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Background: Older hospitalized acute decompensated heart failure (ADHF) patients have persistently poor outcomes and delayed recovery regardless of ejection fraction. We hypothesized that impairments in physical function, frailty, cognition, mood and quality-of-life (QoL) potentially contributing to poor clinical outcomes would be similarly severe in ADHF patients ≥60 years of age with preserved versus reduced ejection fraction (HFpEF, HFrEF). Methods and Results: In 202 consecutive older (≥60 years)hospitalized ADHF patients in a multicenter trial, we prospectively performed at baseline: Short Physical Performance Battery (SPPB), six-minute walk distance (6MWD), frailty assessment, Geriatric Depression Scale (GDS), Montreal Cognitive Assessment, and QoL assessments. Older acute decompensated HFpEF (EF ≥45%, n=96) and HFrEF (EF<45%, n=106) patients had similar impairments in all physical function measures (SPPB [5.9±0.3 versus 6.2±0.2]; 6MWD [184±10 vs 186±9m]; and gait speed [0.60±0.02 versus 0.61±0.02m/sec]) and rates of frailty (55% versus 52%; p=0.70) and cognitive impairment (77% versus 81%; p=0.56) when adjusted for differences in gender, BMI, and comorbidities. However, depression and QoL were consistently worse in HFpEF versus HFrEF. Depression was usually unrecognized clinically with 38% having GDS ≥5 and no documented history of depression. Conclusion: Patients ≥60 years hospitalized with ADHF patients have broad, marked impairments in physical function and high rates of frailty and impaired cognition: these impairments are similar in HFpEF versus HFrEF. Further, depression was common and QOL was reduced, and both were worse in HFpEF than HFrEF. Depression was usually unrecognized clinically. These findings suggest opportunities for novel interventions to improve these important patient-centered outcomes. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT02196038 Identifier: NCT02196038

In metabolic obese HFpEF, the pattern of regional adipose deposition may have important adverse consequences beyond total body adiposity. Interventions targeting intra-abdominal and intermuscular fat could potentially improve exercise intolerance. (Exercise Intolerance in Elderly Patients With Diastolic Heart Failure [SECRET]; NCT00959660).

Heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure (HF) in older adults, particularly women, and is increasing in prevalence as the population ages. With morbidity and mortality on par with HF with reduced ejection fraction, it remains a most challenging clinical syndrome for the practicing clinician and basic research scientist. Originally considered to be predominantly caused by diastolic dysfunction, more recent insights indicate that HFpEF in older persons is typified by a broad range of cardiac and non-cardiac abnormalities and reduced reserve capacity in multiple organ systems. The globally reduced reserve capacity is driven by: 1) inherent age-related changes; 2) multiple, concomitant co-morbidities; 3) HFpEF itself, which is likely a systemic disorder. These insights help explain why: 1) comorbidities are among the strongest predictors of outcomes; 2) approximately 50% of clinical events in HFpEF patients are non-cardiovascular; 3) clinical drug trials in HFpEF have been negative on their primary outcomes. Embracing HFpEF as a true geriatric syndrome, with complex, multi-factorial pathophysiology and clinical heterogeneity could provide new mechanistic insights and opportunities for progress in management.