Risk Factors for Bleeding Following Combined Catheter Ablation and Left Atrial Appendage Occlusion in Patients With Nonvalvular Atrial Fibrillation and Low Baseline Bleeding Risk: An Exploratory Analysis

Background and objective: In patients with nonvalvular atrial fibrillation (NVAF) undergoing combined catheter ablation (CA) and left atrial appendage occlusion (LAAO), bleeding events may occur even among those classified as low risk by the HAS-BLED score (≤2). This exploratory study aimed to identify factors associated with post-procedural bleeding in this specific population. Methods: This single-center retrospective analysis included 209 NVAF patients with HAS-BLED ≤2 who underwent first-time CA and LAAO between 2021 and 2023. Patients with active bleeding or severe hepatic/renal impairment (estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m²) were excluded. The primary outcome was any Bleeding Academic Research Consortium (BARC)-defined bleeding event over a mean follow-up of 30 months. Bleeding severity (BARC 1, ≥2, ≥3) and timing (periprocedural (≤30 days) vs. late) were characterized. Given the limited number of bleeding events (n=10), multivariable analysis employed Firth's penalized-likelihood regression to reduce small-sample bias. Model performance was assessed using the c-statistic with optimism-corrected bootstrap validation. Results: Ten patients (4.78%) experienced bleeding events (incidence rate: 1.96 per 100 person-years). Bleeding was predominantly BARC ≥2 (n=8, 80%), with five events (50%) occurring periprocedurally. In univariable analysis, age (OR 1.17 per year, 95% CI 1.05-1.30), CHA₂DS₂-VASc score (OR 2.04, 95% CI 1.28-3.26), and renal insufficiency (eGFR <60 mL/min/1.73 m²; OR 23.87, 95% CI 5.73-99.49) were associated with bleeding. In multivariable Firth regression, age (adjusted OR (aOR) 1.13 per year, 95% CI 1.03-1.28; absolute risk difference per 10-year increase: +5.2%), history of myocardial infarction (MI) (aOR 36.82, 95% CI 2.62-446.55; absolute risk difference: +41.3%), and renal insufficiency (aOR 21.16, 95% CI 4.50-106.48; absolute risk difference: +35.8%) remained independently associated with bleeding. The optimism-corrected c-statistic was 0.82 (95% CI 0.71-0.91). However, with only 10 events and three predictors examined, the analysis is susceptible to overfitting, and effect estimates, particularly for MI, have limited precision. Conclusion: In this exploratory, hypothesis-generating analysis of NVAF patients with low HAS-BLED scores undergoing combined CA and LAAO, renal insufficiency, history of MI, and advanced age were associated with bleeding events. These findings suggest that conventional risk scores may not fully capture bleeding risk in this setting but require validation in larger, prospective multicenter cohorts before clinical application.