Abstract Body (Do not enter title and authors here): Introduction/Background: Persistent Left Superior Vena Cava (PLSVC) presents unique challenges for atrial fibrillation (AF) ablation due to its arrhythmogenic potential and complex anatomical variations. Understanding tailored approaches and outcomes in patients with PLSVC and AF is essential for improving procedural success and safety.

Research Questions/Hypothesis: This study aims to investigate the efficacy and outcomes of tailored ablation strategies in patients with PLSVC and AF.

Goals/Aims: To evaluate the procedural safety, acute success, and AF recurrence rate post-ablation in patients with PLSVC, and to determine the optimal ablation strategies for this population.

Methods/Approach: This retrospective cohort study included 16 patients with PLSVC who underwent 21 AF ablation procedures between August 1, 2008, and February 14, 2024, at the Hospital of the University of Pennsylvania. Procedures involved pre-ablation imaging, 3D electroanatomical mapping, pulmonary vein isolation (PVI), and targeted ablation strategies focusing on PLSVC-related triggers. The primary endpoints were procedural safety and AF recurrence post-ablation.

Results/Data: The cohort's mean age was 51.9 ± 17.9 years, 31.2% of whom were female. Triggers from the PLSVC were identified in 66.7% of procedures. Tailored ablation strategies were employed to isolate PLSVC-left atrium/coronary sinus connections or directly target the induced triggers, with a success rate of 85% in achieving isolation or targeted ablation once triggers were induced. The recurrence rate of arrhythmia post-ablation was 58.3% in the patient-based analysis and 70.6% in the procedure-based analysis. No major complications occurred.

Conclusion(s): This study highlights the significance of recognizing PLSVC as a potential source of AF triggers. The single procedure success rate is low compared to patients without PLSVC. Further studies are warranted to enhance outcomes in this challenging AF population.