Ethanol Infusion of the Vein of Marshall-Based Strategies for Persistent Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Trials

Abstract Background and Aims Pulmonary vein isolation (PVI) alone achieves modest arrhythmia freedom in persistent atrial fibrillation (PeAF). Ethanol infusion of the vein of Marshall (EIVOM) overcomes heat-sink effects, facilitating mitral isthmus (MI) block, and may represent an effective adjunctive ablation strategy. We aimed to quantify the efficacy and safety of EIVOM through a meta-analysis of randomized controlled trials (RCTs). Methods and Results Systematic review of MEDLINE, Web of Science, and PubMed identified 5 RCTs enrolling 1,179 patients (602 EIVOM, 577 control). The primary endpoint was 12-month freedom from any atrial arrhythmia. Random-effects models generated risk ratios (RR) with 95% confidence intervals (CI). Time-to-event data were pooled using a generic inverse-variance approach to derive hazard ratios (HR). EIVOM-based strategies improved freedom from any arrhythmia (RR 1.16, 95% CI 1.04–1.29; P<0.001; NNT=10) and from AF (RR 1.11, 95% CI 1.05–1.18; P<0.001; NNT=13). Time-to-event analysis demonstrated a sustained reduction in recurrence hazard (HR 0.72, 95% CI 0.64–0.81; P=0.003; I2=0%). Repeat ablation was reduced (RR 0.61; P=0.009). Fluoroscopy time increased (+9.08 minutes; P=0.007), while major complications were comparable (2.5% vs 2.8%; P=0.47). Trial Sequential Analysis confirmed that the cumulative Z-curve crossed the monitoring boundary for benefit for the primary endpoint, indicating that the available evidence is sufficient Conclusion In PeAF, EIVOM-based ablation strategies significantly improve 12-month arrhythmia-free survival and reduce repeat procedures without increasing major adverse events. However, the observed benefit reflects composite ablation sets rather than ethanol infusion in isolation, and the predominance of high-volume expert centres may limit generalizability.