Mapping and ablation outcomes of extra-pulmonary vein triggers in atrial fibrillation: Single-center retrospective study with consistent provocation protocol.

Extra-pulmonary vein triggers (ExPVTs) are recognized as important contributors to atrial fibrillation (AF) recurrence after radio-frequency catheter ablation (RFCA). This study aimed to investigate the clinical characteristics, diagnostic value, and prognostic implications of isoproterenol-induced ExPVTs in patients undergoing de novo RFCA with circumferential pulmonary vein isolation (CPVI). We analyzed 2,619 non-valvular AF patients (25.8% female, mean age 59.4 ± 10.9 years, 60.7% with paroxysmal AF) who underwent CPVI and standardized isoproterenol provocation testing; 98.2% also received empirical right atrial (RA) ablation. We evaluated the clinical and prognostic significance of ExPVTs for AF recurrence within 2 years, considering their anatomical location and targeted ablation status. ExPVTs were identified in 13.5% of patients. Lower mean left atrial (LA) voltage was independently associated with ExPVTs, irrespective of sex. Importantly, ExPVTs remained independently associated with AF recurrence (HR 1.81 [95% CI, 1.39-2.35]), alongside AF type, body mass index, LA volume index, and mean LA voltage as significant predictors. LA (HR 1.50 [1.04-2.17]) and septal (HR 1.51 [1.02-2.23]) triggers were significantly associated with recurrence, while RA triggers were not, given the high rate of empirical RA ablation (98.9%). Recurrence risk was highest in patients with multiple or unmappable triggers and in those without ExPVT-targeted ablation. ExPVTs are strongly associated with lower LA voltage and carry independent prognostic value for AF recurrence, with outcomes varying by anatomical location and targeted ablation status. These findings underscore the importance of systematic ExPVT assessment and selective targeting in individualized ablation strategies. NCT02138695.