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

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.

The purpose of this study was to define clinical, hemodynamic, and biological correlates of frailty in HFpEF and its association with outcomes.

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.

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).

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.