Real-World Data of Sex Differences in Atrial Fibrillation Catheter Ablation: Insights from a Prospective Multicenter Registry

Abstract Background Sex differences in atrial fibrillation (AF) ablation strategies and outcomes remain insufficiently characterized. Objective To evaluate the impact of sex on ablation strategies and clinical outcomes in patients with paroxysmal (PAF) and persistent AF (PsAF) in real-world settings. Methods Data from the REAL-AF Registry were analyzed (January 2018-May 2023). Demographics, intraoperative parameters, and outcomes were compared by sex, stratified by AF type. Results A total of 4,202 patients (41.1% women) were included. Women were older (69.02 ± 9.18 vs. 65.32 ± 10.49 years), had higher CHA2DS2-VASc scores (3.36±1.43 vs. 2.33±1.45), and were more frequently diagnosed with PAF (72.8% vs. 61.3%) (p<.001 for all). Across both AF types, women underwent more complex ablation procedures, including additional substrate modification (SM) (pulmonary vein isolation [PVI] + cavotricuspid isthmus [CTI] + SM: 25.8% vs. 22.7%, p=0.020), particularly posterior wall isolation (53.9% vs. 45.7% in PsAF; 18.2% vs. 12.3% in PAF). Generalized linear mixed models revealed similar acute success (first-pass PVI) between sexes; however, women required more repeat ablations after the blanking period (7.2% vs. 5.5%, p=0.022). Multivariable COX analysis showed women had a significantly higher long-term recurrence risk (adjusted HR 1.24, 95% CI: 1.06–1.45, p=0.009). Subgroup analysis identified female sex as an independent predictor of recurrence in ablation strategies incorporating SM, while PVI-only and PVI+CTI approaches yielded comparable outcomes. Complication rates were comparable, but women with PsAF had a higher incidence of vascular access complications (1.3% vs. 0.1%, p=0.010). Conclusions Women face higher long-term arrhythmia recurrence risks, especially in ablation strategies involving SM, despite comparable acute and short-term outcomes.