Sex-Related Differences in Non-Pulmonary Vein Triggers During Initial Atrial Fibrillation Ablation

Importance: Atrial fibrillation (AF) ablation aims to eliminate all AF triggers. Non-pulmonary vein (PV) triggers are observed in up to 10% of patients referred for a first AF ablation procedure. However, there are limited data on sex-specific differences in non-PV triggers. Objective: To assess the sex-specific prevalence, type, and site of origin of non-PV triggers among patients referred for a first-time AF ablation procedure. Design, Setting, and Participants: This cohort study was conducted at the Hospital of the University of Pennsylvania among 2038 consecutive patients who underwent first-time AF ablation between January 1, 2018, and December 31, 2022, and received at least 1 step of the non-PV trigger provocation protocol. Statistical analysis was performed from October 2024 to May 2025. Exposures: Patients underwent a first-time AF ablation and received at least 1 step of the non-PV trigger provocation protocol: (1) cardioversion of spontaneous AF to identify any spontaneous triggers during sinus rhythm, (2) isoproterenol infusion up to 20 to 30 µg/min, and (3) rapid atrial burst pacing. Non-PV triggers were defined as non-PV ectopic beats triggering AF or sustained focal atrial tachycardia (AT). Main Outcomes and Measures: The primary end point was atrial arrhythmia recurrence within 1 year, defined as any atrial arrhythmia lasting more than 30 seconds after the 90-day blanking period. Results: A total of 2038 patients were included (mean [SD] age, 64.7 [10.5] years; 1369 men [67.2%]). The prevalence of non-PV triggers was significantly higher among women than men (72 of 669 [10.8%] vs 91 of 1369 [6.6%]; P = .001). Right atrial triggers were more common among women than men (42 of 669 [6.3%] vs 44 of 1369 [3.2%]; P = .001). Left atrial triggers were not significantly different among women compared with men (35 of 669 [5.2%] vs 50 of 1369 [3.7%]; P = .09). Although the proportion of non-PV triggers initiating AF and sustained AT was balanced among women (AF, 34 of 72 [47.2%]; AT, 36 of 72 [50.0%]; and both, 2 of 72 [2.8%]), non-PV triggers initiating AT were predominant among men (AT, 62 of 91 [68.1%]; AF, 28 of 91 [30.8%]; and both, 1 of 91 [1.1%]). Triggers from 2 or more locations were more frequent among women than men (18 of 72 [23.6%] vs 11 of 91 [12.1%]; P = .03). Among patients for whom non-PV triggers were identified (n = 163), women had a higher 1-year atrial arrhythmia recurrence rate (adjusted hazard ratio, 1.77 [95% CI, 1.02-3.08]; P = .04). Conclusions and Relevance: In this cohort study of 2038 patients, women exhibited a higher prevalence of non-PV triggers, especially from the right atrium, than men. Women with non-PV triggers were more likely to have multiple triggers and worse postablation outcomes. These findings highlight the importance of performing systematic provocation protocol with increased vigilance among women, particularly for those with additional risk factors.