Introduction: Increasing evidence suggests early rhythm-control therapy in atrial fibrillation (AF) results in higher freedom from atrial arrhythmia (AA) recurrence and improved cardiovascular outcomes. However, the impact of specifically early cryoballoon ablation (CBA) is not well known.

Methods: We evaluated AA recurrence (≥30 sec after a 90-day blanking period), repeat ablation, and serious procedure-related complications in patients with early vs. later CBA (≤12 vs. >12 months from diagnosis) in patients enrolled in the prospective, multicenter (121 centers in 37 countries) Cryo Global Registry (NCT02752737). Subjects underwent CBA and were followed either 12 or 24 months per local standard of care.

Results: A total of 3447 subjects were followed through 12 months and a subset of 1220 through 24 months. In summary, 1573 patients (46%) had early CBA treatment at a median [IQR] of 0.3 [0.1 – 0.6] years from AF diagnosis (age 62±12 years, 35.8% female, 71.4% paroxysmal AF), and 1874 (54%) had later treatment at a median of 3.4 [1.9 – 6.7] years after diagnosis (age 61±11 years, 36.2% female, 75.0% paroxysmal AF). Early treatment patients were less hypertensive (53.5% vs 57.9%, p=0.01), had smaller left atrial diameters (41±7mm vs 42±7mm, p<0.01), lower BMI (27±5kg/m^{2 vs 28±5kg/m2, p<0.01), and less AF symptoms (1.5±1.1 vs 1.8±1.1, p<0.01). Early treatment was associated with higher acute procedural success (97.1% vs 95.2%, p<0.01). Freedom from AA recurrence in the early vs. later group was 86.0% (95% CI: 83.9-87.9%) vs. 81.0% (95% CI: 79.0-82.8%) at 12 months and 80.9% (95% CI: 77.9 – 83.5%) vs. 72.0% (95% CI: 69.0 – 74.7%) at 24 months (both P<0.01). Freedom from repeat ablation was high and not different between early and later treatment groups at 12 (93.6% vs 93.8%) and 24 months (90.2 vs. 89.2%), respectively (p=0.82). Serious procedure-related adverse events occurred in 2.4% and 3.5% of patients in the early and later treatment groups (p=0.045), respectively.}

Conclusions: After AF diagnosis, early vs. later CBA results in higher freedom from AA recurrence and is associated with fewer safety events in a real-world evaluation. The difference in comorbidities at baseline between the two cohorts may contribute to the CBA being less effective in the later treatment cohort.