Background: Pulmonary vein isolation (PVI) is the cornerstone of ablation in AF patients. Cryoballoon ablation (CBA) is a safe and effective strategy to achieve durable PVI in the first procedure, however patients still experience recurrence of atrial arrhythmias associated with electrical reconnection of pulmonary veins (PVs). It is unclear whether clinical parameters predict PV reconnection. The aim was to identify clinical predictors of electrical PV reconnection in patients undergoing repeat ablation due to recurrence of atrial arrhythmia after initial advanced CBA.

Methods: From the local prospective observational single-center registry all patients undergoing repeat ablation due to recurrence after a single initial advanced CBA were included in this analysis. At repeat ablation, electroanatomical 3D imaging of the LA was performed prior to RFA. Statistical analysis comprised all relevant baseline characteristics at the initial ablation. Two groups were formed. Group A included only patients with complete durable isolation of all PVs and group B including only patients showing one or more reconnected PVs at repeat ablation.

Results: A total of 2,410 patients underwent CBA performed with generation 2, 3 or 4 between 5/2012 and 3/2021. Of those, 219 patients (9.1%) underwent repeat ablation, after a median time span of 15 months. Fifty three (24%) of the patients presented with paroxysmal AF and 166 (76%) with persistent AF. Median age was 70 years. Ninety three (42%) were female. Durable PVI was found in 139 patients (63.4%). Eighty seven percent of the veins were still isolated.

Univariate regression analysis demonstrated that patients showing PV reconnection (Group B; n=80) were younger (OR1.039; p=0.003), taller (OR0.03; p=0.03), more often male (OR2.107; p=0.01), had

less structural heart disease (OR2.4; p=0.009) and a lower CHA2DS2-VASc-Score (OR1.68; p=0.001) than patients with complete durable PVI at repeat ablation (Group A; n=139).
No differences between the groups were shown for AF type, LA diameter, diabetes, chronic kidney disease, BMI, coronary artery disease, prior myocardial infarction and heart failure.

Multivariate regression analysis including all significant univariate parameters demonstrated no independent predictor of electrical PV reconnection due to intervariable multicollinearity. A trend towards earlier reablation was seen in the group showing PV reconnections.

Conclusion: Cryoballoon ablation is an effective procedure to achieve durable PVI, however PV reconnection is observed in one third of patients presenting for reablation due to symptomatic arrhythmia recurrence.
Younger age, male sex, less structural heart disease and lower CHA2DS2-VASc-Score were dependent predictors of electrical PV reconnection and show the clinical relevance of PV-triggered AF recurrence in younger and healthier patients. The data suggest that older and sicker patients tend to present later with atrial arrhythmia recurrence more frequently due to non-pulmonary vein dependent arrhythmia mechanisms.