Pulmonary vein isolation (PVI) alone achieves modest arrhythmia control in persistent atrial fibrillation (PeAF), prompting evaluation of adjunctive strategies such as ethanol infusion of the vein of Marshall (EIVOM). A systematic review and meta-analysis of randomized controlled trials (RCTs), published in Europace, evaluated the efficacy and safety of EIVOM-based ablation strategies in this population.

MEDLINE, Web of Science, and PubMed were searched to identify eligible RCTs. Five trials enrolling 1,179 patients were included, with 602 assigned to EIVOM-based strategies and 577 to control groups. The primary endpoint was 12-month freedom from any atrial arrhythmia. Random-effects models were used to estimate risk ratios (RR) with 95% confidence intervals (CI), and time-to-event outcomes were analyzed using hazard ratios (HR) derived through a generic inverse-variance approach.

EIVOM-based strategies improved freedom from any atrial arrhythmia (RR 1.16, 95% CI 1.04-1.29; P<0.001; number needed to treat [NNT]=10) and atrial fibrillation (AF) (RR 1.11, 95% CI 1.05-1.18; P<0.001; NNT=13). Time-to-event analysis showed reduced recurrence hazard (HR 0.72, 95% CI 0.64-0.81; P=0.003; I²=0%). Repeat ablation rates were lower (RR 0.61; P=0.009).

Fluoroscopy time increased by 9.08 minutes (P=0.007), while major complication rates were comparable (2.5% vs 2.8%; P=0.47). Trial Sequential Analysis indicated that available evidence was sufficient for benefit.

EIVOM-based ablation strategies were associated with improved arrhythmia outcomes and reduced repeat procedures without increased major complications; however, findings reflect combined ablation approaches and may have limited generalizability beyond high-volume centers.