Prognostic values of extra-pulmonary vein triggers after pulmonary vein isolation in patients with atrial fibrillation

Abstract Background Extra-pulmonary vein triggers (ExPVTs) have been recognized as a significant predictor of clinical recurrence of atrial fibrillation (AF) following radio-frequency catheter ablation (RFCA). This study comprehensively analyzes the clinical characteristics and prognostic value of ExPVTs. Methods We included 2,619 non-valvular AF patients (men 74.2%, 59.4 ± 10.9 years, paroxysmal AF 60.7%) who underwent de novo RFCA and consistent isoproterenol provocation tests after circumferential pulmonary vein isolation (CPVI). We assessed the ExPVT-associated clinical factors and their sensitivity and specificity in predicting 2-year AF recurrence. The prognostic value of ExPVTs based on their anatomical location and the impact of additional ablation were also investigated. Results ExPVTs were identified in 13.5% of patients. Smaller atrial epicardial adipose tissue (EAT) volumes (OR 0.99 [0.99–1.00]) and lower mean left atrial (LA) voltage (OR 0.32 [0.20–0.51], N=2,090) were independently associated with the presence of ExPVTs. The diagnostic accuracy of ExPVT for 2-year AF recurrence after RFCA showed a sensitivity of 20.3% and specificity of 88.7%, with a negative predictive value (NPV) of 77.8%. Patients with LA (HR 1.46 [1.01–2.12]) and septal (HR 1.51 [1.02–2.23]) triggers had higher 2-year AF recurrence rates compared to those without ExPVTs, but no significant difference was observed in right atrial (HR 1.28 [0.83–1.97]) triggers. Regardless of additional ablation, AF recurrence remained higher in patients with ExPVTs. During the mean follow-up of 18.1 months, patients with multiple/unmappable triggers and ExPVTs without additional ablation had the worst rhythm outcomes (log-rank p<0.001). In patients with ExPVTs, a lower mean LA wall thickness was independently associated with the absence of 2-year AF recurrence. Conclusion ExPVTs are linked to smaller atrial EAT, lower LA voltages, and higher AF recurrence, demonstrating significant diagnostic and prognostic value for predicting AF recurrence based on their anatomical and treatment characteristics, highlighting the need for a comprehensive understanding of ExPVTs in AF ablation strategies.