Ethanol infusion of the vein of marshall-based strategies for persistent atrial fibrillation: a systematic review and meta-analysis of randomized trials

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).

Systematic review of MEDLINE, Web of Science, and PubMed identified 5 RCTs enrolling 1179 patients (602 EIVOM, 577 control). The primary endpoint was 12-month freedom from any atrial arrhythmia. Random-effects models generated risk ratios (RRs) 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; number needed to treat (NNT) = 10) and from atrial fibrillation (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 min; 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.

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.