BACKGROUND Heart failure with preserved ejection fraction (HFpEF) following acute myocardial infarction (AMI) carries substantial morbidity and mortality, yet reliable prognostic markers beyond conventional cardiovascular factors remain limited. Frailty, reflecting diminished physiological reserve, has emerged as a potential determinant of adverse outcomes in this high-risk population. Therefore, the aim of this study was to address a critical knowledge gap and to provide evidence that may guide frailty-adapted management strategies to improve prognosis and quality of life in this high-risk population.
METHODS We conducted a multicenter retrospective cohort study including 4507 patients with HFpEF discharged after AMI across 82 hospitals in China (from January 2010 to March 2024). Frailty was assessed using the Hospital Frailty Risk Score (HFRS), with HFRS < 5 defined as non-frail and HFRS ≥ 5 as frail. Multivariable Cox proportional hazards models, adjusted for demographics, comorbidities, left ventricular ejection fraction, and therapies, were applied to evaluate associations between frailty and clinical outcomes. The primary endpoints were all-cause death and major adverse cardiovascular events (MACE), which defined as the composite of cardiovascular death and heart failure rehospitalization. Secondary endpoints included net adverse clinical events (NACE), which defined as the composite of all-cause death, stroke, recurrent myocardial infarction, revascularization, and major bleeding, as well as the individual components of MACE.
RESULTS Frailty was independently associated with a higher risk of all-cause death adjusted hazard ratio (aHR) = 1.52, 95% CI: 1.31–2.03, P = 0.005 and NACE (aHR = 1.20, 95% CI: 1.02–1.41, P = 0.026). At one year, frail patients had higher unadjusted rates of all-cause death (9.0% vs. 2.9%) and NACE (19.8% vs. 13.7%) compared with non-frail patients. For cardiovascular death, the association did not reach statistical significance (aHR = 1.42, 95% CI: 0.99–2.03, P = 0.053). No significant associations were found for MACE (aHR = 1.05, 95% CI: 0.86–1.28, P = 0.636) or heart failure rehospitalization (aHR = 0.94, 95% CI: 0.75–1.19, P = 0.616).
CONCLUSIONS Frailty, as measured by the HFRS, is an independent predictor of one-year mortality and composite adverse events in post-AMI HFpEF patients. These findings support the use of HFRS at discharge to identify high-risk population who may benefit from closer follow-up, optimization of medical therapy, and targeted frailty-focused interventions.
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