Physical rehabilitation for older patients with acute HFpEF (REHAB-HFpEF) trial: Design and rationale

Older patients hospitalized for acute decompensated heart failure with preserved ejection fraction (HFpEF) experience persistently poor outcomes, including physical disability, cognitive impairment, depression, impaired health-related quality of life (HRQOL), rehospitalizations, loss of independence, and mortality. In our previous phase 2 REHAB-HF trial, an innovative physical rehabilitation intervention, delivered across three phases-inpatient, 12-week outpatient, and 3-month home-based maintenance-produced large improvements in physical function and HRQOL, with signals of reduced clinical events among patients with acute HFpEF. These findings provide a compelling rationale for a definitive, event-powered trial to evaluate clinical outcomes.

Targeting physical frailty and multisystem functional impairments using the REHAB-HF intervention-a transitional, tailored, structured, and progressive multidomain rehabilitation program focused on balance, mobility, strength, and endurance-will reduce clinical events in older, predominantly frail patients hospitalized for acute HFpEF.

REHAB-HFpEF is a multicenter, randomized, single-blind, attention-controlled phase 3 trial across 22 U.S. health system centers, enrolling 880 patients aged ≥60 years hospitalized for acute HFpEF. The primary endpoint is combined all-cause rehospitalizations and mortality at 6 months. Key secondary endpoints include major mobility disability (defined as inability to walk ≥160 meters on the 6-minute walk test) and HRQOL measured by the Kansas City Cardiomyopathy Questionnaire. Healthcare costs will also be assessed.

REHAB-HFpEF is designed to address care gaps for frail older adults with acute HFpEF, who currently lack an evidence-based rehabilitation pathway. If successful in meeting endpoints, this trial could establish a scalable rehabilitation intervention that improves recovery, reduces adverse events, and lowers healthcare costs. Findings may shift HF management paradigms, inform guidelines, and influence national coverage policy for this growing, high-risk population.

Enrollment ongoing, 478 of 880 (66%) as of 24Feb2027.

Clinicaltrials.gov ID NCT05525663, https://clinicaltrials.gov/study/NCT05525663?term=NCT05525663&rank=1.