Mortality Impact of Stroke and Major Bleeding Across the Ejection Fraction Spectrum in Patients Hospitalized for Acute Heart Failure With Prevalent Atrial Fibrillation

BACKGROUND: Whether the mortality impact of ischemic stroke and major bleeding differs across left ventricular ejection fraction (LVEF) categories in patients hospitalized for acute heart failure (AHF) with atrial fibrillation (AF) remains uncertain. METHODS: We retrospectively analyzed 716 patients hospitalized for AHF with prevalent AF (mean age 79±11 years; 49% female). During up to 3 years of follow-up (median 1.4 years), 53 patients developed stroke and 89 developed major bleeding. Time-dependent Cox models were used to evaluate associations between post-stroke and post-major bleeding states and all-cause and cardiovascular mortality, stratified by LVEF category: heart failure with reduced ejection fraction (HFrEF), mildly reduced ejection fraction (HFmrEF), and preserved ejection fraction (HFpEF). RESULTS: There were 160 deaths, including 106 cardiovascular deaths. As first qualifying events, 34 were stroke-first and 74 were bleeding-first, with the remaining patients experiencing death-first or being censored. In time-dependent Cox models, post-major bleeding status was associated with higher all-cause mortality, whereas the post-stroke association was imprecise (hazard ratio [HR] 2.00, 95% confidence interval [CI] 1.22-3.28 vs. HR 1.35, 95% CI 0.67-2.70). For cardiovascular death, neither exposure reached conventional statistical significance (HR 1.97 [95% CI 0.93-4.17] after stroke and 1.69 [0.88-3.26] after bleeding). LVEF-stratified estimates were imprecise, and interaction tests did not support definitive effect modification. CONCLUSIONS: In patients hospitalized for AHF with prevalent AF, transition into a post-major bleeding state was associated with higher subsequent all-cause mortality, whereas the post-stroke association was imprecise. LVEF-stratified findings were exploratory because interaction tests were not significant and event counts were limited. Bleeding-risk mitigation should accompany continued stroke prevention, not replace it.