Atrial fibrillation (AF) frequently coexists with heart failure with preserved ejection fraction (HFpEF), and frailty is common in this population. This post hoc analysis of the randomized TOPCAT trial evaluated 721 participants from the Americas subgroup with AF and HFpEF. The study was published in the BMC Cardiovascular Disorders. Frailty was quantified at baseline using a deficit accumulation frailty index (FI) and categorized as FI <0.3 (Group 1), 0.3–0.4 (Group 2), and ≥0.4 (Group 3). The primary outcome was stroke; secondary outcomes included heart failure hospitalization, cardiovascular death, and all-cause mortality.

Overall, 97.8% of participants met criteria for frailty. During a mean follow-up of 36±19 months, stroke incidence was higher in Groups 2 and 3 compared with Group 1 (adjusted HR 5.01; 95% CI 2.00–12.53; P=0.001 and adjusted HR 6.35; 95% CI 2.26–17.86; P<0.001, respectively). Restricted cubic spline analysis demonstrated a linear dose–response relationship between FI and stroke risk. Higher frailty was also associated with increased cardiovascular and all-cause mortality, whereas the association with heart failure hospitalization was not statistically significant.

Limitations include post hoc design, baseline-only frailty assessment, small sample size, potential residual confounding, and restriction to the Americas subgroup.

Greater frailty severity was associated with higher stroke and mortality risk in AF with HFpEF. Larger multicenter studies are needed to validate these findings across broader populations.