heart failure, and radiographic cardiomegaly were associated with a lower probability of having an ejection fraction > or =0.50. Total mortality was lower in patients with an ejection fraction > or =0.50 than in those with an ejection fraction < or =0.39 (odds ratio [OR] = 0.69, 95% confidence interval [CI 0.49 to 0.98, P = 0.04). Among hospital survivors with an ejection fraction of 0.40 to 0.49, the 65% who were prescribed ACE inhibitors at discharge had better mean adjusted quality-of-life scores (7.0 versus 6.2, P = 0.02), and lower adjusted mortality (OR = 0.34, 95% CI: 0.17 to 0.70, P = 0.01) during follow-up than those who were not prescribed ACE inhibitors. Among hospital survivors with an ejection fraction > or =0.50, the 45% who were prescribed ACE inhibitors at discharge had better (lower) adjusted New York Heart Association (NYHA) functional class (2.1 versus 2.4, P = 0.04) although there was no significant improvement in survival. Among patients treated for heart failure in community hospitals, 42% of those whose ejection fraction was measured had a relatively normal systolic function (ejection fraction > or 0.40). The clinical characteristics and mortality of these patients differed from those in patients with low ejection fractions. Among the patients with ejection fractions > or =0.40, the prescription of ACE inhibitors at discharge was associated favorable effects.

Preoperative levosimendan decreases mortality and the development of low cardiac output in high-risk patients with severe left ventricular dysfunction undergoing coronary artery bypass grafting with cardiopulmonary bypass

PubMed Central

Levin, Ricardo; Degrange, Marcela; Del Mazo, Carlos; Tanus, Eduardo; Porcile, Rafael

2012-01-01

BACKGROUND: The calcium sensitizer levosimendan has been used in cardiac surgery for the treatment of postoperative low cardiac output syndrome (LCOS) and difficult weaning from cardiopulmonary bypass (CPB). OBJECTIVES: To evaluate the effects of preoperative treatment with levosimendan on 30-day mortality, the risk of developing LCOS and the requirement for inotropes, vasopressors and intra-aortic balloon pumps in patients with severe left ventricular dysfunction. METHODS: Patient with severe left ventricular dysfunction and an ejection fraction <25% undergoing coronary artery bypass grafting with CPB were admitted 24 h before surgery and were randomly assigned to receive levosimendan (loading dose 10 μg/kg followed by a 23 h continuous infusion of 0.1μg/kg/min) or a placebo. RESULTS: From December 1, 2002 to June 1, 2008, a total of 252 patients were enrolled (127 in the levosimendan group and 125 in the control group). Individuals treated with levosimendan exhibited a lower incidence of complicated weaning from CPB (2.4% versus 9.6%; P<0.05), decreased mortality (3.9% versus 12.8%; P<0.05) and a lower incidence of LCOS (7.1% versus 20.8%; P<0.05) compared with the control group. The levosimendan group also had a lower requirement for inotropes (7.9% versus 58.4%; P<0.05), vasopressors (14.2% versus 45.6%; P<0.05) and intra-aortic balloon pumps (6.3% versus 30.4%; P<0.05). CONCLUSION: Patients with severe left ventricle dysfunction (ejection fraction <25%) undergoing coronary artery bypass grafting with CPB who were pretreated with levosimendan exhibited lower mortality, a decreased risk for developing LCOS and a reduced requirement for inotropes, vasopressors and intra-aortic balloon pumps. Studies with a larger number of patients are required to confirm whether these findings represent a new strategy to reduce the operative risk in this high-risk patient population. PMID:23620700

Left atrial dysfunction in patients with patent foramen ovale and atrial septal aneurysm: an alternative concurrent mechanism for arterial embolism?

PubMed

Rigatelli, Gianluca; Aggio, Silvio; Cardaioli, Paolo; Braggion, Gabriele; Giordan, Massimo; Dell'avvocata, Fabio; Chinaglia, Mauro; Rigatelli, Giorgio; Roncon, Loris; Chen, Jack P

2009-07-01

We postulate that, in patients with large patent foramen ovales (PFO) and atrial septal aneurysms (ASA), left atrial (LA) dysfunction simulating "atrial fibrillation (AF)-like" pathophysiology might represent an alternate mechanism in the promotion of arterial embolism. Despite prior reports concerning paradoxical embolism through a PFO, the magnitude of this phenomenon as a risk factor for stroke remains undefined, because deep venous thrombosis is infrequently detected in such patients. To test our hypothesis, we prospectively enrolled 98 consecutive patients with previous stroke (mean age 37 +/- 12.5 years, 58 women) referred to our center for catheter-based PFO closure. Baseline values of LA passive and active emptying, LA conduit function, LA ejection fraction, and spontaneous echocontrast (SEC) in the LA and LA appendage were compared with those of 50 AF patients as well as a sex/age/cardiac risk-matched population of 70 healthy control subjects. Pre-closure PFO subjects demonstrated significantly greater reservoir function as well as passive and active emptying, with significantly reduced conduit function and LA ejection fraction, when compared with AF and control patients. Furthermore, in PFO patients, 66.3% (65 of 98) had moderate-to-severe ASA and basal shunt; SEC was observed in 52% of PFO plus ASA patients before closure. Multivariate stepwise logistic regression revealed moderate-to-severe ASA (odds ratio: 9.4, 95% confidence interval: 7.0 to 23.2, p < 0.001) as the most powerful predictor of LA dysfunction. After closure, all LA parameters normalized to the levels of control subjects: no SEC, device-related thrombosis, or aortic erosion were observed on follow-up echocardiography. This study suggests that moderate-to-severe ASA might be associated with LA dysfunction in patients with PFO. The resultant similarities to the pathophysiology of AF might represent an additional contributing mechanism for arterial embolism in such patients.

Ejection Fraction: What Does It Measure?

MedlinePlus

... does the term "ejection fraction" mean? What does it measure? Answers from Rekha Mankad, M.D. Ejection fraction ... percentage of blood leaving your heart each time it contracts. During each heartbeat pumping cycle, the heart ...

High Serum sTREM-1 Correlates With Myocardial Dysfunction and Predicts Prognosis in Septic Patients.

PubMed

Li, Zhenyu; Zhang, Enyuan; Hu, Yipeng; Liu, Yi; Chen, Bing

2016-06-01

This study aimed to evaluate the predictive and prognostic value of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in patients with myocardial dysfunction induced by severe sepsis and septic shock. A total of 84 patients with severe sepsis and septic shock were enrolled between May 2013 and December 2014.The patients were monitored by pulse indicator continuous cardiac output system and divided into myocardial depression group (cardiac function index [CFI] < 4.1/minute, n = 37) and nonmyocardial depression group (CFI ≥ 4.1/minute, n = 47 ). Additionally, the patients were divided into survival group (n = 40) and nonsurvival group (n = 44) based on 28-day mortality. Hemodynamic parameters and serum sTREM-1, B-type natriuretic peptide (BNP) and cardiac troponin I (cTnI) levels were collected on days 1, 3 and 5 after admission to intensive care unit. (1) The serum values of sTREM-1, BNP and cTnI in myocardial depression group were higher than those in nonmyocardial depression group (P < 0.01); and CFI, cardiac index, stroke volume, global ejection fraction and left ventricular contractility index (dpmax) in myocardial depression group were lower than those in nonmyocardial depression group on day 1 (P < 0.05); (2) serum sTREM-1 negatively correlated with left ventricular ejection fraction, CFI, cardiac index, global ejection fraction and dpmax, and it positively correlated with BNP and cTnI (P < 0.01); (3) the area under the receiver operating characteristics curve for sTREM-1 in the prediction of myocardial depression was 0.671 with a sensitivity of 83.8% and a specificity of 46.8% when cutoff point was 174.5ng/mL, the power of predicting septic depression for sTREM-1 was lower than that of BNP; logistic regression analysis showed that serum sTREM-1 was not an independent predictor of septic myocardial depression; the area under the receiver operating characteristics curve was 0.773 for sTREM-1 in predicting outcome with a sensitivity of 86.4% and a specificity of 80% when cutoff point was 182.3ng/mL, the power of predicting prognosis for sTREM-1 was superior to those of BNP and cTnI; (4) there was a decrease trend for sTREM-1 levels and an increasing trend for CFI in the survival group (P < 0.05). Myocardial dysfunction is common in patients with severe sepsis and septic shock and high serum levels of sTREM-1 correlates with myocardial dysfunction to some extent but is not an independent predictor, which more importantly showed prognostic value for septic shock outcome. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

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.

New diagnostic and therapeutic possibilities for diastolic heart failure.

PubMed

Jeong, Euy-Myoung; Dudley, Samuel C

2014-02-03

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

Rate of change of left ventricular ejection fraction during exercise is superior to the peak ejection fraction for predicting functionally significant coronary artery disease.

PubMed Central

Sridhara, B S; Bhattacharya, S; Liu, X J; Broadhurst, P; Lahiri, A

1993-01-01

OBJECTIVE--To detect and characterise rapid temporal changes in the left ventricular response to exercise in patients with ischaemic heart disease and to relate these changes to the functional severity of coronary artery disease. BACKGROUND--The gamma camera does not allow the detection of rapid changes in cardiac function during exercise radionuclide ventriculography, the monitoring of which may improve the assessment of patients with ischaemic heart disease. METHODS--A miniature nuclear probe (Cardioscint) was used to monitor continuously left ventricular function during exercise in 31 patients who had coronary angiography for suspected coronary artery disease. A coronary angiographic jeopardy score was calculated for each patient. RESULTS--The coronary jeopardy score ranged from 0 to 12 (median 4). Ejection fraction fell significantly during exercise from 46% to 34%. Patients were divided into two groups based on the response of their ejection fraction to exercise. In 14 patients (group I), the peak change in ejection fraction coincided with the end of exercise, whereas in the other 17 patients (group II) the peak change in ejection fraction occurred before the end of exercise, resulting in a brief plateau. The peak change in ejection fraction and the time to its occurrence were independent predictors of coronary jeopardy (r = -0.59, p < 0.001 for peak change and r = -0.69, p < 0.001 for time to that change). The rate of change in ejection fraction was the strongest predictor of coronary jeopardy (r = -0.81, p < 0.001). In group I the peak change in ejection fraction was a poor predictor severity of coronary disease (r = -0.28, NS), whereas the time to peak and the rate of change in ejection fraction were good predictors (r = -0.65 and r = -0.73, p < 0.01). In group II the peak, the time to the peak, and the rate of change in ejection fraction were good predictors of coronary jeopardy (r = -0.75, r = -0.61, and r = -0.83, p < 0.01). CONCLUSION--The rate of change of ejection fraction during exercise can be assessed by continuous monitoring of left ventricular function with the nuclear probe, and is the best predictor of functionally significant coronary artery disease. PMID:8280514

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

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

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.

Physiologic abnormalities of cardiac function in progressive systemic sclerosis with diffuse scleroderma

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

Follansbee, W.P.; Curtiss, E.I.; Medsger, T.A. Jr.

1984-01-19

To investigate cardiopulmonary function in progressive systemic sclerosis with diffuse scleroderma, we studied 26 patients with maximal exercise and redistribution thallium scans, rest and exercise radionuclide ventriculography, pulmonary-function testing, and chest roentgenography. Although only 6 patients had clinical evidence of cardiac involvement, 20 had abnormal thallium scans, including 10 with reversible exercise-induced defects and 18 with fixed defects (8 had both). Seven of the 10 patients who had exercise-induced defects and underwent cardiac catheterization had normal coronary angiograms. Mean resting left ventricular ejection fraction and mean resting right ventricular ejection fraction were lower in patients with post-exercise left ventricular thalliummore » defect scores above the median (59 +/- 13 per cent vs. 69 +/- 6 per cent, and 36 +/- 12 per cent vs. 47 +/- 7 per cent, respectively). The authors conclude that in progressive systemic sclerosis with diffuse scleroderma, abnormalities of myocardial perfusion are common and appear to be due to a disturbance of the myocardial microcirculation. Both right and left ventricular dysfunction appear to be related to this circulatory disturbance, suggesting ischemically mediated injury.« less

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.

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

PubMed

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

1978-03-01

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

Extracting and analyzing ejection fraction values from electronic echocardiography reports in a large health maintenance organization.

PubMed

Xie, Fagen; Zheng, Chengyi; Yuh-Jer Shen, Albert; Chen, Wansu

2017-12-01

The left ventricular ejection fraction value is an important prognostic indicator of cardiovascular outcomes including morbidity and mortality and is often used clinically to indicate severity of heart disease. However, it is usually reported in free-text echocardiography reports. We developed and validated a computerized algorithm to extract ejection fraction values from echocardiography reports and applied the algorithm to a large volume of unstructured echocardiography reports between 1995 and 2011 in a large health maintenance organization. A total of 621,856 echocardiography reports with a description of ejection fraction values or systolic functions were identified, of which 70 percent contained numeric ejection fraction values and the rest (30%) were text descriptions explicitly indicating the systolic left ventricular function. The 12.1 percent (16.0% for male and 8.4% for female) of these extracted ejection fraction values are <45 percent. Validation conducted based on a random sample of 200 reports yielded 95.0 percent sensitivity and 96.9 percent positive predictive value.

Impact of a systolic parameter, defined as the ratio of right brachial pre-ejection period to ejection time, on the relationship between brachial-ankle pulse wave velocity and left ventricular diastolic function.

PubMed

Hsu, Po-Chao; Lin, Tsung-Hsien; Lee, Chee-Siong; Chu, Chun-Yuan; Su, Ho-Ming; Voon, Wen-Chol; Lai, Wen-Ter; Sheu, Sheng-Hsiung

2011-04-01

Arterial stiffness is correlated with left ventricular (LV) diastolic function as well as susceptibility to LV systolic function. Therefore, if LV systolic function is not known, the relationship between arterial stiffness and LV diastolic function is difficult to determine. A total of 260 patients were included in the study. The brachial-ankle pulse wave velocity (baPWV) and the ratio of right brachial pre-ejection period to ejection time (rbPEP/rbET) were measured using an ABI-form device. Patients were classified into four groups. Groups 1, 2, 3 and 4 were patients with rbPEP/rbET and baPWV below the median, rbPEP/rbET above but baPWV below the median, rbPET/rbET below but baPWV above the median, and rbPET/rbET and baPWV above the median, respectively. The LV ejection fractions in groups 1 and 3 were higher than those in groups 2 and 4 (P<0.001 for all). Patients in group 1 had a lower left atrial volume index (LAVI) and higher early diastolic mitral annular velocity (Ea) than patients in the other groups (P≤0.002). Patients in group 2 had a LAVI and ratio of transmitral E wave velocity to Ea that were comparable to those in groups 3 and 4. In conclusion, rbPEP/rbET had an impact on the relationship between baPWV and LV diastolic function. In patients with high rbPEP/rbET but low baPWV, low baPWV may not indicate good LV diastolic function but implies that cardiac dysfunction may precede vascular dysfunction in such patients. When interpreting the relationship between baPWV and LV diastolic function, the rbPEP/rbET value obtained from the same examination should be considered.

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

PubMed

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

2017-01-01

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

Oxidative stress contributes to methamphetamine-induced left ventricular dysfunction.

PubMed

Lord, Kevin C; Shenouda, Sylvia K; McIlwain, Elizabeth; Charalampidis, Dimitrios; Lucchesi, Pamela A; Varner, Kurt J

2010-07-01

Our aim was to test the hypothesis that the repeated, binge administration of methamphetamine would produce oxidative stress in the myocardium leading to structural remodeling and impaired left ventricular function. Echocardiography and Millar pressure-volume catheters were used to monitor left ventricular structure and function in rats subjected to four methamphetamine binges (3 mg/kg, iv for 4 days, separated by a 10-day drug-free period). Hearts from treated and control rats were used for histological or proteomic analysis. When compared with saline treatment, four methamphetamine binges produced eccentric left ventricular hypertrophy. The drug also significantly impaired systolic function (decreased fractional shortening, ejection fraction, and adjusted maximal power) and produced significant diastolic dysfunction (increased -dP/dt and tau). Dihydroethedium staining showed that methamphetamine significantly increased (285%) the levels of reactive oxygen species in the left ventricle. Treatment with methamphetamine also resulted in the tyrosine nitration of myofilament (desmin, myosin light chain) and mitochondrial (ATP synthase, NADH dehydrogenase, cytochrome c oxidase, prohibitin) proteins. Treatment with the superoxide dismutase mimetic, tempol in the drinking water prevented methamphetamine-induced left ventricular dilation and systolic dysfunction; however, tempol (2.5 mM) did not prevent the diastolic dysfunction. Tempol significantly reduced, but did not eliminate dihydroethedium staining in the left ventricle, nor did it prevent the tyrosine nitration of mitochondrial and contractile proteins. This study shows that oxidative stress plays a significant role in mediating methamphetamine-induced eccentric left ventricular dilation and systolic dysfunction.

Oxidative stress contributes to methamphetamine-induced left ventricular dysfunction

PubMed Central

Lord, Kevin C.; Shenouda, Sylvia K.; McIlwain, Elizabeth; Charalampidis, Dimitrios; Lucchesi, Pamela A.; Varner, Kurt J.

2010-01-01

Aims Our aim was to test the hypothesis that the repeated, binge administration of methamphetamine would produce oxidative stress in the myocardium leading to structural remodeling and impaired left ventricular function. Methods and results Echocardiography and Millar pressure–volume catheters were used to monitor left ventricular structure and function in rats subjected to four methamphetamine binges (3 mg/kg, iv for 4 days, separated by a 10-day drug-free period). Hearts from treated and control rats were used for histological or proteomic analysis. When compared with saline treatment, four methamphetamine binges produced eccentric left ventricular hypertrophy. The drug also significantly impaired systolic function (decreased fractional shortening, ejection fraction, and adjusted maximal power) and produced significant diastolic dysfunction (increased −dP/dt and tau). Dihydroethedium staining showed that methamphetamine significantly increased (285%) the levels of reactive oxygen species in the left ventricle. Treatment with methamphetamine also resulted in the tyrosine nitration of myofilament (desmin, myosin light chain) and mitochondrial (ATP synthase, NADH dehydrogenase, cytochrome c oxidase, prohibitin) proteins. Treatment with the superoxide dismutase mimetic, tempol in the drinking water prevented methamphetamine-induced left ventricular dilation and systolic dysfunction; however, tempol (2.5 mM) did not prevent the diastolic dysfunction. Tempol significantly reduced, but did not eliminate dihydroethedium staining in the left ventricle, nor did it prevent the tyrosine nitration of mitochondrial and contractile proteins. Conclusion This study shows that oxidative stress plays a significant role in mediating methamphetamine-induced eccentric left ventricular dilation and systolic dysfunction. PMID:20139112

Folic acid prevents cardiac dysfunction and reduces myocardial fibrosis in a mouse model of high-fat diet-induced obesity.

PubMed

Li, Wei; Tang, Renqiao; Ouyang, Shengrong; Ma, Feifei; Liu, Zhuo; Wu, Jianxin

2017-01-01

Folic acid (FA) is an antioxidant that can reduce reactive oxygen species generation and can blunt cardiac dysfunction during ischemia. We hypothesized that FA supplementation prevents cardiac fibrosis and cardiac dysfunction induced by obesity. Six-week-old C57BL6/J mice were fed a high-fat diet (HFD), normal diet (ND), or an HFD supplemented with folic acid (FAD) for 14 weeks. Cardiac function was measured using a transthoracic echocardiographic exam. Phenotypic analysis included measurements of body and heart weight, blood glucose and tissue homocysteine (Hcy) content, and heart oxidative stress status. HFD consumption elevated fasting blood glucose levels and caused obesity and heart enlargement. FA supplementation in HFD-fed mice resulted in reduced fasting blood glucose, heart weight, and heart tissue Hcy content. We also observed a significant cardiac systolic dysfunction when mice were subjected to HFD feeding as indicated by a reduction in the left ventricular ejection fraction and fractional shortening. However, FAD treatment improved cardiac function. FA supplementation protected against cardiac fibrosis induced by HFD. In addition, HFD increased malondialdehyde concentration of the heart tissue and reduced the levels of antioxidant enzyme, glutathione, and catalase. HFD consumption induced myocardial oxidant stress with amelioration by FA treatment. FA supplementation significantly lowers blood glucose levels and heart tissue Hcy content and reverses cardiac dysfunction induced by HFD in mice. These functional improvements of the heart may be mediated by the alleviation of oxidative stress and myocardial fibrosis.

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.

Left ventricular diastolic dysfunction in women with nonobstructive ischemic heart disease: insights from magnetic resonance imaging and spectroscopy.

PubMed

Nelson, Michael D

2017-10-01

Ischemic heart disease, in the absence of obstructive coronary artery disease, is prevalent in women and constitutes a major risk factor for developing major adverse cardiovascular events, including myocardial infarction, stroke, and heart failure. For decades, diagnosis was considered benign and often minimized; however, it is now known that this etiology carries much risk and is a significant burden to the health care system. This review summarizes the current state of knowledge on nonobstructive ischemic heart disease (NOIHD), the association between NOIHD and left ventricular diastolic dysfunction, potential links between NOIHD and the development of heart failure with preserved ejection fraction (HFpEF), and therapeutic options and knowledge gaps for patients living with NOIHD. Copyright © 2017 the American Physiological Society.

[Understanding heart failure].

PubMed

Boo, José Fernando Guadalajara

2006-01-01

Heart failure is a disease with several definitions. The term "heart failure" is used by has brougth about confusion in the terminology. For this reason, the value of the ejection fraction (< 0.40 or < 0.35) is used in most meganalyses on the treatment of heart failure, avoiding the term "heart failure" that is a confounding concept. In this paper we carefully analyze the meaning of contractility, ventricular function or performance, preload, afterload, heart failure, compensation mechanisms in heart failure, myocardial oxygen consumption, inadequate, adequate and inappropriate hypertrophy, systole, diastole, compliance, problems of relaxation, and diastolic dysfunction. Their definitions are supported by the original scientific descriptions in an attempt to clarify the concepts about ventricular function and heart failure and, in this way, use the same scientific language about the meaning of ventricular function, heart failure, and diastolic dysfunction.

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.

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.

Usefulness of Electrocardiographic QT Interval to Predict Left Ventricular Diastolic Dysfunction

PubMed Central

Wilcox, Jane E.; Rosenberg, Jonathan; Vallakati, Ajay; Gheorghiade, Mihai; Shah, Sanjiv J.

2013-01-01

Whether a normal electrocardiogram excludes left ventricular (LV) diastolic dysfunction (DD) and whether electrocardiographic parameters are associated with DD is unknown. We therefore sought to investigate the relation between electrocardiographic parameters and DD. We first evaluated 75 consecutive patients referred for echocardiography for clinical suspicion of heart failure (phase 1). Electrocardiography and comprehensive echocardiography were performed on all patients and were analyzed separately in a blinded fashion. Receiver operating characteristic curves and multivariate regression analyses were used to determine which electrocardiographic parameters were most closely associated with DD. Next, we prospectively validated our results in 100 consecutive, unselected patients undergoing echocardiography (phase 2). In phase 1 of our study, the mean age was 59 ± 14 years, 41% were women, 31% had coronary disease, 53% had hypertension, and 25% had diabetes. The mean ejection fraction was 54 ± 15%, and 64% had DD. Of all the electrocardiographic parameters, the QTc interval was most closely associated with DD. QTc was inversely associated with E′ velocity (r = −0.54, p <0.0001), and the area under the receiver operating characteristic curve for QTc as a predictor of DD was 0.82. QTc prolongation was independently associated with reduced E′ velocity (p = 0.021 after adjustment for age, gender, medications, QRS duration, and ejection fraction). In phase 2 of our study QTc was the electrocardiographic parameter most associated with reduced E′ velocity (435 ± 31 vs 419 ± 24 ms; p = 0.004), confirming our phase 1 study findings. In conclusion, QTc prolongation was the electrocardiographic marker most predictive of DD and was independently associated with DD. PMID:21907948

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

PubMed

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

2017-05-01

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

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.

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

PubMed

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

2015-09-15

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

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

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)

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

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.

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

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.

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.

Is mitral valve repair superior to replacement for chronic ischemic mitral regurgitation with left ventricular dysfunction?

PubMed Central

2010-01-01

Background This study was undertaken to compare mitral valve repair and replacement as treatments for ischemic mitral regurgitation (IMR) with left ventricular dysfunction (LVD). Specifically, we sought to determine whether the choice of mitral valve procedure affected survival, and discover which patients were predicted to benefit from mitral valve repair and which from replacement. Methods A total of 218 consecutive patients underwent either mitral valve repair (MVP, n = 112) or mitral valve replacement (MVR, n = 106). We retrospectively reviewed the clinical material, operation methods, echocardiography check during operation and follow-up. Patients details and follow-up outcomes were compared using multivariate and Kaplan-Meier analyses. Results No statistical difference was found between the two groups in term of intraoperative data. Early mortality was 3.2% (MVP 2.7% and MVR 3.8%). At discharge, Left ventricular end-systolic and end-diastolic diameter and left ventricular ejection fraction (LVEF) were improved more in the MVP group than MVR group (P < 0.05), however, in follow-up no statistically significant difference was observed between the MVR and MVP group (P > 0.05). Follow-up mitral regurgitation grade was significantly improved in the MVR group compared with the MVP group (P < 0.05). The Kaplan-Meier survival estimates at 1, 3, and 5 years were simlar between MVP and MVR group. Logistic regression revealed poor survival was associated with old age(#75), preoperative renal insufficiency and low left ventricular ejection fraction (< 30%). Conclusion Mitral valve repair is the procedure of choice in the majority of patients having surgery for severe ischemic mitral regurgitation with left ventricular dysfunction. Early results of MVP treatment seem to be satisfactory, but several lines of data indicate that mitral valve repair provided less long-term benefit than mitral valve replacement in the LVD patients. PMID:21059216

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

PubMed

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

2016-04-01

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

ASSESSMENT OF DIASTOLIC DYSFUNCTION, ARTERIAL STIFFNESS, AND CAROTID INTIMA-MEDIA THICKNESS IN PATIENTS WITH ACROMEGALY.

PubMed

Cansu, Güven Barış; Yılmaz, Nusret; Yanıkoğlu, Atakan; Özdem, Sebahat; Yıldırım, Aytül Belgi; Süleymanlar, Gültekin; Altunbaş, Hasan Ali

2017-05-01

Early diagnosis and treatment of cardiovascular diseases, the most frequent cause of morbidity and mortality in acromegaly, may be an efficient approach to extending the lifespan of affected patients. Therefore, it is crucial to determine any cardiovascular diseases in the subclinical period. The study objectives were to determine markers of subclinical atherosclerosis and asses heart structure and function. This was a cross-sectional, single-center study of 53 patients with acromegaly and 22 age- and sex-matched healthy individuals. Carotid intima-media thickness (CIMT), pulse-wave velocity (PWV), and echocardiographic data were compared between these groups. CIMT and PWV were higher in the acromegaly group than in the healthy group (P = .008 and P = .002, respectively). Echocardiography showed that left ventricular diastolic dysfunction was present in 11.3% of patients. Left ventricular mass index and left atrial volume index were higher in the patients (P = .016 and P<.001, respectively). No differences in the CIMT, PWV, or echocardiographic measurements were identified between the patients with biochemically controlled and uncontrolled acromegaly and the control group. Our results showed that subclinical atherosclerosis (i.e., CIMT and PWV markers) and heart structure and function were worse in patients with acromegaly than in healthy individuals. Because there were no differences in these parameters between patients with controlled and uncontrolled acromegaly, our results suggest that the structural and functional changes do not reverse with biochemical control. AA = active acromegaly BSA = body surface area CA = biochemically controlled acromegaly CH = concentric hypertrophy CIMT = carotid intima-media thickness DBP = diastolic blood pressure DM = diabetes mellitus ECHO = echocardiography EDV = enddiastolic volume EF = ejection fraction ESV = endsystolic volume GH = growth hormone HC = healthy control HL = hyperlipidemia HT = hypertension IGF-1 = insulin-like growth factor 1 LA = left atrial LAV = left atrial volume LAVI = left atrial volume index LV = left ventricular LVDD = left ventricular diastolic dysfunction LVEF = left ventricular ejection fraction LVH = left ventricular hypertrophy LVMI = left ventricular mass index PWV = pulse-wave velocity RWT = relative wall thickness.

Right Atrial Dysfunction in the Fetus with Severely Regurgitant Tricuspid Valve Disease: A Potential Source of Cardiovascular Compromise.

PubMed

Howley, Lisa W; Khoo, Nee Scze; Moon-Grady, Anita J; Patel, Sonali S; Alrais, Fayeza; Tworetzky, Wayne; Colen, Timothy; Brooks, Paul; Trines, Jean; Ojala, Tiina; Hornberger, Lisa K

2017-06-01

In severe right heart obstruction (RHO), redistribution of cardiac output to the left ventricle (LV) is well tolerated by the fetal circulation. Although the same should be true of severely regurgitant tricuspid valve disease (rTVD) with reduced or no output from the right ventricle, affected fetuses more frequently develop hydrops or suffer intrauterine demise. We hypothesized that right atrium (RA) function is altered in rTVD but not in RHO, which could contribute to differences in outcomes. Multi-institutional retrospective review of fetal echocardiograms performed over a 10-year period on fetuses with rTVD (Ebstein's anomaly, tricuspid valve dysplasia) or RHO (pulmonary atresia/intact ventricular septum, tricuspid atresia) and a healthy fetal control group. Offline velocity vector imaging and Doppler measurements of RA size and function and LV function were made. Thirty-four fetuses with rTVD, 40 with RHO, and 79 controls were compared. The rTVD fetuses had the largest RA size and lowest RA expansion index, fractional area of change, and RA indexed filling and emptying rates compared with fetuses with RHO and controls. The rTVD fetuses had the shortest LV ejection time and increased Tei index with a normal LV ejection fraction. RA dilation (odds ratio, 1.27; 95% CI, 1.05-1.54) and reduced indexed emptying rate (odds ratio, 2.49; 95% CI, 1.07-5.81) were associated with fetal or neonatal demise. Fetal rTVD is characterized by more severe RA dilation and dysfunction compared with fetal RHO and control groups. RA dysfunction may be an important contributor to reduced ventricular filling and output, potentially playing a critical role in the worsened outcomes observed in fetal rTVD. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Regional and global right ventricular dysfunction in asymptomatic or minimally symptomatic patients with congenitally corrected transposition.

PubMed

Tulevski, Igor I; Zijta, Frank M; Smeijers, Anika S; Dodge-Khatami, Ali; van der Wall, Ernst E; Mulder, Barbara J M

2004-04-01

Patients with congenitally corrected transposition are at risk of right ventricular dysfunction and failure. With this in mind, we examined 13 patients with congenitally corrected transposition, 7 not having undergone surgery, and 6 after physiological repair, comparing them with 6 healthy subjects matched for age and sex, using cardiac magnetic resonance imaging, at rest and during dobutamine stress, in order to determine regional and global right ventricular response to stress. At rest, the patients had significantly decreased overall wall motion compared to their healthy peers (7.2 +/- 0.5, versus 9.8 +/- 0.4 mm). During infusion of dobutamine, overall wall motion increased to 12.8 +/- 0.4 mm in the healthy subjects, versus 8.8 +/- 1.0 mm in patients. At the regional level, significant differences in mural motion were found between patients and controls in the anterior (9.5 +/- 1.1, versus 13.2 +/- 0.6 mm), posterior (10.2 +/- 1.6, versus 13.2 +/- 0.8 mm), and septal segments (5.0 +/- 0.8, versus 11.2 +/- 0.6 mm). At rest, overall mural thickening in patients was similar to that of controls, but significantly less in patients during stress. During dobutamine stress, patients showed significantly less regional wall thickening than controls, particularly in the septal (2.7 +/- 0.6, versus 6.0 +/- 0.4 mm, respectively) and in the anterior segments (4.2 +/- 0.6, versus 7.8 +/- 0.6 mm, respectively). Right ventricular ejection fraction strongly correlated with mural motion and thickening, both at rest and during stress. Abnormal regional function in the systemic morphologically right ventricle may occur in patients with congenitally corrected transposition, which strongly correlates with right ventricular ejection fraction. Our findings support the hypothesis that, in patients with congenitally corrected transposition, ischemia of the right ventricular myocardium contributes to the development of right ventricular dysfunction.

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

PubMed Central

Chirinos, Julio A.; Zamani, Payman

2016-01-01

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

Potential Expanded Indications for Neprilysin Inhibitors

PubMed Central

Riddell, Elizabeth; Vader, Justin M.

2017-01-01

Purpose of review The goal of this article is to review potential expanded indications for neprilysin inhibitors. This article reviews the rationale and design for ongoing and future trials of sacubitril/valsartan in cardiovascular and non-cardiovascular disease. Recent findings Randomized trial data are lacking for use of sacubitril/valsartan in acute heart failure and advanced heart failure. Mechanistic data from animal studies suggest a role for neprilysin inhibition in the treatment of post-myocardial infarction systolic dysfunction and heart failure with preserved ejection fraction. Beyond the cardiovascular system, renal and neurological function may be impacted by neprilysin inhibition. Forthcoming randomized trials will address the clinical impact of sacubitril/valsartan on these conditions. Summary Neprolysin inhibition with sacubitril/valsartan offers a new therapeutic strategy with a broad range of potential therapeutic actions. In PARADIGM-HF, the combination of neprolysin and RAAS inhibition was proven to be superior to enalapril for patients with stable NYHA class II–III heart failure and reduced left ventricular ejection fraction. Preliminary data suggests it may also have a role in other cardiovascular and non-cardiovascular disease. Several ongoing and planned studies will determine the extent of its benefit for these other indications. PMID:28281174

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/.

Radionuclide evaluation of left ventricular function with nonimaging probes.

PubMed

Wexler, J P; Blaufox, M D

1979-10-01

Portable nonimaging probes have been developed that can evaluate left ventricular function using radionuclide techniques. Two modes of data acquisition are possible with these probe systems, first-pass and gated. Precordial radiocardiograms obtained after a bolus injection can be used to determine cardiac output, pulmonary transit time, pulmonary blood volume, left ventricle ejection fraction, and left-to-right shunts. Gated techniques can be used to determine left ventricular ejection fraction and sytolic time intervals. Probe-determined indices of left ventricular function agree excellently with comparable measurements determined by conventional camera-computer methods as well as by invasive techniques. These have begun to be used in a preliminary manner in a variety of clinical problems associated with left ventricular dysfunction. This review discusses the types of probe systems available, the methods used in positioning them, and details the specifics of their data acquisition and processing capacity. The major criticisms of probe methods are that they are nonimaging and that they measure global rather than regional left ventricular function. In spite of these criticisms, probe systems, because of their portability, high sensitivity, and relatively low cost are useful supplements to conventional camera-computer systems for the measurement of parameters of left ventricular performance using radionuclide techniques.

The Prevalence, Correlates, and Impact on Cardiac Mortality of Right Ventricular Dysfunction in Nonischemic Cardiomyopathy.

PubMed

Pueschner, Andreas; Chattranukulchai, Pairoj; Heitner, John F; Shah, Dipan J; Hayes, Brenda; Rehwald, Wolfgang; Parker, Michele A; Kim, Han W; Judd, Robert M; Kim, Raymond J; Klem, Igor

2017-10-01

This study sought to determine the prevalence, correlates, and impact on cardiac mortality of right ventricular (RV) dysfunction in nonischemic cardiomyopathy. Current heart failure guidelines place little emphasis on RV assessment due to limited available data on determinants of RV function, mechanisms leading to its failure, and relation to outcomes. We prospectively studied 423 patients with cardiac magnetic resonance (CMR). The pre-specified study endpoint was cardiac mortality. In 100 patients, right heart catheterization was performed as clinically indicated. During a median follow-up time of 6.2 years (interquartile range: 2.9 to 7.6 years), 101 patients (24%) died of cardiac causes. CMR right ventricular ejection fraction (RVEF) was a strong independent predictor of cardiac mortality after adjustment for age, heart failure-functional class, blood pressure, heart rate, serum sodium, serum creatinine, myocardial scar, and left ventricular ejection fraction (LVEF). Patients with the lowest quintile of RVEF had a nearly 5-fold higher cardiac mortality risk than did patients with the highest quintile (hazard ratio: 4.68; 95% confidence interval [CI]: 2.43 to 9.02; p < 0.0001). RVEF was positively correlated with LVEF (r = 0.60; p < 0.0001), and inversely correlated with right atrial pressure (r = -0.32; p = 0.001), pulmonary artery pressure (r = -0.34; p = 0.0005), transpulmonary gradient (r = -0.28; p = 0.006) but not with pulmonary wedge pressure (r = -0.15; p = 0.13). In multivariable logistic regression analysis of CMR, clinical, and hemodynamic data the strongest predictors of right ventricular dysfunction were LVEF (odds ratio [OR]: 0.85; 95% CI: 0.78 to 0.92; p < 0.0001), transpulmonary gradient (OR: 1.20; 95% CI: 1.09 to 1.32; p = 0.0003), and systolic blood pressure (OR: 0.97; 95% CI: 0.94 to 0.99; p = 0.02). CMR assessment of RVEF provides important prognostic information independent of established risk factors and LVEF in heart failure patients with nonischemic cardiomyopathy. Right ventricular dysfunction is strongly associated with both indices of intrinsic myocardial contractility and increased afterload from pulmonary vascular dysfunction. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

[Left ventricular dysfunction measured in diabetic patients with chronic renal failure on continuous ambulatory peritoneal dialysis].

PubMed

Díaz-Arrieta, Gustavo; Mendoza-Hernández, María Elsa; Pacheco-Aranda, Erika; Rivas-Duro, Miguel; Robles-Parra, Héctor Manuel; Espinosa-Vázquez, Raúl Arturo; Hernández-Cabrera, Jorge

2010-01-01

In diabetic patients with chronic renal failure (CRF) treated with dialysis, the diastolic and systolic left ventricular dysfunction is frequent. The aim was to assess by echocardiography the prevalence of diastolic and systolic ventricular dysfunction in diabetic patients with CRF treated with continuous ambulatory peritoneal dialysis (CAPD). Sixty diabetic patients with CRF in CAPD were studied. The mean age was 54.5 +/- 12 years (27-78 years). The left ventricular filling pattern (LVFP) as a diastolic function parameter and left ventricular ejection fraction (LVEF) as a systolic function parameter were measured by transthoracic echocardiography. Descriptive statistical analysis was used. 27 (45 %) patients were women and 33 (55 %) were men. In 55 (91.7 %) left ventricular concentric hypertrophy was observed. Fifty-two patients (86.7 %) showed LVFP type I; three (5 %) had the type II; two (3.3 %) showed pseudonormal pattern and three (5 %) had a normal LVFP. The LVEF was 0.63 +/- 0.09 (CI = 0.41-0.82). Forty nine (81.7 %) patients had LVEF equal or greater than 0.55. The prevalence of diastolic left ventricular dysfunction was 95 % and the prevalence of systolic left ventricular dysfunction was 18.3%.

Is the epicardial left ventricular lead implantation an alternative approach to percutaneous attempt in patients with Steinert disease? A case report

PubMed Central

PAPA, ANDREA ANTONIO; RAGO, ANNA; PETILLO, ROBERTA; D’AMBROSIO, PAOLA; SCUTIFERO, MARIANNA; FEO, MARISA DE; MAIELLO, CIRO; PALLADINO, ALBERTO

2017-01-01

Steinert’s disease or Myotonic Dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder characterized by myotonia, muscle and facial weakness, cataracts, cognitive, endocrine and gastrointestinal involvement, and cardiac conduction abnormalities. Although mild myocardial dysfunction may be detected in this syndrome with age, overt myocardial dysfunction with heart failure is not frequent. Cardiac resynchronization therapy is an effective treatment to improve morbidity and reduce mortality in patients with DM1 showing intra-ventricular conduction delay and/or congestive heart failure. We report the case of a patient with Steinert disease showing an early onset ventricular dysfunction due to chronic right ventricular apical pacing, in which an epicardial left ventricular lead implantation was performed following the failure of the percutaneous attempt. As no relief in symptoms of heart failure, nor an improvement of left ventricular ejection fraction and reverse remodelling was observed six months later, the patient was addressed to the heart transplantation.

Right ventricular function after coronary artery bypass graft surgery--a magnetic resonance imaging study.

PubMed

Joshi, Subodh B; Roswell, Robert O; Salah, Ali K; Zeman, Peter R; Corso, Paul J; Lindsay, Joseph; Fuisz, Anthon R

2010-01-01

A reduction in right ventricular function commonly occurs in the early postoperative period after coronary artery bypass graft surgery (CABG). We sought to determine the longer-term effect of CABG on right ventricular function. Cardiac magnetic resonance imaging was performed before and approximately 3 months after surgery in 28 patients undergoing elective CABG. Right ventricular (RV) ejection fraction was assessed by planimetry of electrocardiographically gated cine images. There was a statistically significant increase in left ventricular ejection fraction from 50% to 58% (P=.003) after CABG. RV ejection fraction also increased from 54% to 60% (P=.002). In patients with lower baseline RV ejection fraction (below the median, < 53%), this parameter improved from 47% to 57% (P<.001). Both on-pump (47% vs. 62%, P=.003) as well as off-pump CABG (47% vs. 55%, P=.009) lead to an improvement in RV function in patients in the initial low RV ejection fraction group. Long-term right ventricular function was not adversely affected by CABG. An improvement in RV function occurred after surgery in patients with low baseline RV ejection fraction and was similar in patients who underwent surgery with or without cardiopulmonary bypass.

Dimensional correlates of left ventricular dilation in the presence of hypertrophy.

PubMed

Al-Nouri, M B; Ford, L E; Wix, H

1983-01-01

Twelve normal subjects, 50 patients with valvular heart disease, and 14 with hypertension were studied. Those with valvular disease were divided into two groups: 28 with angiographically measured ejection fractions greater than or equal to 0.6 and 22 with ejection fractions less than 0.6. The echocardiographically measured ventricular thickness divided by radius ratio (t/r) was approximately proportional to peak systolic pressure (P) in all groups having ejection fractions greater than or equal to 0.6, so that the t/r divided by P ratios were nearly the same. Patients with ejection fractions less than 0.6 had significantly lower t/r divided by P values. No single component of the t/r divided by P ratio would identify the patients with lower ejection fractions. The t/r divided by P ratios in 14 hypertensive patients were nearly identical to the ratios in six patients with aortic stenosis and ejection fractions greater than or equal to 0.6, indicating that an aortic valve gradient does not cause a grossly abnormal form of pressure hypertrophy. The t/r ratio is thus a double sensitive, noninvasive index of dilation when correlated with systolic pressure.

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.

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.

Cardio-oncology: cardiovascular complications of cancer therapy.

PubMed

Henning, Robert J; Harbison, Raymond D

2017-07-01

This paper focuses on three classes of commonly used anticancer drugs, which can cause cardiotoxicity: anthracyclines, monoclonal antibodies exemplified by trastuzumab and tyrosine kinase inhibitors. Anthracyclines can induce cardiomyocyte necrosis and fibrosis. Trastuzumab can cause cardiac stunning. The tyrosine kinase inhibitors can increase systemic arterial pressure and impair myocyte contractility. In addition, radiation therapy to the mediastinum or left chest can exacerbate the cardiotoxicity of these anticancer drugs and can also cause accelerated atherosclerosis, myocardial infarction, heart failure and arrhythmias. Left ventricular ejection fraction measurements are most commonly used to assess cardiac function in patients who receive chemo- or radiation-therapy. However, echocardiographic determinations of global longitudinal strain are more sensitive for detection of early left ventricular systolic dysfunction. Information on patient-risk stratification and monitoring is presented and guidelines for the medical treatment of cardiac dysfunction due to cancer therapies are summarized.

Benefits of Permanent His Bundle Pacing Combined With Atrioventricular Node Ablation in Atrial Fibrillation Patients With Heart Failure With Both Preserved and Reduced Left Ventricular Ejection Fraction.

PubMed

Huang, Weijian; Su, Lan; Wu, Shengjie; Xu, Lei; Xiao, Fangyi; Zhou, Xiaohong; Ellenbogen, Kenneth A

2017-04-01

Clinical benefits from His bundle pacing (HBP) in heart failure patients with preserved and reduced left ventricular ejection fraction are still inconclusive. This study evaluated clinical outcomes of permanent HBP in atrial fibrillation patients with narrow QRS who underwent atrioventricular node ablation for heart failure symptoms despite rate control by medication. The study enrolled 52 consecutive heart failure patients who underwent attempted atrioventricular node ablation and HBP for symptomatic atrial fibrillation. Echocardiographic left ventricular ejection fraction and left ventricular end-diastolic dimension, New York Heart Association classification and use of diuretics for heart failure were assessed during follow-up visits after permanent HBP. Of 52 patients, 42 patients (80.8%) received permanent HBP and atrioventricular node ablation with a median 20-month follow-up. There was no significant change between native and paced QRS duration (107.1±25.8 versus 105.3±23.9 milliseconds, P =0.07). Left ventricular end-diastolic dimension decreased from the baseline ( P <0.001), and left ventricular ejection fraction increased from baseline ( P <0.001) in patients with a greater improvement in heart failure with reduced ejection fraction patients (N=20) than in heart failure with preserved ejection fraction patients (N=22). New York Heart Association classification improved from a baseline 2.9±0.6 to 1.4±0.4 after HBP in heart failure with reduced ejection fraction patients and from a baseline 2.7±0.6 to 1.4±0.5 after HBP in heart failure with preserved ejection fraction patients. After 1 year of HBP, the numbers of patients who used diuretics for heart failure decreased significantly ( P <0.001) when compared to the baseline diuretics use. Permanent HBP post-atrioventricular node ablation significantly improved echocardiographic measurements and New York Heart Association classification and reduced diuretics use for heart failure management in atrial fibrillation patients with narrow QRS who suffered from heart failure with preserved or reduced ejection fraction. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

The value of right ventricular longitudinal strain in the evaluation of adult patients with repaired tetralogy of Fallot: a new tool for a contemporary challenge.

PubMed

Almeida-Morais, Luís; Pereira-da-Silva, Tiago; Branco, Luísa; Timóteo, Ana T; Agapito, Ana; de Sousa, Lídia; Oliveira, José A; Thomas, Boban; Jalles-Tavares, Nuno; Soares, Rui; Galrinho, Ana; Cruz-Ferreira, Rui

2017-04-01

The role of right ventricular longitudinal strain for assessing patients with repaired tetralogy of Fallot is not fully understood. In this study, we aimed to evaluate its relation with other structural and functional parameters in these patients. Patients followed-up in a grown-up CHD unit, assessed by transthoracic echocardiography, cardiac MRI, and treadmill exercise testing, were retrospectively evaluated. Right ventricular size and function and pulmonary regurgitation severity were assessed by echocardiography and MRI. Right ventricular longitudinal strain was evaluated in the four-chamber view using the standard semiautomatic method. In total, 42 patients were included (61% male, 32±8 years). The mean right ventricular longitudinal strain was -16.2±3.7%, and the right ventricular ejection fraction, measured by MRI, was 42.9±7.2%. Longitudinal strain showed linear correlation with tricuspid annular systolic excursion (r=-0.40) and right ventricular ejection fraction (r=-0.45) (all p<0.05), which in turn showed linear correlation with right ventricular fractional area change (r=0.50), pulmonary regurgitation colour length (r=0.35), right ventricular end-systolic volume (r=-0.60), and left ventricular ejection fraction (r=0.36) (all p<0.05). Longitudinal strain (β=-0.72, 95% confidence interval -1.41, -0.15) and left ventricular ejection fraction (β=0.39, 95% confidence interval 0.11, 0.67) were independently associated with right ventricular ejection fraction. The best threshold of longitudinal strain for predicting a right ventricular ejection fraction of <40% was -17.0%. Right ventricular longitudinal strain is a powerful method for evaluating patients with tetralogy of Fallot. It correlated with echocardiographic right ventricular function parameters and was independently associated with right ventricular ejection fraction derived by MRI.

Hyperdynamic left ventricular ejection fraction in the intensive care unit.

PubMed

Paonessa, Joseph R; Brennan, Thomas; Pimentel, Marco; Steinhaus, Daniel; Feng, Mengling; Celi, Leo Anthony

2015-08-07

Limited information exists on the etiology, prevalence, and significance of hyperdynamic left ventricular ejection fraction (HDLVEF) in the intensive care unit (ICU). Our aim in the present study was to compare characteristics and outcomes of patients with HDLVEF with those of patients with normal left ventricular ejection fraction in the ICU using a large, public, deidentified critical care database. We conducted a longitudinal, single-center, retrospective cohort study of adult patients who underwent echocardiography during a medical or surgical ICU admission at the Beth Israel Deaconess Medical Center using the Multiparameter Intelligent Monitoring in Intensive Care II database. The final cohort had 2867 patients, of whom 324 had HDLVEF, defined as an ejection fraction >70%. Patients with an ejection fraction <55% were excluded. Compared with critically ill patients with normal left ventricular ejection fraction, the finding of HDLVEF in critically ill patients was associated with female sex, increased age, and the diagnoses of hypertension and cancer. Patients with HDLVEF had increased 28-day mortality compared with those with normal ejection fraction in multivariate logistic regression analysis adjusted for age, sex, Sequential Organ Failure Assessment score, Elixhauser score for comorbidities, vasopressor use, and mechanical ventilation use (odds ratio 1.38, 95% confidence interval 1.039-1.842, p =0.02). The presence of HDLVEF portended increased 28-day mortality, and may be helpful as a gravity marker for prognosis in patients admitted to the ICU. Further research is warranted to gain a better understanding of how these patients respond to common interventions in the ICU and to determine if pharmacologic modulation of HDLVEF improves outcomes.

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.

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

PubMed

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

2017-03-01

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

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

PubMed

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

2016-08-01

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

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.

Hyperinsulinemia and sulfonylurea use are independently associated with left ventricular diastolic dysfunction in patients with type 2 diabetes mellitus with suboptimal blood glucose control

PubMed Central

Inoue, Tomoaki; Maeda, Yasutaka; Sonoda, Noriyuki; Sasaki, Shuji; Kabemura, Teppei; Kobayashi, Kunihisa; Inoguchi, Toyoshi

2016-01-01

Objective Although diabetes mellitus is associated with an increased risk of heart failure with preserved ejection fraction, the underlying mechanisms leading to left ventricular diastolic dysfunction (LVDD) remain poorly understood. The study was designed to assess the risk factors for LVDD in patients with type 2 diabetes mellitus. Research design and methods The study cohort included 101 asymptomatic patients with type 2 diabetes mellitus without overt heart disease. Left ventricular diastolic function was estimated as the ratio of early diastolic velocity (E) from transmitral inflow to early diastolic velocity (e’) of tissue Doppler at mitral annulus (E/e’). Parameters of glycemic control, plasma insulin concentration, treatment with antidiabetic drugs, lipid profile, and other clinical characteristics were evaluated, and their association with E/e’ determined. Patients with New York Heart Association class >1, ejection fraction <50%, history of coronary artery disease, severe valvulopathy, chronic atrial fibrillation, or creatinine clearance <30 mL/min, as well as those receiving insulin treatment, were excluded. Results Univariate analysis showed that E/e’ was significantly correlated with age (p<0.001), sex (p<0.001), duration of diabetes (p=0.002), systolic blood pressure (p=0.017), pulse pressure (p=0.010), fasting insulin concentration (p=0.025), and sulfonylurea use (p<0.001). Multivariate linear regression analysis showed that log E/e’ was significantly and positively correlated with log age (p=0.034), female sex (p=0.019), log fasting insulin concentration (p=0.010), and sulfonylurea use (p=0.027). Conclusions Hyperinsulinemia and sulfonylurea use may be important in the development of LVDD in patients with type 2 diabetes mellitus. PMID:27648285

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.

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

PubMed

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

2018-02-01

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

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

The relationship between inotrope exposure, six-hour postoperative physiological variables, hospital mortality and renal dysfunction in patients undergoing cardiac surgery.

PubMed

Shahin, Jason; DeVarennes, Benoit; Tse, Chun Wing; Amarica, Dan-Alexandru; Dial, Sandra

2011-07-07

Acute haemodynamic complications are common after cardiac surgery and optimal perioperative use of inotropic agents, typically guided by haemodynamic variables, remains controversial. The aim of this study was to examine the relationship of inotrope use to hospital mortality and renal dysfunction. A retrospective cohort study of 1,326 cardiac surgery patients was carried out at two university-affiliated ICUs. Multivariable logistic regression analysis and propensity matching were performed to evaluate whether inotrope exposure was independently associated with mortality and renal dysfunction. Patients exposed to inotropes had a higher mortality rate than those not exposed. After adjusting for differences in Parsonnet score, left ventricular ejection fraction, perioperative intraaortic balloon pump use, bypass time, reoperation and cardiac index, inotrope exposure appeared to be independently associated with increased hospital mortality (adjusted odds ratio (OR) 2.3, 95% confidence interval (95% CI) 1.2 to 4.5) and renal dysfunction (adjusted OR 2.7, 95% CI 1.5 to 4.6). A propensity score-matched analysis similarly demonstrated that death and renal dysfunction were significantly more likely to occur in patients exposed to inotropes (P = 0.01). Postoperative inotrope exposure was independently associated with worse outcomes in this cohort study. Further research is needed to better elucidate the appropriate use of inotropes in cardiac surgery.

Electrophysiological correlates of word recognition memory process in patients with ischemic left ventricular dysfunction.

PubMed

Giovannelli, Fabio; Simoni, David; Gavazzi, Gioele; Giganti, Fiorenza; Olivotto, Iacopo; Cincotta, Massimo; Pratesi, Alessandra; Baldasseroni, Samuele; Viggiano, Maria Pia

2016-09-01

The relationship between left ventricular ejection fraction (LVEF) and cognitive performance in patients with coronary artery disease without overt heart failure is still under debate. In this study we combine behavioral measures and event-related potentials (ERPs) to verify whether electrophysiological correlates of recognition memory (old/new effect) are modulated differently as a function of LVEF. Twenty-three male patients (12 without [LVEF>55%] and 11 with [LVEF<40%] left ventricular dysfunction), and a Mini Mental State Examination score >25 were enrolled. ERPs were recorded while participants performed an old/new visual word recognition task. A late positive ERP component between 350 and 550ms was differentially modulated in the two groups: a clear old/new effect (enhanced mean amplitude for old respect to new items) was observed in patients without LVEF dysfunction; whereas patients with overt LVEF dysfunction did not show such effect. In contrast, no significant differences emerged for behavioral performance and neuropsychological evaluations. These data suggest that ERPs may reveal functional brain abnormalities that are not observed at behavioral level. Detecting sub-clinical measures of cognitive decline may contribute to set appropriate treatments and to monitor asymptomatic or mildly symptomatic patients with LVEF dysfunction. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

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.

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.

Prevalence of scarred and dysfunctional myocardium in patients with heart failure of ischaemic origin: A cardiovascular magnetic resonance study

PubMed Central

2011-01-01

Background Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) can provide unique data on the transmural extent of scar/viability. We assessed the prevalence of dysfunctional myocardium, including partial thickness scar, which could contribute to left ventricular contractile dysfunction in patients with heart failure and ischaemic heart disease who denied angina symptoms. Methods We invited patients with ischaemic heart disease and a left ventricular ejection fraction < 50% by echocardiography to have LGE CMR. Myocardial contractility and transmural extent of scar were assessed using a 17-segment model. Results The median age of the 193 patients enrolled was 70 (interquartile range: 63-76) years and 167 (87%) were men. Of 3281 myocardial segments assessed, 1759 (54%) were dysfunctional, of which 581 (33%) showed no scar, 623 (35%) had scar affecting ≤50% of wall thickness and 555 (32%) had scar affecting > 50% of wall thickness. Of 1522 segments with normal contractile function, only 98 (6%) had evidence of scar on CMR. Overall, 182 (94%) patients had ≥1 and 107 (55%) patients had ≥5 segments with contractile dysfunction that had no scar or ≤50% transmural scar suggesting viability. Conclusions In this cohort of patients with left ventricular systolic dysfunction and ischaemic heart disease, about half of all segments had contractile dysfunction but only one third of these had > 50% of the wall thickness affected by scar, suggesting that most dysfunctional segments could improve in response to an appropriate intervention. PMID:21936915

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 impact of isolated right ventricular dysfunction in sepsis and septic shock: an 8-year historical cohort study.

PubMed

Vallabhajosyula, Saraschandra; Kumar, Mukesh; Pandompatam, Govind; Sakhuja, Ankit; Kashyap, Rahul; Kashani, Kianoush; Gajic, Ognjen; Geske, Jeffrey B; Jentzer, Jacob C

2017-09-07

Echocardiographic myocardial dysfunction is reported commonly in sepsis and septic shock, but there are limited data on sepsis-related right ventricular dysfunction. This study sought to evaluate the association of right ventricular dysfunction with clinical outcomes in patients with severe sepsis and septic shock. Historical cohort study of adult patients admitted to all intensive care units at the Mayo Clinic from January 1, 2007 through December 31, 2014 for severe sepsis and septic shock, who had an echocardiogram performed within 72 h of admission. Patients with prior heart failure, cor-pulmonale, pulmonary hypertension and valvular disease were excluded. Right ventricular dysfunction was defined by the American Society of Echocardiography criteria. Outcomes included 1-year survival, in-hospital mortality and length of stay. Right ventricular dysfunction was present in 214 (55%) of 388 patients who met the inclusion criteria-isolated right ventricular dysfunction was seen in 100 (47%) and combined right and left ventricular dysfunction in 114 (53%). The baseline characteristics were similar between cohorts except for the higher mechanical ventilation use in patients with isolated right ventricular dysfunction. Echocardiographic findings demonstrated lower right ventricular and tricuspid valve velocities in patients with right ventricular dysfunction and lower left ventricular ejection fraction and increased mitral E/e' ratios in patients with combined right and left ventricular dysfunction. After adjustment for age, comorbidity, illness severity, septic shock and use of mechanical ventilation, isolated right ventricular dysfunction was independently associated with worse 1-year survival-hazard ratio 1.6 [95% confidence interval 1.2-2.1; p = 0.002) in patients with sepsis and septic shock. Isolated right ventricular dysfunction is seen commonly in sepsis and septic shock and is associated with worse long-term survival.

Experimental study of the intraventricular filling vortex in diastolic dysfunction

NASA Astrophysics Data System (ADS)

Santhanakrishnan, Arvind; Samaee, Milad; Nelsen, Nicholas

2016-11-01

Heart failure with normal ejection fraction (HFNEF) is a clinical syndrome that is prevalent in over half of heart failure patients. HFNEF patients typically show diastolic dysfunction, caused by a decrease in relaxation capability of the left ventricular (LV) muscle tissue and/or an increase in LV chamber stiffness. Numerous studies using non-invasive medical imaging have shown that an intraventricular filling vortex is formed in the LV during diastole. We conducted 2D particle image velocimetry and hemodynamics measurements on a left heart simulator to investigate diastolic flow under increasing LV wall stiffness, LV wall thickness and heart rate (HR) conditions. Flexible-walled, optically clear LV physical models cast from silicone were fitted within a fluid-filled acrylic chamber. Pulsatile flow within the LV model was generated using a piston pump and 2-component Windkessel elements were used to tune the least stiff (baseline) LV model to physiological conditions. The results show that peak circulation of the intraventricular filling vortex is diminished in conditions of diastolic dysfunction as compared to the baseline case. Increasing HR exacerbated the circulation of the filling vortex across all cases.

Non-functional tricuspid valve disease

PubMed Central

2017-01-01

Only 75% of severe tricuspid regurgitation is classified as functional, or related primarily to pulmonary hypertension, right ventricular dysfunction, or a combination of both. Non-functional tricuspid regurgitation occurs when there is damage to the tricuspid leaflets, chordae, papillary muscles, or annulus, independent of right ventricular dysfunction or pulmonary hypertension. The entities that cause non-functional tricuspid regurgitation include rheumatic and myxomatous disease, acquired and genetic connective tissue disorders, endocarditis, sarcoid, pacing, RV biopsy, blunt trauma, radiation, carcinoid, ergot alkaloids, dopamine agonists, fenfluramine, cardiac tumors, atrial fibrillation, and congenital malformations. Over time, severe tricuspid regurgitation that is initially non-functional, can blend into functional tricuspid regurgitation, related to progressive right ventricular dysfunction. Symptoms and signs, including a falling right ventricular ejection fraction, cardiac cirrhosis, ascites, esophageal varices, and anasarca, may occur insidiously and late, but are associated with substantial morbidity and mortality. Attempted valve repair or replacement at late stages carries a high mortality. Crucial to following patients with severe non-functional tricuspid regurgitation is attention to echo quantification of the tricuspid regurgitation and right ventricular function, patient symptoms, and the physical examination. PMID:28706863

Non-functional tricuspid valve disease.

PubMed

Adler, Dale S

2017-05-01

Only 75% of severe tricuspid regurgitation is classified as functional, or related primarily to pulmonary hypertension, right ventricular dysfunction, or a combination of both. Non-functional tricuspid regurgitation occurs when there is damage to the tricuspid leaflets, chordae, papillary muscles, or annulus, independent of right ventricular dysfunction or pulmonary hypertension. The entities that cause non-functional tricuspid regurgitation include rheumatic and myxomatous disease, acquired and genetic connective tissue disorders, endocarditis, sarcoid, pacing, RV biopsy, blunt trauma, radiation, carcinoid, ergot alkaloids, dopamine agonists, fenfluramine, cardiac tumors, atrial fibrillation, and congenital malformations. Over time, severe tricuspid regurgitation that is initially non-functional, can blend into functional tricuspid regurgitation, related to progressive right ventricular dysfunction. Symptoms and signs, including a falling right ventricular ejection fraction, cardiac cirrhosis, ascites, esophageal varices, and anasarca, may occur insidiously and late, but are associated with substantial morbidity and mortality. Attempted valve repair or replacement at late stages carries a high mortality. Crucial to following patients with severe non-functional tricuspid regurgitation is attention to echo quantification of the tricuspid regurgitation and right ventricular function, patient symptoms, and the physical examination.

Exercise haemodynamics may unmask the diagnosis of diastolic dysfunction among patients with pulmonary hypertension.

PubMed

Maor, Elad; Grossman, Yoni; Balmor, Ronen Gingy; Segel, Michael; Fefer, Paul; Ben-Zekry, Sagit; Buber, Jonathan; DiSegni, Elio; Guetta, Victor; Ben-Dov, Issahar; Segev, Amit

2015-02-01

Heart failure with preserved ejection fraction can lead to pulmonary hypertension. The aim of the present study was to evaluate the role of exercise during right heart catheterization in the unmasking of diastolic dysfunction. Between 2004 and 2012, 200 symptomatic patients with exertional dyspnoea, preserved left ventricular systolic function and suspected pulmonary hypertension, underwent right heart catheterization. Included in the study were 63 patients with resting pulmonary arterial wedge pressure (PAWP) ≤15 mmHg. Patients were divided to three tertiles based on their peak exercise PAWP. Mean age was 60 ± 20 years and 29% were males. Mean pulmonary arterial pressure was 31 ± 14 mmHg at rest and 42 ± 18 mmHg upon exercise. Mean change in PAWP between rest and exercise was 0.0 ± 4.3, 4.6 ± 2.4, and 16.6 ± 7.1 mmHg in the lower, middle, and upper tertiles, respectively (P < 0.001). Higher exercise PAWP tertiles were associated with reduced pulmonary vascular resistance (8.3 ± 6.7, 2.9 ± 2.7, and 5.8 ± 4.6 Woods units, respectively; P = 0.004). A multivariate linear regression model demonstrated that each 5 kg/m(2) increase in body mass index was associated with 2.5 ± 1.0 mmHg increase in exercise PAWP (P = 0.017). A multivariate binary logistic model showed that subjects with borderline PAWP at rest (12-15 mmHg) were 4.5 times more likely to be in the upper tertile of exercise PAWP (P = 0.011). In symptomatic patients with pulmonary hypertension, preserved left ventricular ejection fraction and PAWP ≤15 mmHg, exercise during right heart catheterization may unmask diastolic dysfunction. This is especially true for obese patients and patients with borderline resting PAWP. © 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.

Usefulness of N-terminal pro-brain natriuretic Peptide and brain natriuretic peptide to predict cardiovascular outcomes in patients with heart failure and preserved left ventricular ejection fraction.

PubMed

Grewal, Jasmine; McKelvie, Robert S; Persson, Hans; Tait, Peter; Carlsson, Jonas; Swedberg, Karl; Ostergren, Jan; Lonn, Eva

2008-09-15

More than 40% of patients hospitalized with heart failure have preserved left ventricular ejection fraction (HF-PLVEF) and are at high risk for cardiovascular (CV) events. The purpose of this study was to determine the value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) in predicting CV outcomes in patients with HF-PLVEF. Participants with an ejection fraction >40% in the prospective CHARM Echocardiographic Substudy were included in this analysis. Plasma NT-proBNP levels were measured, and 2 cut-offs were selected prospectively at 300 pg/ml and 600 pg/ml. BNP cut-off was set at 100 pg/ml. Clinical characteristics were recorded, and systolic and diastolic function were evaluated by echocardiography. The primary substudy outcome was the composite of CV mortality, hospitalization for heart failure, and myocardial infarction or stroke. A total of 181 patients were included, and there were 17 primary CV events (9.4%) during a median follow-up time of 524 days. In a model including clinical characteristics, echocardiographic measures, and BNP or NT-proBNP, the composite CV event outcome was best predicted by NT-proBNP >300 pg/ml (hazard ratio 5.8, 95% confidence intervals [CI] 1.3 to 26.4, p = 0.02) and moderate or severe diastolic dysfunction on echocardiography. When NT-proBNP >600 pg/ml was used in the model, it was the sole independent predictor of primary CV events (hazard ratio 8.0, 95% CI 2.6 to 24.8, p = 0.0003) as was BNP >100 pg/ml (hazard ratio 3.1, 95% CI 1.2 to 8.2, p = 0.02) in the BNP model. In conclusion, both elevated NT-proBNP and BNP are strong independent predictors of clinical events in patients with HF-PLVEF.

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

PubMed

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

2015-01-21

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

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.

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.

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

PubMed

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

2018-05-01

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

Histopathological Correlates of Global and Segmental Left Ventricular Systolic Dysfunction in Experimental Chronic Chagas Cardiomyopathy.

PubMed

de Oliveira, Luciano Fonseca Lemos; Romano, Minna Moreira Dias; de Carvalho, Eduardo Elias Vieira; Cabeza, Jorge Mejia; Salgado, Hélio Cesar; Fazan Júnior, Rubens; Costa, Renata Sesti; da Silva, João Santana; Higuchi, Maria de Lourdes; Maciel, Benedito Carlos; Cunha-Neto, Edécio; Marin-Neto, José Antônio; Simões, Marcus Vinícius

2016-01-21

Chronic Chagas cardiomyopathy in humans is characterized by segmental left ventricular wall motion abnormalities (WMA), mainly in the early stages of disease. This study aimed at investigating the detection of WMA and its correlation with the underlying histopathological changes in a chronic Chagas cardiomyopathy model in hamsters. Female Syrian hamsters (n=34) infected with 3.5×10(4) or 10(5) blood trypomastigote Trypanosoma cruzi (Y strain) forms and an uninfected control group (n=7) were investigated. After 6 or 10 months after the infection, the animals were submitted to in vivo evaluation of global and segmental left ventricular systolic function by echocardiography, followed by euthanasia and histological analysis for quantitative assessment of fibrosis and inflammation with tissue sampling in locations coinciding with the left ventricular wall segmentation employed at the in vivo echocardiographic evaluation. Ten of the 34 infected animals (29%) showed reduced left ventricular ejection fraction (<73%). Left ventricular ejection fraction was more negatively correlated with the intensity of inflammation (r=-0.63; P<0.0001) than with the extent of fibrosis (r=-0.36; P=0.036). Among the 24 animals with preserved left ventricular ejection fraction (82.9±5.5%), 8 (33%) showed segmental WMA predominating in the apical, inferior, and posterolateral segments. The segments exhibiting WMA, in comparison to those with normal wall motion, showed a greater extent of fibrosis (9.3±5.7% and 7±6.3%, P<0.0001) and an even greater intensity of inflammation (218.0±111.6 and 124.5±84.8 nuclei/mm², P<0.0001). Isolated WMA with preserved global systolic left ventricular function is frequently found in Syrian hamsters with experimental chronic Chagas cardiomyopathy whose underlying histopathological features are mainly inflammatory. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Galectin-3 Reflects the Echocardiographic Grades of Left Ventricular Diastolic Dysfunction.

PubMed

Ansari, Uzair; Behnes, Michael; Hoffmann, Julia; Natale, Michele; Fastner, Christian; El-Battrawy, Ibrahim; Rusnak, Jonas; Kim, Seung Hyun; Lang, Siegfried; Hoffmann, Ursula; Bertsch, Thomas; Borggrefe, Martin; Akin, Ibrahim

2018-07-01

The level of Galectin-3 (Gal-3) protein purportedly reflects an ongoing cardiac fibrotic process and has been associated with ventricular remodeling, which is instrumental in the development of heart failure with preserved ejection fraction (HFpEF) syndrome. The aim of this study was to investigate the potential use of Gal-3 in improved characterization of the grades of diastolic dysfunction as defined by echocardiography. Seventy HFpEF patients undergoing routine echocardiography were prospectively enrolled in the present monocentric study. Blood samples for measurements of Gal-3 and amino-terminal pro-brain natriuretic peptide (NT-proBNP) were collected within 24 hours pre- or post-echocardiographic examination. The classification of patients into subgroups based on diastolic dysfunction grade permitted detailed statistical analyses of the derived data. The Gal-3 serum levels of all patients corresponded to echocardiographic indices, suggesting HFpEF (E/A, P=0.03 and E/E', P=0.02). Gal-3 was also associated with progressive diastolic dysfunction, and increased levels corresponded to the course of disease (P=0.012). Detailed analyses of ROC curves suggested that Gal-3 levels could discriminate patients with grade III diastolic dysfunction (area under the curve [AUC]=0.770, P=0.005). Gal-3 demonstrates remarkable effectiveness in the diagnosis of patients suffering from severe grade diastolic dysfunction. Increasing levels of Gal-3 possibly reflect the progressive course of HFpEF, as classified by the echocardiographic grades of diastolic dysfunction. © The Korean Society for Laboratory Medicine.

Case report: paradoxical ventricular septal motion in the setting of primary right ventricular myocardial failure.

PubMed

Maslow, Andrew; Schwartz, Carl; Mahmood, Feroze; Singh, Arun; Heerdt, Paul M

2009-07-01

In this report, a case of right ventricular (RV) failure, hemodynamic instability, and systemic organ failure is described to highlight how paradoxical ventricular systolic septal motion (PVSM), or a rightward systolic displacement of the interventricular septum, may contribute to RV ejection. Multiple inotropic medications and vasopressors were administered to treat right heart failure and systemic hypotension in a patient following combined aortic and mitral valve replacement. In the early postoperative period, echocardiographic evaluation revealed adequate left ventricular systolic function, akinesis of the RV myocardial tissues, and PVSM. In the presence of PVSM, RV fractional area of contraction was > or =35% despite akinesis of the primary RV myocardial walls. The PVSM appeared to contribute toward RV ejection. As a result, the need for multiple inotropes was re-evaluated, in considering that end-organ dysfunction was the result of systemic hypotension and prolonged vasopressor administration. After discontinuation of phosphodiesterase inhibitors, native vascular tone returned and the need for vasopressors declined. This was followed by recovery of systemic organ function. Echocardiographic re-evaluation two years later, revealed persistent akinesis of the RV myocardial tissues and PVSM, the latter appearing to contribute toward RV ejection. This case highlights the importance of left to RV interactions, and how PVSM may mediate these hemodynamic interactions.

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.

PreSERVE-AMI: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Intracoronary Administration of Autologous CD34+ Cells in Patients With Left Ventricular Dysfunction Post STEMI.

PubMed

Quyyumi, Arshed A; Vasquez, Alejandro; Kereiakes, Dean J; Klapholz, Marc; Schaer, Gary L; Abdel-Latif, Ahmed; Frohwein, Stephen; Henry, Timothy D; Schatz, Richard A; Dib, Nabil; Toma, Catalin; Davidson, Charles J; Barsness, Gregory W; Shavelle, David M; Cohen, Martin; Poole, Joseph; Moss, Thomas; Hyde, Pamela; Kanakaraj, Anna Maria; Druker, Vitaly; Chung, Amy; Junge, Candice; Preti, Robert A; Smith, Robin L; Mazzo, David J; Pecora, Andrew; Losordo, Douglas W

2017-01-20

Despite direct immediate intervention and therapy, ST-segment-elevation myocardial infarction (STEMI) victims remain at risk for infarct expansion, heart failure, reinfarction, repeat revascularization, and death. To evaluate the safety and bioactivity of autologous CD34+ cell (CLBS10) intracoronary infusion in patients with left ventricular dysfunction post STEMI. Patients who underwent successful stenting for STEMI and had left ventricular dysfunction (ejection fraction≤48%) ≥4 days poststent were eligible for enrollment. Subjects (N=161) underwent mini bone marrow harvest and were randomized 1:1 to receive (1) autologous CD34+ cells (minimum 10 mol/L±20% cells; N=78) or (2) diluent alone (N=83), via intracoronary infusion. The primary safety end point was adverse events, serious adverse events, and major adverse cardiac event. The primary efficacy end point was change in resting myocardial perfusion over 6 months. No differences in myocardial perfusion or adverse events were observed between the control and treatment groups, although increased perfusion was observed within each group from baseline to 6 months (P<0.001). In secondary analyses, when adjusted for time of ischemia, a consistently favorable cell dose-dependent effect was observed in the change in left ventricular ejection fraction and infarct size, and the duration of time subjects was alive and out of hospital (P=0.05). At 1 year, 3.6% (N=3) and 0% deaths were observed in the control and treatment group, respectively. This PreSERVE-AMI (Phase 2, randomized, double-blind, placebo-controlled trial) represents the largest study of cell-based therapy for STEMI completed in the United States and provides evidence supporting safety and potential efficacy in patients with left ventricular dysfunction post STEMI who are at risk for death and major morbidity. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01495364. © 2016 American Heart Association, Inc.

Left ventricular mechanics in isolated mild mitral stenosis: a three dimensional speckle tracking study.

PubMed

Poyraz, Esra; Öz, Tuğba Kemaloğlu; Zeren, Gönül; Güvenç, Tolga Sinan; Dönmez, Cevdet; Can, Fatma; Güvenç, Rengin Çetin; Dayı, Şennur Ünal

2017-09-01

In a fraction of patients with mild mitral stenosis, left ventricular systolic function deteriorates despite the lack of hemodynamic load imposed by the dysfunctioning valve. Neither the predisposing factors nor the earlier changes in left ventricular contractility were understood adequately. In the present study we aimed to evaluate left ventricular mechanics using three-dimensional (3D) speckle tracking echocardiography. A total of 31 patients with mild rheumatic mitral stenosis and 27 healthy controls were enrolled to the study. All subjects included to the study underwent echocardiographic examination to collect data for two- and three-dimensional speckle-tracking based stain, twist angle and torsion measurements. Data was analyzed offline with a echocardiographic data analysis software. Patients with rheumatic mild MS had lower global longitudinal (p < 0.001) circumferential (p = 0.02) and radial (p < 0.01) strain compared to controls, despite ejection fraction was similar for both groups [(p = 0.45) for three dimensional and (p = 0.37) for two dimensional measurement]. While the twist angle was not significantly different between groups (p = 0.11), left ventricular torsion was significantly higher in mitral stenosis group (p = 0.03). All strain values had a weak but significant positive correlation with mitral valve area measured with planimetry. Subclinical left ventricular systolic dysfunction develops at an early stage in rheumatic mitral stenosis. Further work is needed to elucidate patients at risk for developing overt systolic dysfunction.

The less familiar side of heart failure: symptomatic diastolic dysfunction.

PubMed

Morris, Spencer A; Van Swol, Mark; Udani, Bela

2005-06-01

Arrange for echocardiography or radionuclide angiography within 72 hours of a heart failure exacerbation. An ejection fraction >50% in the presence of signs and symptoms of heart failure makes the diagnosis of diastolic heart failure probable. To treat associated hypertension, use angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, calcium channel blockers, or diuretics to achieve a blood pressure goal of <130/80 mm Hg. When using beta-blockers to control heart rate, titrate doses more aggressively than would be done for systolic failure, to reach a goal of 60 to 70 bpm. Use ACE inhibitors/ARBs to decrease hospitalizations, decrease symptoms, and prevent left ventricular remodeling.

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.

The relationship between inotrope exposure, six-hour postoperative physiological variables, hospital mortality and renal dysfunction in patients undergoing cardiac surgery

PubMed Central

2011-01-01

Introduction Acute haemodynamic complications are common after cardiac surgery and optimal perioperative use of inotropic agents, typically guided by haemodynamic variables, remains controversial. The aim of this study was to examine the relationship of inotrope use to hospital mortality and renal dysfunction. Material and methods A retrospective cohort study of 1,326 cardiac surgery patients was carried out at two university-affiliated ICUs. Multivariable logistic regression analysis and propensity matching were performed to evaluate whether inotrope exposure was independently associated with mortality and renal dysfunction. Results Patients exposed to inotropes had a higher mortality rate than those not exposed. After adjusting for differences in Parsonnet score, left ventricular ejection fraction, perioperative intraaortic balloon pump use, bypass time, reoperation and cardiac index, inotrope exposure appeared to be independently associated with increased hospital mortality (adjusted odds ratio (OR) 2.3, 95% confidence interval (95% CI) 1.2 to 4.5) and renal dysfunction (adjusted OR 2.7, 95% CI 1.5 to 4.6). A propensity score-matched analysis similarly demonstrated that death and renal dysfunction were significantly more likely to occur in patients exposed to inotropes (P = 0.01). Conclusions Postoperative inotrope exposure was independently associated with worse outcomes in this cohort study. Further research is needed to better elucidate the appropriate use of inotropes in cardiac surgery. PMID:21736726

Right ventricular systolic function in hypertensive heart failure.

PubMed

Oketona, O A; Balogun, M O; Akintomide, A O; Ajayi, O E; Adebayo, R A; Mene-Afejuku, T O; Oketona, O T; Bamikole, O J

2017-01-01

Heart failure (HF) is a major cause of cardiovascular admissions and hypertensive heart failure (HHF) is the most common cause of HF admissions in sub-Saharan Africa, Nigeria inclusive. Right ventricular (RV) dysfunction is being increasingly recognized in HF and found to be an independent predictor of adverse outcomes in HF. This study aimed to determine the prevalence of RV systolic dysfunction in HHF by several echocardiographic parameters. One hundred subjects with HHF were recruited consecutively into the study along with 50 age and sex-matched controls. All study participants gave written informed consent, and had a full physical examination, blood investigations, 12-lead electrocardiogram, and transthoracic echocardiography. RV systolic function was assessed in all subjects using different methods based on the American Society of Echocardiography guidelines for echocardiographic assessment of the right heart in adults. This included tricuspid annular plane systolic excursion (TAPSE), RV myocardial performance index (MPI), and RV systolic excursion velocity by tissue Doppler (S'). RV systolic dysfunction was found in 53% of subjects with HHF by TAPSE, 56% by RV MPI, and 48% by tissue Doppler systolic excursion S'. RV systolic dysfunction increased with reducing left ventricular ejection fraction (LVEF) in subjects with HHF. A high proportion of subjects with HHF were found to have RV systolic functional abnormalities using TAPSE, RV MPI, and RV S'. Prevalence of RV systolic dysfunction increased with reducing LVEF.

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

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.

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

Percutaneous closure of patent ductus arteriosus in children: Immediate and short-term changes in left ventricular systolic and diastolic function.

PubMed

Gupta, Saurabh Kumar; Krishnamoorthy, Km; Tharakan, Jaganmohan A; Sivasankaran, S; Sanjay, G; Bijulal, S; Anees, T

2011-07-01

To evaluate the effect of percutaneous closure of patent ductus arteriosus (PDA) on left ventricular (LV) systolic and diastolic function in children. Limited studies are available on alteration in LV hemodynamics, especially diastolic function, after PDA closure. Thirty-two consecutive children with isolated PDA treated by trans-catheter closure were studied. The LV systolic and diastolic function were assessed by two-dimensional (2D) echocardiography and tissue Doppler imaging 1 day before the PDA closure, on day 1, and on follow-up. At baseline, none of the patients had LV systolic dysfunction. On day 1 post-PDA closure, 8 (25%) children developed LV systolic dysfunction. The baseline LV ejection fraction (LVEF), LV end-systolic dimension (LVESD), and PDA diastolic gradient predicted the post-closure LVEF. Patients who developed post-closure LV systolic dysfunction had poorer LV diastolic function than those who did not. LV diastolic properties improved after PDA closure; however, the improvement in LV diastolic properties lagged behind the improvement in the LV systolic function. All children were asymptomatic and had normal LVEF on follow up of >3 months. Percutaneous closure of PDA is associated with the reversible LV systolic dysfunction. Improvement in the LV diastolic function lags behind that in the LV systolic function.

A young patient with atypical type-B Wolff–Parkinson–White syndrome accompanied by left ventricular dysfunction

PubMed Central

Takeuchi, Takahiro; Tomita, Takeshi; Kasai, Hiroki; Kashiwagi, Daisuke; Yoshie, Koji; Yaguchi, Tomonori; Oguchi, Yasutaka; Kozuka, Ayako; Gautam, Milan; Motoki, Hirohiko; Okada, Ayako; Shiba, Yuji; Aizawa, Kazunori; Izawa, Atsushi; Miyashita, Yusuke; Koyama, Jun; Hongo, Minoru; Ikeda, Uichi

2014-01-01

A 15-year-old asymptomatic male patient presented with an electrocardiographic abnormality and left ventricular (LV) dysfunction (left ventricle ejection fraction of 40%) in a physical examination performed 2 years previously. LV dysfunction did not improve despite optimal medical therapy for dilated cardiomyopathy. Twelve-lead electrocardiography revealed a normal PR interval (138 ms) with a small delta-like wave in V2, but not a typical diagnostic wave that could be diagnosed as Wolff–Parkinson–White (WPW) syndrome by an electrocardiogram auto-analysis. Transthoracic echocardiography showed a remarkable asynchronous septal motion. An electrophysiological study was performed to exclude WPW syndrome. An accessory pathway (AP) was revealed on the lateral wall of the right ventricle, and radiofrequency catheter ablation was successfully performed to disconnect the AP. Thereafter, the dyssynchrony disappeared, and LV function improved. The intrinsic atrioventricular nodal conduction was very slow (A-H, 237 ms). The results of electrocardiogram auto-analysis could not be used to confirm the diagnosis of WPW syndrome because of the atypical delta wave. Conduction via the right lateral AP caused electrical dyssynchrony in the LV. This case suggests that atypical delta waves should be evaluated without depending on electrocardiographic auto-analyses in patients with LV dysfunction accompanied by dyssynchrony. PMID:26336525

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

PubMed

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

2006-10-01

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

Minimally invasive surgical implantation of left ventricular epicardial leads for ventricular resynchronization using video-assisted thoracoscopy.

PubMed

Fernández, Angel L; García-Bengochea, José B; Ledo, Ramiro; Vega, Marino; Amaro, Antonio; Alvarez, Julián; Rubio, José; Sierra, Juan; Sánchez, Daniel

2004-04-01

Cardiac resynchronization via left ventricular or biventricular pacing is an option for selected patients with ventricular systolic dysfunction and widened QRS complex. Stimulation through a coronary vein is the technique of choice for left ventricular pacing, but this approach results in a failure rate of approximately 8%. We describe our initial experience with minimally invasive surgical implantation of left ventricular epicardial leads using video-assisted thoracoscopy. A total of 14 patients with congestive heart failure, NYHA functional class 3.2 (0.6) and mean ejection fraction 22.9 (6.8)% were included in this study. Left bundle branch block, QRS complex >140 ms and abnormal septal motion were observed in all cases. Epicardial leads were implanted on the left ventricular free wall under general anesthesia using video-assisted thoracoscopic surgery. Lead implantation was successful in 13 patients. Conversion to a small thoracotomy was necessary in one patient. All patients were extubated in the operating room. None of the patients died during their hospital stay. Follow-up showed reversal of ventricular asynchrony and significant improvement in ejection fraction and functional class. Minimally invasive surgery for ventricular resynchronization using video-assisted thoracoscopy in selected patients is a safe procedure that makes it possible to choose the best site for lead implantation and provides adequate short- and medium-term stimulation.

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.

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.

First report of atretic coronary sinus stenting in a 5-kg infant resulting in dramatic improvement of ventricular function in functional single ventricle.

PubMed

El-Said, Howaida; Hegde, Sanjeet; Moore, John

2014-01-01

The patient was a male infant with L-transposition of great arteries (L-TGA), Ebstein's anomaly of the tricuspid valve, subvalvar aortic stenosis, ventricular septal defect (VSD), hypoplastic right ventricle, arch hypoplasia, and congenital complete heart block. He underwent a Norwood procedure, aortic arch repair, permanent pacemaker implantation, and a 3.5-mm aortopulmonary shunt at 4 days of age. At the time of his surgery, left ventricular function was in the normal range (ejection fraction [EF] = 67%). However by 3 months of age, he was noted to have developed moderate-severe biventricular dysfunction (left ventricular ejection fraction [LVEF] = 34%). Atresia of the coronary sinus with a small left superior venacava (LSVC) and a bridging vein was discovered during cardiac catheterization at this time. The coronary sinus mean pressure was 17 mm Hg, and the common atrial mean pressure was 6 mmHg. We opened the atretic coronary sinus ostium using radiofrequency ablation and stent placement. There was dramatic improvement in ventricular function observed over a 2-month period. Follow-up cardiac catheterization 5 months later revealed the stent in the coronary sinus to be widely patent with no intimal buildup, and the ventricular function was normal (LVEF = 58%). The patient had a bidirectional Glenn procedure with an uncomplicated postoperative course and is currently awaiting Fontan completion. © 2013 Wiley Periodicals, Inc.

Cardiac-Specific Deletion of Pyruvate Dehydrogenase Impairs Glucose Oxidation Rates and Induces Diastolic Dysfunction.

PubMed

Gopal, Keshav; Almutairi, Malak; Al Batran, Rami; Eaton, Farah; Gandhi, Manoj; Ussher, John Reyes

2018-01-01

Obesity and type 2 diabetes (T2D) increase the risk for cardiomyopathy, which is the presence of ventricular dysfunction in the absence of underlying coronary artery disease and/or hypertension. As myocardial energy metabolism is altered during obesity/T2D (increased fatty acid oxidation and decreased glucose oxidation), we hypothesized that restricting myocardial glucose oxidation in lean mice devoid of the perturbed metabolic milieu observed in obesity/T2D would produce a cardiomyopathy phenotype, characterized via diastolic dysfunction. We tested our hypothesis via producing mice with a cardiac-specific gene knockout for pyruvate dehydrogenase (PDH, gene name Pdha1 ), the rate-limiting enzyme for glucose oxidation. Cardiac-specific Pdha1 deficient ( Pdha1 Cardiac-/- ) mice were generated via crossing a tamoxifen-inducible Cre expressing mouse under the control of the alpha-myosin heavy chain (αMHC-MerCreMer) promoter with a floxed Pdha1 mouse. Energy metabolism and cardiac function were assessed via isolated working heart perfusions and ultrasound echocardiography, respectively. Tamoxifen administration produced an ~85% reduction in PDH protein expression in Pdha1 Cardiac-/- mice versus their control littermates, which resulted in a marked reduction in myocardial glucose oxidation and a corresponding increase in palmitate oxidation. This myocardial metabolism profile did not impair systolic function in Pdha1 Cardiac-/- mice, which had comparable left ventricular ejection fractions and fractional shortenings as their αMHC-MerCreMer control littermates, but did produce diastolic dysfunction as seen via the reduced mitral E/A ratio. Therefore, it does appear that forced restriction of glucose oxidation in the hearts of Pdha1 Cardiac-/- mice is sufficient to produce a cardiomyopathy-like phenotype, independent of the perturbed metabolic milieu observed in obesity and/or T2D.

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.

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.

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.

Rationale and design of a randomized controlled trial of allogeneic mesenchymal stem cells in patients with nonischemic cardiomyopathy.

PubMed

Greene, Stephen J; Epstein, Stephen E; Kim, Raymond J; Quyyumi, Arshed A; Cole, Robert T; Anderson, Allen S; Wilcox, Jane E; Skopicki, Hal A; Sikora, Sergey; Verkh, Lev; Tankovich, Nikolai I; Gheorghiade, Mihai; Butler, Javed

2017-04-01

This article describes an ongoing study investigating the safety and efficacy of ischemia-tolerant mesenchymal stem cell (MSC) therapy in patients with nonischemic heart failure and dysfunctional viable myocardium without scarring. This study will follow principles of the previously described mechanistic translational-phase concept whereby the effect of the study agent on laboratory and imaging markers of cardiac structure and function will be tested in a small homogenous cohort with the goal to enhance the understanding of the effect of interventions on cardiac remodeling and performance. This single-blind, placebo-controlled, crossover, multicenter, randomized study will assess the safety, tolerability, and preliminary efficacy of a single intravenous (i.v.) dose of allogeneic ischemia-tolerant MSCs in individuals with heart failure of nonischemic cause, ejection fraction 40% or less, and dysfunctional viable myocardium who have been receiving guideline-directed medical therapy. Eligible patients will have no evidence of baseline replacement scarring on delayed-enhancement cardiac magnetic resonance (CMR). Approximately 20 patients will be randomized in a 1 : 1 ratio to receive an i.v. infusion of ischemia-tolerant MSCs or placebo. At 90 days, the two groups will undergo crossover and received the alternative treatment. The primary endpoint is safety, as evaluated through at least 1-year post-MSC infusion. Additional efficacy endpoints will include measures of cardiac structure and function, as evaluated by serial cine-CMR and transthoracic echocardiography at 90 and 180 days post-initial infusion. This pilot study will explore the safety and effects on cardiac structure and function of i.v. injection of ischemia-tolerant MSCs in a small homogenous cohort of nonischemic heart failure patients with reduced ejection fraction and absent replacement scarring on CMR. This study also represents a prospective mechanistic translational-phase study using baseline and serial CMR imaging in heart failure patients and serves as a potential model for design of future heart failure trials (ClinicalTrials.gov identifier: NCT02467387).

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

PubMed

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

2018-04-18

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

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

PubMed

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

2018-05-25

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

[Heart rate as a therapeutic target after acute coronary syndrome and in chronic coronary heart disease].

PubMed

Ambrosetti, Marco; Scardina, Giuseppe; Favretto, Giuseppe; Temporelli, Pier Luigi; Faggiano, Pompilio Massimo; Greco, Cesare; Pedretti, Roberto Franco

2017-03-01

For patients with stable coronary artery disease (SCAD), either after hospitalization for acute cardiac events or in the chronic phase, comprehensive treatment programs should be devoted to: (i) reducing mortality and major adverse cardiovascular events, (ii) reducing the ischemic burden and related symptoms, and (iii) increasing exercise capacity and quality of life.Heart rate (HR) has demonstrated to have prognostic value and patients beyond the limit of 70 bpm display increased risk of all the above adverse outcomes, even after adjustment for parameters such as the extension of myocardial infarction and the presence of heart failure. It is well known that a sustained HR elevation may contribute to the pathogenesis of SCAD, being the likelihood of developing ischemia, plaque instability, trigger for arrhythmias, increased vascular oxidative stress, and endothelial dysfunction the mechanisms resulting in this effect. Moreover, high HR could promote chronotropic incompetence, leading to functional disability and reduced quality of life.Despite the strong relationship between HR and prognosis, there is heterogeneity among current guidelines in considering HR as a formal therapeutic target for secondary prevention in SCAD, as far as the cut-off limit. This expert opinion document considered major trials and observational registries in the modern treatment era with beta-blockers and ivabradine, suggesting that an adequate HR control could represent a target for (i), (ii), and (iii) therapeutic goals in SCAD patients with systolic dysfunction (with major evidence for reduced left ventricular ejection fraction <40%), and a target for (ii) and (iii) goals in SCAD patients with preserved left ventricular ejection fraction. The defined cut-off limit is 70 bpm. To date, there is room for improvement of HR control, since in contemporary SCAD patients HR values <70 bpm are present in less than half of cases, even in the vulnerable phase after an acute coronary syndrome.

Reducing RBM20 activity improves diastolic dysfunction and cardiac atrophy.

PubMed

Hinze, Florian; Dieterich, Christoph; Radke, Michael H; Granzier, Henk; Gotthardt, Michael

2016-12-01

Impaired diastolic filling is a main contributor to heart failure with preserved ejection fraction (HFpEF), a syndrome with increasing prevalence and no treatment. Both collagen and the giant sarcomeric protein titin determine diastolic function. Since titin's elastic properties can be adjusted physiologically, we evaluated titin-based stiffness as a therapeutic target. We adjusted RBM20-dependent cardiac isoform expression in the titin N2B knockout mouse with increased ventricular stiffness. A ~50 % reduction of RBM20 activity does not only maintain cardiac filling in diastole but also ameliorates cardiac atrophy and thus improves cardiac function in the N2B-deficient heart. Reduced RBM20 activity partially normalized gene expression related to muscle development and fatty acid metabolism. The adaptation of cardiac growth was related to hypertrophy signaling via four-and-a-half lim-domain proteins (FHLs) that translate mechanical input into hypertrophy signals. We provide a novel link between cardiac isoform expression and trophic signaling via FHLs and suggest cardiac splicing as a therapeutic target in diastolic dysfunction. Increasing the length of titin isoforms improves ventricular filling in heart disease. FHL proteins are regulated via RBM20 and adapt cardiac growth. RBM20 is a therapeutic target in diastolic dysfunction.

Is preeclampsia an independent predictor of diastolic dysfunction? A retrospective cohort study.

PubMed

Guirguis, George F; Aziz, Michael M; Boccia Liang, Claire; Williams, Shauna F; Apuzzio, Joseph J; Bilinski, Robyn; Mornan, Adenieki J D; Shah, Leena P

2015-10-01

To determine if preeclampsia is an independent predictor of diastolic dysfunction and what factors among patients with preeclampsia are associated with diastolic dysfunction. This is a retrospective cohort study of patients who delivered between 2008 and 2013 at a single institution who had a maternal echocardiogram during their pregnancy or within 5months of delivery. Patients with structural heart disease, ejection fraction less than 45%, pulmonary embolus, or age over 45years were excluded. Medical records were reviewed for medical and obstetric complications and echocardiogram findings. Demographic characteristics and rate of diastolic dysfunction were compared between patients with preeclampsia and without preeclampsia. Multivariate logistic regression was performed controlling for age, ethnicity, gestational age at delivery, diabetes, preeclampsia, intrauterine growth restriction (IUGR), antihypertensive use and magnesium sulfate administration. Sixty-six patients were identified, of which 39 (59%) had preeclampsia. Past history of preeclampsia, IUGR in the current pregnancy, antihypertensive use and magnesium sulfate use were higher in the preeclampsia group. Fifteen patients (39%) in the preeclampsia group were African-American compared to 2 (3%) in the control group (p<0.01). Seventeen (44%) of the patients with preeclampsia were found to have diastolic dysfunction compared to 3 (11%) controls (OR=6.18, 95% CI 1.59,24.02; p=0.006). Logistic regression analysis did not reveal other independent predictors of diastolic dysfunction. In the patients with preeclampsia, history of preeclampsia with severe features and IUGR were not associated with diastolic dysfunction. Our study supports previous findings that preeclampsia is associated with diastolic dysfunction. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

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.

Cardiac acetylcholine inhibits ventricular remodeling and dysfunction under pathologic conditions.

PubMed

Roy, Ashbeel; Dakroub, Mouhamed; Tezini, Geisa C S V; Liu, Yin; Guatimosim, Silvia; Feng, Qingping; Salgado, Helio C; Prado, Vania F; Prado, Marco A M; Gros, Robert

2016-02-01

Autonomic dysfunction is a characteristic of cardiac disease and decreased vagal activity is observed in heart failure. Rodent cardiomyocytes produce de novo ACh, which is critical in maintaining cardiac homeostasis. We report that this nonneuronal cholinergic system is also found in human cardiomyocytes, which expressed choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter (VAChT). Furthermore, VAChT expression was increased 3- and 1.5-fold at the mRNA and protein level, respectively, in ventricular tissue from patients with heart failure, suggesting increased ACh secretion in disease. We used mice with genetic deletion of cardiomyocyte-specific VAChT or ChAT and mice overexpressing VAChT to test the functional significance of cholinergic signaling. Mice deficient for VAChT displayed an 8% decrease in fractional shortening and 13% decrease in ejection fraction compared with angiotensin II (Ang II)-treated control animals, suggesting enhanced ventricular dysfunction and pathologic remodeling in response to Ang II. Similar results were observed in ChAT-deficient mice. Conversely, no decline in ventricular function was observed in Ang II-treated VAChT overexpressors. Furthermore, the fibrotic area was significantly greater (P < 0.05) in Ang II-treated VAChT-deficient mice (3.61 ± 0.64%) compared with wild-type animals (2.24 ± 0.11%). In contrast, VAChT overexpressing mice did not display an increase in collagen deposition. Our results provide new insight into cholinergic regulation of cardiac function, suggesting that a compensatory increase in cardiomyocyte VAChT levels may help offset cardiac remodeling in heart failure. © FASEB.

Chemotherapy and Cardiotoxicity in Hematologic Malignancies.

PubMed

Stellitano, Antonio; Fedele, Roberta; Barilla, Santina; Iaria, Antonino; Rao, Carmelo Massimiliano; Martino, Massimo

2017-01-01

Antineoplastic agents affect the cardiovascular system, and the incidence of cardiotoxicity is continuously growing in patients with hematologic malignancies and treated with antineoplastic therapy. In this mini-review, we analyzed existing literature which evaluates the likelihood of cardiotoxicity related to the main agents employed in the treatment of hematologic malignancies. There is a significant need to optimize the early identification of patients who are at risk of cardiotoxicity. The conventional echocardiographic measurements used to detect cardiac alterations, such as LVEF, fractional shortening, diameters and volumes, allow only a late diagnosis of cardiac dysfunction, which might be already irreversible. The early identification of patients at risk for rapid progression towards irreversible cardiac failure has a primary purpose, the opportunity for them to benefit from early preventive and therapeutic measures. A useful imaging technique that points in this direction detecting subclinical LVD may be the speckle tracking echocardiography, that has demonstrated a previous detection of myocardial contractile dysfunction compared to the traditional left ventricular ejection fraction. In this view, the discovery of new biomarkers to identify patients at a high risk for the development of these complications is another priority. Cardiotoxicity induced by anticancer drugs is always the outcome of several concurrent factors. It is plausible that an asymptomatic dysfunction precedes clinical events. During this asymptomatic phase, an early treatment prepares the patient for cardiovascular "safety" conditions; on the other hand, a late or missing treatment paves the ground for the development of future cardiac events. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

Prognostic value of systolic mitral annular velocity measured with Doppler tissue imaging in patients with chronic heart failure caused by left ventricular systolic dysfunction

PubMed Central

Nikitin, N P; Loh, P H; de Silva, R; Ghosh, J; Khaleva, O Y; Goode, K; Rigby, A S; Alamgir, F; Clark, A L; Cleland, J G F

2006-01-01

Objective To assess the prognostic value of various conventional and novel echocardiographic indices in patients with chronic heart failure (CHF) caused by left ventricular (LV) systolic dysfunction. Methods 185 patients with a mean (SD) age of 67 (11) years with CHF and LV ejection fraction < 45% despite optimal pharmacological treatment were prospectively enrolled. The patients underwent two dimensional echocardiography with tissue harmonic imaging to assess global LV systolic function and obtain volumetric data. Transmitral flow was assessed with conventional pulse wave Doppler. Systolic (Sm), early, and late diastolic mitral annular velocities were measured with the use of colour coded Doppler tissue imaging. Results During a median follow up of 32 months (range 24–38 months in survivors), 34 patients died and one underwent heart transplantation. Sm velocity (hazard ratio (HR) 0.648, 95% confidence interval (CI) 0.463 to 0.907, p  =  0.011), diastolic arterial pressure (HR 0.965, 95% CI 0.938 to 0.993, p  =  0.015), serum creatinine (HR 1.006, 95% CI 1.001 to 1.011, p  =  0.023), LV ejection fraction (HR 0.945, 95% CI 0.899 to 0.992, p  =  0.024), age (HR 1.035, 95% CI 1.000 to 1.071, p  =  0.052), LV end systolic volume index (HR 1.009, 95% CI 0.999 to 1.019, p  =  0.067), and restrictive pattern of transmitral flow (HR 0.543, 95% CI 0.278 to 1.061, p  =  0.074) predicted the outcome of death or transplantation on univariate analysis. On multivariate analysis, only Sm velocity (HR 0.648, 95% CI 0.460 to 0.912, p  =  0.013) and diastolic arterial pressure (HR 0.966, 95% CI 0.938 to 0.994, p  =  0.016) emerged as independent predictors of outcome. Conclusions In patients with CHF and LV systolic dysfunction despite optimal pharmacological treatment, the strongest independent echocardiographic predictor of prognosis was Sm velocity measured with quantitative colour coded Doppler tissue imaging. PMID:16251233

Short-term Effects of High-Dose Caffeine on Cardiac Arrhythmias in Patients With Heart Failure: A Randomized Clinical Trial.

PubMed

Zuchinali, Priccila; Souza, Gabriela C; Pimentel, Maurício; Chemello, Diego; Zimerman, André; Giaretta, Vanessa; Salamoni, Joyce; Fracasso, Bianca; Zimerman, Leandro I; Rohde, Luis E

2016-12-01

The presumed proarrhythmic action of caffeine is controversial. Few studies have assessed the effect of high doses of caffeine in patients with heart failure due to left ventricular systolic dysfunction at high risk for ventricular arrhythmias. To compare the effect of high-dose caffeine or placebo on the frequency of supraventricular and ventricular arrhythmias, both at rest and during a symptom-limited exercise test. Double-blinded randomized clinical trial with a crossover design conducted at the heart failure and cardiac transplant clinic of a tertiary-care university hospital. The trial included patients with chronic heart failure with moderate-to-severe systolic dysfunction (left ventricular ejection fraction <45%) and New York Heart Association functional class I to III between March 5, 2013, and October 2, 2015. Caffeine (100 mg) or lactose capsules, in addition to 5 doses of 100 mL decaffeinated coffee at 1-hour intervals, for a total of 500 mg of caffeine or placebo during a 5-hour protocol. After a 1-week washout period, the protocol was repeated. Number and percentage of ventricular and supraventricular premature beats assessed by continuous electrocardiographic monitoring. We enrolled 51 patients (37 [74%] male; mean [SD] age, 60.6 [10.9] years) with predominantly moderate-to-severe left ventricular systolic dysfunction (mean [SD] left ventricular ejection fraction, 29% [7%]); 31 [61%] had an implantable cardioverter-defibrillator device. No significant differences between the caffeine and placebo groups were observed in the number of ventricular (185 vs 239 beats, respectively; P = .47) and supraventricular premature beats (6 vs 6 beats, respectively; P = .44), as well as in couplets, bigeminal cycles, or nonsustained tachycardia during continuous electrocardiographic monitoring. Exercise test-derived variables, such as ventricular and supraventricular premature beats, duration of exercise, estimated peak oxygen consumption, and heart rate, were not influenced by caffeine ingestion. We observed no increases in ventricular premature beats (91 vs 223 vs 207 beats, respectively) in patients with higher levels of plasma caffeine concentration compared with lower plasma levels (P = .91) or with the placebo group (P = .74). Acute ingestion of high doses of caffeine did not induce arrhythmias in patients with systolic heart failure and at high risk for ventricular arrhythmias. clinicaltrials.gov Identifier: NCT02045992.

Diagnosis of Nonischemic Stage B Heart Failure in Type 2 Diabetes Mellitus: Optimal Parameters for Prediction of Heart Failure.

PubMed

Wang, Ying; Yang, Hong; Huynh, Quan; Nolan, Mark; Negishi, Kazuaki; Marwick, Thomas H

2018-05-11

This study sought to identify whether impaired global longitudinal strain (GLS), diastolic dysfunction (DD), or left atrial enlargement (LAE) should be added to stage B heart failure (SBHF) criteria in asymptomatic patients with type 2 diabetes mellitus. SBHF is a precursor to clinical heart failure (HF), and its recognition justifies initiation of cardioprotective therapy. However, original definitions of SBHF were based on LV hypertrophy and impaired ejection fraction. Patients with asymptomatic type 2 diabetes mellitus ≥65 years-of-age (age 71 ± 4 years; 55% men) with preserved ejection fraction and no ischemic heart disease were recruited from a community-based population. All underwent a standard clinical evaluation, and a comprehensive echocardiogram, including assessment of left ventricular hypertrophy (LVH), LAE, DD (abnormal E/e'), and GLS (<16%). Over a median follow-up of 1.5 years (range 0.5 to 3), 20 patients were lost to follow-up, and 290 individuals were entered into the final analyses. In this asymptomatic group, LV dysfunction was identified in 30 (10%) by DD, 68 (23%) by LVH, 102 (35%) by LAE, and 68 (23%) by impaired GLS. New-onset HF developed in 45 patients and 4 died, giving an event rate of 112/1,000 person-years. Survival free of the composite endpoint (HF and death) was about 1.5-fold higher in patients without a normal, compared with an abnormal echocardiogram. LVH, LAE, and GLS <16% were associated with increased risk of the composite endpoint, independent of ARIC risk score and glycosylated hemoglobin, but abnormal E/e' was not. The addition of left atrial volume and GLS provided incremental value to the current standard of clinical risk (ARIC score) and LVH. In a competing-risks regression analysis, LVH (hazard ratio: 2.90; p < 0.001) and GLS <16% (hazard ratio: 2.26; p = 0.008), but not DD and LAE were associated with incident HF. Subclinical left ventricular systolic dysfunction is prevalent in asymptomatic elderly patients with type 2 diabetes mellitus, and impaired GLS is independent and incremental to LVH in the prediction of incident HF. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. 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.

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.

Effect of diastolic dysfunction on postoperative outcomes after cardiovascular surgery: A systematic review and meta-analysis.

PubMed

Kaw, Roop; Hernandez, Adrian V; Pasupuleti, Vinay; Deshpande, Abhishek; Nagarajan, Vijaiganesh; Bueno, Hector; Coleman, Craig I; Ioannidis, John P A; Bhatt, Deepak L; Blackstone, Eugene H

2016-10-01

The objective of this study was to investigate the effect of preoperative diastolic dysfunction on postoperative mortality and morbidity after cardiovascular surgery. We systematically searched for articles that assessed the prognostic role of diastolic dysfunction on cardiovascular surgery in PubMed, Cochrane Library, Web of Science, Embase, and Scopus until February 2016. Twelve studies (n = 8224) met our inclusion criteria. Because of the scarcity of outcome events, fixed-effects meta-analysis was performed via the Mantel-Haenszel method. Preoperative diagnosis of diastolic dysfunction was associated with greater postoperative mortality (odds ratio [OR], 2.41; 95% confidence interval [CI], 1.54-3.71; P < .0001), major adverse cardiac events (OR, 2.07; 95% CI, 1.55-2.78; P ≤ .0001), and prolonged mechanical ventilation (OR, 2.08; 95% CI, 1.04-4.16; P = .04) compared with patients without diastolic dysfunction among patients who underwent cardiovascular surgery. The odds of postoperative myocardial infarction (OR, 1.29; 95% CI, 0.82-2.05; P = .28) and atrial fibrillation (OR, 2.67; 95% CI, 0.49-14.43; P = .25) did not significantly differ between the 2 groups. Severity of preoperative diastolic dysfunction was associated with increased postoperative mortality (OR, 21.22; 95% CI, 3.74-120.33; P = .0006) for Grade 3 diastolic dysfunction compared with patients with normal diastolic function. Inclusion of left ventricular ejection fraction (LVEF) <40% accompanying diastolic dysfunction did not further impact postoperative mortality (P = .27; I(2) = 18%) compared with patients with normal LVEF and diastolic dysfunction. Presence of preoperative diastolic dysfunction was associated with greater postoperative mortality and major adverse cardiac events, regardless of LVEF. Mortality was significantly greater in grade III diastolic dysfunction. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Preoperative intra-aortic balloon pump improves the clinical outcomes of off-pump coronary artery bypass grafting in left ventricular dysfunction patients

PubMed Central

Yang, Feng; Wang, Jinhong; Hou, Dengbang; Xing, Jialin; Liu, Feng; Xing, Zhi chen; Jiang, Chunjing; Hao, Xing; Du, Zhongtao; Yang, Xiaofang; Zhao, Yanyan; Miao, Na; Jiang, Yu; Dong, Ran; Gu, Chengxiong; Sun, Lizhong; Wang, Hong; Hou, Xiaotong

2016-01-01

Severe left ventricular (LV) dysfunction patients undergoing off-pump coronary artery bypass grafting (OPCAB) are often associated with a higher mortality. The efficacy and safety of the preoperative prophylactic intra-aortic balloon pump (IABP) insertion is not well established. 416 consecutive patients with severe LV dysfunction (ejection fraction ≤35%) undergoing isolated OPCAB were enrolled in a retrospective observational study. 191 patients was enrolled in the IABP group; the remaining 225 patients was in control group. A total of 129 pairs of patients were propensity-score matched. No significant differences in demographic and preoperative risk factors were found between the two groups. The postoperative 30-day mortality occurred more frequently in the control group compared with the IABP group (8.5% vs. 1.6%, p = 0.02). There was a significant reduction of low cardiac output syndrome in the IABP group compared with the control group (14% vs. 6.2%, p = 0.04). Prolonged mechanical ventilation (≥48 h) occurred more frequently in the control group (34.9% vs. 20.9%, p = 0.02). IABP also decreased the postoperative length of stay. Preoperative IABP was associated with a lower 30-day mortality, suggesting that it is effective in patients with severe LV dysfunction undergoing OPCAB. PMID:27279591

Survival after aortic valve replacement for severe aortic stenosis with low transvalvular gradients and severe left ventricular dysfunction

NASA Technical Reports Server (NTRS)

Pereira, Jeremy J.; Lauer, Michael S.; Bashir, Mohammad; Afridi, Imran; Blackstone, Eugene H.; Stewart, William J.; McCarthy, Patrick M.; Thomas, James D.; Asher, Craig R.

2002-01-01

OBJECTIVE: We sought to assess whether aortic valve replacement (AVR) among patients with severe aortic stenosis (AS), severe left ventricular (LV) dysfunction and a low transvalvular gradient (TVG) is associated with improved survival. BACKGROUND: The optimal management of patients with severe AS with severe LV dysfunction and a low TVG remains controversial. METHODS: Between 1990 and 1998, we evaluated 68 patients who underwent AVR at our institution (AVR group) and 89 patients who did not undergo AVR (control group), with an aortic valve area < or = 0.75 cm(2), LV ejection fraction < or = 35% and mean gradient < or = 30 mm Hg. Using propensity analysis, survival was compared between a cohort of 39 patients in the AVR group and 56 patients in the control group. RESULTS: Despite well-matched baseline characteristics among propensity-matched patients, the one- and four-year survival rates were markedly improved in patients in the AVR group (82% and 78%), as compared with patients in the control group (41% and 15%; p < 0.0001). By multivariable analysis, the main predictor of improved survival was AVR (adjusted risk ratio 0.19, 95% confidence interval 0.09 to 0.39; p < 0.0001). The only other predictors of mortality were age and the serum creatinine level. CONCLUSIONS: Among select patients with severe AS, severe LV dysfunction and a low TVG, AVR was associated with significantly improved survival.

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.

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.

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

PubMed

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

2014-10-01

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

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.

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

PubMed

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

2017-01-01

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

Routine implantation of cardioverter/defibrillator devices in patients aged 75 years and older with prior myocardial infarction and left ventricular ejection fraction < 30: antagonist viewpoint.

PubMed

Basta, Lofty L

2003-01-01

The Multicenter Automatic Defibrillator Implantation Trial (MADIT II) investigators assert that their results justify the placement of artificial implantable defibrillator cardioverter devices in patients aged 75 years and older with prior myocardial infarction and left ventricular dysfunction (ejection fraction of 30 or less). The authors claim that the results of the trial do not justify this conclusion. The majority of patients were male (84%) and aged 64+/-10 years. Also, 2.8% of patients assigned to the defibrillator group and 1.5% had their device removed. Of the latter subgroup, nine patients (1.3%) received a heart transplant. Twelve had their artificial implantable defibrillator cardioverter device deactivated mostly because of terminal illness. Although the study results show a significant reduction in mortality over the control group (absolute reduction=5.6%), almost the same percentage required hospitalization because of manifestation of congestive heart failure (absolute value 5%; p=0.09). Also, 1.8% had lead problems, 0.7% had infections, and the benefits were only seen after the first year. Caution is needed before the results of this study are applied to a much older cohort comprised mainly of women in whom heart transplant is contraindicated and who have multiple health problems, including cognitive impairment. Artificial implantable cardioverter/defibrillator devices are expensive and this study's results need to be duplicated in other comparable cohorts.

Wall Thickness, Pulmonary Hypertension, and Diastolic Filling Abnormalities Predict Response to Postoperative Biventricular Pacing

PubMed Central

Brusen, Robin M.; Hahn, Rebecca; Cabreriza, Santos E.; Cheng, Bin; Wang, Daniel Y.; Truong, Wanda; Spotnitz, Henry M.

2017-01-01

Objective Post-cardiopulmonary bypass biventricular pacing improves hemodynamics but without clearly defined predictors of response. Based on preclinical studies and prior observations, it was suspected that diastolic dysfunction or pulmonary hypertension is predictive of hemodynamic benefit. Design Randomized controlled study of temporary biventricular pacing after cardiopulmonary bypass. Setting Single-center study at university-affiliated tertiary care hospital. Interventions Patients who underwent bypass with pre-operative ejection fraction ≤40% and QRS duration ≥100 ms or double-valve surgery were enrolled. At 3 time points between separation from bypass and postoperative day 1, pacing delays were varied to optimize hemodynamics. Participants Data from 43 patients were analyzed. Measurements and Main Results Cardiac output and arterial pressure were measured under no pacing, atrial pacing, and biventricular pacing. Preoperative echocardiograms and pulmonary artery catheterizations were reviewed, and measures of both systolic and diastolic function were compared to hemodynamic response. Early after separation, improvement in cardiac output was positively correlated with pulmonary vascular resistance (R2 = 0.97, p < 0.001), ventricle wall thickness (R2 = 0.72, p = 0.002)), and E/e′, a measure of abnormal diastolic ventricular filling velocity (R2 = 0.56, p = 0.04). Similar trends were seen with mean arterial pressure. QRS duration and ejection fraction did not correlate significantly with improvements in hemodynamics. Conclusions There may be an effect of biventricular pacing related to amelioration of abnormal diastolic filling patterns rather than electrical resynchronization in the postoperative state. PMID:25998068

Cardiac structure and function predicts functional decline in the oldest old.

PubMed

Leibowitz, David; Jacobs, Jeremy M; Lande-Stessman, Irit; Gilon, Dan; Stessman, Jochanan

2018-02-01

Background This study examined the association between cardiac structure and function and the deterioration in activities of daily living (ADLs) in an age-homogenous, community-dwelling population of patients born in 1920-1921 over a five-year follow-up period. Design Longitudinal cohort study. Methods Patients were recruited from the Jerusalem Longitudinal Cohort Study, which has followed an age-homogenous cohort of Jerusalem residents born in 1920-1921. Patients underwent home echocardiography and were followed up for five years. Dependence was defined as needing assistance with one or more basic ADL. Standard echocardiographic assessment of cardiac structure and function, including systolic and diastolic function, was performed. Reassessment of ADLs was performed at the five-year follow-up. Results A total of 459 patients were included in the study. Of these, 362 (79%) showed a deterioration in at least one ADL at follow-up. Patients with functional deterioration had a significantly higher left ventricular mass index and left atrial volume with a lower ejection fraction. There was no significant difference between the diastolic parameters the groups in examined. When the data were examined categorically, a significantly larger percentage of patients with functional decline had an abnormal left ventricular ejection fraction and left ventricular hypertrophy. The association between left ventricular mass index and functional decline remained significant in all multivariate models. Conclusions In this cohort of the oldest old, an elevated left ventricular mass index, higher left atrial volumes and systolic, but not diastolic dysfunction, were predictive of functional disability.

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.

Evaluation of Left Ventricle Function by Regional Fractional Area Change (RFAC) in a Mouse Model of Myocardial Infarction Secondary to Valsartan Treatment

PubMed Central

Castiglioni, Laura; Colazzo, Francesca; Fontana, Lucia; Colombo, Gualtiero I.; Piacentini, Luca; Bono, Elisa; Milano, Giuseppina; Paleari, Serena; Palermo, Annamaria; Guerrini, Uliano; Tremoli, Elena; Sironi, Luigi

2015-01-01

Aim Left ventricle (LV) regional fractional area change (RFAC) measured by cardiac magnetic resonance (CMR) allows the non-invasive localization and quantification of the degree of myocardial infarction (MI), and could be applied to assess the effectiveness of pharmacological or regenerative therapies. Here we investigate the ability of RFAC to identify regional dysfunction and discriminate the effect of pharmacological treatment with valsartan, a selective antagonist of angiotensin II type 1 receptor, in a model of MI. Methods and Results C57BL/6N mice, undergoing coronary artery ligation, were divided into two groups: untreated (MI) or treated with valsartan (MI+Val). Sham-operated mice were used as a control. Cardiac dimensions and function were assessed at baseline, 24 hours, 1 and 4 weeks post surgery by CMR and echocardiography. At sacrifice histology and whole-genome gene expression profiling were performed. RFAC was able to detect significant differences between treatment groups whereas the global ejection fraction was not. RFAC showed greater loss of regional contraction in remote non-infarcted myocardium in MI group than in MI+Val group. Consistently, in the same region MI+Val mice showed reduced myocyte hypertrophy, fibroblast proliferation, and fibrosis and modulation of target genes; in addition, left atrium volumes, appendage length and duct contraction were preserved. Conclusion In this study, RFAC effectively estimated the degree of systolic dysfunction and discriminated the regions preserved by pharmacological treatment. RFAC index is a promising tool to monitor changes in LV contraction and to assess the effectiveness of therapeutic regimens in clinical settings. PMID:26291973

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.

Early myocardial dysfunction in streptozotocin-induced diabetic mice: a study using in vivo magnetic resonance imaging (MRI)

PubMed Central

Yu, Xichun; Tesiram, Yasvir A; Towner, Rheal A; Abbott, Andrew; Patterson, Eugene; Huang, Shijun; Garrett, Marion W; Chandrasekaran, Suresh; Matsuzaki, Satoshi; Szweda, Luke I; Gordon, Brian E; Kem, David C

2007-01-01

Background Diabetes is associated with a cardiomyopathy that is independent of coronary artery disease or hypertension. In the present study we used in vivo magnetic resonance imaging (MRI) and echocardiographic techniques to examine and characterize early changes in myocardial function in a mouse model of type 1 diabetes. Methods Diabetes was induced in 8-week old C57BL/6 mice with two intraperitoneal injections of streptozotocin. The blood glucose levels were maintained at 19–25 mmol/l using intermittent low dosages of long acting insulin glargine. MRI and echocardiography were performed at 4 weeks of diabetes (age of 12 weeks) in diabetic mice and age-matched controls. Results After 4 weeks of hyperglycemia one marker of mitochondrial function, NADH oxidase activity, was decreased to 50% of control animals. MRI studies of diabetic mice at 4 weeks demonstrated significant deficits in myocardial morphology and functionality including: a decreased left ventricular (LV) wall thickness, an increased LV end-systolic diameter and volume, a diminished LV ejection fraction and cardiac output, a decreased LV circumferential shortening, and decreased LV peak ejection and filling rates. M-mode echocardiographic and Doppler flow studies of diabetic mice at 4 weeks showed a decreased wall thickening and increased E/A ratio, supporting both systolic and diastolic dysfunction. Conclusion Our study demonstrates that MRI interrogation can identify the onset of diabetic cardiomyopathy in mice with its impaired functional capacity and altered morphology. The MRI technique will lend itself to repetitive study of early changes in cardiac function in small animal models of diabetic cardiomyopathy. PMID:17309798

Left Ventricular Function in Patients with Pulmonary Arterial Hypertension: The Role of Two-Dimensional Speckle Tracking Strain.

PubMed

de Amorim Corrêa, Ricardo; de Oliveira, Fernanda Brito; Barbosa, Marcia M; Barbosa, Jose Augusto A; Carvalho, Taís Soares; Barreto, Michele Campos; Campos, Frederico Thadeu A F; Nunes, Maria Carmo Pereira

2016-09-01

Pulmonary arterial hypertension (PAH) is characterized by elevated mean pulmonary arterial pressure with abnormal right ventricular (RV) pressure overload that may alter left ventricular (LV) function. The aim of this study was to assess the impact of RV pressure overload on LV function in PAH patients using two-dimensional (2D) speckle tracking strain. The study enrolled 37 group 1 PAH patients and 38 age- and gender-matched healthy controls. LV longitudinal and radial 2D strains were measured with and without including the ventricular septum. Six-minute walk test (6MWT) and brain natriuretic peptide (BNP) levels were also obtained in patients with PAH. The mean age of patients was 46.4 ± 14.8 years, 76% women, and 16 patients (43%) had schistosomiasis. Sixteen patients (43%) were in WHO class III or IV under specific treatment for PAH. The overall 6MWT distance was 441 meters, and the BNP levels were 80 pg/mL. Patients with PAH more commonly presented with LV diastolic dysfunction and impairment of RV function when compared to controls. LV global longitudinal and radial strains were lower in patients than in controls (-17.9 ± 2.8 vs. -20.5 ± 1.9; P < 0.001 and 30.8 ± 10.5 vs. 49.8 ± 15.4; P < 0.001, respectively). After excluding septal values, LV longitudinal and radial strains remained lower in patients than in controls. The independent factors associated with global LV longitudinal strain were LV ejection fraction, RV fractional area change, and tricuspid annular systolic motion. This study showed impaired LV contractility in patients with PAH assessed by speckle tracking strain, irrespective of ventricular septal involvement. Global LV longitudinal strain was associated independently with RV fractional area change and tricuspid annular systolic motion, after adjustment for LV ejection fraction. © 2016, Wiley Periodicals, Inc.

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.

A single-centre report on the characteristics of Tako-tsubo syndrome.

PubMed

Teh, Andrew W; New, Gishel; Cooke, Jennifer

2010-02-01

Tako-tsubo cardiomyopathy is an increasingly recognised phenomenon characterised by chest pain, ECG abnormalities, cardiac biomarker elevation and transient left ventricular dysfunction without significant coronary artery obstruction. To report the clinical and echocardiographic characteristics from a large single-centre Australian series of patients with Tako-tsubo syndrome. We prospectively collected data on 23 consecutive patients presenting between November 2005 and November 2007. Baseline demographics, ECG, echocardiography and coronary angiography were performed on nearly all patients. All patients presented with chest pain; 87% were female. Various stressors were noted and cardiac Troponin-T was elevated in 91% of patients. All patients had non-obstructive coronary disease at angiography. 19/23 patients had initial and subsequent echocardiography. Mean ejection fraction was 50% at baseline and 64% at follow-up (p<0.0001). Right ventricular dysfunction was present in eight, dynamic left ventricular outflow tract obstruction in two, diastolic dysfunction in seven and two patients had the mid-cavity variant. This large prospective single-centre Australian series of Tako-tsubo syndrome is in concert with previous published series. Complete recovery of left ventricular function on echocardiographic follow-up was typical. Although its pathogenesis remains unclear, early distinction from acute coronary syndromes is important and the prognosis is reassuringly good. Crown Copyright (c) 2009. Published by Elsevier B.V. All rights reserved.

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

PubMed

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

2017-11-29

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

Impact of a pure reduction in heart rate for the treatment of left ventricular dysfunction: clinical benefits of ivabradine in the BEAUTIFUL trial.

PubMed

Danchin, Nicolas

2009-01-01

Ivabradine is an I(f) current inhibitor, that has documented antianginal efficacy. The BEAUTIFUL trial tested ivabradine against placebo in a large population of 10,917 patients in sinus rhythm, with coronary artery disease and left ventricular dysfunction, defined as left ventricular ejection fraction < or =35%. Overall, there was no impact of ivabradine on the primary end-point of the trial (cardiovascular mortality, hospitalisation for myocardial infarction, new onset or worsening heart failure). In the placebo arm of the trial, baseline heart rate > or = 70 bpm was associated with an increased risk of cardiovascular mortality, myocardial infarction, heart failure and coronary revascularisation. In the subgroup of patients with a baseline heart rate > or =70 bpm, treatment with ivabradine resulted in a significant, 36% reduction in the risk of myocardial infarction and a 20% reduction in the need for coronary revascularisation. Ivabradine was well tolerated, with an increased rate of treatment discontinuation, mainly due to bradycardia, compared with placebo. Because of its safety and efficacy to control angina, ivabradine should be considered first-line antianginal treatment in coronary artery disease patients with left ventricular dysfunction and increased heart rate, already receiving beta-blocker therapy or in whom these medications are not tolerated.

Finerenone : third-generation mineralocorticoid receptor antagonist for the treatment of heart failure and diabetic kidney disease.

PubMed

Liu, Licette C Y; Schutte, Elise; Gansevoort, Ron T; van der Meer, Peter; Voors, Adriaan A

2015-01-01

The mineralocorticoid receptor antagonists (MRAs) spironolactone and eplerenone reduce the risk of hospitalizations and mortality in patients with heart failure (HF) with reduced ejection fraction (HFrEF), and attenuate progression of diabetic kidney disease. However, their use is limited by the fear of inducing hyperkalemia, especially in patients with renal dysfunction. Finerenone is a novel nonsteroidal MRA, with higher selectivity toward the mineralocorticoid receptor (MR) compared to spironolactone and stronger MR-binding affinity than eplerenone. This paper discusses the chemistry, pharmacokinetics, clinical efficacy and safety of finerenone. The selectivity and greater binding affinity of finerenone to the MR may reduce the risk of hyperkalemia and renal dysfunction and thereby overcome the reluctance to start and uptitrate MRAs in patients with HF and diabetic kidney disease. Studies conducted in patients with HFrEF and moderate chronic kidney disease and diabetic kidney disease, showed promising results. Phase III trials will have to show whether finerenone might become the third-generation MRA for the treatment of HF and diabetic kidney disease.

Detection and quantification by deformation imaging of the functional impact of septal compared to free wall preexcitation in the Wolff-Parkinson-White syndrome.

PubMed

De Boeck, Bart W L; Teske, Arco J; Leenders, Geert E; Mohamed Hoesein, Firdaus A A; Loh, Peter; van Driel, Vincent J; Doevendans, Pieter A; Prinzen, Frits W; Cramer, Maarten J

2010-08-15

Pacing experiments in healthy animal hearts have suggested a larger detrimental effect of septal compared to free wall preexcitation. We investigated the intrinsic relation among the site of electrical preexcitation, mechanical dyssynchrony, and dysfunction in human patients. In 33 patients with Wolff-Parkinson-White (WPW) syndrome and 18 controls, regional myocardial deformation was assessed by speckle tracking mapping (ST-Map) to assess the preexcitation site, shortening sequences and dyssynchrony, and the extent of local and global ejecting shortening. The ST-Map data in patients with accessory atrioventricular pathways correctly diagnosed as located in the interventricular septum (IVS) (n = 11) or left ventricular free wall (LFW) (n = 12) were compared to the corresponding control values. A local ejecting shortening of <2 SD of the control values identified hypokinetic segments. The localization of the atrioventricular pathways by ST-Map matched with the invasive electrophysiology findings in 23 of 33 patients and was one segment different in 5 of 33 patients. In both WPW-IVS and WPW-LFW, local ejecting shortening was impaired at the preexcitation site (p <0.01). However, at similar electrical and mechanical dyssynchrony, WPW-IVS had more extensive hypokinesia than did WPW-LFW (3.6 +/- 0.9 vs 1.8 +/- 1.3 segments, p <0.01). Compared to controls, the left ventricular function was significantly reduced only in WPW-IVS (global ejecting shortening 17 +/- 2% vs 19 +/- 2%, p = 0.01; ejection fraction 55 +/- 5% vs 59 +/- 3%, p = 0.02). In conclusion, preexcitation is associated with local hypokinesia, which at comparable preexcitation is more extensive in WPW-IVS than in WPW-LFW and could adversely affect ventricular function. ST-Map might have a future role in detecting and guiding treatment of septal pathways with significant mechanical effects.

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

Association between left ventricular perfusion defects and myocardial deformation indexes in heart transplantation recipients.

PubMed

D'Andrea, Antonello; De Rimini, Maria Luisa; America, Raffaella; Cirillo, Chiara; Riegler, Lucia; Limongelli, Giuseppe; D'Alto, Michele; Salerno, Gemma; Maiello, Ciro; Muto, Pietro; Russo, Maria Giovanna; Calabrò, Raffaele; Bossone, Eduardo; Pacileo, Giuseppe

2017-10-01

The aim of the study was to analyze possible correlations between strain echocardiography (STE) and PET myocardial perfusion in a population of heart transplantation (HTx) recipients showing preserved left ventricular (LV) ejection fraction. By STE, LV global longitudinal strain (LV GLS) was lower in HTx. PET showed no transient or chronic ischemia in 83 of 115 HTx (73%). Fixed perfusion defects were observed in 17% of HTx and reversible ischemia in 10%. Significant coronary stenosis was observed only in 10 cases. GLS was independently associated with age at HTx and fixed perfusion defects (HR 0.41; P<.001). Such relationships underline STE ability to early identify HTx pts with subclinical myocardial dysfunction during long-term follow-up. © 2017, Wiley Periodicals, Inc.

Exercise-induced pulmonary artery hypertension in a patient with compensated cardiac disease: hemodynamic and functional response to sildenafil therapy.

PubMed

Nikolaidis, Lazaros; Memon, Nabeel; O'Murchu, Brian

2015-02-01

We describe the case of a 54-year-old man who presented with exertional dyspnea and fatigue that had worsened over the preceding 2 years, despite a normally functioning bioprosthetic aortic valve and stable, mild left ventricular dysfunction (left ventricular ejection fraction, 0.45). His symptoms could not be explained by physical examination, an extensive biochemical profile, or multiple cardiac and pulmonary investigations. However, abnormal cardiopulmonary exercise test results and a right heart catheterization-combined with the use of a symptom-limited, bedside bicycle ergometer-revealed that the patient's exercise-induced pulmonary artery hypertension was out of proportion to his compensated left heart disease. A trial of sildenafil therapy resulted in objective improvements in hemodynamic values and functional class.

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.

Monitoring ventricular function at rest and during exercise with a nonimaging nuclear detector.

PubMed

Wagner, H N; Rigo, P; Baxter, R H; Alderson, P O; Douglass, K H; Housholder, D F

1979-05-01

A portable nonimaging device, the nuclear stethoscope, for measuring beat to beat ventricular time-activity curves in normal people and patients with heart disease, both at rest and during exercise, is being developed and evaluated. The latest device has several operating modes that facilitate left ventricular and background localization, measurement of transit times and automatic calculation and display of left ventricular ejection fraction. The correlation coefficient of left ventricular ejection fraction obtained with the device and with a camera-computer system was 0.92 in 35 subjects. During bicycle exercise the ejection fraction in 15 normal persons increased from 44 to 64 percent (P less than 0.001), whereas among 12 patients with heart disease it was unchanged in 5 and decreased in 7.

Adenoviral short hairpin RNA therapy targeting phosphodiesterase 5a relieves cardiac remodeling and dysfunction following myocardial infarction.

PubMed

Li, Longhu; Haider, Husnain Kh; Wang, Linlin; Lu, Gang; Ashraf, Muhammad

2012-05-15

We previously showed that treatment with tadalafil, a long-acting phosphodiesterase-5a (PDE5a) inhibitor, effectively prevented adverse left ventricular (LV) remodeling of the infarcted heart. We hypothesized that short-hairpin RNA (shRNA) therapy targeting PDE5a would simulate the effects of pharmacological intervention for treatment of postinfarction LV remodeling and dysfunction. Experimental model of myocardial infarction was developed in female mice by permanent ligation of left coronary artery. Immediately after that, an adenoviral vector encoding for shRNA sequence targeting PDE5a (Ad-shPDE5a) was injected intramyocardially, which specifically inhibited PDE5a in the heart. Four weeks later, Ad-shPDE5a treated mice showed significant mitigation of the left ventricle (LV) dilatation and dysfunction as indicated by smaller LV cavity and more preserved ejection fraction and fractional shortening. Infarction size and fibrosis were significantly reduced in Ad-shPDE5a-treated mice. Additionally, more salvaged cardiomyocytes, significantly reduced collagen contents, and higher blood vessel density were observed in Ad-shPDE5a-treated mice. The cytoprotective effects of Ad-shPDE5a were demonstrated in vitro in Ad-shPDE5a transfected cardiomyocytes cultured under oxygen glucose deprivation. Among downstream mediators of PDE5a signaling, cyclic GMP (cGMP) and cGMP-dependent protein kinase G (PKG) were activated with concomitant reduction in caspase-3 activity. However, no significant change in PKA and cAMP activities were observed in Ad-shPDE5a-treated hearts. Inhibition with shRNA improved cardiac remodeling and dysfunction by reducing infarction size and cardiac fibrosis and increased cGMP and PKG activity. These findings suggest that PDE5 inhibition with Ad-shPDE5a is a novel approach for treatment of myocardial infarction.

Adenoviral short hairpin RNA therapy targeting phosphodiesterase 5a relieves cardiac remodeling and dysfunction following myocardial infarction

PubMed Central

Li, Longhu; Haider, Husnain Kh.; Wang, Linlin; Lu, Gang

2012-01-01

We previously showed that treatment with tadalafil, a long-acting phosphodiesterase-5a (PDE5a) inhibitor, effectively prevented adverse left ventricular (LV) remodeling of the infarcted heart. We hypothesized that short-hairpin RNA (shRNA) therapy targeting PDE5a would simulate the effects of pharmacological intervention for treatment of postinfarction LV remodeling and dysfunction. Experimental model of myocardial infarction was developed in female mice by permanent ligation of left coronary artery. Immediately after that, an adenoviral vector encoding for shRNA sequence targeting PDE5a (Ad-shPDE5a) was injected intramyocardially, which specifically inhibited PDE5a in the heart. Four weeks later, Ad-shPDE5a treated mice showed significant mitigation of the left ventricle (LV) dilatation and dysfunction as indicated by smaller LV cavity and more preserved ejection fraction and fractional shortening. Infarction size and fibrosis were significantly reduced in Ad-shPDE5a-treated mice. Additionally, more salvaged cardiomyocytes, significantly reduced collagen contents, and higher blood vessel density were observed in Ad-shPDE5a-treated mice. The cytoprotective effects of Ad-shPDE5a were demonstrated in vitro in Ad-shPDE5a transfected cardiomyocytes cultured under oxygen glucose deprivation. Among downstream mediators of PDE5a signaling, cyclic GMP (cGMP) and cGMP-dependent protein kinase G (PKG) were activated with concomitant reduction in caspase-3 activity. However, no significant change in PKA and cAMP activities were observed in Ad-shPDE5a-treated hearts. Inhibition with shRNA improved cardiac remodeling and dysfunction by reducing infarction size and cardiac fibrosis and increased cGMP and PKG activity. These findings suggest that PDE5 inhibition with Ad-shPDE5a is a novel approach for treatment of myocardial infarction. PMID:22447941

Comparison of LVEF assessed by 2D echocardiography, gated blood pool SPECT, 99mTc tetrofosmin gated SPECT, and 18F-FDG gated PET with ERNV in patients with CAD and severe LV dysfunction.

PubMed

Raja, Senthil; Mittal, Bhagwant R; Santhosh, Sampath; Bhattacharya, Anish; Rohit, Manoj K

2014-11-01

Left ventricular ejection fraction (LVEF) is the single most important predictor of prognosis in patients with coronary artery disease (CAD) and left ventricular (LV) dysfunction. Equilibrium radionuclide ventriculography (ERNV) is considered the most reliable technique for assessing LVEF. Most of these patients undergo two dimensional (2D) echocardiography and myocardial viability study using gated myocardial perfusion imaging (MPI) or gated F-fluorodeoxyglucose (F-FDG) PET. However, the accuracy of LVEF assessed by these methods is not clear. This study has been designed to assess the correlation and agreement between the LVEF measured by 2D echocardiography, gated blood pool single photon emission computed tomography (SPECT), Tc tetrofosmin gated SPECT, and F-FDG gated PET with ERNV in CAD patients with severe LV dysfunction. Patients with CAD and severe LV dysfunction [ejection fraction (EF) <35 assessed by 2D echocardiography] were prospectively included in the study. These patients underwent ERNV along with gated blood pool SPECT, Tc tetrofosmin gated SPECT, and F-FDG gated PET as per the standard protocol for myocardial viability assessment and LVEF calculation. Spearman's coefficient of correlation (r) was calculated for the different sets of values with significance level kept at a P-value less than 0.05. Bland-Altman plots were inspected to visually assess the between-agreement measurements from different methods. Forty-one patients were prospectively included. LVEF calculated by various radionuclide methods showed good correlation with ERNV as follows: gated blood pool SPECT, r=0.92; MPI gated SPECT, r=0.85; and F-FDG gated PET, r=0.76. However, the correlation between 2D echocardiography and ERNV was poor (r=0.520). The Bland-Altman plot for LVEF measured by all radionuclide methods showed good agreement with ERNV. However, agreement between 2D echocardiography and ERNV is poor, as most of the values in this plot gave a negative difference for low EF and a positive difference for high EF. The mean difference between various techniques [2D echocardiography (a), gated blood pool SPECT (b), MPI gated SPECT (c), F-FDG gated PET (d)] and ERNV (e) was as follows: (a)-(e), 3.3; (b)-(e), 5; (c)-(e), 1.1; and (d)-(e), 2.9. The best possible correlation and agreement was found between MPI gated SPECT and ERNV. This study showed good correlation and agreement between MPI gated SPECT and F-FDG gated PET with ERNV for LVEF calculation in CAD patients with severe LV dysfunction. Thus, subjecting patients who undergo viability assessment by MPI gated SPECT or F-FDG gated PET to a separate procedure like ERNV for LVEF assessment may not be warranted. As the gated blood pool SPECT also showed good correlation and agreement with ERNV for LVEF assessment in CAD patients with severe LV dysfunction, with better characteristics than ERNV, it can be routinely used whenever accurate LVEF assessment is needed.

Evaluation of left ventricular function in obese children without hypertension by a tissue Doppler imaging study.

PubMed

Ghandi, Yazdan; Sharifi, Mehrzad; Habibi, Danial; Dorreh, Fatemeh; Hashemi, Mojtaba

2018-01-01

The prevalence of obesity is increasing worldwide. Obese children without hypertension are becoming an important health challenge. Complications of obesity in adults are well established, but in obese children, cardiac dysfunction has not been reported clinically. The present crosssectional study investigates subclinical systolic and diastolic dysfunction using echocardiographic modalities. Twentyfive youngsters with body mass index (BMI) >30 and 25 healthy children with BMI <25 were assigned into case and control group, respectively. In all participants, complete cardiovascular examination, electrocardiography, and echocardiography were fulfilled. Echocardiography surveys included standard, pulsed wave Doppler (PWD), and tissue Doppler imaging (TDI). SPSS software, version 24. The two groups were matched for age and sex. The resting heart rate and blood pressure were markedly higher in the obese group ( P = 0.0001) though they were within the normal range in either category. Ejection fraction in the two groups was similar. Left ventricular (LV) mass ( P = 0.0001), LV mass index ( P = 0.029), left atrialtoaortic diameter ratio ( P = 0.0001), and LV enddiastolic diameter ( P = 0.008) were significantly greater in the case group, indicating cardiomegaly and subclinical systolic and diastolic dysfunction. Except for the aortic velocity, all PWD variables were considerably lower in the case group, suggesting subclinical diastolic dysfunction. All TDI parameters varied significantly between the two categories. There was a direct correlation between isovolumetric relaxation time and BMI. Obesity in children without hypertension is associated with subclinical systolic and diastolic cardiac dysfunction. We propose the evaluation of blood pressure as well as myocardial performance using PWD and TDI in all obese children without hypertension, regularly.

Reversal of mitochondrial dysfunction by coenzyme Q10 supplement improves endothelial function in patients with ischaemic left ventricular systolic dysfunction: a randomized controlled trial.

PubMed

Dai, Yuk-Ling; Luk, Ting-Hin; Yiu, Kai-Hang; Wang, Mei; Yip, Pandora M C; Lee, Stephen W L; Li, Sheung-Wai; Tam, Sidney; Fong, Bonnie; Lau, Chu-Pak; Siu, Chung-Wah; Tse, Hung-Fat

2011-06-01

Coronary artery disease (CAD) is associated with endothelial dysfunction and mitochondrial dysfunction (MD). The aim of this study was to investigate whether co-enzyme Q10 (CoQ) supplementation, which is an obligatory coenzyme in the mitochondrial respiratory transport chain, can reverse MD and improve endothelial function in patients with ischaemic left ventricular systolic dysfunction (LVSD). We performed a randomized, double-blind, placebo-controlled trial to determine the effects of CoQ supplement (300 mg/day, n=28) vs. placebo (controls, n=28) for 8 weeks on brachial flow-mediated dilation (FMD) in patients with ischaemic LVSD(left ventricular ejection fraction <45%). Mitochondrial function was determined by plasma lactate/pyruvate ratio (LP ratio). After 8 weeks, CoQ-treated patients had significant increases in plasma CoQ concentration (treatment effect 2.20 μg/mL, P<0.001) and FMD (treatment effect 1.51%, P=0.03); and decrease in LP ratio (treatment effect -2.46, P=0.03) compared with controls. However, CoQ treatment did not alter nitroglycerin-mediated dilation, blood pressure, blood levels of fasting glucose, haemoglobin A1c, lipid profile, high-sensitivity C-reactive protein and oxidative stress as determined by serum superoxide dismutase and 8-isoprostane (all P>0.05). Furthermore, the reduction in LP ratio significantly correlated with improvement in FMD (r=-0.29, P=0.047). In patients with ischaemic LVSD, 8 weeks supplement of CoQ improved mitochondrial function and FMD; and the improvement of FMD correlated with the change in mitochondrial function, suggesting that CoQ improved endothelial function via reversal of mitochondrial dysfunction in patients with ischaemic LVSD. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Modern nuclear cardiac imaging in diagnosis and clinical management of patients with left ventricular dysfunction.

PubMed

Abidov, A; Hachamovitch, R; Berman, D S

2004-12-01

Congestive heart failure (CHF) has become a large social burden in modern Western society, with very high morbidity and mortality and extremely large financial costs. The largest cause of CHF is coronary heart disease, with ventricular dysfunction that may or may not be reversible by revascularization. Thus, evaluation of the viable myocardial tissue in patients with ischemic left ventricular (LV) dysfunction has important clinical and therapeutic implications. Furthermore, since patients with ventricular dysfunction are at higher operative risk, cardiologists and cardiac surgeons are commonly faced with issues regarding the balance between the potential risk vs benefit of revascularization procedures. Cardiac nuclear imaging [myocardial perfusion SPECT (MPS) and positron emission tomography (PET)] provide objective information that augments standard clinical and angiographic assessments of patients with ventricular dysfunction with respect to diagnosis (etiology), prognosis, and potential benefit from intervention. Development of the technology and methodology of gated MPS, now the routine method for MPS, allows assessment of the extent and severity of inducible ischemia as well as hypoperfused but viable myocardium, and also provides measurements of LV ejection fraction, regional wall motion, LV volume measurements, diastolic function and LV geometry. With PET, myocardial metabolism and blood flow reserve can be added to the measurements provided by nuclear cardiology procedures. This paper provides insight into the current evidence regarding settings in which nuclear cardiac imaging procedures are helpful in assessment of patients in the setting of coronary artery disease with severe LV dysfunction. A risk-benefit approach to MPS results is proposed, with principal focus on identifying patients at risk for major cardiac events who may benefit from myocardial revascularization.

Drp1-Dependent Mitochondrial Autophagy Plays a Protective Role Against Pressure Overload-Induced Mitochondrial Dysfunction and Heart Failure.

PubMed

Shirakabe, Akihiro; Zhai, Peiyong; Ikeda, Yoshiyuki; Saito, Toshiro; Maejima, Yasuhiro; Hsu, Chiao-Po; Nomura, Masatoshi; Egashira, Kensuke; Levine, Beth; Sadoshima, Junichi

2016-03-29

Mitochondrial autophagy is an important mediator of mitochondrial quality control in cardiomyocytes. The occurrence of mitochondrial autophagy and its significance during cardiac hypertrophy are not well understood. Mice were subjected to transverse aortic constriction (TAC) and observed at multiple time points up to 30 days. Cardiac hypertrophy developed after 5 days, the ejection fraction was reduced after 14 days, and heart failure was observed 30 days after TAC. General autophagy was upregulated between 1 and 12 hours after TAC but was downregulated below physiological levels 5 days after TAC. Mitochondrial autophagy, evaluated by electron microscopy, mitochondrial content, and Keima with mitochondrial localization signal, was transiently activated at ≈3 to 7 days post-TAC, coinciding with mitochondrial translocation of Drp1. However, it was downregulated thereafter, followed by mitochondrial dysfunction. Haploinsufficiency of Drp1 abolished mitochondrial autophagy and exacerbated the development of both mitochondrial dysfunction and heart failure after TAC. Injection of Tat-Beclin 1, a potent inducer of autophagy, but not control peptide, on day 7 after TAC, partially rescued mitochondrial autophagy and attenuated mitochondrial dysfunction and heart failure induced by overload. Haploinsufficiency of either drp1 or beclin 1 prevented the rescue by Tat-Beclin 1, suggesting that its effect is mediated in part through autophagy, including mitochondrial autophagy. Mitochondrial autophagy is transiently activated and then downregulated in the mouse heart in response to pressure overload. Downregulation of mitochondrial autophagy plays an important role in mediating the development of mitochondrial dysfunction and heart failure, whereas restoration of mitochondrial autophagy attenuates dysfunction in the heart during pressure overload. © 2016 American Heart Association, Inc.

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.

Right Ventricular Systolic Dysfunction in Chagas Disease Defined by Speckle-Tracking Echocardiography: A Comparative Study with Cardiac Magnetic Resonance Imaging.

PubMed

Moreira, Henrique T; Volpe, Gustavo J; Marin-Neto, José A; Nwabuo, Chike C; Ambale-Venkatesh, Bharath; Gali, Luis G; Almeida-Filho, Oswaldo C; Romano, Minna M D; Pazin-Filho, Antonio; Maciel, Benedito C; Lima, João A C; Schmidt, André

2017-05-01

Chagas disease leads to biventricular heart failure, usually with prominent systemic congestion. Although echocardiography is widely used in clinical routine, the utility of echocardiographic parameters to detect right ventricular (RV) systolic dysfunction in patients with Chagas disease is unknown. We sought to study the diagnostic value of echocardiography, including speckle-tracking parameters, to distinguish individuals with RV systolic dysfunction from those with normal RV systolic function in Chagas disease using cardiac magnetic resonance (CMR) as the reference method. In this cross-sectional study, 63 individuals with Chagas disease underwent echocardiography and CMR evaluations. Conventional echocardiographic parameters for RV functional evaluation were tricuspid annular plane systolic excursion, RV systolic excursion velocity, fractional area change, and RV index of myocardial performance. Strain and strain rate were obtained by two-dimensional speckle-tracking echocardiography and defined as "RV free wall," when based only in segments from RV free wall, or "RV free wall and septum," when segments from both free RV wall and interventricular septum were included. RV systolic dysfunction was defined as RV ejection fraction (RVEF) < 50% by CMR. Mean age was 56 ± 14 years, and 58.7% of the patients were men. RV systolic dysfunction was detected by CMR in 18 (28.6%) individuals. RV free wall strain showed the highest correlation with RVEF by CMR (r = -0.62, P < .001), followed by fractional area change (r = 0.56, P < .001), RV free wall and septum strain (r = -0.54, P < .001), RV free wall and septum strain rate (r = -0.47, P < .001), RV free wall strain rate (r = -0.45, P < .001), and RV systolic excursion velocity (r = 0.30, P = .016). The RV index of myocardial performance and tricuspid annular plane systolic excursion showed a small and not significant correlation with RVEF (r = -0.20, P = .320; r = 0.14; P = .289, respectively). Using predefined cutoffs for RV systolic dysfunction, RV free wall strain (>-22.5% for men and >-23.3% for women) exhibited the highest area under the receiver operating characteristic curve (area under the curve = 0.829) to differentiate the presence from the absence of RV systolic dysfunction in Chagas disease, with a sensitivity and specificity of 67% and 83%, respectively. RV free wall strain is an appropriate and superior echocardiographic variable for evaluating RV systolic function in Chagas disease, and it should be the method of choice for this purpose. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

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)

EPA, not DHA, prevents fibrosis in pressure overload-induced heart failure: potential role of free fatty acid receptor 4[S

PubMed Central

Eclov, Julie A.; Qian, Qingwen; Redetzke, Rebecca; Chen, Quanhai; Wu, Steven C.; Healy, Chastity L.; Ortmeier, Steven B.; Harmon, Erin; Shearer, Gregory C.; O’Connell, Timothy D.

2015-01-01

Heart failure with preserved ejection fraction (HFpEF) is half of all HF, but standard HF therapies are ineffective. Diastolic dysfunction, often secondary to interstitial fibrosis, is common in HFpEF. Previously, we found that supra-physiologic levels of ω3-PUFAs produced by 12 weeks of ω3-dietary supplementation prevented fibrosis and contractile dysfunction following pressure overload [transverse aortic constriction (TAC)], a model that resembles aspects of remodeling in HFpEF. This raised several questions regarding ω3-concentration-dependent cardioprotection, the specific role of EPA and DHA, and the relationship between prevention of fibrosis and contractile dysfunction. To achieve more clinically relevant ω3-levels and test individual ω3-PUFAs, we shortened the ω3-diet regimen and used EPA- and DHA-specific diets to examine remodeling following TAC. The shorter diet regimen produced ω3-PUFA levels closer to Western clinics. Further, EPA, but not DHA, prevented fibrosis following TAC. However, neither ω3-PUFA prevented contractile dysfunction, perhaps due to reduced uptake of ω3-PUFA. Interestingly, EPA did not accumulate in cardiac fibroblasts. However, FFA receptor 4, a G protein-coupled receptor for ω3-PUFAs, was sufficient and required to block transforming growth factor β1-fibrotic signaling in cultured cardiac fibroblasts, suggesting a novel mechanism for EPA. In summary, EPA-mediated prevention of fibrosis could represent a novel therapy for HFpEF. PMID:26435012

Patients with a hypertensive response to exercise have impaired systolic function without diastolic dysfunction or left ventricular hypertrophy.

PubMed

Mottram, Philip M; Haluska, Brian; Yuda, Satoshi; Leano, Rodel; Marwick, Thomas H

2004-03-03

We sought to determine if a hypertensive response to exercise (HRE) is associated with myocardial changes consistent with early hypertensive heart disease. An HRE predicts the development of chronic hypertension (HT) and may reflect a preclinical stage of HT. Patients with a normal left ventricular (LV) ejection fraction and a negative stress test were recruited into three matched groups: 41 patients (age 56 +/- 10 years) with HRE (>210/105 mm Hg in men; >190/105 in women), comprising 22 patients with (HT+) and 19 without resting hypertension (HT-); and 17 matched control subjects without HRE. Long-axis function was determined by measurement of the strain rate (SR), peak systolic strain, and cyclic variation (CV) of integrated backscatter in three apical views. An HRE was not associated with significant differences in LV mass index. Exercise performance and diastolic function were reduced in HRE(HT+) patients, but similar in HRE(HT-) patients and controls. Systolic dysfunction (peak systolic strain, SR, and CV) was significantly reduced in HRE patients (p < 0.001 for all). These reductions were equally apparent in patients with and without a history of resting HT (p = NS) and were independent of LV mass index and blood pressure (p < 0.01). An HRE is associated with subtle systolic dysfunction, even in the absence of resting HT. These changes occur before the development of LV hypertrophy or detectable diastolic dysfunction and likely represent early hypertensive heart disease.

Interpretation and use of natriuretic peptides in non-congestive heart failure settings.

PubMed

Tsai, Shih-Hung; Lin, Yen-Yue; Chu, Shi-Jye; Hsu, Ching-Wang; Cheng, Shu-Meng

2010-03-01

Natriuretic peptides (NPs) have been found to be useful markers in differentiating acute dyspneic patients presenting to the emergency department (ED) and emerged as potent prognostic markers for patients with congestive heart failure (CHF). The best-established and widely used clinical application of BNP and NT-proBNP testing is for the emergent diagnosis of CHF in patients presenting with acute dyspnea. Nevertheless, elevated NPs levels can be found in many circumstances involving left ventricular (LV) dysfunction or hypertrophy; right ventricular (RV) dysfunction secondary to pulmonary diseases; cardiac inflammatory or infectious diseases; endocrinology diseases and high output status without decreased LV ejection fraction. Even in the absence of significant clinical evidence of volume overload or LV dysfunction, markedly elevated NP levels can be found in patients with multiple comorbidities with a certain degree of prognostic value. Potential clinical applications of NPs are expanded accompanied by emerging reports regarding screening the presence of secondary cardiac dysfunction; monitoring the therapeutic responses, risk stratifications and providing prognostic values in many settings. Clinicians need to have expanded knowledge regarding the interpretation of elevated NPs levels and potential clinical applications of NPs. Clinicians should recognize that currently the only reasonable application for routine practice is limited to differentiation of acute dyspnea, rule-out-diagnostic-tests, monitoring of therapeutic responses and prognosis of acute or decompensated CHF. The rationales as well the potential applications of NPs in these settings are discussed in this review article.

Interpretation and Use of Natriuretic Peptides in Non-Congestive Heart Failure Settings

PubMed Central

Lin, Yen-Yue; Chu, Shi-Jye; Hsu, Ching-Wang; Cheng, Shu-Meng

2010-01-01

Natriuretic peptides (NPs) have been found to be useful markers in differentiating acute dyspneic patients presenting to the emergency department (ED) and emerged as potent prognostic markers for patients with congestive heart failure (CHF). The best-established and widely used clinical application of BNP and NT-proBNP testing is for the emergent diagnosis of CHF in patients presenting with acute dyspnea. Nevertheless, elevated NPs levels can be found in many circumstances involving left ventricular (LV) dysfunction or hypertrophy; right ventricular (RV) dysfunction secondary to pulmonary diseases; cardiac inflammatory or infectious diseases; endocrinology diseases and high output status without decreased LV ejection fraction. Even in the absence of significant clinical evidence of volume overload or LV dysfunction, markedly elevated NP levels can be found in patients with multiple comorbidities with a certain degree of prognostic value. Potential clinical applications of NPs are expanded accompanied by emerging reports regarding screening the presence of secondary cardiac dysfunction; monitoring the therapeutic responses, risk stratifications and providing prognostic values in many settings. Clinicians need to have expanded knowledge regarding the interpretation of elevated NPs levels and potential clinical applications of NPs. Clinicians should recognize that currently the only reasonable application for routine practice is limited to differentiation of acute dyspnea, rule-out-diagnostic-tests, monitoring of therapeutic responses and prognosis of acute or decompensated CHF. The rationales as well the potential applications of NPs in these settings are discussed in this review article. PMID:20191004

Clinical Features Associated With Nascent Left Ventricular Diastolic Dysfunction in a Population Aged 40 to 55 Years.

PubMed

Mosley, Jonathan D; Levinson, Rebecca T; Brittain, Evan L; Gupta, Deepak K; Farber-Eger, Eric; Shaffer, Christian M; Denny, Josh C; Roden, Dan M; Wells, Quinn S

2018-06-15

Diastolic dysfunction (DD), an abnormality in cardiac left ventricular (LV) chamber compliance, is associated with increased morbidity and mortality. Although DD has been extensively studied in older populations, co-morbidity patterns are less well characterized in middle-aged subjects. We screened 156,434 subjects with transthoracic echocardiogram reports available through Vanderbilt's electronic heath record and identified 6,612 subjects 40 to 55 years old with an LV ejection fraction ≥50% and diastolic function staging. We tested 452 incident and prevalent clinical diagnoses for associations with early-stage DD (n = 1,676) versus normal function. There were 44 co-morbid diagnoses associated with grade 1 DD including hypertension (odds ratio [OR] = 2.02, 95% confidence interval [CI] 1.78 to 2.28, p <5.3 × 10-29), type 2 diabetes (OR 1.96, 95% CI 1.68 to 2.29, p = 2.1 × 10-17), tachycardia (OR 1.38, 95% CI 0.53 to 2.19, p = 2.9 × 10-6), obesity (OR 1.76, 95% CI 1.51 to 2.06, p = 1.7 × 10-12), and clinical end points, including end-stage renal disease (OR 3.29, 95% CI 2.19 to 4.96, p = 1.2 × 10-8) and stroke (OR 1.5, 95% CI 1.12 to 2.02, p = 6.9 × 10-3). Among the 60 incident diagnoses associated with DD, heart failure with preserved ejection fraction (OR 4.63, 95% CI 3.39 to 6.32, p = 6.3 × 10-22) had the most significant association. Among subjects with normal diastolic function and blood pressure at baseline, a blood pressure measurement in the hypertensive range at the time of the second echocardiogram was associated with progression to stage 1 DD (p = 0.04). In conclusion, DD was common among subjects 40 to 55 years old and was associated with a heavy burden of co-morbid disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Prognosis of individuals with asymptomatic left ventricular systolic dysfunction in the multi-ethnic study of atherosclerosis (MESA).

PubMed

Yeboah, Joseph; Rodriguez, Carlos J; Stacey, Brandon; Lima, Joao A; Liu, Songtao; Carr, J Jeffrey; Hundley, W Gregory; Herrington, David M

2012-12-04

Limited data exist on the prevalence, associations, and prognosis of individuals with asymptomatic left ventricular systolic dysfunction (ALVSD), especially in populations without previous clinical cardiovascular disease (CVD). Kaplan-Meier and Cox proportional hazard analyses were used to assess the association between ALVSD, defined as left ventricular ejection fraction <50%, and adjudicated incident congestive heart failure (CHF), all-cause mortality, and CVD events. Of 5004 participants, 112 participants had CHF, 321 had a CVD event, and 278 died after 9 years of follow-up. The overall prevalence of ALVSD was 1.7%, with a higher prevalence in blacks (2.6%). ALVSD had a worse cardiovascular risk profile and was also associated with increased risk in unadjusted and adjusted models for incident CHF (HR [hazard ratio] [95% CI {confidence interval}]: 12.0 [7.04-20.3], P<0.0001 and 8.69 [4.89-15.45], P<0.001 respectively), CVD (HR [95% CI]: 3.32 [1.98-5.58], P<0.001 and 2.21 [1.30-3.73], P=0.003 respectively), and all-cause mortality (HR [95% CI]: 3.47 [2.03-5.94], P<0.0001 and 2.00 [1.13-3.54], P=0.017, respectively). A 10% decrement in left ventricular ejection fraction at baseline was associated with an increase in risk in unadjusted and adjusted models for clinical CHF (HR [95% CI]: 2.17 [1.82-2.63], P<0.0001 and 2.13 [1.73-2.51], P<0.001, respectively) and all-cause mortality (HR [95% CI]: 1.22 [1.05-1.41], P=0.009 and 1.17 [1.00-1.36], P=0.047, respectively). Among the subset of participants with ALVSD, the left ventricular mass index was particularly informative about risk for incident CHF (c-index=0.74). ALVSD is uncommon in individuals without previous clinical CVD, but it is associated with high risk for CHF, CVD, and all-cause mortality. The left ventricular mass index had good discrimination for incident CHF in Multi-Ethnic Study of Atherosclerosis (MESA) participants with ALVSD.

Clinical validation of the planar radionuclide ventriculography in patients with right ventricular dysfunction.

PubMed

Bontemps, L; Merabet, Y; Chevalier, P; Itti, R

2013-01-01

Gated radionuclide ventriculography (RNV) may be used for the evaluation of the right ventricular function. However, the accuracy of the method should be clinically validated in patients suffering from diseases with specific pathology of the right ventricle (RV) and with possible left ventricular (LV) interaction. Three groups of 15 patients each, diagnosed with arrhythmogenic right ventricular dysplasia (ARVD), pulmonary artery hypertension (PAH) or atrial septal defect (ASD) were compared to a group of normal subjects. The parameters for both ventricles were evaluated separately (ejection fractions: LVEF and RVEF, and intraventricular synchronism quantified as phase standard deviation: LVPSD and RVPSD) as well as the relation or interdependence of the right to left ventricle (RV/LV volume ratio, LV/RV ejection fraction and stroke volume ratios, and interventricular synchronism). All the variables as a whole were analyzed to identify groups of patients according to their functional behaviour. Significant differences were found between the patients and control group for the RV function while the LV function remained mostly within normal limits. When the RV function was considered, the control group and ASD patient group showed differences regarding the ARVD and PAH patients. On evaluating the RV/LV ratios, differences were found between the control group and the ASD group. In the PAH patients, LV function showed differences in relation to the rest of the groups. RNV is a reliable clinical tool to evaluate RV function in patients with RV abnormality. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Echocardiographic predictors of change in renal function with intravenous diuresis for decompensated heart failure.

PubMed

Gannon, Stephen A; Mukamal, Kenneth J; Chang, James D

2018-06-14

The aim of this study was to identify echocardiographic predictors of improved or worsening renal function during intravenous diuresis for decompensated heart failure. Secondary aim included defining the incidence and clinical risk factors for acute changes in renal function with decongestion. A retrospective review of 363 patients admitted to a single centre for decompensated heart failure who underwent intravenous diuresis and transthoracic echocardiography was conducted. Clinical, echocardiographic, and renal function data were retrospectively collected. A multinomial logistic regression model was created to determine relative risk ratios for improved renal function (IRF) or worsening renal function (WRF). Within this cohort, 36% of patients experienced WRF, 35% had stable renal function, and 29% had IRF. Patients with WRF were more likely to have a preserved left ventricular ejection fraction compared with those with stable renal function or IRF (P = 0.02). Patients with IRF were more likely to have a dilated, hypokinetic right ventricle compared with those with stable renal function or WRF (P ≤ 0.01), although this was not significant after adjustment for baseline characteristics. Left atrial size, left ventricular linear dimensions, and diastolic function did not significantly predict change in renal function. An acute change in renal function occurred in 65% of patients admitted with decompensated heart failure. WRF was statistically more likely in patients with a preserved left ventricular ejection fraction. A trend towards IRF was noted in patients with global right ventricular dysfunction. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Impaired in vivo mitochondrial Krebs cycle activity after myocardial infarction assessed using hyperpolarized magnetic resonance spectroscopy.

PubMed

Dodd, Michael S; Atherton, Helen J; Carr, Carolyn A; Stuckey, Daniel J; West, James A; Griffin, Julian L; Radda, George K; Clarke, Kieran; Heather, Lisa C; Tyler, Damian J

2014-11-01

Myocardial infarction (MI) is one of the leading causes of heart failure. An increasing body of evidence links alterations in cardiac metabolism and mitochondrial function with the progression of heart disease. The aim of this work was to, therefore, follow the in vivo mitochondrial metabolic alterations caused by MI, thereby allowing a greater understanding of the interplay between metabolic and functional abnormalities. Using hyperpolarized carbon-13 ((13)C)-magnetic resonance spectroscopy, in vivo alterations in mitochondrial metabolism were assessed for 22 weeks after surgically induced MI with reperfusion in female Wister rats. One week after MI, there were no detectable alterations in in vivo cardiac mitochondrial metabolism over the range of ejection fractions observed (from 28% to 84%). At 6 weeks after MI, in vivo mitochondrial Krebs cycle activity was impaired, with decreased (13)C-label flux into citrate, glutamate, and acetylcarnitine, which correlated with the degree of cardiac dysfunction. These changes were independent of alterations in pyruvate dehydrogenase flux. By 22 weeks, alterations were also seen in pyruvate dehydrogenase flux, which decreased at lower ejection fractions. These results were confirmed using in vitro analysis of enzyme activities and metabolomic profiles of key intermediates. The in vivo decrease in Krebs cycle activity in the 6-week post-MI heart may represent an early maladaptive phase in the metabolic alterations after MI in which reductions in Krebs cycle activity precede a reduction in pyruvate dehydrogenase flux. Changes in mitochondrial metabolism in heart disease are progressive and proportional to the degree of cardiac impairment. © 2014 American Heart Association, Inc.

Impaired In Vivo Mitochondrial Krebs Cycle Activity After Myocardial Infarction Assessed Using Hyperpolarized Magnetic Resonance Spectroscopy

PubMed Central

Carr, Carolyn A.; Stuckey, Daniel J.; West, James A.; Griffin, Julian L.; Radda, George K.; Clarke, Kieran; Heather, Lisa C.; Tyler, Damian J.

2015-01-01

Background Myocardial infarction (MI) is one of the leading causes of heart failure. An increasing body of evidence links alterations in cardiac metabolism and mitochondrial function with the progression of heart disease. The aim of this work was to, therefore, follow the in vivo mitochondrial metabolic alterations caused by MI, thereby allowing a greater understanding of the interplay between metabolic and functional abnormalities. Methods and Results Using hyperpolarized carbon-13 (13C)-magnetic resonance spectroscopy, in vivo alterations in mitochondrial metabolism were assessed for 22 weeks after surgically induced MI with reperfusion in female Wister rats. One week after MI, there were no detectable alterations in in vivo cardiac mitochondrial metabolism over the range of ejection fractions observed (from 28% to 84%). At 6 weeks after MI, in vivo mitochondrial Krebs cycle activity was impaired, with decreased 13C-label flux into citrate, glutamate, and acetylcarnitine, which correlated with the degree of cardiac dysfunction. These changes were independent of alterations in pyruvate dehydrogenase flux. By 22 weeks, alterations were also seen in pyruvate dehydrogenase flux, which decreased at lower ejection fractions. These results were confirmed using in vitro analysis of enzyme activities and metabolomic profiles of key intermediates. Conclusions The in vivo decrease in Krebs cycle activity in the 6-week post-MI heart may represent an early maladaptive phase in the metabolic alterations after MI in which reductions in Krebs cycle activity precede a reduction in pyruvate dehydrogenase flux. Changes in mitochondrial metabolism in heart disease are progressive and proportional to the degree of cardiac impairment. PMID:25201905

Left atrium measurement in patients suspected of having heart failure with preserved ejection fraction.

PubMed

Jorge, Antônio José Lagoeiro; Ribeiro, Mario Luiz; Rosa, Maria Luiza Garcia; Licio, Fernanda Volponi; Fernandes, Luiz Cláudio Maluhy; Lanzieri, Pedro Gemal; Jorge, Bruno Afonso Lagoeiro; Brito, Flavia Oliveira Xavier; Mesquita, Evandro Tinoco

2012-02-01

The pathophysiological model of heart failure (HF) with preserved ejection fraction (HFPEF) focuses on the presence of diastolic dysfunction, which causes left atrial (LA) structural and functional changes. The LA size, an indicator of the chronic elevation of the left ventricular (LV) filling pressure, can be used as a marker of the presence of HFPEF, and it is easily obtained. To estimate the accuracy of measuring the LA size by using indexed LA volume and diameter (ILAV and ILAD, respectively) for diagnosing HFPEF in ambulatory patients. This study assessed 142 patients (mean age, 67.3 ± 11.4 years; 75% of the female sex) suspected of having HF, divided into two groups: with HFPEF (n = 35) and without HFPEF (n = 107). The diastolic function, assessed by use of Doppler echocardiography, showed a significant difference between the groups regarding the parameters assessing ventricular relaxation (E': 6.9 ± 2.0 cm/s vs. 9.3 ± 2.5 cm/s; p < 0.0001) and LV filling pressure (E/E' ratio: 15.2 ± 6.4 vs. 7.6 ± 2.2; p < 0.0001). The ILAV cutoff point of 35 mL/m² best correlated with the diagnosis of HFPEF, showing sensitivity, specificity, and accuracy of 83%. The ILAD cutoff point of 2.4 cm/m² showed sensitivity of 71%, specificity of 66%, and accuracy of 67%. For diagnosing HFPEF in ambulatory patients, the ILAV proved to be a more accurate parameter than ILAD. On echocardiographic assessment, ILAV, rather than ILAD, should be routinely measured.

Characteristics of Saudi patients with congestive heart failure and adherence to management guidelines in a tertiary hospital in Riyadh.

PubMed

Alqahtani, Mohammad; Alanazi, Thari; Binsalih, Salih; Aljohani, Naji; Alshammari, Mohammed; Ashagag, Ali; Abdullah, Mohammed; Buabbas, Sara; Abdulbaqi, Manar

2012-01-01

There is limited data available on the characteristics of local Saudi patients diagnosed with congestive heart failure (CHF) and on their adherence to guidelines for managing the disease. This study aimed to fill this gap. Retrospective study of patients treated at King Abdulaziz Medical City from 20022008. The records were reviewed of subjects admitted secondary to heart failure (defined as systolic heart failure [ejection fraction < 55%] and/or heart failure with preserved ejection fraction diagnosed either clinically and/or by echocardiogram and/or cardiac catheterization) or who visited the outpatient department for the same complaint. Of 392 CHF cases, the mean age was 67.8 (12.8) years and the majority were males (53.1%). Hypertension was the predominant comorbid illness, accounting for 84.9% of cases, followed by diabetes mellitus type 2 and hyperlipidemia. Almost three-fourths (73.7%) of the subjects had mild to severe left ventricular dysfunction, with 68.5% of the cases having right ischemic cardiomyopathy. Spironolactone, exercise and vaccination were the the least least adhered to recommendations (30.0%, 20.5% and 15.2%, respectively). The study highlights the need for proper education of patients and caregivers to increase compliance to medications. Physicians are also encouraged to undergo continuing medical education and training courses to properly implement current recommendations in the management of heart failure. Further studies are needed on a larger scale in order to formulate an effective management scheme that will address the current challenges faced by both clinicians and CHF patients.

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

PubMed

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

2017-06-23

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

Incomplete aneurysm coverage after patent foramen ovale closure in patients with huge atrial septal aneurysm: effects on left atrial functional remodeling.

PubMed

Rigatelli, Gianluca; Ronco, Federico; Cardaioli, Paolo; Dell'avvocata, Fabio; Braggion, Gabriele; Giordan, Massimo; Aggio, Silvio

2010-08-01

Large devices are often implanted to treat patent foramen ovale (PFO) and atrial septal aneurysm (ASA) with increase risk of erosion and thrombosis. Our study is aimed to assess the impact on left atrium functional remodeling and clinical outcomes of partial coverage of the approach using moderately small Amplatzer ASD Cribriform Occluder in patients with large PFO and ASA. We prospectively enrolled 30 consecutive patients with previous stroke (mean age 36 +/- 9.5 years, 19 females), significant PFO, and large ASA referred to our center for catheter-based PFO closure. Left atrium (LA) passive and active emptying, LA conduit function, and LA ejection fraction were computed before and after 6 months from the procedure by echocardiography. The preclosure values were compared to values of a normal healthy population of sex and heart rate matched 30 patients. Preclosure values demonstrated significantly greater reservoir function as well as passive and active emptying, with significantly reduced conduit function and LA ejection fraction, when compared normal healthy subjects. All patients underwent successful transcatheter closure (25 mm device in 15 patients, 30 mm device in 6 patients, mean ratio device/diameter of the interatrial septum = 0.74). Incomplete ASA coverage in both orthogonal views was observed in 21 patients. Compared to patients with complete coverage, there were no differences in LA functional parameters and occlusion rates. This study confirmed that large ASAs are associated with LA dysfunction. The use of relatively small Amplatzer ASD Cribriform Occluder devices is probably effective enough to promote functional remodeling of the left atrium.

Abdominal adiposity, general obesity, and subclinical systolic dysfunction in the elderly: A population-based cohort study.

PubMed

Russo, Cesare; Sera, Fusako; Jin, Zhezhen; Palmieri, Vittorio; Homma, Shunichi; Rundek, Tatjana; Elkind, Mitchell S V; Sacco, Ralph L; Di Tullio, Marco R

2016-05-01

General obesity, measured by body mass index (BMI), and abdominal adiposity, measured as waist circumference (WC) and waist-to-hip ratio (WHR), are associated with heart failure and cardiovascular events. However, the relationship of general and abdominal obesity with subclinical left ventricular (LV) dysfunction is unknown. We assessed the association of general and abdominal obesity with subclinical LV systolic dysfunction in a population-based elderly cohort. Participants from the Cardiovascular Abnormalities and Brain Lesions study underwent measurement of BMI, WC, and WHR. Left ventricular systolic function was assessed by two-dimensional echocardiographic LV ejection fraction (LVEF) and speckle-tracking global longitudinal strain (GLS). The study population included 729 participants (mean age 71 ± 9 years, 60% women). In multivariate analysis, higher BMI (but not WC and WHR) was associated with higher LVEF (β = 0.11, P = 0.003). Higher WC (β = 0.08, P = 0.038) and higher WHR (β = 0.15, P < 0.001) were associated with lower GLS, whereas BMI was not (P = 0.720). Compared with normal WHR, high WHR was associated with lower GLS in all BMI categories (normal, overweight, and obese), and was associated with subclinical LV dysfunction by GLS both in participants without [adjusted odds ratio (OR) 2.0, 95% confidence interval (CI) 1.1-3.6, P = 0.020] and with general obesity (adjusted OR 5.4, 95% CI 1.1-25.9, P = 0.034). WHR was incremental to BMI and risk factors in predicting LV dysfunction. Abdominal adiposity was independently associated with subclinical LV systolic dysfunction by GLS in all BMI categories. BMI was not associated with LV dysfunction. Increased abdominal adiposity may be a risk factor for LV dysfunction regardless of the presence of general obesity. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

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.

Echocardiographic evaluation of right ventricular systolic function: The traditional and innovative approach.

PubMed

Smolarek, Dorota; Gruchała, Marcin; Sobiczewski, Wojciech

2017-01-01

Estimation of right ventricular (RV) performance still remains technically challenging due to its anatomical and functional distinctiveness. The current guidelines for the echocardiographic quantification of RV function recommend using multiple indices to describe the RV in a thorough and comprehensive manner, such as RV index of myocardial performance, tricuspid annular plane systolic excursion, fractional area change, Doppler tissue imaging-derived tricuspid lateral annular systolic velocity (S'-wave), three-dimensional RV ejection fraction (3D RVEF), RV longitudinal strain (RVLS)/strain rate by speckle- tracking echocardiography (STE). Among these, the last one mentioned here is an innovative and a particularly promising tool that yields more precise information about complex regional and global RV mechanics. STE was initially designed to evaluate left ventricular function, but recently it has been introduced to assess RV performance, which is difficult due to its unique structure and physiology. Many studies have shown that both free wall and 6-segment RVLS present a stronger correlation with the RVEF assessed by cardiac magnetic resonance than conventional parameters and seem to be more sensitive in detecting myocardial dysfunction at an earlier, subclinical stage.

Myocardial dysfunction in mitochondrial diabetes treated with Coenzyme Q10.

PubMed

Salles, João Eduardo; Moisés, Valdir A; Almeida, Dirceu R; Chacra, Antonio R; Moisés, Regina S

2006-04-01

Maternally-inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial tRNA Leu (UUR) gene at the base pair 3243. Although some previous articles have reported that this mutation may be a cause of cardiomyopathy in diabetes, the degree of cardiac involvement and a specific treatment has not been established. Here, we reported a case of a patient with MIDD who developed congestive heart failure and the therapeutic usefulness of Coenzyme Q10 (CoQ10). In our patient, after the introduction of Coenzyme Q10 150 mg/day, there was a gradual improvement on left ventricular function evaluated by echocardiography. The fractional shortening (FS) and ejection fraction (EF) increased from 26 to 34% and from 49 to 64%, respectively. No side effects were noted. Three months after CoQ10 discontinuation, the parameters of systolic function evaluated by echocardiography decreased, suggesting that CoQ10 had a beneficial effect. Identification of diabetes and cardiomyopathy due to mitochondrial gene mutation may have therapeutic implications and Coenzyme Q10 is a possible adjunctive treatment in such patients.

Cellular apoptosis and cardiac dysfunction in STZ-induced diabetic rats attenuated by anthocyanins via activation of IGFI-R/PI3K/Akt survival signaling.

PubMed

Huang, Pei-Chen; Wang, Guei-Jane; Fan, Ming-Jen; Asokan Shibu, Marthandam; Liu, Yin-Tso; Padma Viswanadha, Vijaya; Lin, Yi-Lin; Lai, Chao-Hung; Chen, Yu-Feng; Liao, Hung-En; Huang, Chih-Yang

2017-12-01

Anthocyanins are known cyto-protective agents against various stress conditions. In this study cardio-protective effect of anthocyanins from black rice against diabetic mellitus (DM) was evaluated using a streptozotocin (STZ)-induced DM rat model. Five-week-old male Wistar rats were administered with STZ (55 mg kg -1 , IP) to induce DM; rats in the treatment group received 250 mg oral anthocyanin/kg/day during the 4-week treatment period. DM and the control rats received normal saline through oral gavage. The results reveal that STZ-induced DM elevates myocardial apoptosis and associated proapoptotic proteins but down-regulates the proteins of IGF1R mediated survival signaling mechanism. Furthermore, the functional parameters such as the ejection-fraction and fraction-shortening in the DM rat hearts declined considerably. However, the rats treated with anthocyanins significantly reduced apoptosis and the associated proapoptotic proteins and further increased the survival signals to restore the cardiac functions in DM rats. Anthocyanin supplementation enhances cardiomyocyte survival and restores cardiac function. © 2017 Wiley Periodicals, Inc.

Transgenic over-expression of YY1 induces pathologic cardiac hypertrophy in a sex-specific manner

PubMed Central

Stauffer, Brian L.; Dockstader, Karen; Russell, Gloria; Hijmans, Jamie; Walker, Lisa; Cecil, Mackenzie; Demos-Davies, Kimberly; Medway, Allen; McKinsey, Timothy A.; Sucharov, Carmen C.

2015-01-01

YY1 can activate or repress transcription of various genes. In cardiac myocytes in culture YY1 has been shown to regulate expression of several genes involved in myocyte pathology. YY1 can also acutely protect the heart against detrimental changes in gene expression. In this study we show that cardiac over-expression of YY1 induces pathologic cardiac hypertrophy in male mice, measured by changes in gene expression and lower ejection fraction/fractional shortening. In contrast, female animals are protected against pathologic gene expression changes and cardiac dysfunction. Furthermore, we show that YY1 regulates, in a sex-specific manner, the expression of mammalian enable (Mena), a factor that regulates cytoskeletal actin dynamics and whose expression is increased in several models of cardiac pathology, and that Mena expression in humans with heart failure is sex-dependent. Finally, we show that sex differences in YY1 expression are also observed in human heart failure. In summary, this is the first work to show that YY1 has a sex-specific effect in the regulation of cardiac pathology. PMID:25935483

Kawasaki syndrome in an adult: endomyocardial histology and ventricular function during acute and recovery phases of illness.

PubMed

Marcella, J J; Ursell, P C; Goldberger, M; Lovejoy, W; Fenoglio, J J; Weiss, M B

1983-08-01

Kawasaki syndrome, an acute systemic inflammatory illness of unknown origin usually affecting children, may develop into a serious illness complicated by coronary artery aneurysms or myocarditis. This report describes an adult with Kawasaki syndrome studied by right ventricular endomyocardial biopsy and cardiac catheterization during the acute and recovery phases of illness. The initial biopsy specimen showed acute myocarditis and was associated with hemodynamic evidence of biventricular dysfunction, a severely depressed left ventricular ejection fraction and global hypokinesia. With time, there was spontaneous and rapid resolution of the inflammatory cell infiltrate with concurrent return to normal myocardial function. Right ventricular endomyocardial biopsy studies early in the course of the cardiac disease associated with Kawasaki syndrome may correlate with ventricular function and may be useful for monitoring immunosuppressive therapy in patients with this syndrome.

Alterations in left ventricular diastolic function in conscious dogs with pacing-induced heart failure

NASA Technical Reports Server (NTRS)

Komamura, K.; Shannon, R. P.; Pasipoularides, A.; Ihara, T.; Lader, A. S.; Patrick, T. A.; Bishop, S. P.; Vatner, S. F.

1992-01-01

We investigated in conscious dogs (a) the effects of heart failure induced by chronic rapid ventricular pacing on the sequence of development of left ventricular (LV) diastolic versus systolic dysfunction and (b) whether the changes were load dependent or secondary to alterations in structure. LV systolic and diastolic dysfunction were evident within 24 h after initiation of pacing and occurred in parallel over 3 wk. LV systolic function was reduced at 3 wk, i.e., peak LV dP/dt fell by -1,327 +/- 105 mmHg/s and ejection fraction by -22 +/- 2%. LV diastolic dysfunction also progressed over 3 wk of pacing, i.e., tau increased by +14.0 +/- 2.8 ms and the myocardial stiffness constant by +6.5 +/- 1.4, whereas LV chamber stiffness did not change. These alterations were associated with increases in LV end-systolic (+28.6 +/- 5.7 g/cm2) and LV end-diastolic stresses (+40.4 +/- 5.3 g/cm2). When stresses and heart rate were matched at the same levels in the control and failure states, the increases in tau and myocardial stiffness were no longer observed, whereas LV systolic function remained depressed. There were no increases in connective tissue content in heart failure. Thus, pacing-induced heart failure in conscious dogs is characterized by major alterations in diastolic function which are reversible with normalization of increased loading condition.

Left atrial strain: a new parameter for assessment of left ventricular filling pressure.

PubMed

Cameli, Matteo; Mandoli, Giulia Elena; Loiacono, Ferdinando; Dini, Frank Lloyd; Henein, Michael; Mondillo, Sergio

2016-01-01

In order to obtain accurate diagnosis, treatment and prognostication in many cardiac conditions, there is a need for assessment of left ventricular (LV) filling pressure. While systole depends on ejection function of LV, diastole and its disturbances influence filling function and pressures. The commonest condition that represents the latter is heart failure with preserved ejection fraction in which LV ejection is maintained, but diastole is disturbed and hence filling pressures are raised. Significant diastolic dysfunction results in raised LV end-diastolic pressure, mean left atrial (LA) pressure and pulmonary capillary wedge pressure, all referred to as LV filling pressures. Left and right heart catheterization has traditionally been used as the gold standard investigation for assessing these pressures. More recently, Doppler echocardiography has taken over such application because of its noninvasive nature and for being patient friendly. A number of indices are used to achieve accurate assessment of filling pressures including: LV pulsed-wave filling velocities (E/A ratio, E wave deceleration time), pulmonary venous flow (S wave and D wave), tissue Doppler imaging (E' wave and E/E' ratio) and LA volume index. LA longitudinal strain derived from speckle tracking echocardiography (STE) is also sensitive in estimating intracavitary pressures. It is angle-independent, thus overcomes Doppler limitations and provides highly reproducible measures of LA deformation. This review examines the application of various Doppler echocardiographic techniques in assessing LV filling pressures, in particular the emerging role of STE in assessing LA pressures in various conditions, e.g., HF, arterial hypertension and atrial fibrillation.

Cardiac dysfunction and peri-weaning mortality in malonyl-coenzyme A decarboxylase (MCD) knockout mice as a consequence of restricting substrate plasticity.

PubMed

Aksentijević, Dunja; McAndrew, Debra J; Karlstädt, Anja; Zervou, Sevasti; Sebag-Montefiore, Liam; Cross, Rebecca; Douglas, Gillian; Regitz-Zagrosek, Vera; Lopaschuk, Gary D; Neubauer, Stefan; Lygate, Craig A

2014-10-01

Inhibition of malonyl-coenzyme A decarboxylase (MCD) shifts metabolism from fatty acid towards glucose oxidation, which has therapeutic potential for obesity and myocardial ischemic injury. However, ~40% of patients with MCD deficiency are diagnosed with cardiomyopathy during infancy. To clarify the link between MCD deficiency and cardiac dysfunction in early life and to determine the contributing systemic and cardiac metabolic perturbations. MCD knockout mice ((-/-)) exhibited non-Mendelian genotype ratios (31% fewer MCD(-/-)) with deaths clustered around weaning. Immediately prior to weaning (18days) MCD(-/-) mice had lower body weights, elevated body fat, hepatic steatosis and glycogen depletion compared to wild-type littermates. MCD(-/-) plasma was hyperketonemic, hyperlipidemic, had 60% lower lactate levels and markers of cellular damage were elevated. MCD(-/-) hearts exhibited hypertrophy, impaired ejection fraction and were energetically compromised (32% lower total adenine nucleotide pool). However differences between WT and MCD(-/-) converged with age, suggesting that, in surviving MCD(-/-) mice, early cardiac dysfunction resolves over time. These observations were corroborated by in silico modelling of cardiomyocyte metabolism, which indicated improvement of the MCD(-/-) metabolic phenotype and improved cardiac efficiency when switched from a high-fat diet (representative of suckling) to a standard post-weaning diet, independent of any developmental changes. MCD(-/-) mice consistently exhibited cardiac dysfunction and severe metabolic perturbations while on a high-fat, low carbohydrate diet of maternal milk and these gradually resolved post-weaning. This suggests that dysfunction is a common feature of MCD deficiency during early development, but that severity is dependent on composition of dietary substrates. Copyright © 2014. Published by Elsevier Ltd.

Left ventricular diastolic dysfunction in type 2 diabetes patients: a novel 2D strain analysis based on cardiac magnetic resonance imaging.

PubMed

Chen, Qiang; Gan, Yan; Li, Zhi-Yong

2016-09-01

This study was to develop a strain analysis method to evaluate the left ventricular (LV) functions in type 2 diabetic patients with an asymptomatic LV diastolic dysfunction. Two groups (10 asymptomatic type 2 diabetic subjects and 10 control ones) were considered. All of the subjects had normal ejection fraction values but impaired diastolic functions assessed by the transmitral blood flow velocity. For each subject, based on cardiac MRI, global indexes including LV volume, LV myocardial mass, cardiac index (CI), and transmitral peak velocity, were measured, and regional indexes (i.e., LV deformation, strain and strain rate) were calculated through an image-registration technology. Most of the global indexes did not differentiate between the two groups, except for the CI, LV myocardial mass and transmitral peak velocity. While for the regional indexes, the global LV diastolic dysfunction of the diabetic indicated an increased strain (0.08 ± 0.044 vs. -0.031 ± 0.077, p = 0.001) and a reduced strain rate (1.834 ± 0.909 vs. 3.791 ± 2.394, p = 0.033) compared to the controls, moreover, the local LV diastolic dysfunction reflected by the strain and strain rate varied, and the degree of dysfunction gradually decreased from the basal level to the apical level. The results showed that the strain and strain rates are effective to capture the subtle alterations of the LV functions, and the proposed method can be used to estimate the LV myocardial function based on cardiac MRI.

Metabolic Profiling of Right Ventricular-Pulmonary Vascular Function Reveals Circulating Biomarkers of Pulmonary Hypertension.

PubMed

Lewis, Gregory D; Ngo, Debby; Hemnes, Anna R; Farrell, Laurie; Domos, Carly; Pappagianopoulos, Paul P; Dhakal, Bishnu P; Souza, Amanda; Shi, Xu; Pugh, Meredith E; Beloiartsev, Arkadi; Sinha, Sumita; Clish, Clary B; Gerszten, Robert E

2016-01-19

Pulmonary hypertension and associated right ventricular (RV) dysfunction are important determinants of morbidity and mortality, which are optimally characterized by invasive hemodynamic measurements. This study sought to determine whether metabolite profiling could identify plasma signatures of right ventricular-pulmonary vascular (RV-PV) dysfunction. We measured plasma concentrations of 105 metabolites using targeted mass spectrometry in 71 individuals (discovery cohort) who underwent comprehensive physiological assessment with right-sided heart catheterization and radionuclide ventriculography at rest and during exercise. Our findings were validated in a second cohort undergoing invasive hemodynamic evaluations (n = 71), as well as in an independent cohort with or without known pulmonary arterial (PA) hypertension (n = 30). In the discovery cohort, 21 metabolites were associated with 2 or more hemodynamic indicators of RV-PV function (i.e., resting right atrial pressure, mean PA pressure, pulmonary vascular resistance [PVR], and PVR and PA pressure-flow response [ΔPQ] during exercise). We identified novel associations of RV-PV dysfunction with circulating indoleamine 2,3-dioxygenase (IDO)-dependent tryptophan metabolites (TMs), tricarboxylic acid intermediates, and purine metabolites and confirmed previously described associations with arginine-nitric oxide metabolic pathway constituents. IDO-TM levels were inversely related to RV ejection fraction and were particularly well correlated with exercise PVR and ΔPQ. Multisite sampling demonstrated transpulmonary release of IDO-TMs. IDO-TMs also identified RV-PV dysfunction in a validation cohort with known risk factors for pulmonary hypertension and in patients with established PA hypertension. Metabolic profiling identified reproducible signatures of RV-PV dysfunction, highlighting both new biomarkers and pathways for further functional characterization. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Myocardial tissue deformation is reduced in subjects with coronary microvascular dysfunction but not rescued by treatment with Ranolazine

PubMed Central

Nelson, Michael D.; Sharif, Behzad; Shaw, Jaime L.; Cook-Wiens, Galen; Wei, Janet; Shufelt, Chrisandra; Mehta, Puja K.; Thomson, Louise EJ; Berman, Daniel S.; Thompson, Richard B.; Handberg, Eileen M.; Pepine, Carl J.; Li, Debiao; Bairey Merz, C. Noel

2016-01-01

Background Patients with coronary microvascular dysfunction (CMD) often have diastolic dysfunction, representing an important therapeutic target. Ranolazine—a late-sodium current inhibitor—improves diastolic function in animal models, and subjects with obstructive CAD. We hypothesized that ranolazine would beneficially alter diastolic function in CMD. Methods To test this hypothesis, we performed retrospective tissue tracking analysis to evaluate systolic/diastolic strain, using cardiac magnetic resonance imaging cine images: a) acquired in a recently completed, randomized, double-blind, placebo-controlled, crossover trial of short-term ranolazine in subjects with CMD, and b) from 43 healthy reference controls. Results Diastolic strain rate was impaired in CMD vs. controls (circumferential diastolic strain rate: 99.9 ± 2.5%/s vs. 120.1 ± 4.0%/s, p=0.0003; radial diastolic strain rate: −199.5 ± 5.5%/s vs. −243.1 ± 9.6%/s, p=0.0008, case vs. control). Moreover, peak systolic circumferential (CS) and radial (RS) strain were also impaired in cases vs. controls (CS: −18.8 ± 0.3% vs. −20.7 ± 0.3%; RS: 35.8 ± 0.7% vs. 41.4 ± 0.9%; respectively; both p < 0.0001), despite similar and preserved ejection fraction. In contrast to our hypothesis however, we observed no significant changes in left ventricular diastolic function in CMD cases after two weeks of ranolazine vs. placebo. Conclusions The case-control comparison both confirms and extends our prior observations of diastolic dysfunction in CMD. That CMD cases were also found to have sub-clinical systolic dysfunction is a novel finding, highlighting the utility of this retrospective approach. In contrast to previous studies in obstructive CAD, ranolazine did not improve diastolic function in CMD. PMID:28004395

Evaluation of left ventricular function in obese children without hypertension by a tissue Doppler imaging study

PubMed Central

Ghandi, Yazdan; Sharifi, Mehrzad; Habibi, Danial; Dorreh, Fatemeh; Hashemi, Mojtaba

2018-01-01

Background: The prevalence of obesity is increasing worldwide. Obese children without hypertension are becoming an important health challenge. Aims: Complications of obesity in adults are well established, but in obese children, cardiac dysfunction has not been reported clinically. Settings and Design: The present crosssectional study investigates subclinical systolic and diastolic dysfunction using echocardiographic modalities. Materials and Methods: Twentyfive youngsters with body mass index (BMI) >30 and 25 healthy children with BMI <25 were assigned into case and control group, respectively. In all participants, complete cardiovascular examination, electrocardiography, and echocardiography were fulfilled. Echocardiography surveys included standard, pulsed wave Doppler (PWD), and tissue Doppler imaging (TDI). Statistical Analysis Used: SPSS software, version 24. Results: The two groups were matched for age and sex. The resting heart rate and blood pressure were markedly higher in the obese group (P = 0.0001) though they were within the normal range in either category. Ejection fraction in the two groups was similar. Left ventricular (LV) mass (P = 0.0001), LV mass index (P = 0.029), left atrialtoaortic diameter ratio (P = 0.0001), and LV enddiastolic diameter (P = 0.008) were significantly greater in the case group, indicating cardiomegaly and subclinical systolic and diastolic dysfunction. Except for the aortic velocity, all PWD variables were considerably lower in the case group, suggesting subclinical diastolic dysfunction. All TDI parameters varied significantly between the two categories. There was a direct correlation between isovolumetric relaxation time and BMI. Conclusions: Obesity in children without hypertension is associated with subclinical systolic and diastolic cardiac dysfunction. We propose the evaluation of blood pressure as well as myocardial performance using PWD and TDI in all obese children without hypertension, regularly. PMID:29440827

Cardiac dysfunction and peri-weaning mortality in malonyl-coenzyme A decarboxylase (MCD) knockout mice as a consequence of restricting substrate plasticity

PubMed Central

Aksentijević, Dunja; McAndrew, Debra J.; Karlstädt, Anja; Zervou, Sevasti; Sebag-Montefiore, Liam; Cross, Rebecca; Douglas, Gillian; Regitz-Zagrosek, Vera; Lopaschuk, Gary D.; Neubauer, Stefan; Lygate, Craig A.

2014-01-01

Inhibition of malonyl-coenzyme A decarboxylase (MCD) shifts metabolism from fatty acid towards glucose oxidation, which has therapeutic potential for obesity and myocardial ischemic injury. However, ~ 40% of patients with MCD deficiency are diagnosed with cardiomyopathy during infancy. Aim To clarify the link between MCD deficiency and cardiac dysfunction in early life and to determine the contributing systemic and cardiac metabolic perturbations. Methods and results MCD knockout mice (−/−) exhibited non-Mendelian genotype ratios (31% fewer MCD−/−) with deaths clustered around weaning. Immediately prior to weaning (18 days) MCD−/− mice had lower body weights, elevated body fat, hepatic steatosis and glycogen depletion compared to wild-type littermates. MCD−/− plasma was hyperketonemic, hyperlipidemic, had 60% lower lactate levels and markers of cellular damage were elevated. MCD−/− hearts exhibited hypertrophy, impaired ejection fraction and were energetically compromised (32% lower total adenine nucleotide pool). However differences between WT and MCD−/− converged with age, suggesting that, in surviving MCD−/− mice, early cardiac dysfunction resolves over time. These observations were corroborated by in silico modelling of cardiomyocyte metabolism, which indicated improvement of the MCD−/− metabolic phenotype and improved cardiac efficiency when switched from a high-fat diet (representative of suckling) to a standard post-weaning diet, independent of any developmental changes. Conclusions MCD−/− mice consistently exhibited cardiac dysfunction and severe metabolic perturbations while on a high-fat, low carbohydrate diet of maternal milk and these gradually resolved post-weaning. This suggests that dysfunction is a common feature of MCD deficiency during early development, but that severity is dependent on composition of dietary substrates. PMID:25066696

Nitric Oxide Bioavailability and Adiponectin Production in Chronic Systolic Heart Failure: Relation to Severity of Cardiac Dysfunction

PubMed Central

Tang, W.H. Wilson; Shrestha, Kevin; Tong, Wilson; Wang, Zeneng; Troughton, Richard W.; Borowski, Allen G.; Klein, Allan L.; Hazen, Stanley L.

2013-01-01

Adiponectin is an anti-inflammatory, anti-atherogenic adipokine elevated in heart failure (HF) that may protect against endothelial dysfunction by influencing underlying nitric oxide bioavailablity. In this study, we examine the relationship between plasma adiponectin levels and measures of nitric oxide bioavailability and myocardial performance in patients with chronic systolic HF. In 139 ambulatory patients with stable, chronic systolic HF (left ventricular [LV] ejection fraction ≤40%, New York Heart Association [NYHA] class I to IV), we measured plasma levels of adiponectin, asymmetric dimethylarginine (ADMA) and global arginine bioavailability (GABR), and performed comprehensive echocardiography with assessment of cardiac structure and performance. Adverse events (all-cause mortality or cardiac transplantation) were prospectively tracked for a median of 39 months. Plasma adiponectin levels directly correlated with plasma ADMA levels (Spearman’s r=0.41, p<0.001) and NT-proBNP levels (r=0.55, p<0.001), inversely correlated with GABR (r= −0.39, p<0.001), and were not associated with hsCRP (p=0.81) or MPO (p=0.07). Interestingly, increased plasma adiponectin levels remained positively correlated with plasma ADMA levels only in patients with elevated NT-proBNP levels (r= 0.33, p=0.009). Higher plasma adiponectin levels were associated with worse LV diastolic dysfunction (rank sums p=0.002), RV systolic dysfunction (rank sums p=0.002), and RV diastolic dysfunction (rank sums p=0.011), but not after adjustment for plasma ADMA and NT-proBNP levels. Plasma adiponectin levels predicted increased risk of adverse clinical events (HR [95% CI]: 1.45 [1.02–2.07], p=0.038) but not after adjustment for plasma ADMA and NT-proBNP levels, or echocardiographic indices of diastolic or RV systolic dysfunction. In patients with chronic systolic HF, adiponectin production is more closely linked with nitric oxide bioavailability than inflammation, and appears to be more robust in the setting of cardiac dysfunction or elevated natriuretic peptide levels. PMID:23499315

Ultrasound tissue characterization does not differentiate genotype, but indexes ejection fraction deterioration in becker muscular dystrophy.

PubMed

Giglio, Vincenzo; Puddu, Paolo Emilio; Holland, Mark R; Camastra, Giovanni; Ansalone, Gerardo; Ricci, Enzo; Mela, Julia; Sciarra, Federico; Di Gennaro, Marco

2014-12-01

The aims of the study were, first, to assess whether myocardial ultrasound tissue characterization (UTC) in Becker muscular dystrophy (BMD) can be used to differentiate between patients with deletions and those without deletions; and second, to determine whether UTC is helpful in diagnosing the evolution of left ventricular dysfunction, a precursor of dilated cardiomyopathy. Both cyclic variation of integrated backscatter and calibrated integrated backscatter (cIBS) were assessed in 87 patients with BMD and 70 controls. The average follow-up in BMD patients was 48 ± 12 mo. UTC analysis was repeated only in a subgroup of 40 BMD patients randomly selected from the larger overall group (15 with and 25 without left ventricular dysfunction). Discrimination between BMD patients with and without dystrophin gene deletion was not possible on the basis of UTC data: average cvIBS was 5.2 ± 1.2 and 5.5 ± 1.4 dB, and average cIBS was 29.9 ± 4.7 and 29.6 ± 5.8, respectively, significantly different (p < 0.001) only from controls (8.6 ± 0.5 and 24.6 ± 1.2 dB). In patients developing left ventricular dysfunction during follow-up, cIBS increased to 31.3 ± 5.4 dB, but not significantly (p = 0.08). The highest cIBS values (34.6 ± 5.3 dB, p < 0.09 vs. baseline, p < 0.01 vs BMD patients without left ventricular dysfunction) were seen in the presence of severe left ventricular dysfunction. Multivariate statistics indicated that an absolute change of 6 dB in cIBS is associated with a high probability of left ventricular dysfunction. UTC analysis does not differentiate BMD patients with or without dystrophin gene deletion, but may be useful in indexing left ventricular dysfunction during follow-up. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2016-10-14

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

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.

Right ventricular remodeling and dysfunction with subsequent annular dilatation and tethering as a mechanism of isolated tricuspid regurgitation.

PubMed

Seo, Hye-Sun; Ha, Jong-Won; Moon, Jae Youn; Choi, Eui-Young; Rim, Se-Joong; Jang, Yangsoo; Chung, Namsik; Shim, Won-Heum; Cho, Seung-Yun; Kim, Sung Soon

2008-10-01

Secondary tricuspid regurgitation (TR) as a result of pulmonary hypertension and/or left-sided heart disease is caused by tricuspid valve (TV) annular dilatation and tethering of the tricuspid leaflet after right ventricular (RV) dilatation. However, the mechanism of isolated TR without significant pulmonary hypertension remains unknown. The present study investigated the RV function and TV deformations in patients with isolated TR to find out the mechanism and etiology of the disease. Twelve patients with isolated, severe TR were included. RV area, volume, ejection fraction (EF), tenting distance and tenting area were measured. These parameters were compared with 12 age-and gender-matched controls and 12 patients with secondary TR. The cause of isolated TR was incomplete coaptation associated with annular dilatation without other problems. Compared with the controls, RV end-diastolic volumes and annular diameters were significantly larger and RVEF was significantly lower in patients with isolated TR. Tenting area and tenting distance were also significantly higher. However, there were no significant differences in these parameters between patients with isolated and secondary TR. Isolated TR was associated with RV remodeling, systolic dysfunction and resultant annular dilatation and tethering of tricuspid leaflets.

3D cardiac wall thickening assessment for acute myocardial infarction

NASA Astrophysics Data System (ADS)

Khalid, A.; Chan, B. T.; Lim, E.; Liew, Y. M.

2017-06-01

Acute myocardial infarction (AMI) is the most severe form of coronary artery disease leading to localized myocardial injury and therefore irregularities in the cardiac wall contractility. Studies have found very limited differences in global indices (such as ejection fraction, myocardial mass and volume) between healthy subjects and AMI patients, and therefore suggested regional assessment. Regional index, specifically cardiac wall thickness (WT) and thickening is closely related to cardiac function and could reveal regional abnormality due to AMI. In this study, we developed a 3D wall thickening assessment method to identify regional wall contractility dysfunction due to localized myocardial injury from infarction. Wall thickness and thickening were assessed from 3D personalized cardiac models reconstructed from cine MRI images by fitting inscribed sphere between endocardial and epicardial wall. The thickening analysis was performed in 5 patients and 3 healthy subjects and the results were compared against the gold standard 2D late-gadolinium-enhanced (LGE) images for infarct localization. The notable finding of this study is the highly accurate estimation and visual representation of the infarct size and location in 3D. This study provides clinicians with an intuitive way to visually and qualitatively assess regional cardiac wall dysfunction due to infarction in AMI patients.

Clinical significance of hyperglycaemia in acute coronary syndrome patients.

PubMed

Cherneva, Zheyna Vlaeva; Denchev, Stefan Veselinov; Gospodinova, Mariana Vasileva; Milcheva, Nora Petrova; Petrova, Mariana Genova; Cherneva, Radostina Vlaeva

2011-12-01

The clinical significance of moment measurements (admission and fasting glycaemia), persistent (hyperglycaemic index, HGI; time average glucose, TAG; mean glucose; maximum glucose) or chronic hyperglycaemia (HbA1c), estimated average glucose, eAG) is still elusive in clinical practice. To identify the clinical significance of hyperglycaemia in ACS. The study included 226 consecutive patients with ACS. Indicators for hyperglycaemia were defined, calculated and a correlation analysis with standard parameters-EF, maximum CPK, maximum CPK-MB and troponin was performed. Patients were followed up for 12 months. Indicators for persistent and chronic hyperglycaemia correlated neither to ejection fraction, nor to the enzymes for myocardial necrosis (P > 0.05). In contrast, acute hyperglycaemia correlated negatively with ventricular systolic dysfunction (P = 0.001/0.007) and positively with maximum CPK, MB and troponin (P = 0.0001/0.008). TAG was an independent predictor for 6-month re-hospitalization (P = 0.027) because of cardiac complications. Glycaemia at admission and fasting glucose could be used as metabolic surrogate markers for ventricular systolic dysfunction and TAG as an independent surrogate marker for six-month re-hospitalization. None of the indicators for hyperglycaemia could be used as independent prognostic factors for survival. Hyperglycaemia rather reflects an underlying impairment in glucose metabolism.

Heart rate turbulence.

PubMed

Cygankiewicz, Iwona

2013-01-01

Heart rate turbulence (HRT) is a baroreflex-mediated biphasic reaction of heart rate in response to premature ventricular beats. Heart rate turbulence is quantified by: turbulence onset (TO) reflecting the initial acceleration of heart rate following premature beat and turbulence slope (TS) describing subsequent deceleration of heart rate. Abnormal HRT identifies patients with autonomic dysfunction or impaired baroreflex sensitivity due to variety of disorders, but also may reflect changes in autonomic nervous system induced by different therapeutic modalities such as drugs, revascularization, or cardiac resynchronization therapy. More importantly, impaired HRT has been shown to identify patients at high risk of all-cause mortality and sudden death, particularly in postinfarction and congestive heart failure patients. It should be emphasized that abnormal HRT has a well-established role in stratification of postinfarction and heart failure patients with relatively preserved left ventricular ejection fraction. The ongoing clinical trials will document whether HRT can be used to guide implantation of cardioverter-defibrillators in this subset of patients, not covered yet by ICD guidelines. This review focuses on the current state-of-the-art knowledge regarding clinical significance of HRT in detection of autonomic dysfunction and regarding the prognostic significance of this parameter in predicting all-cause mortality and sudden death. © 2013.

Comparison of five-year outcomes of coronary artery bypass grafting versus percutaneous coronary intervention in patients with left ventricular ejection fractions≤50% versus >50% (from the CREDO-Kyoto PCI/CABG Registry Cohort-2).

PubMed

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

2014-10-01

Coronary heart disease is a major risk factor for left ventricular (LV) systolic dysfunction. However, limited data are available regarding long-term benefits of percutaneous coronary intervention (PCI) in the era of drug-eluting stent or coronary artery bypass grafting (CABG) in patients with LV systolic dysfunction with severe coronary artery disease. We identified 3,584 patients with 3-vessel and/or left main disease of 15,939 patients undergoing first myocardial revascularization enrolled in the CREDO-Kyoto PCI/CABG Registry Cohort-2. Of them, 2,676 patients had preserved LV systolic function, defined as an LV ejection fraction (LVEF) of >50% and 908 had impaired LV systolic function (LVEF≤50%). In patients with preserved LV function, 5-year outcomes were not different between PCI and CABG regarding propensity score-adjusted risk of all-cause and cardiac deaths. In contrast, in patients with impaired LV systolic function, the risks of all-cause and cardiac deaths after PCI were significantly greater than those after CABG (hazard ratio 1.49, 95% confidence interval 1.04 to 2.14, p=0.03 and hazard ratio 2.39, 95% confidence interval 1.43 to 3.98, p<0.01). In both patients with moderate (35%

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.

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.

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.

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.).

Beta-Adrenergic Receptor Polymorphisms and Cardiac Graft Function in Potential Organ Donors

PubMed Central

Khush, K.K.; Pawlikowska, L.; Menza, R.L.; Goldstein, B.A.; Hayden, V.; Nguyen, J.; Kim, H.; Poon, A.; Sapru, A.; Matthay, M.A.; Kwok, P.Y.; Young, W.L.; Baxter-Lowe, L.A.; Zaroff, J.G.

2012-01-01

Prior studies have demonstrated associations between β-adrenergic receptor polymorphisms and left ventricular dysfunction—an important cause of allograft non-utilization for transplantation. We hypothesized that βAR polymorphisms predispose donor hearts to LV dysfunction after brain death. 1,043 organ donors managed from 2001-2006 were initially studied. The following βAR single nucleotide polymorphisms were genotyped: β1AR 1165C/G (Arg389Gly), β1AR 145A/G (Ser49Gly), β2AR 46G/A (Gly16Arg), and β2AR 79C/G (Gln27Glu). In multivariable regression analyses, the β2AR46 SNP was significantly associated with LV systolic dysfunction, with each minor allele additively decreasing the odds for LV ejection fraction<50%. The β1AR1165 and β2AR46 SNPs were associated with higher dopamine requirement during the donor management period: donors with the GG and AA genotypes had ORs of 2.64 (95% CI 1.52-4.57) and 2.70 (1.07-2.74) respectively for requiring >10 mcg/kg/min of dopamine compared to those with the CC and GG genotypes. However, no significant associations were found between βAR SNPs and cardiac dysfunction in 364 donors managed from 2007-2008, perhaps due to changes in donor management, lack of power in this validation cohort, or the absence of a true association. βAR polymorphisms may be associated with cardiac dysfunction after brain death, but these relationships require further study in independent donor cohorts. PMID:22994654

Assessment of tenascin-C levels in ventricular noncompaction/hypertrabeculation patients: a cross-sectional study.

PubMed

Erer, Hatice Betul; Guvenc, Tolga Sinan; Kemik, Ahu Sarbay; Yilmaz, Hale; Kul, Seref; Altay, Servet; Oz, Dilaver; Zeren, Gonul; Ekmekci, Ahmet; Zencirci, Aycan Esen; Sayar, Nurten; Eren, Mehmet

2014-02-01

Ventricular noncompaction/hypertrabeculation (NC/HT) is a rare form of congenital cardiomyopathy. We aimed to investigate the presence of serum tenascin-C (TN-C) in adult patients with NC/HT and evaluate its value. Serum TN-C levels were measured by ELISA in 50 NC/HT patients both with/without systolic dysfunction and in 23 normal controls. Systolic dysfunction was defined as ejection fraction (EF) ≤ 40. Mann-Whitney U-test and ROC curve analysis were done. Of 49 NC/HT patients, 24 (49%) patients had systolic dysfunction (mean age 36 ± 15) and 25 patients (51%) had normal systolic function (mean age 36 ± 17). The ages between groups were not different. The mean levels of serum TN-C in patients with or without systolic dysfunction were 26 ± 10 ng/mL and 26 ± 8 ng/mL respectively, compared to normal controls, 7 ± 2 ng/mL (P < 0.001). No significance was observed between 2 groups of NC/HT patients regarding TN-C levels (P = 0.8). The ROC curve analysis revealed that a TN-C value of 11.7 ng/mL identified patients with NC/HT with 100% sensitivity and specifity. High serum TN-C levels are present in adult NC/HT cardiomyopathy even when left ventricular systolic function remains normal. Also, serum TN-C levels could be regarded as a candidate biomarker in the diagnosis of NC/HT which needs to be tested in larger prospective studies. © 2013, Wiley Periodicals, Inc.

Mitochondrial reactive oxygen species production and respiratory complex activity in rats with pressure overload-induced heart failure

PubMed Central

Schwarzer, Michael; Osterholt, Moritz; Lunkenbein, Anne; Schrepper, Andrea; Amorim, Paulo; Doenst, Torsten

2014-01-01

We investigated the impact of cardiac reactive oxygen species (ROS) during the development of pressure overload-induced heart failure. We used our previously described rat model where transverse aortic constriction (TAC) induces compensated hypertrophy after 2 weeks, heart failure with preserved ejection fraction at 6 and 10 weeks, and heart failure with systolic dysfunction after 20 weeks. We measured mitochondrial ROS production rates, ROS damage and assessed the therapeutic potential of in vivo antioxidant therapies. In compensated hypertrophy (2 weeks of TAC) ROS production rates were normal at both mitochondrial ROS production sites (complexes I and III). Complex I ROS production rates increased with the appearance of diastolic dysfunction (6 weeks of TAC) and remained high thereafter. Surprisingly, maximal ROS production at complex III peaked at 6 weeks of pressure overload. Mitochondrial respiratory capacity (state 3 respiration) was elevated 2 and 6 weeks after TAC, decreased after this point and was significantly impaired at 20 weeks, when contractile function was also impaired and ROS damage was found with increased hydroxynonenal. Treatment with the ROS scavenger α-phenyl-N-tert-butyl nitrone or the uncoupling agent dinitrophenol significantly reduced ROS production rates at 6 weeks. Despite the decline in ROS production capacity, no differences in contractile function between treated and untreated animals were observed. Increased ROS production occurs early in the development of heart failure with a peak at the onset of diastolic dysfunction. However, ROS production may not be related to the onset of contractile dysfunction. PMID:24951621

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

PubMed Central

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

2017-01-01

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

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

PubMed Central

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

2014-01-01

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

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

PubMed Central

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

2017-01-01

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

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.

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

PubMed

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

2016-11-01

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

[Routine hormonal therapy in the heart transplant donor].

PubMed

Zetina-Tun, Hugo; Lezama-Urtecho, Carlos; Careaga-Reyna, Guillermo

2016-01-01

Successful heart transplantation depends largely on donor heart function. During brain death many hormonal changes occur. These events lead to the deterioration of the donor hearts. The 2002 Crystal Consensus advises the use of a triple hormonal scheme to rescue marginal cardiac organs. A prospective, longitudinal study was conducted on potential donor hearts during the period 1 July 2011 to 31 May 2013. All donor hearts received a dual hormonal rescue scheme, with methylprednisolone 15mg/kg IV and 200mcg levothyroxine by the enteral route. There was at least a 4 hour wait prior to the harvesting. The preload and afterload was optimised. The variables measured were: left ventricular ejection fraction cardiac graft recipient; immediate and delayed mortality. A total of 30 orthotopic heart transplants were performed, 11 female and 19 male patients, with age range between 19 and 63 years-old (Mean: 44.3, SD 12.92 years). The donor hearts were 7 female and 23 male, with age range between 15 and 45 years-old (mean 22.5, SD 7.3 years). Immediate mortality was 3.3%, 3.3% intermediate, and delayed 3.3%, with total 30 day-mortality of 10%. Month survival was 90%. The immediate graft left ventricular ejection fraction was 45%, 60% intermediate, and 68% delayed. The causes of death were: 1 primary graft dysfunction, one massive pulmonary embolism, and one due to nosocomial pneumonia. It was concluded that the use of double rescue scheme hormonal therapy is useful for the recovery and preservation of the donor hearts. This scheme improves survival within the first 30 days after transplantation. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

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.

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

PubMed

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

2018-01-27

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

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

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

PubMed

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

2015-02-10

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

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

PubMed

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

2006-11-14

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

Role of cardioprotective therapy for prevention of cardiotoxicity with chemotherapy: a systematic review and meta-analysis.

PubMed

Kalam, Kashif; Marwick, Thomas H

2013-09-01

Cardiotoxicity is a well-recognised complication of chemotherapy with anthracycline and/or trastuzumab, and its prevention remains an important challenge in cancer survivorship. Several successful preventative strategies have been identified in animal trials. We sought to assemble the clinical evidence that prophylactic pharmacological interventions could prevent left ventricular (LV) dysfunction and heart failure in patients undergoing chemotherapy. We undertook a systemic review of the evidence from randomised trials and observational studies where a prophylactic intervention was compared with a control arm in patients with a normal ejection fraction and no past history of heart failure. The primary outcome was development of heart failure (HF), a drop in ejection fraction (EF) or both. A random-effects model was used to combine relative risks (RR) and 95% confidence intervals (CIs), and a meta-regression was undertaken to assess the impact of potential covariates. Data were collated from 14 published articles (n=2015 paediatric and adult patients) comprising 12 randomised controlled trials and two observational studies. The most studied chemotherapeutic agents were anthracyclines, and prophylactic agents included dexrazoxane, statins, beta-blocker and angiotensin antagonists. There were 304 cardiac events in the control arm compared to 83 in the prophylaxis arm (RR=0.31 [95% CI: 0.25-0.39], p<0.00001). Cardiac events were reduced with dexrazoxane (RR=0.35 [95% CI 0.27-0.45], p<0.00001), beta-blockade (RR=0.31 [95% CI 0.16-0.63], p=0.001), statin (RR=0.31 [95% CI 0.13-0.77], p=0.01) and angiotensin antagonists (RR=0.11 [95% CI 0.04-0.29], p<0.0001). Prophylactic treatment with dexrazoxane, beta-blocker, statin or angiotensin antagonists appear to have similar efficacy for reducing cardiotoxicity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Role of gender in heart failure with normal left ventricular ejection fraction.

PubMed

Regitz-Zagrosek, Vera; Brokat, Sebastian; Tschope, Carsten

2007-01-01

Heart failure with normal ejection fraction (HF-NEF) is frequently believed to be more common in women than in men. However, the interaction of gender and age has rarely been analyzed in detail, and knowledge of the distinction between pre- and postmenopausal women is lacking. Some of the studies that have described a higher prevalence of HF-NEF in women relied on clinical diagnoses of HF together with normal systolic function and did not measure diastolic function. This applies to the analysis of patients hospitalized for HF and some epidemiological investigations that agree on the greater prevalence of HF-NEF in women. Population-based studies with echocardiographic determination of diastolic function have suggested equal or greater prevalence of diastolic dysfunction in men. Major risk factors for HF-NEF include hypertension, aging, obesity, diabetes, and ischemia. Hypertension is more frequent in women and can contribute to left ventricular and arterial stiffening in a gender-specific way. Aging, obesity, and diabetes affect myocardial and vascular stiffness differently and lead to different forms of myocardial hypertrophy in women and men. In contrast, ischemia may play a greater role in men. Gender differences in ventricular diastolic distensibility, in vascular stiffness and ventricular/vascular coupling, in skeletal muscle adaptation to HF, and in the perception of symptoms may contribute to a greater rate of HF-NEF in women. The underlying molecular mechanisms include gender differences in calcium handling, in the NO system, and in natriuretic peptides. Estrogen affects collagen synthesis and degradation and inhibits the renin-angiotensin system. Effects of estrogen may provide benefit to premenopausal women, and the loss of its protective mechanisms may render the heart of postmenopausal women more vulnerable. Thus, a number of molecular mechanisms can contribute to the gender differences in HF-NEF.

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

PubMed

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

2018-05-01

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

Health related quality of life in patients with congestive heart failure: comparison with other chronic diseases and relation to functional variables

PubMed Central

Juenger, J; Schellberg, D; Kraemer, S; Haunstetter, A; Zugck, C; Herzog, W; Haass, M

2002-01-01

Objective: To assess health related quality of life of patients with congestive heart failure; to compare their quality of life with the previously characterised general population and in those with other chronic diseases; and to correlate the different aspects of quality of life with relevant somatic variables. Setting: University hospital. Patients and design: A German version of the generic quality of life measure (SF-36) containing eight dimensions was administered to 205 patients with congestive heart failure and systolic dysfunction. Cardiopulmonary evaluation included assessment of New York Heart Association (NYHA) functional class, left ventricular ejection fraction, peak oxygen uptake, and the distance covered during a standardised six minute walk test. Results: Quality of life significantly decreased with NYHA functional class (linear trend: p < 0.0001). In NYHA class III, the scores of five of the eight quality of life domains were reduced to around one third of those in the general population. The pattern of reduction was different in patients with chronic hepatitis C and major depression, and similar in patients on chronic haemodialysis. Multiple regression analysis showed that only the NYHA functional class was consistently and closely associated with all quality of life scales. The six minute walk test and peak oxygen uptake added to the explanation of the variance in only one of the eight quality of life domains (physical functioning). Left ventricular ejection fraction, duration of disease, and age showed no clear association with quality of life. Conclusions: In congestive heart failure, quality of life decreases as NYHA functional class worsens. Though NYHA functional class was the most dominant predictor among the somatic variables studied, the major determinants of reduced quality of life remain unknown. PMID:11847161

Health related quality of life in patients with congestive heart failure: comparison with other chronic diseases and relation to functional variables.

PubMed

Juenger, J; Schellberg, D; Kraemer, S; Haunstetter, A; Zugck, C; Herzog, W; Haass, M

2002-03-01

To assess health related quality of life of patients with congestive heart failure; to compare their quality of life with the previously characterised general population and in those with other chronic diseases; and to correlate the different aspects of quality of life with relevant somatic variables. University hospital. A German version of the generic quality of life measure (SF-36) containing eight dimensions was administered to 205 patients with congestive heart failure and systolic dysfunction. Cardiopulmonary evaluation included assessment of New York Heart Association (NYHA) functional class, left ventricular ejection fraction, peak oxygen uptake, and the distance covered during a standardised six minute walk test. Quality of life significantly decreased with NYHA functional class (linear trend: p < 0.0001). In NYHA class III, the scores of five of the eight quality of life domains were reduced to around one third of those in the general population. The pattern of reduction was different in patients with chronic hepatitis C and major depression, and similar in patients on chronic haemodialysis. Multiple regression analysis showed that only the NYHA functional class was consistently and closely associated with all quality of life scales. The six minute walk test and peak oxygen uptake added to the explanation of the variance in only one of the eight quality of life domains (physical functioning). Left ventricular ejection fraction, duration of disease, and age showed no clear association with quality of life. In congestive heart failure, quality of life decreases as NYHA functional class worsens. Though NYHA functional class was the most dominant predictor among the somatic variables studied, the major determinants of reduced quality of life remain unknown.

Leptin-Aldosterone-Neprilysin Axis: Identification of Its Distinctive Role in the Pathogenesis of the Three Phenotypes of Heart Failure in People With Obesity.

PubMed

Packer, Milton

2018-04-10

Obesity (especially visceral adiposity) can be associated with 3 different phenotypes of heart failure: heart failure with a reduced ejection fraction, heart failure with a preserved ejection fraction, and high-output heart failure. All 3 phenotypes are characterized by an excessive secretion of aldosterone and sodium retention. In addition, obesity is accompanied by increased signaling through the leptin receptor, which can promote activation of both the sympathetic nervous system and the renin-angiotensin system and can directly stimulate the secretion of aldosterone. The deleterious interaction of leptin and aldosterone is potentiated by the simultaneous action of adiposity and the renal sympathetic nerves to cause overactivity of neprilysin; the loss of the counterbalancing effects of natriuretic peptides is exacerbated by an additional effect of both obesity and heart failure to interfere with adiponectin signaling. This intricate neurohormonal interplay leads to plasma volume expansion as well as to adverse ventricular remodeling and cardiac fibrosis. Furthermore, the activity of aldosterone and neprilysin is not only enhanced by obesity, but these mechanisms can also promote adipogenesis and adipocyte dysfunction, thereby enhancing the positive feedback loop. Last, in elderly obese women, changes in quantity and biology of epicardial adipose tissue further enhances the release of leptin and other proinflammatory adipokines, thereby leading to cardiac and systemic inflammation, end-organ fibrosis, and multiple comorbidities. Regardless of the phenotypic expression, activation of the leptin-aldosterone-neprilysin axis appears to contribute importantly to the evolution and progression of heart failure in people with obesity. Efforts to interfere with the detrimental interactions of this distinctive neurohormonal ecosystem with existing or novel therapeutic agents are likely to yield unique clinical benefits. © 2018 American Heart Association, Inc.

Changes in Left Ventricular Morphology and Function After Mitral Valve Surgery

PubMed Central

Shafii, Alexis E.; Gillinov, A. Marc; Mihaljevic, Tomislav; Stewart, William; Batizy, Lillian H.; Blackstone, Eugene H.

2015-01-01

Degenerative mitral valve disease is the leading cause of mitral regurgitation in North America. Surgical intervention has hinged on symptoms and ventricular changes that develop as compensatory ventricular remodeling takes place. In this study, we sought to characterize the temporal response of left ventricular (LV) morphology and function to mitral valve surgery for degenerative disease, and identify preoperative factors that influence reverse remodeling. From 1986–2007, 2,778 patients with isolated degenerative mitral valve disease underwent valve repair (n=2,607/94%) or replacement (n=171/6%) and had at least 1 postoperative transthoracic echocardiogram (TTE); 5,336 TTEs were available for analysis. Multivariable longitudinal repeated-measures analysis was performed to identify factors associated with reverse remodeling. LV dimensions decreased in the first year after surgery (end-diastolic from 5.7±0.80 to 4.9±1.4 cm; end-systolic from 3.4±0.71 to 3.1±1.4 cm). LV mass index decreased from 139±44 to 112±73 g·m−2. Reduction of LV hypertrophy was less pronounced in patients with greater preoperative left heart enlargement (P<.0001) and greater preoperative LV mass (P<.0001). Postoperative LV ejection fraction initially decreased from 58±7.0 to 53±20, increased slightly over the first postoperative year, and was negatively influenced by preoperative heart failure symptoms (P<.0001) and lower preoperative LV ejection fraction (P<.0001). Risk-adjusted response of LV morphology and function to valve repair and replacement was similar (P>.2). In conclusion, a positive response toward normalization of LV morphology and function after mitral valve surgery is greatest in the first year. The best response occurs when surgery is performed before left heart dilatation, LV hypertrophy, or LV dysfunction develop. PMID:22534055

Heart failure: when form fails to follow function.

PubMed

Katz, Arnold M; Rolett, Ellis L

2016-02-01

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

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

Effects of upright and supine position on cardiac rest and exercise response in aortic regurgitation.

PubMed

Shen, W F; Roubin, G S; Fletcher, P J; Choong, C Y; Hutton, B F; Harris, P J; Kelly, D T

1985-02-01

The effects of upright and supine position on cardiac response to exercise were assessed by radionuclide ventriculography in 15 patients with moderate to severe aortic regurgitation (AR) and in 10 control subjects. In patients with AR, heart rate was higher during upright exercise, but systolic and diastolic blood pressure and left ventricular (LV) output were similar during both forms of exercise. LV stroke volume and end-diastolic volume were not altered during supine exercise. LV end-systolic volume increased and ejection fraction decreased during supine exercise, but both were unchanged during upright exercise. Of 15 patients, 5 in the upright and 12 in the supine position had an abnormal LV ejection fraction response to exercise (p less than 0.01). Right ventricular ejection fraction increased and regurgitant index decreased with both forms of exercise and was not significantly different between the 2 positions. Thus, posture is important in determining LV response to exercise in patients with moderate to severe AR.

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.

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.

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.

Effects of auto-servo ventilation on patients with sleep-disordered breathing, stable systolic heart failure and concomitant diastolic dysfunction: subanalysis of a randomized controlled trial.

PubMed

Birner, Christoph; Series, Frederic; Lewis, Keir; Benjamin, Amit; Wunderlich, Silke; Escourrou, Pierre; Zeman, Florian; Luigart, Ruth; Pfeifer, Michael; Arzt, Michael

2014-01-01

Systolic heart failure (HF) is frequently accompanied by diastolic dysfunction and sleep-disordered breathing (SDB). The objective of this subset analysis was to determine effect sizes of auto-servo ventilation (ASV and biphasic positive airway pressure ASV) on echocardiographic measures of diastolic function in patients with systolic HF and SDB. Thirty-two patients with stable systolic HF, concomitant diastolic dysfunction [age 66 ± 9 years old, left ventricular (LV) ejection fraction: 30 ± 7% and New York Heart Association class II: 72%] and SDB (apnea-hypopnea index, AHI: 48 ± 19/h; 53% had predominantly obstructive sleep apnea) receiving either ASV (n = 19) or optimal medical treatment (control, n = 13) were analyzed in a randomized controlled clinical trial. Polysomnographic and echocardiographic measurements were obtained at baseline and after 12 weeks. AHI significantly improved in the ASV group compared to the control group (-39 ± 18 vs. -0.2 ± 13.2/h, p < 0.001). At baseline, 24 (75%) patients had impaired LV relaxation, and 8 (25%) had a pseudo-normalized filling pattern. At the 12-week control visit, diastolic function assessed by the isovolumetric relaxation time (-10.3 ± 26.1 vs. 9.3 ± 49.1, p = 0.48) and deceleration time (-43.9 ± 88.8 vs. 12.4 ± 68.8, p = 0.40) tended to improve after ASV treatment, but did not reach statistical significance. Likewise, the proportion of patients whose diastolic dysfunction improved was nonsignificantly higher in the ASV than in the control group, respectively (37 vs. 15%, p = 0.25). ASV treatment efficiently abolishes SDB in patients with stable systolic HF and concomitant diastolic dysfunction, and was associated with a statistically nonsignificant improvement in measures of diastolic dysfunction. Thus, these data provide estimates of effect size and justify the evaluation of the effects of ASV on diastolic function in larger randomized controlled trials. Copyright © 2013 S. Karger AG, Basel.

Effect of left ventricular diastolic dysfunction on left atrial appendage function and thrombotic potential in nonvalvular atrial fibrillation.

PubMed

Demirçelik, Muhammed Bora; Çetin, Mustafa; Çiçekcioğlu, Hülya; Uçar, Özgül; Duran, Mustafa

2014-05-01

We aimed to investigate effects of left ventricular diastolic dysfunction on left atrial appendage functions, spontaneous echo contrast and thrombus formation in patients with nonvalvular atrial fibrillation. In 58 patients with chronic nonvalvular atrial fibrilation and preserved left ventricular systolic function, left atrial appendage functions, left atrial spontaneous echo contrast grading and left ventricular diastolic functions were evaluated using transthoracic and transoesophageal echocardiogram. Patients divided in two groups: Group D (n=30): Patients with diastolic dysfunction, Group N (n=28): Patients without diastolic dysfunction. Categorical variables in two groups were evaluated with Pearson's chi-square or Fisher's exact test. The significance of the lineer correlation between the degree of spontaneous echo contrast (SEC) and clinical measurements was evaluated with Spearman's correlation analysis. Peak pulmonary vein D velocity of the Group D was significantly higher than the Group N (p=0.006). However, left atrial appendage emptying velocity, left atrial appendage lateral wall velocity, peak pulmonary vein S, pulmonary vein S/D ratio were found to be significantly lower in Group D (p=0.028, p<0.001, p<0.001; p<0.001). Statistically significant negative correlation was found between SEC in left atrium and left atrial appendage emptying, filling, pulmonary vein S/D levels and lateral wall velocities respectively (r=-0.438, r=-0.328, r=-0.233, r=-0.447). Left atrial appendage emptying, filling, pulmonary vein S/D levels and lateral wall velocities were significantly lower in SEC 2-3-4 than SEC 1 (p=0.003, p=0.029, p<0.001, p=0.002). In patients with nonvalvular atrial fibrillation and preserved left ventricular ejection fraction, left atrial appendage functions are decreased in patients with left ventricular diastolic dysfunction. Left ventricular diastolic dysfunction may constitute a potential risk for formation of thrombus and stroke.

Predictors of Long-Term Mortality and Frequent Re-Hospitalization in Patients with Acute Decompensated Heart Failure and Kidney Dysfunction Treated with Renin-Angiotensin System Blockers.

PubMed

Baydemir, Canan; Ural, Dilek; Karaüzüm, Kurtuluş; Balci, Sibel; Argan, Onur; Karaüzüm, Irem; Kozdağ, Güliz; Ağır, Ayşen A

2017-07-10

BACKGROUND Assessment of risk for all-cause mortality and re-hospitalization is an important task during discharge of acute heart failure (AHF) patients, as they warrant different management strategies. Treatment with optimal medical therapy may change predictors for these 2 end-points in AHF patients with renal dysfunction. The aim of this study was to evaluate the predictors for long-term outcome in AHF patients with kidney dysfunction who were discharged on optimal medical therapy. MATERIAL AND METHODS The study was conducted retrospectively. The study group consisted of 225 AHF patients with moderate-to-severe kidney dysfunction, who were hospitalized at Kocaeli University Hospital Cardiology Clinic and who were prescribed beta-blockers and ACE-inhibitors or angiotensin II receptor blockers at discharge. Clinical, echocardiographic, and biochemical predictors of the composite of total mortality and frequent re-hospitalization (≥3 hospitalizations during the follow-up) were assessed using Cox regression and the predictors for each end-point were assessed by competing risk regression analysis. RESULTS Incidence of all-cause mortality was 45.3% and frequent readmissions were 49.8% in a median follow-up of 54 months. The associates of the composite end-point were age, NYHA class, respiration rate on admission, eGFR, hypoalbuminemia, mitral valve E/E' ratio, and ejection fraction. In competing risk regression analysis, right-sided HF, hypoalbuminemia, age, and uric acid appeared as independent associates of all-cause mortality, whereas NYHA class, NT-proBNP, mitral valve E/E' ratio, and uric acid were predictors for re-hospitalization. CONCLUSIONS Predictors for all-cause mortality in AHF with kidney dysfunction treated with optimal therapy are mainly related to advanced HF with right-sided dysfunction, whereas frequent re-hospitalization is associated with volume overload manifested by increased mitral E/E' ratio and NT-proBNP levels.

Effects of statin therapy on clinical outcomes after acute myocardial infarction in patients with advanced renal dysfunction: A propensity score-matched analysis.

PubMed

Kim, Jin Sug; Kim, Weon; Park, Ji Yoon; Woo, Jong Shin; Lee, Tae Won; Ihm, Chun Gyoo; Kim, Yang Gyun; Moon, Ju-Young; Lee, Sang Ho; Jeong, Myung Ho; Jeong, Kyung Hwan

2017-01-01

Lipid lowering therapy is widely used for the prevention of cardiovascular complications after acute myocardial infarction (AMI). However, some studies show that this benefit is uncertain in patients with renal dysfunction, and the role of statins is based on the severity of renal dysfunction. In this study, we investigated the impact of statin therapy on major adverse cardiac events (MACEs) and all-cause mortality in patients with advanced renal dysfunction undergoing percutaneous coronary intervention (PCI) after AMI. This study was based on the Korea Acute Myocardial Infarction Registry database. We included 861 patients with advanced renal dysfunction from among 33,205 patients who underwent PCI after AMI between November 2005 and July 2012. Patients were divided into two groups: a statin group (n = 537) and a no-statin group (n = 324). We investigated the 12-month MACEs (cardiac death, myocardial infarction, repeated PCI or coronary artery bypass grafting) and all-cause mortality of each group. Subsequently, a propensity score-matched analysis was performed. In the total population studied, no significant differences were observed between the two groups with respect to the rate of recurrent MI, repeated PCI, coronary artery bypass grafting (CABG), or all-cause mortality. However, the cardiac death rate was significantly lower in the statin group (p = 0.009). Propensity score-matched analysis yielded 274 pairs demonstrating, results similar to those obtained from the total population. However, there was no significant difference in the cardiac death rate in the propensity score-matched population (p = 0.103). Cox-regression analysis revealed only left ventricular ejection fraction to be an independent predictor of 12-month MACEs (Hazard ratio [HR] of 0.979, 95% confidence interval [CI], 0962-0.996, p = 0.018). Statin therapy was not significantly associated with a reduction in the 12-month MACEs or all-cause mortality in patients with advanced renal dysfunction undergoing PCI after AMI.

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.

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.

The Prognostic Impact of the Evolution of RV Function in Idiopathic DCM.

PubMed

Merlo, Marco; Gobbo, Marco; Stolfo, Davide; Losurdo, Pasquale; Ramani, Federica; Barbati, Giulia; Pivetta, Alberto; Di Lenarda, Andrea; Anzini, Marco; Gigli, Marta; Pinamonti, Bruno; Sinagra, Gianfranco

2016-09-01

In this study, the authors analyzed the prognostic role of right ventricular systolic function (RVF) longitudinal trends in a large cohort of patients affected by dilated cardiomyopathy (DCM). RVF is a known prognostic predictor in DCM; however, whether RVF changes over time to better predict the long-term disease progression has not been investigated. From 1993 to 2008, we analyzed 512 patients with DCM (46 years of age [36 to 55 years of age], left ventricular ejection fraction 32% [25% to 41%]) with a potential follow-up of ≥72 months and available data at baseline and at least 1 pre-specified follow-up evaluation (i.e., 6, 24, 48, or 72 months). RV dysfunction was defined as RV fractional area change <35% at 2-dimensional echocardiography. The primary outcome measure was a composite of death or heart transplantation. At enrollment, 103 (20%) patients had RV dysfunction. During follow-up, 89 of them (86%, 17% of the overall cohort) normalized RVF at a median time of 6 months, whereas 38 of the remaining 409 patients with normal baseline RVF (9%; 7% of the overall population) exhibited a new-onset RV dysfunction (median time: 36 months). RVF normalization was significantly associated with subsequent left ventricular reverse remodeling that was observed at a median time of 24 months (odds ratio: 2.49; 95% confidence interval [CI]: 1.17 to 5.3; p = 0.018). At baseline multivariate analysis, RV dysfunction was independently associated with the primary outcome measure (hazard ratio: 1.71; 95% CI: 1.02 to 2.85; p = 0.0413). At time-dependent model, RVF revaluation over time maintained an independent predictive value (hazard ratio: 2.83; 95% CI: 1.57 to 5.11; p = 0.0006). Patients with DCM frequently present RV dysfunction at first evaluation. However, a complete RVF recovery is largely observed early after optimization of medical therapy and predates subsequent left ventricular reverse remodeling. Systematic revaluation of patients including RVF throughout regular follow-up conferred additive long-term prognostic value to the baseline evaluation. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The effects of acute oral antioxidants on diving-induced alterations in human cardiovascular function

PubMed Central

Obad, Ante; Palada, Ivan; Valic, Zoran; Ivančev, Vladimir; Baković, Darija; Wisløff, Ulrik; Brubakk, Alf O; Dujić, Željko

2007-01-01

Diving-induced acute alterations in cardiovascular function such as arterial endothelial dysfunction, increased pulmonary artery pressure (PAP) and reduced heart function have been recently reported. We tested the effects of acute antioxidants on arterial endothelial function, PAP and heart function before and after a field dive. Vitamins C (2 g) and E (400 IU) were given to subjects 2 h before a second dive (protocol 1) and in a placebo-controlled crossover study design (protocol 2). Seven experienced divers performed open sea dives to 30 msw with standard decompression in a non-randomized protocol, and six of them participated in a randomized trial. Before and after the dives ventricular volumes and function and pulmonary and brachial artery function were assessed by ultrasound. The control dive resulted in a significant reduction in flow-mediated dilatation (FMD) and heart function with increased mean PAP. Twenty-four hours after the control dive FMD was still reduced 37% below baseline (8.1 versus 5.1%, P = 0.005), while right ventricle ejection fraction (RV-EF), left ventricle EF and endocardial fractional shortening were reduced much less (∼2–3%). At the same time RV end-systolic volume was increased by 9% and mean PAP by 5%. Acute antioxidants significantly attenuated only the reduction in FMD post-dive (P < 0.001), while changes in pulmonary artery and heart function were unaffected by antioxidant ingestion. These findings were confirmed by repeating the experiments in a randomized study design. FMD returned to baseline values 72 h after the dive with pre-dive placebo, whereas for most cardiovascular parameters this occurred earlier (24–48 h). Right ventricular dysfunction and increased PAP lasted longer. Acute antioxidants attenuated arterial endothelial dysfunction after diving, while reduction in heart and pulmonary artery function were unchanged. Cardiovascular changes after diving are not fully reversed up to 3 days after a dive, suggesting longer lasting negative effects. PMID:17110413

Adeno-associated Virus Serotype 9 – Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts with Left Ventricular Dysfunction Secondary to a Myocardial Infarction

PubMed Central

Knezevic, Tijana; Myers, Valerie D.; Su, Feifei; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Gao, Erhe; Gao, Guofeng; Muniswamy, Madesh; Gupta, Manish K.; Gordon, Jennifer; Weiner, Kristen N.; Rabinowitz, Joseph; Ramsey, Frederick V.; Tilley, Douglas G.; Khalili, Kamel; Cheung, Joseph Y.; Feldman, Arthur M.

2016-01-01

Objectives The present study was undertaken to test the hypothesis that gene delivery of BCL2-Associated Athanogene 3 (BAG3) to the heart of mice with left ventricular dysfunction secondary to a myocardial infarction could enhance cardiac performance. Background BAG3 is a 575 amino acid protein that has pleotropic functions in the cell including pro-autophagy and anti-apoptosis. Mutations in BAG3 have been associated with both skeletal muscle dysfunction and familial dilated cardiomyopathy and BAG3 levels are diminished in non-familial heart failure. Methods Eight-week-old C57/BL6 mice underwent ligation of the left coronary artery (MI) or sham surgery (Sham). Eight weeks later, mice in both groups were randomly assigned to receive either a retro-orbital injection of rAAV9-BAG3 (MI-BAG3 or Sham-BAG3) or rAAV9-GFP (MI-GFP or Sham GFP). Mice were sacrificed at 3 weeks post-injection and myocytes were isolated from the left ventricle. Results MI-BAG3 mice demonstrated a significantly (p < 0.0001) higher left ventricular ejection fraction (LVEF) 9 days after rAAV9-BAG3 injection with further improvement in LVEF, fractional shortening and stroke volume at 3 weeks post-injection without changes in LV mass or LV volume. Injection of rAAV9-BAG3 had no effect on LVEF in Sham mice. The salutary benefits of rAAV9-BAG3 were also observed in myocytes isolated from MI hearts including improved cell shortening (p<0.05), increased systolic [Ca2+]i, increased [Ca2+]i transient amplitudes and increased maximal ICa amplitude. Implications The results suggest that BAG3 gene therapy may provide a novel therapeutic option for the treatment of heart failure. PMID:28164169

Adeno-associated Virus Serotype 9 - Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts with Left Ventricular Dysfunction Secondary to a Myocardial Infarction.

PubMed

Knezevic, Tijana; Myers, Valerie D; Su, Feifei; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Gao, Erhe; Gao, Guofeng; Muniswamy, Madesh; Gupta, Manish K; Gordon, Jennifer; Weiner, Kristen N; Rabinowitz, Joseph; Ramsey, Frederick V; Tilley, Douglas G; Khalili, Kamel; Cheung, Joseph Y; Feldman, Arthur M

2016-12-01

The present study was undertaken to test the hypothesis that gene delivery of BCL2-Associated Athanogene 3 (BAG3) to the heart of mice with left ventricular dysfunction secondary to a myocardial infarction could enhance cardiac performance. BAG3 is a 575 amino acid protein that has pleotropic functions in the cell including pro-autophagy and anti-apoptosis. Mutations in BAG3 have been associated with both skeletal muscle dysfunction and familial dilated cardiomyopathy and BAG3 levels are diminished in non-familial heart failure. Eight-week-old C57/BL6 mice underwent ligation of the left coronary artery (MI) or sham surgery (Sham). Eight weeks later, mice in both groups were randomly assigned to receive either a retro-orbital injection of rAAV9-BAG3 (MI-BAG3 or Sham-BAG3) or rAAV9-GFP (MI-GFP or Sham GFP). Mice were sacrificed at 3 weeks post-injection and myocytes were isolated from the left ventricle. MI-BAG3 mice demonstrated a significantly (p < 0.0001) higher left ventricular ejection fraction (LVEF) 9 days after rAAV9-BAG3 injection with further improvement in LVEF, fractional shortening and stroke volume at 3 weeks post-injection without changes in LV mass or LV volume. Injection of rAAV9-BAG3 had no effect on LVEF in Sham mice. The salutary benefits of rAAV9-BAG3 were also observed in myocytes isolated from MI hearts including improved cell shortening (p<0.05), increased systolic [Ca 2+ ] i , increased [Ca 2+ ] i transient amplitudes and increased maximal I Ca amplitude. The results suggest that BAG3 gene therapy may provide a novel therapeutic option for the treatment of heart failure.

The effects of acute oral antioxidants on diving-induced alterations in human cardiovascular function.

PubMed

Obad, Ante; Palada, Ivan; Valic, Zoran; Ivancev, Vladimir; Baković, Darija; Wisløff, Ulrik; Brubakk, Alf O; Dujić, Zeljko

2007-02-01

Diving-induced acute alterations in cardiovascular function such as arterial endothelial dysfunction, increased pulmonary artery pressure (PAP) and reduced heart function have been recently reported. We tested the effects of acute antioxidants on arterial endothelial function, PAP and heart function before and after a field dive. Vitamins C (2 g) and E (400 IU) were given to subjects 2 h before a second dive (protocol 1) and in a placebo-controlled crossover study design (protocol 2). Seven experienced divers performed open sea dives to 30 msw with standard decompression in a non-randomized protocol, and six of them participated in a randomized trial. Before and after the dives ventricular volumes and function and pulmonary and brachial artery function were assessed by ultrasound. The control dive resulted in a significant reduction in flow-mediated dilatation (FMD) and heart function with increased mean PAP. Twenty-four hours after the control dive FMD was still reduced 37% below baseline (8.1 versus 5.1%, P = 0.005), while right ventricle ejection fraction (RV-EF), left ventricle EF and endocardial fractional shortening were reduced much less (approximately 2-3%). At the same time RV end-systolic volume was increased by 9% and mean PAP by 5%. Acute antioxidants significantly attenuated only the reduction in FMD post-dive (P < 0.001), while changes in pulmonary artery and heart function were unaffected by antioxidant ingestion. These findings were confirmed by repeating the experiments in a randomized study design. FMD returned to baseline values 72 h after the dive with pre-dive placebo, whereas for most cardiovascular parameters this occurred earlier (24-48 h). Right ventricular dysfunction and increased PAP lasted longer. Acute antioxidants attenuated arterial endothelial dysfunction after diving, while reduction in heart and pulmonary artery function were unchanged. Cardiovascular changes after diving are not fully reversed up to 3 days after a dive, suggesting longer lasting negative effects.

[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.

Predictor of left ventricular dysfunction after aortic valve replacement in mixed aortic valve disease.

PubMed

Egbe, Alexander C; Warnes, Carole A

2017-02-01

The fate of the left ventricle (LV) after aortic valve replacement (AVR) in mixed aortic valve disease (MAVD) is unknown. Patients with moderate-severe MAVD, ejection fraction ≥50%, and no coronary artery disease who underwent AVR were identified. Moderate-severe MAVD was defined as a combination of ≥moderate aortic stenosis and ≥moderate aortic regurgitation. Assessment for LVD was performed at 1 and 5years after AVR. The purpose of the study was to determine prevalence and predictors of early and late left ventricular dysfunction (LVD) defined as ejection fraction <50% at 1 and 5years post-AVR. The severity of LV hypertrophy was assessed using LV mass index (LVMI), while relative wall thickness (RWT) was used to determine the type of hypertrophy. RWT was calculated as (2×posterior wall thickness)/LV end-diastolic dimension (LVEDD). A RWT score ≥0.42 and <0.42 indicates concentric and eccentric hypertrophy respectively. Patients with MAVD (n=179); age 63±8years, males 134 (75%); underwent AVR at Mayo Clinic, 1994-2010. Early LVD occurred in 38(21%). Predictors of early LVD were LVMI/LVEDD >3.1 (HR 1.83, CI 1.59-1.98); RWT >0.46 (HR 2.16, CI 1.21-4.99); and older age (HR 1.62, CI 1.23-3.02). Assessment of LV function was performed in 124 patients at 5-years post-AVR, and late LVD was present in 29(23%). Predictors of late LVD were LVMI/LVEDD >3.1 (HR 1.77, CI 1.24-2.01) and RWT >0.46 (HR 1.65, CI 1.29-2.24). All-cause mortality occurred in 21(12%), and was more common in patients with LVMI/LVEDD >3.1 (P=0.043) and RWT >0.46 (P=0.029). Patients with postoperative LVD showed less regression of LV mass after AVR even after controlling for blood pressure. LVD can occur after AVR even in the setting of normal preoperative LV function and absence of coronary artery disease. Preoperative LV mass was predictive of LVD and should be taken into consideration when determining the timing of AVR. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Tako-tsubo cardiomyopathy observed in a patient with sepsis and transient hyperthyroidism.

PubMed

Sarullo, Filippo M; Americo, Luigi; Accardo, Salvatore; Cicero, Sergio; Schicchi, Rossella; Schirò, Maria; Castello, Antonio

2009-03-01

A 55-years-old woman, with a history of hypertension and ischemic stroke with residual left hemiparesis, was admitted to our hospital because of dyspnoea with clinical evidence of acute pulmonary edema. She was found to have a sinus tachycardia with ST-elevation in leads D1, aVL and V1-V4 in the electrocardiogram, and akinesis of the left ventricular apex with overall left ventricular systolic function being severely impaired and an ejection fraction of 28% on echocardiography. Orotracheal intubation was performed and mechanical ventilation was immediately started. Emergency cardiac catheterization was performed 2 h after the symptom onset. Coronary angiography showed no significant coronary artery disease. Blood analysis revealed an increase in the creatine kinase MB fraction, a significant positive detection in troponin T, a white blood cell count of 35000 per microliter, C-reactive protein of 59,9 mg/dl, and transient elevation in the concentration of free triiodothyronine, free thyroxine, thyroid globulin antibody, and thyroid peroxidase antibody. The symptoms improved during the next days, and follow-up echocardiography 18 days later showed complete resolution of the left ventricular dysfunction. These data suggest that tako-tsubo cardiomyopathy may be induced in patients with sepsis and transient hyperthyroidism.

Left ventricular mass index as a prognostic factor in patients with severe aortic stenosis and ventricular dysfunction.

PubMed

Fuster, Rafael García; Montero Argudo, José A; Albarova, Oscar Gil; Hornero Sos, Fernando; Cánovas López, Sergio; Bueno Codoñer, María; Buendía Miñano, José A; Rodríguez Albarran, Ignacio

2005-06-01

Ventricular dysfunction and high hypertrophy may influence surgical outcome in aortic stenosis. Our aim was to determine whether an excessive left ventricular mass index (LVMI) discriminates different risk profiles in aortic stenosis with low ventricular ejection fraction (LVEF). Three hundred and thirty-nine patients with severe aortic stenosis underwent valve replacement (Mar-1994 and Nov-2001). LVMI values over the superior quartile were considered increased. Mortality models were constructed in global and LVEF

Methamphetamine-associated cardiomyopathy: patterns and predictors of recovery.

PubMed

Voskoboinik, A; Ihle, J F; Bloom, J E; Kaye, D M

2016-06-01

Methamphetamine abuse is a growing public health problem, and increasing numbers of patients are admitted with methamphetamine-associated cardiomyopathy (MAC). We sought to characterise the patterns of this disease and identify predictors of recovery. We retrospectively studied consecutive patients diagnosed with MAC between January 2006 and July 2015. We identified 20 patients (14 males, 6 females) with mean age 35 ± 9 years. Most had very severe systolic dysfunction (mean left ventricular ejection fraction (LVEF) 19.7 ± 11.4%) at presentation with 14 requiring inotropes and 5 requiring mechanical support. The pattern of systolic dysfunction was global in 14 patients, while 6 patients had a 'reverse Takotsubo' (RT) pattern with severely hypokinetic basal-mid segments and apical preservation. RT patients were predominantly female, had a short history of methamphetamine abuse and had higher cardiac enzyme levels. Patients with global dysfunction tended to have mid-wall fibrosis on cardiac magnetic resonance imaging. On follow-up transthoracic echocardiography, 6 out of 19 (32%) had normalisation of LVEF (LVEF ≥ 50%) within 6 weeks. Smaller left ventricular and left atrial size, shorter duration of methamphetamine use and RT pattern appeared to predict early recovery. A subset of MAC patients, particularly those with a RT pattern and lesser ventricular dilatation have the potential for early recovery of ventricular function. By contrast, those with evidence of myocardial fibrosis and ventricular enlargement have limited scope for recovery. © 2016 Royal Australasian College of Physicians.

Eplerenone: a selective aldosterone receptor antagonist for patients with heart failure.

PubMed

Barnes, Brian J; Howard, Patricia A

2005-01-01

To evaluate the pharmacology, pharmacokinetics, safety, and clinical use of eplerenone in heart failure (HF). English-language MEDLINE searches were performed from 1966 to May 2004. Key words included eplerenone, aldosterone receptor antagonist, heart failure, myocardial infarction, left-ventricular dysfunction, and cost-effectiveness. Additional references were identified from bibliographies of selected articles. Human trials evaluating the efficacy, safety, and cost-effectiveness of aldosterone receptor antagonists in HF were evaluated. Eplerenone is the first selective aldosterone receptor antagonist. The drug is indicated to improve the survival of stable patients with left-ventricular systolic dysfunction (ejection fraction <40%) and clinical evidence of HF following acute myocardial infarction. Efficacy and safety in this population have been demonstrated in a large, randomized clinical trial. Eplerenone is associated with severe and sometimes life-threatening hyperkalemia. Patients with reduced renal function and diabetes, as well as those on other drugs that increase potassium levels, are at highest risk. Eplerenone is metabolized by the cytochrome P450 system and may interact with drugs that interfere with this system. A major advantage of eplerenone over the nonselective aldosterone receptor antagonist spironolactone is lack of binding to progesterone and androgen receptors, which is associated with drug-induced gynecomastia, breast pain, and impotence. The addition of eplerenone to traditional HF therapy has been shown to reduce morbidity and mortality in patients who develop left-ventricular dysfunction after acute myocardial infarction. Eplerenone's selectivity reduces sex hormone-related adverse effects. Despite these benefits, the overall cost-effectiveness has yet to be determined.

Quantification of coronary flow reserve in patients with ischaemic and non-ischaemic cardiomyopathy and its association with clinical outcomes.

PubMed

Majmudar, Maulik D; Murthy, Venkatesh L; Shah, Ravi V; Kolli, Swathy; Mousavi, Negareh; Foster, Courtney R; Hainer, Jon; Blankstein, Ron; Dorbala, Sharmila; Sitek, Arkadiusz; Stevenson, Lynne W; Mehra, Mandeep R; Di Carli, Marcelo F

2015-08-01

Patients with left ventricular systolic dysfunction frequently show abnormal coronary vascular function, even in the absence of overt coronary artery disease. Moreover, the severity of vascular dysfunction might be related to the aetiology of cardiomyopathy.We sought to determine the incremental value of assessing coronary vascular dysfunction among patients with ischaemic (ICM) and non-ischaemic (NICM) cardiomyopathy at risk for adverse cardiovascular outcomes. Coronary flow reserve (CFR, stress/rest myocardial blood flow) was quantified in 510 consecutive patients with rest left ventricular ejection fraction (LVEF) ≤45% referred for rest/stress myocardial perfusion PET imaging. The primary end point was a composite of major adverse cardiovascular events (MACE) including cardiac death, heart failure hospitalization, late revascularization, and aborted sudden cardiac death.Median follow-up was 8.2 months. Cox proportional hazards model was used to adjust for clinical variables. The annualized MACE rate was 26.3%. Patients in the lowest two tertiles of CFR (CFR ≤ 1.65) experienced higher MACE rates than those in the highest tertile (32.6 vs. 15.5% per year, respectively, P = 0.004), irrespective of aetiology of cardiomyopathy. Impaired coronary vascular function, as assessed by reduced CFR by PET imaging, is common in patients with both ischaemic and non-ischaemic cardiomyopathy and is associated with MACE. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

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.

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.

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.

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.

Impact of HIV Infection on Diastolic Function and Left Ventricular Mass

PubMed Central

Hsue, Priscilla Y.; Hunt, Peter W.; Ho, Jennifer E.; Farah, Husam H.; Schnell, Amanda; Hoh, Rebecca; Martin, Jeffrey N.; Deeks, Steven G.; Bolger, Ann F.

2010-01-01

Background HIV patients have increased risk for cardiovascular disease, but the underlying mechanisms remain unknown. The purpose of this study was to determine the prevalence of echocardiographic abnormalities among asymptomatic HIV-infected individuals compared to HIV-uninfected individuals. Methods/Results We performed echocardiography in 196 HIV-infected adults and 52 controls. Left ventricular ejection fraction (LVEF), left ventricular mass indexed to the body surface area (LVMI), and diastolic function were assessed according to American Society of Echocardiography standards. LVMI was higher in HIV-infected patients (77.2g/m2 in HIV patients vs. 66.5g/m2 in controls, p<0.0001). LVEF was similar in both groups. Eight(4%) of the HIV patients had evidence of LV systolic dysfunction (defined as an EF<50%) versus none of the controls; 97(50%) had mild diastolic dysfunction compared to 29% of the HIV-uninfected subjects (p=0.008). After adjustment for hypertension and race, HIV-infected participants had a mean 8g/m2 larger LVMI compared to controls (p=0.001). Higher LVMI was independently associated with lower nadir CD4 T cell count, suggesting that immunodeficiency may play a role in this process. After adjustment for age and traditional risk factors, HIV patients had a 2.4 greater odds of having diastolic dysfunction as compared to controls (p=0.019). Conclusions HIV-infected patients had a higher prevalence of diastolic dysfunction and higher LVMI compared to controls. These differences were not readily explained by differences in traditional risk factors and were independently associated with HIV infection. These results suggest that contemporary asymptomatic HIV patients manifest mild functional and morphological cardiac abnormalities which are independently associated with HIV infection. PMID:19933410

Routine Chest X-ray: Still Valuable for the Assessment of Left Ventricular Size and Function in the Era of Super Machines?

PubMed Central

Morales, Maria-Aurora; Prediletto, Renato; Rossi, Giuseppe; Catapano, Giosuè; Lombardi, Massimo; Rovai, Daniele

2012-01-01

Objectives: The development of technologically advanced, expensive techniques has progressively reduced the value of chest X-ray in clinical practice for the assessment of left ventricular (LV) dilatation and dysfunction. Although controversial data are reported on the role of this widely available technique in cardiac assessment, it is known that the cardio-thoracic ratio is predictive of risk of progression in the NYHA Class, hospitalization, and outcome in patients with LV dysfunction. This study aimed to evaluate the reliability of the transverse diameter of heart shadow [TDH] by chest X-ray for detecting LV dilatation and dysfunction as compared to Magnetic Resonance Imaging (MRI) performed for different clinical reasons. Materials and Methods: In 101 patients, TDH was measured in digital chest X-ray and LV volumes and ejection fraction (EF) by MRI, both exams performed within 2 days. Results: A direct correlation between TDH and end-diastolic volumes (r = .75, P<0.0001) was reported. TDH cut-off values of 14.5 mm in females identified LV end-diastolic volumes >150 mL (sensitivity: 82%, specificity: 69%); in males a cut-off value of 15.5 mm identified LV end-diastolic volumes >210 mL (sensitivity: 84%; specificity: 72%). A negative relation was found between TDH and LVEF (r = -.54, P<0.0001). The above cut-off values of TDH discriminated patients with LV systolic dysfunction – LVEF <35% (sensitivity and specificity: 67% and 57% in females; 76% and 59% in males, respectively). Conclusions: Chest X-ray may still be considered a reliable technique in predicting LV dilatation by the accurate measurement of TDH as compared to cardiac MRI. Technologically advanced, expensive, and less available imaging techniques should be performed on the basis of sound clinical requests. PMID:22754739

Routine Chest X-ray: Still Valuable for the Assessment of Left Ventricular Size and Function in the Era of Super Machines?

PubMed

Morales, Maria-Aurora; Prediletto, Renato; Rossi, Giuseppe; Catapano, Giosuè; Lombardi, Massimo; Rovai, Daniele

2012-01-01

The development of technologically advanced, expensive techniques has progressively reduced the value of chest X-ray in clinical practice for the assessment of left ventricular (LV) dilatation and dysfunction. Although controversial data are reported on the role of this widely available technique in cardiac assessment, it is known that the cardio-thoracic ratio is predictive of risk of progression in the NYHA Class, hospitalization, and outcome in patients with LV dysfunction. This study aimed to evaluate the reliability of the transverse diameter of heart shadow [TDH] by chest X-ray for detecting LV dilatation and dysfunction as compared to Magnetic Resonance Imaging (MRI) performed for different clinical reasons. In 101 patients, TDH was measured in digital chest X-ray and LV volumes and ejection fraction (EF) by MRI, both exams performed within 2 days. A direct correlation between TDH and end-diastolic volumes (r = .75, P<0.0001) was reported. TDH cut-off values of 14.5 mm in females identified LV end-diastolic volumes >150 mL (sensitivity: 82%, specificity: 69%); in males a cut-off value of 15.5 mm identified LV end-diastolic volumes >210 mL (sensitivity: 84%; specificity: 72%). A negative relation was found between TDH and LVEF (r = -.54, P<0.0001). The above cut-off values of TDH discriminated patients with LV systolic dysfunction - LVEF <35% (sensitivity and specificity: 67% and 57% in females; 76% and 59% in males, respectively). Chest X-ray may still be considered a reliable technique in predicting LV dilatation by the accurate measurement of TDH as compared to cardiac MRI. Technologically advanced, expensive, and less available imaging techniques should be performed on the basis of sound clinical requests.

Tei index correlates with tissue Doppler parameters and reflects neurohormonal activation in patients with an abnormal transmitral flow pattern.

PubMed

Greco, Stefania; Troisi, Federica; Brunetti, Natale Daniele; Di Biase, Matteo

2009-10-01

Tei index (TI) is a Doppler parameter which reflects combined systolic and diastolic function. We aimed to study the relationship between TI, both traditional and tissue Doppler imaging (TDI) echocardiographic parameters and neurohormonal profile in outpatients with diastolic dysfunction expressed by an abnormal transmitral flow pattern. A total of 67 consecutive outpatients with diastolic dysfunction (abnormal transmitral flow pattern) were studied; all patients underwent clinical evaluation, blood sampling for B-type natriuretic peptide (BNP) plasma assaying, echocardiography for the determination of left ventricular ejection fraction (LVEF), dP/dt, left atrium (LA) dimensions, longitudinal systolic (S) and diastolic wall velocities (E'and A'), TI measured with Doppler echocardiography, and mitral regurgitation (MR) quantified on a semicontinuous scale. TI values were significantly correlated with BNP levels (r = 0.33; P < 0.01), LVEF (r =-0.56; P < 0.001), dP/dt (r =-0.52; P < 0.01), S (r =-0.45; P < 0.001), E'(r =-0.36; P < 0.01), A'(r =-0.27; P < 0.05), LA volume (r = 0.35; P < 0.01), and MR (P for trend < 0.05). In a multivariate regression analysis, TI was an independent predictor of increased BNP levels (beta= 0.32; P < 0.05), even after correction for potential confounders. ROC analysis showed as values of TI >0.59 identified subjects with combined systolic and diastolic dysfunction with a sensitivity of 73.8% and a specificity of 71.4%. In outpatients with diastolic dysfunction, TI, an easy to perform parameter for global ventricular performance assessment, might be useful in identifying subjects with concomitant systolic impairment and neurohormonal activation.

Resting Heart Rate as Predictor for Left Ventricular Dysfunction and Heart Failure: The Multi-Ethnic Study of Atherosclerosis

PubMed Central

Opdahl, Anders; Venkatesh, Bharath Ambale; Fernandes, Veronica R. S.; Wu, Colin O.; Nasir, Khurram; Choi, Eui-Young; Almeida, Andre L. C.; Rosen, Boaz; Carvalho, Benilton; Edvardsen, Thor; Bluemke, David A.; Lima, Joao A. C.

2014-01-01

OBJECTIVE To investigate the relationship between baseline resting heart rate and incidence of heart failure (HF) and global and regional left ventricular (LV) dysfunction. BACKGROUND The association of resting heart rate to HF and LV function is not well described in an asymptomatic multi-ethnic population. METHODS Participants in the Multi-Ethnic Study of Atherosclerosis had resting heart rate measured at inclusion. Incident HF was registered (n=176) during follow-up (median 7 years) in those who underwent cardiac MRI (n=5000). Changes in ejection fraction (ΔEF) and peak circumferential strain (Δεcc) were measured as markers of developing global and regional LV dysfunction in 1056 participants imaged at baseline and 5 years later. Time to HF (Cox model) and Δεcc and ΔEF (multiple linear regression models) were adjusted for demographics, traditional cardiovascular risk factors, calcium score, LV end-diastolic volume and mass in addition to resting heart rate. RESULTS Cox analysis demonstrated that for 1 bpm increase in resting heart rate there was a 4% greater adjusted relative risk for incident HF (Hazard Ratio: 1.04 (1.02, 1.06 (95% CI); P<0.001). Adjusted multiple regression models demonstrated that resting heart rate was positively associated with deteriorating εcc and decrease in EF, even in analyses when all coronary heart disease events were excluded from the model. CONCLUSION Elevated resting heart rate is associated with increased risk for incident HF in asymptomatic participants in MESA. Higher heart rate is related to development of regional and global LV dysfunction independent of subclinical atherosclerosis and coronary heart disease. PMID:24412444

Pharmacologic inhibition of the enzymatic effects of tissue transglutaminase reduces cardiac fibrosis and attenuates cardiomyocyte hypertrophy following pressure overload.

PubMed

Shinde, Arti V; Su, Ya; Palanski, Brad A; Fujikura, Kana; Garcia, Mario J; Frangogiannis, Nikolaos G

2018-04-01

Tissue transglutaminase (tTG) is a multifunctional protein with a wide range of enzymatic and non-enzymatic functions. We have recently demonstrated that tTG expression is upregulated in the pressure-overloaded myocardium and exerts fibrogenic actions promoting diastolic dysfunction, while preventing chamber dilation. Our current investigation dissects the in vivo and in vitro roles of the enzymatic effects of tTG on fibrotic remodeling in pressure-overloaded myocardium. Using a mouse model of transverse aortic constriction, we demonstrated perivascular and interstitial tTG activation in the remodeling pressure-overloaded heart. tTG inhibition through administration of the selective small molecule tTG inhibitor ERW1041E attenuated left ventricular diastolic dysfunction and reduced cardiomyocyte hypertrophy and interstitial fibrosis in the pressure-overloaded heart, without affecting chamber dimensions and ejection fraction. In vivo, tTG inhibition markedly reduced myocardial collagen mRNA and protein levels and attenuated transcription of fibrosis-associated genes. In contrast, addition of exogenous recombinant tTG to fibroblast-populated collagen pads had no significant effects on collagen transcription, and instead increased synthesis of matrix metalloproteinase (MMP)3 and tissue inhibitor of metalloproteinases (TIMP)1 through transamidase-independent actions. However, enzymatic effects of matrix-bound tTG increased the thickness of pericellular collagen in fibroblast-populated pads. tTG exerts distinct enzymatic and non-enzymatic functions in the remodeling pressure-overloaded heart. The enzymatic effects of tTG are fibrogenic and promote diastolic dysfunction, but do not directly modulate the pro-fibrotic transcriptional program of fibroblasts. Targeting transamidase-dependent actions of tTG may be a promising therapeutic strategy in patients with heart failure and fibrosis-associated diastolic dysfunction. Copyright © 2018 Elsevier Ltd. All rights reserved.

Echocardiography Criteria for Structural Heart Disease in Patients With End-Stage Renal Disease Initiating Hemodialysis.

PubMed

Hickson, LaTonya J; Negrotto, Sara M; Onuigbo, Macaulay; Scott, Christopher G; Rule, Andrew D; Norby, Suzanne M; Albright, Robert C; Casey, Edward T; Dillon, John J; Pellikka, Patricia A; Pislaru, Sorin V; Best, Patricia J M; Villarraga, Hector R; Lin, Grace; Williams, Amy W; Nkomo, Vuyisile T

2016-03-15

Cardiovascular disease among hemodialysis (HD) patients is linked to poor outcomes. The Acute Dialysis Quality Initiative Workgroup proposed echocardiographic (ECHO) criteria for structural heart disease (SHD) in dialysis patients. The association of SHD with important patient outcomes is not well defined. This study sought to determine prevalence of ECHO-determined SHD and its association with survival among incident HD patients. We analyzed patients who began chronic HD from 2001 to 2013 who underwent ECHO ≤1 month prior to or ≤3 months following initiation of HD (n = 654). Mean patient age was 66 ± 16 years, and 60% of patients were male. ECHO findings that met 1 or more and ≥3 of the new criteria were discovered in 87% and 54% of patients, respectively. Over a median of 2.4 years, 415 patients died: 108 (26%) died within 6 months. Five-year mortality was 62%. Age- and sex-adjusted structural heart disease variables associated with death were left ventricular ejection fraction (LVEF) ≤45% (hazard ratio [HR]: 1.48; confidence interval [CI]: 1.20 to 1.83) and right ventricular (RV) systolic dysfunction (HR: 1.68; CI: 1.35 to 2.07). An additive of higher death risk included LVEF ≤45% and RV systolic dysfunction rather than neither (HR: 2.04; CI: 1.57 to 2.67; p = 0.53 for test for interaction). Following adjustment for age, sex, race, diabetic kidney disease, and dialysis access, RV dysfunction was independently associated with death (HR: 1.66; CI 1.34 to 2.06; p < 0.001). SHD was common in our HD study population, and RV systolic dysfunction independently predicted mortality. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Knockout of TRPV1 Exacerbates Left Ventricular Diastolic Dysfunction Induced by A High-fat Diet in Mice.

PubMed

Zhong, Beihua; Rubinstein, Jack; Ma, Shuangtao; Wang, Donna H

2018-05-03

Transient receptor potential vanilloid 1 (TRPV1) channels in sensory nerves have anti-oxidative properties and counteract obesity and diabetes that are associated with diastolic dysfunction with preserved ejection fraction. We tested the hypothesis that TRPV1 knockout exacerbates high-fat diet (HFD)-induced glucose intolerance and diastolic dysfunction. Trpv1-/- and wild-type (WT) mice were fed chow diet or HFD for 20 weeks. Then, we performed the intraperitoneal glucose tolerance test, measured the heart function through transthoracic echocardiography and Langendorff heart perfusion system, analyzed cardiac histology, and measured the myocardial superoxide production and the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. HFD increased body weight, heart weight, and levels of fasting glucose, insulin, and leptin in both strains, with no differences between two strains. HFD impaired glucose tolerance in both strains with a more profound effect in Trpv1-/- than WT mice. HFD increased left ventricular (LV) internal diameter in diastole in both strains, while increased LV posterior wall thickness in diastole in Trpv1-/- but not in WT mice. HFD increased LV end-diastolic pressure in both strains with a further increase in Trpv1-/- mice, while decreased -dP/dt in Trpv1-/- but not in WT mice. HFD-induced cardiac collagen deposition and superoxide production were enhanced in Trpv1-/- mice. HFD upregulated cardiac p22phox in both strains, while increased p47phox in Trpv1-/- but not in WT mice. In summary, TRPV1 knockout exacerbates HFD-induced glucose intolerance, cardiac oxidative stress and collagen deposition, leading to aggravated LV diastolic dysfunction. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Overweight female rats selectively breed for low aerobic capacity exhibit increased myocardial fibrosis and diastolic dysfunction

PubMed Central

Johnson, Megan S.; Ma, Lixin; Pulakat, Lakshmi; Mugerfeld, Irina; Hayden, Melvin R.; Garro, Mona; Knight, William; Britton, Steven L.; Koch, Lauren G.; Sowers, James R.

2012-01-01

The statistical association between endurance exercise capacity and cardiovascular disease suggests that impaired aerobic metabolism underlies the cardiovascular disease risk in men and women. To explore this connection, we applied divergent artificial selection in rats to develop low-capacity runner (LCR) and high-capacity runner (HCR) rats and found that disease risks segregated strongly with low running capacity. Here, we tested if inborn low aerobic capacity promotes differential sex-related cardiovascular effects. Compared with HCR males (HCR-M), LCR males (LCR-M) were overweight by 34% and had heavier retroperitoneal, epididymal, and omental fat pads; LCR females (LCR-F) were 20% heavier than HCR females (HCR-F), and their retroperitoneal, but not perireproductive or omental, fat pads were heavier as well. Unlike HCR-M, blood pressure was elevated in LCR-M, and this was accompanied by left ventricular (LV) hypertrophy. Like HCR-F, LCR-F exhibited normal blood pressure and LV weight as well as increased spontaneous cage activity compared with males. Despite normal blood pressures, LCR-F exhibited increased myocardial interstitial fibrosis and diastolic dysfunction, as indicated by increased LV stiffness, a decrease in the initial filling rate, and an increase in diastolic relaxation time. Although females exhibited increased arterial stiffness, ejection fraction was normal. Increased interstitial fibrosis and diastolic dysfunction in LCR-F was accompanied by the lowest protein levels of phosphorylated AMP-actived protein kinase [phospho-AMPK (Thr172)] and silent information regulator 1. Thus, the combination of risk factors, including female sex, intrinsic low aerobic capacity, and overweightness, promote myocardial stiffness/fibrosis sufficient to induce diastolic dysfunction in the absence of hypertension and LV hypertrophy. PMID:22345570

Significant effects of atrioventricular node ablation and pacemaker implantation on left ventricular function and long-term survival in patients with atrial fibrillation and left ventricular dysfunction.

PubMed

Ozcan, Cevher; Jahangir, Arshad; Friedman, Paul A; Munger, Thomas M; Packer, Douglas L; Hodge, David O; Hayes, David L; Gersh, Bernard J; Hammill, Stephen C; Shen, Win-Kuang

2003-07-01

Control of ventricular rate by atrioventricular node ablation and pacemaker implantation in patients with drug-refractory atrial fibrillation (AF) is associated with improved left ventricular (LV) function. The objective of this study was to determine the effect of atrioventricular node ablation on long-term survival in patients with AF and LV dysfunction. Survival was determined by the Kaplan-Meier method for 56 study patients with LV ejection fraction (EF) < or =40% who underwent atrioventricular node ablation and pacemaker implantation and 56 age- and gender-matched control patients with AF and LVEF >40%, and age- and gender-matched control subjects from Minnesota. Groups were compared using the log-rank test. In study patients (age 69 +/- 10 years; 45 men), LVEF was 26% +/- 8% and 34% +/- 13% (p <0.001) before and after ablation, respectively. During follow-up (40 +/- 23 months), 23 patients died. Observed survival was worse than that of normal subjects (p <0.001) and control patients (p = 0.005). After ablation, LVEF nearly normalized (> or =45%) in 16 study patients (29%), in whom observed survival was comparable to that of normal subjects (p = 0.37). Coronary artery disease, hyperlipidemia, chronic renal failure, previous myocardial infarction, and coronary artery operation were independent predictors for mortality. Near normalization of LVEF occurred in 29% of study patients, suggesting that AF-induced EF reduction is reversible in many patients. Normal survival in patients with reversible LV dysfunction highlights potential survival benefits of rate control. Poor survival in patients with persistent LV dysfunction confirms the importance of optimal medical therapy.

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.

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).

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.

Cardiac dysfunction in the diabetic rat: quantitative evaluation using high resolution magnetic resonance imaging.

PubMed

Loganathan, Rajprasad; Bilgen, Mehmet; Al-Hafez, Baraa; Alenezy, Mohammed D; Smirnova, Irina V

2006-04-04

Diabetes is a major risk factor for cardiovascular disease. In particular, type 1 diabetes compromises the cardiac function of individuals at a relatively early age due to the protracted course of abnormal glucose homeostasis. The functional abnormalities of diabetic myocardium have been attributed to the pathological changes of diabetic cardiomyopathy. In this study, we used high field magnetic resonance imaging (MRI) to evaluate the left ventricular functional characteristics of streptozotocin treated diabetic Sprague-Dawley rats (8 weeks disease duration) in comparison with age/sex matched controls. Our analyses of EKG gated cardiac MRI scans of the left ventricle showed a 28% decrease in the end-diastolic volume and 10% increase in the end-systolic volume of diabetic hearts compared to controls. Mean stroke volume and ejection fraction in diabetic rats were decreased (48% and 28%, respectively) compared to controls. Further, dV/dt changes were suggestive of phase sensitive differences in left ventricular kinetics across the cardiac cycle between diabetic and control rats. Thus, the MRI analyses of diabetic left ventricle suggest impairment of diastolic and systolic hemodynamics in this rat model of diabetic cardiomyopathy. Our studies also show that in vivo MRI could be used in the evaluation of cardiac dysfunction in this rat model of type 1 diabetes.

Clinical significance of noninvasive coronary flow reserve assessment in patients with ischemic heart disease.

PubMed

Taqueti, Viviany R; Di Carli, Marcelo F

2016-11-01

The importance of physiologic assessments in ischemic heart disease is well recognized. Coronary flow reserve (CFR) is a novel physiologic imaging biomarker that complements both anatomic and semiquantitative perfusion assessments of coronary artery disease (CAD) severity. Beyond this, assessment of CFR may provide clinical insights useful for refining diagnosis, prognosis, and eventually, management of patients along the full range of ischemic heart disease phenotypes, from multivessel obstructive CAD to diffuse coronary microvascular dysfunction. We begin by defining the concept of noninvasive CFR, specifically focusing on quantification of blood flow using PET, for which robust observational data exist. Next, we describe the continuum of cardiovascular risk by CFR values in patients across the anatomic spectrum of CAD, including those with diabetes, chronic kidney disease, and nonobstructive CAD and coronary microvascular dysfunction. Finally, we summarize the impact of CFR on prognosis, with a focus on future directions for management strategies and potential novel therapies, particularly in patients with very low CFR and less obstructive CAD. This latter phenotype may provide a critical link to understanding hidden biological risk of ischemic heart disease in vulnerable populations, including women and patients with heart failure with preserved ejection fraction, metabolic syndrome, cardio-oncologic complications, and inflammatory-related disease.

Initial Experience of Transaortic Catheter Venting in Patients with Venoarterial Extracorporeal Membrane Oxygenation for Cardiogenic Shock.

PubMed

Hong, Tae Hee; Byun, Joung Hun; Lee, Hee Moon; Kim, Yong Hwan; Kang, Gu-Hyun; Oh, Ju Hyeon; Hwang, Sang Won; Kim, Han Yong; Park, Jae Hong; Jung, Jae Jun

2016-01-01

Extracorporeal membrane oxygenation (ECMO) has become one of the often applied mechanical support for acute cardiogenic shock. During venoarterial (VA) ECMO support, left heart decompression should be considered when left ventricular (LV) distension develops with pulmonary edema and LV dysfunction. The aim of this study was to report the results of transaortic catheter venting (TACV), as an alternative venting method, performed during VA-ECMO in patients with acute cardiogenic shock. We retrospectively reviewed the records of seven patients who underwent both ECMO and TACV between February 2013 and February 2014. Extracorporeal membrane oxygenation was performed uneventfully, and TACV was introduced under transthoracic echocardiographic guidance in all cases. Hemodynamic parameters, LV ejection fraction, and LV end-diastolic dimension (LVEDD) were measured 24 hours after initiating TACV in survivors. There were no procedure-related complications. Four of the seven patients (58%) survived. Transaortic catheter venting led to an increase in mean blood pressure in all patients (p = 0.050). There was a significant difference between pre- and post-TACV-LVEDD (59 ± 14 vs. 50 ± 12 mm, p = 0.044), with a 10-23% reduction in LVEDD in survivors. Transaortic catheter venting might be an acceptable alternative to venting procedures and useful for LV recovery during VA-ECMO in patients with severe LV dysfunction.

Cardiac-restricted Overexpression of TRAF3 Interacting Protein 2 (TRAF3IP2) Results in Spontaneous Development of Myocardial Hypertrophy, Fibrosis, and Dysfunction *

PubMed Central

Sakamuri, Siva S. V. P.; Siddesha, Jalahalli M.; Saifudeen, Zubaida; Ma, Lixin; Siebenlist, Ulrich; Gardner, Jason D.; Chandrasekar, Bysani

2016-01-01

TRAF3IP2 (TRAF3 interacting protein 2; previously known as CIKS or Act1) is a key intermediate in the normal inflammatory response and the pathogenesis of various autoimmune and inflammatory diseases. Induction of TRAF3IP2 activates IκB kinase (IKK)/NF-κB, JNK/AP-1, and c/EBPβ and stimulates the expression of various inflammatory mediators with negative myocardial inotropic effects. To investigate the role of TRAF3IP2 in heart disease, we generated a transgenic mouse model with cardiomyocyte-specific TRAF3IP2 overexpression (TRAF3IP2-Tg). Echocardiography, magnetic resonance imaging, and pressure-volume conductance catheterization revealed impaired cardiac function in 2-month-old male transgenic (Tg) mice as evidenced by decreased ejection fraction, stroke volume, cardiac output, and peak ejection rate. Moreover, the male Tg mice spontaneously developed myocardial hypertrophy (increased heart/body weight ratio, cardiomyocyte cross-sectional area, GATA4 induction, and fetal gene re-expression). Furthermore, TRAF3IP2 overexpression resulted in the activation of IKK/NF-κB, JNK/AP-1, c/EBPβ, and p38 MAPK and induction of proinflammatory cytokines, chemokines, and extracellular matrix proteins in the heart. Although myocardial hypertrophy decreased with age, cardiac fibrosis (increased number of myofibroblasts and enhanced expression and deposition of fibrillar collagens) increased progressively. Despite these adverse changes, TRAF3IP2 overexpression did not result in cell death at any time period. Interestingly, despite increased mRNA expression, TRAF3IP2 protein levels and activation of its downstream signaling intermediates remained unchanged in the hearts of female Tg mice. The female Tg mice also failed to develop myocardial hypertrophy. In summary, these results demonstrate that overexpression of TRAF3IP2 in male mice is sufficient to induce myocardial hypertrophy, cardiac fibrosis, and contractile dysfunction. PMID:27466370

Right ventricular systolic dysfunction and vena cava dilatation precede alteration of renal function in adult patients undergoing cardiac surgery: An observational study.

PubMed

Guinot, Pierre Grégoire; Abou-Arab, Osama; Longrois, Dan; Dupont, Herve

2015-08-01

Several authors have suggested that right ventricular dysfunction (RVd) may contribute to renal dysfunction in nonsurgical patients. We tested the hypothesis that RVd diagnosed immediately after cardiac surgery may be associated with subsequent development of renal dysfunction and tried to identify the possible mechanisms. A single-centre, prospective observational study. Amiens University Hospital, France. All adult patients undergoing cardiac surgery were considered eligible for participation. Patients who had undergone pulmonary or tricuspid valve surgery, repeat surgery or who underwent immediate postoperative renal replacement therapy were excluded. Data from 74 patients were analysed. Left ventricular and right ventricular function were assessed before surgery and on admission to ICU by transthoracic echocardiography (TTE): left ventricular and right ventricular ejection fractions (LVEF/RVEF), tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (Sr(t)) and right ventricular dilatation. RVd was defined as values in the lowest quartile of at least two echocardiographic variables. Renal dysfunction was defined as an increase in serum creatinine concentration (sCr) on postoperative day 1. All right ventricular TTE variables decreased (P < 0.05) after surgery: RVEF from 50% (49 to 60) to 40% (35 to 50); TAPSE from 22.3 mm (19.4 to 25.3) to 12.2 mm (8.8 to 14.8); and Sr(t) from 15.0 cm s(-1) (12.0 to 18.0) to 8.1 cm s(-1) (6.3 to 9.2). Fourteen (19%) patients had right ventricular dilatation and RVd was present in 23 (31%) patients. Forty patients had a positive variation in sCr. In multivariate analysis, patients with RVd had an odds ratio (OR) of 12.7 [95% confidence interval (95% CI) 2.6 to 63.4, P = 0.02] for development of renal dysfunction. Renal dysfunction was associated with increased central venous pressure but was not associated with cardiac index (CI). These results suggest that early postoperative RVd is associated with a subsequent increase of sCr and that the mechanism involved is congestion (vena cava dilatation/elevated CVP) rather than decreased CI.

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.

Effect of percutaneous transvenous mitral commissurotomy on left atrial appendage function: an immediate and 6-month follow-up transesophageal Doppler study.

PubMed

Vijayvergiya, Rajesh; Sharma, Rajat; Shetty, Ranjan; Subramaniyan, Anand; Karna, Sunil; Chongtham, Dhanraj

2011-11-01

The left atrial appendage (LAA) is a common site of thrombus formation and is the source of systemic thromboembolism in patients with rheumatic mitral stenosis. LAA contractile dysfunction is a common finding in these patients. The aim of this study was to assess immediate and 6-month follow-up LAA function by transesophageal Doppler echocardiography in patients who underwent percutaneous transvenous mitral commissurotomy (PTMC). Forty-seven consecutive patients with symptomatic critical mitral stenosis who underwent PTMC were enrolled. All had underwent transthoracic and transesophageal echocardiography before, 24 hours after, and 6 months after PTMC. Pulse Doppler velocities of the LAA were measured, including peak early diastolic (E wave), peak late diastolic (A wave), and peak systolic (S wave). The corresponding tissue Doppler velocities of the LAA, including peak early diastolic (E(LAA)), peak late diastolic (A(LAA)), and peak systolic (S(LAA)), were also measured. LAA ejection fraction was measured using the modified Simpson's method. The mean age of the 47 enrolled patients was 31.7 ± 10.26 years. Thirty-eight patients were in sinus rhythm, and the remaining nine were in atrial fibrillation. PTMC was successful in all patients. The pulse Doppler velocities of the LAA at baseline, after PTMC, and at 6-month follow-up were as follows: for the E wave, 15.29 ± 2.26, 17.02 ± 2.25, and 17.97 ± 2.55 cm/sec, respectively (P < .001); for the A wave 22.45 ± 4.11, 24.19 ± 4.21, and 25.99 ± 4.51 cm/sec, respectively (P < .001); and for the S wave, 28.52 ± 4.37, 31.45 ± 5.37, and 33.06 ± 4.99 cm/sec, respectively (P < .001). The corresponding tissue Doppler velocities of LAA were as follows: for E(LAA), 4.65 ± 0.91, 5.28 ± 0.85, and 5.80 ± 0.84 cm/sec, respectively (P < .001); for A(LAA), 6.67 ± 1.12, 7.33 ± 1.17, and 7.88 ± 1.22 cm/sec, respectively (P < .001); and for S(LAA), 4.67 ± 1.12, 5.52 ± 1.18, 6.07 ± 1.11 cm/sec, respectively (P < .001). There was a nonsignificant increase in LAA ejection fraction (48.97 ± 8.14% vs 52.3 ± 13.76% vs 52.11 ± 16.3%, respectively, P = .052). On subgroup analysis between patients in sinus rhythm and those with atrial fibrillation, there was no significant difference for LAA ejection fraction and pulse and tissue Doppler velocities. Very good intraclass correlation of the LAA parameters was also observed for the reproducibility of the data. The present study shows contractile dysfunction of the LAA in patients with critical mitral stenosis, which significantly improved after PTMC, and a further improvement was observed at 6-month follow-up. Favorable 6-month improvements in LAA parameters suggest continuous structural remodeling of the LAA after PTMC, which is clinically attributed to the absence of thromboembolism. Although there was an improvement in LAA function, it was far below the normal range, suggesting a need for continuous long-term monitoring and management of thromboembolism in these patients. Copyright © 2011 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

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.

Cardiospecific CD36 suppression by lentivirus-mediated RNA interference prevents cardiac hypertrophy and systolic dysfunction in high-fat-diet induced obese mice.

PubMed

Zhang, Yijie; Bao, Mingwei; Dai, Mingyan; Wang, Xin; He, Wenbo; Tan, Tuantuan; Lin, Dandan; Wang, Wei; Wen, Ying; Zhang, Rui

2015-06-03

Fatty acid (FA) catabolism abnormality has been proved to play an important role in obesity-related cardiomyopathy. We hypothesized that cardiospecific suppression of CD36, the predominant membrane FA transporter, would protect against obesity-related cardiomyopathy. Four-wk-old male C57BL/6 J mice were fed with either high-fat-diet (HFD) or control-normal-diet for 2 wk. Then they were subjected to intramyocardial injection with recombinant lentiviral vectors containing short hairpin RNAs to selectively downregulate the expression of either cardiac CD36 or irrelevant gene by RNA interference. After a 10-wk continuation of the diet, biochemical, functional, morphological, histological, metabolic and molecular profiles were assessed. HFD administration elicited obesity, cardiac hypertrophy and systolic dysfunction accompanied with elevated serum levels of blood urea nitrogen (BUN), creatinine, fasting serum glucose (FSG), total cholesterol (TC) and triglyceride. Additionally, HFD consumption promoted lipid accumulation and reactive oxygen species (ROS) generation in the cardiomyocytes. Cardiospecific CD36 inhibition protected against HFD induced cardiac remodeling by decreasing heart/body weight ratio, increasing left ventricular (LV) ejection fraction and fractional shortening as well as normalizing LV diameter, without influencing body weight gain. Inhibition of cardiac CD36 also mitigated obesity induced alteration in BUN, creatinine and triglyceride, but had no effect on FSG or TC. Moreover, cardiospecific CD36 deficiency corrected myocardial lipid overaccumulation and intracellular ROS overproduction that were induced by HFD feeding. Cardiospecific CD36 inhibition protects against the aggravation of cardiac functional and morphological changes associated with HFD induced obesity. CD36 represents a potential therapeutic target for obesity cardiomyopathy.

Optimal right heart filling pressure in acute respiratory distress syndrome determined by strain echocardiography.

PubMed

Garcia-Montilla, Romel; Imam, Faryal; Miao, Mi; Stinson, Kathryn; Khan, Akram; Heitner, Stephen

2017-06-01

Right ventricular (RV) systolic dysfunction is common in acute respiratory distress syndrome (ARDS). While preload optimization is crucial in its management, dynamic fluid responsiveness indices lack reliability, and there is no consensus on target central venous pressure (CVP). We analyzed the utility of RV free wall longitudinal strain (RVFWS) in the estimation of optimal RV filling pressure in ARDS. A retrospective cross-sectional analysis of clinical data and echocardiograms of patients with ARDS was performed. Tricuspid annular plane systolic excursion (TAPSE), tricuspid peak systolic velocity (S'), RV fractional area change (RVFAC), RVFWS, CVP, systolic pulmonary artery pressure (SPAP), and left ventricular ejection fraction (LVEF) were measured. Fifty-one patients with moderate-severe ARDS were included. There were inverse correlations between CVP and TAPSE, S', RVFAC, RVFWS, and LVEF. The most significant was with RVFWS (r:.74, R 2 :.55, P:.00001). Direct correlations with creatinine and lactate were noted. Receiver operating characteristic analysis showed that RVFWS -21% (normal reference value) was associated with CVP: 13 mm Hg (AUC: 0.92, 95% CI: 0.83-1.00). Regression model analysis of CVP, and RVFWS interactions established an RVFWS range from -18% to -24%. RVFWS -24% corresponded to CVP: 11 mm Hg and RVFWS -18% to CVP: 15 mm Hg. Beyond a CVP of 15 mm Hg, biventricular systolic dysfunction rapidly ensues. Our data are the first to show that an RV filling pressure of 13±2 mm Hg-as by CVP-correlates with optimal RV mechanics as evaluated by strain echocardiography in patients with moderate-severe ARDS. © 2017, Wiley Periodicals, Inc.

Cannabidiol Protects against Doxorubicin-Induced Cardiomyopathy by Modulating Mitochondrial Function and Biogenesis.

PubMed

Hao, Enkui; Mukhopadhyay, Partha; Cao, Zongxian; Erdélyi, Katalin; Holovac, Eileen; Liaudet, Lucas; Lee, Wen-Shin; Haskó, György; Mechoulam, Raphael; Pacher, Pál

2015-01-06

Doxorubicin (DOX) is a widely used, potent chemotherapeutic agent; however, its clinical application is limited because of its dose-dependent cardiotoxicity. DOX's cardiotoxicity involves increased oxidative/nitrative stress, impaired mitochondrial function in cardiomyocytes/endothelial cells and cell death. Cannabidiol (CBD) is a nonpsychotropic constituent of marijuana, which is well tolerated in humans, with antioxidant, antiinflammatory and recently discovered antitumor properties. We aimed to explore the effects of CBD in a well-established mouse model of DOX-induced cardiomyopathy. DOX-induced cardiomyopathy was characterized by increased myocardial injury (elevated serum creatine kinase and lactate dehydrogenase levels), myocardial oxidative and nitrative stress (decreased total glutathione content and glutathione peroxidase 1 activity, increased lipid peroxidation, 3-nitrotyrosine formation and expression of inducible nitric oxide synthase mRNA), myocardial cell death (apoptotic and poly[ADP]-ribose polymerase 1 [PARP]-dependent) and cardiac dysfunction (decline in ejection fraction and left ventricular fractional shortening). DOX also impaired myocardial mitochondrial biogenesis (decreased mitochondrial copy number, mRNA expression of peroxisome proliferator-activated receptor γ coactivator 1-alpha, peroxisome proliferator-activated receptor alpha, estrogen-related receptor alpha), reduced mitochondrial function (attenuated complex I and II activities) and decreased myocardial expression of uncoupling protein 2 and 3 and medium-chain acyl-CoA dehydrogenase mRNA. Treatment with CBD markedly improved DOX-induced cardiac dysfunction, oxidative/nitrative stress and cell death. CBD also enhanced the DOX-induced impaired cardiac mitochondrial function and biogenesis. These data suggest that CBD may represent a novel cardioprotective strategy against DOX-induced cardiotoxicity, and the above-described effects on mitochondrial function and biogenesis may contribute to its beneficial properties described in numerous other models of tissue injury.

Cannabidiol Protects against Doxorubicin-Induced Cardiomyopathy by Modulating Mitochondrial Function and Biogenesis

PubMed Central

Hao, Enkui; Mukhopadhyay, Partha; Cao, Zongxian; Erdélyi, Katalin; Holovac, Eileen; Liaudet, Lucas; Lee, Wen-Shin; Haskó, György; Mechoulam, Raphael; Pacher, Pál

2015-01-01

Doxorubicin (DOX) is a widely used, potent chemotherapeutic agent; however, its clinical application is limited because of its dose-dependent cardiotoxicity. DOX’s cardiotoxicity involves increased oxidative/nitrative stress, impaired mitochondrial function in cardiomyocytes/endothelial cells and cell death. Cannabidiol (CBD) is a nonpsychotropic constituent of marijuana, which is well tolerated in humans, with antioxidant, antiinflammatory and recently discovered antitumor properties. We aimed to explore the effects of CBD in a well-established mouse model of DOX-induced cardiomyopathy. DOX-induced cardiomyopathy was characterized by increased myocardial injury (elevated serum creatine kinase and lactate dehydrogenase levels), myocardial oxidative and nitrative stress (decreased total glutathione content and glutathione peroxidase 1 activity, increased lipid peroxidation, 3-nitrotyrosine formation and expression of inducible nitric oxide synthase mRNA), myocardial cell death (apoptotic and poly[ADP]-ribose polymerase 1 [PARP]-dependent) and cardiac dysfunction (decline in ejection fraction and left ventricular fractional shortening). DOX also impaired myocardial mitochondrial biogenesis (decreased mitochondrial copy number, mRNA expression of peroxisome proliferator-activated receptor γ coactivator 1-alpha, peroxisome proliferator-activated receptor alpha, estrogen-related receptor alpha), reduced mitochondrial function (attenuated complex I and II activities) and decreased myocardial expression of uncoupling protein 2 and 3 and medium-chain acyl-CoA dehydrogenase mRNA. Treatment with CBD markedly improved DOX-induced cardiac dysfunction, oxidative/nitrative stress and cell death. CBD also enhanced the DOX-induced impaired cardiac mitochondrial function and biogenesis. These data suggest that CBD may represent a novel cardioprotective strategy against DOX-induced cardiotoxicity, and the above-described effects on mitochondrial function and biogenesis may contribute to its beneficial properties described in numerous other models of tissue injury. PMID:25569804

Diagnostic and prognostic value of right ventricular strain in patients with pulmonary arterial hypertension and relatively preserved functional capacity studied with echocardiography and magnetic resonance.

PubMed

da Costa Junior, Augusto Alberto; Ota-Arakaki, Jaquelina Sonoe; Ramos, Roberta Pulcheri; Uellendahl, Marly; Mancuso, Frederico José Neves; Gil, Manuel Adan; Fischer, Cláudio Henrique; Moises, Valdir Ambrosio; de Camargo Carvalho, Antonio Carlos; Campos, Orlando

2017-01-01

Right ventricular (RV) dysfunction harbingers adverse prognosis in pulmonary arterial hypertension (PAH). Although conventional two-dimensional echocardiography (2DE) is limited for RV systolic function quantitation, RV strain can be a useful tool. The diagnostic and prognostic impact of 2DE speckle-tracking RV longitudinal strain was evaluated, including other 2DE systolic indexes, in a group of PAH patients without severe impairment of functional capacity, chronic pulmonary thromboembolism or left ventricular dysfunction. Sixty-six group I PAH patients, 67 % NYHA functional class I or II (none in IV) were studied by 2DE to obtain: RV fractional area change, tricuspid annular plane systolic excursion, RV myocardial performance index, tissue Doppler tricuspid annulus systolic velocity. Global, free wall (RVFreeWSt) and septal RV longitudinal systolic strain were obtained. RV ejection fraction by cardiac magnetic resonance (CMR-RVEF) was also assessed. All patients were followed up to 3.9 years (mean 3.3 years). Combined endpoints were hospitalization for worsening PAH or cardiovascular death. Among all the 2DE indexes of RV systolic function, RVFreeWSt exhibited the best correlation with CMR-RVEF (r = 0.83; p < 0.005). Combined endpoints occurred in 15 (22.7 %) patients (6 hospitalizations and 9 deaths). Multivariate analysis identified RVFreeWSt ≤-14 % as the only 2DE independent variable associated with combined endpoints [HR 4.66 (1.25-17.37); p < 0.05]. We conclude that RVFreeWSt may be a suitable non-geometric 2DE surrogate of CMR-RVEF in PAH patients, constituting a powerful independent predictor of long-term outcome in this cohort with relatively preserved functional capacity.

Right ventricular end-systolic area as a simple first-line marker predicting right ventricular enlargement and decreased systolic function in children referred for cardiac magnetic resonance imaging.

PubMed

Barczuk-Falęcka, M; Małek, Ł A; Roik, D; Werys, K; Werner, B; Brzewski, M

2018-06-01

To assess the accuracy of simple cardiovascular magnetic resonance imaging (CMR) parameters for first-line analysis of right ventricle (RV) dysfunction in children to identify those who require in-depth analysis and those in whom simple assessment is sufficient. Sixty paediatric CMR studies were analysed. The following CMR parameters were measured: RV end-diastolic and end-systolic area (4CH EDA and 4CH ESA), fractional area change (FAC), RV diameter in end-diastole (RVD1), tricuspid annular plane systolic excursion (TAPSE), and RV outflow tract diameter in end-diastole (RVOT prox). They were correlated with RV end-diastolic volume (RVEDVI) and RV ejection fraction (RVEF). RVEDVI correlated best with 4CH ESA (r=0.85, <0.001) and EDA (r=0.82, <0.001). For RVEF only a moderate reverse correlation was found for 4CH ESA (-0.56, <0.001), 4CH EDA (-0.49, 0.001) and positive correlation for FAC (0.49, <0.001). There was no correlation between TAPSE and RVEF and only weak between RVD1 and RVEDVI. A 4CH ESA cut-off value of 8.5 cm 2 /m 2 had a very high diagnostic accuracy for predicting an enlarged RV (AUC=0.912, p<0.001, sensitivity 92.3%, specificity 79%) and a cut-off value of 10.5 cm 2 /m 2 was also a good predictor of depressed RV systolic function (AUC=0.873, p<0.001, sensitivity 83%, specificity 89%). For routine screening in clinical practice, 4CH ESA seems a reliable and easy method to identify patients with RV dysfunction. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2016-01-01

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

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.

Saxagliptin Prevents Increased Coronary Vascular Stiffness in Aortic-Banded Mini Swine.

PubMed

Fleenor, Bradley S; Ouyang, An; Olver, T Dylan; Hiemstra, Jessica A; Cobb, Melissa S; Minervini, Gianmaria; Emter, Craig A

2018-06-11

Increased peripheral conduit artery stiffness has been shown in patients with heart failure (HF) with preserved ejection fraction. However, it is unknown whether this phenomenon extends to the coronary vasculature. HF with preserved ejection fraction may be driven, in part, by coronary inflammation, and inhibition of the enzyme DPP-4 (dipeptidyl-peptidase 4) reduces inflammation and oxidative stress. The purpose of this study was to determine the effect of saxagliptin-a DPP-4 inhibitor-on coronary stiffness in aortic-banded mini swine. We hypothesized saxagliptin would prevent increased coronary artery stiffness in a translational swine model with cardiac features of HF with preserved ejection fraction by inhibiting perivascular adipose tissue inflammation. Yucatan mini swine were divided into 3 groups: control, aortic-banded untreated HF, and aortic-banded saxagliptin-treated HF. Ex vivo mechanical testing was performed on the left circumflex and right coronary arteries, and advanced glycation end product, NF-κB (nuclear factor-κB), and nitrotyrosine levels were measured. An increase in the coronary elastic modulus of HF animals was associated with increased vascular advanced glycation end products, NF-κB, and nitrotyrosine levels compared with control and prevented by saxagliptin treatment. Aortas from healthy mice were treated with media from swine perivascular adipose tissue culture to assess its role on vascular stiffening. Conditioned media from HF and saxagliptin-treated HF animals increased mouse aortic stiffness; however, only perivascular adipose tissue from the HF group showed increased advanced glycation end products and NF-κB levels. In conclusion, our data show increased coronary conduit vascular stiffness was prevented by saxagliptin and associated with decreased advanced glycation end products, NF-κB, and nitrotyrosine levels in a swine model with potential relevance to HF with preserved ejection fraction. © 2018 American Heart Association, Inc.

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

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.

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.

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.

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.

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.

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.

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.

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

Cardio-oncology: a multidisciplinary approach for detection, prevention and management of cardiac dysfunction in cancer patients.

PubMed

Tajiri, Kazuko; Aonuma, Kazutaka; Sekine, Ikuo

2017-08-01

Cardiac dysfunction that develops during or after completion of cancer therapy is a growing health concern that should be addressed in a multidisciplinary setting. Cardio-oncology is a new discipline that focuses on screening, monitoring and treating cardiovascular disease during and after cancer treatment. A baseline cardiovascular risk assessment is essential. For high-risk patients, a tailored and detailed plan for cardiovascular management throughout treatment and beyond should also be established. Anthracycline and/or trastuzumab-containing chemotherapy and chest-directed radiation therapy are well known cardiotoxic cancer therapies. Monitoring for the development of subclinical cardiotoxicity is crucial for the prevention of clinical heart failure. Detecting a decreased left ventricular ejection fraction after cancer therapy might be a late finding; therefore, earlier markers of cardiac injury are being actively explored. Abnormal myocardial strain and increased serum cardiac biomarkers (e.g. troponins and natriuretic peptides) are possible candidates for this purpose. An important method for preventing heart failure is the avoidance or minimization of the use of cardiotoxic therapies. Decisions must balance the anti-tumor efficacy of the treatment with its potential cardiotoxicity. If patients develop cardiac dysfunction or heart failure, they should be treated in accordance with established guidelines for heart failure. Cancer survivors who have been exposed to cardiotoxic cancer therapies are at high risk of developing heart failure. The management of cardiovascular risk factors and periodic screening with cardiac imaging and biomarkers should be considered in high-risk survivors. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Risk Stratification of Future Left Ventricular Dysfunction for Patients with Indications for Right Ventricular Pacing due to Bradycardia.

PubMed

Ooka, Junichi; Tanaka, Hidekazu; Hatani, Yutaka; Hatazawa, Keiko; Matsuzoe, Hiroki; Shimoura, Hiroyuki; Sano, Hiroyuki; Sawa, Takuma; Motoji, Yoshiki; Mochizuki, Yasuhide; Ryo-Koriyama, Keiko; Matsumoto, Kensuke; Fukuzawa, Koji; Hirata, Ken-Ichi

2017-10-21

Although right ventricular (RV) pacing is the only effective treatment for patients with symptomatic bradycardia, it creates left ventricular (LV) dyssynchrony, which can induce LV dysfunction and heart failure. The current criterion for consideration of cardiac resynchronization therapy (CRT) is LV ejection fraction (LVEF) ≤ 35%, but indication for CRT in patients required for RV pacing with LVEF > 35% remains unclear.We studied 40 patients, all LVEF ≥ 35%, who had undergone implantable cardioverter-defibrillator implantation with RV pacing < 5%. Echocardiography was performed at baseline and during RV pacing. LV dyssynchrony was defined as anteroseptal-to-posterior wall delay from the mid-LV short-axis view using two-dimensional speckle-tracking radial strain (significant: ≥ 130 ms). Patients were divided into two groups based on baseline LVEF: normal LVEF ( ≥ 50%; n = 20) and mildly reduced LVEF (35-50%; n = 20).LVEF and LV dyssynchrony in patients with mildly reduced LVEF deteriorated significantly during RV pacing compared to those in patients with normal LVEF. Moreover, changes in LV dyssynchrony during RV pacing significantly correlated with changes in LVEF (r = -0.44, P < 0.01). Multivariate logistic regression analysis showed that baseline LVEF was the only independent predictor and baseline LVEF < 48% predictive of significant LV dyssynchrony during RV pacing.The extent of RV pacing-induced LV dysfunction may be associated with baseline LV function. These adverse effects on patients with mildly reduced LVEF of 35-50% and indications for RV pacing due to bradycardia can thus be prevented by CRT.

Left ventricular remodelling in patients with moderate systolic dysfunction after myocardial infarction: favourable effects of exercise training and predictive role of N-terminal pro-brain natriuretic peptide.

PubMed

Giallauria, Francesco; Cirillo, Plinio; Lucci, Rosa; Pacileo, Mario; De Lorenzo, Anna; D'Agostino, Mariantonietta; Moschella, Sabino; Psaroudaki, Marianna; Del Forno, Domenico; Orio, Francesco; Vitale, Dino Franco; Chiariello, Massimo; Vigorito, Carlo

2008-02-01

To investigate the effects of exercise training (ET) on left ventricular (LV) volumes, cardiopulmonary functional capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in postinfarction patients with moderate LV dysfunction. Sixty-one postinfarction patients were randomized into two groups: group T [n=30, LV ejection fraction (EF) 41.6+/-11.3%, mean+/-SD] entered a 6-month ET programme, whereas group C (n=31, EF 42.0+/-7.6%, P=NS) did not. NT-proBNP assay, Doppler-echocardiography and cardiopulmonary exercise test were performed upon enrolment and at sixth months. At sixth months, trained patients showed an improvement in workload (+26%, P<0.001), Vo2peak (+31%, P<0.001), LV end-diastolic volume index (LVEDVI; -9%, P<0.001), a reduction in NT-proBNP (-71%, P<0.001) and a significant correlation between changes in NT-proBNP and in LVEDVI (r=0.858, P<0.001). Baseline NT-proBNP correlated with changes in LVEDVI in both trained (r=0.673, P<0.001) and untrained (r=0.623, P<0.001) patients. Group C showed unfavourable LVEDVI dilation (+8%, P<0.001; T vs. C group, P<0.001) and a smaller reduction in NT-proBNP (-40%, P<0.001; T vs. C group, P<0.001). Six month ET induced a favourable LV remodelling and a marked fall in NT-proBNP that could predict LV remodelling in postinfarction patients with moderate LV dysfunction.

Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death.

PubMed

Fischer, D; Rossa, S; Landmesser, U; Spiekermann, S; Engberding, N; Hornig, B; Drexler, H

2005-01-01

Endothelial dysfunction of coronary and peripheral arteries has been demonstrated in patients with chronic heart failure (CHF) and appears to be associated with functional implications. However, it is unknown whether endothelial dysfunction in CHF is independently associated with impaired outcome or progression of the disease. We assessed the follow-up of 67 consecutive patients with CHF [New York Heart Association (NYHA) functional class II-III] in which flow-dependent, endothelium-mediated vasodilation (FDD) of the radial artery was assessed by high resolution ultrasound. The primary endpoint was defined by cardiac death, hospitalization due to worsening of heart failure (NYHA class IV, pulmonary oedema), or heart transplantation. Cox regression analysis was used to determine whether FDD was associated with these heart failure-related events. During a median follow-up of 45.7 months 24 patients had an event: 18 patients were hospitalized due to worsening of heart failure or heart transplantation, six patients died for cardiac reasons. Cox regression analysis demonstrated that FDD (P<0.01), diabetes mellitus (P<0.01), and ejection fraction (P<0.01) were independent predictive factors for the occurrence of the primary endpoint. The Kaplan-Meier survival curve revealed a significantly better clinical outcome in patients with FDD above the median (6.2%) compared with those with FDD below the median (P<0.013). These observations suggest that endothelium-mediated vasodilation represents an independent predictor of cardiac death and hospitalization in patients with CHF, consistent with the notion that endothelium-derived nitric oxide may play a protective role in heart failure.

Myocardial oedema as the sole marker of acute injury in Takotsubo cardiomyopathy: a cardiovascular magnetic resonance (CMR) study.

PubMed

Iacucci, Ilaria; Carbone, Iacopo; Cannavale, Giuseppe; Conti, Bettina; Iampieri, Ilaria; Rosati, Riccardo; Sardella, Gennaro; Frustaci, Andrea; Fedele, Francesco; Catalano, Carlo; Francone, Marco

2013-12-01

The main hallmark of Takotsubo cardiomyopathy (TT-CMP) is transient ischaemia, with completely reversible regional contractile dysfunction, which involves the mid-apical segments and shows no angiographic signs of coronary artery disease (CAD). The acute and reversible myocardial injury suggests that tissue oedema may be an important marker of disease. Seventeen patients with a clinical and angiographic diagnosis of TT-CMP underwent cardiovascular magnetic resonance (CMR) imaging in the acute phase and at follow-up after 4 months. A standard acquisition protocol including turbo spin echo (TSE) T2-weighted short-tau inversion-recovery (T2 STIR), steady-state free-precession cine (SSFP cine) and lateenhancement (LE) imaging after gadolinium benzyloxypropionic tetraacetic acid (Gd-BOPTA) administration was performed. All images were analysed, and data on oedema and LE were correlated with regional dysfunction and histological findings from endomyocardial biopsy (EMB) where available. In all patients, T2 STIR images showed a diffuse homogeneous hyperintensity that extended to all mid-apical segments and perfectly matched the area of regional dysfunction, reflecting tissue oedema. In the five patients who underwent EMB, histology confirmed the massive interstitial oedema associated with typical contraction-band necrosis. No cases of LE were observed. At follow-up, complete regression of oedema was observed in all cases, with significant recovery of regional and global left ventricular (LV) function (ejection fraction from 48.7% to 59.8%). Myocardial oedema on CMR is a characteristic feature of acute TT-CMP, which reflects acute inflammation and acute myocardial injury. It could therefore be used as a specific marker of disease severity.

The VO(2)-on kinetics in constant load exercise sub-anaerobic threshold reflects endothelial function and dysfunction in muscle microcirculation.

PubMed

Maione, D; Cicero, A Fg; Bacchelli, S; Cosentino, E R; Degli Esposti, D; Manners, D N; Rinaldi, E R; Rosticci, M; Senaldi, R; Ambrosioni, E; Borghi, C

2015-01-01

To propose a test to evaluate endothelial function, based on VO(2) on-transition kinetics in sub-anaerobic threshold (AT) constant load exercise, we tested healthy subjects and patients with ischemic-hypertensive cardiopathy by two cardiopulmonary tests on a cycle ergometer endowed with an electric motor to overcome initial inertia: a pre-test and, after at least 24 h, one 6 min constant load exercise at 90 % AT. We measured net phase 3 VO(2)-on kinetics and, by phase 2 time constant (tau), valued endothelial dysfunction. We found shorter tau in repeated tests, shorter time between first and second test, by persisting endothelium-dependent arteriolar vasodilatation and/or several other mechanisms. Reducing load to 80 % and 90 % AT did not produce significant changes in tau of healthy volunteers, while in heart patients an AT load of 70 %, compared to 80 % AT, shortened tau (delta=4.38+/-1.65 s, p=0.013). In heart patients, no correlation was found between NYHA class, ejection fraction (EF), and the two variables derived from incremental cycle cardio-pulmonary exercise, as well as between EF and tau; while NYHA class groups were well correlated with tau duration (r=0.92, p=0.0001). Doxazosin and tadalafil also significantly reduced tau. In conclusion, the O(2) consumption kinetics during the on-transition of constant load exercise below the anaerobic threshold are highly sensitive to endothelial function in muscular microcirculation, and constitute a marker for the evaluation of endothelial dysfunction.

Relationship of Office and Ambulatory Blood Pressure With Left Ventricular Global Longitudinal Strain.

PubMed

Sera, Fusako; Jin, Zhezhen; Russo, Cesare; Lee, Edward S; Schwartz, Joseph E; Rundek, Tatjana; Elkind, Mitchell S V; Homma, Shunichi; Sacco, Ralph L; Di Tullio, Marco R

2016-11-01

Left ventricular (LV) global longitudinal strain (GLS) is an early indicator of subclinical cardiac dysfunction, even when LV ejection fraction (LVEF) is normal, and is an independent predictor of cardiovascular events. Ambulatory blood pressure (BP) is a better predictor of cardiovascular events, including heart failure, than office BP. We investigated the association of office and ambulatory BP measurements with subclinical LV systolic dysfunction in a community-based cohort with normal LVEF. Two-dimensional speckle-tracking echocardiography and 24-hour ambulatory BP monitoring were performed in 577 participants (mean age 70±9 years; 60% women) with LVEF ≥50% from the Cardiovascular Abnormalities and Brain Lesions (CABL) study. Univariable and multivariable linear regression analyses were used to assess the associations of BP measures with GLS. Higher ambulatory and office BP values were consistently associated with impaired GLS. After adjustment for pertinent covariates (age, sex, race/ethnicity, body mass index, diabetes mellitus, coronary artery disease, LV mass index, and antihypertensive medication), office diastolic BP and ambulatory systolic and diastolic BPs (24-hour, daytime and nighttime) were independently associated with GLS (P = 0.003 for office DBP, P ≤ 0.001 for all ambulatory BPs). When ambulatory and office BP values were included in the same model, all ambulatory BP measures remained significantly associated with GLS (all P < 0.01), whereas office BP values were not. Ambulatory BP values are significantly associated with impaired GLS and the association is stronger than for office BP. Ambulatory BP monitoring might have a role in the risk stratification of hypertensive patients for early LV dysfunction.

Prominent left ventricular trabeculations in competitive athletes: A proposal for risk stratification and management.

PubMed

Caselli, Stefano; Ferreira, Diana; Kanawati, Eyad; Di Paolo, Fernando; Pisicchio, Cataldo; Attenhofer Jost, Christine; Spataro, Antonio; Jenni, Rolf; Pelliccia, Antonio

2016-11-15

Recently, an unexpectedly large prevalence of Left Ventricular Non Compaction (LVNC) has been reported in athletes, raising the question of the appropriateness of current diagnostic criteria. We sought to describe prevalence and clinical characteristics of athletes with suspected LVNC in a large cohort of Olympic athletes. Over 29months, 2501 consecutive athletes underwent a cardiac evaluation including physical examination, ECG, exercise test and echocardiography. Additional investigations (Cardiac Magnetic Resonance and/or genetic testing) were selectively performed in athletes with abnormal ECGs, ventricular arrhythmias, borderline LV dysfunction or positive family history. Of the 2501 athletes, 36 (1.4%) showed prominent trabeculations suggestive for LVNC. Of these, 3 (0.1%) were considered to be affected by LVNC, based on presence of LV dysfunction (ejection fraction<50%) and/or positive family history and genetic testing; these athletes were cautiously restricted from competitions and entered a clinical follow-up program. The remaining 33 athletes, in the absence of LV impairment or familial cardiac diseases, were considered normal (n=24) or unlikely affected (n=9), regardless of the extent of the trabeculations. In a large athlete population, a marked LV trabecular pattern was seen in 1.4%. Only a small subset of these athletes (0.1%) showed familial, clinical and morphologic changes supporting the diagnosis of LVNC. In the vast majority of the athletes, the increased trabeculations were not associated with LV dysfunction and/or positive family history, likely representing a morphologic LV variant, deprived of clinical significance. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Evaluation of mechanical dyssynchrony and myocardial perfusion using phase analysis of gated SPECT imaging in patients with left ventricular dysfunction

PubMed Central

Trimble, Mark A.; Borges-Neto, Salvador; Honeycutt, Emily F.; Shaw, Linda K.; Pagnanelli, Robert; Chen, Ji; Iskandrian, Ami E.; Garcia, Ernest V.; Velazquez, Eric J.

2010-01-01

Background Using phase analysis of gated single photon emission computed tomography (SPECT) imaging, we examined the relation between myocardial perfusion, degree of electrical dyssynchrony, and degree of SPECT-derived mechanical dyssynchrony in patients with left ventricular (LV) dysfunction. Methods and Results We retrospectively examined 125 patients with LV dysfunction and ejection fraction of 35% or lower. Fourier analysis converts regional myocardial counts into a continuous thickening function, allowing resolution of phase of onset of myocardial thickening. The SD of LV phase distribution (phase SD) and histogram bandwidth describe LV phase dispersion as a measure of dyssynchrony. Heart failure (HF) patients with perfusion abnormalities ities have higher degrees of dyssynchrony measured by median phase SD (45.5° vs 27.7°, P < .0001) and bandwidth (117.0° vs 73.0°, P = .0006). HF patients with prolonged QRS durations have higher degrees of dyssynchrony measured by median phase SD (54.1° vs 34.7°, P < .0001) and bandwidth (136.5° vs 99.0°, P = .0005). Mild to moderate correlations exist between QRS duration and phase analysis indices of phase SD (r = 0.50) and bandwidth (r = 0.40). Mechanical dyssynchrony (phase SD >43°) was 43.2%. Conclusions HF patients with perfusion abnormalities or prolonged QRS durations QRS durations have higher degrees of mechanical dyssynchrony. Gated SPECT myocardial perfusion imaging can quantify myocardial function, perfusion, and dyssynchrony and may help in evaluating patients for cardiac resynchronization therapy. PMID:18761269

Cardiac dysfunction and ferritin as early markers of severity in pediatric sepsis.

PubMed

Tonial, Cristian T; Garcia, Pedro Celiny R; Schweitzer, Louise Cardoso; Costa, Caroline A D; Bruno, Francisco; Fiori, Humberto H; Einloft, Paulo R; Garcia, Ricardo Branco; Piva, Jefferson Pedro

The aim of this study was to verify the association of echocardiogram, ferritin, C-reactive protein, and leukocyte count with unfavorable outcomes in pediatric sepsis. A prospective cohort study was carried out from March to December 2014, with pediatric critical care patients aged between 28 days and 18 years. Inclusion criteria were diagnosis of sepsis, need for mechanical ventilation for more than 48h, and vasoactive drugs. Serum levels of C-reactive protein, ferritin, and leukocyte count were collected on the first day (D0), 24h (D1), and 72h (D3) after recruitment. Patients underwent transthoracic echocardiography to determine the ejection fraction of the left ventricle on D1 and D3. The outcomes measured were length of hospital stay and in the pediatric intensive care unit, mechanical ventilation duration, free hours of VM, duration of use of inotropic agents, maximum inotropic score, and mortality. Twenty patients completed the study. Patients with elevated ferritin levels on D0 had also fewer ventilator-free hours (p=0.046) and higher maximum inotropic score (p=0.009). Patients with cardiac dysfunction by echocardiogram on D1 had longer hospital stay (p=0.047), pediatric intensive care unit stay (p=0.020), duration of mechanical ventilation (p=0.011), maximum inotropic score (p=0.001), and fewer ventilator-free hours (p=0.020). Cardiac dysfunction by echocardiography and serum ferritin value was significantly associated with unfavorable outcomes in pediatric patients with sepsis. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Assessment of myocardial viability by dynamic tomographic iodine 123 iodophenylpentadecanoic acid imaging: comparison with rest-redistribution thallium 201 imaging.

PubMed

Iskandrian, A S; Powers, J; Cave, V; Wasserleben, V; Cassell, D; Heo, J

1995-01-01

This study examined the ability of dynamic 123I-labeled iodophenylpentadecanoic acid (IPPA) imaging to detect myocardial viability in patients with left ventricular (LV) dysfunction caused by coronary artery disease. Serial 180-degree single-photon emission computed tomographic (SPECT) images (five sets, 8 minutes each) were obtained starting 4 minutes after injection of 2 to 6 mCi 123I at rest in 21 patients with LV dysfunction (ejection fraction [EF] 34% +/- 11%). The segmental uptake was compared with that of rest-redistribution 201Tl images (20 segments/study). The number of perfusion defects (reversible and fixed) was similar by IPPA and thallium (11 +/- 5 vs 10 +/- 5 segments/patient; difference not significant). There was agreement between IPPA and thallium for presence or absence (kappa = 0.78 +/- 0.03) and nature (reversible, mild fixed, or severe fixed) of perfusion defects (kappa = 0.54 +/- 0.04). However, there were more reversible IPPA defects than reversible thallium defects (7 +/- 4 vs 3 +/- 4 segments/patient; p = 0.001). In 14 patients the EF (by gated pool imaging) improved after coronary revascularization from 33% +/- 11% to 39% +/- 12% (p = 0.002). The number of reversible IPPA defects was greater in the seven patients who had improvement in EF than in the patients without such improvement (10 +/- 4 vs 5 +/- 4 segments/patient; p = 0.075). 123I-labeled IPPA SPECT imaging is a promising new technique for assessment of viability. Reversible defects predict recovery of LV dysfunction after coronary revascularization.

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.

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.

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.

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

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

The diagnostic ability of echocardiography for infective endocarditis and its associated complications.

PubMed

Vilacosta, Isidre; Olmos, Carmen; de Agustín, Alberto; López, Javier; Islas, Fabián; Sarriá, Cristina; Ferrera, Carlos; Ortiz-Bautista, Carlos; Sánchez-Enrique, Cristina; Vivas, David; San Román, Alberto

2015-11-01

Echocardiography, transthoracic and transoesophageal, plays a key role in the diagnosis and prognosis assessment of patients with infective endocarditis. It constitutes a major Duke criterion and is pivotal in treatment guiding. Seven echocardiographic findings are major criteria in the diagnosis of infective endocarditis (IE) (vegetation, abscess, pseudoaneurysm, fistulae, new dehiscence of a prosthetic valve, perforation and valve aneurysm). Echocardiography must be performed as soon as endocarditis is suspected. Transoesophageal echocardiography should be done in most cases of left-sided endocarditis to better define the anatomic lesions and to rule out local complications. Transoesophageal echocardiography is not necessary in isolated right-sided native valve IE with good quality transthoracic examination and unequivocal echocardiographic findings. Echocardiography is a very useful tool to assess the prognosis of patients with IE at any time during the course of the disease. Echocardiographic predictors of poor outcome include presence of periannular complications, prosthetic dysfunction, low left ventricular ejection fraction, pulmonary hypertension and very large vegetations.

Three-dimensional entertainment as a novel cause of takotsubo cardiomyopathy.

PubMed

Taylor, Montoya; Amin, Anish; Bush, Charles

2011-11-01

Takotsubo cardiomyopathy (TC) is an uncommon entity. It is known to occur in the setting of extreme catecholamine release and results in left ventricular dysfunction without evidence of angiographically definable coronary artery disease. There have been no published reports of TC occurring with visual stimuli, specifically 3-dimensional (3D) entertainment. We present a 55-year-old woman who presented to her primary care physician's office with extreme palpitations, nausea, vomiting, and malaise <48 hours after watching a 3D action movie at her local theater. Her electrocardiogram demonstrated ST elevations in aVL and V1, prolonged QTc interval, and T-wave inversions in leads I, II, aVL, and V2-V6. Coronary angiography revealed angiographically normal vessels, elevated left ventricular filling pressures, and decreased ejection fraction with a pattern of apical ballooning. The presumed final diagnosis was TC, likely due to visual-auditory-triggered catecholamine release causing impaired coronary microcirculation. © 2011 Wiley Periodicals, Inc.

Late Na+ current and protracted electrical recovery are critical determinants of the aging myopathy

PubMed Central

Signore, Sergio; Sorrentino, Andrea; Borghetti, Giulia; Cannata, Antonio; Meo, Marianna; Zhou, Yu; Kannappan, Ramaswamy; Pasqualini, Francesco; O'Malley, Heather; Sundman, Mark; Tsigkas, Nikolaos; Zhang, Eric; Arranto, Christian; Mangiaracina, Chiara; Isobe, Kazuya; Sena, Brena F.; Kim, Junghyun; Goichberg, Polina; Nahrendorf, Matthias; Isom, Lori L.; Leri, Annarosa; Anversa, Piero; Rota, Marcello

2015-01-01

The aging myopathy manifests itself with diastolic dysfunction and preserved ejection fraction. We raised the possibility that, in a mouse model of physiological aging, defects in electromechanical properties of cardiomyocytes are important determinants of the diastolic characteristics of the myocardium, independently from changes in structural composition of the muscle and collagen framework. Here we show that an increase in the late Na+ current (INaL) in aging cardiomyocytes prolongs the action potential (AP) and influences temporal kinetics of Ca2+ cycling and contractility. These alterations increase force development and passive tension. Inhibition of INaL shortens the AP and corrects dynamics of Ca2+ transient, cell contraction and relaxation. Similarly, repolarization and diastolic tension of the senescent myocardium are partly restored. Thus, INaL offers inotropic support, but negatively interferes with cellular and ventricular compliance, providing a new perspective of the biology of myocardial aging and the aetiology of the defective cardiac performance in the elderly. PMID:26541940

A Case of Subclavian Artery Aneurysm with History of Ischemic Heart Disease Operated Under Cervical Epidural Anesthesia.

PubMed

Rath, Amrita; Abhinay, J; Loha, Sandeep; Singh, Atul Kumar

2017-01-01

Subclavian artery aneurysm is usually operated under general anesthesia (GA), but in specific situations, it can also be conducted under regional anesthesia (RA) such as cervical epidural anesthesia (CEA). A 48-year-old male presented with chief complaint of progressive swelling in the right side of the neck for the past 3 months following trauma. He was diagnosed as subclavian artery aneurysm, and surgical intervention was advised. He had previous history of angina 4 months back for which tablet aspirin 75 mg and tablet clopidogrel 75 mg once daily was prescribed. Cardiological evaluation revealed of an ejection fraction of around 30% with mild left ventricular hypokinesia and grade 2 diastolic dysfunction. Due to the poor cardiac functional status of the patient, RA with CEA was planned. The risk with GA in cases with a history of myocardial ischemia is more than RA, hence, it is better to use CEA which is equally efficacious in such high-risk cases.

[Anomalous origin of the left coronary artery from the pulmonary trunk with myocardial infarction and severe left ventricular dysfunction in infancy--assessment of myocardial damage using SPECT studies with 201TlCl and 123I-BMIPP].

PubMed

Miyamoto, T; Horigome, H; Sato, H; Yamada, M; Inai, K; Takeda, T; Ishikawa, N; Hoshino, H; Itai, Y

1996-02-01

A 4-month-old male infant with Bland-White-Garland (BWG) syndrome complicated myocardial infarction was reported. Signs included tachypnea, coughing, and failure to thrive. However, there was no sign of myocardial infarction. A chest radiograph revealed cardiomegaly (CTR = 65%) and electrocardiogram showed abnormal Q waves in I, aVL, V6 leads. Cardiac catheterization and angiography revealed marked dilatation of left ventricle (end-diastolic volume = 384 ml/m2) and extremely depressed ejection fraction (16%), confirming the diagnosis of BWG syndrome. A 201TlCl-myocardial SPECT demonstrated apical defect and hypoperfusion in the anterolateral, inferoposterior walls, whereas 123I-beta-methyl-p-iodophenylpentadecanoic-acid (123I-BMIPP) SPECT showed a wider defect area. SPECT studies with 201TlCl and 123I-BMIPP, are useful to assess myocardial viability more accurately in BWG syndrome.

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

PubMed Central

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

2014-01-01

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

Postinfarction Functional Recovery Driven by a Three-Dimensional Engineered Fibrin Patch Composed of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells.

PubMed

Roura, Santiago; Soler-Botija, Carolina; Bagó, Juli R; Llucià-Valldeperas, Aida; Férnandez, Marco A; Gálvez-Montón, Carolina; Prat-Vidal, Cristina; Perea-Gil, Isaac; Blanco, Jerónimo; Bayes-Genis, Antoni

2015-08-01

Considerable research has been dedicated to restoring myocardial cell slippage and limiting ventricular remodeling after myocardial infarction (MI). We examined the ability of a three-dimensional (3D) engineered fibrin patch filled with human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) to induce recovery of cardiac function after MI. The UCBMSCs were modified to coexpress luciferase and fluorescent protein reporters, mixed with fibrin, and applied as an adhesive, viable construct (fibrin-cell patch) over the infarcted myocardium in mice (MI-UCBMSC group). The patch adhered well to the heart. Noninvasive bioluminescence imaging demonstrated early proliferation and differentiation of UCBMSCs within the construct in the postinfarct mice in the MI-UCBMSC group. The implanted cells also participated in the formation of new, functional microvasculature that connected the fibrin-cell patch to both the subjacent myocardial tissue and the host circulatory system. As revealed by echocardiography, the left ventricular ejection fraction and fractional shortening at sacrifice were improved in MI-UCBMSC mice and were markedly reduced in mice treated with fibrin alone and untreated postinfarction controls. In conclusion, a 3D engineered fibrin patch composed of UCBMSCs attenuated infarct-derived cardiac dysfunction when transplanted locally over a myocardial wound. ©AlphaMed Press.

Cardiac overexpression of Mammalian enabled (Mena) exacerbates heart failure in mice

PubMed Central

Belmonte, Stephen L.; Ram, Rashmi; Mickelsen, Deanne M.; Gertler, Frank B.

2013-01-01

Mammalian enabled (Mena) is a key regulator of cytoskeletal actin dynamics, which has been implicated in heart failure (HF). We have previously demonstrated that cardiac Mena deletion produced cardiac dysfunction with conduction abnormalities and hypertrophy. Moreover, elevated Mena expression correlates with HF in human and animal models, yet the precise role of Mena in cardiac pathophysiology is unclear. In these studies, we evaluated mice with cardiac myocyte-specific Mena overexpression (TTA/TgTetMena) comparable to that observed in cardiac pathology. We found that the hearts of TTA/TgTetMena mice were functionally and morphologically comparable to wild-type littermates, except for mildly increased heart mass in the transgenic mice. Interestingly, TTA/TgTetMena mice were particularly susceptible to cardiac injury, as these animals experienced pronounced decreases in ejection fraction and fractional shortening as well as heart dilatation and hypertrophy after transverse aortic constriction (TAC). By “turning off” Mena overexpression in TTA/TgTetMena mice either immediately prior to or immediately after TAC surgery, we discovered that normalizing Mena levels eliminated cardiac hypertrophy in TTA/TgTetMena animals but did not preclude post-TAC cardiac functional deterioration. These findings indicate that hearts with increased levels of Mena fare worse when subjected to cardiac injury and suggest that Mena contributes to HF pathophysiology. PMID:23832697

Cardiac overexpression of Mammalian enabled (Mena) exacerbates heart failure in mice.

PubMed

Belmonte, Stephen L; Ram, Rashmi; Mickelsen, Deanne M; Gertler, Frank B; Blaxall, Burns C

2013-09-15

Mammalian enabled (Mena) is a key regulator of cytoskeletal actin dynamics, which has been implicated in heart failure (HF). We have previously demonstrated that cardiac Mena deletion produced cardiac dysfunction with conduction abnormalities and hypertrophy. Moreover, elevated Mena expression correlates with HF in human and animal models, yet the precise role of Mena in cardiac pathophysiology is unclear. In these studies, we evaluated mice with cardiac myocyte-specific Mena overexpression (TTA/TgTetMena) comparable to that observed in cardiac pathology. We found that the hearts of TTA/TgTetMena mice were functionally and morphologically comparable to wild-type littermates, except for mildly increased heart mass in the transgenic mice. Interestingly, TTA/TgTetMena mice were particularly susceptible to cardiac injury, as these animals experienced pronounced decreases in ejection fraction and fractional shortening as well as heart dilatation and hypertrophy after transverse aortic constriction (TAC). By "turning off" Mena overexpression in TTA/TgTetMena mice either immediately prior to or immediately after TAC surgery, we discovered that normalizing Mena levels eliminated cardiac hypertrophy in TTA/TgTetMena animals but did not preclude post-TAC cardiac functional deterioration. These findings indicate that hearts with increased levels of Mena fare worse when subjected to cardiac injury and suggest that Mena contributes to HF pathophysiology.

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

PubMed Central

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

2016-01-01

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

Loss of Female Sex Hormones Exacerbates Cerebrovascular and Cognitive Dysfunction in Aortic Banded Miniswine Through a Neuropeptide Y-Ca2+-Activated Potassium Channel-Nitric Oxide Mediated Mechanism.

PubMed

Olver, T Dylan; Hiemstra, Jessica A; Edwards, Jenna C; Schachtman, Todd R; Heesch, Cheryl M; Fadel, Paul J; Laughlin, M Harold; Emter, Craig A

2017-10-31

Postmenopausal women represent the largest cohort of patients with heart failure with preserved ejection fraction, and vascular dementia represents the most common form of dementia in patients with heart failure with preserved ejection fraction. Therefore, we tested the hypotheses that the combination of cardiac pressure overload (aortic banding [AB]) and the loss of female sex hormones (ovariectomy [OVX]) impairs cerebrovascular control and spatial memory. Female Yucatan miniswine were separated into 4 groups (n=7 per group): (1) control, (2) AB, (3) OVX, and (4) AB-OVX. Pigs underwent OVX and AB at 7 and 8 months of age, respectively. At 14 months, cerebral blood flow velocity and spatial memory (spatial hole-board task) were lower in the OVX groups ( P <0.05), with significant impairments in the AB-OVX group ( P <0.05). Resting carotid artery β stiffness and vascular resistance during central hypovolemia were increased in the AB-OVX group ( P <0.05), and blood flow recovery after central hypovolemia was reduced in both OVX groups ( P <0.05). Isolated pial artery (pressure myography) vasoconstriction to neuropeptide Y was greatest in the AB-OVX group ( P <0.05), and vasodilation to the Ca 2+ -activated potassium channel α-subunit agonist NS-1619 was impaired in both AB groups ( P <0.05). The ratio of phosphorylated endothelial nitric oxide synthase:total endothelial nitric oxide synthase was depressed and Ca 2+ -activated potassium channel α-subunit protein was increased in AB groups ( P <0.05). Mechanistically, impaired cerebral blood flow control in experimental heart failure may be the result of heightened neuropeptide Y-induced vasoconstriction along with reduced vasodilation associated with decreased Ca 2+ -activated potassium channel function and impaired nitric oxide signaling, the effects of which are exacerbated in the absence of female sex hormones. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Prognostication of valvular aortic stenosis using tissue Doppler echocardiography: underappreciated importance of late diastolic mitral annular velocity.

PubMed

Poh, Kian-Keong; Chan, Mark Yan-Yee; Yang, Hong; Yong, Quek-Wei; Chan, Yiong-Huak; Ling, Lieng H

2008-05-01

Intact left atrial booster pump function helps maintain cardiac compensation in patients with aortic valve stenosis (AS). Because late diastolic mitral annular (A') velocity reflects left atrial systolic function, we hypothesized that A' velocity correlates with plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and clinical outcome in AS. We prospectively enrolled 53 consecutive patients (median age 74 years) with variable degrees of AS, in sinus rhythm, and left ventricular ejection fraction greater than 50%. Indices of valvular stenosis, left ventricular diastolic dysfunction, and mitral annular motion were correlated with plasma NT-proBNP and a composite clinical end point comprising cardiac death and symptom-driven aortic valve replacement. Tissue Doppler echocardiographic parameters, including early diastolic (E') velocity and A' velocity and ratio of early diastolic transmitral (E) to E' velocity (E/E') at the annular septum correlated better with NT-proBNP levels than body surface area-indexed aortic valve area. Eighteen patients had the composite end point, which was univariately predicted by body surface area-indexed aortic valve area, NT-proBNP, and all tissue Doppler echocardiographic indices. This outcome was most strongly predicted by the combination of septal A' velocity and E/E' ratio in bivariate Cox modeling. Septal annular A' velocity less than 9.6 cm/s was associated with significantly reduced event-free survival (Kaplan Meier log rank = 27.3, P < .0001) and predicted the end point with a sensitivity, specificity, and accuracy of 94%, 80%, and 85%, respectively. In patients with AS and normal ejection fraction, annular tissue Doppler echocardiographic indices may better reflect the physiologic consequences of afterload burden on the left ventricle than body surface area-indexed aortic valve area. Lower A' velocity is a predictor of cardiac death and need for valve surgery, suggesting an important role for compensatory left atrial booster pump function.

Clinical presentation, management, in-hospital and 90-day outcomes of heart failure patients in Trivandrum, Kerala, India: the Trivandrum Heart Failure Registry.

PubMed

Harikrishnan, Sivadasanpillai; Sanjay, Ganapathi; Anees, Thajudeen; Viswanathan, Sunitha; Vijayaraghavan, Govindan; Bahuleyan, Charantharayil G; Sreedharan, Madhu; Biju, Ramabhadran; Nair, Tiny; Suresh, Krishnan; Rao, Ashok C; Dalus, Dae; Huffman, Mark D; Jeemon, Panniyammakal

2015-08-01

To evaluate the presentation, management, and outcomes of patients hospitalized for heart failure (HF) in Trivandrum, India. The Trivandrum Heart Failure Registry (THFR) enrolled consecutive admissions from 13 urban and five rural hospitals in Trivandrum with a primary diagnosis of HF from January to December 2013. Clinical characteristics at presentation, treatment, in-hospital outcomes, and 90-day mortality data were collected. 'Guideline-based' medical treatment was defined as the combination of beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and aldosterone receptor blockers in patients with left ventricular systolic dysfunction (LVSD). We enrolled 1205 cases (834 men, 69%) into the registry. Mean (standard deviation) age was 61.2 (13.7) years. The most common HF aetiology was ischaemic heart disease (IHD) (72%). Heart failure with preserved ejection fraction (≥45%) constituted 26% of the population. The median hospital stay was 6 days (interquartile range = 4-9 days) with an in-hospital mortality rate of 8.5% (95% confidence interval 6.9-10.0). The 90-day all-cause mortality rate was 2.43 deaths per 1000 person-days (95% confidence interval 2.11-2.78). Guideline-based medical treatment was given to 19% and 25% of patients with LVSD during hospital admission and at discharge, respectively. Older age, lower education, poor ejection fraction, higher serum creatinine, New York Heart Association functional class IV, and suboptimal medical treatment were associated with higher risk of 90-day mortality. Patients hospitalized with HF in the THFR were younger, more likely to be men, had a higher prevalence of IHD, reported longer length of hospital stay, and higher mortality compared with published data from other registries. We also identified key areas for improving hospital-based HF medical care in Trivandrum. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.

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

PubMed

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

2018-02-01

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

Effect of Bone Marrow-Derived Mononuclear Cell Treatment, Early or Late After Acute Myocardial Infarction: Twelve Months CMR and Long-Term Clinical Results.

PubMed

Sürder, Daniel; Manka, Robert; Moccetti, Tiziano; Lo Cicero, Viviana; Emmert, Maximilian Y; Klersy, Catherine; Soncin, Sabrina; Turchetto, Lucia; Radrizzani, Marina; Zuber, Michel; Windecker, Stephan; Moschovitis, Aris; Bühler, Ines; Kozerke, Sebastian; Erne, Paul; Lüscher, Thomas F; Corti, Roberto

2016-07-22

Intracoronary delivery of autologous bone marrow-derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction (AMI). To demonstrate long-term efficacy of BM-MNC treatment after AMI. In a multicenter study, we randomized 200 patients with large AMI in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were either administered 5 to 7 days (early) or 3 to 4 weeks (late) after AMI. Cardiac magnetic resonance imaging was performed at baseline and after 12 months. The current analysis investigates the change from baseline to 12 months in global LV ejection fraction, LV volumes, scar size, and N-terminal pro-brain natriuretic peptide values comparing the 2 treatment groups with control in a linear regression model. Besides the complete case analysis, multiple imputation analysis was performed to address for missing data. Furthermore, the long-term clinical event rate was computed. The absolute change in LV ejection fraction from baseline to 12 months was -1.9±9.8% for control (mean±SD), -0.9±10.5% for the early treatment group, and -0.7±10.1% for the late treatment group. The difference between the groups was not significant, both for complete case analysis and multiple imputation analysis. A combined clinical end point occurred equally in all the groups. Overall, 1-year mortality was low (2.25%). Among patients with AMI and LV dysfunction, treatment with BM-MNC either 5 to 7 days or 3 to 4 weeks after AMI did not improve LV function at 12 months, compared with control. The results are limited by an important drop out rate. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00355186. © 2016 American Heart Association, Inc.

A systematic review of diastolic stress tests in heart failure with preserved ejection fraction, with proposals from the EU-FP7 MEDIA study group.

PubMed

Erdei, Tamás; Smiseth, Otto A; Marino, Paolo; Fraser, Alan G

2014-12-01

Cardiac function should be assessed during stress in patients with suspected heart failure with preserved ejection fraction (HFPEF), but it is unclear how to define impaired diastolic reserve. We conducted a systematic review to identify which pathophysiological changes serve as appropriate targets for diagnostic imaging. We identified 38 studies of 1111 patients with HFPEF (mean age 65 years), 744 control patients without HFPEF, and 458 healthy subjects. Qualifying EF was >45-55%; diastolic dysfunction at rest was a required criterion in 45% of studies. The initial workload during bicycle exercise (25 studies) varied from 12.5 to 30 W (mean 23.1 ± 4.6), with increments of 10-25 W (mean 19.9 ± 6) and stage duration 1-5 min (mean 2.5 ± 1); targets were submaximal (n = 8) or maximal (n = 17). Other protocols used treadmill exercise, handgrip, dobutamine, lower body negative pressure, nitroprusside, fluid challenge, leg raising, or atrial pacing. Reproducibility of echocardiographic variables during stress and validation against independent reference criteria were assessed in few studies. Change in E/e' was the most frequent measurement, but there is insufficient evidence to establish this or other tests for routine use when evaluating patients with HFPEF. To meet the clinical requirements of performing stress testing in elderly subjects, we propose a ramped exercise protocol on a semi-supine bicycle, starting at 15 W, with increments of 5 W/min to a submaximal target (heart rate 100-110 b.p.m., or symptoms). Measurements during submaximal and recovery stages should include changes from baseline in LV long-axis function and indirect echocardiographic indices of LV diastolic pressure. © 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.

Milrinone Use is Associated With Postoperative Atrial Fibrillation Following Cardiac Surgery

PubMed Central

Fleming, Gregory A.; Murray, Katherine T.; Yu, Chang; Byrne, John G.; Greelish, James P.; Petracek, Michael R.; Hoff, Steven J.; Ball, Stephen K.; Brown, Nancy J.; Pretorius, Mias

2009-01-01

Background Postoperative atrial fibrillation (AF), a frequent complication following cardiac surgery, causes morbidity and prolongs hospitalization. Inotropic drugs are commonly used perioperatively to support ventricular function. This study tested the hypothesis that the use of inotropic drugs is associated with postoperative AF. Methods and Results We evaluated perioperative risk factors in 232 patients who underwent elective cardiac surgery. All patients were in sinus rhythm at surgery. Sixty-seven (28.9%) patients developed AF a mean of 2.9±2.1 days after surgery. Patients who developed AF stayed in the hospital longer (P<0.001) and were more likely to die (P=0.02). Milrinone use was associated with an increased risk of postoperative AF (58.2% versus 26.1% in non-users, P<0.001). Older age (63.4±10.7 versus 56.7±12.3 years, P<0.001), hypertension (P=0.04), lower preoperative ejection fraction (P=0.03), mitral valve surgery (P=0.02), right ventricular dysfunction (P=0.03), and higher mean pulmonary artery pressure (PAP) (27.1±9.3 versus 21.8±7.5 mmHg, P=0.001) were also associated with postoperative AF. In multivariable logistic regression, age (P<0.001), ejection fraction (P=0.02), and milrinone use (odds ratio 4.86, 95% CI 2.31-10.25, P<0.001) independently predicted postoperative AF. When data only from patients with pulmonary artery catheters were analyzed and PAP was included in the model, age, milrinone use (odds ratio 4.45, 95% CI 2.01-9.84, P<0.001), and higher PAP (P=0.02) were associated with an increased risk of postoperative AF. Adding other potential confounders or stratifying analysis by mitral valve surgery did not change the association of milrinone use with postoperative AF. Conclusion Milrinone use is an independent risk factor for postoperative AF following elective cardiac surgery. PMID:18824641

Bridging the gap: Hybrid cardiac echo in the critically ill.

PubMed

Glaser, Jacob J; Cardarelli, Cassandra; Galvagno, Samuel; Scalea, Thomas M; Murthi, Sarah B

2016-11-01

Point-of-care ultrasound often includes cardiac ultrasound. It is commonly used to evaluate cardiac function in critically ill patients but lacks the specific quantitative anatomic assessment afforded by standard transthoracic echocardiography (TTE). We developed the Focused Rapid Echocardiographic Examination (FREE), a hybrid between a cardiac ultrasound and TTE that places an emphasis on cardiac function rather than anatomy. We hypothesized that data obtained from FREE correlate well with TTE while providing actionable information for clinical decision making. FREE examinations evaluating cardiac function (left ventricular ejection fraction), diastolic dysfunction (including early mitral Doppler flow [E] and early mitral tissue Doppler [E']), right ventricular function, cardiac output, preload (left ventricular internal dimension end diastole), stroke volume, stroke volume variation, inferior vena cava diameter, and inferior vena cava collapse were performed. Patients who underwent both a TTE and FREE on the same day were identified as the cohort, and quantitative measurements were compared. Correlation analyses were performed to assess levels of agreement. A total of 462 FREE examinations were performed, in which 69 patients had both a FREE and TTE. FREE ejection fraction was strongly correlated with TTE (r = 0.89, 95% confidence interval). Left ventricular outflow tract, left ventricular internal dimension end diastole, E, and lateral E' derived from FREE were also strongly correlated with TTE measurements (r = 0.83, r = 0.94, r = 0.77, and r = 0.88, respectively). In 82% of the patients, right ventricular function for FREE was the same as that reported for TTE; pericardial effusion was detected on both examinations in 94% of the cases. No significant valvular anatomy was missed with the FREE examination. Functionally rather than anatomically based hybrid ultrasound examinations, like the FREE, facilitate decision making for critically ill patients. The FREE's functional assessment correlates well with TTE measurements and may be of significant clinical value in critically ill patients, especially when used in remote operating environments where resources are limited. Diagnostic test, level III.

Rationale and design of a multicentre, randomized, placebo-controlled trial of mirabegron, a Beta3-adrenergic receptor agonist on left ventricular mass and diastolic function in patients with structural heart disease Beta3-left ventricular hypertrophy (Beta3-LVH).

PubMed

Pouleur, Anne-Catherine; Anker, Stefan; Brito, Dulce; Brosteanu, Oana; Hasenclever, Dirk; Casadei, Barbara; Edelmann, Frank; Filippatos, Gerasimos; Gruson, Damien; Ikonomidis, Ignatios; Lhommel, Renaud; Mahmod, Masliza; Neubauer, Stefan; Persu, Alexandre; Gerber, Bernhard L; Piechnik, Stefan; Pieske, Burkert; Pieske-Kraigher, Elisabeth; Pinto, Fausto; Ponikowski, Piotr; Senni, Michele; Trochu, Jean-Noël; Van Overstraeten, Nancy; Wachter, Rolf; Balligand, Jean-Luc

2018-06-22

Progressive left ventricular (LV) remodelling with cardiac myocyte hypertrophy, myocardial fibrosis, and endothelial dysfunction plays a key role in the onset and progression of heart failure with preserved ejection fraction. The Beta3-LVH trial will test the hypothesis that the β 3 adrenergic receptor agonist mirabegron will improve LV hypertrophy and diastolic function in patients with hypertensive structural heart disease at high risk for developing heart failure with preserved ejection fraction. Beta3-LVH is a randomized, placebo-controlled, double-blind, two-armed, multicentre, European, parallel group study. A total of 296 patients will be randomly assigned to receive either mirabegron 50 mg daily or placebo over 12 months. The main inclusion criterion is the presence of LV hypertrophy, that is, increased LV mass index (LVMi) or increased wall thickening by echocardiography. The co-primary endpoints are a change in LVMi by cardiac magnetic resonance imaging and a change in LV diastolic function (assessed by the E/e' ratio). Secondary endpoints include mirabegron's effects on cardiac fibrosis, left atrial volume index, maximal exercise capacity, and laboratory markers. Two substudies will evaluate mirabegron's effect on endothelial function by pulse amplitude tonometry and brown fat activity by positron emission tomography using 17F-fluorodeoxyglucose. Morbidity and mortality as well as safety aspects will also be assessed. Beta3-LVH is the first large-scale clinical trial to evaluate the effects of mirabegron on LVMi and diastolic function in patients with LVH. Beta3-LVH will provide important information about the clinical course of this condition and may have significant impact on treatment strategies and future trials in these patients. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

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

PubMed Central

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

2012-01-01

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

Left atrial enlargement increases the risk of major adverse cardiac events independent of coronary vasodilator capacity.

PubMed

Koh, Angela S; Murthy, Venkatesh L; Sitek, Arkadiusz; Gayed, Peter; Bruyere, John; Wu, Justina; Di Carli, Marcelo F; Dorbala, Sharmila

2015-09-01

Longstanding uncontrolled atherogenic risk factors may contribute to left atrial (LA) hypertension, LA enlargement (LAE) and coronary vascular dysfunction. Together they may better identify risk of major adverse cardiac events (MACE). The aim of this study was to test the hypothesis that chronic LA hypertension as assessed by LAE modifies the relationship between coronary vascular function and MACE. In 508 unselected subjects with a normal clinical (82)Rb PET/CT, ejection fraction ≥40 %, no prior coronary artery disease, valve disease or atrial fibrillation, LAE was determined based on LA volumes estimated from the hybrid perfusion and CT transmission scan images and indexed to body surface area. Absolute myocardial blood flow and global coronary flow reserve (CFR) were calculated. Subjects were systematically followed-up for the primary end-point - MACE - a composite of all-cause death, myocardial infarction, hospitalization for heart failure, stroke, coronary artery disease progression or revascularization. During a median follow-up of 862 days, 65 of the subjects experienced a composite event. Compared with subjects with normal LA size, subjects with LAE showed significantly lower CFR (2.25 ± 0.83 vs. 1.95 ± 0.80, p = 0.01). LAE independently and incrementally predicted MACE even after accounting for clinical risk factors, medication use, stress left ventricular ejection fraction, stress left ventricular end-diastolic volume index and CFR (chi-squared statistic increased from 30.9 to 48.3; p = 0.001). Among subjects with normal CFR, those with LAE had significantly worse event-free survival (risk adjusted HR 5.4, 95 % CI 2.3 - 12.8, p < 0.0001). LAE and reduced CFR are related but distinct cardiovascular adaptations to atherogenic risk factors. LAE is a risk marker for MACE independent of clinical factors and left ventricular volumes; individuals with LAE may be at risk of MACE despite normal coronary vascular function.

Analysis of transthoracic echocardiographic data in major vascular surgery from a prospective randomised trial comparing sevoflurane and fentanyl with propofol and remifentanil anaesthesia.

PubMed

Lindholm, E E; Aune, E; Frøland, G; Kirkebøen, K A; Otterstad, J E

2014-06-01

The aim of this study was to define pre-operative echocardiographic data and explore if postoperative indices of cardiac function after open abdominal aortic surgery were affected by the anaesthetic regimen. We hypothesised that volatile anaesthesia would improve indices of cardiac function compared with total intravenous anaesthesia. Transthoracic echocardiography was performed pre-operatively in 78 patients randomly assigned to volatile anaesthesia and 76 to total intravenous anaesthesia, and compared with postoperative data. Pre-operatively, 16 patients (10%) had left ventricular ejection fraction < 46%. In 138 patients with normal left ventricular ejection fraction, 5/8 (62%) with left ventricular dilatation and 41/130 (33%) without left ventricular dilatation had evidence of left ventricular diastolic dysfunction (p < 0.001). Compared with pre-operative findings, significant increases in left ventricular end-diastolic volume, left atrial maximal volume, cardiac output, velocity of early mitral flow and early myocardial relaxation occurred postoperatively (all p < 0.001). The ratio of the velocity of early mitral flow to early myocardial relaxation remained unchanged. There were no significant differences in postoperative echocardiographic findings between patients anaesthetised with volatile anaesthesia or total intravenous anaesthesia. Patients had an iatrogenic surplus of approximately 4.1 l of fluid volume by the first postoperative day. N-terminal prohormone of brain natriuretic peptide increased on the first postoperative day (p < 0.001) and remained elevated after 30 days (p < 0.001) in both groups. Although postoperative echocardiographic alterations were most likely to be related to increased preload due to a substantial iatrogenic surplus of fluid, a component of peri-operative myocardial ischaemia cannot be excluded. Our hypothesis that volatile anaesthesia improved indices of cardiac function compared with total intravenous anaesthesia could not be verified. © 2014 The Association of Anaesthetists of Great Britain and Ireland.

Tricuspid regurgitation in patients with beta-thalassemia major.

PubMed

Wu, K H; Chang, J S; Su, B H; Peng, C T

2004-12-01

Although cardiac complications remain the main causes of death in thalassemic patients, right heart dysfunction has been little studied and the mechanism is still unclear. Echocardiography was performed in 39 patients with beta-thalassemia major and 35 aged-matched controls. The gender, age, heart rate, blood pressure, left ventricular ejection fraction (LVEF), acceleration time (AcT) of right ventricular outflow and right ventricular ejection time (RVET), AcT/RVET, and the presence of tricuspid regurgitation (TR) were compared between the two groups. We also compared the gender, age, age at first blood transfusion, serum ferritin level, alanine aminotransferase (ALT), the presence of antibodies to hepatitis C virus, liver fibrosis, splenectomy, platelet counts, diabetes mellitus, arrhythmia, cardiomegaly, LVEF, AcT, RVET, AcT/RVET, and signal intensity ratio (SIR) of myocardial magnetic resonance imaging (MRI) between thalassemic patients with and without TR. The incidence of TR in thalassemic patients was significantly higher than that in the control group (30.8 vs 11.4%, p=0.03). The incidences of splenectomy (p=0.03), platelet counts (p=0.01), and SIR of myocardial MRI (p=0.03) in thalassemic patients with TR were significantly higher than in those without TR. The AcT was shorter and the AcT/RVET ratio was smaller, suggesting higher pulmonary pressure in the thalassemic patients with TR. Occurrence of TR in patients with beta-thalassemia major may be a consequence of cardiac iron deposit, thrombocytosis, splenectomy, or pulmonary hypertension.

Effects of exercise training on brain-derived neurotrophic factor in skeletal muscle and heart of rats post myocardial infarction.

PubMed

Lee, Heow Won; Ahmad, Monir; Wang, Hong-Wei; Leenen, Frans H H

2017-03-01

What is the central question of this study? Exercise training increases brain-derived neurotrophic factor (BDNF) in the hippocampus, which depends on a myokine, fibronectin type III domain-containing protein 5 (FNDC5). Whether exercise training after myocardial infarction induces parallel increases in FNDC5 and BDNF expression in skeletal muscle and the heart has not yet been studied. What is the main finding and its importance? Exercise training after myocardial infarction increases BDNF protein in skeletal muscle and the non-infarct area of the LV without changes in FNDC5 protein, suggesting that BDNF is not regulated by FNDC5 in skeletal muscle and heart. An increase in cardiac BDNF may contribute to the improvement of cardiac function by exercise training. Exercise training after myocardial infarction (MI) attenuates progressive left ventricular (LV) remodelling and dysfunction, but the peripheral stimuli induced by exercise that trigger these beneficial effects are still unclear. We investigated as possible mediators fibronectin type III domain-containing protein 5 (FNDC5) and brain-derived neurotrophic factor (BDNF) in the skeletal muscle and heart. Male Wistar rats underwent either sham surgery or ligation of the left descending coronary artery, and surviving MI rats were allocated to either a sedentary (Sed-MI) or an exercise group (ExT-MI). Exercise training was done for 4 weeks on a motor-driven treadmill. At the end, LV function was evaluated, and FNDC5 and BDNF mRNA and protein were assessed in soleus muscle, quadriceps and non-, peri- and infarct areas of the LV. At 5 weeks post MI, FNDC5 mRNA was decreased in soleus muscle and all areas of the LV, but FNDC5 protein was increased in the soleus muscle and the infarct area. Mature BDNF (mBDNF) protein was decreased in the infarct area without a change in mRNA. Exercise training attenuated the decrease in ejection fraction and the increase in LV end-diastolic pressure post MI. Exercise training had no effect on FNDC5 mRNA and protein, but increased mBDNF protein in soleus muscle, quadriceps and the non-infarct area of the LV. The mBDNF protein in the non-infarct area correlated positively with ejection fraction and inversely with LV end-diastolic pressure. In conclusion, mBDNF is induced by exercise training in skeletal muscle and the non-infarct area of the LV, which may contribute to improvement of muscle dysfunction and cardiac function post MI. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

EFFECTS OF A HIGH SATURATED FAT DIET ON CARDIAC HYPERTROPHY AND DYSFUNCTION IN RESPONSE TO PRESSURE OVERLOAD

PubMed Central

Chess, David; Lei, Biao; Hoit, Brian; Azimzadeh, Agnes M.; Stanley, William

2009-01-01

Background Dietary lipid content effects activation of peroxisome proliferator-activated receptor-α (PPARα) and may accelerate cardiac hypertrophy and dysfunction in response to pressure overload. This study investigated the effects of a high fat diet on the development of cardiac hypertrophy. Methods and Results C57BL/6J mice (n=14–16/group) underwent transverse aortic constriction (TAC) or sham surgery and were fed either standard low fat diet (STD; 10% fat) or a high fat diet (HFD; 60% fat) for 16 weeks. Sham mice showed no differences between STD and HFD for heart mass or echocardiographic parameters despite greater plasma free fatty acid and leptin concentrations with HFD. TAC increased heart mass and decreased ejection fraction similarly in both groups. Left ventricular end systolic and diastolic diameters with TAC were increased compared to shams on the HFD (p < 0.05) but were not different from STD TAC mice. High fat feeding increased expression of PPARα-regulated genes. The activity of medium chain acyl-coenzyme A dehydrogenase (MCAD), a marker of fatty acid oxidation capacity, was increased in HFD TAC mice compared to STD, consistent with PPARα activation. Conclusion Increased fat intake prevented the fall in MCAD activity and did not exacerbate the hypertrophic response to TAC compared to a low-fat diet. PMID:18226777

Heart-Derived Stem Cells in Miniature Swine with Coronary Microembolization: Novel Ischemic Cardiomyopathy Model to Assess the Efficacy of Cell-Based Therapy

PubMed Central

Young, Rebeccah F.; Leiker, Merced M.; Suzuki, Takayuki

2016-01-01

A major problem in translating stem cell therapeutics is the difficulty of producing stable, long-term severe left ventricular (LV) dysfunction in a large animal model. For that purpose, extensive infarction was created in sinclair miniswine by injecting microspheres (1.5 × 106 microspheres, 45 μm diameter) in LAD. At 2 months after embolization, animals (n = 11) were randomized to receive allogeneic cardiosphere-derived cells derived from atrium (CDCs: 20 × 106, n = 5) or saline (untreated, n = 6). Four weeks after therapy myocardial function, myocyte proliferation (Ki67), mitosis (phosphor-Histone H3; pHH3), apoptosis, infarct size (TTC), myocyte nuclear density, and cell size were evaluated. CDCs injected into infarcted and remodeled remote myocardium (global infusion) increased regional function and global function contrasting no change in untreated animals. CDCs reduced infarct volume and stimulated Ki67 and pHH3 positive myocytes in infarct and remote regions. As a result, myocyte number (nuclear density) increased and myocyte cell diameter decreased in both infarct and remote regions. Coronary microembolization produces stable long-term ischemic cardiomyopathy. Global infusion of CDCs stimulates myocyte regeneration and improves left ventricular ejection fraction. Thus, global infusion of CDCs could become a new therapy to reverse LV dysfunction in patients with asymptomatic heart failure. PMID:27738436

A Novel Positron Emission Tomography (PET) Approach to Monitor Cardiac Metabolic Pathway Remodeling in Response to Sunitinib Malate.

PubMed

O'Farrell, Alice C; Evans, Rhys; Silvola, Johanna M U; Miller, Ian S; Conroy, Emer; Hector, Suzanne; Cary, Maurice; Murray, David W; Jarzabek, Monika A; Maratha, Ashwini; Alamanou, Marina; Udupi, Girish Mallya; Shiels, Liam; Pallaud, Celine; Saraste, Antti; Liljenbäck, Heidi; Jauhiainen, Matti; Oikonen, Vesa; Ducret, Axel; Cutler, Paul; McAuliffe, Fionnuala M; Rousseau, Jacques A; Lecomte, Roger; Gascon, Suzanne; Arany, Zoltan; Ky, Bonnie; Force, Thomas; Knuuti, Juhani; Gallagher, William M; Roivainen, Anne; Byrne, Annette T

2017-01-01

Sunitinib is a tyrosine kinase inhibitor approved for the treatment of multiple solid tumors. However, cardiotoxicity is of increasing concern, with a need to develop rational mechanism driven approaches for the early detection of cardiac dysfunction. We sought to interrogate changes in cardiac energy substrate usage during sunitinib treatment, hypothesising that these changes could represent a strategy for the early detection of cardiotoxicity. Balb/CJ mice or Sprague-Dawley rats were treated orally for 4 weeks with 40 or 20 mg/kg/day sunitinib. Cardiac positron emission tomography (PET) was implemented to investigate alterations in myocardial glucose and oxidative metabolism. Following treatment, blood pressure increased, and left ventricular ejection fraction decreased. Cardiac [18F]-fluorodeoxyglucose (FDG)-PET revealed increased glucose uptake after 48 hours. [11C]Acetate-PET showed decreased myocardial perfusion following treatment. Electron microscopy revealed significant lipid accumulation in the myocardium. Proteomic analyses indicated that oxidative metabolism, fatty acid β-oxidation and mitochondrial dysfunction were among the top myocardial signalling pathways perturbed. Sunitinib treatment results in an increased reliance on glycolysis, increased myocardial lipid deposition and perturbed mitochondrial function, indicative of a fundamental energy crisis resulting in compromised myocardial energy metabolism and function. Our findings suggest that a cardiac PET strategy may represent a rational approach to non-invasively monitor metabolic pathway remodeling following sunitinib treatment.

A Novel Positron Emission Tomography (PET) Approach to Monitor Cardiac Metabolic Pathway Remodeling in Response to Sunitinib Malate

PubMed Central

Silvola, Johanna M. U.; Miller, Ian S.; Conroy, Emer; Hector, Suzanne; Cary, Maurice; Murray, David W.; Jarzabek, Monika A.; Maratha, Ashwini; Alamanou, Marina; Udupi, Girish Mallya; Shiels, Liam; Pallaud, Celine; Saraste, Antti; Liljenbäck, Heidi; Jauhiainen, Matti; Oikonen, Vesa; Ducret, Axel; Cutler, Paul; McAuliffe, Fionnuala M.; Rousseau, Jacques A.; Lecomte, Roger; Gascon, Suzanne; Arany, Zoltan; Ky, Bonnie; Force, Thomas; Knuuti, Juhani; Gallagher, William M.; Roivainen, Anne; Byrne, Annette T.

2017-01-01

Sunitinib is a tyrosine kinase inhibitor approved for the treatment of multiple solid tumors. However, cardiotoxicity is of increasing concern, with a need to develop rational mechanism driven approaches for the early detection of cardiac dysfunction. We sought to interrogate changes in cardiac energy substrate usage during sunitinib treatment, hypothesising that these changes could represent a strategy for the early detection of cardiotoxicity. Balb/CJ mice or Sprague-Dawley rats were treated orally for 4 weeks with 40 or 20 mg/kg/day sunitinib. Cardiac positron emission tomography (PET) was implemented to investigate alterations in myocardial glucose and oxidative metabolism. Following treatment, blood pressure increased, and left ventricular ejection fraction decreased. Cardiac [18F]-fluorodeoxyglucose (FDG)-PET revealed increased glucose uptake after 48 hours. [11C]Acetate-PET showed decreased myocardial perfusion following treatment. Electron microscopy revealed significant lipid accumulation in the myocardium. Proteomic analyses indicated that oxidative metabolism, fatty acid β-oxidation and mitochondrial dysfunction were among the top myocardial signalling pathways perturbed. Sunitinib treatment results in an increased reliance on glycolysis, increased myocardial lipid deposition and perturbed mitochondrial function, indicative of a fundamental energy crisis resulting in compromised myocardial energy metabolism and function. Our findings suggest that a cardiac PET strategy may represent a rational approach to non-invasively monitor metabolic pathway remodeling following sunitinib treatment. PMID:28129334

Exercise-induced changes in mitral regurgitation in patients with prior myocardial infarction and left ventricular dysfunction: relation to mitral deformation and left ventricular function and shape.

PubMed

Giga, Vojislav; Ostojic, Miodrag; Vujisic-Tesic, Bosiljka; Djordjevic-Dikic, Ana; Stepanovic, Jelena; Beleslin, Branko; Petrovic, Milan; Nedeljkovic, Milan; Nedeljkovic, Ivana; Milic, Natasa

2005-09-01

The aim of this study was to assess the relationship between exercise-induced changes in mitral regurgitation (MR) and echocardiographic characteristics of mitral deformation, global left ventricular (LV) function and shape at rest and after exercise. Forty consecutive patients with ischaemic MR due to prior myocardial infarction (MI), ejection fraction <45% in sinus rhythm underwent exercise-echocardiographic testing. Exercise-induced changes in effective regurgitant orifice (ERO) were compared with baseline and exercise-induced changes in mitral deformation and global LV function and shape. There was significant correlation between exercise-induced changes in ERO and changes in coaptation distance (r=0.80, P<0.0001), tenting area (r=0.79, P<0.0001) and mitral annular diameter (r=0.65, P<0.0001), as well as in end-systolic sphericity index (r=-0.50, P=0.001, respectively), and wall motion score index (r=0.44, P=0.004). In contrast, exercise-induced changes in ERO were not related to the echocardiographic features at rest. By stepwise multiple regression model, the exercise-induced changes in mitral deformation were found to independently correlate with exercise-induced changes in ERO (generalized r(2)=0.80, P<0.0001). Exercise-induced changes in severity of ischaemic MR in patients with LV dysfunction due to prior MI were independently related to changes in mitral deformation.

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.

2D-speckle tracking right ventricular strain to assess right ventricular systolic function in systolic heart failure. Analysis of the right ventricular free and posterolateral walls.

PubMed

Mouton, Stéphanie; Ridon, Héléne; Fertin, Marie; Pentiah, Anju Duva; Goémine, Céline; Petyt, Grégory; Lamblin, Nicolas; Coisne, Augustin; Foucher-Hossein, Claude; Montaigne, David; de Groote, Pascal

2017-10-15

Right ventricular (RV) systolic function is a powerful prognostic factor in patients with systolic heart failure. The accurate estimation of RV function remains difficult. The aim of the study was to determine the diagnostic accuracy of 2D-speckle tracking RV strain in patients with systolic heart failure, analyzing both free and posterolateral walls. Seventy-six patients with dilated cardiopathy (left ventricular end-diastolic volume≥75ml/m 2 ) and left ventricular ejection fraction≤45% had an analysis of the RV strain. Feasibility, reproducibility and diagnostic accuracy of RV strain were analyzed and compared to other echocardiographic parameters of RV function. RV dysfunction was defined as a RV ejection fraction≤40% measured by radionuclide angiography. RV strain feasibility was 93.9% for the free-wall and 79.8% for the posterolateral wall. RV strain reproducibility was good (intra-observer and inter-observer bias and limits of agreement of 0.16±1.2% [-2.2-2.5] and 0.84±2.4 [-5.5-3.8], respectively). Patients with left heart failure have a RV systolic dysfunction that can be unmasked by advanced echocardiographic imaging: mean RV strain was -21±5.7% in patients without RV dysfunction and -15.8±5.1% in patients with RV dysfunction (p=0.0001). Mean RV strain showed the highest diagnostic accuracy to predict depressed RVEF (area under the curve (AUC) 0.75) with moderate sensitivity (60.5%) but high specificity (87.5%) using a cutoff value of -16%. RV strain seems to be a promising and more efficient measure than previous RV echocardiographic parameters for the diagnosis of RV systolic dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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

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

Salivary gland function 5 years after radioactive iodine ablation in patients with differentiated thyroid cancer: direct comparison of pre- and postablation scintigraphies and their relation to xerostomia symptoms.

PubMed

Jeong, Shin Young; Kim, Hae Won; Lee, Sang-Woo; Ahn, Byeong-Cheol; Lee, Jaetae

2013-05-01

Chronic sialadenitis is one of the most frequent chronic complications after radioactive iodine (RAI) therapy for thyroid cancer. To evaluate the long-term effects of RAI ablation on salivary gland function, we investigated scintigraphic changes in salivary glands by direct comparison of two salivary gland scintigraphies (SGSs) taken before and at 5 years after an RAI ablation. SGS was performed just before RAI ablation (pre-SGS) and ∼5 years after RAI ablation (F/U SGS) in 213 subjects who underwent thyroidectomy for thyroid cancer. The uptake score (U score) was graded, and the ejection fraction (EF) was quantified for the parotid and submandibular glands at pre-SGS and F/U SGS. Changes in salivary gland function were graded as mild, moderate, or severe according to the differences in U score and EF between the two SGSs. Xerostomia was assessed and compared with the SGS findings. Worsening of the U score was observed in 182 of 852 salivary glands (total: 21.3%; mild: 4.2%, moderate: 7.4%, severe: 9.7%), and 47.4% of the patients had a worsening U score for at least one of four salivary glands. A decrease in EF was observed in 173 of 852 salivary glands (total: 20.3%; mild: 5.4%, moderate: 6.8%, severe: 8.1%), and 43.7% of the patients experienced a decrease in the EF of at least one of the four salivary glands. Bilateral parotid gland dysfunction was the most commonly observed condition. Thirty-five (16.4%) patients complained of xerostomia at 5 years after RAI ablation. Scintigraphic changes in salivary gland function and xerostomia were more common in patients receiving 5.55 GBq, compared with 3.7 GBq. Xerostomia was more common in patients with submandibular gland dysfunction than those with parotid gland dysfunction (68.8% vs. 33.3%, p<0.05). The number of dysfunctional salivary glands was correlated with xerostomia (p<0.01). About 20% of the salivary glands were dysfunctional on SGS 5 years after a single RAI ablation, especially in patients who received higher doses of RAI. While parotid glands are more susceptible to (131)I-related damage, xerostomia was more associated with submandibular gland dysfunction and the prevalence of dysfunctional salivary glands.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Associated Clinical and Laboratory Markers of Donor on Allograft Function After Heart Transplant.

PubMed

Braulio, Renato; Sanches, Marcelo Dias; Teixeira Junior, Antonio Lúcio; Costa, Paulo Henrique Nogueira; Moreira, Maria da Consolação Vieira; Rocha, Monaliza Angela; Andrade, Silvio Amadeu de; Gelape, Cláudio Léo

2016-04-01

Primary graft dysfunction is a major cause of mortality after heart transplantation. To evaluate correlations between donor-related clinical/biochemical markers and the occurrence of primary graft dysfunction/clinical outcomes of recipients within 30 days of transplant. The prospective study involved 43 donor/recipient pairs. Data collected from donors included demographic and echocardiographic information, noradrenaline administration rates and concentrations of soluble tumor necrosis factor receptors (sTNFR1 and sTNFR2), interleukins (IL-6 and IL-10), monocyte chemoattractant protein-1, C-reactive protein and cardiac troponin I. Data collected from recipients included operating, cardiopulmonary bypass, intensive care unit and hospitalization times, inotrope administration and left/right ventricular function through echocardiography. Recipients who developed moderate/severe left ventricular dysfunction had received organs from significantly older donors (P =0.020). Recipients from donors who required moderate/high doses of noradrenaline (>0.23 µg/kg/min) around harvesting time exhibited lower post-transplant ventricular ejection fractions (P =0.002) and required longer CPB times (P =0.039). Significantly higher concentrations of sTNFR1 (P =0.014) and sTNFR2 (P =0.030) in donors were associated with reduced intensive care unit times (≤5 days) in recipients, while higher donor IL-6 (P =0.029) and IL-10 (P =0.037) levels were correlated with reduced hospitalization times (≤25 days) in recipients. Recipients who required moderate/high levels of noradrenaline for weaning off cardiopulmonary bypass were associated with lower donor concentrations of sTNFR2 (P =0.028) and IL-6 (P =0.001). High levels of sTNFR1, sTNFR2, IL-6 and IL-10 in donors were associated with enhanced evolution in recipients. Allografts from older donors, or from those treated with noradrenaline doses >0.23 µg/kg/min, were more frequently affected by primary graft dysfunction within 30 days of surgery.

Is plasma N-BNP a good indicator of the functional reserve of failing hearts? The FRESH-BNP study.

PubMed

Williams, Simon G; Ng, Leong L; O'Brien, Russell J; Taylor, Steve; Wright, D Jay; Tan, Lip-Bun

2004-12-01

Whether plasma N-terminal brain natriuretic peptide (N-BNP) is useful in the diagnosis of heart failure (HF) depends traditionally on whether it is as good as the putative 'gold-standard', left ventricular ejection fraction (LVEF), in indicating cardiac dysfunction. However, since HF is primarily an impairment of function of the cardiac pump, we explored the relationship between N-BNP and direct and indirect indicators of cardiac pump dysfunction. Eighty-six HF patients (mean age 56 years) with a range of LVEF's (mean 36.9+/-15.2%, range 15-66%) and 10 age-matched healthy controls were recruited into the study and had resting N-BNP measured. Cardiopulmonary exercise testing was performed to assess peak oxygen consumption (Vo(2)). A subgroup of 23 subjects underwent further exercise haemodynamic assessment to evaluate peak cardiac power output (CPO). The CHF group had significantly higher N-BNP (median [interquartile range]) levels (299 [705] fmol/ml) than the control group (7 [51] fmol/ml, P<0.005). Significant correlations between N-BNP and peak Vo(2), and N-BNP and peak CPO were observed (R> or =0.5, P<0.005). Although significant correlation was observed between N-BNP and LVEF (R=0.34, P=0.01), the correlations between LVEF and peak Vo(2) or peak CPO (all R<0.3, P>0.3) were not significant. Multivariate analysis identified plasma N-BNP and NYHA class, but not LVEF, as independent predictors of peak Vo(2). We have found that N-BNP was surprisingly good as a simple indicator of cardiac pump dysfunction. Since heart failure is an inadequacy of function, these results strongly support the notion that N-BNP is a useful blood test in estimating the extent of cardiac pump dysfunction and helpful in establishing positive diagnosis of heart failure.

Severe right ventricular dysfunction is an independent predictor of pre- and post-transplant mortality among candidates for heart transplantation.

PubMed

Ravis, Eleonore; Theron, Alexis; Mancini, Julien; Jaussaud, Nicolas; Morera, Pierre; Chalvignac, Virginie; Guidon, Catherine; Grisoli, Dominique; Gariboldi, Vlad; Riberi, Alberto; Habib, Gilbert; Mouly-Bandini, Annick; Collart, Frederic

2017-03-01

Heart transplantation is the gold-standard treatment for end-stage heart failure. However, the shortage of grafts has led to longer waiting times and increased mortality for candidates without priority. To study waiting-list and post-transplant mortality, and their risk factors among patients registered for heart transplantation without initial high emergency procedure. All patients registered on the heart transplantation waiting list (2004-2015) without initial high emergency procedure were included. Clinical, biological, echocardiographic and haemodynamic data were collected. Waiting list and 1-year post-transplant survival were analysed with a Kaplan-Meier model. Of 221 patients enrolled, 168 (76.0%) were men. Mean age was 50.0±12.0 years. Forty-seven patients died on the waiting list, resulting in mortality rates of 11.2±2.7% at 1 year, 31.9±5.4% at 2 years and 49.4±7.1% at 3 years. Median survival was 36.0±4.6 months. In the multivariable analysis, left ventricular ejection fraction<30% (hazard ratio [HR]: 3.76, 95% confidence interval [CI]: 1.38-10.24; P=0.010) and severe right ventricular systolic dysfunction (HR: 2.89, 95% CI: 1.41-5.92; P=0.004) were associated with increased waiting-list mortality. The post-transplant survival rate was 73.1±4.4% at 1 year. Pretransplant severe right ventricular dysfunction and age>50 years were strong predictors of death after transplantation (HR: 5.38, 95% CI: 1.38-10.24 [P=0.020] and HR: 6.16, 95% CI: 1.62-9.32 [P=0.0130], respectively). Mortality among candidates for heart transplantation remains high. Patients at highest risk of waiting-list mortality have to be promoted, but without compromising post-transplant outcomes. For this reason, candidates with severe right ventricular dysfunction are of concern, because, for them, transplantation is hazardous. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Importance of angina in patients with coronary disease, heart failure, and left ventricular systolic dysfunction: insights from STICH.

PubMed

Jolicœur, E Marc; Dunning, Allison; Castelvecchio, Serenella; Dabrowski, Rafal; Waclawiw, Myron A; Petrie, Mark C; Stewart, Ralph; Jhund, Pardeep S; Desvigne-Nickens, Patrice; Panza, Julio A; Bonow, Robert O; Sun, Benjamin; San, Tan Ru; Al-Khalidi, Hussein R; Rouleau, Jean L; Velazquez, Eric J; Cleland, John G F

2015-11-10

Patients with left ventricular (LV) systolic dysfunction, coronary artery disease (CAD), and angina are often thought to have a worse prognosis and a greater prognostic benefit from coronary artery bypass graft (CABG) surgery than those without angina. This study investigated: 1) whether angina was associated with a worse prognosis; 2) whether angina identified patients who had a greater survival benefit from CABG; and 3) whether CABG improved angina in patients with LV systolic dysfunction and CAD. We performed an analysis of the STICH (Surgical Treatment for Ischemic Heart Failure) trial, in which 1,212 patients with an ejection fraction ≤35% and CAD were randomized to CABG or medical therapy. Multivariable Cox and logistic models were used to assess long-term clinical outcomes. At baseline, 770 patients (64%) reported angina. Among patients assigned to medical therapy, all-cause mortality was similar in patients with and without angina (hazard ratio [HR]: 1.05; 95% confidence interval [CI]: 0.79 to 1.38). The effect of CABG was similar whether the patient had angina (HR: 0.89; 95% CI: 0.71 to 1.13) or not (HR: 0.68; 95% CI: 0.50 to 0.94; p interaction = 0.14). Patients assigned to CABG were more likely to report improvement in angina than those assigned to medical therapy alone (odds ratio: 0.70; 95% CI: 0.55 to 0.90; p < 0.01). Angina does not predict all-cause mortality in medically treated patients with LV systolic dysfunction and CAD, nor does it identify patients who have a greater survival benefit from CABG. However, CABG does improve angina to a greater extent than medical therapy alone. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Relation between N-terminal pro-brain natriuretic peptide and cardiac remodeling and function assessed by cardiovascular magnetic resonance imaging in patients with arrhythmogenic right ventricular cardiomyopathy.

PubMed

Cheng, Huaibing; Lu, Minjie; Hou, Cuihong; Chen, Xuhua; Wang, Jing; Yin, Gang; Chu, Jianmin; Zhang, Shu; Prasad, Sanjay K; Pu, Jielin; Zhao, Shihua

2015-02-01

Although N-terminal pro-brain natriuretic peptide (NT-proBNP) is a useful screening test of impaired right ventricular (RV) function in conditions affecting the right-sided cardiac muscle, the role of NT-proBNP remains unclear in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). This study was designed to clarify the relation between the plasma NT-proBNP level and the RV function evaluated by cardiovascular magnetic resonance (CMR) imaging. We selected 56 patients with confirmed ARVC only when their blood specimens for NT-proBNP measurements were collected within 48 hours of a CMR scan. The NT-proBNP level was significantly higher in patients with RV dysfunction than in patients without RV dysfunction (median of 655.3 [interquartile range 556.4 to 870.0] vs 347.0 [interquartile range 308.0 to 456.2] pmol/L, p <0.001). The NT-proBNP levels were positively correlated with RV end-diastolic and end-systolic volume indices (r = 0.49 and 0.70, respectively) and negatively correlated with RV ejection fraction (r = -0.76, all p <0.001), which remained significant after adjustment for age, gender, and body mass index. The area under the receiver-operating characteristic curve for NT-proBNP was 0.91 (95% confidence interval 0.80 to 0.97, p <0.001). The cut-off value of NT-proBNP (458 pmol/L) was associated with sensitivity, specificity, and positive and negative predictive values of 91%, 89%, 67%, and 98%, respectively. In conclusion, NT-proBNP is a useful marker for the detection of RV dysfunction and associated with extent of RV dilatation and dysfunction determined by CMR in patients with ARVC. Copyright © 2015 Elsevier Inc. All rights reserved.

A second prosthesis as a procedural rescue option in trans-apical aortic valve implantation.

PubMed

Kempfert, Jörg; Rastan, Ardawan J; Schuler, Gerhard; Linke, Axel; Holzhey, David; van Linden, Arnaud; Mohr, Friedrich-W; Walther, Thomas

2011-07-01

Trans-apical aortic valve implantation (TA-AVI) using the Edwards SAPIEN™ prosthesis has evolved to a routine procedure for selected high-risk elderly patients. In rare cases, misplacement of the SAPIEN™ valve (too low a position), dysfunction of the leaflets or perforation of the interventricular septum (ventricular septal defect, VSD) occurs and requires immediate implantation of a second prosthesis within the first one. Results of this 'bailout' maneuver have not been reported yet. Of 305 TA-AVI procedures, 15 patients required a second prosthesis due to dysfunctional leaflets (n = 6), low position (n = 7), or VSD (n = 2). Mean age was 82.5 ± 1.3 years, mean logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) was 45.5 ± 5.4, and Society of Thoracic Surgeons (STS) Score was 13.5 ± 1.5. All second SAPIEN™ valves could be implanted successfully within the first one. The second prosthesis solved leaflet dysfunction, sealed the VSD (lower position of the second prosthesis), or corrected the initial misplacement (higher position of the second prosthesis) in all patients. Within 30 days, four patients died (low cardiac output n = 3, all with preoperative ejection fraction (EF) <35%; intestinal ischemia n = 1). Intra-operative echocardiogram and angiogram revealed mild paravalvular leak in three and none/trace in 12 patients. Transvalvular gradients were low despite the implantation of the second valve (P(max)/mean 13.7 ± 4.3/6.4 ± 2.0). Placement of a second SAPIEN™ valve is a valuable 'bailout' technique in case of VSD, dysfunctional leaflets, or too low placement of the first prosthesis. The technique leads to an excellent functional result with low transvalvular gradients. The simple, straight, tubular stent design of the SAPIEN™ prosthesis may be the ideal design for such valve-in-valve procedures. Copyright © 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

INCREASED MYOCARDIAL STIFFNESS DUE TO CARDIAC TITIN ISOFORM SWITCHING IN A MOUSE MODEL OF VOLUME OVERLOAD LIMITS ECCENTRIC REMODELING

PubMed Central

Hutchinson, Kirk R; Saripalli, Chandra; Chung, Charles S.; Granzier, Henk

2014-01-01

We investigated the cellular and molecular mechanisms of diastolic dysfunction in pure volume overload induced by aortocaval fistula (ACF) surgery in the mouse. Four weeks of volume overload resulted in significant biventricular hypertrophy; protein expression analysis in left ventricular (LV) tissue showed a marked decrease in titin's N2BA/N2B ratio with no change in phosphorylation of titin's spring region. Titin-based passive tensions were significantly increased; a result of the decreased N2BA/N2B ratio. Conscious echocardiography in ACF mice revealed eccentric remodeling and pressure volume analysis revealed systolic dysfunction: reductions in ejection fraction (EF), +dP/dt, and the slope of the endsystolic pressure volume relationships (ESPVR). ACF mice also had diastolic dysfunction: increased LV end-diastolic pressure and reduced relaxation rates. Additionally, a decrease in the slope of the end diastolic pressure volume relationship (EDPVR) was found. However, correcting for altered geometry of the LV normalized the change in EDPVR and revealed, in line with our skinned muscle data, increased myocardial stiffness in vivo. ACF mice also had increased expression of the signaling proteins FHL-1, FHL-2, and CARP that bind to titin's spring region suggesting that titin stiffening is important to the volume overload phenotype. To test this we investigated the effect of volume overload in the RBM20 heterozygous (HET) mouse model, which exhibits reduced titin stiffness. It was found that LV hypertrophy was attenuated and that LV eccentricity was exacerbated. We propose that pure volume overload induces an increase in titin stiffness that is beneficial and limits eccentric remodeling. PMID:25450617

Cardiac Dysfunction, Congestion and Loop Diuretics: their Relationship to Prognosis in Heart Failure.

PubMed

Pellicori, Pierpaolo; Cleland, John G F; Zhang, Jufen; Kallvikbacka-Bennett, Anna; Urbinati, Alessia; Shah, Parin; Kazmi, Syed; Clark, Andrew L

2016-12-01

Diuretics are the mainstay of treatment for congestion but concerns exist that they adversely affect prognosis. We explored whether the relationship between loop diuretic use and outcome is explained by the underlying severity of congestion amongst patients referred with suspected heart failure. Of 1190 patients, 712 had a left ventricular ejection fraction (LVEF) ≤50 %, 267 had LVEF >50 % with raised plasma NTproBNP (>400 ng/L) and 211 had LVEF >50 % with NTproBNP ≤400 ng/L; respectively, 72 %, 68 % and 37 % of these groups were treated with loop diuretics including 28 %, 29 % and 10 % in doses ≥80 mg furosemide equivalent/day. Compared to patients with cardiac dysfunction (either LVEF ≤50 % or NT-proBNP >400 ng/L) but not taking a loop diuretic, those taking a loop diuretic were older and had more clinical evidence of congestion, renal dysfunction, anaemia and hyponatraemia. During a median follow-up of 934 (IQR: 513-1425) days, 450 patients were hospitalized for HF or died. Patients prescribed loop diuretics had a worse outcome. However, in multi-variable models, clinical, echocardiographic (inferior vena cava diameter), and biochemical (NTproBNP) measures of congestion were strongly associated with an adverse outcome but not the use, or dose, of loop diuretics. Prescription of loop diuretics identifies patients with more advanced features of heart failure and congestion, which may account for their worse prognosis. Further research is needed to clarify the relationship between loop diuretic agents and outcome; imaging and biochemical measures of congestion might be better guides to diuretic dose than symptoms or clinical signs.

Circulating Endothelial Cells and Endothelial Function predict Major Adverse Cardiac Events and Early Adverse Left Ventricular Remodeling in Patients with ST-Segment Elevation Myocardial Infarction

PubMed Central

Magdy, Abdel Hamid; Bakhoum, Sameh; Sharaf, Yasser; Sabry, Dina; El-Gengehe, Ahmed T; Abdel-Latif, Ahmed

2016-01-01

Endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) are mobilized from the bone marrow and increase in the early phase after ST-elevation myocardial infarction (STEMI). The aim of this study was to assess the prognostic significance of CECs and indices of endothelial dysfunction in patients with STEMI. In 78 patients with acute STEMI, characterization of CD34+/VEGFR2+ CECs, and indices of endothelial damage/dysfunction such as brachial artery flow mediated dilatation (FMD) were determined. Blood samples for CECs assessment and quantification were obtained within 24 hours of admission and FMD was assessed during the index hospitalization. At 30 days follow up, the primary composite end point of major cardiac adverse events (MACE) consisting of all-cause mortality, recurrent non-fatal MI, or heart failure and the secondary endpoint of early adverse left ventricular (LV) remodeling were analyzed. The 17 patients (22%) who developed MACE had significantly higher CEC level (P = 0.004), vWF level (P =0.028), and significantly lower FMD (P = 0.006) compared to the remaining patients. Logistic regression analysis showed that CECs level and LV ejection fraction were independent predictors of MACE. The areas under the receiver operating characteristic curves (ROC) for CEC level, FMD, and the logistic model with both markers were 0.73, 0.75, and 0.82 respectively for prediction of the MACE. The 16 patients who developed the secondary endpoint had significantly higher CEC level compared to remaining patients (p =0.038). In conclusion, increased circulating endothelial cells and endothelial dysfunction predicted the occurrence of major adverse cardiac events and adverse cardiac remodeling in patients with STEMI. PMID:26864952

Latent cardiac dysfunction as assessed by echocardiography in bed-bound patients following cerebrovascular accidents: comparison with nutritional status.

PubMed

Masugata, Hisashi; Senda, Shoichi; Goda, Fuminori; Yoshihara, Yumiko; Yoshikawa, Kay; Fujita, Norihiro; Himoto, Takashi; Okuyama, Hiroyuki; Taoka, Teruhisa; Imai, Masanobu; Kohno, Masakazu

2007-07-01

The aim of this study was to elucidate the cardiac function in bed-bound patients following cerebrovascular accidents. In accord with the criteria for activities of daily living (ADL) of the Japanese Ministry of Health, Labour and Welfare, 51 age-matched poststroke patients without heart disease were classified into 3 groups: rank A (house-bound) (n = 16, age, 85 +/- 6 years), rank B (chair-bound) (n = 16, age, 84 +/- 8 years), and rank C (bed-bound) (n = 19, age, 85 +/- 9 years). Using echocardiography, the left ventricular (LV) diastolic function was assessed by the ratio of early filling (E) and atrial contraction (A) transmitral flow velocities (E/A) of LV inflow. LV systolic function was assessed by LV ejection fraction (LVEF), and the Tei index was also measured to assess both LV systolic and diastolic function. No difference was observed in the E/A and LVEF among the 3 groups. The Tei index was higher in rank C (0.56 +/- 0.17) than in rank A (0.39 +/- 0.06) and rank B (0.48 +/- 0.17), and a statistically significant difference was observed between rank A and rank C (P < 0.05). Serum albumin and blood hemoglobin were significantly lower in rank C (3.1 +/- 0.4 and 10.6 +/- 1.8 g/dL) than in rank A (4.1 +/- 0.3 and 12.4 +/- 1.2 g/dL) (P < 0.001 and P < 0.05, respectively). These results indicate that latent cardiac dysfunction and poor nutritional status may exist in bed-bound patients (rank C) following cerebrovascular accidents. The Tei index may be a useful index of cardiac dysfunction in bed-bound patients because it is independent of the cardiac loading condition.

Dietary pattern, the metabolic syndrome, and left ventricular mass and systolic function: the Multi-Ethnic Study of Atherosclerosis.

PubMed

Liu, Longjian; Nettleton, Jennifer A; Bertoni, Alain G; Bluemke, David A; Lima, João A; Szklo, Moyses

2009-08-01

Little is known about the relations between dietary patterns, metabolic dysfunction, and left ventricular (LV) function. The objective was to examine associations of dietary patterns with LV mass and function and to explore the potential role of metabolic dysfunction in the association between diet and LV function. Dietary patterns that maximally explained the variation in metabolic syndrome (MetSyn) components were derived by using reduced rank regression (RRR). LV mass, stroke volume, and LV ejection fraction (LVEF) were measured by magnetic resonance imaging. Associations between dietary pattern and LV indexes were analyzed cross-sectionally. A total of 4601 participants aged 45-84 y and free of clinical cardiovascular disease were studied. The primary RRR dietary pattern score was positively correlated with intake of foods with a high glycemic index, high-fat meats, cheeses, and processed foods and negatively correlated with low intakes of vegetables, soy, fruit, green and black tea, low-fat dairy desserts, seeds and nuts, and fish. Multivariate analyses showed that each 1-unit increase in the RRR dietary pattern score was associated with a 0.32-g/m(2) increase in LV mass/body surface area, a 0.43-mL/m(2) decrease in stroke volume/body surface area, and a 0.21% decrease in LVEF. The associations of the RRR dietary pattern score with LV mass and stroke indexes were attenuated and became nonsignificant after adjustment for all MetSyn components (P > 0.05). The results suggest that the RRR dietary pattern is significantly associated with unfavorable LV function, and this association might be mediated by metabolic dysfunction. Given the cross-sectional nature of our study, these results must be confirmed with the use of longitudinal data.

Cardiorenal Syndrome Type 5 in Sepsis: Role of Endotoxin in Cell Death Pathways and Inflammation.

PubMed

Virzì, Grazia Maria; Clementi, Anna; Brocca, Alessandra; de Cal, Massimo; Marcante, Stefano; Ronco, Claudio

2016-01-01

Cardiorenal Syndrome Type 5 (CRS Type 5) is characterized by concomitant cardiac and renal dysfunction in the setting of different systemic disorders, such as sepsis. In this study, we investigated the possible relationship between endotoxin levels, renal cell death and inflammation in septic patients with CRS Type 5. We enrolled 11 patients with CRS Type 5. CRS Type 5 was defined according to the current classification system. AKI was defined by Acute Kidney Injury Network (AKIN) criteria. Acute cardiac dysfunction was documented by echocardiography as acute left and/or right ventricular dysfunction leading to decreased ejection fraction. Endotoxin activity was measured by the Endotoxin Activity Assay (EAA). Plasma from CRS Type 5 patients was incubated with renal tubular cells (RTCs) and cell death levels were evaluated. Plasma cytokines levels were measured as well. Accordingly to EAA levels, patients were divided into two groups: 45.4% of patients had low endotoxin activity level (negative EAA), while 54.5% of patients showed high endotoxin activity (positive EAA). RTCs incubated with plasma from EAA positive patients showed significantly higher apoptosis levels and higher caspase-3 activation compared to cells incubated with plasma from EAA negative patients, and a significant positive correlation was observed between EAA levels and RTC apoptosis levels. Furthermore, IL-6 and IFN-γ levels were significantly higher in CRS Type 5 patients with positive EAA. Our data suggest a possible relationship between endotoxin levels and renal cell death in septic patients with CRS Type 5. Furthermore, this study highlights the presence of renal apoptosis, the immune deregulation and the strong inflammation in CRS Type 5 patients, especially in those with high endotoxin activity. © 2017 S. Karger AG, Basel.

Importance of SERCA2a on early isolated diastolic dysfunction induced by supravalvular aortic stenosis in rats

PubMed Central

Silveira, C.F.S.M.P.; Campos, D.H.S.; Freire, P.P.; Deus, A.F.; Okoshi, K.; Padovani, C.R.; Cicogna, A.C.

2017-01-01

Cardiac remodeling is defined as changes in shape and function of the heart in response to aggression (pressure overload). The sarcoplasmic reticulum calcium ATPase cardiac isoform 2a (SERCA2a) is a known factor that influences function. A wide spectrum of studies report a decrease in SERCA2a in heart failure, but none evaluate it's the role in early isolated diastolic dysfunction in supravalvular aortic stenosis (AoS). Our hypothesis was that SERCA2a participates in such dysfunction. Thirty-day-old male Wistar rats (60-80 g) were divided into AoS and Sham groups, which were submitted to surgery with or without aorta clipping, respectively. After 6 weeks, the animals were submitted to echocardiogram and functional analysis by isolated papillary muscle (IPM) in basal condition, hypoxia, and SERCA2a blockage with cyclopiazonic acid at calcium concentrations of 0.5, 1.5, and 2.5 mM. Western-blot analyses were used for SERCA2a and phospholamban detection. Data analysis was carried out with Student's t-test and ANOVA. AoS enhanced left atrium and E and A wave ratio, with preserved ejection fraction. Basal condition in IPM showed similar increases in developed tension (DT) and resting tension (RT) in AoS, and hypoxia was similar between groups. After cyclopiazonic acid blockage, final DT was equally decreased and RT was similar between groups, but the speed of relaxation was decreased in the AoS group. Western-blot was uniform in all evaluations. The hypothesis was confirmed, since functional parameters regarding SERCA2a were changed in the AoS group. PMID:28423119

Association of Low-Grade Albuminuria with Adverse Cardiac Mechanics: Findings from the HyperGEN Study

PubMed Central

Katz, Daniel H.; Selvaraj, Senthil; Aguilar, Frank G.; Martinez, Eva E.; Beussink, Lauren; Kim, Kwang-Youn A.; Peng, Jie; Sha, Jin; Irvin, Marguerite R.; Eckfeldt, John H.; Turner, Stephen T.; Freedman, Barry I.; Arnett, Donna K.; Shah, Sanjiv J.

2013-01-01

Introduction Albuminuria is a marker of endothelial dysfunction and has been associated with adverse cardiovascular outcomes. The reasons for this association are unclear, but may be due to the relationship between endothelial dysfunction and intrinsic myocardial dysfunction. Methods and Results In the HyperGEN study, a population- and family-based study of hypertension, we examined the relationship between urine albumin-to-creatinine ratio (UACR) and cardiac mechanics (N=1894, all of whom had normal left ventricular ejection fraction and wall motion). We performed speckle-tracking echocardiographic analysis to quantify global longitudinal, circumferential, and radial strain (GLS, GCS, and GRS, respectively), and early diastolic (e′) tissue velocities. We used E/e′ ratio as a marker of increased LV filling pressures. We used multivariable-adjusted linear mixed effect models to determine independent associations between UACR and cardiac mechanics. The mean age was 50±14 years, 59% were female, and 46% were African-American. Comorbidities were increasingly prevalent among higher UACR quartiles. Albuminuria was associated with GLS, GCS, GRS, e′ velocity, and E/e′ ratio on unadjusted analyses. After adjustment for covariates, UACR was independently associated with lower absolute GLS (multivariable-adjusted mean GLS [95% CI] for UACR Quartile 1 = 15.3 [15.0–15.5]% vs. UACR Q4 = 14.6 [14.3–14.9]%, P for trend <0.001) and increased E/e′ ratio (Q1 = 25.3 [23.5–27.1] vs. Q4 = 29.0 [27.0–31.0], P= 0.003). The association between UACR and GLS was present even in participants with UACR < 30 mg/g (P<0.001 after multivariable adjustment). Conclusions Albuminuria, even at low levels, is associated with adverse cardiac mechanics and higher E/e′ ratio. PMID:24077169

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.

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