Adjunctive empirical superior vena cava isolation with fourth-generation cryoballoon in paroxysmal atrial fibrillation does not improve outcomes and increases complications: the randomized CISPAF trial.

BACKGROUND: Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation, but non-pulmonary vein triggers, particularly the superior vena cava (SVC), may contribute to recurrence. Cryoballoon (CB) ablation has been applied for empirical SVC isolation (SVCI), yet evidence is limited and inconsistent. OBJECTIVE: The CISPAF trial evaluated the feasibility, safety, and efficacy of adjunctive SVCI using a fourth-generation CB in patients undergoing first-time PVI for paroxysmal AF (PAF). METHODS: CISPAF was a prospective, randomized, single-centre trial including 149 patients with PAF assigned to PVI alone (n = 74) or PVI + SVCI (n = 75). Ablations were performed with a fourth-generation 28-mm CB. The primary endpoint was 12-month freedom from AF; safety endpoints included a composite of major procedure-related complications, with particular attention to phrenic nerve injury (PNI) and sinus node impairment. RESULTS: Acute PVI was achieved in all patients. SVCI succeeded in 62/75 (84.9%), with real-time isolation in 45 (60.0%). Major complications occurred only in the PVI + SVCI group (2.6% vs. 0%), including one sinus node injury requiring pacemaker implantation and one vascular complication requiring surgical repair. Transient or impending PNI and transient bradycardia/junctional rhythm were more frequent with PVI + SVCI (34.7% vs. 10.8% and 17.3% vs. 2.7%; respectively; both p < 0.01), but these events were self-limited and resolved after interruption of energy delivery. At 12 months, AF-free survival did not differ significantly between groups (89.3% vs. 79.7%; log-rank p = 0.096). CONCLUSION: Adjunctive SVCI using a fourth-generation CB did not demonstrate a statistically significant improvement in arrhythmia-free survival at one year and was associated with a higher incidence of procedure-related complications. These findings do not support the routine use of empirical SVCI during initial CB ablation for PAF and should be interpreted as hypothesis-generating.