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Pulmonary vein isolation (PVI) represents the mainstay of atrial fibrillation (AF) ablation, and PVI with cryoballoon catheter (CB) ablation (CB-A) has proven to be as effective and safe as radiofrequency ablation (RF-A). Although AF is initiated by triggers arising from the pulmonary veins (PV) and non-PV foci, the intrinsic cardiac nervous system (ICNS) plays a significant role in the induction and maintenance of AF. The ICNS is an epicardial neural system composed of ganglionated plexi (GPs) and a complex network of interconnecting neurons. In the left atrium, the major GPs are located in proximity to the PV-left atrial junction. Vagal reactions have been described as markers of autonomic modulation during PVI with both RF-A and CB-A. The occurrence of neuromodulation during PVI with CB-A may be explained by both the anatomical relationship between the GPs and the PVs and the characteristics of the CB. Due to the CB/PV size mismatch, the CB creates a wide ablation area that extends from the PV ostium toward the antrum, possibly including the GPs. Although targeted GPs ablation, as a supplemental strategy to PVI, has been associated with a better AF outcome in patients undergoing RF-A, the additional clinical benefit of neuromodulation during PVI with CB-A remains a matter of debate. In this review, we provide an overview of the anatomy of the ICNS, the relationship between the ICNS and AF pathophysiology, and the current evidence on the clinical relevance of neuromodulation during PVI with CB-A., Competing Interests: Author AB is consultant for Biotronik. Author GBC received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Boston Scientific, and Acutus Medical. Author CdA receives research grants on behalf of the center from Biotronik, Medtronic, Abbott, LivaNova, Boston Scientific, AtriCure, Philips, Acutus Medical, and received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, LivaNova, Boston Scientific, AtriCure, Acutus Medical, and Daiichi Sankyo. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Del Monte, Pannone, Bisignani, Osório, Iacopino, Chierchia and de Asmundis.)

Background: Catheter ablation for persistent atrial fibrillation (persAF) is associated with less favorable outcomes than for paroxysmal AF. To improve success rates, left atrial (LA) substrate modification is frequently performed in addition to pulmonary vein isolation (PVI). The purpose of the study was to compare 4 different ablation approaches using radiofrequency catheter ablation (RFCA) or cryoballoon ablation (CB-A) for persAF and to evaluate the respective outcomes on a midterm follow-up of 12 months., Methods: We did a propensity score-matched comparison of 30 patients undergoing PVI + LA posterior wall isolation (LAPWI) with CB-A, 30 patients who underwent PVI + linear ablation (roof and mitral lines) using RFCA, 60 patients with PVI alone using CB-A, and 60 patients who had PVI alone using RFCA. The endpoint was recurrence of documented atrial tachyarrhythmias (ATas) > 30 s at 1-year follow-up., Results: After 12 months, freedom from ATas after a single procedure was 83.3% in the PVI + LAPWI group, 46.7% in the PVI + linear ablation group, 58.3% in the PVI-alone CB-A group, and 61.6% PVI-alone RFCA (p = 0.03). Moreover, freedom from ATas was significantly higher comparing the PVI + LAPWI group with each of the other groups., Conclusions: In this propensity-matched comparison of strategies for persAF, LAPW ablation in addition to PVI with CB-A seems to improve 1-year outcome in comparison to PVI + linear ablation using RFCA and to PVI alone using RFCA or CB-A. Randomized comparisons are eagerly awaited., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Left atrial posterior wall isolation (LAPWI) is often performed in addition to pulmonary vein isolation (PVI) in the setting of persistent atrial fibrillation (AF) ablation. The aim of this study was to evaluate the feasibility and safety of a new cryoballoon ablation system in achieving PVI + LAPWI isolation., Methods: The study was a prospective, non-randomized, single center study. Forty consecutive patients, undergoing PVI + LAPWI with the novel POLARx™, were compared to 40 consecutive patients who underwent the same procedure with the established Arctic Front Advance PRO™., Results: Acute isolation was achieved in all PVs in both groups and left posterior wall isolation (LAPWI) was achieved in 38 patients (95%) in the POLARx group and in 36 patients (90%) in Arctic Front group. Procedural outcomes were similar between both groups, except for lower temperatures during cryoenergy in the POLARx group, for both pulmonary vein isolation (PVI) and LAPWI., Conclusion: LAPWI + PVI with the novel POLARx™ Cryoballoon is feasible and safe; the results are comparable with the Arctic Front Advance PRO™ system., (© 2022 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Background: The pathogenesis of Brugada syndrome (BrS) and consequently of abnormal electrograms (aEGMs) found in the epicardium of the right ventricular outflow tract (RVOT-EPI) is controversial., Objective: The purpose of this study was to analyze aEGM from high-density RVOT-EPI electroanatomic mapping (EAM)., Methods: All patients undergoing RVOT-EPI EAM with the HD-Grid catheter for BrS were retrospectively included. Maps were acquired before and after ajmaline, and all patients had concomitant noninvasive electrocardiographic imaging with annotation of RVOT-EPI latest activation time (RVOTat). High-frequency potentials (HFPs) were defined as ventricular potentials occurring during or after the far-field ventricular EGM showing a local activation time (HFPat). Low-frequency potentials (LFPs) were defined as aEGMs occurring after near-field ventricular activation showing fractionation or delayed components. Their activation time from surface ECG was defined as LFPat., Results: Fifteen consecutive patients were included in the study. At EAM before ajmaline, 7 patients (46.7%) showed LFPs. All patients showed HFPs before and after ajmaline and LFPs after ajmaline. Mean HFPat (134.4 vs 65.3 ms, P <.001), mean LFPat (224.6 vs 113.6 ms, P <.001), and mean RVOTat (124.8 vs 55.9 ms, P <.001) increased after ajmaline. RVOTat correlated with HFPat before (ρ = 0.76) and after ajmaline (ρ = 0.82), while RVOTat was shorter than LFPat before (P <.001) and after ajmaline (P <.001). BrS patients with history of aborted sudden cardiac death had longer aEGMs after ajmaline., Conclusion: Two different types of aEGMs are described from BrS high-density epicardial mapping. This might correlate with depolarization and repolarization abnormalities., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background The rate of sudden cardiac death (SCD) in Brugada syndrome (BrS) is ≈1%/y. Noninvasive electrocardiographic imaging is a noninvasive mapping system that has a role in assessing BrS depolarization and repolarization abnormalities. This study aimed to analyze electrocardiographic imaging parameters during ajmaline test (AJT). Methods and Results All consecutive epicardial maps of the right ventricle outflow tract (RVOT-EPI) in BrS with CardioInsight were retrospectively analyzed. (1) RVOT-EPI activation time (RVOT-AT); (2) RVOT-EPI recovery time, and (3) RVOT-EPI activation-recovery interval (RVOT-ARI) were calculated. ∆RVOT-AT, ∆RVOT-EPI recovery time, and ∆RVOT-ARI were defined as the difference in parameters before and after AJT. SCD-BrS patients were defined as individuals presenting a history of aborted SCD. Thirty-nine patients with BrS were retrospectively analyzed and 12 patients (30.8%) were SCD-BrS. After AJT, an increase in both RVOT-AT [105.9 milliseconds versus 65.8 milliseconds, P <0.001] and RVOT-EPI recovery time [403.4 milliseconds versus 365.7 milliseconds, P <0.001] was observed. No changes occurred in RVOT-ARI [297.5 milliseconds versus 299.9 milliseconds, P =0.7]. Before AJT no differences were observed between SCD-BrS and non SCD-BrS in RVOT-AT, RVOT-EPI recovery time, and RVOT-ARI ( P =0.9, P =0.91, P =0.86, respectively). Following AJT, SCD-BrS patients showed higher RVOT-AT, higher ∆RVOT-AT, lower RVOT-ARI, and lower ∆RVOT-ARI ( P <0.001, P <0.001, P =0.007, P =0.002, respectively). At the univariate logistic regression, predictors of SCD-BrS were the following: RVOT-AT after AJT (specificity: 0.74, sensitivity 1.00, area under the curve 0.92); ∆RVOT-AT (specificity: 0.74, sensitivity 0.92, area under the curve 0.86); RVOT-ARI after AJT (specificity 0.96, sensitivity 0.58, area under the curve 0.79), and ∆RVOT-ARI (specificity 0.85, sensitivity 0.67, area under the curve 0.76). Conclusions Noninvasive electrocardiographic imaging can be useful in evaluating the results of AJT in BrS.

Background: Paroxysmal atrial fibrillation (PAF) can be triggered by non-pulmonary vein foci, like the superior vena cava (SVC). The latter is correlated with improved result in terms of freedom from atrial tachycardias (ATs), when electrical isolation of this vessel utilizing radiofrequency energy (RF) is achieved., Objectives: Evaluate the clinical impact, in patients with PAF, of the SVC isolation (SVCi) in addition to ordinary pulmonary vein isolation (PVI) by means of the second-generation cryoballoon (CB) METHODS: A total of 100 consecutive patients that underwent CB ablation for PAF were retrospectively selected. Fifty consecutive patients received PVI followed by SVCi by CB application, and the following 50 consecutive patients received standard PVI. All patients were followed 12 months., Results: The mean time to SVCi was 36.7 ± 29.0 s and temperature at SVC isolation was - 35 (- 18 to - 40) °C. Real-time recording (RTR) during SVCi was observed in 42 (84.0%) patients. At the end of 12 months of follow-up, freedom from ATs was achieved in 36 (72%) patients in the PVI only group and in 45 (90%) patients of the SVC and PV isolation group (Fisher's exact test p = 0.039, binary logistic regression: p = 0.027, OR = 0.28, 95%CI = 0.09-0.86). In survival analysis, SVC and PV isolation group was also associated with improved freedom from ATs (log-rank test: p = 0.017, Cox regression: p = 0.026, HR = 0.31, 95%CI = 0.11-0.87)., Conclusion: Superior vena cava isolation with the CB in addition to PVI might improve freedom from ATs if compared to PVI alone at 1-year follow-up., (© 2021. The Author(s).)

Aims: To evaluate the clinical outcome in patients undergoing repeat procedures for recurrent persistent atrial fibrillation following an index cryoballoon (CB-A) pulmonary vein isolation ablation on a mid-term follow-up of 12 months., Methods: In this propensity score-matched comparison, 50 patients undergoing left atrial posterior wall isolation (LAPWI) with the CB-A were matched to 50 patients treated with additional linear ablation using radiofrequency catheter ablation (RFCA)., Results: Meantime to repeat the procedure was 9.74 ± 4.36 months. At 12 months follow-up freedom from atrial tachyarrhythmias (ATas) was achieved in 82% of patients in the LAPWI group and in 62% of patients in the linear ablation group ( P  = .03). Regression analysis demonstrated that relapses during the blanking period and LA dimensions were independent predictors of ATas recurrences following the repeat procedure., Conclusion: LAPWI using CB-A is associated with a significantly higher freedom from atrial arrhythmias when compared with the RFCA mediated left atrial linear lesions on a mid-term follow-up of 12 months in patients with persAF undergoing a redo procedure., Competing Interests: GBC reports speaker fees for Medtronic, Biotronik, Biosense Webster, and Abbott; teaching honoraria from Medtronic and Biotronik; proctoring honoraria from Medtronic; AB is consultant for Biotronik; PB reports consulting fees and speaker honoraria from Medtronic; 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., (© 2021 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Heart Rhythm Society.)

Purpose: The purpose of the study was to evaluate the impact of left atrial posterior wall isolation (LAPWI) in addition to pulmonary vein isolation (PVI) vs PVI alone, performed using CB-A, in patients with PAF on a midterm follow-up of 12 months., Methods: Eighty consecutive patients indicated to index cryoballoon ablation (CB-A) for the treatment of drug resistant PAF were included. The first 50 (62.5%) underwent PVI only, and the following 30 patients (37.5%) underwent LAPWI + PVI., Results: Acute isolation was achieved in all PVs in both groups. The LAPW was successfully isolated in 29 out of 30 (97%) patients; in the remaining patient, adjunct radiofrequency ablation was required. The total procedure time and the mean fluoroscopy time were significantly shorter in patients who underwent PV isolation only (p < 0.001). The freedom from atrial fibrillation (AF) at 12 months was not significantly different between the 2 groups (LAPW + PVI = 90% vs PVI = 88%) (log-rank p = 0.816)., Conclusion: LAPW ablation in addition to PVI by the means of CB-A does not seem to reduce the risk of AF recurrence if compared with the standard PVI on a midterm follow-up of 12 months., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: A strategy based on the attainment of the specific parameter of - 40 °C within the first 60 s during cryoenergy applications in the setting of cryoballoon ablation (CB-A) without the use of an inner lumen mapping catheter (ILMC) (Achieve; Medtronic, USA) for the visualization of real-time recordings (RTR) has been previously described. The latter has proven to be very effective in guaranteeing freedom from atrial arrhythmias in patients affected by paroxysmal atrial fibrillation (PAF) at 1-year follow-up. The purpose of this retrospective observational study was to evaluate the clinical outcomes of this strategy in a multicenter experience on a long-term follow-up of 3 years., Methods: A total of 192 patients having undergone CB ablation for paroxysmal AF (PAF) starting from September 2015 to November 2016 that underwent a temperature-guided approach were included., Results: Mean procedural time was 68.77 ± 18.88. The mean number of freezes in the LSPV was 1.2 ± 0.4, 1.2 ± 0.4 in the LIPV, 1.1 ± 0.4 in the RSPV, and 1.2 ± 0.4 in the RIPV. Considering a blanking period of 3 months, freedom from AF off-AAD was achieved in 77.6% (149/192) at mean 34.5 ± 5.5 months and median 35.1 months (IQR, 32.3-37.0 months) follow-up after 1 procedure., Conclusions: A temperature-guided approach affords freedom from AF at a 3-year follow-up period in a large majority of patients affected by PAF having undergone a single CB-A procedure.

Purpose: The purpose of this study was to evaluate the feasibility and safety of superior vena cava (SVC) isolation in addition to standard pulmonary vein isolation (PVI) using the second-generation cryoballoon (CB) in patients with paroxysmal atrial fibrillation., Methods: Thirty-seven consecutive patients that underwent CB ablation for paroxysmal atrial fibrillation (PAF) were prospectively enrolled in our study. After PVI the SVC was mapped for potentials. If the SVC exhibited electrical activity, isolation was achieved performing a single 180-s balloon application., Results: Regarding SVC isolation, 180-s freeze in the SVC could be completed in 32 (86.4%) patients, and 5 patients had at least 120 s of freezing application (13.5%). Real-time recording during SVC isolation was observed in 30 (81.0%) patients. The mean time to isolation was 36.9 ± 28.7 s and the temperature at isolation was - 33 (- 15 to - 40) °C. No cases developed persistent phrenic nerve palsy (PNP) or any other complication., Conclusions: Superior vena cava isolation proved to be safe and feasible with the second generation cryoballoon in a prospective series of patients affected by PAF.

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.

Purpose: High parasympathetic nervous system (PNS) activity is accurately reflected by deceleration capacity (DC) and is involved in atrial fibrillation (AF) recurrence after catheter ablation procedure. When compared with initial catheter ablation procedure, repeated procedures for AF recurrence are followed by a lower success rates, estimated at 50%. Our objective was to evaluate the impact of PNS activity assessed by DC measured before repeated procedure on AF recurrence after repeated procedure., Methods: Consecutive patients who underwent an initial catheter ablation procedure for pulmonary vein (PV) isolation and a repeated catheter ablation procedure for AF recurrence were selected. Additional 24-h ambulatory electrocardiographic recording between procedures for DC measurement was required for inclusion. A total of 110 patients were included. Seventy-two patients underwent cryoballoon (CB) ablation and 38 patients underwent radiofrequency (RF) ablation as initial procedure, while all patients underwent RF ablation as repeated procedure., Results: DC was higher in cases with right-sided PV reconnection (p = 0.04, OR = 1.38, 95% CI = 1.08-1.78). In patients with CB ablation as initial procedure, DC was higher in patients with PV reconnection (p = 0.03, OR = 1.29, 95% CI = 1.11-1.70), and the number of reconnected PVs was higher in patients with DC ≥ 7.0 ms (median DC value used for dichotomization, p = 0.02, OR = 2.19, 95% CI = 1.10-4.37). In multivariate Cox regression, DC predicted AF recurrence after repeated ablation (p = 0.004, HR = 1.68, 95% CI = 1.35-1.82). In multivariate binary regression, DC predicted persistent AF type recurrence after repeated ablation (p = 0.01, OR = 1.50, 95% CI = 1.10-2.02)., Conclusions: DC is a novel predictor of AF recurrence and AF recurrence type after repeated catheter ablation procedure. DC may reflect the need of more intensive treatment strategies in patients with high PNS activity.

Brugada syndrome (BrS) diagnosis requires the presence of a typical type 1 ECG pattern. Owing to the spontaneous ECG variability, the real BrS prevalence in the general population remains unclear. The aim of the present study was to evaluate the prevalence of positive ajmaline challenge for BrS in a cohort of consecutive patients who underwent electrophysiological evaluation for different clinical reasons. All consecutive patients from 2008 to 2019 who underwent ajmaline testing were prospectively included. A total of 2,456 patients underwent ajmaline testing, 742 (30.2%) in the context of familial screening for BrS. In non-familial screening group (1,714) ajmaline testing resulted positive in 186 (10.9%). Indications for ajmaline testing were: suspicious BrS ECG in 23 cases (12.4%), palpitations in 27 (14.5%), syncope in 71 (38.2%), presyncope in 7 (3.8%), family history of sudden cardiac death in 18 (9.7%), documented ventricular arrhythmias in 12 (6.5%), unexplained cardiac arrest in 4 (2.2%), atrial fibrillation in 16 (8.5%), brady-arrhythmias in 1 (0.5%), and cerebrovascular accidents in 7 (3.7%). Compared with the overall population, ajmaline testing positive patients were younger (42.8 ± 15.5 vs 48.9 ± 20.4; p <0.001) and more frequently male (65.1% vs 56.3%; p = 0.023). Implantable cardioverter defibrillator was implanted in 84 patients (45.2%). During a median follow-up of 42.4 months, 12 appropriate shocks and 13 implantable cardioverter defibrillator related complications were reported. In conclusion, the BrS was diagnosed in an unexpected high proportion of patients that underwent ajmaline testing for a variety of cardiovascular symptoms. This can lead to an adequate counseling and clinical management in BrS patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Clinical management of vaso-vagal syncope (VVS) remains challenging since no therapy has proven to completely prevent VVS recurrence., Objective: The purpose of this study was to analyze the mid-term outcome of cryoballoon (CB) cardioneuroablation achieved by pulmonary vein isolation (PVI) in patients with VVS., Methods: Patients who underwent CB cardioneuroablation in our centers between January 2014 to June 2018 were included. All patients had a history of VVS or pre-syncope despite therapeutic attempts with medical and/or pacing treatments. Patients were excluded in case of structural heart diseases, cerebrovascular diseases or suspected drug-related syncope. Both heart rate (HR) and atrio-ventricular (AV) interval were analyzed on the 12-lead electrocardiogram (ECG) the day before the procedure, the day after, and in the follow-up., Results: In total, 26 patients (76.9% males, 37.5 ± 9.0 years old) were included. All patients underwent a successful procedure with the 28 mm second-generation Arctic Front Advance CB. No major complication occurred. At a mean follow-up of 20.1 ± 11.6 months the freedom from VVS or reflex pre-syncope was 83,7%, with 22 patients free from any clinical recurrence. Basal HR significantly increased the day after the procedure (57.2 bpm vs 78.3 bpm, p < 0.001), while at the final follow-up it stabilized at a value halfway between the 2 previous ones (69.8 bpm, p = 0.0086). The AV interval didn't modify significantly after the procedure., Conclusion: Endocardial autonomic denervation achieved by CB PVI appears to be an effective and safe treatment option for patients with refractory VVS and reflex pre-syncope., Competing Interests: Declaration of competing interest Gian-Battista Chierchia and Carlo de Asmundis receive compensation for teaching purposes and proctoring from AF solutions, Medtronic, and Biosense-Webster. Pedro Brugada receives research grants on behalf of the centre from Medtronic. Other authors: no relationships that could be construed as a conflict of interests., (Copyright © 2020 Indian Heart Rhythm Society. Production and hosting by Elsevier B.V. All rights reserved.)

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.)

Background: Vagal hyperactivity is directly related to several clinical conditions as reflex/functional bradyarrhythmias and vagal atrial fibrillation (AF). Cardioneuroablation provides therapeutic vagal denervation through endocardial radiofrequency ablation for these cases. The main challenges are neuromyocardium interface identification and the denervation control and validation. The finding that the AF-Nest (AFN) ablation eliminates the atropine response and decreases RR variability suggests that they are related to the vagal innervation., Method: Prospective, controlled, longitudinal, nonrandomized study enrolling 62 patients in 2 groups: AFN group (AFN group 32 patients) with functional or reflex bradyarrhythmias or vagal AF treated with AFN ablation and a control group (30 patients) with anomalous bundles, ventricular premature beats, atrial flutter, atrioventricular nodal reentry, and atrial tachycardia, treated with conventional ablation (non-AFN ablation). In AFN group, ablation delivered at AFN detected by fragmentation/fractionation of the endocardial electrograms and by 3-dimensional anatomic location of the ganglionated plexus. Vagal response was evaluated before, during, and postablation by 5 s noncontact vagal stimulation at the jugular foramen, through the internal jugular veins (extracardiac vagal stimulation [ECVS]), analyzing 15 s mean heart rate, longest RR, pauses, and atrioventricular block. All patients had current guidelines arrhythmia ablation indication., Results: Preablation ECVS induced sinus pauses, asystole, and transient atrioventricular block in both groups showing a strong vagal response ( P =0.96). Postablation ECVS in the AFN group showed complete abolishment of the cardiac vagal response in all cases (pre/postablation ECVS= P <0.0001), demonstrating robust vagal denervation. However, in the control group, vagal response remained practically unchanged postablation ( P =0.35), showing that non-AFN ablation promotes no significant denervation., Conclusions: AFN ablation causes significant vagal denervation. Non-AFN ablation causes no significant vagal denervation. These results suggest that AFNs are intrinsically related to vagal innervation. ECVS was fundamental to stepwise vagal denervation validation during cardioneuroablation. Visual Overview A visual overview is available for this article.

Background: The prevalence and the clinical impact of conversion of atrial fibrillation (AF) to sinus rhythm (SR) during cryoballoon ablation (CB-A) are unknown., Objective: The purpose of this study was to evaluate the prevalence of restoration of SR during CB-A and the clinical impact of this phenomenon., Methods: Between January 2012 and September 2018, all patients who experienced conversion of AF to SR during CB-A were included. This group was subsequently matched for gender, age, type of AF, diagnosis-to-ablation time, and left atrial size with patients who underwent CB-A and did not experienced conversion of AF to SR. After discharge, patients were scheduled for follow-up visits at 1, 3, 6, and 12 months and 24 hours Holter recordings were obtained at each follow-up visit. All documented AF episodes of >30 seconds were considered as recurrence. A 3 month post-procedural blanking period (BP) was applied., Results: A total of 1559 patients underwent pulmonary veins isolation by CB-A between January 2012 and September 2018; among them, 58 patients (3.7%) experienced restoration of SR during CB-A. In total, 53 patients (41 males [77.3%], mean age 61.4 ± 13.3 years) were included in the case group. During CB-A, restoration of SR occurred more frequently during right-side PVs applications (right inferior pulmonary vein 39.6%, right superior pulmonary vein 30.2%). If considering a BP, at 2 year follow-up, freedom from recurrences was 86.5% in the case group and 68.0% in the control group ( P  = .036)., Conclusion: Conversion of AF to SR is a favorable and relatively frequent phenomenon during cryoballoon pulmonary vein isolation ablation., Competing Interests: Prof. de Asmundis, Prof Brugada, and Prof Chierchia have received consulting fees and speaker honoraria from Medtronic. GBC and C.d.A. have received compensation for teaching and proctoring purposes from AF solutions Medtronic., (© 2020 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Heart Rhythm Society.)

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: 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.)

Aims: The purpose of this study was to evaluate the contribution in the acute loss in vagal innervation after ablation with the second generation cryoballoon (CB-A) in each distinct pulmonary vein (PV) by means of external cardiac vagal stimulation (ECVS) by positioning a catheter in the internal jugular vein in a cohort of 60 patients., Methods: Sixty patients, 50 starting from the left superior pulmonary vein (LSPV) and 10 from the right superior pulmonary vein with symptomatic paroxysmal atrial fibrillation (PAF), having undergone ECVS before the first and after each PV ablation by means of CB-A ablation, were included., Results: The ECVS performed pre-ablation provoked cardioinhibitory responses in all cases with mean pause duration of 10251.83 ms ± 2826.23 ms. At the end of the procedure, the vagal reactions (VR) were significantly diminished. Specifically, compared against the initial pause, responses were 8957.06 ± 2711.66 ms (p < 0.01) after left superior PV, 10017.36 ± 9127.0 ms (p = 0.88) after left inferior PV, 6020.16 ± 3780.709 ms (p < 0.001) after right inferior PV and 1687.5 ± 2183.7 ms (p < 0.001) after right superior PV. Noteworthy, if starting with ablation in the RSPV, VR was immediately reduced by 90.34%, 990.7 ± 379.78 ms (p < 0.001) as compared to baseline response., Conclusion: Although not directly targeting the ganglion plexuses, AF ablation with the CB-A causes a significant acute loss in parasympathetic innervation. The RSPV showed to be associated with the most significant reduction of acute loss in parasympathetic innervation.

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.

Introduction : Pulmonary vein isolation (PVI), by catheter ablation, represents the current treatment for drug-resistant atrial fibrillation (AF). Nowadays cryoballoon (CB) is a recognized ablation method in patients with atrial fibrillation, mainly due to its ease of use, leading to reproducible and fast procedures. This novel single shot technology literally revolutionized the approach to AF ablation. Areas covered : The historical development of the cryoballoon, ablation techniques and new approaches beyond the ordinary PVI and complications are summarized here. Expert opinion : Although cryoballoon ablation has greatly standardized the approach to PVI a few critical points still need to be clarified scientifically in order to further uniform this procedure in cath labs worldwide. Duration and dosage of the cryoapplication is undoubtedly a topic of great interest.

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.

The cardiac autonomic nervous system plays an important role in the genesis and maintenance of atrial fibrillation. Although, pulmonary vein isolation is the cornerstone in today's approach to atrial fibrillation ablation, a considerable proportion of patients will recur with atrial arrhythmias following this procedure, especially in the non-paroxysmal forms. The pulmonary vein isolation indirectly targets and ablate the ganglionated plexi. This might ultimately enhance the efficacy of the procedure, but an optimal ablation strategy and a reliable method to confirm and quantify the efficacy of vagal denervation following the procedure might be necessary, thus leading to significantly better results., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2019 Termedia & Banach.)

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.