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Low-Voltage Area Ablation for Persistent Atrial Fibrillation: Meta-Analysis and Trial Sequential Analysis of RCTs
Raymond Pranata1,2, Wilson Matthew Raffaello1,2, Mohammad Iqbal3
1Faculty of Medicine, Universitas Pelita Harapan, Tangerang, Indonesia.
Background:
Pulmonary vein isolation (PVI) often yields suboptimal success, particularly in persistent atrial fibrillation (AF). This systematic review, frequentist meta-analysis, and Bayesian hierarchical meta-analysis evaluated whether adjunctive low-voltage area (LVA) ablation improves atrial tachyarrhythmia (ATa) outcomes, while assessing safety and potential effect modifiers.
Methods:
PubMed, SCOPUS, and ScienceDirect were systematically searched for randomized controlled trials comparing PVI with versus without adjunctive LVA ablation. The primary outcome was ATa recurrence. Frequentist and Bayesian random-effects models, meta-regression, trial sequential analysis (TSA), and sensitivity analyses were performed.
Results:
Seven RCTs comprising 1468 patients (730 receiving PVI+LVA) with a mean follow-up of 16.2±4.5 months were included. Adjunctive LVA ablation significantly reduced ATa recurrence in the frequentist analysis (RR 0.80, 95% CI 0.70-0.92; p = 0.001; I2 = 0%) and time-to-event analysis (HR 0.78, 95% CI 0.65-0.95; p = 0.012; I2 = 3.2%). Bayesian hierarchical meta-analysis demonstrated concordant findings (posterior pooled RR 0.768, 95% credible interval [CrI] 0.655-0.898) with minimal between-study heterogeneity (τ = 0.077, 95% CrI 0.004-0.241). Bayesian inference showed a 99.9% posterior probability of treatment benefit (RR<1.0), a 97.6% probability of ≥10% relative risk reduction, and a 90.8% probability of ≥15% reduction. Posterior predictive analysis yielded a 97.6% probability of benefit in a future trial. Leave-one-out and prior sensitivity analyses confirmed robust, data-driven results. Meta-regression identified no significant effect modifiers. Procedure and ablation times were not significantly prolonged, and serious complications were comparable between groups (RR 1.52, 95% CI 0.84-2.74; p = 0.169). TSA showed that 47% of the required information size had been accrued. Evidence certainty was moderate by GRADE.
Conclusions:
Adjunctive LVA ablation was associated with reduced ATa recurrence compared with PVI without adjunctive LVA ablation, with consistent findings across frequentist and Bayesian analyses, without increasing serious complications.
