Efficacy of Low-Voltage Area Ablation Across Substrate Size in Persistent Atrial Fibrillation: A Post Hoc Analysis of the SUPPRESS-AF Randomized Trial.
Okada M, Sakamoto D, et al. • Journal of the American Heart Association • 2026
The efficacy of adjunctive low-voltage area ablation increased with substrate size, with a significant benefit observed in patients with extensive LVAs (≥20 cm²), supporting a substrate size-guided ablation strategy to optimize rhythm outcomes in persistent AF.
Key Findings
Results
Adjunctive LVA ablation significantly reduced AF/atrial tachycardia recurrence in patients with extensive LVAs (≥20 cm²) but not in those with small or moderate LVAs.
In patients with extensive LVAs (≥20 cm², n=108), recurrence rates were 34.7% versus 57.6% for PVI+LVA ablation versus PVI alone (P=0.029).
In patients with small LVAs (<10 cm², n=106), recurrence rates were 38.5% versus 29.6% (P=0.28), showing no significant benefit.
In patients with moderate LVAs (≥10 to <20 cm², n=127), recurrence rates were 40.6% versus 53.5% (P=0.15), also showing no significant benefit.
The interaction P-value across LVA size categories was 0.054.
Results
Among patients with extensive LVAs, adjunctive LVA ablation was primarily driven by a reduction in AF recurrence specifically.
In the extensive LVA group, AF recurrence was 18.4% in the PVI+LVA ablation group versus 42.4% in the PVI-alone group (P=0.008).
The authors described this reduction in AF/atrial tachycardia recurrence as being 'driven mainly by lower AF recurrence.'
Results
Spline analysis demonstrated a continuous, increasing treatment benefit of adjunctive LVA ablation with larger LVA size, reaching statistical significance at approximately 20 cm².
A Cox model with restricted cubic splines was used to evaluate treatment effects across the spectrum of LVA sizes.
The spline analysis indicated 'a greater treatment benefit with increasing LVA size, reaching significance around 20 cm².'
This continuous relationship supports a quantitative rather than purely categorical threshold for guiding ablation decisions.
Methods
The SUPPRESS-AF trial screened 1364 patients with persistent AF undergoing initial ablation, of whom 342 with left atrial LVAs ≥5 cm² were randomized.
341 patients were included in the final analysis after randomization.
LVA size was categorized as small (<10 cm², n=106), moderate (≥10 to <20 cm², n=127), or extensive (≥20 cm², n=108).
The primary end point was recurrence of AF or atrial tachycardia within 1 year without antiarrhythmic drugs.
The trial was registered at UMIN (Identifier: UMIN000035940).
Background
Larger low-voltage areas in the left atrium are associated with increased arrhythmia recurrence after AF ablation, motivating a substrate size-guided approach.
The premise of the analysis was that '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 was hypothesized to depend on substrate extent.
This post hoc analysis was designed to examine efficacy 'across a spectrum of LVA sizes' in the context of the SUPPRESS-AF trial.
Conclusions
The findings from this post hoc analysis support a substrate size-guided ablation strategy to optimize rhythm outcomes in persistent AF.
The authors concluded that 'the efficacy of adjunctive LVA ablation increased with substrate size.'
A significant benefit was observed specifically in patients with extensive LVAs (≥20 cm²).
The authors stated these findings 'support a substrate size-guided ablation strategy to optimize rhythm outcomes in persistent AF.'
What This Means
This research examined whether adding a specific extra step to a heart rhythm procedure — ablating (destroying) areas of scarred or damaged tissue in the left atrium called 'low-voltage areas' (LVAs) — actually helps patients with persistent atrial fibrillation (AF) avoid AF recurrence. It analyzed data from the SUPPRESS-AF trial, which studied 341 patients who were randomly assigned to receive either standard pulmonary vein isolation (PVI) alone or PVI plus additional LVA ablation. The key question was whether the benefit of this extra ablation step depends on how much scarred tissue a patient has.
The study found that patients with larger amounts of scarred tissue (extensive LVAs, measuring 20 cm² or more) benefited significantly from the additional ablation: their AF/atrial tachycardia recurrence rate was about 35% with the extra treatment compared to about 58% with standard treatment alone. In contrast, patients with small or moderate amounts of scarred tissue did not show a statistically significant benefit from the additional ablation step. A mathematical modeling analysis confirmed that the benefit of the extra ablation increases continuously as the amount of scarred tissue increases, with the benefit becoming statistically meaningful around the 20 cm² threshold.
This research suggests that not all patients with LVAs may need the additional ablation procedure — rather, it may be most useful to target it toward those with the most extensive scarring. This has practical implications for how electrophysiologists might tailor AF ablation procedures: by measuring the extent of low-voltage areas before or during the procedure, clinicians could potentially identify which patients are most likely to benefit from the extra ablation step, potentially sparing lower-risk patients from a more complex and lengthy procedure while focusing intensive treatment on those most likely to benefit.
Okada M, Sakamoto D, Masuda M, Tanaka N, Watanabe T, Minamiguchi H, et al.. (2026). Efficacy of Low-Voltage Area Ablation Across Substrate Size in Persistent Atrial Fibrillation: A Post Hoc Analysis of the SUPPRESS-AF Randomized Trial.. Journal of the American Heart Association. https://doi.org/10.1161/JAHA.125.047814