The study cohort consisted of consecutive patients undergoing a repeat procedure with a three-dimensional high-density mapping guided radiofrequency ablation for recurrent atrial arrhythmias from 01/2019 to 04/2020 (time of the performance of the redo procedures) after a first-time cryoballoon ablation (time of initial ablation: 04/2016–08/2019) for the treatment of symptomatic AF. Only patients with complete procedural and biophysical datasets of both ablation procedures were included in the study. All procedures were performed at the University Hospital of Münster, Münster, Germany.

The cryoablation was performed as described before [5]. In short, diagnostic catheters were positioned in the coronary sinus and in the right ventricular apex. Subsequently, a single transseptal puncture was performed under fluoroscopic guidance. Angiograms of the pulmonary veins were performed with a multipurpose catheter (MP1SH, Boston Scientific Inc., Natick, MA, USA). Thereafter, a 28-mm cryoballoon catheter (ArcticFront Advance, Medtronic, Minneapolis, MN, USA) was introduced into the left atrium. The cryoballoon was placed at each PV ostium guided by the achieve-mapping-catheter. Heparin was administered adjusted to body weight before transseptal puncture and thereafter ACT-guided. In patients in AF, electrical cardioversion was performed before ablation to facilitate PV potentials discrimination. In the right superior and inferior veins, freezes were delivered under continuous stimulation of the phrenic nerve. Freezes were aborted if phrenic palsy occurred, or the temperature fell below − 65 °C. The number of ablation freezes ranged from 1 to 4 while in most cases one freeze of 180 s or 240 s depending on the achievement of TTI was delivered. Complete PV isolation was confirmed by entrance/exit block using the achieve-mapping catheter and in case of difficult discrimination by adenosine injection. If AF was present at the end of the procedure, electrical cardioversion was performed again.

PVI was performed in accordance with international guidelines and clinical standards with a continuation of anticoagulation during ablation and previous transesophageal echocardiography to exclude atrial thrombus and facilitate transseptal puncture routinely performed in all cases.

All patients scheduled for Redo-PVI had symptomatic documented AF recurrence after Cryo-PVI. All Redo-PVI procedures were performed using 3D high-density mapping (NavX, St. Jude Medical, St Paul, Minnesota). PV reconnection was defined as the presence of sharp near-field PV potential within the PV associated with atrial capture upon PV pacing. If PV reconnection could be proven, RF ablation was performed until complete isolation was proven by re-map as well as loss of PVP. Isolation was controlled by stimulation from the left atrium as well as the coronary sinus and the right ventricle in case of difficult discrimination of the ventricular signal.

Data on patients’ medical history, medication and demographics was taken from medical records. Procedural data was obtained from the ablation protocols, the ablation report and data obtained from the console of the cryoballoon ablation system (Medtronic), in which the temperature course of any freeze delivered is stored. In addition to basic data such as the number and time of freezes delivered, we extracted further parameters such as the temperature at 30 and 60 s of the ablation impulse, nadir temperature, time-to-isolation (TTI) and time-to-temperature (TTT). Furthermore, we defined an additional parameter, the presence of temperature-to-time-catch-up, referred to as T2T-Catch-Up, a binary variable positive when temperature in minus degree caught up with the number of seconds after initiation of the cryoablation impulse (central illustration). The corresponding T2T-Catch-Up time, a continuous variable, was calculated in PVs with T2T-Catch-Up, i.e. 12 s for T2T-Catch-Up at − 12 °C after 12 s duration of the respective freeze. Thaw time was recorded, defined as the time the PV required to warm up from − 30 to + 15 °C according to the literature [4, 6]. In case of two freezes in the same vein, the longer one or, if both were equally long, the first one, was included in the analysis.

Continuous variables were expressed as mean ± SD or median [interquartile range, IQR] for normally and non-normally distributed data, respectively, and were compared using Student’s t test or the Mann–Whitney–Wilcoxon test, as appropriate. Categorical variables were expressed as the frequency (percentage) and compared using a chi-squared test or Fisher’s exact test. Diagnostic performances of cryoballoon procedures characteristics to predict PVI durability were assessed by sensitivity (SEN), specificity (SPE), negative predictive value (NPV) and positive predictive value (PPV) for binary variables and area under the receiver operating characteristic (ROC) curve (AUC) for continuous variables. Cutoffs among continuous variables were selected using the highest Youden index on the ROC curve and according to commonly used values in the literature. Regression analyses involved nominal logistic regression. Variables with p < 0.10 in univariate analyses were included in a multivariate model.

All tests were two-tailed, and the threshold for statistical significance was set to p < 0.05. Statistical analyses were performed with JMP v15.2.0 (SAS Institute Inc., Cary, NC) and schematics were created by GraphPad Prism v9.3.0 (GraphPad Software, San Diego, CA).