Low-Voltage Area Ablation for Persistent Atrial Fibrillation

Importance: Pulmonary vein isolation (PVI) for persistent atrial fibrillation (AF) has demonstrated modest success rates. Ablation of atrial low-voltage areas (LVA) has shown potential results, but more data are required. Objective: To determine whether PVI plus LVA ablation is superior to PVI alone in reducing atrial arrhythmia recurrence in patients with AF. Design, Setting, and Participants: Single-blind randomized clinical trial in 14 AF ablation centers in Canada. Adults with persistent AF of more than 3 months were enrolled between August 2018 and September 2024 and followed up for 18 to 36 months through April 2026. Intervention: Patients were randomized to PVI plus LVA ablation or PVI alone. Main Outcomes and Measures: The primary outcome was atrial arrhythmia recurrence beyond 90 days after a single catheter ablation procedure. Secondary outcomes included repeat ablation for AF, atrial flutter, or atrial tachycardia, emergency visits or hospitalization, arrhythmia recurrence over 18 months, procedure duration, total ablation delivery time, AF burden, and safety outcomes. The primary efficacy analysis was based on the modified intention-to-treat principle for patients who received the intervention. Results: Among 508 enrolled patients, 253 were randomized to PVI plus LVA ablation and 255 to PVI alone. Mean (SD) age was 65.2 (9.0) years, 386 (76%) were male and 268 (54%) had LVA. After a mean (SD) follow-up of 21 (15) months, 124 (49.4%) randomized to PVI plus LVA and 146 (57.5%) randomized to PVI reached the primary outcome (hazard ratio [HR], 0.82; 95% CI, 0.65-1.04; P = .11). In the prespecified principal subgroup analysis of 268 patients with LVA, arrhythmia recurrence occurred in 68 of 138 patients (49.3%) following PVI plus LVA ablation compared with 90 of 130 patients (69.2%) following PVI alone (HR, 0.77; 95% CI, 0.66-0.91; P = .002). Arrhythmia recurrence over 18 months (37.0% vs 56.2%; HR, 0.77; 95% CI, 0.64-0.92) and AF burden were lower after PVI plus LVA ablation in this group. Among patients without LVA, recurrence was similar between ablation groups (56 of 113 [49.6%] vs 51 of 113 [45.1%]; HR, 1.09; 95% CI, 0.90-1.32). Procedure duration and ablation delivery time were longer in the PVI plus LVA ablation group. Safety outcomes were similar between groups. Conclusions and Relevance: In this study, among patients with persistent AF, adjunctive LVA ablation did not significantly reduce atrial arrhythmia recurrence in the overall population over a mean 21-month follow-up. A prespecified principal subgroup analysis of patients with LVA suggested that adjunctive LVA ablation was consistent with reduced recurrence of atrial arrhythmias in this group. Trial Registration: ClinicalTrials.gov, Identifier: NCT03347227.