Introduction: 

Cryoballoon ablation (CBA) for pulmonary vein isolation (PVI) is an established treatment option in symptomatic paroxysmal atrial fibrillation (AF). In symptomatic persistent AF (persAF), PVI is the cornerstone of AF ablation. Additional ablation beyond discrete PVI is controversially discussed. CBA provides broad homogenous lesions and creates wide and antral circumferential PVI. Large data on long-term success and safety of CBA in persAF is missing. 

Objectives: 

To evaluate the safety and efficacy of CBA in persAF, and to give insights in the evolution of the system, the development and implementation of different ablation protocols, and to report single procedure clinical outcome of CBA in persAF. 

Methods: 

This prospective observational single-center registry enrolled consecutive symptomatic patients suffering from persAF scheduled for PVI. All patients were treated with CBA in the initial ablation procedure. Procedural, periprocedural and outcome results were evaluated with a focus on the evolution of the ablation technique, protocols, and lab management over time. 

Results: 

From 2007 to 2019, a total of 1,190 patients with persAF, 66±11 years, underwent CBA. Left atrial size was 45±6 mm, the ejection fraction 54±8%, the CHA2DS2-VaSc-Score 2.8±1.5. A total of 4,755 (99%) of PV were isolated with CBA. The mean LA time and the median dose area product decreased from 190 min, and 4,435 cGyxcm2 (years 2007-2012) to 83 min, and 1,499 cGyxcm2 (years 2013-2019) by 56, and 66%, respectively (p<0.001, Figure).
Major complications occurred in 15 (1.3%) patients including 3 (0.25%) stroke/TIA, 1 (0.1%) tamponade, 6 (0.5%)groin complications undergoing surgery/interventions, 1 (0.1%) ASD with interventional closure, and 4 (0.34%) unresolved phrenic nerve palsy until discharge occurred in patients. Transient phrenic nerve palsy occurred in 66 (5.5%).The following factors were identified as drivers of the faster, more effective and consistently safe procedure: Higher efficacy of the next cryoballoon generation, reduction of freezing time per application, implementation of time-to- isolation guided ablation protocols, omission of the routine bonus application, learning curve, esophageal temperature monitoring, implementation of modern analgo-sedation, optimized access site management, and the use of intracardiac echocardiography.
After a single procedure and a mean follow-up time of 22 months, Kaplan-Meier Analysis of the endpoint “freedom from atrial arrhythmias” demonstrated the superior efficacy of the next generation CB as compared to the first generation CB (log rank p=0.047, Figure). Five deaths (0.4%) unrelated to the procedure occurred very late during long-term follow-up. No atrio-esophageal fistula was documented. 

Conclusion: 

CBA for persAF is safe and effective. Radiation exposure decreased tremendously, and the rate of persistent phrenic nerve palsy is very low. Optimized ablation protocols and the improved efficacy of the next generation cryoballoons provide a very reliable and predictable PVI procedure, with a favorable single-procedure outcome in persAF. However, during the long-term follow-up of up to 10 years a significant proportion of patients experienced at least one episode of AF. Further ablation strategies for patients with symptomatic AF recurrences after successful CBA have to be determined.