Ethanol Infusion in the Vein of Marshall for Persistent Atrial Fibrillation Ablation: Evidence From Randomized Controlled Trials

Background: Pulmonary vein isolation (PVI) is the cornerstone of catheter ablation (CA) for atrial fibrillation (AF), yet outcomes remain suboptimal in persistent AF patients. Ethanol infusion in the vein of Marshal (VoM), an embryological remnant implicated in AF pathogenesis, may enhance ablation efficacy. Objective: To evaluate the effectiveness of VoM ethanol infusion in patients with persistent AF. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) comparing CA with versus without VoM ethanol infusion in patients undergoing first-time ablation of persistent AF. The primary endpoint was freedom from any atrial arrhythmia in a 12-month follow-up. Results: Four RCTs including 1045 patients were analyzed (VoM + CA—535 patients vs. CA alone—510 patients). Ethanol infusion in the VoM significantly increased freedom from atrial arrhythmias (RR 1.21; 95% CI 1.010–1.32; p < 0.0001, NNT 10) and reduced the need of a repeat procedure (RR 0.63; 95% CI 0.45–0.87; p = 0.005). Mitral isthmus (MI) block was more frequently achieved in the VoM group (RR 1.30; 95% CI 1.03–1.65; p = 0.03) There was no significant difference in the rate of major complications (2.8% vs. 3.5%, RR 0.72; 95% CI 0.37–1.43; p = 0.35, NNH 138), although overall complications were more frequent in the VoM ethanol infusion group (RR 2.25; 95% CI 1.08–4.70; p = 0.03). Conclusion: When added to CA, ethanol infusion in the VoM improves freedom from arrhythmia without increasing the risk of major complications. These findings may support its integration into ablation strategies for persistent AF.