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Background: Clinical outcomes after ablation of persistent atrial fibrillation remain suboptimal. Identification of AF drivers using a novel integrated mapping technique may be crucial to ameliorate the clinical outcome., Methods and Results: Persistent AF patients were prospectively enrolled to undergo high-density electrophysiological mapping to identify repetitive-regular activities (RRas) before modified circumferential pulmonary vein (PV) ablation. They have been randomly assigned (1:1 ratio) to ablation of RRa followed by modified circumferential PV ablation (mapping group; n=41) or modified circumferential PV ablation alone (control group; n=40). The primary end point was freedom from arrhythmic recurrences at 1 year. In total, 81 persistent AF patients (74% male; mean age, 61.7±10.6 years) underwent mapping/ablation procedure. The regions exhibiting RRa were 479 in 81 patients (5.9±2.4 RRa per patient): 232 regions in the mapping group (n=41) and 247 in the control group (n=40). Overall, 185 of 479 (39%) RRas were identified within the PVs, whereas 294 of 479 (61%) in non-PV regions. Mapping-guided ablation resulted in higher arrhythmia termination rate when compared with conventional strategy (25/41, 61% versus 12/40, 30%; P <0.007). Total radiofrequency duration ( P =0.38), mapping ( P =0.46), and fluoroscopy times ( P =0.69) were not significantly different between the groups. No major procedure-related adverse events occurred. After 1 year, 73.2% of mapping group patients were free from recurrences versus 50% of control group ( P =0.03)., Conclusions: Targeted ablation of regions showing RRa provided an adjunctive benefit in terms of arrhythmia freedom at 1-year follow-up in the treatment of persistent AF. These findings might support a patient-tailored strategy in subjects with nonparoxysmal AF and should be confirmed by additional larger, randomized, multicenter studies., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier NCT02571218., (© 2018 American Heart Association, Inc.)

Background: Multipoint left ventricular (LV) pacing (MultiPoint™ Pacing [MPP], Abbott, Sylmar, CA, USA) improves the response rate to cardiac resynchronization therapy (CRT). We evaluated the feasibility of noninvasive radial artery tonometry (RAT) to characterize arterial pressure morphology changes (pre-ejection period [PEP] and ejection duration [ED]) between conventional CRT and MPP pacing interventions., Methods: Patients with a MPP-enabled CRT device (Quadra Assura MP™, Abbott) underwent noninvasive RAT assessment (SphygmoCor CVMS, AtCor Medical Inc., Itasca, IL, USA) at 3-6 months after implantation. A pacing protocol was performed in a randomized order including one optimized conventional biventricular CRT (CONV) configuration using the distal electrode and five MPP configurations. The PEP, ED, and PEP/ED ratio were determined for each intervention from the RAT pressure waveform and electrocardiogram., Results: Pressure waveforms were successfully recorded in 19 patients (89% male, QRS 147 ± 16 ms, 63% ischemic). In 17/19 (89%) patients, at least one MPP intervention resulted in improved PEP, ED, and PEP/ED compared to CONV. The MPP intervention with greatest separation of LV cathodes and minimum intra-LV delay significantly improved PEP (mean PEP -15 ± 33% vs -8 ± 32% [CONV], P = 0.04) and ED (mean ED +8 ± 8% [MPP] vs +4 ± 7% [CONV], P = 0.02), and PEP/ED (-0.07 ± 0.14 [MPP] vs -0.04 ± 0.13 [CONV], P = 0.02) compared with CONV., Conclusions: Noninvasive RAT efficiently characterizes changes in PEP and ED between CONV and MPP interventions. MPP configurations using the widest separation among LV cathodes and minimum intra-LV delay may significantly improve RAT-derived parameters as compared to conventional CRT., (© 2017 Wiley Periodicals, Inc.)

Atrial Fibrillation (AF) is the most commonly described cardiac arrhythmia found in the general population and can lead to adverse outcomes. Its onset and maintenance requires the presence of an arrhythmogenic substrate that predisposes the patient for risk of these types of arrhythmias and the occurrence of a trigger event. A major characteristic of AF-related structural remodelling is atrial fibrosis, a process closely related to inflammation. Autoimmune rheumatic diseases constitute systemic inflammatory disorders that can also present with cardiovascular manifestations, including a high incidence of AF, thus supporting the idea of a link between AF and inflammation. A vicious cycle exists in which inflammation leads to a higher prevalence of structural cardiovascular disease, which in turn leads to more inflammation and AF; in fact, inflammation is known to affect signalling pathways that lead to the development of AF. Therapy must first target systemic inflammation, since decreasing the inflammatory burden has consistently shown to positively ameliorate the prognosis. When this approach is not sufficient, rhythm or, when not feasible, rate control is indicated in addition to anticoagulant therapy. As far as the rhythm control strategy is concerned, antiarrhythmic drugs and/or catheter ablation should be considered. New mapping techniques allowing the characterization of the arrhythmic substrate have opened new perspectives and may help in the treatment of AF in these patients, since atrial tissue is the target of inflammation-induced arrhythmic alterations. In cases where the natural history of the arrhythmia itself is more advanced, in order to minimize the impact of AF on cardiac function as well as quality of life, a device-based therapy, including an "ablate and pace" approach could be adopted., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

: A huge thrombus, developing after percutaneous left atrial appendage occlusion, has been successfully treated with dabigatran and aspirin as combination therapy.Although novel oral anticoagulants alone may be effective in thrombus dissolution, the association of an antiplatelet drug may safely enhance this process.

Cardiovascular diseases are the leading cause of death in the Western world. Unfortunately, current therapies are often only palliative, consequently essentially making heart transplantation necessary for many patients. However, several novel therapeutic approaches in the past two decades have yielded quite encouraging results. The generation of induced pluripotent stem cells, through the forced expression of stem cell-specific transcription factors, has inspired the most promising strategies for heart regeneration by direct reprogramming of cardiac fibroblasts into functional cardiomyocytes. Initial attempts at this reprogramming were conducted using a similar approach to the one used with transcription factors, but during years, novel strategies have been tested, e.g., miRNAs, recombinant proteins and chemical molecules. Although preliminary results on animal models are promising, the low reprogramming efficiency, as well as the incomplete maturation of the cardiomyocytes, still represents important obstacles. This review covers direct transdifferentiation strategies that have been proposed and developed and illustrates the pros and cons of each approach. Indeed, as described in the manuscript, there are still many unanswered questions and drawbacks that require a better understanding of the basic signaling pathways and transcription factor networks before functional cells, suitable for cardiac regeneration and safe for the patients, can be generated and used for human therapies.

Some previous studies have proposed the electrocardiographic Tpeak-Tend (TpTe) as a possible predictor of ventricular arrhythmic events in patients with Brugada syndrome (BrS). We sought to analyze the association between the parameters of repolarization dispersion (TpTe, TpTe/QT, TpTe dispersion, QTc, and QTd) and ventricular fibrillation/sudden cardiac death in a large cohort of patients with type 1 BrS. A total of 448 consecutive patients with BrS (men 61%, age 45 ± 16 years) with spontaneous (n = 96, 21%) or drug-induced (n = 352, 79%) type 1 electrocardiogram were retrospectively included. At the time of the diagnosis or during a mean follow-up of 93 ± 47 months (median 88 months), 43 patients (9%) documented ventricular arrhythmias. No significant difference was observed in TpTe, TpTe/QT, maximum TpTe, and TpTe dispersion between asymptomatic patients and those with syncope and malignant arrhythmias. TpTe/QT ratio did not also significantly differ between patients with ventricular fibrillation/sudden cardiac death and those asymptomatic ones. In conclusion, TpTe was not significantly prolonged in those patients with type 1 BrS presenting with unexplained syncope or malignant arrhythmic events during follow-up., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Patients with drug-induced Brugada syndrome (BS) are considered at a lower risk than those with a spontaneous type I pattern. Nevertheless, they can present arrhythmic events., Objective: The purpose of this study was to investigate their clinical characteristics, long-term prognosis and risk factors., Methods: A consecutive cohort of 343 patients with drug-induced BS was included and compared with 78 patients with a spontaneous type I pattern., Results: The mean age was 40.7 ± 18.3 years. Sudden cardiac death (SCD) was the clinical presentation in 13 (3.8%) and syncope in 86 (25.1%); 244 (71.1%) were asymptomatic. Patients with drug-induced BS were less frequently men (180 (52.5%) vs 63 (80.8%); P < .01), were more frequently asymptomatic (244 (71.1%) vs 44 (56.4%); P < .01), and had less ventricular arrhythmias (VAs) induced during electrophysiology study (41 (13.2%) vs 31 (42.4%); P < .01). An implantable cardioverter-defibrillator was implanted in 128 patients (37.3%). During a median follow-up of 62.5 months (interquartile range 28.9-115.6 months), 34 patients presented arrhythmic events. The event rate was 1.1% person-year (vs 2.3% person-year in patients with a spontaneous type I pattern; P < .01). Presentation as SCD and inducible VAs were independent risk factors significantly associated with arrhythmic events (adjusted hazard ratio 22.0 and 3.5). Drug-induced BS was related to a better prognosis only in asymptomatic individuals., Conclusion: Drug-induced BS has a good prognosis if asymptomatic; however, SCD is possible. Clinical presentation as SCD and inducible VAs during electrophysiology study are independent risk factors for arrhythmic events. In asymptomatic patients, proband status and inducible VAs can help to identify patients at higher risk, but further evidence is needed., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Continuous heart rhythm monitoring using implantable cardiac monitors (ICMs) for atrial fibrillation (AF) management is steadily increasing in current clinical practice, even in the absence of an established indication provided by international guidelines. The increasing use of such devices is mainly associated with recent technological improvements including miniaturization, easier implant procedures, and remote monitoring, all of which make this strategy continuously more appealing and promising. For these and other reasons, ICMs have been proven to be a safe and highly effective tool for detecting AF episodes. However, ICMs are not the best option for every patient, as limitations exist. Therefore, it is imperative to weigh the possible benefits against the potential limitations of using these devices when deciding individualized patient care.

Aims: Continuous rhythm monitoring is valuable for adequate atrial fibrillation (AF) management in the clinical setting. Subcutaneous leadless implantable cardiac monitors (ICMs) yield an improved AF detection, overcoming the intrinsic limitations of the currently available external recording systems, thus resulting in a more accurate patient treatment. The study purpose was to assess the detection performance of a novel three-vector ICM device equipped with a dedicated AF algorithm., Methods and Results: Sixty-six patients (86.4% males; mean age 60.4 ± 9.4 years) at risk to present AF episodes, having undergone the novel ICM implant (BioMonitor, Biotronik SE&Co. KG, Berlin, Germany), were enrolled. External 48-h ECG Holter was performed 4 weeks after the device implantation. The automatic ICM AF classification was compared with the manual Holter arrhythmia recordings. Of the overall study population, 63/66 (95.5%) had analysable Holter data, 39/63 (62%) showed at least one true AF episode. All these patients had at least one AF episode stored in the ICM. On Holter monitoring, 24/63 (38%) patients did not show AF episodes, in 16 of them (16/24, 67%), the ICM confirmed the absence of AF. The AF detection sensitivity and positive predictive value for episodes' analysis were 95.4 and 76.3%, respectively., Conclusion: Continuous monitoring using this novel device, equipped with a dedicated detection algorithm, yields an accurate and reliable detection of AF episodes. The ICM is a promising tool for tailoring individual AF patient management. Further long-term prospective studies are necessary to confirm these encouraging results., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Aims: Risk stratification in Brugada Syndrome (BS) remains challenging. Arrhythmic events can occur life-long and studies with long follow-ups are sparse. The aim of our study was to investigate long-term prognosis and risk stratification of BS patients., Methods and Results: A single centre consecutive cohort of 400 BS patients was included and analysed. Mean age was 41.1 years, 78 patients (19.5%) had a spontaneous type I electrocardiogram (ECG). Clinical presentation was aborted sudden cardiac death (SCD) in 20 patients (5.0%), syncope in 111 (27.8%) and asymptomatic in 269 (67.3%). Familial antecedents of SCD were found in 184 individuals (46.0%), in 31 (7.8%) occurred in first-degree relatives younger than 35 years. An implantable cardioverter defibrillator (ICD) was placed in 176 (44.0%). During a mean follow-up of 80.7 months, 34 arrhythmic events occurred (event rate: 1.4% year). Variables significantly associated to events were: presentation as aborted SCD (Hazard risk [HR] 20.0), syncope (HR 3.7), spontaneous type I (HR 2.7), male gender (HR 2.7), early SCD in first-degree relatives (HR 2.9), SND (HR 5.0), inducible VA (HR 4.7) and proband status (HR 2.1). A score including ECG pattern, early familial SCD antecedents, inducible electrophysiological study, presentation as syncope or as aborted SCD and SND had a predictive performance of 0.82. A score greater than 2 conferred a 5-year event probability of 9.2%., Conclusions: BS patients remain at risk many years after diagnosis. Early SCD in first-degree relatives and SND are risk factors for arrhythmic events. A simple risk score might help in the stratification and management of BS patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Background: There is emerging evidence that localization and elimination of abnormal electric activity in the epicardial right ventricular outflow tract may be beneficial in patients with Brugada syndrome., Methods and Results: A total of 135 symptomatic Brugada syndrome patients having implantable cardiac defibrillator were enrolled: 63 (group 1) having documented ventricular tachycardia (VT)/ventricular fibrillation (VF) and Brugada syndrome-related symptoms, and 72 (group 2) having inducible VT/VF without ECG documentation at the time of symptoms. About 27 patients of group 1 experienced multiple implantable cardiac defibrillator shocks for recurrent VT/VF episodes. Three-dimensional maps before and after ajmaline determined the arrhythmogenic electrophysiological substrate (AES) as characterized by prolonged fragmented ventricular potentials. Primary end point was identification and elimination of AES leading to ECG pattern normalization and VT/VF noninducibility. Extensive areas of AES were found in the right ventricle epicardium, which were wider in group 1 ( P =0.007). AES increased after ajmaline in both groups ( P <0.001) and was larger in men ( P =0.008). The increase of type-1 ST-segment elevation correlated with AES expansion ( r =0.682, P <0.001). Radiofrequency ablation eliminated AES leading to ECG normalization and VT/VF noninducibility in all patients. During a median follow-up of 10 months, the ECG remained normal even after ajmaline in all except 2 patients who underwent a repeated effective procedure for recurrent VF., Conclusions: In Brugada syndrome, AES is commonly located in the right ventricle epicardium and ajmaline exposes its extent and distribution, which is correlated with the degree of coved ST-elevation. AES elimination by radiofrequency ablation results in ECG normalization and VT/VF noninducibility. Substrate-based ablation is effective in potentially eliminating the arrhythmic consequences of this genetic disease., Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT02641431., (© 2017 American Heart Association, Inc.)

Aims: The purpose of this study was to analyse the efficacy and complication rates of the simultaneous hybrid procedure in a series of patients with persistent and long-standing persistent atrial fibrillation (AF) in a midterm follow-up., Methods and Results: Sixty-four consecutive patients (56 males, 59.7 ± 8.7 years) having undergone isolation of pulmonary veins (PVs) and posterior wall of left atrium (LA) by means of hybrid thoracoscopic ablation for symptomatic persistent (n = 21, 33%) and long-standing persistent AF (n = 43, 67%) were analysed. At a mean follow-up of 23.1 ± 14.1 months (median 21; range 6-57), the success rate without antiarrhythmic therapy was achieved in 67.2% of patients. Procedure-related complications were observed in 13 patients (20.3%) including 2 LA perforations (3.1%) requiring, respectively, conversion to sternotomy and small left-sided thoracotomy. The success rate did not significantly differ between persistent and long-standing persistent AF (respectively, 71.4 and 65.1%; P = 0.4). Patients with AF relapse during the blanking period were 4.60 times more likely to have AF recurrence after 3 months from the ablation procedure., Conclusion: The hybrid procedure yields promising results in the setting of both persistent and long-standing persistent AF after midterm follow-up, at the expense of a non-negligible rate of adverse events. Our findings need to be confirmed by further larger and prospective studies., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Aim: The aim of our study is to compare two approaches of implantable cardiac defibrillator (ICD) implantation, conventional (supra/subpectoral) and subcostal in young adults in terms of procedural complications and adverse events encountered during follow-up., Methods and Results: From January 2007 to December 2013, all patients under the age of 50 years who received an ICD in our centre were included in this study. Patient's hospital records were analysed for procedural complications and adverse events during follow-up until December 2014. Data from device on first interrogation after implantation and on follow-up were also noted. A total of 106 patients of which 40.6% had Brugada's syndrome (65.1% male, age 33.6 ± 10.97 years) were included in analysis; 71 (61%) had ICD placed in (sub/supra) pectoral and 35 (33%) in subcostal position. Only seven patients received an epicardial lead system. During the follow-up period of 2.1 ± 1.8 years, 84.90% of the patients had no adverse events. Most of the complications, procedural and during follow-up, occur in conventionally placed, pectoral ICD. Lead follow-up data in both groups, conventional and subcostal, showed no difference in right ventricular (RV) shock impedance and R wave sensing, P-value = 0.56 and 0.77, respectively. Lead survival was 95 and 97%, respectively, in conventional and subcostal groups over a mean follow-up of 2.1 ± 1.8 years. Log-rank test for lead survival was not significant in terms of site of implantation., Conclusion: To the best our knowledge, this is the first study demonstrating subcostal ICD placement in young adults and resulting in equivalent to better outcomes when compared with conventionally placed pectoral ICD. Subcostal ICD placement might be considered an alternative option in young adults as it results in better procedural outcomes and also comparable rate of adverse events during follow-up, but bigger studies with a larger number of patients are needed for a definitive conclusion., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Objectives: To compare drug-eluting balloons (DEBs) versus second-generation DES in the treatment of drug-eluting stent restenosis (DES-ISR)., Background: The optimal treatment of DES-ISR remains unclear. Several modes of treatment ranging from plain-old balloon angioplasty to repeated use of DES have yielded disappointing results. DEBs are increasingly been used in restenotic lesions; however, their use in DES-ISR is less established., Methods: We evaluated all procedures between 2009 and 2011, involving DES-ISR that were treated either with DEB or second-generation DES. The measured end-points during the follow-up period were cardiac-death, target-vessel MI, TLR, TVR, and MACE defined as composite of cardiac-death, TV-MI, and TVR., Results: Two hundred and forty-seven patients (302 lesions) with DES-ISR were treated with either DEB (81 patients; 104 lesions) or second-generation DES (166 patients; 198 lesions). The mean age of patients was 66.1 ± 9.4 years. There were higher numbers of patients with diabetes in the DEB group (DEB 47% vs DES 33%; p = 0.03). The mean length of DEB was significantly longer than the DES (35.4 vs 19.8 mm; p < 0.001). During the 12-month follow-up, there were no significant differences in the MACE rates (12.3% vs 8.4%; p = 0.3) and TLR rates (9.9% vs 7.8%; p = 0.6) between DEB and DES, respectively. On the multivariate analysis, use of DEB or DES was not the predictor of MACE (hazard ratio: 0.84, 95% CI: 0.46-1.85; p = 0.6). There were no cases of definite or probable stent thrombosis in either group., Conclusion: There were no significant differences in the clinical outcomes between DEB and second-generation DES in the treatment of DES-ISR. These results should encourage operators to consider DEB in the treatment of DES-ISR, which offers certain advantages over DES. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Background: The phenotypic heterogeneity of Brugada syndrome (BrS) can lead some patients to show an additional inferolateral early repolarization pattern (ERP), or fragmented QRS (f-QRS). The aim of the study was to investigate the prevalence and clinical impact of f-QRS, ERP or combined f-QRS/ERP in high-risk patients with BrS., Methods and results: Patients with spontaneous or drug-induced BrS and an indication to receive an implantable cardioverter-defibrillator (ICD) were considered eligible for this study. From 1992 to 2012, a total of 176 consecutive patients with BrS underwent ICD implantation. Among them, 48 subjects (27.3%) presented with additional depolarization and/or repolarization abnormalities. f-QRS was found in 29 (16.5%), ERP in 15 (8.5%), and combined f-QRS/ERP in 4 patients (2.3%). After a mean follow-up of 95.2±51.9 months, spontaneous sustained ventricular arrhythmias were documented in 8 patients (16.7%). No significant difference was found in the rate of appropriate shocks between patients presenting with f-QRS or ERP and those without abnormalities. Patients with both f-QRS and ERP had a significantly higher rate of appropriate shocks (HR: 4.1; 95% CI: 1.1-19.7; P=0.04)., Conclusions: Fragmented QRS and ERP are common ECG findings in high-risk BrS patients, occurring in up to 27% of cases. When combined, f-QRS and ERP confer a higher risk of appropriate ICD interventions during a very long-term follow-up. (Circ J 2016; 80: 2109-2116).

Aim: Peri-procedural thromboembolic (TE) and hemorrhagic events are complications of major concern for patients undergoing cryoballoon (CB) ablation for atrial fibrillation (AF). While peri-procedural anticoagulation management could decrease the incidence of these complications, data on CB ablation are scarce. The role of novel oral anticoagulants (NOACs) has not been thoroughly tested in this population., Methods: In the present study, we sought to assess acute peri-procedural complications in patients undergoing CB ablation for AF under different anticoagulation regimens; anticoagulation administration was performed according to the CHA2DS2-VASc score guidelines. To the best of our knowledge, this is the first study that compares 1) uninterrupted warfarin, 2) bridging therapy with low molecular weight heparin (LMWH), 3) aspirin and 4) NOACs in this subgroup of patients., Results: NOACs were as effective as uninterrupted warfarin in terms of bleeding complications and TE events. Surprisingly, the aspirin group had more hemorrhagic complications than both the warfarin and NOACs groups., Conclusion: In the current study, the use of NOACs was an effective and safe approach in CB ablation., (Copyright © 2016 Hellenic Cardiological Society. Published by Elsevier B.V. All rights reserved.)

Aims: Phrenic nerve injury (PNI) is the most frequently observed complication during pulmonary vein isolation procedure using the second-generation cryoballoon (CB). Our objective was to analyse the correlation between the fluoroscopic position of the 28 mm CB during ablation in the right superior pulmonary vein (RSPV) and the occurrence of PNI., Methods and Results: A total of 165 patients having undergone the large 28 mm CB ablation were retrospectively reviewed. Positioning of the CB relative to the cardiac silhouette was classified under fluoroscopic guidance in antero-posterior projection during RSPV ablation. Regarding the lower half of the balloon, CB positioning was defined as follows: (A) completely inside the cardiac shadow; (B1) <1/3 outside the cardiac shadow; and (B2) ≥1/3 outside the cardiac shadow. Phrenic nerve injury occurred in 9.7% (16/165) during ablation in the RSPV. The occurrence of PNI was 0.9, 10.6, and 90.1% in positions A, B1, and B2, respectively (A vs. B1, P = 0.01; B1 vs. B2, P < 0.0001). Among other pre-procedural and procedural variables, the B2 position was the strongest independent determinant for predicting PNI at RSPV (P = 0.001, odds ratio: 119.9; 95% confidence interval: 11.6-1234.7) after multivariable analysis., Conclusion: The incidence of PNI at the RSPV significantly increased in case of more distal positioning of the CB relative to the cardiac shadow. This simple and straightforward intra-procedural indicator might prone the operators to attempt occluding the RPSV more proximally in order to avoid PNI., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Introduction: Second-generation cryoballoon (CB-Adv) ablation is highly effective in achieving pulmonary vein isolation (PVI) with promising mid-term clinical outcome. However, the ideal freezing strategy is still under debate. The aim of this study was to assess the efficacy of a single 3-minute approach compared to the conventional 4-minute plus bonus application using CB-Adv., Methods and Results: One hundred and sixty patients (67% male; mean age 58.0 ± 13.3 years) underwent PVI using CB-Adv for paroxysmal atrial fibrillation (PAF). Among 160 patients, 80 received a single 3-minute approach (3-mns group), while the remaining 80 conventional 4-minute plus bonus-freeze (4-mns group). Mean procedure and fluoroscopy times were 90.6 ± 15.8 and 18.3 ± 6.9 in the 4-mns group, 75.2 ± 17.1 and 13.5 ± 8.7 in the 3-mns group (P < 0.001, respectively). First-freeze isolation rate was 91.6% in the 4- versus 90.6% in the 3-mns group (P = 0.78). Persistent phrenic nerve palsy (PNP) occurred in 6/80 (3.5%) in the 4-mns group and 4/80 in the 3-mns group (P = 0.75). The overall freedom from ATas 2 years after the procedure was 78.1% (125/160): 77.5% (62/80 patients) in the 3-mns and 78.8% (63/80 patients) in the 4-mns group (P = 0.82). In multivariate analysis, time to PVI and nadir temperature independently predicted ATa recurrences (P < 0.001)., Conclusions: CB-Adv ablation for PAF is highly effective, resulting in 78% 2-year freedom from arrhythmic recurrences. A "single 3-minute strategy" showed equal efficacy as compared to the conventional 4-minute plus bonus freeze approach at 2-year follow-up, providing shorter procedure and fluoroscopy time. Nadir temperature and time to PVI were predictors of arrhythmic recurrences. "Bonus-freeze" strategy might be unnecessary., (© 2016 Wiley Periodicals, Inc.)

Aims: Prolonged P-wave duration and dispersion are universally accepted noninvasive markers for atrial electrical remodeling. Our aim was to analyze P-wave indices as predictors of atrial fibrillation recurrence after pulmonary vein isolation in patients with normal left atrial size., Methods: From January 2008 to December 2011, 426 patients with drug-resistant symptomatic paroxysmal atrial fibrillation underwent pulmonary vein isolation as an index procedure by conventional radiofrequency or cryoballoon ablation in our center. Patients with left atrial dilatation, poor-quality electrocardiograms, atrial pacemaker stimulation, and those undergoing repeat procedures were excluded. A total of 201 patients were analyzed during a mean follow-up of 22 ± 16 months., Results: Patients with prolonged P-wave duration had higher rates of atrial fibrillation recurrences compared with those without prolonged P-wave duration (49 vs. 14%; P < 0.001). Atrial fibrillation recurrence was significantly associated with prolonged P-wave duration (129 ± 13 vs. 119 ± 11 ms; P < 0.001) and P-wave dispersion (54 ± 12 vs. 42 ± 10 ms; P < 0.001) compared with those who remained in sinus rhythm. P-wave duration and dispersion were independently associated with atrial fibrillation recurrence (hazard ratio 1.045, 95% confidence interval 1.027-1.063, P < 0.001; and hazard ratio 1.049, 95% confidence interval 1.022-1.078, P < 0.001, respectively), after adjusting for left atrial size and age., Conclusion: Prolonged P-wave duration and dispersion were found to be independently associated with higher recurrence rates of atrial fibrillation after pulmonary vein isolation in patients with normal left atrial dimension. Therefore, a prolongation of P-wave indices may help to identify those patients in whom electrical remodeling has already occurred and a more extensive ablation may be indicated.

Objectives: Brugada syndrome (BS) in women is considered an infrequent condition with a more favourable prognosis than in men. Nevertheless, arrhythmic events and sudden cardiac death (SCD) also occur in this population. Long-term follow-up data of this group are sparse. The purpose of the present study was to investigate the clinical characteristics and long-term prognosis of women with BS., Methods: A consecutive cohort of 228 women presenting with spontaneous or drug-induced Brugada type I ECG at our institution were included and compared with 314 men with the same diagnosis., Results: Mean age was 41.5±17.3 years. Clinical presentation was SCD in 6 (2.6%), syncope in 51 (22.4%) and the remaining 171 (75.0%) were asymptomatic. As compared with men, spontaneous type I ECG was less common (7.9% vs 23.2%, p<0.01) and less ventricular arrhythmias were induced during programmed electrical stimulation (5.5% vs 22.3%, p<0.01). An implantable cardioverter defibrillator (ICD) was implanted in 64 women (28.1%). During a mean follow-up of 73.2±56.2 months, seven patients developed arrhythmic events, constituting an event rate of 0.7% per year (as compared with 1.9% per year in men, p=0.02). Presentation as SCD or sinus node dysfunction (SND) was risk factor significantly associated with arrhythmic events (hazard risk (HR) 25.4 and 9.1)., Conclusion: BS is common in women, representing 42% of patients in our database. Clinical presentation is less severe than men, with more asymptomatic status and less spontaneous type I ECG and prognosis is more favourable, with an event rate of 0.7% year. However, women with SCD or previous SND are at higher risk of arrhythmic events., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Aims: To assess the incidence of late pulmonary vein (PV) reconnection following index PV isolation (PVI) procedure initially achieved with radiofrequency contact-force catheter ablation (CFCA) and second-generation cryoballoon ablation (CB-AdvA)., Methods and Results: A total of 56 consecutive patients (41 male, 73.2%; mean age 60.8 ± 11.8 years) underwent a repeat ablation because of recurrent atrial tachyarrhythmias (ATas) after index PVI achieved with CFCA (30 patients) or CB-AdvA (26 patients). All repeat procedures were performed by the means of CFCA. In the CFCA group, among 119 PVs, 43 (36.1%) showed conduction gaps in 24 patients (1.8 per patient), whereas in the CB-AdvA group among 103 veins, 21 (20.4%) showed a PV reconnection in 18 patients (1.2 per patient) (P = 0.01). The left superior pulmonary vein was less frequently reconnected following CB-AdvA when compared with CFCA (2/25, 8% vs. 11/29, 37.9%; P = 0.01). In the CFCA group, the mean CF per-vein was lower in reconnecting veins when compared with those persistently isolated (10.9 ± 2.7 vs. 18.6 ± 3.1 g; P < 0.001). In the CB-AdvA group, late PV reconnection was associated with warmer nadir temperature (-48.9 ± 5.1 vs. -51.2 ± 4.7°C; P = 0.05) and longer time-to-isolation (71.1 ± 20.2 vs. 50.2 ± 32.9 s; P = 0.03)., Conclusion: The rate of late PV reconnection is significantly lower following CB-AdvA when compared with CFCA as index procedure. Lower CF values and warmer nadir temperature with longer time to effect were more frequently associated with PV reconnections in the setting of CFCA and CB-AdvA., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: The second-generation cryoballoon is effective in achieving acute pulmonary vein isolation (PVI) and favorable clinical outcome. To date, no data are available on factors affecting late PV reconnection after second-generation cryoballoon ablation., Methods and Results: A total of 29 consecutive patients (25 male, 86.2%; mean age 57.8±13.8 years) underwent a repeat procedure, after a mean 11.6±4.5 months (range, 3.5-19.7 months), after index ablation using the 28-mm second-generation cryoballoon. All repeat ablations were performed using a 3-dimensional electroanatomical mapping system. Among all 115 PVs, including 1 left common ostiums (LCOs), 25 (21.7%) showed a PV reconnection in 20 patients (1.25 per patient). Persistent PVI could be documented in 90 of 115 PVs (78.2%). In 9 of 29 patients (31%), all PVs were electrically isolated. In the multivariable analysis, time to PVI (P=0.03) and failure to achieve -40°C within 60 s (P=0.05) independently predicted late PV reconnection. At receiver-operator curve analysis, time to PVI <60 s identified the absence of PV reconduction (sensitivity, 86.7%; specificity, 86.2%; positive predictive value, 59.1%; and negative predictive value, 96.4%; area under the curve, 0.85; confidence interval, 0.73-0.97; P<0.001)., Conclusions: The rate of late PV reconnection after second-generation cryoballoon ablation is low (1.25 PVs/patient). Faster time to isolation and achievement of -40°C within 60 s independently predict durable PVI. In addition, 60-s cut-off for time to PVI indicates persistent isolation with 96.4% negative predictive value. These parameters might guide the operator whether to perform further applications to ensure a long-lasting PVI., (© 2015 American Heart Association, Inc.)

Background: Whether Brugada syndrome (BrS) depends on functional epicardial substrates, which may be definitively eliminated by radiofrequency ablation, remains unknown., Methods and Results: Patients with BrS underwent epicardial mapping to identify areas of abnormal electrograms as target for radiofrequency ablation. Substrate identification consisted in mapping right ventricle epicardial surface before and after flecainide (2 mg/kg per 10 minutes). After radiofrequency ablation, flecainide and remap confirmed elimination of abnormal substrate, BrS ECG pattern, and ventricular tachycardia/ventricular fibrillation inducibility. Flecainide testing was performed at each follow-up visits ≤6 months. Fourteen patients with BrS, median age 39 years (30.3-42.3) with implantable cardioverter-defibrillator were enrolled. Low-voltage areas (<1.5 mV) were commonly identified on the anterior right free wall and right ventricular outflow tract, which increased after flecainide from 17.6 cm(2) (12.1-24.2) to 28.5 cm(2) (21.6-30.2; P=0.001). Similarly, areas with abnormal electrograms increased after flecainide from 19.0 (17.5-23.6) to 27.3 cm(2) (24.0-31.2; P=0.001). After 23.8 minutes (18.1-28.5) of radiofrequency ablation, abnormal electrograms disappeared, whereas low-voltage areas were replaced by scar areas (<0.5 mV) of 25.9 cm(2) (19.6-31.0). Substrate elimination resulted in BrS ECG pattern disappearance and no ventricular tachycardia/ventricular fibrillation inducibility without complications. After a median follow-up of 5 months (3.8-5.3), ECG remained normal despite flecainide., Conclusions: In patients with BrS, there is a relationship between abnormal ECG pattern, the extent of abnormal epicardial substrate, and ventricular tachycardia/ventricular fibrillation inducibility. Ablation of the substrate identified in the presence of flecainide can eliminate the BrS phenotype and warrants further study., (© 2015 American Heart Association, Inc.)

Background: Among Brugada syndrome patients, asymptomatic individuals are considered to be at the lowest risk. Nevertheless, arrhythmic events and sudden cardiac death are not negligible. Literature focused on this specific group of patients is sparse. The purpose of this study is to investigate the clinical characteristics, management, and long-term prognosis of asymptomatic Brugada syndrome patients., Methods and Results: Patients presenting with spontaneous or drug-induced Brugada type I ECG and no symptoms at our institution were considered eligible. A total of 363 consecutive patients (200 men, 55.1%; mean age, 40.9±17.2 years; 41 [11.3%] with spontaneous type I ECG) were included. Electrophysiological study was performed in 321 (88.4%) patients, and ventricular arrhythmias were induced in 32 (10%) patients. An implantable cardioverter defibrillator was implanted in 61 (16.8%) patients. After a mean follow-up time of 73.2±58.9 months, 9 arrhythmic events occurred, accounting for an annual incidence rate of 0.5%. Event-free survival was 99.0% at 1 year, 96.2% at 5 years, and 95.4% at 10 and 15 years. Univariate analysis identified as risk factors: electrophysiological study inducibility (hazard ratio, 11.4; P<0.01), spontaneous type I (hazard ratio, 4.0; P=0.04), and previous sinus node dysfunction (hazard ratio, 8.0; 95% confidence interval, 1.0-63.9; P=0.05). At the multivariate analysis, only inducibility remained significant (hazard ratio, 9.1; P<0.01)., Conclusions: Arrhythmic events in asymptomatic Brugada syndrome patients are not insignificant. Ventricular arrhythmia inducibility, spontaneous type I ECG, and presence of sinus node dysfunction might be considered as risk factors and used to drive long-term management., (© 2015 American Heart Association, Inc.)

Background: The aim of this study was to assess the overall incidence of complications in a large sample of consecutive patients having undergone pulmonary vein (PV) isolation, evaluating also the rate of complications in radiofrequency (RF) and cryoballoon (CB) ablation technologies., Methods and Results: From January 2008 to December 2014, 1352 consecutive PV isolation procedures were performed in our center; a total amount of 1233 AF ablation procedures fulfilling inclusion criteria was finally taken into consideration for our analysis. A total of 642 procedures were performed using RF ablation technology and 591 using CB system. Serious adverse events occurred in 36 procedures (2.9%): specifically, vascular complications in 14 (1.1%); cardiac tamponade in 13 (1.0%); a thromboembolic event in 4 (0.3%); and atrial-esophageal fistula, PV intramural hematoma, retroperitoneal hematoma, pleural hematoma and persisting phrenic nerve palsy all occurred in 1 patient individually (0.1%). No deaths related to the procedure occurred. The complication rate did not significantly differ in the RF and CB groups (respectively, 3.6% vs 2.2%; p=0.1). Complication rates considerably decreased over the study period from 4.67% in 2008 to 1.55% in 2014. Interestingly, each 1-point increase in the CHA2DS2-VASc score was found to increase by 51% the likelihood of a serious adverse event., Conclusions: The incidence of serious adverse events following AF ablation procedures was 2.9%. Vascular complications were the most frequent complication followed by tamponade and thromboembolic events. The rate of complications considerably decreased over time. CHA2DS2-VASc score was found to be associated with higher risk of complications., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Right phrenic nerve paralysis (PNP) is the most frequently observed complication occurring during cryoballoon ablation (CB). Our aim was to analyze the impact of the premature interruption (PI) of cryoenergy delivery in a large series of consecutive patients during ablation in the right-sided veins on clinical outcome., Methods and Results: All consecutive patients having undergone second-generation CB ablation for paroxysmal atrial fibrillation (AF) from July 2012 to September 2014 were included in our analysis. Exclusion criteria were persistent AF, presence of an intracavitary thrombus, uncontrolled heart failure, moderate or severe valvular disease, left atrium (LA) diameter ≥55 mm, and contraindications to general anesthesia. A total 287 consecutive patients with drug-resistant paroxysmal AF having undergone pulmonary vein isolation by means of CB technology (male 65%, age 57.6 ± 13.1 years) were included. The incidence of PNP in the study population was 8.0% (23/287). At a mean follow-up of 11.5 ± 3.9 months, the success rate without antiarrhythmic therapy was 81.6%. Patients with PNP had similar rates of AF recurrence compared with those without PNP (17.4% vs. 17.8%; P = 0.9); the former had a mean follow-up of 10.9 ± 3.7 months, the latter 11.8 ± 4.5 months (P = 0.3)., Conclusion: Conclusion: Our findings show that patients in whom freezing was interrupted due to PNP had a similar outcome on 1-year follow-up compared with those in whom freezing cycles were completed in the septal veins. No baseline clinical or procedural characteristics were found to predict AF recurrence in patients having experienced PNP., (© 2015 Wiley Periodicals, Inc.)

Background: Transseptal (TS) catheterization is needed to access the left heart during pulmonary vein isolation (PVI) procedures. In the radiofrequency (RF) ablation procedure, left atrial access is commonly achieved with a double TS puncture; cryoballoon (CB) ablation usually requires only a single TS puncture. Our aim was to compare the incidence of iatrogenic septal defect (IASD) between double transseptal conventional RF and CB ablation., Methods and Results: Individuals having undergone PVI as index procedure by RF or CB ablation and a subsequent transesophageal echocardiography examination during postablation follow-up in our center were consecutively included. A total of 127 patients formed the study group (92 males; mean age 60 ± 11 years). IASD was present in 17 patients (13.4%) after a mean follow-up time of 11.6 months. The incidence of IASD at 1-year follow-up following PVI was significantly higher in the CB ablation group compared with the RF ablation group (22.2% vs 8.5%; P = 0.03). Mean IASD diameter was larger in the CB group (0.60 cm × 0.50 cm vs 0.44 cm × 0.35 cm) without statistical significance. Only left to right atrial shunt was observed. No adverse events were recorded in these patients during the follow-up., Conclusions: the incidence of IASD at 1-year follow-up following CB ablation procedure for PVI is significantly higher with respect to RF procedures. Although no adverse clinical events were recorded in patients with persistence of IASD, more detailed echocardiographic examinations might be advised in all individuals exhibiting this finding., (© 2015 Wiley Periodicals, Inc.)

Background: The prognostic value of electrophysiological investigations in individuals with Brugada syndrome remains controversial. Different groups have published contradictory data. Long-term follow-up is needed to clarify this issue., Methods and Results: Patients presenting with spontaneous or drug-induced Brugada type I ECG and in whom programmed electric stimulation was performed at our institution were considered eligible for this study. A total of 403 consecutive patients (235 males, 58.2%; mean age, 43.2±16.2 years) were included. Ventricular arrhythmias during programmed electric stimulation were induced in 73 (18.1%) patients. After a mean follow-up time of 74.3±57.3 months (median 57.3), 25 arrhythmic events occurred (16 in the inducible group and 9 in the noninducible). Ventricular arrhythmias inducibility presented a hazard ratio for events of 8.3 (95% confidence interval, 3.6-19.4), P<0.01., Conclusions: Programmed ventricular stimulation of the heart is a good predictor of outcome in individuals with Brugada syndrome. It might be of special value to guide further management when performed in asymptomatic individuals. The overall accuracy of the test makes it a suitable screening tool to reassure noninducible asymptomatic individuals., (© 2015 American Heart Association, Inc.)

Background: The second-generation cryoballoon Advance (CB-A) recently launched on the market has technical modifications designed to significantly improve procedural outcome with respect to the first-generation device., Objective: The purpose of this study was to evaluate the overall incidence of complications in a large sample of patients having undergone pulmonary vein (PV) isolation with CB-A technology., Methods: All consecutive patients who underwent PV isolation procedures using CB-A technology between June 2012 and February 2015 were considered. Exclusion criteria were presence of an intracavitary thrombus, uncontrolled heart failure, moderate or severe valvular disease, left atrial diameter ≥55 mm, and contraindications to general anesthesia., Results: During the study period, 500 consecutive patients (67% male, age 57.6 ± 12.9 years) were enrolled. Major complications occurred in 10 patients (2.0%): vascular complications at the puncture site in 6 (1.2%), and thromboembolic events, cardiac tamponade, persisting phrenic nerve palsy, and retroperitoneal hematoma all occurred in a single patient respectively (0.2%). Phrenic nerve palsy occurred in 36 patients (7.2%) and did not revert in only 1 patient at final follow-up of 20 months. No deaths related to the procedure occurred. No predictors of major complication were found., Conclusion: The present findings highlight that PV isolation using CB-A technology can be safely performed with a low incidence of adverse events. The incidence of major complications after atrial fibrillation ablation procedures using CB-A technology was 2% in our study. The most frequent complication consisted of vascular complications at the puncture site. No deaths related to the procedure occurred., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Phrenic nerve palsy (PNP) is the most frequently observed complication in the setting of cryoballoon (CB) ablation (Arctic Front, Medtronic Inc., Minneapolis, MN, USA). Although, usually transient, resolving before the end of the procedure, persistent PNP (not resolving before the end of procedure) can occur. Literature on persistent PNP after second generation CB ablation is relatively sparse., Methods: A total of 316 consecutive patients having undergone large 28-mm CB ablation as index procedure in the Heart Rhythm Management Center, UZ Brussels, Belgium, from January 2009 to December 2013 were retrospectively reviewed for the study. Of these 117 patients were treated with the first generation CB (CB1) and 199 patients with the second generation CB (CB2)., Results: PNP occurred in 10% of the total population. Persistent PNP was only observed following CB2 ablation which occurred in 4.5% of the group. At a mean follow-up of 11 months, diaphragmatic contraction in persistent PNP patients resumed in 78% (7/9) of the patients. In a final follow-up at 5 and 20 months, PNP persisted in two patients, respectively. PNP during ablation in the right inferior pulmonary vein was only observed in the CB2 group. No predictors of persistency of PNP were observed., Conclusion: Persistence of PNP only occurred in the CB2 group in 4.5% of patients. The majority of patients with persistent PNP were asymptomatic. In most of the patients having persistent PNP after ablation, complete phrenic nerve function resumed during follow-up (78%)., (© 2015 Wiley Periodicals, Inc.)

Background: The second-generation cryoballoon (CB-Adv) is effective in achieving pulmonary vein isolation (PVI) with encouraging results. The mid-term clinical efficacy of a single 3-minute freeze, without a routine bonus application, has been recently demonstrated., Objective: The purpose of this study was to assess long-term clinical outcome after PVI with the CB-Adv using a single 3-minute application., Methods: A total of 143 consecutive patients (93 male [65%], mean age 59.6 ± 12.0 years) with paroxysmal atrial fibrillation (PAF; 113/143 [79%]) or early persistent atrial fibrillation (AF; 30/143 [21%]) underwent PVI using CB-Adv with a single 3-minute freeze. Atrial tachyarrhythmia recurrences were defined as symptomatic or documented episodes >30 seconds., Results: After a single freeze, isolation could be reached in 94.1% of all identified pulmonary veins. Complete PVI was successfully achieved with 1.1 ± 0.4 mean freezes. Persistent phrenic nerve palsy occurred in 5 of 143 patients (3.5%). At a mean 12.1 ± 4.4 months of follow-up, after a 3-month blanking period (BP), 80.4% (115/143) were in stable sinus rhythm (93/113 [82.3%] for PAF; 22/30 [73.3%] for early persistent AF). Fifteen patients underwent a second procedure with radiofrequency ablation showing reconnection in 7 of 15 right-sided (46.7%) and 6 of 15 left-sided (40%) pulmonary veins. Relapses during BP (P <.01), time to PVI (P = .02), and longer AF duration (P = .04) were independent predictors of recurrences., Conclusion: A single 3-minute freeze is highly effective, determining an atrial tachyarrhythmia freedom of 80.4% at 1-year follow-up. The incidence of persistent phrenic nerve palsy is 3.5%. Relapses during BP, time to PVI, and longer AF duration are predictors of recurrences. Routine use of an "insurance freeze" may not be needed., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Patients with Brugada syndrome and aborted sudden cardiac death or syncope have higher risks for ventricular arrhythmias (VAs) and should undergo implantable cardioverter-defibrillator (ICD) placement. Device-based management of asymptomatic patients is controversial. ICD therapy is associated with high rates of inappropriate shocks and device-related complications., Objectives: The objective of this study was to investigate clinical features, management, and long-term follow-up of ICD therapy in patients with Brugada syndrome., Methods: Patients presenting with spontaneous or drug-induced Brugada type 1 electrocardiographic findings, who underwent ICD implantation and continuous follow-up at a single institution, were eligible for this study., Results: A total of 176 consecutive patients were included. During a mean follow-up period of 83.8 ± 57.3 months, spontaneous sustained VAs occurred in 30 patients (17%). Eight patients (4.5%) died. Appropriate ICD shocks occurred in 28 patients (15.9%), and 33 patients (18.7%) had inappropriate shocks. Electrical storm occurred in 4 subjects (2.3%). Twenty-eight patients (15.9%) experienced device-related complications. In multivariate Cox regression analysis, aborted sudden cardiac death and VA inducibility on electrophysiologic studies were independent predictors of appropriate shock occurrence., Conclusions: ICD therapy was an effective strategy in Brugada syndrome, treating potentially lethal arrhythmias in 17% of patients during long-term follow-up. Appropriate shocks were significantly associated with the presence of aborted sudden cardiac death but also occurred in 13% of asymptomatic patients. Risk stratification by electrophysiologic study may identify asymptomatic patients at risk for arrhythmic events and could be helpful in investigating syncope not related to VAs. ICD placement is frequently associated with device-related complications, and rates of inappropriate shocks remain high regardless of careful device programming., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Occurrence of atrial tachycardias (ATs) following radiofrequency (RF) pulmonary vein (PV) isolation for the treatment of paroxysmal atrial fibrillation (PAF) is a frequent complication. Cryoballoon (CB) ablation might create more homogeneous and demarcated lesions than traditional point by point RF approach, hypothetically leading to a lower incidence of ATs. Our aim is to compare incidence and mechanism of regular ATs occurring after ablation of PAF by means of circumferential point by point RF vs CB ablation., Methods: Two hundred eighty-six consecutive patients undergoing a first PV isolation procedure, as treatment for PAF, were included and followed up for 12 months. Point by point RF ablation was performed in 186 patients and CB ablation in the remaining 100. Among the last ones, first generation (CB-1) was used in 59 patients and second generation one (CB-2) in 41., Results: Incidence of regular ATs was higher following RF PV isolation when compared with CB ablation (11.3 vs 3.0%, P = 0.028). When compared separately with RF ablation, both CB-1 and CB-2 presented lower incidences of ATs (5.1 and 0.0%) but differences only remained significant for the CB-2 (P = 0.027)., Conclusion: Patients with PAF undergoing a first PV isolation procedure by means of CB ablation present a significantly lower incidence of ATs than those in which PV isolation is achieved by means of circumferential point by point RF ablation.

Background: No data are available about the clinical outcome of pulmonary vein isolation (PVI) as an index procedure for persistent atrial fibrillation (PersAF) ablation using the second-generation cryoballoon (CB-Adv)., Objective: The purpose of this study was to assess the 1-year efficacy of PVI as an index procedure for PersAF ablation using the novel CB-Adv., Methods: Sixty-three consecutive patients (45 male [71.4%], mean age 62.7 ± 9.7 years) with drug-refractory PersAF undergoing PVI using the novel CB-Adv were enrolled. Follow-up was based on outpatient clinic visits including Holter ECGs. Recurrence of atrial tachyarrhythmias (ATas) was defined as a symptomatic or documented episode >30 seconds., Results: A total of 247 PVs were identified and successfully isolated with a mean of 1.7 ± 0.4 freezes. Mean procedural and fluoroscopy times were 87.1 ± 38.2 minutes and 14.9 ± 6.1 minutes, respectively. Among 26 of 63 patients (41.3%) presenting with AF at the beginning of the procedure, 7 of 26 (26.9%) converted to sinus rhythm during ablation. Phrenic nerve palsy occurred in 4 of 63 patients (6.3%). At 1-year follow-up, after a 3-month blanking period (BP), 38 of 63 patients (60.3%) were in sinus rhythm. Because of ATa recurrences, 9 patients underwent a second procedure with radiofrequency ablation showing a pulmonary vein reconnection in 4 right-sided PVs (44.4%) and 3 left-sided PVs (33.3%). Multivariate analysis demonstrated that PersAF duration (P = .01) and relapses during BP (P = .04) were independent predictors of AT recurrences., Conclusion: At 1-year follow-up, freedom from ATas following PersAF ablation with the novel CB-Adv is 60%. Phrenic nerve palsy is the most common complication. PersAF duration and relapses during the BP appear to be significant predictors of arrhythmic recurrences., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to investigate the efficacy and the safety of prophylactic use of protamine in a series of heparinized patients having undergone cryoballoon (CB) ablation for atrial fibrillation (AF)., Methods: From October 2013 to January 2014, 54 consecutive patients received protamine after CB ablation to neutralize unfractionated heparin (UFH) effects. They were prospectively included in this study and compared to a control group of 53 patients who underwent CB ablation without receiving protamine., Results: A total of 54 consecutive patients (33 male, 61%; mean age, 58 ± 12 years) were included. Twenty-one patients (39%) presented with hypertension, 17 (31%) with dyslipidemia, and 4 (7%) with diabetes. Five patients (9%) had a previous episode of ischemic stroke. Mean protamine dose was 68 ± 22 mg. No adverse reaction to protamine was observed. Among patients having received protamine, one (2%) experienced a cardiac tamponade requiring non-surgical drainage. No patient having undergone protamine administration experienced vascular complications. Conversely, the group of patients not treated with protamine had a significantly higher incidence of vascular complications as compared to patients having undergone protamine infusion (11 vs 0%, p = 0.01)., Conclusions: Reversing effects of UFH by the means of protamine administration appears to be safe after CB ablation for AF. It can allow in-laboratory sheath removal with potentially less vascular complications and no increase of thromboembolic risk. Larger randomized studies are needed in order to confirm our findings.

Introduction: Longer observational time and adenosine challenge have proven to be able to detect pulmonary vein (PV) reconnections. The aim of this study was to assess incidence of spontaneous and adenosine-induced PV reconnection after ablation with second-generation cryoballoon (CB-Adv)., Methods and Results: Fifty consecutive patients (76% male, mean age 60.5 ± 11.9 years) having undergone PV isolation (PVI) using the CB-Adv were enrolled. After isolation, reconnections were evaluated using the Achieve catheter over 30 minutes observation and adenosine administration during isoproterenol infusion (adenosine challenge). Among 200 PVs, isolation was achieved in 190 (95%) during the first application. Lower nadir temperature and longer rewarming time were associated with successful PVI (P = 0.02 and 0.04). Spontaneous (4 veins) and adenosine-induced (4 veins) PV reconnections occurred in the 4% of initially isolated veins (8 veins) in 6 patients (12%). At receiver-operator curve analysis, nadir temperature <-51 °C and rewarming time >28 seconds identified absence of reconnections (sensitivity 100% and 87%, area under the curve 0.75 and 0.72). Patients with right-sided early branching frequently experienced reconnections (P < 0.01). After a mean follow-up of 7.0 ± 1.7 months, 86% of patients were free from atrial fibrillation. None of those with PV reconnections experienced recurrences., Conclusions: The incidence of spontaneous and adenosine-induced PV reconnection following ablation with the novel CB-Adv is very low occurring in 4% of initially isolated veins. Nadir temperature <-51 °C and rewarming time >28 seconds identified absence of acute reconnections, thus avoiding prolonged waiting time and adenosine challenge in such cases., (© 2014 Wiley Periodicals, Inc.)

Background: With respect to the first generation Cryoballoon (CB), the second generation (Cryoballoon Advance [CB-A], Medtronic, Minneapolis, MN, USA) was designed with technical modifications resulting in a larger and more uniform zone of freezing on the balloon's surface aiming at procedural outcome improvement in the setting of atrial fibrillation (AF) ablation. However, a comparison between both technologies on a midterm follow-up is missing in today's literature., Methods: A total of 100 patients (the last 50 patients with the first generation CB and the first 50 patients with the second generation CB-A upon its inception in our center) having undergone a single CB ablation for paroxysmal AF (PAF) and having completed a 12-month follow-up, were consecutively included in our study. Freedom from AF off-antiarrhythmic drugs (AADs) after a single procedure was 78% (39/50) in CB-A and 58% (29/50) in the CB group (P = 0.03) during the whole follow-up duration. Considering a blanking period of 3 months, freedom from AF off-AAD was achieved in 84% (42/50) in CB-A, while 66% (33/50) were free from recurrence in the CB group (P = 0.038). Right phrenic nerve palsy (PNP) occurred in 8 patients (16%) in CB-A group and in 4 patients (8%) in the CB group., Conclusion: Freedom from AF on 12 months follow-up was significantly higher in the CB-A group with respect to the first generation device. The most frequent complication observed was PNP., (© 2014 Wiley Periodicals, Inc.)

Objectives: The goal of this study was to investigate the clinical features, management, and long-term follow-up of children with drug-induced Brugada syndrome (BS)., Background: Patients with BS <12 years of age with a spontaneous type I electrocardiogram have a higher risk of arrhythmic events. Data on drug-induced BS in patients <12 years of age are lacking., Methods: Among 505 patients with ajmaline-induced BS, subjects ≤12 years of age at the time of diagnosis were considered as children and eligible for this study., Results: Forty children (60% male; age 8 ± 2.8 years) were included. Twenty-four children (60%) had a family history of sudden death. Two (5%) had a previous episode of aborted sudden death, and 8 (20%) had syncope. Children experienced more frequent episodes of sinus node dysfunction (SND) compared with older subjects (7.5% vs. 1.5%; p = 0.04) and had a comparable incidence of atrial tachyarrhythmias. Children more frequently experienced episodes of ajmaline-induced sustained ventricular arrhythmias (VAs) compared with older patients (10.0% vs. 1.3%; p = 0.005). Twelve children (30%) received an implantable cardioverter-defibrillator (ICD). After a mean follow-up time of 83 ± 51 months, none of the children died suddenly. Spontaneous sustained VAs were documented in 1 child (2%). Among children with ICD, 1 (8%) experienced an appropriate shock, 4 (33%) had inappropriate ICD shocks, and 4 (33%) experienced device-related complications., Conclusions: Drug-induced BS is associated with atrial arrhythmias and SND. Children are at higher risk of ajmaline-induced VAs. The rate of device-related complications, leading to lead replacement or inappropriate shocks, is considerable and even higher than with appropriate interventions. Based on these findings, the optimal management of BS in childhood should remain individualized, taking into consideration the patient's clinical history and family's wishes., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to compare the results of pulmonary vein isolation using conventional irrigated radiofrequency (RF) approach versus the cryoballoon (CB) ablation. From January 2008 to December 2011, a total of 426 patients with drug-resistant symptomatic paroxysmal atrial fibrillation underwent pulmonary vein isolation as the index procedure by conventional manual RF or CB ablation at our center. A final population of 396 patients was considered for analysis and divided into 2 groups: conventional RF ablation (n = 260) and CB ablation (n = 136). At a mean follow-up of 23 ± 13 months (median 27, range 4 to 68), the success rate for RF ablation group was 57.3% (149 patients) and was 63.2% (86 patients) for cryoablation group (p = 0.25). Procedural times were significantly shorter in the cryoablation group (192 ± 49 vs 112 ± 58 minutes, p <0.000001) but not fluoroscopy times (36 ± 14 vs 31 ± 17 minutes, p = 0.45). No clinical predictors were found to predict atrial fibrillation recurrences. Complication rates were similar in both groups except for phrenic nerve palsy that was uniquely observed in the CB group (8.1%, p <0.00001). All phrenic nerve palsies resolved during follow-up. In conclusion, on a medium-term follow-up, conventional point-by-point RF ablation and CB ablation showed similar success rates. Procedural times were significantly shorter in the CB approach. The most frequent complication during CB procedures was phrenic nerve palsy, which occurred in 8.1% of patients and resolved in all during the follow-up period., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The clinical course and prognosis of Brugada syndrome (BS) in the elderly is unknown. The purpose of this study was to investigate the clinical characteristics, management, and prognosis of BS in an elderly population., Methods and Results: A total of 437 patients with BS were included in this study. Patients were categorized in 2 groups according to the age at the time of diagnosis: <60 years (N = 363) and ≥60 years (N = 74). Moreover, an elderly patients' subgroup analysis was performed between patients with an age between 60 and 70 years (N = 49) and subjects older than 70 years (N = 25). Among elderly patients (50% male, mean age: 67 ± 6 years), family history of sudden death (SD) and induction of sustained ventricular arrhythmias during programmed ventricular stimulation were less frequent as compared to younger patients. Two patients (3%) had a previous episode of aborted SD. Elderly patients with BS presented more frequently with ECG conduction disturbances or previous transient advanced atrioventricular block as compared to younger patients. Of the elderly patients, 42% underwent implantable cardioverter defibrillator implantation and 7% received a pacemaker. After a mean follow-up time of 54 ± 18 months, none of the elderly patients with BS older than 70 years experienced documented life-threating ventricular arrhythmias. Family screening was performed in 58 family members and a BS diagnosis was confirmed in 49%., Conclusion: The clinical features and the benign prognosis of BS patients older than 70 years likely identify a lower risk category of patients as compared to younger individuals. The device-guided management in this setting remains individualized and sometimes controversial. Moreover, BS diagnosis in the elderly should not be missed, mainly due to the clinical impact on the family of elderly patients., (© 2014 Wiley Periodicals, Inc.)

Aims: Pharmacological treatment of atrial fibrillation (AF) in the setting of Brugada syndrome (BS) might be challenging as many antiarrhythmic drugs (AADs) with sodium channel blocking properties might expose the patients to the development of ventricular arrhythmias. Moreover, patients with BS and implantable cardioverter-defibrillator (ICD) might experience inappropriate shocks because of AF with rapid ventricular response. The role of pulmonary vein isolation (PVI) in patients with BS and recurrent episodes of AF has not been established yet. In this study, we analysed the outcome of PVI using radiofrequency energy or cryoballoon (CB) ablation at 2 years follow-up., Methods and Results: Consecutive patients with BS having undergone PVI for drug-resistant paroxysmal AF were eligible for this study. Nine patients (three males; mean age: 52 ± 26 years) were included. Six patients (67%) had an ICD implanted of whom three had inappropriate shocks because of rapid AF. At a mean 22.1 ± 6.4 months follow-up, six patients (67%) were free of AF without AADs. None of the three patients who had experienced inappropriate ICD interventions for AF had further ICD shocks after ablation., Conclusion: In our study PVI can be an effective and safe procedure to treat patients with BS and recurrent episodes of paroxysmal AF.

Background: The effects and the safety of ajmaline challenge in elderly patients with suspected atrioventricular (AV) conduction disease have not been systematically investigated. The purpose of this study was to assess the response of intravenous administration of ajmaline in patients older than 75 years suspected to be affected by AV conduction disease with respect to unmask high-degree His-Purkinje block or the typical Brugada ECG pattern., Methods: Consecutive patients older than 75 years having undergone in our centre an electrophysiologic study with intravenous ajmaline administration were eligible for this study., Results: A total of 162 consecutive patients older than 75 years (84 males; mean age: 78±4 years) were included. Ajmaline induced prolongation of the H-V interval up to 100 ms or more in 25 patients (15%). High degree His-Purkinje block was produced in 5 patients (3%). Moreover, ajmaline challenge unmasked a Brugada type 1 ECG in 12 patients (7%). No ventricular tachyarrhythmia was observed during the pharmacologic challenge and no severe side effects occurred. Among the study population, 56 (34%) and 6 patients (4%) underwent a PM and ICD implantation, respectively. For the patients with BS, a family screening was performed in a total of 37 individuals. Eighteen family members (48%) presented a positive ajmaline test and 1 (3%) a spontaneous Brugada type 1 ECG., Conclusions: Ajmaline challenge in the elderly is a safe procedure to unmask AV conduction disease and can lead to an unexpected diagnosis of BS. Although the clinical impact is obvious, the therapeutic management remains controversial., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: The second-generation cryoballoon (CB-A) (Arctic Front Advance, Cryocath, Medtronic, MN, USA) might significantly improve procedural outcome with respect to the first-generation balloon. These technological improvements might also question the current recommendation of the need a 4-min freeze to achieve durable pulmonary vein isolation (PVI)., Objective: The main aim of the study was to analyze the procedural efficacy of a 3-min freeze-thaw cycles with the CB-A balloon in the terms of rates of acute PVI and 6-month outcome., Methods: Patients having undergone CB-A for PAF or early persistent AF, with 3-min freeze-thaw cycles were consecutively included in our analysis. Acute procedural success was measured in terms of the rate of PVI. Short-term follow-up was evaluated by the means of 24-h Holters and clinical examinations at regular intervals., Results: Fifty-two consecutive patients (35 male (67 %); mean age, 59.8 ± 10.5) were included. Mean procedure and fluoroscopy times were 96 ± 15 and 13.2 ± 8.3 min, respectively. Mean time from groin puncture to catheter extraction was 60.4 ± 20 min. After a mean of 1.5 freeze cycles per vein of 3 min in duration, all 208 (100 %) PVs could be isolated with the CB-A. A total 192 (91 %) veins were isolated during the first freeze. At a mean of 5.7-month follow-up, 82 % of patients were free of AF., Conclusion: CB-A is effective in producing PVI by using 3-min-duration freeze cycles. After a mean of 1.5 freeze per vein, freedom from AF was achieved in 82 % of patients at 6-month follow-up.

Introduction: Pulmonary vein (PV) isolation by means of cryoballoon (CB) technology is an effective treatment for symptomatic paroxysmal atrial fibrillation (AF) refractory to antiarrhythmic drug therapy. The CB requires a 15F transseptal sheath that may lead to the creation of a iatrogenic atrial septal defect (IASD)., Methods and Results: Individuals having undergone PV isolation by the means of CB ablation and a subsequent transesophageal echocardiography (TEE) examination during postablation follow-up were consecutively included. Thirty-nine patients formed the study group (31 male, 76.9%; mean age 57.4 ± 13.7 years). IASD was present in 8 (20%) of them after a mean follow-up time of 11.7 months. Mean diameter of the defect was 0.57 cm × 0.48 cm; only left to right shunt was observed. No adverse events were recorded in these patients during the follow-up., Conclusion: IASD after CB ablation of AF is present in up to 20% of patients after 1 year. Although no adverse clinical events were recorded in patients with persistence of IASD, this complication should not be underestimated and systematic echocardiographic examinations might be advised at regular intervals in the follow-up period after CB. Further studies with larger population and follow-up might be required to confirm our findings., (© 2014 Wiley Periodicals, Inc.)

Background: Sustained ventricular arrhythmias (sVAs), such as polymorphic ventricular tachycardia or ventricular fibrillation, can complicate ajmaline challenge in patients with Brugada syndrome (BS)., Objective: To assess the incidence of life-threatening sVAs during ajmaline administration in a large series of patients with BS. In addition, clinical characteristics as well as prognosis of these patients were evaluated., Methods: All consecutive patients with ajmaline-induced diagnosis of BS were eligible for this study., Results: A total of 503 patients were included. Nine (1.8%) patients (44% men; mean age 26 ± 18 years) developed a life-threatening sVA during ajmaline challenge. Three patients (33%)were children, and 2 (22%) patients experienced sVAs refractory to the first external defibrillation. One patient underwent venoarterial extracorporeal membrane oxygenation to restore sinus rhythm. Age at the time of ajmaline challenge was significantly lower in patients with sVAs compared with patients without sVAs (26 ± 18 years vs 41 ± 18 years; P = .01). Moreover, patients with sVAs presented more frequently with sinus node dysfunction compared with patients with normal response to ajmaline (22.2% vs 1.4%; P = .01). After a mean follow-up time of 29 ± 8 months, none of the patients who had developed a sVA during ajmaline challenge died suddenly or developed further life-threatening ventricular arrhythmias., Conclusions: sVA during ajmaline challenge is not a rare event in BS occurring in 9 (1.8%) patients. Despite its challenging acute treatment, the occurrence of ajmaline-induced sVAs in patients with BS might not identify a category at higher risk for further arrhythmic events., (© 2013 Heart Rhythm Society Published by Heart Rhythm Society All rights reserved.)

Background: Lead extraction (LE) techniques have evolved from simple traction to extraction with dilators and powered sheaths with very high success rates. On the basis of the systematic implementation of a stepwise approach, we aimed to identify those characteristics that can predict the need for advanced LE techniques., Methods: Between April 2005 and March 2012, 208 consecutive LE procedures were performed and 456 leads were extracted using an initial superior approach. Advanced techniques for LE (step 4 according to our stepwise approach) were used in 122 patients (58.7%)., Results: Younger patient age (odds ratio [OR] = 0.963, P = 0.002), longer duration of the initial implantation (OR = 1.013, P = 0.002), the number of extracted leads (OR = 2.184, P < 0.001), and the presence of right ventricular defibrillator leads (OR = 2.144, P = 0.049) independently predicted the necessity of using step 4 in multivariate analysis. A prediction tool was created taking into account four categorical variables derived even from Receiver Operating Curve analysis of quantitative characteristics (age < 70.7 years, implant duration > 37 months, extraction of at least two leads, one of them being a defibrillator lead). The absence of all the four characteristics was accompanied by 0% positive predictive value for the requirement of step 4 for LE, whereas the coexistence of all four risk factors is characterized by 87% requirement of advanced LE., Conclusion: In most of the patients with indication for LE, use of a powered sheath extraction is necessary in order to obtain clinical success. We have identified four patient and lead characteristics that may help the operator plan the means of extraction., (©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.)