Empiric and Trigger-Guided Superior Vena Cava Isolation in AF Ablation: Systematic Review and Meta-Analysis

Background: Superior vena cava isolation (SVCI) is performed as an adjunct to pulmonary vein isolation (PVI) for atrial fibrillation, yet whether an empiric or trigger-guided strategy is preferable remains uncertain. Prior meta-analyses have been largely restricted to index procedures in paroxysmal AF and have not explicitly stratified by ablation strategy. We sought to address these gaps through a systematic review of available randomized evidence. Methods: Major databases were searched through November 2025 for RCTs comparing PVI+SVCI versus PVI alone. Trials were stratified by strategy: empiric SVCI (performed irrespective of SVC ectopy) or trigger-guided SVCI (performed only upon demonstrated SVC triggers). The primary outcome was atrial tachyarrhythmia recurrence (≥30 s) beyond the blanking period. Random-effects models, pre-specified subgroup analyses, meta-regression, and GRADE certainty assessment were performed. Results: Eight RCTs (n = 1231) were included; most enrolled paroxysmal AF, while two incorporated non-paroxysmal AF subtypes and one evaluated repeat ablation procedures. Overall, SVCI+PVI significantly reduced recurrence versus PVI alone (97/604 vs. 135/627; RR 0.77, 95% CI 0.61–0.97; p = 0.03; I2 = 0%). On stratified analysis, empiric SVCI demonstrated a significant recurrence reduction (RR 0.70, 95% CI 0.53–0.92; p = 0.01; I2 = 0%), while trigger-guided SVCI did not reach statistical significance (RR 0.80, 95% CI 0.37–1.74; p = 0.57; I2 = 52%). In paroxysmal AF (n = 1038), adjunctive SVCI significantly reduced recurrence compared with PVI alone (RR 0.68, 95% CI 0.52–0.90; p = 0.01; I2 = 0%). Fluoroscopy time was longer with SVCI; total procedure duration was comparable. Major complications were infrequent but numerically higher with SVCI+PVI (15/604 vs. 7/627; RR 1.96, 95% CI 0.87–4.38; p = 0.10). Meta-regression identified no significant effect modifiers. GRADE certainty was high for overall and empiric analyses, and moderate for trigger-guided SVCI. Conclusions: Empiric SVCI significantly reduced AT/AF recurrence as an adjunct to PVI, while trigger-guided SVCI did not demonstrate a significant benefit. These findings suggest SVC isolation confers benefit independent of prior trigger documentation, supporting the role of empiric SVCI as an adjunct to AF ablation. © 2026 Wiley Periodicals LLC.