Low‐Voltage Area Ablation for Persistent Atrial Fibrillation: Meta‐Analysis and Trial Sequential Analysis of RCTs
Raymond Pranata, Wilson Matthew Raffaello, Mohammad Iqbal, Jae‐Sun UhmABSTRACT
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; I 2 = 0%) and time‐to‐event analysis (HR 0.78, 95% CI 0.65–0.95; p = 0.012; I 2 = 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.