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Background: Atrial arrhythmogenic substrate is a key determinant of atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI), and reduced conduction velocities have been linked to adverse outcome. However, a noninvasive method to assess such electrophysiologic substrate is not available to date., Objective: This study aimed to noninvasively assess regional conduction velocities and their association with arrhythmia-free survival after PVI., Methods: A consecutive 52 patients scheduled for AF ablation (PVI only) and 19 healthy controls were prospectively included and received electrocardiographic imaging (ECGi) to noninvasively determine regional atrial conduction velocities in sinus rhythm. A novel ECGi technology obviating the need of additional computed tomography or cardiac magnetic resonance imaging was applied and validated by invasive mapping., Results: Mean ECGi-determined atrial conduction velocities were significantly lower in AF patients than in healthy controls (1.45 ± 0.15 m/s vs 1.64 ± 0.15 m/s; P < .0001). Differences were particularly pronounced in a regional analysis considering only the segment with the lowest average conduction velocity in each patient (0.8 ± 0.22 m/s vs 1.08 ± 0.26 m/s; P < .0001). This average conduction velocity of the "slowest" segment was independently associated with arrhythmia recurrence and better discriminated between PVI responders and nonresponders than previously proposed predictors, including left atrial size and late gadolinium enhancement (magnetic resonance imaging). Patients without slow-conduction areas (mean conduction velocity <0.78 m/s) showed significantly higher 12-month arrhythmia-free survival than those with 1 or more slow-conduction areas (88.9% vs 48.0%; P = .002)., Conclusion: This is the first study to investigate regional atrial conduction velocities noninvasively. The absence of ECGi-determined slow-conduction areas well discriminates PVI responders from nonresponders. Such noninvasive assessment of electrical arrhythmogenic substrate may guide treatment strategies and be a step toward personalized AF therapy., Competing Interests: Disclosures Dr Till Althoff has received research grants for investigator-initiated trials from Biosense Webster and honoraria as consultant from Corify Care. Prof Lluís Mont has received honoraria as a lecturer and consultant and has received research grants from Abbott Medical, Biosense Webster, Boston Scientific, and Medtronic; he is a shareholder of Galgo Medical SL and Corify Care. Drs Andreu Climent and María S. Guillem are co-founders of Corify Care and receive honoraria from the company. Dr Ismael Hernández is co-founder of Corify Care. Jana Reventos is employed by Corify Care. Drs Ivo Roca-Luque, Jose M. Tolosana, and Andreu Porta-Sanchez received honoraria as consultants for Biosense Webster, Boston Scientific, and Medtronic. Dr Jean-Baptiste Guichard reports honoraria as a consultant from Microport CRM and as lecturer from Microport CRM and Abbott and an unrestricted grant support for a fellowship from Abbott Laboratories., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Left bundle branch pacing (LBBP) is considered an alternative to cardiac resynchronization therapy (CRT). However, LBBP is not suitable for all patients with heart failure., Objective: The aim of our study was to identify predictors of unsuccessful LBBP implantation in CRT candidates., Methods: A cohort of consecutive patients with indications for CRT were included. Clinical, echocardiographic, and electrocardiographic variables were prospectively recorded., Results: A total of 187 patients were included in the analysis. LBBP implantation was successful in 152 of 187 patients (81.2%) and failed in 35 of 187 patients (18.7%). The causes of unsuccessful implantation were unsatisfactory paced QRS morphology (28 of 35 [80%]), inability to screw the helix (4 of 35 [11.4%]), lead instability (2 of 35 [5.7%]), and high pacing thresholds (1 of 35 [2.8%]). The left ventricular end-diastolic diameter (LVEDD), non-LBBB (left bundle branch block) QRS morphology, and QRS width were predictors of failed implantation according to the univariate analysis. According to the multivariate regression analysis, LVEDD (odds ratio 1.31 per 5-mm increase; 95% confidence interval 1.05-1.63 per 5-mm increase; P = .02) and non-LBBB (odds ratio 3.07; 95% confidence interval 1.08-8.72; P = .03) were found to be independent predictors of unsuccessful LBBP implantation. An LVEDD of 60 mm has 60% sensitivity and 71% specificity for predicting LBBP implant failure., Conclusion: When LBBP was used as CRT, LVEDD and non-LBBB QRS morphology predicted unsuccessful implantation. Non-LBBB triples the likelihood of failed implantation independent of LVEDD. Caution should be taken when considering these parameters to plan the best pacing strategy for patients., Competing Interests: Disclosures Dr Pujol-López has received speaker honoraria from Medtronic. Dr Tolosana has received honoraria as a lecturer and consultant from Abbott, Boston Scientific, and Medtronic. Dr Mont has received unrestricted research grants, fellowship program support, and honoraria as a lecturer and consultant from Abbott, Biotronik, Boston Scientific, LivaNova, and Medtronic; he holds stock in Galgo Medical and Corify. Dr Roca-Luque has received honoraria as a lecturer and consultant from Abbott and Biosense Webster. Dr Sitges has received consultant fees and speaker honoraria from Abbott, Medtronic, General Electric, and Edwards Lifesciences. Dr Castel has received speaker honoraria from Boston Scientific, Abbott, and MicroPort. Dr Arbelo has received speaker honoraria from Biosense Webster and Bayer. Dr Porta-Sánchez has received honoraria as a lecturer and consultant from Biosense Webster, Abbott, and Boston Scientific. Dr Guichard has received honoraria as a consultant from MicroPort CRM, honoraria as a lecturer from MicroPort CRM and Abbott, and unrestricted grant support for a fellowship from Abbott. The remaining authors declare that they have no conflicts of interest., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Voltage mapping could identify the conducting channels potentially responsible for ventricular tachycardia (VT). Standard thresholds (0.5-1.5 mV) were established using bipolar catheters. No thresholds have been analyzed with high-density mapping catheters. In addition, channels identified by cardiac magnetic resonance (CMR) has been proven to be related with VT., Objective: The purpose of this study was to analyze the diagnostic yield of a personalized voltage map using CMR to guide the adjustment of voltage thresholds., Methods: All consecutive patients with scar-related VT undergoing ablation after CMR (from October 2018 to December 2020) were included. First, personalized CMR-guided voltage thresholds were defined systematically according to the distribution of the scar and channels. Second, to validate these new thresholds, a comparison with standard thresholds (0.5-1.5 mV) was performed. Tissue characteristics of areas identified as deceleration zones (DZs) were recorded for each pair of thresholds. In addition, the relation of VT circuits with voltage channels was analyzed for both maps., Results: Thirty-two patients were included [mean age 66.6 ± 11.2 years; 25 (78.1%) ischemic cardiomyopathy]. Overall, 52 DZs were observed: 44.2% were identified as border zone tissue with standard cutoffs vs 75.0% using personalized voltage thresholds (P = .003). Of the 31 VT isthmuses detected, only 35.5% correlated with a voltage channel with standard thresholds vs 74.2% using adjusted thresholds (P = .005). Adjusted cutoff bipolar voltages that better matched CMR images were 0.51 ± 0.32 and 1.79 ± 0.71 mV with high interindividual variability (from 0.14-1.68 to 0.7-3.21 mV)., Conclusion: Personalized voltage CMR-guided personalized voltage maps enable a better identification of the substrate with a higher correlation with both DZs and VT isthmuses than do conventional voltage maps using fixed thresholds., Competing Interests: Disclosures Drs Mont and Brugada report activities as a consultant, lecturer, and advisory board member for Abbott Medical, Boston Scientific, Biosense Webster, Medtronic, and Biotronik. They are also shareholders of ADAS 3D Medical. Drs Roca-Luque, Tolosana, and Porta-Sánchez report activities as a consultant and lecturer for Biosense Webster, Medtronic, Boston Scientific, and Abbott Medical. All other authors report that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Undifferentiated autoinflammatory diseases are characterized by recurrent or persistent fever, usually combined with other inflammatory manifestations, and negative or inconclusive genetic studies for monogenic autoinflammatory disorders., Aims: To define and characterize disease phenotypes in adult patients diagnosed in an adult reference center with undifferentiated autoinflammatory diseases, and to analyze the efficacy of the drugs used in order to provide practical diagnostic and therapeutic recommendations., Methods: Retrospective study (2015-2022) of patients with undifferentiated autoinflammatory diseases among all patients visited in our reference center. Demographic, clinical, laboratory features and detailed therapeutic information was collected., Results: Of the 334 patients with a suspected autoinflammatory disease, 134 (40%) patients (61% women) were initially diagnosed with undifferentiated autoinflammatory diseases. Mean age at disease onset and at diagnosis was 28.7 and 37.7 years, respectively. In 90 (67.2%) patients, symptoms started during adulthood. Forty-four (32.8%) patients met diagnostic/classification criteria for adult periodic fever with aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome. In the remaining patients, four additional phenotypes were differentiated according to the predominant manifestations: a) Predominantly fever phenotype (n = 18; 13.4%); b) Predominantly abdominal/pleuritic pain phenotype (n = 9; 6.7%); c) Predominantly pericarditis phenotype (n = 18; 13.4%), and d) Complex syndrome phenotype (n = 45; 33.6%). Prednisone (mainly on demand), colchicine and anakinra were the drugs commonly used. Overall, complete responses were achieved with prednisone in 41.3%, colchicine in 40.2%, and anakinra in 58.3% of patients in whom they were used. By phenotypes, prednisone on demand was more effective in adult PFAPA syndrome and colchicine in patients with the abdominal/pleuritic pain pattern and PFAPA syndrome. Patients with complex syndrome achieved complete responses with prednisone (21.9%), colchicine (25.7%) and anakinra (44.4%), and were the group more often requiring additional immunosuppressive drugs., Conclusions: The analysis of the largest single-center series of adult patients with undifferentiated autoinflammatory diseases identified and characterized different disease phenotypes and their therapeutic approaches. This study is expected to contribute to increase the awareness of physicians for an early identification of these conditions, and to provide the best known therapeutic options., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: José Hernández-Rodríguez reports financial support was provided by Hospital Clínic de Barcelona. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The current practice of atrial fibrillation ablation (AFA) as a treatment option for atrial fibrillation (AF) in patients with heart failure (HF) across Europe, their clinical profiles and outcomes is still undefined., Methods: The European Society of Cardiology (ESC) led a prospective observational registry of consecutive patients undergoing AFA, in 27 member countries. The subgroup of patients with HF, followed-up for 1 year, was analyzed and the results are reported., Results: Of the 3582 AF patients in the Registry, 537 (14.9%) had HF. Diabetes, hypertension, hypercholesterolemia, CHA 2 DS 2 -VASc score ≥ 2, structural heart disease and persistent AF were more common in HF than non-HF patients (all p < 0.001). However the in-hospital complications were less frequent in HF patients (5.0% vs. 8.2% p = 0.01). Both in-hospital and 1-year outcomes, including 1-year AF recurrence (15.4%) and repeat ablations (9.5%), were similar in both groups. We subdivided HF patients according to their left ventricular ejection fraction (EF) at baseline into reduced (HFrEF, <40%), mid-range (HFmEF, 40-49%), or preserved EF (HFpEF, ≥ 50%). Most patients were HFpEF (n 375, 77%), 72 (15%) were HFmEF and 8% HFrEF. The most frequent underlying conditions in HFpEF were hypertension and ischemic heart disease, while those most common in HFmEF and HFrEF were valvular and dilated cardiomyopathy., Conclusion: In routine care in Europe, HF patients represent a minority of patients undergoing AFA, and most belong to the HFpEF phenotype. The limited clinical research on AFA HFpEF patients is reflected by the uncertainty expressed in the current AF Guidelines and Expert statements., (Copyright © 2021 Elsevier B.V. All rights reserved.)

During the last decades, the practice of sport and hypertrophic cardiomyopathy (HCM) were considered as incompatible, since evidence was not sufficient to gauge the risk associated to repeat and/or vigorous exercise across the spectrum of HCM. Additionally, it was acknowledged thatrisk stratification tools developed for HCM were not derived from athlete cohorts. Recent epidemiological studies focused on HCM both in the general population and in athletes, however, have de-emphasized the contribution of this condition to the risk of sport-associated sudden death, supporting the possibility of allowing the practice of some sports, even at professional level, for certain low-risk HCM categories. We hereby analyze the complex interaction of vigorous and continuative exercise with HCM, revising the available evidence for sports eligibility in HCM, the challenges and limitations of shared decision-making, as well as the potential harms and benefits of a highly personalised exercise schedule in subjects diagnosed with this complex disease., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Scar characteristics analyzed by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) are related with ventricular arrhythmias. Current guidelines are based only on the left ventricular ejection fraction to recommend an implantable cardioverter-defibrillator (ICD) in primary prevention., Objectives: Our study aims to analyze the role of imaging to stratify arrhythmogenic risk in patients with ICD for primary prevention., Methods: From 2006 to 2017, we included 200 patients with LGE-CMR before ICD implantation for primary prevention. The scar, border zone, core, and conducting channels (CCs) were automatically measured by a dedicated software., Results: The mean age was 60.9 ± 10.9 years; 81.5% (163) were men; 52% (104) had ischemic cardiomyopathy. The mean left ventricular ejection fraction was 29% ± 10.1%. After a follow-up of 4.6 ± 2 years, 46 patients (22%) reached the primary end point (appropriate ICD therapy). Scar mass (36.2 ± 19 g vs 21.7 ± 10 g; P < .001), border zone mass (26.4 ± 12.5 g vs 16.0 ± 9.5 g; P < .001), core mass (9.9 ± 8.6 g vs 5.5 ± 5.7 g; P < .001), and CC mass (3.0 ± 2.6 g vs 1.6 ± 2.3 g; P < .001) were associated with appropriate therapies. Scar mass > 10 g (25.31% vs 5.26%; hazard ratio 4.74; P = .034) and the presence of CCs (34.75% vs 8.93%; hazard ratio 4.07; P = .003) were also strongly associated with the primary end point. However, patients without channels and with scar mass < 10 g had a very low rate of appropriate therapies (2.8%)., Conclusion: Scar characteristics analyzed by LGE-CMR are strong predictors of appropriate therapies in patients with ICD in primary prevention. The absence of channels and scar mass < 10 g can identify patients at a very low risk of ventricular arrhythmias in this population., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Substrate-based ventricular tachycardia (VT) ablation is a first-line treatment in patients with structural cardiac disease and sustained VT refractory to medical therapy. Despite technological improvements and increased knowledge of VT substrate, recurrence still is frequent. Published data are lacking on the possible reduction in VT burden after ablation despite recurrence., Objective: The purpose of this study was to assess VT burden reduction during long-term follow-up after substrate ablation and identify predictors of VT recurrence., Methods: We analyzed 234 consecutive VT ablation procedures in 207 patients (age 63 ± 14.9 years; 92% male; ischemic heart disease in 65%) who underwent substrate ablation in a single center from 2013 to 2018., Results: After follow-up of 3.14 ± 1.8 years, the VT recurrence rate was 41.4%. Overall, a 99.6% reduction in VT burden (median VT episodes per year: preprocedural 3.546 [1.347-13.951] vs postprocedural 0.001 [0-0.689]; P = .001) and a 96.3% decrease in implantable cardioverter-defibrillator (ICD) shocks (preprocedural 1.145 [0.118-4.467] vs postprocedural 0.042 [0-0.111] per year; P = .017) were observed. In the subgroup of patients who experienced VT recurrences, VT burden decreased by 69.2% (median VT episodes per year: preprocedural 2.876 [1.105-8.801] vs postprocedural 0.882 [0.505-2.283]; P <.001). Multivariable analysis showed persistence of late potentials (67% vs 19%; hazard ratio 3.18 [2.18-6.65]; P <.001) and lower left ventricular ejection fraction (EF) (30 [25-40] vs 39 [30-50]; P = .022) as predictors of VT recurrence., Conclusion: Despite a high recurrence rate during long-term follow-up, substrate-based VT ablation is related to a large reduction in VT burden and a decrease in ICD therapies. Lower EF and persistence of late potentials are predictors of recurrence., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: A male predominance in Brugada syndrome (BrS) has been widely reported, but scarce information on female patients with BrS is available., Objective: The purpose of this study was to investigate the clinical characteristics and long-term prognosis of women with BrS., Methods: A multicenter retrospective study of patients diagnosed with BrS and previous electrophysiological study (EPS) was performed., Results: Among 770 patients, 177 (23%) were female. At presentation, 150 (84.7%) were asymptomatic. Females presented less frequently with a type 1 electrocardiographic pattern (30.5% vs 55.0%; P <.001), had a higher rate of family history of sudden cardiac death (49.7% vs 29.8%; P <.001), and had less sustained ventricular arrhythmias (VAs) on EPS (8.5% vs 15.1%; P = .009). Genetic testing was performed in 79 females (45% of the sample) and was positive in 34 (19%). An implantable cardioverter-defibrillator was inserted in 48 females (27.1%). During mean (± SD) follow-up of 122.17 ± 57.28 months, 5 females (2.8%) experienced a cardiovascular event compared to 42 males (7.1%; P = .04). On multivariable analysis, a positive genetic test (18.71; 95% confidence interval [CI] 1.82-192.53; P = .01) and atrial fibrillation (odds ratio 21.12; 95% CI 1.27-350.85; P = .03) were predictive of arrhythmic events, whereas VAs on EPS (neither with 1 or 2 extrastimuli nor 3 extrastimuli) were not., Conclusion: Women with BrS represent a minor fraction among patients with BrS, and although their rate of events is low, they do not constitute a risk-free group. Neither clinical risk factors nor EPS predicts future arrhythmic events. Only atrial fibrillation and positive genetic test were identified as risk factors for future arrhythmic events., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate., Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants., Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 × 10 -18 ) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 × 10 -13 ). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency., Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.

Background: The electrocardiographic (ECG) definition of Brugada syndrome (BS) can be challenging because benign ECG abnormalities, such as right bundle branch block (RBBB), may mimic pathological ECG characteristics of BrS. However, although myocardial delay and deformation can be quantified by advanced imaging, it has not yet been used to differentiate between BrS and RBBB. The aim of this study was to characterize the electro-mechanical behavior of the heart of patients with type-1 BrS and isolated complete RBBB in order to differentiate these conditions., Methods: In this two-center study, 66 subjects were analyzed by standard and speckle-tracking echocardiography (STE): 22 type-1 BrS, 24 isolated complete RBBB, and 20 healthy subjects. The participants were not treated by any drug potentially influencing myocardial conduction., Results: Standard echocardiographic parameters did not differ among the groups. The greatest right ventricular (RV) mechanical dispersion was found in RBBB. Mean absolute deviations (MADs) of time-to-peak longitudinal strain calculated for each left ventricular (LV) region were greater in patients with RBBB as compared to BrS (p < .01). No differences were found between BrS and controls (p = .36). MADs in the basal segments in RBBB group were greater than MADs found in BrS group and controls (37.3 ms vs. 26.7 ms and 29.0 ms, respectively, p < .05). The greatest differences were found in the antero-septal, anterior, lateral, and infero-septal basal segments., Conclusions: Advanced echocardiographic techniques may help to differentiate between BrS and RBBB. Indeed, STE allows to identify an electro-mechanical conduction delay in RBBB patients that is not found in patients affected by type-1 BrS., Competing Interests: Declaration of Competing Interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ever since the first case was reported at the end of 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated coronavirus disease 2019 (COVID-19) has become a serious threat to public health globally in short time. At this point in time, there is no proven effective therapy. The interactions with concomitant disease are largely unknown, and that may be particularly pertinent to inherited arrhythmia syndrome. An arrhythmogenic effect of COVID-19 can be expected, potentially contributing to disease outcome. This may be of importance for patients with an increased risk of cardiac arrhythmias, either secondary to acquired conditions or comorbidities or consequent to inherited syndromes. Management of patients with inherited arrhythmia syndromes such as long QT syndrome, Brugada syndrome, short QT syndrome, and catecholaminergic polymorphic ventricular tachycardia in the setting of the COVID-19 pandemic may prove particularly challenging. Depending on the inherited defect involved, these patients may be susceptible to proarrhythmic effects of COVID-19-related issues such as fever, stress, electrolyte disturbances, and use of antiviral drugs. Here, we describe the potential COVID-19-associated risks and therapeutic considerations for patients with distinct inherited arrhythmia syndromes and provide recommendations, pending local possibilities, for their monitoring and management during this pandemic., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Over the last ten years, analysis of copy number variants has increasingly been applied to the study of arrhythmogenic pathologies associated with sudden death, mainly due to significant advances in the field of massive genetic sequencing. Nevertheless, few published reports have focused on the prevalence of copy number variants associated with sudden cardiac death. As a result, the frequency of these genetic alterations in arrhythmogenic diseases as well as their genetic interpretation and clinical translation has not been established. This review summarizes the current available data concerning copy number variants in sudden cardiac death-related diseases., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The Micra transcatheter pacing system (Micra TPS) is often implanted in patients with atrial fibrillation and thus with increased thromboembolic risk. It is unknown whether the use of anticoagulants, associated with the use of a large venous introducer, implies an increased risk of bleeding in this group of patients., Objective: The purpose of this study was to assess the incidence of bleeding and thromboembolic complications after Micra TPS implantation with and without therapeutic anticoagulation., Methods: This single-center observational study included 107 consecutive patients receiving the Micra TPS from 2014 to 2018. At procedure completion, a figure-of-eight suture was placed at the femoral puncture site after sheath withdrawal and was maintained for 24 hours. In patients receiving enoxaparin or new oral anticoagulants, treatment was discontinued 12 or 24 hours before the procedure, respectively, and was reinitiated 4-6 hours postprocedure. In those receiving vitamin K antagonists (VKAs), dosing was not discontinued and the procedure was performed if the international normalized ratio was less than 3., Results: Sixty-four patients (60%) did not receive anticoagulants. Of the 43 (40%) who did, 29 (67%) received VKAs, 8 (19%) received new oral anticoagulants, and 6 (14%) received enoxaparin. Two patients presented hemorrhagic or thromboembolic complications during short-term follow-up: 1 woman receiving VKAs presented hemorrhagic pericardial effusion without tamponade and 1 woman not receiving anticoagulants presented thrombosis of the ipsilateral saphenous vein., Conclusion: Bleeding and thromboembolic complications after receiving Micra TPSs are infrequent. The use of anticoagulant therapy, regardless of the type, does not increase the complications associated with the procedure., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: There is limited information on ethnic differences between patients with Brugada syndrome (BrS) and arrhythmic events (AEs)., Objective: The purpose of this study was to compare clinical, electrocardiographic (ECG), electrophysiological, and genetic characteristics between white and Asian patients with BrS and AEs., Methods: The Survey on Arrhythmic Events in Brugada Syndrome is a multicenter survey from Western and Asian countries, gathering 678 patients with BrS and first documented AE. After excluding patients with other (n = 14 [2.1%]) or unknown (n = 30 [4.4%]) ethnicity, 364 (53.7%) whites and 270 (39.8%) Asians comprised the study group., Results: There was no difference in AE age onset (41.3 ± 16.1 years in whites vs 43.3 ± 12.3 years in Asians; P = .285). Higher proportions of whites were observed in pediatric and elderly populations. Asians were predominantly men (98.1% vs 85.7% in whites; P < .001) and frequently presented with aborted cardiac arrest (71.1% vs 56%; P < .001). Asians tended to display more spontaneous type 1 BrS-ECG pattern (71.5% vs 64.3%; P = .068). A family history of sudden cardiac death was noted more in whites (29.1% vs 11.5%; P < .001), with a higher rate of SCN5A mutation carriers (40.1% vs 13.2% in Asians; P < .001), as well as more fever-related AEs (8.5% vs 2.9%; P = .011). No difference was observed between the 2 groups regarding history of syncope and ventricular arrhythmia inducibility., Conclusion: There are important differences between Asian and white patients with BrS. Asian patients present almost exclusively as male adults, more often with aborted cardiac arrest and spontaneous type 1 BrS-ECG. However, they have less family history of sudden cardiac death and markedly lower SCN5A mutation rates. The striking difference in SCN5A mutation rates should be tested in future studies., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Previously proposed algorithms to predict the ventricular tachycardia (VT) exit site have been based on diverse left ventricular models, but none of them identify the precise region of origin in the electroanatomic map. Moreover, no electrocardiographic (ECG) algorithm has been tested to predict the region of origin of scar-related VTs in patients with nonischemic cardiomyopathy., Objective: The purpose of this study was to validate a simple ECG algorithm to identify the segment of origin (SgO) of VT relative to the 17-segment American Heart Association model in patients with structural heart disease (SHD)., Methods: The study included 108 consecutive patients with documented VT and SHD [77 (71%) with coronary artery disease]. A novel frontal plane axis-based ECG algorithm (highest positive or negative QRS voltage) together with the polarity in leads V 3 and V 4 was used to predict the SgO of VT. The actual SgO of VT was obtained from the analysis of the electroanatomic map during the procedure. Conventional VT mapping techniques were used to identify the VT exit., Results: In total, 149 12-lead ECGs of successfully ablated VT were analyzed. The ECG-suggested SgO matched with the actual SgO in 122 of the 149 VTs (82%). In 21 of the 27 mismatched ECG-suggested SgOs (77.8%), the actual SgO was adjacent to the segment suggested by the ECG. There were no differences in the accuracy of the algorithm based on the SgO or the type of SHD., Conclusion: This novel QRS axis-based algorithm accurately identifies the SgO of VT in the 17-segment American Heart Association model in patients with SHD., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: There is limited information on gender differences in patients with Brugada syndrome (BrS) who experienced arrhythmic events (AEs)., Objective: The purpose of this study was to compare clinical, electrocardiographic (ECG), electrophysiological, and genetic characteristics between males and females in patients with BrS with their first AE., Methods: The multicenter Survey on Arrhythmic Events in BRUgada Syndrome collected data on the first AE in 678 patients with BrS including 619 males (91.3%) and 59 females (8.7%) aged 0.27-84 years (mean age 42.5 ± 14.1 years) at the time of AE occurrence., Results: After excluding pediatric patients, it was found that females were older than males (49.5 ± 14.4 years vs 43 ± 12.7 years, respectively; P = .001). Higher proportions of females were observed in the pediatric and elderly populations. In Asians, the male to female ratio for AEs was ≈9-fold higher than that in White. Spontaneous type 1 BrS ECG was associated with an earlier onset of AEs in pediatric females. A similar prevalence (≈65%) of spontaneous type 1 BrS ECG was present in males and females above the age of 60 years. Females less frequently showed spontaneous type 1 BrS ECG (41% vs 69%; P < .001) or arrhythmia inducibility at electrophysiology study (36% vs 66%; P < .001). An SCN5A mutation was more frequently found in females (48% vs 28% in males; P = .007)., Conclusion: This study confirms that female patients with BrS are much rarer, display less type 1 Brugada ECG, and exhibit lower inducibility rates than do males. It shows for the first time that female patients with BrS with AE have higher SCN5A mutation rates as well as the relationship between gender vs age at the onset of AEs and ethnicity., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The literature on fever-related arrhythmic events (AEs) in Brugada syndrome (BrS) is currently limited to few case reports and small series., Objective: The present study aimed to describe the characteristics of fever-related AE in a large cohort of patients with BrS., Methods: The Survey on Arrhythmic Events in Brugada Syndrome is a multicenter study on 678 patients with BrS with first AE documented at the time of aborted cardiac arrest (n = 426) or after prophylactic implantable cardioverter-defibrillator implantation (n = 252)., Results: In 35 of 588 patients (6%) with available information, the AE occurred during a febrile illness. Most of the 35 patients were male (80%), Caucasian (83%), and proband (70%). The mean age at the time of AE was 29 ± 24 years (range 0.3-76 years). Most patients (80%) presented with aborted cardiac arrest and 6 (17%) with arrhythmic storm. Family history of sudden death, history of syncope, and spontaneous type 1 Brugada electrocardiogram were noted in 17%, 40%, and 71% of patients, respectively. Ventricular fibrillation was induced at electrophysiology study in 9 of 19 patients (47%). An SCN5A mutation was found in 14 of 28 patients (50%). The highest proportion of fever-related AE was observed in the pediatric population (age <16 years), with a disproportionally higher event rate in the very young (age 0-5 years) (65%). Males were involved in all age groups and females only in the pediatric and elderly groups. Fever-related AE affected 17 Caucasians aged <24 years, but no Asians aged <24 years., Conclusion: The risk of fever-related AE in BrS markedly varies according to age group, sex, and ethnicity. Taking these factors into account could help the clinical management of patients with BrS with fever., (Copyright © 2018 Heart Rhythm Society. All rights reserved.)

Background: Ventricular fibrillation in patients with Brugada syndrome (BrS) is often initiated by premature ventricular contractions (PVCs). Presence of SCN5A mutation increases the risk of PVCs upon exposure to sodium channel blockers (SCB) in patients with baseline type-1 ECG. In patients without baseline type-1 ECG, however, the effect of SCN5A mutation on the risk of SCB-induced arrhythmia is unknown. We aimed to establish whether presence/absence, type, and topology of SCN5A mutation correlates with PVC occurrence during ajmaline infusion., Methods and Results: We investigated 416 patients without baseline type-1 ECG who underwent ajmaline testing and SCN5A mutation analysis. A SCN5A mutation was identified in 88 patients (S + ). Ajmaline-induced PVCs occurred more often in patients with non-missense mutations (S non-missense ) or missense mutations in transmembrane or pore regions of SCN5A-encoded channel protein (S missense-TP ) than patients with missense mutations in intra-/extracellular channel regions (S missense-IE ) and patients without SCN5A mutation (S - ) (29%, 24%, 9%, and 3%, respectively; P<0.001). The proportion of patients with ajmaline-induced BrS was similar in different mutation groups but lower in S - (71% S non-missense , 63% S missense-TP , 70% S missense-IE , and 34% S - ; P<0.001). Logistic regression indicated S non-missense and S missense-TP as predictors of ajmaline-induced PVCs., Conclusions: SCN5A mutation is associated with an increased risk of drug-induced ventricular arrhythmia in patients without baseline type-1 ECG. In particular, S non-missense and S missense-TP are at high risk., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Detailed information on the profile of patients with Brugada syndrome (BrS) presenting their first arrhythmic event (AE) after prophylactic implantation of an implantable cardioverter-defibrillator (ICD) is limited., Objectives: The objectives of this study were (1) to compare clinical, electrocardiographic, electrophysiologic, and genetic profiles of patients who exhibited their first documented AE as aborted cardiac arrest (group A) with profiles of those in whom the AE was documented after prophylactic ICD implantation (group B) and (2) to characterize group B patients' profile using the class II indications for ICD implantation established by HRS/EHRA/APHRS expert consensus statement in 2013., Methods: A survey of 23 centers from 10 Western and 4 Asian countries enabled data collection of 678 patients with BrS who exhibited their AE (group A, n = 426; group B, n = 252)., Results: The first AE occurred in group B patients 6.7 years later than in group A (mean age 46.1 ± 13.3 years vs 39.4 ± 15.1 years; P < .001). Group B patients had a higher incidence of family history of sudden cardiac death and SCN5A mutations. Of the 252 group B patients, 189 (75%) complied with the HRS/EHRA/APHRS indications whereas the remaining 63 (25%) did not., Conclusion: Patients with BrS with the first AE documented after prophylactic ICD implantation exhibited their AE at a later age with a higher incidence of positive family history of sudden cardiac death and SCN5A mutations as compared with those presenting with aborted cardiac arrest. Only 75% of patients who exhibited an AE after receiving a prophylactic ICD complied with the 2013 class II indications, suggesting that efforts are still required for improving risk stratification., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The role and optimal sequence of ventricular tachycardia (VT) induction, mapping, and ablation when combined with substrate modification is unclear., Objective: The purpose of this study was to test the benefits of starting the scar-related VT ablation procedure with substrate modification vs the standard protocol of VT induction, mapping, and ablation as the first step., Methods: Forty-eight consecutive patients with structural heart disease and clinical VTs were randomized to simplified substrate ablation procedure with scar dechanneling as the first step (group 1, n = 24) or standard procedure with VT induction, mapping, and ablation followed by scar dechanneling (group 2, n = 24). Procedure and fluoroscopy times, the need for external cardioversion, acute results, and VT recurrence during follow-up were compared between groups., Results: Thirty-seven patients had ischemic cardiomyopathy, 10 nonischemic cardiomyopathy, and 1 arrhythmogenic cardiomyopathy. Before substrate ablation, 32 VTs were induced and targeted for ablation in 23 patients of group 2. Procedure time (209 ± 70 minutes vs 262 ± 63 minutes; P = .009), fluoroscopy time (14 ± 6 minutes vs 21± 9 minutes; P = .005), and electrical cardioversion (25% vs 54%; P = .039) were lower in group 1. After substrate ablation, 16 patients (66%) of group 1 and 12 patients (50%) of group 2 were noninducible (P = .242). End-procedure success (after residual inducible VT ablation) was achieved in 87.5% and 70.8% of patients, respectively (P = .155). There were no differences in VT recurrence rate between groups during a mean follow-up of 22 ± 14 months (log rank, P = .557)., Conclusion: VT induction and mapping before substrate ablation prolongs the procedure, radiation exposure, and the need for electrical cardioversion without improving acute results and long-term ablation outcomes., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Isolated cases of monomorphic ventricular tachycardia (MVT) in patients with Brugada syndrome (BrS) have been reported., Objective: We aimed to describe the incidence and characteristics of MVT in a cohort of patients with BrS who had received an implantable cardioverter-defibrillator (ICD)., Methods: Data from 834 patients with BrS implanted with an ICD in 15 tertiary hospitals between 1993 and 2014 were included., Results: The mean age of enrolled patients was 45.3 ± 13.9 years; 200 patients (24%) were women. During a mean follow-up of 69.4 ± 54.3 months, 114 patients (13.7%) experienced at least 1 appropriate ICD intervention, with MVT recorded in 35 patients (4.2%) (sensitive to antitachycardia pacing in 15 [42.8%]). Only QRS width was an independent predictor of MVT in the overall population. Specifically, 6 (17.1%) patients presented with right ventricular outflow tract tachycardia (successfully ablated from the endocardium in 4 and epicardial and endocardial ablation in 1), 2 patients with MVT arising from the left ventricle (1 successfully ablated in the supra lateral mitral annulus), and 2 (5.7%) patients with bundle branch reentry ventricular tachycardia. Significant structural heart disease was ruled out by echocardiography and/or cardiac magnetic resonance imaging., Conclusion: In this retrospective study, 4.2% of patients with BrS implanted with an ICD presented with MVT confirmed as arising from the right ventricular outflow tract tachycardia in 6, patients with MVT arising from the left ventricle in 2, and patients with bundle branch reentry ventricular tachycardia in 2. Endocardial and/or epicardial ablation was successful in 80% of these cases. These data imply that the occurrence of MVT should not rule out the possibility of BrS. This finding may also be relevant for ICD model selection and programming., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Brugada syndrome is a rare, inherited cardiac disease leading to ventricular fibrillation and sudden cardiac death in structurally normal hearts. Clinical diagnosis requires a Brugada type I electrocardiographic pattern in combination with other clinical features. The most effective approach to unmasking this diagnostic pattern is the use of ajmaline and flecainide tests, and the most effective intervention to reducing the risk of death is the implantation of a cardioverter defibrillator. To date, 18 genes have been associated with the disease, with the voltage-gated sodium channel α type V gene (SCN5A) being the most common one to date. However, only 30-35% of diagnosed cases are attributable to pathogenic variants in known genes, emphasizing the need for further genetic studies. Despite recent advances in clinical diagnoses and genetic testing, risk stratification and clinical management of patients with Brugada syndrome remain challenging.Genet Med 18 1, 3-12.

We present a case of a magnetic resonance imaging-assisted ablation of an atrial tachycardia in a patient with previous atrial fibrillation ablation. A 3-D reconstruction of the delayed-enhanced cardiac magnetic resonance (CMR; CMR model) was created to identify previous ablation lesions and gaps. Multiple gaps around right-sided pulmonary veins were observed. The activation map identified a dual-loop re-entry around both right-sided pulmonary veins, confirming that the substrate identified using delayed-enhanced CMR was critical to sustain the tachycardia. Ablation at this site converted to sinus rhythm. The present case shows the usefulness of delayed-enhanced CMR substrate characterization to complement activation mapping of the tachycardia and more accurately define the anatomical circuit., (Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to test the feasibility and usefulness of a new delayed-enhancement cardiac magnetic resonance (DE-CMR)-guided approach to ablate gaps in redo procedures., Background: Recurrences of atrial fibrillation (AF) after pulmonary vein isolation (PVI) may be related to gaps at the ablation lines. DE-CMR allows identification of radiofrequency lesions and gaps (CMR gaps)., Methods: Fifteen patients undergoing repeated AF ablations were included (prior procedure was PVI in all patients and roof-line ablation in 8 patients). Pre-procedure 3-dimensional (3D) DE-CMR was performed with a respiratory-navigated (free-breathing) and electrocardiographically gated inversion-recovery gradient-echo sequence (voxel size 1.25 × 1.25 × 2.5 mm). Endocardium and epicardium were manually segmented to create a 3D reconstruction (DE-CMR model). A pixel signal intensity map was projected on the DE-CMR model and color-coded (thresholds 40 ± 5% and 60 ± 5% of maximum intensity). The DE-CMR model was imported into the navigation system to guide the ablation of CMR gaps, with the operator blinded to electrical data. Fifteen conventional procedures were used as controls to compare procedural duration, radiofrequency, and fluoroscopy times., Results: Fifteen patients (56 pulmonary veins [PVs]; 57 ± 8 years of age; 9 with paroxysmal AF) were analyzed. In total, 67 CMR gaps were identified around PVs (mean 4.47 gaps/patient; median length 13.33 mm/gap) and 9 at roof line. All of the electrically reconnected PVs (87.5%) had CMR gaps. The site of electrical PV reconnection (assessed by circular mapping catheter) matched with a CMR gap in 79% of PVs. CMR-guided ablation led to reisolation of 95.6% of reconnected PVs (median radiofrequency time of 13.3 [interquartile range: 7.5 to 21.7] min/patient) and conduction block through the roof line in all patients (1.4 [interquartile range: 0.7 to 3.1] min/patient). Compared with controls, the CMR-guided approach shortened radiofrequency time (1,441 ± 915 s vs. 930 ± 662 s; p = 0.026) but not the procedural duration or fluoroscopy time., Conclusions: DE-CMR can successfully guide repeated PVI procedures by accurately identifying and localizing gaps and may reduce procedural duration and radiofrequency application time., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Long QT syndrome (LQTS) is associated with sudden cardiac death and the prolongation of the QT interval on the electrocardiogram. A comprehensive screening of all genes previously associated with this disease leaves 30% of the patients without a genetic diagnosis. Pathogenic mutations in the sodium channel β subunits have been associated with cardiac channelopathies, including SCN4B mutations in LQTS., Objective: To evaluate the role of mutations in the sodium channel β subunits in LQTS., Methods: We screened for mutations in the genes encoding the 5 sodium β subunits (SCN1B isoforms a and b, SCN2B, SCN3B, and SCN4B) from 30 nonrelated patients who were clinically diagnosed with LQTS without mutations in common LQTS-related genes. We used the patch-clamp technique to study the properties of sodium currents and the action potential duration in human embryonic kidney and HL-1 cells, respectively, in the presence of β1b subunits., Results: The genetic screening revealed a novel mutation in the SCN1Bb gene (β1bP213T) in an 8-year-old boy. Our electrophysiological analysis revealed that β1bP213T increases late sodium current. In addition, β1bP213T subtly altered Nav1.5 function by shifting the window current, accelerating recovery from inactivation, and decreasing the slow inactivation rate. Moreover, experiments using HL-1 cells revealed that the action potential duration significantly increases when the mutant β1b was overexpressed compared with β1bWT., Conclusion: These data revealed SCN1Bb as a susceptibility gene responsible for LQTS, highlighting the importance of continuing the search for new genes and mechanisms to decrease the percentage of patients with LQTS remaining without genetic diagnosis., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The identification of conducting channels (CCs) based on its relative high voltage or the presence of electrograms with delayed components has been proposed for substrate-guided scar-related ventricular tachycardia (VT) ablation. The relationship of these channels with the VT isthmuses remains unclear., Objective: To assess the link between CCs identified during sinus rhythm (SR) and VT isthmuses in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC)., Methods: Twenty-two consecutive patients with ARVC undergoing substrate-guided VT ablation (scar dechanneling technique) were analyzed. High-density endocardial and epicardial electroanatomic maps were obtained during SR. Standard bipolar cutoff values (0.5-1.5 and <0.5 mV) were used to define border zone and dense scar. The CCs were identified by voltage threshold adjustment (voltage channels) or by tagging the electrograms with delayed components that are sequentially activated (late potential channels)., Results: A total of 87 CCs were identified; 65 (74.7%) of them on the epicardial surface. Twenty-four (27.6%) CCs were voltage channels, and compared with late potential CCs, these had a higher bipolar voltage (0.96 [0.48-1.29] mV vs 0.39 [0.26-0.50] mV; P < .001] and required more radiofrequency applications (5 [4-7] vs 3 [2-5]; P = .048]. Eighteen (90%) of 20 identified VT isthmuses were located on the epicardium. Only 8 (40%) VT isthmuses were related to a voltage CC. The remaining 12 (60%) VT isthmuses were linked to a late potential CC., Conclusion: Late potential CCs more frequently act as the VT substrate in ARVC and therefore should also be considered to guide SR substrate-guided ablation., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Atrial fibrillation (AF) is a recognized treatable cause of tachycardiomyopathy (TMP), with class IIb indication for catheter ablation (CA). The aim of this study is to analyze the prevalence, clinical characteristics and effect of CA in patients with TMP and to evaluate TMP as a prognostic factor for AF recurrence in these patients (TMP group), compared to controls with normal left ventricular ejection fraction (LVEF) and patients with heart failure due to structural cardiomyopathy (HF group)., Methods and Results: The study groups included 659 consecutive patients undergoing CA between 2003 and 2011: TMP group (n = 61), HF group (n = 36) and control group (n = 562). Compared to controls, patients with TMP were younger, had a shorter AF course and more often had persistent AF. Regarding echocardiographic parameters, the TMP group had lower LVEF (40% vs. 62%, P < 0.05), larger left atrial diameter (LAD: 46 vs. 41 mm, P < 0.05) and LV end-diastolic diameter (LVEDD: 55 vs. 51 mm, P < 0.05) compared to controls, with significant improvement at six-month follow-up, including those patients with AF recurrence. The probability of being arrhythmia-free did not differ between the TMP group and the other groups after a first or last procedure. The only independent predictor of AF recurrence was LAD., Conclusions: Patients with tachycardiomyopathy secondary to AF benefit from CA, with a significant improvement in LVEF, LVEDD and LAD. The outcome after CA of this group did not differ from patients with no structural cardiomyopathy., (© 2013.)