Long-Term Progression to Permanent Atrial Fibrillation After Cryoballoon Pulmonary Vein Isolation: Insights From the Multicenter 1STOP Project

Background: Atrial fibrillation (AF) often progresses from paroxysmal to persistent forms, culminating in permanent AF, a transition associated with increased risks of stroke, heart failure, and hospitalization. Cryoballoon pulmonary vein isolation (CB-PVI) is an established rhythm-control strategy; however, long-term data on AF progression following ablation remain limited. This study aimed to assess the incidence of progression to permanent AF after CB-PVI and to identify clinical predictors of such progression to guide patient management. Methods: We analyzed 1330 consecutive patients enrolled in the prospective, multicenter 1STOP registry who underwent CB-PVI between 2012 and 2018 across 13 Italian centers, with ≥ 5 years of follow-up. Baseline clinical, echocardiographic, and procedural characteristics were prospectively collected. Results: During a median follow-up of 81 months, 93 patients (7.0%) progressed to permanent AF. Independent predictors of progression included baseline persistent AF (HR ≈ 2.2, p < 0.001), need for cardioversion during index procedure (HR ≈ 2.2, p = 0.001), and older age (HR 1.05 per year, p < 0.001). Patients progressing to permanent AF had larger left atrium dimensions, higher CHA2DS2-VA scores, and a greater burden of comorbidities. Among patients experiencing AF recurrence, those undergoing repeat ablation had lower rates of progression compared to those without reintervention (11.0% vs. 17.6%). Conclusion: In this large multicenter cohort, long-term progression to permanent AF after CB-PVI was relatively uncommon (7%). Baseline AF type, age, and intra-procedural cardioversion independently predicted progression. Early rhythm-control strategies and individualized risk stratification may help delay the transition to permanent AF and improve long-term rhythm outcomes.