Strategy-specific effects of low-voltage area-targeted ablation added to pulmonary vein isolation: a meta-analysis of randomized controlled trials

Background Low-voltage areas (LVAs) within the left atrium represent an arrhythmogenic substrate in atrial fibrillation (AF). LVA-targeted ablation is increasingly used as an adjunct to pulmonary vein isolation (PVI), but outcomes vary markedly, potentially due to differences in ablation strategies—primarily LVA isolation versus LVA homogenization. Objectives To evaluate the effectiveness of LVA-targeted ablation added to PVI, and to compare treatment effects between LVA isolation and LVA homogenization strategies. Methods Following PRISMA, we systematically searched PubMed and CENTRAL for randomized controlled trials (RCTs). Eligible studies included patients with any AF type undergoing LVA mapping, with intervention arms performing LVA-targeted ablation in addition to PVI (PVI+LVA group) and control arms performing PVI alone (PVI-alone group). Non-randomized or observational studies were excluded. The primary outcome was AF/atrial tachyarrhythmia recurrence beyond the blanking period. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using random-effects models. Subgroup analyses compared isolation versus homogenization approaches. Results Six RCTs involving 1,565 patients (PVI+LVA group, n=780; PVI-alone group, n=785) were included. Overall, adding LVA-targeted ablation to PVI reduced AF recurrence compared with PVI alone (OR 0.72; 95% CI 0.54–0.96). In strategy-specific analyses, LVA isolation was associated with a significantly lower recurrence risk (OR 0.57; 95% CI 0.38–0.87), whereas LVA homogenization showed a smaller and non-significant effect (OR 0.85; 95%CI 0.59-1.24). There was substantial heterogeneity between the two strategies (I²=90.4%), indicating a genuine difference in efficacy. Conclusions In patients with AF, LVA-targeted ablation improves rhythm outcomes when added to PVI. The benefit appears to be driven predominantly by isolation of LVA regions, rather than homogenization. These findings highlight the importance of the specific substrate-modification technique and support LVA isolation as the more effective strategy among current approaches.