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The U.S. population is aging with concurrent increases in heart failure (HF) burden. However, HF-related mortality trends among adults ≥75 years have not been investigated.The purpose of this study was to assess the trends and regional differences in HF-related mortality among older adults in the United States.Death certificates from the CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research) database were examined from 1999 to 2019 for HF-related mortality in adults ≥75 years of age. Age-adjusted mortality rates (AAMRs) per 10,000 persons and annual percent change (APC) were calculated and stratified by year, sex, race/ethnicity, and geographic region.Between 1999 and 2019, 5,014,919 HF-related deaths occurred among adults ≥75 years. The AAMR declined from 141.0 in 1999 to 108.3 in 2012 (APC: -2.1; 95% CI: -2.4 to -1.9), after which it increased to 121.3 in 2019 (APC: 1.7; 95% CI: 1.2-2.2). Men had consistently higher AAMR than women from 1999 (AAMR men: 158.3 vs women: 131.0) to 2019 (AAMR men: 141.1 vs women: 107.8). Non-Hispanic (NH) White adults had the highest overall AAMR (127.2), followed by NH Black (108.7), NH American Indian/Alaska Native (102.0), Hispanic or Latino (78.0), and NH Asian or Pacific Islander adults (57.1) AAMR also varied substantially by region (overall AAMR: Midwest 133.9; South: 119.2; West: 116.3; Northeast: 113.5), and nonmetropolitan areas had higher HF-related AAMR (147.0) than metropolitan areas (115.2). States in the top 90th percentile of HF-related AAMR were Mississippi, Oklahoma, West Virginia, Oregon, and Indiana, which had approximately double the AAMRs compared with states that fell into the lower 10th percentile.Following a period of steady decline, HF-related mortality in U.S. adults ≥75 years has increased since 2012. The highest AAMRs were observed among White adults and men, and among patients living in the Midwestern and nonmetropolitan United States. Targeted strategies are needed to prevent and treat HF among older adults to curb increasing levels of HF-related mortality.

The aim of this study was to assess trends in heart failure (HF) hospitalizations among young adults.Data are limited regarding clinical characteristics and outcomes of young adults hospitalized for HF.The National Inpatient Sample database was analyzed to identify adults aged 18 to 45 years who were hospitalized for HF between 2004 and 2018.In total, 767,180 weighted hospitalizations for HF in young adults were identified, equivalent to 4.32 (95% CI: 4.31-4.33) per 10,000 person-years. Overall HF hospitalizations per 10,000 U.S. population of young adults decreased from 2.43 in 2004 to 1.82 in 2012, followed by an increase to 2.51 in 2018. Black adults (50.1%) had a significantly higher proportion of HF hospitalizations compared with White (31.9%) and Hispanic adults (12.2%) throughout the study period. Nearly half of patients (45.8%) lived in zip codes in the lowest quartile of national household income. Overall, in-hospital mortality was 1.3%, which decreased over time; this trend was consistent by sex and race. The overall mean LOS (5.2 days) remained stable over time, while the mean inflation-adjusted cost increased from $12,449 in 2004 to $16,786 in 2018, with significant overall differences by race and sex.This longitudinal examination of U.S. clinical practice revealed that HF hospitalizations among young adults have increased since 2013. Approximately half of these patients are Black and reside in zip codes in the lowest quartile of national household income. Temporal trends showed decreased in-hospital mortality, stable adjusted lengths of stay, and increased inflation-adjusted costs, with significant racial differences in hospitalization rates.

Objectives This study investigates the prevalence and prognostic significance of mitral regurgitation (MR) in acute decompensated heart failure (ADHF) patients. Background Few studies characterize the burden of MR in heart failure. Methods The ARIC (Atherosclerosis Risk In Communities) study surveilled ADHF hospitalizations for residents ≥55 years of age in 4 U.S. communities. ADHF cases were stratified by left ventricular ejection fraction (LVEF): Results From 2005 to 2014, there were 17,931 weighted ADHF hospitalizations of which 49.2% had an LVEF Conclusions Patients with ADHF have a significant MR burden that varies with sex and race. In ADHF patients with an LVEF

Objectives The aim of this study was to evaluate the association between age and invasive cardiovascular hemodynamics during upright exercise among healthy adults. Background The marked age-related decline in maximal exercise oxygen uptake (peak VO2) may contribute to the high burden of heart failure among older individuals and their greater severity of exertional symptoms. However, the mechanisms underlying this decline are not well understood. Methods A total of 104 healthy community-dwelling volunteers age 20 to 76 years well screened for cardiovascular disease underwent exhaustive upright exercise with brachial and pulmonary artery catheters; radionuclide ventriculography; and expired gas analysis for the measurement of peak VO2, cardiac output, left ventricular stroke volume, end-diastolic volume, end-systolic volume, ejection fraction, pulmonary capillary wedge pressure, and arteriovenous oxygen difference. Results Over a 5.5-decade age range, there was a 40% decline in peak VO2 due primarily to reduced peak exercise cardiac output; peak arteriovenous oxygen difference was unaffected by age. The lower age-related exercise cardiac output was related to lower peak exercise heart rate and stroke volume. Aging was also associated with lower peak exercise ejection fraction, indicating reduced inotropic reserve. Peak exercise end-diastolic volume was lower with aging despite similar left ventricular filling pressure, suggesting age-related reduced diastolic compliance limiting the use of the Frank-Starling mechanism to compensate for reduced chronotropic and inotropic reserves. These age relationships were unaffected by sex. Conclusions The age-related decline in exercise capacity among healthy persons is due predominantly to cardiac mechanisms, including reduced chronotropic and inotropic reserve and possibly reduced Frank-Starling reserve. Peak exercise left ventricular filling pressure and arteriovenous oxygen difference are unchanged with healthy aging.

Frailty, a syndrome characterized by an exaggerated decline in function and reserve of multiple physiological systems, is common in older patients with heart failure (HF) and is associated with worse clinical and patient-reported outcomes. Although several detailed assessment tools have been developed and validated in the geriatric population, they are cumbersome, not validated in patients with HF, and not commonly used in routine management of patients with HF. More recently, there has been an increasing interest in developing simple frailty screening tools that could efficiently and quickly identify frail patients with HF in routine clinical settings. As the burden and recognition of frailty in older patients with HF increase, a more comprehensive approach to management is needed that targets deficits across multiple domains, including physical function and medical, cognitive, and social domains. Such a multidomain approach is critical to address the unique, multidimensional challenges to the care of these high-risk patients and to improve their functional status, quality of life, and long-term clinical outcomes. This review discusses the burden of frailty, the conceptual underpinnings of frailty in older patients with HF, and potential strategies for the assessment, screening, and management of frailty in this vulnerable patient population.

Objectives 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). Background In contrast to the outpatient population with chronic HF, much less is known regarding frailty in older, hospitalized patients with ADHF. Methods 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. Results 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). Conclusions 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.

Heart failure with preserved ejection fraction (HFpEF) is common, increasing in prevalence, and refractory to available pharmacotherapies. Our understanding of HFpEF has evolved from a disorder of diastolic dysfunction to a constellation of physiologic impairments that lead to elevated left ventricular filling pressures and exercise intolerance. Accordingly, the therapeutic and preventive focus has shifted to identifying lifestyle factors that may have more pleotropic effects on the pathophysiologic mechanisms that define HFpEF. Recent studies have demonstrated that physical inactivity, low fitness, and obesity are potential modifiable targets for prevention as well as management of HFpEF. In this review, we have discussed the emerging epidemiological, mechanistic, and clinical evidence that support the role of these lifestyle factors as key determinants of development and progression of HFpEF. We also summarize the available evidence and major knowledge gaps with regard to developing exercise training and weight loss as unique and effective therapeutic strategies for management of HFpEF.

Objectives The aim of this study was to compare the relative impairment in different exercise hemodynamic reserve parameters in patients with heart failure with preserved ejection fraction (HFpEF) and control patients using a study-level meta-analysis. Background A cardinal manifestation of chronic HFpEF is severely decreased exercise capacity. Developing effective therapies for exercise intolerance in HFpEF requires optimal understanding of the factors underlying exercise intolerance. Methods Data were included from 17 unique cohorts that measured peak oxygen uptake and hemodynamic or echocardiographic parameters during exercise in patients with HFpEF and control subjects in this meta-analysis. Standardized mean differences (SMDs) in the exercise reserve (exercise − resting) measures of hemodynamic or echocardiographic parameters between the HFpEF and control groups were pooled in a random-effects meta-analysis. Results The pooled analysis included 910 patients with HFpEF and 476 control subjects. In pooled analysis, patients with HFpEF had significantly lower peak oxygen uptake (SMD: −2.13; 95% confidence interval [CI]: −2.68 to −1.57). Among hemodynamic exercise reserve parameters, the largest impairment was observed in chronotropic response reserve (change in heart rate from rest to peak exercise; SMD: −1.87; 95% CI: −2.44 to −1.29), followed by exaggerated increase in pulmonary capillary wedge pressure with exercise (SMD: 1.78; 95% CI: 1.46 to 2.09). Significant abnormalities were also observed in the arteriovenous oxygen difference reserve and stroke volume reserve between the HFpEF and control groups. Conclusions The most consistent and severe hemodynamic reserve abnormalities observed in patients with HFpEF were impairment in chronotropic reserve and exaggerated increase in pulmonary capillary wedge pressure with exercise. These may be important targets for therapeutic strategies to improve exercise tolerance in patients with HFpEF.

Objectives This study evaluated the contributions of obesity and changes in body mass index (BMI) in mid-life to long-term heart failure (HF) risk independent of cardiorespiratory fitness (CRF) levels. Background Obesity and low CRF are well-established risk factors for HF. However, given the inverse association between CRF and obesity, the independent contributions of BMI toward HF risk are not fully understood. Methods We included 19,485 participants from the Cooper Center Longitudinal Study who survived to receive Medicare coverage, from 1999 to 2009. CRF was estimated in metabolic equivalents (METS) according to Balke treadmill time. Associations of BMI and BMI change with HF hospitalization after age 65 were assessed by applying a proportional hazards recurrent events model to the failure time data. Results After 127,110 person-years of follow-up, we observed 1,038 HF hospitalization events. Higher mid-life BMI was significantly associated with greater risk of HF hospitalization after adjusting for established HF risk factors (hazard ratio [HR]: 1.19; 95% confidence interval [CI]: 1.12 to 1.26) per 3 kg/m 2 higher BMI). This association was attenuated after adjusting for CRF (HR: 1.10; 95% CI: 1.03 to 1.17 per 3 kg/m 2 higher BMI). CRF accounted for 47% of the HF risk associated with BMI. BMI change was not significantly associated with risk of HF in older age after adjustment for CRF change. Conclusions Higher BMI-associated risk of HF is explained largely by differences in CRF levels. Furthermore, BMI change is not significantly associated with HF risk after adjusting for CRF changes. These findings highlight the importance of CRF in mediating BMI-associated HF risk.

Objectives This study sought to evaluate the association between early-life cardiorespiratory fitness (CRF) and measures of left ventricular (LV) structure and function in midlife. Background Low CRF in midlife is associated with a higher risk of heart failure. However, the unique contributions of early-life CRF toward measures of LV structure and function in middle age are not known. Methods CARDIA (Coronary Artery Risk Development in Young Adults) study participants with a baseline maximal treadmill test and an echocardiogram at year 25 were included. Associations among baseline CRF, CRF change, and echocardiographic LV parameters (global longitudinal strain [GLS] and global circumferential strain, E/e′) were assessed using multivariable linear regression. Results The study included 3,433 participants. After adjustment for baseline demographic and clinical characteristics, lower baseline CRF was significantly associated with higher LV strain (standardized parameter estimate [Std β] = −0.06; p = 0.03 for GLS) and ratio of early transmitral flow velocity to early peak diastolic mitral annular velocity (E/e′) (Std β = −0.10; p = 0.0001 for lateral E/e′), findings suggesting impaired contractility and elevated diastolic filling pressure in midlife. After additional adjustment for cumulative cardiovascular risk factor burden observed over the follow-up period, the association of CRF with LV strain attenuated substantially (p = 0.36), whereas the association with diastolic filling pressure remained significant (Std β = −0.05; p = 0.02 for lateral E/e′). In a subgroup of participants with repeat CRF tests at year 20, greater decline in CRF was significantly associated with increased abnormalities in GLS (Std β = −0.05; p = 0.02) and higher diastolic filling pressure (Std β = −0.06; p = 0.006 for lateral E/e′) in middle age. Conclusions CRF in young adulthood and CRF change were associated with measures of LV systolic function and diastolic filling pressure in middle age. Low CRF–associated abnormalities in systolic function were related to the associated higher cardiovascular risk factor burden. In contrast, the inverse association between CRF and LV diastolic filling pressure was independent of cardiovascular risk factor burden.

Objectives This study sought to determine whether processes of care and long-term clinical outcomes for heart failure (HF) admissions across Get With The Guidelines-Heart Failure (GWTG-HF) program participating centers differ according to HF-specific risk-adjusted 30-day readmission rates (excess readmission ratio [ERR]) as determined by the Hospital Readmission Reduction Program (HRRP). Background HRRP penalizes hospitals with higher than expected risk-adjusted 30-day readmission rates (ERR >1) for common conditions including HF. However, it is unclear whether the differences in this metric of hospital performance used by HRRP and related penalties are associated with measured quality of care and long-term outcomes. Methods We analyzed data from the GWTG-HF registry linked to Medicare claims from July 2008 to June 2011. Using publically available data on HF-ERR in 2013, we stratified the participating centers into groups with low (HF-ERR ≤1) versus high (HF-ERR >1) risk-adjusted readmission rates. We compared the care quality, in-hospital, and 1-year clinical outcomes across the 2 groups in unadjusted and multivariable adjusted analysis. Results The analysis included 171 centers with 43,143 participants; 49% of centers had high risk-adjusted 30-day readmission rates (HF-ERR >1). There were no differences between the low and high risk-adjusted 30-day readmission groups in median adherence rate to all performance measures (95.7% vs. 96.5%; p = 0.37) or median percentage of defect-free care (90.0% vs. 91.1%; p = 0.47). The composite 1-year outcome of death or all-cause readmission rates was also not different between the 2 groups (median 62.9% vs. 65.3%; p = 0.10). The high HF-ERR group had higher 1-year all-cause readmission rates (median 59.1% vs. 54.7%; p = 0.01). However, the 1-year mortality rates were lower among high versus low HF-ERR group with a trend toward statistical significance (median 28.2% vs. 31.7%; p = 0.07). Conclusions Quality of care and clinical outcomes were comparable among hospitals with high versus low risk-adjusted 30-day HF readmission rates. These findings raise questions about the validity of the HRRP performance metric in identifying and penalizing low-performance centers.

Objectives The purpose of this study was to determine the temporal trends in the adherence to heart failure (HF)–related process of care measures and clinical outcomes among patients with acute decompensated HF with reduced ejection fraction (HFrEF) and end-stage renal disease (ESRD). Background Previous studies have demonstrated significant underuse of evidence-based HF therapies among patients with coexisting ESRD and HFrEF. However, it is unclear if the proportional use of evidence-based medical therapies and associated clinical outcomes among these patients has changed over time. Methods Get With The Guidelines-HF study participants who were admitted for acute HFrEF between January 2005 and June 2014 were stratified into 3 groups on the basis of their admission renal function: normal renal function, renal insufficiency without dialysis, and dialysis. Temporal change in proportional adherence to the HF-related process of care measures and incidence of clinical outcomes (1-year mortality, HF hospitalization, and all-cause hospitalization) during the study period was evaluated across the 3 renal function groups. Results The study included 111,846 patients with HFrEF from 390 participating centers, of whom 19% had renal insufficiency but who did not require dialysis, and 3% were on dialysis. There was a significant temporal increase in adherence to evidence-based medical therapies (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker: p trend Conclusions In a large contemporary cohort of HFrEF patients with ESRD, adherence to the HF process of care measures has improved significantly over the past 10 years. Unlike patients with normal renal function, there was no significant change in 1-year clinical outcomes over time among HF patients on dialysis.

Objectives This study sought to compare the cross-sectional associations between fitness and echocardiographic measures of cardiac structure and function. Background Cardiorespiratory fitness is inversely associated with heart failure risk. However, the mechanism through which fitness lowers heart failure risk is not fully understood. Methods We included 1,678 men and 1,247 women from the Cooper Center Longitudinal Study who received an echocardiogram from 1999 to 2011. Fitness was estimated by Balke protocol (in metabolic equivalents) and also categorized into age-specific quartiles, with quartile 1 representing low fitness. Cross-sectional associations between fitness (in metabolic equivalents) and relative wall thickness, left ventricular end-diastolic diameter indexed to body surface area, left atrial volume indexed to body surface area, left ventricular systolic function, and E/e′ ratio were determined using multivariable linear regression analysis. Results Higher levels of mid-life fitness (metabolic equivalents) were associated with larger indexed left atrial volume (men: beta = 0.769, p Conclusions Low fitness is associated with a higher prevalence of concentric remodeling and diastolic dysfunction, suggesting that exercise may lower heart failure risk through its effect on favorable cardiac remodeling and improved diastolic function.