Frailty Status Predicts Adverse Outcomes in Ambulatory Heart Failure With Preserved Ejection Fraction

BACKGROUND: Frailty reflects multisystem physiologic dysfunction and is linked to adverse outcomes. Its prevalence and prognostic importance in ambulatory heart failure with preserved ejection fraction (HFpEF) are unclear. OBJECTIVES: The purpose of this study was to define clinical, hemodynamic, and biological correlates of frailty in HFpEF and its association with outcomes. METHODS: Ambulatory HFpEF patients referred to the Johns Hopkins HFpEF Clinic frailty assessment defined by the five-component Physical Frailty Phenotype score (0-5) along with clinical, laboratory and echocardiographic assessment. Subsets of patients underwent pulmonary function testing, right heart catheterization and research endomyocardial biopsy. The primary outcome was HF-related hospitalization or death through 3 years. RESULTS: Among 184 patients (age 65 ± 11 years; 66% women), 75 (41%) were frail. Compared with nonfrail/prefrail patients, frail patients had worse functional class, higher N-terminal pro B-type natriuretic peptide, higher ferritin, lower hemoglobin, higher pulmonary capillary wedge pressure (PCWP), and greater endomyocardial biopsy inflammatory infiltrate. Age and PCWP correlated with higher frailty scores. Over 3 years, 87 composite events occurred. Frailty was associated with a higher risk of the primary outcomes (HR: 1.60; 95% CI: 1.05-2.44; P = 0.028; HR for men 2.49; 95% CI: 1.15-5.39; HR for women 1.32; 95% CI: 0.79-2.19). Associations remained significant after adjusting for age, body mass index, and comorbidities, but attenuated after adjusting for PCWP (HR: 1.58; 95% CI: 0.92-2.72; P = 0.100) or hemoglobin and ferritin (HR: 1.08; 95% CI: 0.65-1.78; P = 0.763). CONCLUSIONS: Frailty is common in ambulatory HFpEF. In unadjusted models, frailty is associated with higher risk, but this is attenuated after accounting for congestion and anemia/iron markers, supporting a shared pathophysiologic pathway linking frailty and HFpEF.