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Frailty Status Predicts Adverse Outcomes in Ambulatory Heart Failure With Preserved Ejection Fraction.
Radu Tanacli1, Rishi K Trivedi1, Masih Tajdini1
1Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
JACC. Advances
|February 26, 2026
Summary
Frailty is common in heart failure with preserved ejection fraction (HFpEF). Its association with adverse outcomes is linked to congestion and anemia, not an independent effect.
Area of Science:
- Cardiology
- Geriatrics
- Internal Medicine
Background:
- Frailty, a state of multisystem physiologic dysfunction, is associated with adverse outcomes.
- The prevalence and prognostic significance of frailty in ambulatory heart failure with preserved ejection fraction (HFpEF) remain unclear.
Purpose of the Study:
- To determine the clinical, hemodynamic, and biological factors associated with frailty in HFpEF patients.
- To investigate the relationship between frailty and adverse outcomes in this population.
Main Methods:
- 184 ambulatory HFpEF patients were assessed using the Physical Frailty Phenotype score.
- Subsets underwent right heart catheterization, pulmonary function testing, and endomyocardial biopsy.
- The primary outcome was hospitalization for heart failure or death within 3 years.
Main Results:
- 41% of patients were identified as frail.
- Frail patients exhibited worse functional class, elevated N-terminal pro B-type natriuretic peptide, higher ferritin, lower hemoglobin, and increased pulmonary capillary wedge pressure (PCWP).
- Frailty was linked to a higher risk of adverse outcomes, an association attenuated by adjusting for PCWP or anemia/iron markers.
Conclusions:
- Frailty is prevalent in ambulatory HFpEF patients.
- The prognostic impact of frailty appears mediated by factors such as fluid overload (congestion) and anemia/iron deficiency.
- These findings suggest a shared pathophysiologic pathway between frailty and HFpEF.
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