Atrial substrate burden determines mitral regurgitation improvement after low-voltage area ablation: a post-hoc analysis of the SUPPRESS-AF randomized trial

Background The SUPPRESS-AF randomized trial demonstrated that adjunctive low-voltage area (LVA) ablation did not improve rhythm outcomes compared with pulmonary vein isolation (PVI) alone in patients with persistent atrial fibrillation (AF). However, the impact of substrate modification on structural reverse remodeling, including improvement in functional mitral regurgitation (MR), remains unclear. Purpose To determine whether atrial substrate burden identifies patients who derive structural benefit from adjunctive low-voltage area ablation after AF ablation. Methods This study represents a post-hoc analysis of the SUPPRESS-AF randomized trial comparing PVI alone with PVI plus adjunctive LVA ablation. Patients with persistent AF, left atrial low-voltage areas ≥5 cm², and paired pre- and post-ablation echocardiographic assessments were included. MR improvement was defined as a ≥1-grade reduction between baseline and follow-up echocardiography among patients with baseline MR ≥1. Logistic regression analysis was used to evaluate the association between randomized treatment allocation and MR improvement. Effect modification was assessed according to atrial substrate burden using interaction analyses. Continuous interaction analyses were performed to evaluate treatment effect across LVA extent. Results A total of 275 patients with baseline MR ≥1 were included. MR improvement occurred more frequently in the LVA ablation group than in the PVI-alone group (37% vs 25%, Figure 1). Adjunctive LVA ablation was associated with a significantly higher likelihood of MR improvement (odds ratio 1.76, 95% confidence interval 1.05–2.95, p=0.033). The association between LVA ablation and MR improvement was significantly modified by atrial substrate burden (P for interaction = 0.02). Patients with smaller LVAs (<20 cm²) demonstrated the greatest treatment effect, with MR improvement rates of 42% in the LVA ablation group compared with 23% in the PVI-alone group (Figure 2). In contrast, little or no additional benefit of LVA ablation was observed in patients with more extensive LVAs. Continuous interaction analyses showed that the probability of MR improvement was consistently higher with LVA ablation than with PVI alone, with the greatest benefit observed in patients with smaller substrate burden. AF recurrence rates did not differ between ablation strategies. Conclusions In this post-hoc analysis of the SUPPRESS-AF randomized trial, adjunctive LVA ablation was associated with improvement in mitral regurgitation after AF ablation. The benefit of substrate modification was greatest in patients with smaller atrial substrate burden, suggesting that substrate extent determines the reversibility of functional mitral regurgitation after AF ablation. These findings suggest that substrate burden may serve as a practical marker to guide patient selection for adjunctive LVA ablation.Figure 1Figure 2