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Aims: To identify predictors of individual late pulmonary vein (PV) reconnection after second-generation cryoballoon (CB2) ablation. Anatomic indicators of late pulmonary vein reconnection (LPVR) post-CB2 ablation have not yet been studied on an individual PV level, nor weighed against clinical and procedural factors., Methods and Results: Clinical, procedural, and PV anatomic data from 125 patients with a repeat procedure for arrhythmia recurrence after index CB2 ablation were analyzed. Preprocedural computed tomography (CT) evaluated 486 PVs for measurement of size; shape (ovality index); carina width; and orientation angle in frontal (superior/inferior) and transversal (anterior/posterior) plane (with horizontal line 0° as reference and upper/lower half circle as positive/negative value, respectively). Durable isolation in all PVs was demonstrated in 50/125 (40%) patients. Late reconnection rates at the different PVs were as follows: 16% left superior (LS), 12% left inferior (LI), 17% right superior (RS), and 31% right inferior (RI) PV. Multivariable analysis performed per vein showed following independent determinants predicting LPVR: ovality index [odds ratio (OR) 1.61, 95% confidence interval (CI) 1.07-2.41, P = 0.022] and carina width (OR 0.75, CI 0.59-0.96, P = 0.024) for LSPV; carina width (OR 0.71, CI 0.53-0.95, P = 0.020) for LIPV; frontal angle (OR 0.91, CI 0.87-0.95, P < 0.001) for RIPV; and transversal angle (OR 1.15, CI 1.03-1.31, P = 0.032) for RSPV., Conclusion: Cardiac CT-based evaluation of anatomic PV characteristics presented higher predictive value compared to clinical and procedural variables for individual LPVR after CB2 ablation. Pre-procedural identification of unfavourable PV anatomy might be important to tailor the ablation approach., Competing Interests: Conflict of interest: C.d.A. reports speaker fees for Medtronic, Biotronik, Biosense Webster, Abbott, and Boston Scientific; teaching honoraria from Medtronic, Biotronik, Abbott and Boston Scientific; proctoring honoraria from Medtronic, Abbott, and Biotronik; G.-B.C. reports speaker fees for Medtronic, Biotronik, Biosense Webster, and Abbott; teaching honoraria from Medtronic and Biotronik; proctoring honoraria from Medtronic; P.B. reports consulting fees and speaker honoraria from Medtronic. Other authors: no relationships that could be construed as a conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: There is still sparse information regarding phrenic nerve palsy (PNP) during the cryoablation of both right-sided pulmonary vein (PV) and its anatomical predictors., Methods: Consecutive patients who had undergone pulmonary vein isolation (PVI) using CB-A and suffered PNP during both right-sided PVs were retrospectively included in our study. Two other groups were then selected among patients who experienced PNP during RIPV application only (group 2) and RSPV application only (group 3)., Results: The incidence of PNI during both right-sided PVs cryoapplications was 2.1%, (32 of 1542 patients). There were no significant clinical differences between the 3 groups. Time from basal temperature to -40 °C significantly differed among the groups for both RIPV (p = 0.0026) and RSPV applications (p = 0.0382). Patients with PNP occurring during RSPV applications had significantly larger RSPV cross-sectional area compared to patients without PNP (p = 0.0116), while in patients with PNP during RIPV application, the angle of RIPV ostium on the transverse plane was significantly smaller compared to patients without PNP (p = 0.0035). The carina width was significantly smaller in patients with PNP occurring during both right-sided PVs cryoapplications compared to patients in which PNP occurred only during one right-sided PV application (p < 0.0001); a cutoff value of 8.5 mm had a sensitivity of 87.3% and a specificity of 75.0%., Conclusion: PNP in both right-sided PVs applications is a complication that occurred in 2.1% of cases during CB-A. Pre-procedural evaluation of right PVs anatomy might be useful in evaluating the risk of PNP.

Aims: The main cause of atrial fibrillation recurrence after catheter ablation is pulmonary vein reconnection. The purpose of this retrospective study was to analyse the electophysiological findings in patients undergoing repeat procedures after an index cryoballoon ablation (CB-A) and presenting with permanency of pulmonary vein isolation (PVI) in all veins. In addition, we sought to compare the latter with a similar group of patients with reconnected veins at the redo procedure., Methods: A total of 132 patients (81 men, 60.7 ± 12.4 years) who underwent CB-A for paroxysmal atrial fibrillation (PAF) were enrolled. Indication for the redo procedure was symptomatic PAF in 83 (63%), persistent atrial fibrillation (PerAF) in 32 (24%) or persistent regular atrial tachycardia (RAT) in 17 (13%) patients., Results: Seventy-five (57%) patients presented a pulmonary vein reconnection (pulmonary vein group) during the redo procedure, whereas 57 (43%) had no pulmonary vein reconnection (non-pulmonary vein group). The non-pulmonary vein group exhibited significantly more non-pulmonary vein foci and atrial flutters than the pulmonary vein group after induction protocol (51 vs. 24%, P = 0.002 and 67 vs. 36%, P = 0.003, respectively). Twenty-two (29.3%) patients of the pulmonary vein group and 20 (35%) patients of the non-pulmonary vein group had atrial fibrillation/RAT recurrence after a mean follow-up of 12.5 ± 8 months. The survival analysis demonstrated no statistical significance in recurrence between both groups (log rank P = 0.358)., Conclusion: Atrial fibrillation/RAT recurrence in patients after CB-A with durable PVI is significantly associated with non-pulmonary vein foci and atrial flutters. No statistically different success rate regarding atrial fibrillation/RAT freedom was detected between the pulmonary vein and non-pulmonary vein groups after redoing RF-CA.

Background: The impact of pulmonary vein isolation (PVI) performed with cryoballoon (CB) on the intrinsic cardiac autonomic nervous system (ICANS) remains unclear., Objective: The purpose of this study was to evaluate the predictors and the clinical meaning of cardiac neuromodulation achieved by CB-ablation as assessed by sinus heart rate (HR) response after the procedure., Methods: Patients who underwent CB-ablation for drug-resistant atrial fibrillation (AF) from January 2014 to October 2018 were included. Twelve‑leads rest ECG was taken both before and after the procedure. After discharge, patients were scheduled for follow-up visits at 1, 3, 6, and 12 months and 24 h Holter recordings were obtained at each follow-up visit. All documented AF episodes of >30 s were considered as recurrence., Results: Four-hundred seventy-two patients (62.3% male, age 56.7 ± 13.6 years, 97.2% paroxysmal AF) were included. Mean HR before the procedure was 60.17 ± 10.4 bpm, while the morning after the procedure mean HR was 75.48 ± 12.0 bpm. Age at enrollment (R = -0.26; p < 0.001), baseline HR before the CB-A (R = -0.32; p < 0.001), nadir temperature in each right pulmonary vein (R = -0.11, p = 0.022; R = -0.16; p = 0.001) were significantly associated with the ∆HR. At 2-year follow-up, freedom from recurrences was 83.1% for the patients with HR increase ≥15 bpm after CB-A and 66.3% in patients with HR increase ˂15 bpm (p = 0.021)., Conclusion: Sinus HR increase is a frequent phenomenon after CB-A, that can be predicted by both clinical and procedural factors and that correlates with better outcome after cryo-PVI., Competing Interests: Declaration of competing interest Prof. de Asmundis, Prof Brugada, and Prof Chierchia have received consulting fees and speaker honoraria from Medtronic. G.B.C. and C.d.A. have received compensation for teach-ing and proctoring purposes from AF solutions Medtronic., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: The aim of the study was to investigate the role of anatomical characteristics of the pulmonary veins (PVs) determining cooling kinetics during second-generation cryoballoon ablation (CbA)., Methods and Results: we enrolled all consecutive patients who underwent CbA for symptomatic atrial fibrillation in our center from January 2019 to March 2019. All patients had complete computed tomography scans of the heart before the ablation. Anatomical characteristics were tested for prediction of a nadir temperature (NT) ≤ -48°C. Significant differences were noted among PV max diameter (20.8 ± 2.8 vs 18.5 ± 2.5 mm; P < .001); PV minimum diameter (15.2 ± 3.0 vs 13.0 ± 3.1 mm; P < .001); PV area (268.1 ± 71.9 vs 206.2 ± 58.7 mm 2 ; P < .001); PV ovality (1.4 ± 0.3 vs 1.5 ± 0.3; P = .005); and PV trunk length (27.4 ± 7.4 vs 21.3 ± 6.5 mm; P < .001). A scoring system was created by assigning one point each ranging from 0 (best anatomical combination) to 5. In the group with a score of 0, 94.0% of the CbA could reach a NT ≤ -48°C whereas with a score of 5, only 29.0% (P < .001). Left superior pulmonary vein with short trunk length and acute angle of PV branch was significantly associated with warmer NT (11.8% satisfactory CbA; P = .003). Regarding right inferior pulmonary vein, trunk length (P = .004), maximum diameter (P = .044), and transverse angle (P = .008) were independently associated with good NT., Conclusion: Anatomical PV features are associated with cooling kinetics and an anatomical score could predict lower NT during second-generation CbA. Specific characteristics were identified for inferior PV. Although heart imaging is not mandatory prior CbA, it can be a useful tool to predict cooling kinetics., (© 2020 Wiley Periodicals, Inc.)

Aim: The aim of this study is to assess specific per-vein procedural predictors of pulmonary vein (PV) late reconnection in cryoballoon ablation (CbA) METHODS AND RESULTS: We enrolled 148 consecutive patients undergoing a redo procedure after a previous index CbA in our center. A reconnection in at least one PV was found in 80 patients (54.1%) and the most frequently reconnected PV was the right inferior pulmonary vein (RIPV). Overall, pulmonary vein reconnection (PVr) was associated with longer time to -40°C (Tt-40°C) (54.4 ± 21.7 vs 67.6 ± 27.6 seconds; P < .001), warmer nadir temperature (NT) (-49.7°C ± 5.4°C vs -46.5°C ± 5.8°C; P < .001) and temperature at 60 seconds (-41.8°C ± 4.5°C vs -39.8°C ± 4.2°C; P < .001). The performance of these predictors differed between the veins. In particular, a comparable behavior was observed for left superior pulmonary vein (LSPV) and right superior pulmonary vein (RSPV), where NT ≤ -48°C showed a sensibility and a specificity, respectively, of 62% and 65% and 71% and 72% in predicting durable PV isolation. For RIPV, NT ≤ -48°C showed a sensitivity of 74% but low specificity (53%). Tt -40°C less than 60 seconds showed good negative predictive values, respectively, 83.9% for LSPV, 94.9% for left inferior pulmonary vein (LIPV), 90.2% for RSPV, and 82.7% for RIPV. Previous predictors cannot be used for LIPV., Conclusions: Freezing behavior and reconnection rates differ significantly among the four PVs. Freezing temperature parameters strongly predict late PVr in superior PVs and are slightly different in RIPV but can be applied as well. LIPV freezing behavior is the most different. Its reconnection is uncommon even in the subset of worse freezing temperatures and specific CB predictors cannot be identified., (© 2019 Wiley Periodicals, Inc.)

Background: A left common pulmonary vein (LCPV) accounts as the most frequent pulmonary vein (PV) variation. Our aim was to compare the performance of radiofrequency (RF) versus second-generation cryoballoon (CB-A) ablation in patients with atrial fibrillation (AF) and LCPVs., Methods: In a total cohort of 716 patients undergoing PV isolation with preprocedural CT-scanning, LCPV+ patients were selected with measurement of PV ostial area and trunk distance. All LCPV+ patients were matched between RF and CB-A group in a 1:1 ratio based on propensity scores, and compared for outcome., Results: Left common pulmonary veins were found in 31% (88/283) RF versus 34% (146/433) CB-A patients, respectively, (P = .44). In the matched population of 83 LCPV+ patients in each group, electrical isolation could be achieved in all left-sided PVs. No significant difference was noted for the rate of AF/left atrial tachyarrhythmia (LAT) recurrence between RF and CB-A group (30% vs 28%, P = .86), with similar AF/LAT-free survival (log rank, P = .71). There were 48 patients with AF/LAT recurrence (29%) during the follow-up. Recurrence rate between paroxysmal versus persistent AF was 27/120 (22.5%) versus 21/46 (46%), P = .004. Cox proportional regression analysis withheld LA volume and persistent AF as independent variables to predict AF/LAT recurrence. No increased hazard for AF/LAT recurrence was observed for patients with a long (>15 mm) vs short (5-15 mm) LCPV trunk (OR 1.14, 95% CI 0.6-2.2, P = .7)., Conclusions: In our study, equal efficacy and outcome was noted in LCPV+ patients between RF and CB-A technology., (© 2019 Wiley Periodicals, Inc.)

Introduction: The right inferior pulmonary vein (RIPV) accounts as the most frequently reconnected vein after pulmonary vein isolation using second-generation cryoballoon ablation (CB-A). Our objective was to assess anatomic predictors of late RIPV reconnection based on preprocedural computed tomography scan., Methods: Patients with a repeat procedure for atrial tachyarrhythmia recurrence after index CB-A procedure were included. A total of 129 RIPVs were evaluated for ostial diameters, ostial area, and branching pattern. Interior angle between RIPV and horizontal line in the frontal/transversal plane was used to measure the RIPV orientation: RIPV frontal/transversal angle, respectively. In addition, interior angle between RIPV and the line perpendicular on the septal intersection line at the level of the fossa ovalis, estimated as trans-septal (TS) puncture site, was measured in the frontal/transversal view: RIPV-TS frontal/transversal angle, respectively., Results: Late vein reconnection was present in 36/129 RIPVs (28%). Warmer balloon nadir temperature (P = .01), more inferior (P < .001) and posterior (P < .01) RIPV orientation (ie, more positive RIPV frontal and RIPV transversal angle, respectively), and sharper RIPV-TS frontal angle (P < .001) were associated with late RIPV reconnection on univariate analysis. Independent variables after multivariate analysis were nadir temperature (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.03-1.23; P = .013) and RIPV frontal angle (OR, 1.13, CI, 1.07-1.19; P < .001)., Conclusion: Frontal RIPV orientation could significantly predict late RIPV electrical reconnection after CB-A. Therefore, preprocedural anatomic assessment of the RIPV might be useful to plan the correct ablation strategy., (© 2019 Wiley Periodicals, Inc.)

Background: The creation of a posterior box isolation of the left atrium (LAPWI) in addition to pulmonary vein isolation (PVI) with the second-generation cryoballoon (CB-A) seems to offer promising clinical outcome in patients affected by persistent atrial fibrillation (PersAF)., Aim: This work aims to study the clinical outcome of an ablation strategy based on the creation of a LAPWI during repeat procedures for recurrent AF after an index CB-A procedure for PersAF., Methods and Results: A total of 33 patients having undergone a repeat procedure consisting in redo PVI plus LAPWI for recurrent PersAF with the CB-A after an index PVI ablation were retrospective included in our study. Electrical reconnection could be documented in 18 veins (13%). The LAPW was successfully isolated solely by CB-A ablation in 30 out of 33 (91%) patients; in the remaining 3 patients, isolation of the LAPW was completed by focal tip-irrigated RF ablation. The mean number of CB-A applications required for the superior portion of the LAPW and the inferior portion of the LAPW creation were 5.4 ± 0.9 and 4 ± 0.6, respectively. After a mean follow-up of 11.8 ± 3 months, 28 patients (85%) did not experience recurrence of any atrial arrhythmias during follow-up, without the need of further ablation or class I or III AADs., Conclusion: Left posterior wall isolation with the CB-A is feasible and safe during repeat ablation procedures for recurrent PersAF. In our study, the 12-month freedom from any arrhythmia was 85% following this ablation strategy.

Purpose: Currently, information on the mid-term outcome of cryoballoon ablation (CB-A) for drug-resistant atrial fibrillation in patients with reduced left ventricular systolic function is limited., Methods: Thirty-eight consecutive patients with paroxysmal or persistent atrial fibrillation (84.2% male), with median left ventricular ejection fraction of 37.3% were included in our study. All patients underwent the procedure with the 28-mm cryoballoon advance., Results: There were no mayor complications related to the CB-A procedure. Median follow-up was 26.5 ± 13.7 months. The freedom from atrial fibrillation after a blanking period of 3 months was 42.9% in our cohort of patients. During the follow-up period, 13 patients underwent at least a new electrophysiological procedure. After a single procedure, the univariate predictors of clinical recurrence after the blanking period were age and persistent atrial fibrillation., Conclusion: Second-generation CB-A of atrial fibrillation seems feasible and safe in patients with heart failure with reduced ejection fraction and heart failure with mid-range ejection fraction, in terms of complications rate and number of applications per vein. All pulmonary veins could be isolated with the 28-mm cryoballoon advance only.

Purpose: The purpose of this study was to clarify the behavior of the luminal esophageal temperature (LET) in a cohort of patients undergoing second-generation cryoballoon (CB-A) for pulmonary vein isolation (PVI) and additional left atrium posterior wall (LAPW) ablation by means of CB-A., Methods: Thirty patients with symptomatic persistent AF (PersAF), having undergone PVI + LAPW cryoballoon ablation with LET monitoring., Results: Interruption of the application due to a LET below 15 °C occurred in 5 patients (16.6%), 2 at the LIPV and 3 in the LAPW. The 5 patients underwent gastroscopy the day after ablation. In all individuals, esophageal thermal lesion (ETL) was absent., Conclusion: The evaluation of LET might be an additional tool in helping to prevent damage to the esophagus during the LAPW ablation with the CB-A by stopping the freeze application when temperature reaches values of < 15 °C.

Aims: The purpose of this study was to systematically quantify the level of acute parasympathetic denervation in a stepwise fashion by means of extracardiac vagal stimulation (ECVS) by positioning a quadripolar catheter in the internal jugular vein, in a cohort of patients undergoing second-generation cryoballoon ablation for paroxysmal atrial fibrillation., Methods: Fifty patients with symptomatic paroxysmal atrial fibrillation, having undergone extracardiac vagal stimulation before and after ablation by means of second-generation cryoballoon second-generation cryoballoon ablation, were included., Results: The extracardiac vagal stimulation performed preablation provoked cardioinhibitory responses in all patients with mean pause duration of 10130.6 ± 3280.0 ms. At the end of the procedure, the VRs were significantly diminished with mean pause of 1687.5 ms ± 2183.7 ms (P = 0.00 compared with the pause before the procedure)., Conclusion: The ECVS proved to be a reproducible, feasible and reliable method to quantify the degree of parasympathetic denervation during CB-A. In all patients, significant cardiac parasympathetic denervation could be observed at the end of the procedure. Responses to ECVS were more specific to quantify the vagal denervation than the increase in the heart rate. However larger studies are needed to confirm this observation.

Background: The second-generation cryoballoon (CB) is effective in achieving pulmonary vein isolation. Continuous monitoring would eliminate any over- or underestimated freedom from atrial fibrillation (AF) postablation., Objective: The purpose of this study was to differentiate between arrhythmias occurring after cryoballoon ablation (CBA), detecting true AF in symptomatic patients and detecting silent subclinical AF., Methods: Between June 2012 and January 2015, 54 patients with a preexisting cardiac implantable electronic device (CIED) who had undergone CBA for paroxysmal atrial fibrillation (PAF) were included in our retrospective study. Regular CIED controls, physical examination, and ECG recordings were performed by an experienced cardiologist blinded to the ablation procedure. Data on any hospitalization during follow-up were gathered. Patients were encouraged to note all clinical symptoms during follow-up., Results: Continuous monitoring showed a success rate of 83.3% after 1 year and 75.93% after 3 years of follow-up. During the first year, 68% of episodes of palpitations after ablation were due to sinus tachycardia, nonsustained ventricular tachycardia, or supraventricular tachycardia. AF recurrence was detected in 15.6% of asymptomatic patients during follow-up. Total AF burden post-CBA had decreased to 0.64% ± 4.34% (P <.001) during long-term follow-up of 3.3 years., Conclusion: Although this is a selected group of patients with a preexisting CIED, continuous monitoring showed freedom from AF in 83.3% of patients post-CBA after 1 year and 75.93% after 3 years of follow-up., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of the present study was to assess the long-term success rate of a single 3-min freeze per vein ablation strategy in the setting of pulmonary vein isolation (PVI) by means of second-generation cryoballoon (CB-A; Arctic Front Advance, Medtronic, Minneapolis, MN, USA) in a large cohort of patients., Methods: Three hundred and one patients with drug resistant atrial fibrillation (AF) having undergone PVI by means of CB-A using a single 3-min freeze per vein ablation strategy were included in the analysis., Results: Paroxysmal AF (PAF) was documented in 70.8% of the patients, while 29.2% presented with persistent AF (PersAF). The mean number of CB applications was 1.09 ± 0.3 in the left superior pulmonary vein (LSPV), 1.04 ± 0.2 in the left inferior pulmonary vein (LIPV), 1.12 ± 0.3 in the right superior pulmonary vein (RSPV), and 1.12 ± 0.3 in the right inferior pulmonary vein (RIPV). All PVs were successfully isolated with a 28-mm CB-A only. After a mean follow-up of 38.1 ± 7.5 months, 207 (68.8%) patients were free of atrial tachyarrhythmia (ATa) recurrences following a single procedure. Specifically, 72.8% of patients presenting with PAF and 59.1% of individuals with PersAF did not experience a recurrence., Conclusions: A single 3-min freeze per vein strategy is effective in treating AF on a long term follow-up of 38 months. Specifically, it can afford freedom from ATa recurrences in 72.8% of patients affected by PAF and 59.1% of patients initially presenting with PersAF after a single CB-A procedure.