Efficacy of Vein of Marshall Ethanol Infusion in Patients with Paroxysmal Atrial Fibrillation Resistant to Radiofrequency Ablation

Background ​ Paroxysmal atrial fibrillation (PAF) is a common arrhythmia where pulmonary vein isolation (PVI) is the cornerstone of catheter ablation. However, achieving durable PVI, particularly at the left superior pulmonary vein (LSPV) anterior ridge, remains challenging due to complex epicardial connections via the Vein of Marshall (VOM). Objective ​ To evaluate the efficacy and safety of adjunctive VOM ethanol infusion in specific PAF patients exhibiting difficulty in left-sided PVI or inducibility of AF after PVI. Methods ​ This prospective, single-center, randomized controlled trial enrolled consecutive PAF patients (June 2021 – March 2025) meeting either criterion: 1) Persistent entrance/exit block after complete circumferential ablation around left pulmonary veins (LPVs), or 2) Inducible sustained AF (> 3 minutes) after PVI. Patients were randomized to: the VOM group (n = 28, receiving VOM ethanol infusion after standard PVI) or the Control group (n = 25, receiving supplemental radiofrequency ablation only). The primary endpoint was AF recurrence after a 3-month blanking period. VOM morphology was classified angiographically as Pencil, Tree, or Bush type. Results ​ Baseline characteristics were comparable. Over a mean follow-up of 1011.96 ± 440.64 days (VOM group) vs. 698.44 ± 523.53 days (Control group), only 1 patient (3.6%) in the VOM group experienced recurrence, compared to 9 (36.0%) in the Control group (Log-rank P = 0.0021). Kaplan-Meier analysis showed a significant difference in AF-free survival. Among the 9 recurrent patients in the Control group, 7 underwent repeat procedures, all confirming LPV reconnection. VOM morphology analysis indicated that most recurrent patients in the Control group (6/9) had the Bush type. No major procedure-related complications occurred. Conclusion ​ For PAF patients with difficult LPV isolation or inducible AF, adjunctive VOM ethanol infusion significantly reduces long-term recurrence rates with a favorable safety profile. The Bush-type VOM may be an angiographic marker for high recurrence risk after conventional ablation, suggesting a tailored approach for this specific patient subset.