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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: 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: 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.)

Background: Atrial fibrillation (AF) is a growing health burden, and pulmonary vein isolation (PVI) using cryoballoon (CB) or radiofrequency (RF) represents an attractive therapeutic option. Sex-specific differences in the epidemiology, pathophysiology, and clinical presentation of AF and PVI are recognized., Objective: We aimed at comparing the efficacy, safety, and procedural characteristics of CB and RF in women and men undergoing a first PVI procedure., Methods: We searched for randomized controlled trials and prospective observational studies comparing CB and RF ablation with at least 1 year of follow-up. After merging individual patient data from 18 data sets, we investigated the sex-specific (procedure failure defined as recurrence of atrial arrhythmia, reablation, and reinitiation of antiarrhythmic medication), safety (periprocedural complications), and procedural characteristics of CB vs RF using Kaplan-Meier and multilevel models., Results: From the 18 studies, 4840 men and 1979 women were analyzed. An analysis stratified by sex correcting for several covariates showed a better efficacy of CB in men (hazard ratio for recurrence 0.88; 95% confidence interval 0.78-0.98, P = .02) but not in women (hazard ratio 0.98; 95% confidence interval 0.83-1.16; P = .82). For women and men, the energy source had no influence on the occurrence of at least 1 complication. For both sexes, the procedure time was significantly shorter with CB (-22.5 minutes for women and -27.1 minutes for men)., Conclusion: CB is associated with less long-term failures in men. A better understanding of AF-causal sex-specific mechanisms and refinements in CB technologies could lead to higher success rates in women., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. 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: 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: 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: 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.)

Background: Catheter contact force (CF) has a strong correlation with lesion formation during radiofrequency ablation. Delayed-enhancement cardiac magnetic resonance (DE-CMR) provides lesion information in patients with prior atrial fibrillation (AF) ablation., Objective: The aim of this study was to determine the CF threshold to create permanent lesions detected by DE-CMR., Methods: A total of 36 patients referred for AF ablation were included. A CF catheter was used during the ablation procedure, and DE-CMR was performed 3 months after the ablation procedure. Eighteen pulmonary vein (PV) segments were defined, and 3-dimensional (3D) reconstructions of the left atrium (LA) derived from the DE-CMR images were obtained. One observer evaluated the presence of any discontinuity of previous ablation lesions (gap) in the 3D reconstructions of the LA, and another observer (blinded to the gap findings) determined the minimum CF value in each PV segment., Results: The PV segments where a gap was observed had a lower maximal CF value than did the segments without gap in the 3D LA reconstructions (6.7 ± 4.4 g vs 12.2 ± 4.7 g; P < .001). In receiver operating characteristic analysis, a CF threshold of >8 g provided 73% sensitivity and 81% specificity in the prediction of a complete PV lesion (positive predictive value [PPV] 84%). A CF threshold of >12 g had a specificity of 94% and increased the PPV to 91% in creating a complete lesion in the LA wall (area under the curve 0.834)., Conclusion: A CF threshold of >12 g H5H20 predicts a complete lesion with high specificity and PPV when a dragging ablation strategy is used in AF ablation., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: There is no consensus on the appropriate indications for the epicardial approach in substrate ablation of post-myocardial infarction (MI) ventricular tachycardia (VT)., Objective: The purpose of this study was to investigate whether infarct transmurality (IT) could identify patients who would benefit from a combined first-line endo-epicardial approach., Methods: Before ablation, IT was assessed by contrast-enhanced cardiac magnetic resonance imaging (hyperenhancement ≥75% of the wall thickness in ≥1 segment), echocardiography (dyskinesia/akinesia + hyperrefringency + wall thinning), computed tomography (wall thinning), or scintigraphy (transmural necrosis). Prospectively from January 2011, an endocardial approach was used in patients with subendocardial MI (group 1) and a combined endo-epicardial approach in patients with transmural MI (group 2). Outcomes in both groups were compared with those in patients with transmural MI and only endocardial approach due to previous cardiac surgery or procedure performed before January 2011 (group 3). The primary end point was VT/ventricular fibrillation recurrence-free survival., Results: Ninety patients (92.2% men; mean age 67.4 ± 9.8 years) undergoing VT substrate ablation were included: group 1, n = 34; group 2, n = 24; group 3, n = 32. During a mean follow-up duration of 22.5 ± 13.7 months, 5 patients in group 1 (14.7%), 3 patients in group 2 (12.5%), and 13 patients in group 3 (40.6%) had VT recurrences (P = .011). Time to recurrence was the shortest in group 3 (log-rank, P = .018). The endocardial approach in patients with transmural MI was associated with an increased risk of recurrence (hazard ratio 4.01; 95% confidence interval 1.41-11.3; P = .009)., Conclusion: The endocardial approach in patients with transmural MI undergoing VT substrate ablation is associated with an increased risk of recurrence. IT may be a useful criterion for the selection of a first-line combined endo-epicardial approach., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Premature ventricular complex (PVC) ablation has been shown to improve left ventricular ejection fraction (LVEF) and New York Heart Association functional class in patients with left ventricular dysfunction. Both are considered key variables in predicting risk of sudden cardiac death., Objective: The objective of this study was to assess whether ablation might remove the primary prevention (PP) implantable cardioverter-defibrillator (ICD) indication in patients with frequent PVC., Methods: Sixty-six consecutive patients with PP-ICD indication and frequent PVC [33 (50%) men; mean age 53 ± 13 years; 11 (17%) with ischemic heart disease] underwent PVC ablation. The ICD was withheld and the indication was reevaluated at 6 and 12 months., Results: LVEF progressively improved from 28% ± 4% at baseline to 42% ± 12% at 12 months (P < .001). New York Heart Association functional class improved from 2 patients with NYHA functional class I (3%) at baseline to 35 (53%) at 12 months (P < .001). The brain natriuretic peptide level decreased from 246 ± 187 to 176 ± 380 pg/mL (P = .004). The PP-ICD indication was removed in 42 patients (64%) during follow-up, from 38 (92%) of them at 6 months, showing an independent association with baseline PVC burden and successful sustained ablation. In patients with successful sustained ablation, a cutoff value of 13% PVC burden had a sensitivity of 100% and a specificity of 93% (area under the curve 99%) for removing ICD indication postablation. No sudden cardiac deaths or malignant ventricular arrhythmias were observed., Conclusion: In patients with frequent PVC and PP-ICD indication, ablation improves LVEF and, in most cases, allows removal of the indication. Withholding the ICD and reevaluating within 6 months of ablation seems to be a safe and appropriate strategy., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a difficult-to-diagnose cause of sudden cardiac death (SCD). We identified a family of 1400 individuals with multiple cases of CPVT, including 36 SCDs during youth., Objectives: We sought to identify the genetic cause of CPVT in this family, to preventively treat and clinically characterize the mutation-positive individuals, and to functionally characterize the pathogenic mechanisms of the mutation., Methods: Genetic testing was performed for 1404 relatives. Mutation-positive individuals were preventively treated with β-blockers and clinically characterized with a serial exercise treadmill test (ETT) and Holter monitoring. In vitro functional studies included caffeine sensitivity and store overload-induced calcium release activity of the mutant channel in HEK293 cells., Results: We identified the p.G357S&#95;RyR2 mutation, in the cardiac ryanodine receptor, in 179 family members and in 6 SCD cases. No SCD was observed among treated mutation-positive individuals over a median follow-up of 37 months; however, 3 relatives who had refused genetic testing (confirmed mutation-positive individuals) experienced SCD. Holter monitoring did not provide relevant information for CPVT diagnosis. One single ETT was unable to detect complex cardiac arrhythmias in 72% of mutation-positive individuals, though the serial ETT improved the accuracy. Functional studies showed that the G357S mutation increased caffeine sensitivity and store overload-induced calcium release activity under conditions that mimic catecholaminergic stress., Conclusion: Our study supports the use of genetic testing to identify individuals at risk of SCD to undertake prophylactic interventions. We also show that the pathogenic mechanisms of p.G357S&#95;RyR2 appear to depend on β-adrenergic stimulation., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Electrocardiographic (ECG) fusion with intrinsic QRS could reduce the benefit of atrial synchronous biventricular pacing (AS-BiVP) in patients with hypertrophic obstructive cardiomyopathy (HOCM)., Objectives: The purpose of this study was to assess the benefit of AS-BiVP and the influence of ECG fusion for reduction of left ventricular outflow tract gradient (LVOTG) in these patients., Methods: Twenty-one symptomatic HOCM patients with severe LVOTG were included. Twelve patients were evaluated retrospectively for the prevalence of fusion and its influence on outcomes after AS-BiVP. Eleven patients (2 of the first population were also evaluated retrospectively) were prospectively included to evaluate the benefit of performing atrioventricular node ablation (AVNA) to achieve full ventricular capture if fusion was present during AS-BiVP., Results: Seven of the first 12 patients (58%) had ECG fusion. After 54 ± 24 months of AS-BiVP, the presence of fusion was associated with lower values for reduction of resting, dynamic LVOTG and New York Heart Association (NYHA) class. In the prospectively evaluated patients, after 12 months of follow-up, resting LVOTG decreased from 98 ± 39 to 39 ± 24 mm Hg (P = .008); dynamic LVOTG decreased from 112 ± 38 to 60 ± 24 mm Hg (P = .013); NYHA class decreased from 2.8 ± 0.4 to 1.7 ± 0.6 (P = .014); endurance time during constant work rate cycling exercise (80% of peak oxygen consumption) increased from 399 ± 148 to 691 ± 249 seconds (P = .046); quality of life improved from 46 ± 22 to 22 ± 20 points (P = .02); and brain natriuretic peptide levels decreased from 318 ± 238 to 152 ± 118 pg/mL (P = .09). Eight of the 11 prospectively evaluated patients (73%) needed AVNA, which further decreased LVOTG from 108 ± 40 mm Hg at baseline to 89 ± 29 mm Hg after BiVP to 54 ± 22 mm Hg after AVNA (P = .003)., Conclusion: As-BiVP that ensures no ECG fusion, by means of AVNA when needed, appears to be the optimal pacing mode in HOCM patients., (Copyright © 2015. Published by Elsevier Inc.)

Background: The earliest activation site (EAS) location in the septal right ventricular outflow tract (RVOT) could be an additional mapping data predictor of left ventricular outflow tract (LVOT) vs RVOT origin of idiopathic ventricular arrhythmias (VAs)., Objective: The purpose of this study was to assess the impact of EAS location in predicting LVOT vs RVOT origin., Methods: Macroscopic and histologic study was performed in 12 postmortem hearts. Electroanatomic maps (EAMs) from 37 patients with outflow tract (OT) VA with the EAS in the septal RVOT were analyzed. Pulmonary valve (PV) was defined by voltage scanning after validation of voltage thresholds by image integration. EAM measurements were correlated with those of macroscopic/histologic study., Results: A cutoff value of 1.9 mV discriminated between subvalvular and supravalvular positions (90% sensitivity, 96% specificity). EAS ≥1 cm below PV excluded RVOT site of origin (SOO). According to anatomic findings (distance PV-left coronary cusp = 5 ± 3 vs PV-right coronary cusp = 11 ± 5 mm), EAS-PV distance was significantly shorter in VAs arising from left coronary cusp than from the other LVOT locations (4.2 ± 5.4 mm vs 9.2 ± 7 mm; P = .034). The 10-ms isochronal longitudinal/perpendicular diameter ratio was higher in the RVOT vs the LVOT SOO group (1.97 ± 1.2 vs 0.79 ± 0.49; P = .001). An algorithm based on EAS-PV distance and the 10-ms isochronal longitudinal/perpendicular diameter ratio predicted LVOT SOO with 91% sensitivity and 100% specificity., Conclusion: An algorithm based on the EAS-PV distance and the 10-ms isochronal longitudinal/perpendicular diameter ratio accurately predicts LVOT vs RVOT SOO in outflow tract VAs with EAS in the septal RVOT., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Predictors of second radiofrequency catheter ablation (RFCA) success are not well known. Surgical ablation is accepted for failed first RFCA, but second RFCA has fewer complications., Objective: The purpose of this study was to evaluate left atrial (LA) size and function as potential predictors of second RFCA for atrial fibrillation (AF)., Methods: Thirty-three healthy volunteers (group I) and 83 patients with symptomatic drug-refractory AF treated with a first RFCA (group II, n = 48) or a second RFCA (group III, n = 35 patients) were included. Echocardiography was performed in all patients in sinus rhythm before RFCA and in all volunteers. LA size and function were measured using longitudinal strain and strain rate during ventricular systole (LASs, LASRs) and during early diastole (LASRe) or late diastole (LASRa) with speckle tracking echocardiography. The effectiveness of RFCA on arrhythmia recurrence was evaluated at 6-month follow-up., Results: LASs, LASRs, and LASRa were significantly lower in group III patients compared to other groups (P < .001 for all). LA diameter or volumes did not predict success after RFCA. LASs was an independent predictor of arrhythmia suppression after a first RFCA and after a second RFCA, with the best cutoff at LASs >20% (sensitivity 86%, specificity 70%) and LASs >12% (sensitivity 84%, specificity 90%), respectively., Conclusion: LA myocardial deformation imaging is a reliable tool for predicting success after a first and a second RFCA. These parameters could improve candidate selection, especially for a second RFCA., (Copyright © 2015 Heart Rhythm Society. 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.)

Background: Perimitral flutter (PMF) is a common form of left atrial tachycardia after atrial fibrillation (AF) ablation. The mitral isthmus (MI) is the standard ablation target. However, in some cases bidirectional block cannot be achieved., Objective: The purpose of this study was to describe the first experience using a transthoracic epicardial (TTE) approach to treat recurrent PMF after prior unsuccessful ablation., Methods: This is a case series of four patients with recurrence of highly symptomatic drug-refractory PMF (all male, median age 55 years, 3/4 hypertensive, 2/4 persistent AF, median AF period 24 months). Three patients presented with PMF-related tachymyocardiopathy. TTE ablation of MI was performed after a median of two prior endocardial MI and coronary sinus ablation attempts, using an open-tip 3.5-mm irrigated catheter (40 W, 45ºC). Persistent bidirectional block was assessed by activation mapping and differential pacing and was achieved in all patients., Results: No PMF recurrence was observed after median follow-up of 18 months (range 15-22 months; two patients without antiarrhythmic drugs and two with previously ineffective amiodarone). Left ventricular function normalized in all three patients with tachycardiomyopathy. There were no complications related to TTE approach., Conclusion: The present study is the first to report the feasibility of a TTE approach for highly symptomatic PMF refractory to endocardial and coronary sinus MI ablation., (© 2013 Heart Rhythm Society Published by Heart Rhythm Society All rights reserved.)

Background: During premature ventricular contractions (PVCs), a spatial displacement of the ventricles and the target ablation site with respect to the sinus rhythm (SR) position is observed during mapping and ablation., Objectives: To analyze this displacement and its relevance for image integration and PVC ablation., Methods: The electroanatomical activation maps (EAMs) of 55 consecutive patients who underwent PVC ablation were analyzed. Spatial displacement between each point position during PVC and SR was obtained., Results: A total of 6923 points from 71 EAMs were analyzed. Overall, the median distance between the point position during SR and PVC for all the points was 9.42 mm (interquartile range [IQR]: 6.19-12.85). The EAM points from the right ventricle showed more displacement than did those from the left ventricle: 10.35 mm (IQR: 7.16-13.95) vs 7.62 mm (IQR: 5.20-10.81); P <.001. The ventricular end-diastolic volume of the EAM during SR was greater than that during PVC (median difference: 9.75 [IQR: 0.37-19.67] mL; P = .002). A shorter coupling interval of the PVC was associated with greater spatial displacement (r = -.521; P <.001), higher end-diastolic volume reduction with respect to the SR beat (r = -.718; P = .001), and worse image integration (mean point-to-surface distance between EAM and 3-dimensional computed tomography-derived structure; r = -.642; P = .018)., Conclusions: There is a significant spatial displacement between the point position in SR and PVC, mainly in the right ventricle. This displacement increases with the shortening of the PVC coupling interval and can result in poorer image fusion and difficult catheter navigation/positioning for ablation., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Right ventricular apex pacing for gradient reduction in hypertrophic obstructive cardiomyopathy (HOCM) with severe left ventricular (LV) obstruction has yielded conflicting results., Objective: The purpose of this study was to assess the feasibility and effectiveness of biventricular pacing in HOCM., Methods: Transvenous biventricular pacing was attempted in 12 severely symptomatic HOCM patients. Optimal intervals were programmed after implant. Echocardiographic LV pressure gradient and synchrony were assessed. LV lead implantation was successful in 9 patients. Optimal pacing mode was biventricular in 6 patients, left ventricular only in 2 patients, and right ventricular only in 1 patient., Results: Functional capacity and quality of life progressively improved. New York Heart Association functional class decreased from 3.2 ± 0.4 at baseline to 1.9 ± 0.3 at 3 months and to 1.4 ± 0.5 at 1 year (P <.05); 6-minute walk test increased from 349 ± 116 m at baseline to 454 ± 144 m at 3 months and to 517 ± 206 m (P <.05); and quality of life increased from 54 ± 16 points at baseline to 28 ± 13 points at 3 months and 27 ± 15 points at 1 year (P <.05). There was also a progressive reduction in LV gradient from 74 ± 23 mmHg at baseline to 50 ± 27 mmHg acutely, 40 ± 26 mmHg at 3 months, and 28 ± 17 mmHg at 1 year (P <.05). Gradient reduction was associated with diminished peak longitudinal displacement of the LV septum and earlier displacement of the lateral wall. A progressive reduction of LV mass was observed, from 356 ± 110 g at baseline to 315 ± 70 g at 3 months (P = .13) and to 284 ± 42 g at 1 year (P <.05)., Conclusion: Biventricular pacing is feasible and usually the best configuration for gradient reduction in HOCM. Biventricular pacing reduces LV hypertrophy., (Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Analysis of myocardial strain using two-dimensional (2D) echocardiography to assess left ventricular (LV) mechanical dyssynchrony by measuring time differences in peak systolic strains from opposing LV walls has been proposed. However, peak systolic strain may be difficult to identify., Objective: The purpose of this study was to evaluate (1) LV dyssynchrony by assessing the overlap among strain traces of the LV walls throughout the cardiac cycle and (2) its usefulness in identifying responders to cardiac resynchronization therapy (CRT)., Methods: Fifty patients with heart failure and LV systolic dysfunction undergoing CRT were studied with 2D echocardiography at baseline and 6-month follow-up. Myocardial radial strain and circumferential strain were analyzed using commercially available software. The resulting strain traces were postprocessed with a mathematical script., Results: Quantification of LV dyssynchrony was expressed as an index of temporal overlap from the analyzed traces. Responders to CRT were defined by ≥15% reduction of LV end-systolic volume at 6-month follow-up. Responders to CRT had higher LV dyssynchrony in both radial strain and circumferential strain analysis. A cutoff time overlap ≥7% for radial strain (area under the curve 0.79) and ≥8.5% for circumferential strain (area under the curve 0.66) identified responders to CRT., Conclusion: Quantifying the temporal superposition of LV wall deformations with a computed algorithm allows measurement of LV intraventricular dyssynchrony throughout the cardiac cycle. The derived index is useful in stratifying the probability of response to CRT., (Copyright © 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Differential diagnosis of wide QRS complex tachycardias using the 12-lead ECG may be difficult in many clinical settings., Objective: The purpose of this study was to determine the value of ECG lead II, specifically, the duration at its beginning, defined as R-wave peak time (RWPT), in differentiating ventricular tachycardia (VT) from supraventricular tachycardia (SVT) in patients with wide QRS complex tachycardia., Methods: Two hundred eighteen ECGs showing wide QRS complex tachycardias were evaluated. Two cardiologists blinded to the diagnosis measured RWPT duration at lead II (from the isoelectric line to the point of first change in polarity), and results between VT and SVT were compared, with the findings of electrophysiologic study used as the gold standard., Results: One hundred sixty-three VTs had a significantly longer RWPT at DII (76.7 +/- 21.7 ms vs 26.8 +/- 9.5 ms in 55 SVT, P = .00001). Receiver operating characteristic curve identified RWPT > or =50 ms at lead II as having greater specificity and sensitivity in discriminating VT from SVT. Area under the curve was 0.97 (95% confidence interval 0.95-0.99), positive likelihood ratio was 34.8, and kappa coefficient (kappa) was 0.86. Bivariate analysis identified higher age in VT patients (60.7 vs 50.1 years, P < or =.01) and wider QRS complex duration at lead II in VT patients (169.4 vs 128.3 ms, P <.0001). QRS width at DII was not superior to RWPT in diagnosing VT., Conclusion: RWPT > or =50 ms at DII is a simple and highly sensitive criterion that discriminates VT from SVT in patients with wide QRS complex tachycardia., (Copyright 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The best method for performing atrial fibrillation (AF) ablation is still under debate. The importance of using a circular mapping (CM) catheter for assessing isolation of the pulmonary vein (PV) antrum on the outcome of the procedure has not been clearly established., Objective: The purpose of this study was to evaluate whether use of a CM catheter improves the arrhythmia-free proportion after circumferential pulmonary vein ablation (CPVA)., Methods: A series of 146 consecutive patients (83% males, age 53 +/- 10 years, 53% paroxysmal AF) were randomized to two ablation strategies. In both groups, ipsilateral PV encirclement was performed until disappearance or dissociation of the local electrogram within the surrounded area. In the first group, only the radiofrequency catheter was used to both map and ablate (CPVA group, n = 73). In the other group, a CM catheter was added to assess the electrical activity of the PV antrum (CPVA-CM group, n = 73). An ablation line along the left atrial roof was also created in all patients., Results: Procedural and fluoroscopic times were longer in the CPVA-CM group (P <.05). Severe procedure-related complications occurred in 1 (1.4%) patient in the CPVA group and in 3 (4.1%) patients in the CPVA-CM group (P = .317). After mean follow-up of 9 +/- 3 months, 31 (42.5%) patients in the CPVA group and 47 (64.4%) patients in the CPVA-CM group were arrhythmia-free without antiarrhythmic medication (P = .008)., Conclusion: Use of a CM catheter to ensure isolation of the PV antrum improved the success of CPVA but increased some procedural requirements., (Copyright 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The transient outward current I(to) is of critical importance in regulating myocardial electrical properties during the very early phase of the action potential. The auxiliary beta subunit KCNE2 recently was shown to modulate I(to)., Objective: The purpose of this study was to examine the contributions of KCNE2 and its two published variants (M54T, I57T) to I(to)., Methods: The functional interaction between Kv4.3 (alpha subunit of human I(to)) and wild-type (WT), M54T, and I57T KCNE2, expressed in a heterologous cell line, was studied using patch-clamp techniques., Results: Compared to expression of Kv4.3 alone, co-expression of WT KCNE2 significantly reduced peak current density, slowed the rate of inactivation, and caused a positive shift of voltage dependence of steady-state inactivation curve. These modifications rendered Kv4.3 channels more similar to native cardiac I(to). Both M54T and I57T variants significantly increased I(to) current density and slowed the inactivation rate compared with WT KCNE2. Moreover, both variants accelerated the recovery from inactivation., Conclusion: The study results suggest that KCNE2 plays a critical role in the normal function of the native I(to) channel complex in human heart and that M54T and I57T variants lead to a gain of function of I(to), which may contribute to generating potential arrhythmogeneity and pathogenesis for inherited fatal rhythm disorders.

Background: Brugada syndrome (BrS) is a common heritable channelopathy. Mutations in the SCN5A-encoded sodium channel (BrS1) culminate in the most common genotype., Objective: This study sought to perform a retrospective analysis of BrS databases from 9 centers that have each genotyped >100 unrelated cases of suspected BrS., Methods: Mutational analysis of all 27 translated exons in SCN5A was performed. Mutation frequency, type, and localization were compared among cases and 1,300 ostensibly healthy volunteers including 649 white subjects and 651 nonwhite subjects (blacks, Asians, Hispanics, and others) that were genotyped previously., Results: A total of 2,111 unrelated patients (78% male, mean age 39 +/- 15 years) were referred for BrS genetic testing. Rare mutations/variants were more common among BrS cases than control subjects (438/2,111, 21% vs. 11/649, 1.7% white subjects and 31/651, 4.8% nonwhite subjects, respectively, P <10(-53)). The yield of BrS1 genetic testing ranged from 11% to 28% (P = .0017). Overall, 293 distinct mutations were identified in SCN5A: 193 missense, 32 nonsense, 38 frameshift, 21 splice-site, and 9 in-frame deletions/insertions. The 4 most frequent BrS1-associated mutations were E1784K (14x), F861WfsX90 (11x), D356N (8x), and G1408R (7x). Most mutations localized to the transmembrane-spanning regions., Conclusion: This international consortium of BrS genetic testing centers has added 200 new BrS1-associated mutations to the public domain. Overall, 21% of BrS probands have mutations in SCN5A compared to the 2% to 5% background rate of rare variants reported in healthy control subjects. Additional studies drawing on the data presented here may help further distinguish pathogenic mutations from similarly rare but otherwise innocuous ones found in cases.

Background: Worldwide, the Brugada syndrome has been recognized as an important cause of sudden cardiac death in individuals at a relatively young age. Importantly, many drugs have been reported to induce the characteristic Brugada syndrome-linked ECG abnormalities and/or (fatal) ventricular tachyarrhythmias., Objective: The purpose of this study was to review the literature on the use of drugs in Brugada syndrome patients, to make recommendations based on the literature and on expert opinion regarding drug safety, and to ensure worldwide online and up-to-date availability of this information to all physicians who treat Brugada syndrome patients., Methods: We performed an extensive review of the literature, formed an international expert panel to produce a consensus recommendation to each drug, and initiated a website (www.brugadadrugs.org)., Results: The literature search yielded 506 reports for consideration. Drugs were categorized into one of four categories: (1) drugs to be avoided (n = 18); (2) drugs preferably avoided (n = 23); (3) antiarrhythmic drugs (n = 4); and (4) diagnostic drugs (n = 4). Level of evidence for most associations was C (only consensus opinion of experts, case studies, or standard-of-care) as there are no randomized studies and few nonrandomized studies in Brugada syndrome patients., Conclusion: Many drugs have been associated with adverse events in Brugada syndrome patients. We have initiated a website (www.brugadadrugs.org) to ensure worldwide availability of information on safe drug use in Brugada syndrome patients.

Background: Type 3 long-QT syndrome (LQT-3) is caused by gain-of-function mutations in the SCN5A encoding the cardiac sodium channel. Familial atrial fibrillation (AF), previously considered a potassium channelopathy, has recently been related to sodium genetic variants, both in isolated forms and in patients with underlying heart disease., Objective: The purpose of this study was to describe the first family associating LQT-3 and AF due to a gain-of-function mutation in SCN5A and assess the usefulness of the sodium blocker flecainide in individuals with both phenotypes., Methods: Complete family screening was performed after identifying a proband showing paroxysmal AF and a long QT interval suggestive of LQT-3. Secondary causes of AF were ruled out in all individuals. Flecainide was used in two patients for LQT-3 diagnosis and therapeutic treatment of AF. Genetic screening was performed by direct sequencing of the exons and exon-intron boundaries of SCN5A., Results: We identified a three-generation family (eight members), all of them showing long QT intervals. Paroxysmal AF initiated between 20 and 35 years of age in all three adults. The flecainide test led to shortening of the QTc interval. Flecainide was also effective in acutely restoring sinus rhythm. A Y1795C mutation was identified in all members., Conclusion: This is the first report showing an association of familial AF and LQT-3 due to a mutation in SCN5A. This finding provides further evidence of the role of SCN5A in AF. We also confirm the usefulness of flecainide in this particular complex phenotype, both as a diagnostic tool for LQT-3 and as an acute treatment for AF.

Since its introduction as a clinical entity in 1992, the Brugada syndrome has progressed from being a rare disease to one that is second only to automobile accidents as a cause of death among young adults in some countries. Electrocardiographically characterized by a distinct ST-segment elevation in the right precordial leads, the syndrome is associated with a high risk for sudden cardiac death in young and otherwise healthy adults, and less frequently in infants and children. Patients with a spontaneously appearing Brugada ECG have a high risk for sudden arrhythmic death secondary to ventricular tachycardia/fibrillation. The ECG manifestations of Brugada syndrome are often dynamic or concealed and may be unmasked or modulated by sodium channel blockers, a febrile state, vagotonic agents, alpha-adrenergic agonists, beta-adrenergic blockers, tricyclic or tetracyclic antidepressants, a combination of glucose and insulin, hypo- and hyperkalemia, hypercalcemia, and alcohol and cocaine toxicity. In recent years, an exponential rise in the number of reported cases and a striking proliferation of articles defining the clinical, genetic, cellular, ionic, and molecular aspects of the disease have occurred. The report of the first consensus conference, published in 2002, focused on diagnostic criteria. The present report, which emanated from the second consensus conference held in September 2003, elaborates further on the diagnostic criteria and examines risk stratification schemes and device and pharmacological approaches to therapy on the basis of the available clinical and basic science data.