Efficacy of Low‐Voltage Area Ablation Across Substrate Size in Persistent Atrial Fibrillation: A Post Hoc Analysis of the SUPPRESS‐AF Randomized Trial

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Background Larger low‐voltage areas (LVAs) in the left atrium are associated with increased arrhythmia recurrence after atrial fibrillation (AF) ablation. The benefit of adjunctive LVA ablation may therefore depend on substrate extent. This study examined the efficacy of LVA ablation across a spectrum of LVA sizes in persistent AF. Methods The SUPPRESS‐AF (Efficacy and Safety of Left Atrial Low‐Voltage Area Guided Ablation for Recurrence Prevention Compared to Pulmonary Vein Isolation Alone in Patients With Persistent Atrial Fibrillation) trial screened 1364 patients undergoing initial ablation for persistent AF, of whom 342 with left atrial LVAs (≥5 cm 2 ) were randomized to pulmonary vein isolation with or without adjunctive LVA ablation. In the 341 analyzed patients, LVA size was categorized as small (<10 cm 2 , n=106), moderate (≥10 to <20 cm 2 , n=127), or extensive (≥20 cm 2 , n=108). The primary end point was recurrence of AF or atrial tachycardia within 1 year without antiarrhythmic drugs. Treatment effects across LVA sizes were evaluated using a Cox model with restricted cubic splines. Results AF/atrial tachycardia recurrence rates were similar between the pulmonary vein isolation+LVA ablation and pulmonary vein isolation‐alone groups in patients with small (38.5% versus 29.6%; P =0.28) and moderate LVA sizes (40.6% versus 53.5%; P =0.15). However, adjunctive LVA ablation significantly reduced recurrence in patients with extensive LVAs (34.7% versus 57.6%; P =0.029; interaction P =0.054), driven mainly by lower AF recurrence (18.4% versus 42.4%, P =0.008). Spline analysis indicated a greater treatment benefit with increasing LVA size, reaching significance around 20 cm 2 . Conclusions The efficacy of adjunctive LVA ablation increased with substrate size, with a significant benefit observed in patients with extensive LVAs. These findings support a substrate size–guided ablation strategy to optimize rhythm outcomes in persistent AF. Registration URL: https://www.umin.ac.jp/ctr ; Identifier: UMIN000035940.

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