Feasibility, Acute Efficacy and Safety of Empirical Superior Vena Cava Isolation in Addition to Pulmonary Vein Isolation Using the Fourth-Generation Cryoballoon: Insights from a Randomized Trial.

Background/Objectives: Pulmonary vein isolation (PVI) is the standard treatment for atrial fibrillation (AF), but medium-term success rates remain suboptimal. Non-pulmonary vein triggers, particularly from the superior vena cava (SVC), contribute to AF recurrence. Empirical SVC isolation (SVCi) in addition to standard PVI may improve outcomes. This study evaluated the acute procedural efficacy and safety of PVI with adjunctive SVCi versus PVI alone in patients with paroxysmal AF (PAF). Methods: In this randomized, controlled, single-center study, 149 patients with PAF were assigned to either standard PVI (n = 74) or PVI with adjunctive empirical SVCi (n = 75) using a fourth-generation CB. Primary endpoints were acute procedural success and the incidence of procedure-related complications, particularly phrenic nerve injury (PNI) and sinus node dysfunction. Results: Acute PVI was achieved in all patients; SVCi was successful in 84.9% of the PVI + SVCi group. Major complication rates were low and comparable between groups (0% vs. 2.6%, p = 0.157). However, the overall complication rate was significantly higher in the PVI + SVCi group (50.6% vs. 6.8%, p < 0.001), driven primarily by transient or impending right PNI (38.6% vs. 6.8%, p < 0.001) and sinus node dysfunction. All PNI events resolved before the end of the procedure. Conclusions: Empirical SVCi using a fourth-generation CB is feasible and generally safe, but carries a higher risk of transient PNI and reversible sinus node dysfunction. Therefore, CB SVCi should be approached with caution. Further studies are needed to evaluate long-term outcomes and assess whether the potential benefits outweigh these procedural risks.