Association of left ventricular geometry with outcomes and treatment response in atrial fibrillation and heart failure with preserved ejection fraction

Background Left ventricular (LV) geometric remodeling is a key pathophysiological feature in heart failure with preserved ejection fraction (HFpEF), yet its prognostic implications among patients with concomitant atrial fibrillation (AF) remain unclear. Methods In this prospective multicenter China-AF cohort study, we categorized baseline LV geometry as normal, eccentric hypertrophy, concentric remodeling, or concentric hypertrophy based on left ventricular mass index (LVMI) and relative wall thickness (RWT). The primary endpoint was a composite of cardiovascular death, thromboembolism, and major bleeding. Secondary outcomes included all-cause death and individual components. Associations were assessed using multivariable Cox regression. Results A total of 1,691 patients were included, with a median follow-up of 4.8 years. Abnormal LV geometry was present in 50.9% of patients. Concentric remodeling (adjusted HR aHR 1.53, 1.17–2.01) and concentric hypertrophy (aHR 1.48, 1.10–1.99) were independently associated with higher primary endpoint risk, with concentric hypertrophy also associated with increased cardiovascular mortality and thromboembolism. Catheter ablation was associated with a lower risk of the primary outcome, with the lowest point estimate observed in the concentric remodeling subgroup (aHR 0.29, 95% CI 0.12–0.74); however, no significant interaction by LV geometry was detected ( P for interaction = 0.147). Neither renin-angiotensin-aldosterone system inhibitors (RAASi) nor beta-blockers demonstrated benefit across geometry subtypes. Conclusion LV geometric patterns provide meaningful prognostic stratification in patients with concomitant AF and HFpEF. Concentric remodeling and concentric hypertrophy were associated with higher risks of the primary outcome and cardiovascular mortality, whereas thromboembolic risk was most evident in concentric hypertrophy. The association between catheter ablation and a lower risk of the primary outcome in the concentric remodeling subgroup should be interpreted cautiously, given the observational design and the absence of a significant interaction by LV geometry. Further studies are warranted to validate potential phenotype-guided treatment strategies in this population. Clinical trial registration URL: clinicaltrials.gov/study/NCT06987825 , Identifier NCT06987825.