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The superior vena cava (SVC) is a main source of nonpulmonary vein (PV) ectopies initiating atrial fibrillation (AF). Empiric SVC isolation may improve rhythm outcomes after catheter ablation of AF. Because the SVC passes immediately adjacent to the right superior PV (RSPV), an electrophysiological relation could be present between the two structures. The present study aimed to estimate the interrelation between the SVC and RSPV by evaluating arrhythmogenic activities observed during catheter ablation of AF.Study subjects comprised 121 consecutive patients referred for catheter ablation of paroxysmal AF. Isoproterenol infusion was used to induce ectopies and AF. Patients were divided into two groups depending on the presence of arrhythmogenic SVC: arrhythmogenic-SVC (A-SVC) and nonarrhythmogenic SVC (Non-A-SVC) groups. The prevalence of females was higher and body surface area was smaller in the A-SVC group (N = 22) than Non-A-SVC group (N = 99). Arrhythmogenic activities were observed in 60 (49%) RSPVs, 24 (20%) right inferior PVs, 72 (59%) left superior PVs, and 31 (25%) left inferior PVs. Arrhythmogenic RSPVs were more prevalent in the A-SVC group than Non-A-SVC group (86% vs. 41%, P = 0.0001), whereas these prevalences in the other three PVs were not different between groups (P >0.3). In multivariable analysis, arrhythmogenic RSPV was the only independent predictor of arrhythmogenicity of the SVC (OR, 8.53; 95% CI 2.31–31.46; P = 0.001).An electrophysiological interrelation may be present between the SVC and RSPV in patients with paroxysmal AF. Semiempiric SVC isolation limited to patients with an arrhythmogenic RSPV may be a more efficient treatment strategy.