Heterogeneous Outcomes of Heart Failure with Better Ejection Fraction.
Ontology highlight
ABSTRACT:
SUBMITTER: Van Kirk J
PROVIDER: S-EPMC7170767 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
Publications
Heterogeneous Outcomes of Heart Failure with Better Ejection Fraction.
Van Kirk Jenny J Fudim Marat M Green Cynthia L CL Karra Ravi R
Journal of cardiovascular translational research 20191113 2
We evaluated the heterogeneity of outcomes among heart failure patients with ventricular recovery. The BEST trial studied patients with left ventricular ejection fraction (LVEF) ≤ 35%. Serial LVEF assessment was performed at baseline, 3 months, and 12 months. Heart failure with better ejection fraction (HFbEF) was defined as an LVEF > 40% at any point. Of the patients who survived to 1 year, 399 (21.3%) had HFbEF. Among subjects with HFbEF, 173 (43.4%) had "extended" recovery, 161 (40.4%) had "l ...[more]
Similar Datasets
Project description:The aim of this study was to determine whether left atrial ejection fraction (LAEF) quantified with cardiovascular magnetic resonance (CMR) was different between heart failure with preserved ejection fraction (HFpEF) and controls, and its relation to prognosis. As part of our single-centre, prospective, observational study, 188 subjects (HFpEF n?=?140, controls n?=?48) underwent phenotyping with contrast-enhanced CMR, transthoracic echocardiography, blood sampling and six-minute walk testing. LAEF was calculated using the biplane method. Atrial fibrillation (AF) was present in 43 (31%) of HFpEF subjects. Overall, LAEF (%) was lower in HFpEF patients inclusive of AF (32?±?16) or those in sinus rhythm alone (41?±?12) compared to controls (51?±?11), p?<?0.0001. LAEF correlated inversely with maximal and minimal left atrial volumes indexed (r?=??-?0.602, r?=??-?0.762), and plasma N-terminal pro-atrial natriuretic peptide (r?=??-?0.367); p?<?0.0001. During median follow-up (1429 days), there were 67 composite events of all-cause death or hospitalization for heart failure (22 deaths, 45 HF hospitalizations) in HFpEF. Lower LAEF (below median) was associated with an increased risk of composite endpoints (Log-Rank: all p?=?0.028; sinus p?=?0.036). In multivariable Cox regression analysis, LAEF (adjusted hazard ratio [HR] 0.767, 95% confidence interval [CI] 0.591-0.996; p?=?0.047) and indexed extracellular volume (HR 1.422, CI 1.015-1.992; p?=?0.041) were the only parameters that remained significant when added to a base prognostic model comprising age, prior HF hospitalization, diastolic blood pressure, lung disease, NYHA, six-minute-walk-test-distance, haemoglobin, creatinine and B-type natriuretic peptide. CMR-derived LAEF is lower in HFpEF compared to healthy controls and is a strong prognostic biomarker.
| S-EPMC6942575 | biostudies-literature
Project description:Heart failure with preserved ejection fraction (HFpEF) represents one of the greatest challenges facing cardiovascular medicine today. Despite being the most common form of heart failure worldwide, there has been limited success in developing therapeutics for this syndrome. This is largely due to our incomplete understanding of the biology driving its systemic pathophysiology and the heterogeneity of clinical phenotypes, which are increasingly being recognized as distinct HFpEF phenogroups. Development of efficacious therapeutics fundamentally relies on robust preclinical models that not only faithfully recapitulate key features of the clinical syndrome but also enable rigorous investigation of putative mechanisms of disease in the context of clinically relevant phenotypes. In this review, we propose a preclinical research strategy that is conceptually grounded in model diversification and aims to better align with our evolving understanding of the heterogeneity of clinical HFpEF. Although heterogeneity is often viewed as a major obstacle in preclinical HFpEF research, we challenge this notion and argue that embracing it may be the key to demystifying its pathobiology. Here, we first provide an overarching guideline for developing HFpEF models through a stepwise approach of comprehensive cardiac and extra-cardiac phenotyping. We then present an overview of currently available models, focused on the 3 leading phenogroups, which are primarily based on aging, cardiometabolic stress, and chronic hypertension. We discuss how well these models reflect their clinically relevant phenogroup and highlight some of the more recent mechanistic insights they are providing into the complex pathophysiology underlying HFpEF.
| S-EPMC10035274 | biostudies-literature
Project description:BackgroundGuideline recommendations for the treatment of heart failure with mildly reduced ejection fraction (HFmrEF) derive from small subgroups in post-hoc analyses of randomized trials.ObjectivesWe investigated predictors of renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors (RASI/ARNI) and beta-blockers use, and the associations between these medications and mortality/morbidity in a large real-world cohort with HFmrEF.Methods and resultsPatients with HFmrEF (EF 40-49%) from the Swedish HF Registry were included. The associations between medications and cardiovascular (CV) mortality/HF hospitalization (HFH), and all-cause mortality were assessed through Cox regressions in a 1:1 propensity score-matched cohort. A positive control analysis was performed in patients with EF < 40%, while a negative control outcome analysis had cancer-related hospitalization as endpoint. Of 12 421 patients with HFmrEF, 84% received RASI/ARNI and 88% beta-blockers. Shared-independent predictors of RASI/ARNI and beta-blockers use were younger age, being an outpatient, follow-up in specialty care, and hypertension. In the matched cohorts, use of both RASI/ARNI and beta-blocker use was separately associated with lower risk of CV mortality/HFH [hazard ratio (HR) = 0.90, 95% confidence interval (CI): 0.83-0.98 and HR = 0.82, 95% CI: 0.74-0.90, respectively] and of all-cause mortality (HR = 0.75, 95% CI: 0.69-0.81 and HR = 0.79, 95% CI: 0.72-0.87, respectively). Results were consistent at the positive control analysis, and there were no associations between treatment use and the negative control outcome.ConclusionsRASI/ARNI and beta-blockers were extensively used in this large real-world cohort with HFmrEF. Their use was safe since associated with lower mortality and morbidity. Our findings confirm the real-world evidence from previous post-hoc analyses of trials, and represent a further call for implementing guideline recommendations.
| S-EPMC10509568 | biostudies-literature
Project description:Evidence-based therapies for heart failure (HF) differ significantly according to left ventricular ejection fraction (LVEF). However, few data are available on the phenotype and prognosis of patients with HF with midrange LVEF of 40% to 55%, and the impact of recovered systolic function on the clinical features, functional capacity, and outcomes of this population is not known.We studied 944 patients with HF who underwent clinically indicated cardiopulmonary exercise testing. The study population was categorized according to LVEF as follows: HF with reduced LVEF (HFrEF; LVEF<40%; n=620); HF with midrange ejection fraction and no recovered ejection fraction (LVEF was consistent between 40% and 55%; n=107); HF with recovered midrange ejection fraction (LVEF, 40%-55% but previous LVEF<40%; n=170); and HF with preserved LVEF (HFpEF; LVEF>55%; n=47). HF with midrange ejection fraction and no recovered ejection fraction and HF with recovered midrange ejection fraction had similar clinical characteristics, which were intermediate between those of HFrEF and HFpEF, and comparable values of predicted peak oxygen consumption and minute-ventilation/carbon dioxide production slope, which were better than HFrEF and similar to HFpEF. After a median of 4.4 (2.9-5.7) years, there were 253 composite events (death, left ventricular assistant device implantation, or transplantation). In multivariable Cox-regression analysis, HF with recovered midrange ejection fraction had lower risk of composite events than HFrEF (hazard ratio, 0.25; 95% confidence interval, 0.13-0.47) and HF with midrange ejection fraction and no recovered ejection fraction (hazard ratio, 0.31; 95% confidence interval, 0.15-0.67), and similar prognosis when compared with HFpEF. In contrast, HF with midrange ejection fraction and no recovered ejection fraction tended to show intermediate risk of outcomes in comparison with HFpEF and HFrEF, albeit not reaching statistical significance in fully adjusted analyses.Patients with HF with midrange LVEF demonstrate a distinct clinical profile from HFpEF and HFrEF patients, with objective measures of functional capacity similar to HFpEF. Within the midrange LVEF HF population, recovered systolic function is a marker of more favorable prognosis.
| S-EPMC4807736 | biostudies-literature
Project description:AimsWorsening heart failure (HF) is associated with shorter left ventricular systolic ejection time (SET), but there are limited data describing the relationship between SET and clinical outcomes. Thus, the objective was to describe the association between SET and clinical outcomes in an ambulatory HF population irrespective of ejection fraction (EF).Methods and resultsWe identified ambulatory patients with HF with reduced EF (HFrEF) and HF with preserved EF (HFpEF) who had an outpatient transthoracic echocardiogram performed between August 2008 and July 2010 at a tertiary referral centre. Multivariable logistic regression was used to evaluate the association between SET and 1-year outcomes. A total of 545 HF patients (171 HFrEF, 374 HFpEF) met eligibility criteria. Compared with HFpEF, HFrEF patients were younger [median age 60 years (25th-75th percentiles 50-69) vs. 64 years (25th-75th percentiles 53-74], with fewer females (30% vs. 56%) and a similar percentage of African Americans (36% vs. 35%). Median (25th-75th percentiles) EF with HFrEF was 30% (25-35%) and with HFpEF was 54% (48-58%). Median SET was shorter (280 ms vs. 315 ms, P < 0.001), median pre-ejection period was longer (114 ms vs. 89 ms, P < 0.001), and median relaxation time was shorter (78.7 ms vs. 93.3 ms, P < 0.001) among patients with HFrEF vs. HFpEF. Death or HF hospitalization occurred in 26.9% (n = 46) HFrEF and 11.8% (n = 44) HFpEF patients. After adjustment, longer SET was associated with lower odds of the composite of death or HF hospitalization at 1 year among HFrEF but not HFpEF patients.ConclusionLonger SET is independently associated with improved outcomes among HFrEF patients but not HFpEF patients, supporting a potential role for normalizing SET as a therapeutic strategy with systolic dysfunction.
| S-EPMC7493053 | biostudies-literature
Project description:The prevalence of heart failure with preserved ejection fraction (HFpEF) is constantly increasing and no evidence-based pharmacological treatment option is available. While exercise training (ET) improves diastolic function, its metabolic mechanisms in HFpEF are unclear. We assessed the metabolic response to 12 weeks of ET in patients with HFpEF by performing a post hoc analysis of the EX-DHF-P trial (ISRCTN86879094). Plasma concentrations of 188 endogenous metabolites were measured in 44 ET and 20 usual care (UC) patients at baseline and 3-months follow-up. Metabolic differences between ET and UC from baseline to follow-up were compared and differential responses to ET were examined by random forest feature selection. ET prevented the increase of acetylornithine and carnitine as well as the decrease of three glycerophospholipids. After ET, two opposite metabolic response clusters were identified. Cluster belonging was associated with perceived well-being at baseline and changes in low-density lipoprotein but not with cardiorespiratory, ventilatory or echocardiographic parameters. These two ET-induced metabolic response patterns illustrate the heterogeneity of the HFpEF patient population. Our results suggest that other biological parameters might be helpful besides clinical variables to improve HFpEF patient stratification. Whether this approach improves response prediction regarding ET and other treatments should be explored.
| S-EPMC6572398 | biostudies-literature
Project description:We hypothesized that patients with heart failure (HF) who recover left ventricular function (HF-Recovered) have a distinct clinical phenotype, biology, and prognosis compared with patients with HF with reduced ejection fraction (HF-REF) and those with HF with preserved ejection fraction (HF-PEF).The Penn Heart Failure Study (PHFS) is a prospective cohort of 1821 chronic HF patients recruited from tertiary HF clinics. Participants were divided into 3 categories based on echocardiograms: HF-REF if EF was <50%, HF-PEF if EF was consistently ?50%, and HF-Recovered if EF on enrollment in PHFS was ?50% but prior EF was <50%. A significant portion of HF-Recovered patients had an abnormal biomarker profile at baseline, including 44% with detectable troponin I, although in comparison, median levels of brain natriuretic factor, soluble fms-like tyrosine kinase receptor-1, troponin I, and creatinine were greater in HF-REF and HF-PEF patients. In unadjusted Cox models over a maximum follow-up of 8.9 years, the hazard ratio for death, transplantation, or ventricular assist device placement in HF-REF patients was 4.1 (95% confidence interval, 2.4-6.8; P<0.001) and in HF-PEF patients was 2.3 (95% confidence interval, 1.2-4.5; P=0.013) compared with HF-Recovered patients. The unadjusted hazard ratio for cardiac hospitalization in HF-REF patients was 2.0 (95% confidence interval, 1.5-2.7; P<0.001) and in HF-PEF patients was 1.3 (95% confidence interval, 0.90-2.0; P=0.15) compared with HF-Recovered patients. Results were similar in adjusted models.HF-Recovered is associated with a better biomarker profile and event-free survival than HF-REF and HF-PEF. However, these patients still have abnormalities in biomarkers and experience a significant number of HF hospitalizations, suggesting persistent HF risk.
| S-EPMC4053508 | biostudies-literature
Project description:Background Many patients with heart failure ( HF ) with reduced ejection fraction ( HF r EF ) experience improvement or recovery of left ventricular ejection fraction ( LVEF ). Data on clinical characteristics, outcomes, and medical therapy in patients with HF with improved ejection fraction (HFiEF) are scarce. Methods and Results Of 5625 consecutive patients hospitalized for acute HF in the KorAHF (Registry [Prospective Cohort] for Heart Failure in Korea) study, 5103 patients had baseline echocardiography and 2302 patients had follow-up echocardiography at 12 months. HF phenotypes were defined as persistent HF r EF ( LVEF ≤40% at baseline and at 1-year follow-up), HF i EF ( LVEF ≤40% at baseline and improved up to 40% at 1-year follow-up), HF with midrange ejection fraction (LVEF between 40% and <50%), and HF with preserved ejection fraction ( LVEF ≥50%). The primary outcome was 4-year all-cause mortality from the time of HF i EF diagnosis. Among 1509 HF r EF patients who had echocardiography 1 year after index hospitalization, 720 (31.3%) were diagnosed as having HF i EF . Younger age, female sex, de novo HF , hypertension, atrial fibrillation, and β-blocker use were positive predictors and diabetes mellitus and ischemic heart disease were negative predictors of HF i EF . During 4-year follow-up, patients with HF i EF showed lower mortality than those with persistent HF r EF in univariate, multivariate, and propensity-score-matched analyses. β-Blockers, but not renin-angiotensin system inhibitors or mineralocorticoid receptor antagonists, were associated with a reduced all-cause mortality risk (hazard ratio: 0.59; 95% CI , 0.40-0.87; P=0.007). Benefits for outcome seemed similar among patients receiving low- or high-dose β-blockers (log-rank, P=0.304). Conclusions HF i EF is a distinct HF phenotype with better clinical outcomes than other phenotypes. The use of β-blockers may be beneficial for these patients. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT01389843.
| S-EPMC6475046 | biostudies-literature
Project description:AimsWhile heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF) are well described, determinants and outcomes of heart failure with mid-range ejection fraction (HFmrEF) remain unclear. We sought to examine clinical and biochemical predictors of incident HFmrEF in the community.Methods and resultsWe pooled data from four community-based longitudinal cohorts, with ascertainment of new heart failure (HF) classified into HFmrEF [ejection fraction (EF) 41-49%], HFpEF (EF ≥50%), and HFrEF (EF ≤40%). Predictors of incident HF subtypes were assessed using multivariable Cox models. Among 28 820 participants free of HF followed for a median of 12 years, there were 200 new HFmrEF cases, compared with 811 HFpEF and 1048 HFrEF. Clinical predictors of HFmrEF included age, male sex, systolic blood pressure, diabetes mellitus, and prior myocardial infarction (multivariable adjusted P ≤ 0.003 for all). Biomarkers that predicted HFmrEF included natriuretic peptides, cystatin-C, and high-sensitivity troponin (P ≤ 0.0004 for all). Natriuretic peptides were stronger predictors of HFrEF [hazard ratio (HR) 2.00 per 1 standard deviation increase, 95% confidence interval (CI) 1.81-2.20] than of HFmrEF (HR 1.51, 95% CI 1.20-1.90, P = 0.01 for difference), and did not differ in their association with incident HFmrEF and HFpEF (HR 1.56, 95% CI 1.41-1.73, P = 0.68 for difference). All-cause mortality following the onset of HFmrEF was worse than that of HFpEF (50 vs. 39 events per 1000 person-years, P = 0.02), but comparable to that of HFrEF (46 events per 1000 person-years, P = 0.78).ConclusionsWe found overlap in predictors of incident HFmrEF with other HF subtypes. In contrast, mortality risk after HFmrEF was worse than HFpEF, and similar to HFrEF.
| S-EPMC5899688 | biostudies-literature
Project description:Heart failure with preserved ejection fraction (HFpEF) represents a heterogeneous collection of conditions that are unified by the presence of a left ventricular ejection fraction ≥50%, evidence of impaired diastolic function and elevated natriuretic peptide levels, all within the context of typical heart failure signs and symptoms. However, while HFpEF is steadily becoming the predominant form of heart failure, disease-modifying treatment options for this population remain sparse. This review provides an overview of the diagnosis, management and prevention of HFpEF for general physicians.
| S-EPMC6334030 | biostudies-literature