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The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory (HFC) and the Academic Research Consortium (ARC) composed of patients, academic investigators from the United States and Europe, the U.S. Food and Drug Administration, the National Institutes of Health, payers, and industry. Members discussed the measure, remote capture, and clinical utility of functional and quality-of-life endpoints for use in clinical trials of heart failure and cardiovascular therapeutics, with the goal of improving the efficiency of heart failure and cardiovascular clinical research, evidence generation, and thereby patient quality of life, functional status, and survival. Assessments of patient-reported outcomes and maximal and submaximal exercise tolerance are standardized and validated, but actigraphy remains inconsistent as a potential endpoint. This paper details those discussions and consensus recommendations.

This study evaluated the association of transthyretin (TTR) gene variant, in which isoleucine substitutes for valine at position 122 (V142I), with cardiac structure, function, and heart failure (HF) risk among middle-aged Black adults.The valine-to-isoleucine substitution in the TTR protein is prevalent in Black individuals and causes cardiac amyloidosis.Jackson Heart Study participants without HF at baseline who had available data on the TTR V142I variant were included. The association of the TTR V142I variant with baseline echocardiographic parameters and repeated measures of high-sensitivity cardiac troponin-I (hs-cTnI) was assessed using adjusted linear regression models and linear mixed models, respectively. Adjusted Cox models, restricted mean survival time analysis, and Anderson-Gill models were constructed to determine the association of TTR V142I variant with the risk of incident HF, survival free of HF, and total HF hospitalizations.A total of 119 of 2,960 participants (4%) were heterozygous carriers of the TTR V142I variant. The TTR V142I variant was not associated with measures of cardiac parameters at baseline but was associated with a greater increase in high-sensitivity troponin I (hs-TnI) levels over time. In adjusted Cox models, TTR V142I variant carriers had significantly higher risk of incident HF (HR: 1.80; 95% CI: 1.07-3.05; P = 0.03), lower survival free of HF (mean difference: 4.0 year; 95% CI: 0.6-6.2 years); P = 0.02), and higher risk of overall HF hospitalizations (HR: 2.12; 95% CI: 1.23-3.63; P = 0.007).The TTR V142I variant in middle-aged Black adults is not associated with adverse cardiac remodeling but was associated with a significantly higher burden of chronic myocardial injury, and greater risk of incident HF and overall HF hospitalizations.

Using latent class analysis (LCA) of EMPA-REG OUTCOME (BI 10773 [Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), this study identified distinct phenotypes in subjects with type 2 diabetes (T2D) and cardiovascular (CV) disease and explored treatment effects across phenotypes.In the EMPA-REG OUTCOME trial, empagliflozin reduced risk of CV death or hospitalization for heart failure (HHF) by 34% in subjects with T2D and CV disease. Among such subjects, there has been limited evaluation of clinical phenotypes.Overall, 7,020 participants were treated with empagliflozin 25 mg, 10 mg, or placebo. For this post hoc analysis, participants were randomly separated into training (two-thirds of patients) and validation (remaining one-third) sets. LCA identified 3 phenotype groups (n = 6,639 with complete data). The phenotype association with CV death or HHF and empagliflozin treatment effect across groups was explored by Cox regression (in training and validation sets).In the training set, phenotype group 1 (n = 1,463; 33.1%) included younger patients with shorter T2D duration and the highest estimated glomerular filtration rate (eGFR). Phenotype group 2 (n = 1,172; 26.5%) included more women with non-coronary artery disease. Phenotype group 3 (n = 1,785; 40.4%) included older patients with advanced coronary disease and the lowest eGFR. The risk of CV death varied across phenotypes (group 2 vs. 1: hazard ratio [HR]; 1.83; 95% confidence interval [CI]: 1.23 to 2.71; group 3 vs. 1: HR: 1.86; 95% CI: 1.30 to 2.67) with similar patterns for CV death or HHF. Consistent treatment effects of empagliflozin were seen across phenotypes in the training and validation sets (interaction p0.30).Among participants with T2D, this study identified 3 phenotypes with varying CV risk. The treatment effect across phenotypes reaffirms the robustness of CV death or HHF reduction with empagliflozin. (BI 10773 [Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients [EMPA-REG OUTCOME]; NCT01131676).

Objectives This study sought to evaluate the independent associations and interactions between high-sensitivity cardiac troponin I (hs-cTnI) and physical activity (PA) with risk of heart failure (HF) subtypes, HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). Background Black adults are at high risk for developing HF. Physical inactivity and subclinical myocardial injury, as assessed by hs-cTnI concentration, are independent risk factors for HF. Methods Black adults from the Jackson Heart Study without prevalent HF who had hs-cTnI concentration and self-reported PA assessed at baseline were included. Adjusted Cox models were used to evaluate the independent and joint associations and interaction between hs-cTnI concentrations and PA with risk of HFpEF and HFrEF. Results Among 3,959 participants, 25.1% had subclinical myocardial injury (hs-cTnI ≥4 and ≥6 ng/l in women and men, respectively), and 48.2% were inactive (moderate-to-vigorous PA = 0 min/week). Over 12.0 years of follow-up, 163 and 150 participants had an incident HFpEF and HFrEF event, respectively. In adjusted analysis, higher hs-cTnI concentration (per 1-U log increase) was associated with higher risk of HFpEF (hazard ratio [HR]: 1.47; 95% confidence interval [CI]: 1.25 to 1.72]) and HFrEF (HR: 1.57; 95% CI: 1.35 to 1.83]). In contrast, higher PA (per 1-U log increase) was associated with a lower risk of HFpEF (HR: 0.93; 95% CI: 0.88 to 0.99]) but not HFrEF. There was a significant interaction between hs-cTnI and PA for risk of HFpEF (p interaction = 0.04) such that inactive participants with subclinical myocardial injury were at higher risk of HFpEF but active participants were not. Conclusions Among Black adults with subclinical myocardial injury, higher levels of PA were associated with attenuated risk of HFpEF.

The goal of this study was to evaluate differences in clinical and patient-reported outcomes between women and men hospitalized for acute HF.Among patients hospitalized for heart failure (HF), it is unclear if symptom burden, response to therapy, and patient-reported quality of life (QOL) are different in women as compared with men.The ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial randomized 7,141 patients hospitalized for HF with reduced or preserved ejection fraction (EF) to receive nesiritide or placebo in addition to standard care. Clinical endpoints included 30-day mortality and rehospitalization and 180-day mortality. Patient-reported QOL was assessed at baseline, discharge, and 30 days using the EuroQOL 5 dimensions (EQ-5D) survey.Among 7,141 total patients, 4,697 (65.8%) were men and 2,444 (34.2%) were women. Among patients with EF ≤40%, women were less likely to receive angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker and beta-blocker therapy, and less likely to have an implantable cardioverter-defibrillator (all p 0.03). Signs and symptoms of HF were similar between men and women (all p0.05), but women experienced less in-hospital weight loss and urine output (all p 0.01). In unadjusted and adjusted analyses, men and women had similar risk of all mortality and rehospitalization endpoints (all p ≥ 0.41). Women reported lower EQ-5D utility and visual analogue scores at admission, discharge, and 30 days. Women continued to have significantly lower EQ-5D scores at all in-hospital and post-discharge time points after adjustment for clinical characteristics (all p 0.01).In this acute HF population, women had similar risk of mortality and rehospitalization as compared with men, but experienced worse patient-reported QOL during and after hospitalization that persisted after adjustment for demographic and clinical factors. Current acute HF management may work similarly in either sex for purposes of preventing clinical events, but may be less equipped to improve patient-reported outcomes in women as compared with men.

This study sought to assess the prevalence of frailty, its associations with physical function, quality of life (QoL), cognition, and depression and to investigate more efficient methods of detection in older patients hospitalized with acute decompensated heart failure (ADHF).In contrast to the outpatient population with chronic HF, much less is known regarding frailty in older, hospitalized patients with ADHF.Older hospitalized patients (N = 202) with ADHF underwent assessment of frailty (using Fried criteria), short physical performance battery (SPPB), 6-min walk test (6-MWT) distance, quality of life (QoL using the Kansas City Cardiomyopathy Questionnaire), cognition (using the Montreal Cognition Assessment), and depression (using the Geriatric Depression Screen [GDS]). The associations of frailty with these patient-centered outcomes were assessed by using adjusted linear regression models. Novel strategies to identify frailty were examined.A total of 50% of older, hospitalized patients with ADHF were frail, 48% were pre-frail, and 2% were non-frail. Female sex, burden of comorbidity, and prior HF hospitalization were significantly associated with higher likelihood of frailty. Frailty (vs. pre-frail status) was associated with a significantly worse SPPB score (5 ± 2.2 vs. 7 ± 2.4, respectively), 6-MWT distance (143 ± 79 m vs. 221 ± 99 m, respectively), QoL (35 ± 19 vs. 46 ± 21, respectively), and more depression (GDS score: 5.5 ± 3.5 vs. 4.2 ± 3.3, respectively) but similar cognition. These associations were unchanged after adjustment for age, sex, race, total comorbidities, and body mass index. Slow gait speed plus low physical activity signaled frailty status as well (C-statistic = 0.85).Ninety-eight percent of older, hospitalized patients with ADHF are frail or pre-frail. Frailty (vs. pre-frail status) is associated with worse physical function, QoL, comorbidity, and depression. The simple 4-m walk test combined with self-reported physical activity may quickly and efficiently identify frailty in older patients with ADHF.

This study sought to evaluate the influence of baseline physical activity (PA) on responses to aerobic exercise training and clinical events in outpatients with chronic systolic heart failure (HF) from the multicenter HF-ACTION (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure) trial.The influence of baseline PA on exercise capacity, responses to exercise training and clinical outcomes in patients with chronic HF is unclear.Of 2,130 participants who provided consent for this analysis, 1,494 patients (64%) had complete baseline PA data, using a modified version of the International Physical Activity Questionnaire-Short Form questionnaire and were included in the analysis; 742 received usual care and 752 were allocated to the exercise training group. Changes in exercise capacity, all-cause mortality and hospitalization, cardiovascular (CV) mortality and hospitalization, and CV mortality and HF hospitalization were evaluated as a function of baseline PA tertile.At baseline, the highest PA tertile showed greater peak oxygen uptake, cardiopulmonary exercise test duration, and 6-min walk test distance than the other 2 PA tertiles, as well as lower New York Heart Association functional class, lower Beck depression score, and lower atrial fibrillation prevalence than the lowest PA tertile. Compared to the lowest PA tertile, the middle tertile had 18% lower risk of CV death/CV hospitalizations, and the upper tertile showed 23% lower risk of CV death/HF hospitalizations. Exercise capacity and clinical outcome responses to training were similar and largely nonsignificant across baseline PA tertiles with significant benefit of training on exercise test duration for all tertiles.In patients with chronic systolic HF, aerobic exercise training significantly improves exercise test duration to a similar extent across baseline PA tertiles. Although higher baseline PA was associated with lower risk of clinical events, no significant differences in event rates within each PA tertile were seen between subgroups randomized to exercise training versus usual care. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure [HF-ACTION]; NCT00047437).

This study sought to evaluate and contribute to the limited data on U.S. hospital practice patterns with respect to respiratory vaccination in patients hospitalized with heart failure (HF).Respiratory infection is a major driver of morbidity in patients with HF, and many influenza and pneumococcal infections may be prevented by vaccination.This study evaluated patients hospitalized at centers participating in the Get With The Guidelines-HF (GWTG-HF) registry from October 2012 to March 2017. The proportion of patients receiving vaccination was described for influenza and pneumococcal vaccination, respectively. The association of hospital-level vaccination rates with individual GWTG-HF performance measures and defect-free care was evaluated using multivariable modeling.This study evaluated 313,761 patients discharged from 392 hospitals during the study period. The proportion of patients receiving influenza vaccination was 68% overall and declined from 70% in 2012 to 2013 to 66% in 2016 to 2017 (p 0.001), although this was not statistically significant after adjustment (odds ratio: 1.05 per flu season; 95% confidence interval [CI]: 0.94 to 1.18). The proportion of patients receiving pneumococcal vaccination was 66% overall and decreased over the study period from 71% in 2013 to 60% in 2016 (p 0.001), remaining significant after adjustment (odds ratio: 0.75 per calendar year; 95% CI: 0.67 to 0.84). Hospitals with higher vaccination rates were more likely to discharge patients with higher performance on defect-free care and individual GWTG-HF performance measures (p 0.001). In a subset of patients with linked Medicare claims, vaccinated patients had similar rates of 1-year all-cause mortality (adjusted hazard ratio: 0.96 [95% CI: 0.89 to 1.03] for influenza vaccination; adjusted hazard ratio: 0.95 [95% CI: 0.89 to 1.01] for pneumococcal vaccination) compared with those not vaccinated.Nearly 1 in 3 patients hospitalized with HF at participating hospitals were not vaccinated for influenza or pneumococcal pneumonia, and vaccination rates did not improve from 2012 to 2017. Hospitals that exhibited higher vaccination rates performed well with respect to other HF quality of care measures. Vaccination status was not associated with differences in clinical outcomes. Further randomized controlled data are needed to assess the relationship between vaccination and outcomes.

Acute heart failure (HF) is a major public health problem with substantial associated economic costs. Because most patients who present to hospitals are admitted irrespective of their level of risk, novel approaches to manage acute HF are needed, such as the use of same-day access clinics for outpatient diuresis and observation units from the emergency department. Current published data lacks a comprehensive overview of the present state of acute HF management in various clinical settings. This review summarizes the strengths and limitations of acute HF care in the outpatient and emergency department settings. Finally, a variety of innovative technologies that have the potential to improve acute HF management are discussed.