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Background: Brugada syndrome (BrS) is caused by mutations in SCN5A gene in 15%-20% of cases. Previous studies showed worse prognosis in SCN5A mutation carriers (SCN5A+). To date, there are no data on genotype–phenotype correlation with electrocardiographic (ECG) imaging (ECGI) and high-density epicardial electroanatomic map. Objective: This study aimed to correlate SCN5A mutation with substrate severity in BrS assessed by ECGI and high-density electroanatomic map. Methods: All consecutive BrS patients undergoing ECGI and high-density epicardial electroanatomic map with HD Grid Mapping Catheter were retrospectively analyzed. On ECGI, the following parameters were analyzed before and after ajmaline administration: right ventricular outflow tract (RVOT) activation time (RVOT-AT) and RVOT recovery time (RVOT-RT). On electroanatomic map, the parameters analyzed before and after ajmaline were high-frequency potential activation time (HFPat), high-frequency potential duration (HFPd), high-frequency potential amplitude (HFPa), low-frequency potential activation time (LFPat), low-frequency potential duration (LFPd), and low-frequency potential amplitude (LFPa). Results: Thirty-nine BrS patients with ECGI were included. Eight patients (20.5%) were SCN5A+. At baseline ECGI map, mean RVOT-RT was longer in SCN5A+ (P = .024). After ajmaline administration, SCN5A+ patients showed longer RVOT-AT (125.6 vs 100.8 ms; P = .045) and longer RVOT-RT (426.4 vs 397 ms; P = .033). After ajmaline administration, SCN5A+ showed longer HFPat (164.1 vs 119.5 ms; P = .041); longer LFPat (272.7 vs 200.5 ms; P = .018); and longer LFPd (211.9 vs 151.2 ms; P = .033). Conclusion: In BrS, SCN5A+ patients compared with SCN5A– patients exhibit marked depolarization and repolarization abnormalities as assessed by ECGI and epicardial high-density electroanatomic map.

Purpose: Drug-induced type I Brugada syndrome (BrS) is associated with a ventricular arrhythmia (VA) rate of 1 case per 100 person-years. This study aims to evaluate changes in electrocardiographic (ECG) parameters such as microvolt T wave alternans (mTWA) and heart rate variability (HRV) at baseline and during ajmaline testing for BrS diagnosis. Methods: Consecutive patients diagnosed with BrS during ajmaline testing with 5-year follow-up were included in this study. For comparison, a negative ajmaline control group and an isoproterenol control group were also included. ECG recordings during ajmaline or isoproterenol test were divided in two timeframes from which ECG parameters were calculated: a 5-min baseline timeframe and a 5-min drug timeframe. Results: A total of 308 patients with BrS were included, 22 (0.7%) of which suffered VAs during follow-up. One hundred patients were included in both isoproterenol and negative ajmaline control groups. At baseline, there was no difference in ECG parameters betweencontrol groups and patients with BrS, nor between BrS with and without VAs. During ajmaline testing, BrS with VAs presented longer QRS duration [159 ± 34 ms versus 138 (122–155) ms, p = 0.006], higher maximum mTWA [33.8 (14.0–114) µV versus 8.00 (3.67–28.2) µV, p = 0.001], and lower power in low frequency band [25.6 (5.8–53.8) ms 2 versus 129.5 (52.7–286) ms 2, p < 0.0001] when compared to BrS without VAs. Conclusions: Ajmaline induced important HRV changes similar to those observed during isoproterenol. Increased mTWA was observed only in patients with BrS. BrS with VAs during follow-up presented worse changes during ajmaline test, including lower LF power and higher maximum mTWA which were independent predictors of events.

Management of ventricular arrhythmias (VAs) beyond implantable cardioverter-defibrillator positioning in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is challenging. Catheter ablation of the ventricular substrate often requires a combination of endocardial and epicardial approaches, with disappointing outcomes due to the progressive nature of the disease. We report the Universitair Ziekenhuis Brussel experience through a case series of 16 patients with drug-refractory ARVC, who have undergone endocardial and/or epicardial catheter ablation of VAs with a thoracoscopic hybrid-approach. After a mean follow-up time of 5.16 years (SD 2.9 years) from the first hybrid-approach ablation, VA recurrence was observed in 5 patients (31.25%): among these, patients 4 patients (80%) received a previous ablation and 1 of 11 patients (9.09%) who had a hybrid ablation as first approach had a VA recurrence (80% vs 9.09%; log-rank p = 0.04). Despite the recurrence rate of arrhythmic events, all patients had a significant reduction in the arrhythmic burden after ablation, with a mean of 4.65 years (SD 2.9 years) of freedom from clinically significant arrhythmias, defined as symptomatic VAs or implantable cardioverter-defibrillator-delivered therapies. In conclusion, our case series confirms that management of VAs in patients with ARVC is difficult because patients do not always respond to antiarrhythmic medications and can require multiple invasive procedures. A multidisciplinary approach involving cardiologists, cardiac surgeons, and cardiac electrophysiologists, together with recent cardiac mapping techniques and ablation tools, might mitigate these difficulties and improve outcomes.

Myotonia congenita is a rare neuromuscular disorder caused by CLCN1 mutations resulting in delayed muscle relaxation. Extramuscular manifestations are not considered to be present in chloride skeletal channelopathies, although recently some cardiac manifestations have been described. We report a family with autosomal dominant myotonia congenita and Brugada syndrome. Bearing in mind the previously reported cases of cardiac arrhythmias in myotonia congenita patients, we discuss the possible involvement of the CLCN1-gene mutations in primary cardiac arrhythmia.

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

BACKGROUND: The pathogenesis of Brugada syndrome (BrS) and consequently of abnormal electrograms (aEGMs) found in the epicardium of the right ventricular outflow tract (RVOT-EPI) is controversial. OBJECTIVE: The purpose of this study was to analyze aEGM from high-density RVOT-EPI electroanatomic mapping (EAM). METHODS: All patients undergoing RVOT-EPI EAM with the HD-Grid catheter for BrS were retrospectively included. Maps were acquired before and after ajmaline, and all patients had concomitant noninvasive electrocardiographic imaging with annotation of RVOT-EPI latest activation time (RVOTat). High-frequency potentials (HFPs) were defined as ventricular potentials occurring during or after the far-field ventricular EGM showing a local activation time (HFPat). Low-frequency potentials (LFPs) were defined as aEGMs occurring after near-field ventricular activation showing fractionation or delayed components. Their activation time from surface ECG was defined as LFPat. RESULTS: Fifteen consecutive patients were included in the study. At EAM before ajmaline, 7 patients (46.7%) showed LFPs. All patients showed HFPs before and after ajmaline and LFPs after ajmaline. Mean HFPat (134.4 vs 65.3 ms, P

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): ESC Research Grant Background Brugada syndrome is a heritable disorder with a high risk of sudden death. Although being a primary electrical disorder, subtle structural changes have repeatedly been described. Little is known about the long-term structural evolution in Brugada syndrome. Purpose We aimed to assess the evolution of echocardiographic parameters in Brugada syndrome and the presence of markers of structural evolution. Methods Brugada syndrome patients with minimum two complete transthoracic echocardiographic examinations were included. Clinical data were collected retrospectively. We analyzed all available echocardiographic examinations and assessed the evolution of cardiac parameters over time and its association with patient characteristics. Results The study included 113 Brugada syndrome patients [47 (33-55) years, 59 (52%) female, spontaneous type 1 ECG in 26 (23%)], with a total of 258 echocardiographies, collected over a period of 6.8 (6.6-7.1) years. Proximal and distal right ventricular outflow tract and basal right ventricular diameter dilated at a rate of 0.2 (0.1-0.3) mm/year (p = 0.004), 0.4 (0.3-0.5) mm/year (p Conclusion We observed progressive right ventricular outflow tract and basal right ventricle dilation and an increasing contractile dyssynchrony in Brugada syndrome, potentially indicating a progressive structural affection. Further research is warranted to unravel underlying mechanisms and possible clinical implications of progressive structural changes in Brugada syndrome. Abstract Figure.

Brugada syndrome (BrS) diagnosis requires the presence of a typical type 1 ECG pattern. Owing to the spontaneous ECG variability, the real BrS prevalence in the general population remains unclear. The aim of the present study was to evaluate the prevalence of positive ajmaline challenge for BrS in a cohort of consecutive patients who underwent electrophysiological evaluation for different clinical reasons. All consecutive patients from 2008 to 2019 who underwent ajmaline testing were prospectively included. A total of 2,456 patients underwent ajmaline testing, 742 (30.2%) in the context of familial screening for BrS. In non-familial screening group (1,714) ajmaline testing resulted positive in 186 (10.9%). Indications for ajmaline testing were: suspicious BrS ECG in 23 cases (12.4%), palpitations in 27 (14.5%), syncope in 71 (38.2%), presyncope in 7 (3.8%), family history of sudden cardiac death in 18 (9.7%), documented ventricular arrhythmias in 12 (6.5%), unexplained cardiac arrest in 4 (2.2%), atrial fibrillation in 16 (8.5%), brady-arrhythmias in 1 (0.5%), and cerebrovascular accidents in 7 (3.7%). Compared with the overall population, ajmaline testing positive patients were younger (42.8 ± 15.5 vs 48.9 ± 20.4; p

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

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

This study analyzes the natural history of a large cohort of probands with Brugada syndrome (BrS) to assess the predictive value of different clinical and electrocardiographic parameters for the development of ventricular fibrillation (VF) or sudden cardiac death (SCD) during a long-term follow-up. Baseline characteristics of 289 consecutive probands (203 men; mean age 45 ± 16 years) with a Brugada type 1 electrocardiogram were analyzed. After a mean follow-up of 10.1 ± 4.6 years, 29 malignant arrhythmias occurred. On multivariate analysis, a history of VF and syncopal episodes, fragmented QRS (f-QRS), spontaneous type 1 electrocardiogram, and early repolarization pattern were significantly associated with later occurrence of VF/SCD. In patients with drug-induced BrS, the accentuation or de novo appearance of f-QRS in other leads was always associated with VF/SCD. Cerebrovascular events occurred in 8 patients with atrial fibrillation (15.1%), most of them (75%) presenting as the first clinical manifestation. The time-to-diagnosis was found to be significantly shorter in those patients who directly came to our center than in those who referred to our center for a second opinion. In conclusion, systematic use of the pharmacologic challenge in patients with unexplained cardiovascular symptoms and/or atrial fibrillation might significantly improve the identification of BrS with a shortening of the time-to-diagnosis. The CHA2DS2VASc score might be inappropriate for predicting transient ischemic attack or stroke in BrS. This study confirms the independent predictive value of previous VF and syncopal episodes, f-QRS, type 1 electrocardiogram, and early repolarization pattern. In BrS a sufficiently long follow-up is necessary before conclusions on prognosis are apparent.

BACKGROUND The present study sought to evaluate the incidence of cerebrovascular events in a large cohort of patients with Brugada syndrome (BrS) analysing possible predictors, clinical characteristics and prognosis of cardioembolic events secondary to atrial fibrillation. METHODS A total of 671 consecutive patients (age 42.1 ± 17.0 years; men 63%) with a diagnosis of BrS were retrospectively analysed over a mean follow-up period of 10.8 ± 5.5 years. The diagnosis of ischemic stroke was made according to the AHA/ASA guidelines using computed tomography (CT) and angio-CT in the emergency department. RESULTS Among 671 patients with BrS, 79 (11.8%) had atrial fibrillation. The incidence of cardioembolic stroke in patients with BrS and atrial fibrillation was 13.9% (11 events). These patients had a low CHA2DS2Vasc score (82%, 0 and 1). Patients with transient ischemic attack/stroke were more frequently asymptomatic (91 vs. 25%; P

BACKGROUND Young patients presenting with symptomatic Brugada syndrome have very high risks for ventricular arrhythmias and should be carefully considered for implantable cardioverter-defibrillator (ICD) placement. However, this therapy is associated with high rates of inappropriate shocks and device-related complications. OBJECTIVES This study investigated clinical features, management, and long-term follow-up of young patients with Brugada syndrome and ICD. METHODS Patients diagnosed with Brugada syndrome, who underwent implantation of an ICD at an age of 25% of patients during follow-up. Appropriate shocks were significantly associated with previously aborted sudden cardiac death and spontaneous type I electrocardiograms. However, ICDs are frequently associated with complications and inappropriate shocks, both of which remain high regardless of careful device implantation and programming. (c) 2018 by the American College of Cardiology Foundation.

SCN5A mutations involving the α-subunit of the cardiac voltage-gated muscle sodium channel (NaV1.5) result in different cardiac channelopathies with an autosomal-dominant inheritance such as Brugada syndrome. On the other hand, mutations in SCN4A encoding the α-subunit of the skeletal voltage-gated sodium channel (NaV1.4) cause non-dystrophic myotonia and/or periodic paralysis. In this study, we investigated whether cardiac arrhythmias or channelopathies such as Brugada syndrome can be part of the clinical phenotype associated with SCN4A variants and whether patients with Brugada syndrome present with non-dystrophic myotonia or periodic paralysis and related gene mutations. We therefore screened seven families with different SCN4A variants and non-dystrophic myotonia phenotypes for Brugada syndrome and performed a neurological, neurophysiological and genetic work-up in 107 Brugada families. In the families with an SCN4A-associated non-dystrophic myotonia, three patients had a clinical diagnosis of Brugada syndrome, whereas we found a remarkably high prevalence of myotonic features involving different genes in the families with Brugada syndrome. One Brugada family carried an SCN4A variant that is predicted to probably affect function, one family suffered from a not genetically confirmed non-dystrophic myotonia, one family was diagnosed with myotonic dystrophy (DMPK gene) and one family had a Thomsen disease myotonia congenita (CLCN1 variant that affects function). Our findings and data suggest a possible involvement of SCN4A variants in the pathophysiological mechanism underlying the development of a spontaneous or drug-induced type 1 electrocardiographic pattern and the occurrence of malignant arrhythmias in some patients with Brugada syndrome.European Journal of Human Genetics advance online publication, 3 June 2015; doi:10.1038/ejhg.2015.125.

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

Risk stratification in Brugada syndrome in young patients remains challenging. We investigated the clinical characteristics, prognosis, and risk in young patients with the Brugada syndrome. We studied 95 patients with the Brugada syndrome aged = 4 conferred a 5-year event probability of 30% that increased to 53% if the score was >= 6. In conclusion, our study validated a model to predict risk in young patients with the Brugada syndrome, which takes into account 4 clinical measures. (C) 2017 Elsevier Inc. All rights reserved.

Objectives: The goal of this study was to investigate the clinical features, management, and long-term follow-up of children with drug-induced Brugada syndrome (BS).Background: Patients with BS

The clinical course and prognosis of Brugada syndrome (BS) in the elderly is unknown. The purpose of this study was to investigate the clinical characteristics, management, and prognosis of BS in an elderly population.

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

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

OBJECTIVES: Brugada syndrome (BS) in women is considered an infrequent condition with a more favourable prognosis than in men. Nevertheless, arrhythmic events and sudden cardiac death (SCD) also occur in this population. Long-term follow-up data of this group are sparse. The purpose of the present study was to investigate the clinical characteristics and long-term prognosis of women with BS. METHODS: A consecutive cohort of 228 women presenting with spontaneous or drug-induced Brugada type I ECG at our institution were included and compared with 314 men with the same diagnosis. RESULTS: Mean age was 41.5±17.3 years. Clinical presentation was SCD in 6 (2.6%), syncope in 51 (22.4%) and the remaining 171 (75.0%) were asymptomatic. As compared with men, spontaneous type I ECG was less common (7.9% vs 23.2%, p

Aims To investigate the clinical characteristics, prognoses, and presence of risk factors in young patients with Brugada syndrome (BS). Methods and results A consecutive cohort of 128 young BS patients (

Background A proband of Brugada syndrome (BrS) is the first patient diagnosed in a family. There are no data regarding this specific, high-risk population. Objectives This study sought to investigate the Brugada probands diagnosed from 1986 through the next 28 years. Methods We included 447 probands belonging to families with a diagnostic type 1 electrocardiogram Brugada pattern. The database was divided into 2 periods: the first period identified patients who were part of the initial cohort that became the consensus document on BrS in 2002 (early group); the second period reflected patients first diagnosed from 2003 to January 2014 (latter group). Results There were 165 probands in the early group and 282 in the latter group. Aborted sudden death as the first manifestation of the disease occurred in 12.1% of the early group versus 4.6% of the latter group (p = 0.005). Inducibility during programmed electrical stimulation was achieved in 34.4% and 19.2% of patients, respectively (p Conclusions Since being first described, the presentation of BrS has changed. There has been a decrease in aborted sudden cardiac death as the first manifestation of the disease among patients who were more recently diagnosed. These variations in initial presentation have important clinical consequences. In this setting, the value of inducibility to stratify individuals with BrS has changed.

A proband of Brugada syndrome (BrS) is the first patient diagnosed in a family. There are no data regarding this specific, high-risk population.This study sought to investigate the Brugada probands diagnosed from 1986 through the next 28 years.We included 447 probands belonging to families with a diagnostic type 1 electrocardiogram Brugada pattern. The database was divided into 2 periods: the first period identified patients who were part of the initial cohort that became the consensus document on BrS in 2002 (early group); the second period reflected patients first diagnosed from 2003 to January 2014 (latter group).There were 165 probands in the early group and 282 in the latter group. Aborted sudden death as the first manifestation of the disease occurred in 12.1% of the early group versus 4.6% of the latter group (p = 0.005). Inducibility during programmed electrical stimulation was achieved in 34.4% and 19.2% of patients, respectively (p 0.001). A spontaneous type 1 electrocardiogram pattern at diagnosis was present in 50.3% early versus 26.2% latter patients (p = 0.0002). Early group patients had a higher probability of a recurrent arrhythmia during follow-up (19%) than those of the latter group (5%) (p = 0.007). The clinical suspicion and use of a sodium-channel blocker to unmask BrS has allowed earlier diagnoses in many patients.Since being first described, the presentation of BrS has changed. There has been a decrease in aborted sudden cardiac death as the first manifestation of the disease among patients who were more recently diagnosed. These variations in initial presentation have important clinical consequences. In this setting, the value of inducibility to stratify individuals with BrS has changed.

Background: Brugada syndrome (BrS) is an inheritable cardiac disease associated with syncope, malignant ventricular arrhythmias and sudden cardiac death. The largest proportion of mutations in BrS is found in the SCN5A gene encoding the α-subunit of cardiac sodium channels (Nav1.5). Causal SCN5A mutations are present in 18–30% of BrS patients. The additional genetic diagnostic yield of variants in cardiac sodium channel β-subunits in BrS patients was explored and functional studies on 3 novel candidate variants were performed. Methods and Results: The SCN1B-SCN4B genes were screened, which encode the 5 sodium channel β-subunits, in a SCN5A negative BrS population (n=74). Five novel variants were detected; in silico pathogenicity prediction classified 4 variants as possibly disease causing. Three variants were selected for functional study. These variants caused only limited alterations of Nav1.5 function. Next generation sequencing of a panel of 88 arrhythmia genes could not identify other major causal mutations. Conclusions: It was hypothesized that the studied variants are not the primary cause of BrS in these patients. However, because small functional effects of these β-subunit variants can be discriminated, they might contribute to the BrS phenotype and be considered a risk factor. The existence of these risk factors can give an explanation to the reduced penetrance and variable expressivity seen in this syndrome. We therefore recommend including the SCN1-4B genes in a next generation sequencing-based gene panel.

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

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

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

BACKGROUND: The clinical course and prognosis of Brugada syndrome (BS) in the elderly is unknown. The purpose of this study was to investigate the clinical characteristics, management and prognosis of BS in an elderly population. METHODS AND RESULTS: A total of 437 patients with BS were included in this study. Patients were categorized in 2 groups according to the age at the time of diagnosis: CONCLUSION: The clinical features and the benign prognosis of BS patients older than 70 years likely identify a lower risk category of patients as compared to younger individuals. The device-guided management in this setting remains individualized and sometimes controversial. Moreover, BS diagnosis in the elderly should not be missed, mainly due to the clinical impact on the family of elderly patients.

The goal of this study was to investigate the clinical features, management, and long-term follow-up of children with drug-induced Brugada syndrome (BS).Patients with BS12 years of age with a spontaneous type I electrocardiogram have a higher risk of arrhythmic events. Data on drug-induced BS in patients12 years of age are lacking.Among 505 patients with ajmaline-induced BS, subjects ≤12 years of age at the time of diagnosis were considered as children and eligible for this study.Forty children (60% male; age 8 ± 2.8 years) were included. Twenty-four children (60%) had a family history of sudden death. Two (5%) had a previous episode of aborted sudden death, and 8 (20%) had syncope. Children experienced more frequent episodes of sinus node dysfunction (SND) compared with older subjects (7.5% vs. 1.5%; p = 0.04) and had a comparable incidence of atrial tachyarrhythmias. Children more frequently experienced episodes of ajmaline-induced sustained ventricular arrhythmias (VAs) compared with older patients (10.0% vs. 1.3%; p = 0.005). Twelve children (30%) received an implantable cardioverter-defibrillator (ICD). After a mean follow-up time of 83 ± 51 months, none of the children died suddenly. Spontaneous sustained VAs were documented in 1 child (2%). Among children with ICD, 1 (8%) experienced an appropriate shock, 4 (33%) had inappropriate ICD shocks, and 4 (33%) experienced device-related complications.Drug-induced BS is associated with atrial arrhythmias and SND. Children are at higher risk of ajmaline-induced VAs. The rate of device-related complications, leading to lead replacement or inappropriate shocks, is considerable and even higher than with appropriate interventions. Based on these findings, the optimal management of BS in childhood should remain individualized, taking into consideration the patient's clinical history and family's wishes.

We thank Drs. Steinfurt and Odening for their thoughtful comments on our recent publication [(1)][1]. Apart from the coved-type ST-segment elevation in the right precordial leads, the heterogeneity of Brugada syndrome (BS) can lead to additional electrocardiographic (ECG) repolarization

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

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

Item does not contain fulltext BACKGROUND: Since their implementation in clinical practice, remote home monitoring systems (HM) have undoubtedly become an added value in patients with implantable devices for cardiac rhythm management. The aim of this study was to investigate the impact of HM on clinical management and outcome in patients with channelopathies and other arrhythmogenic diseases who received an implantable cardioverter defibrillator (ICD). METHODS: Fifty-four patients (age 6 months--74 years) were followed by means of HM in our ICD clinic. Alerts and/or device-related clinical events were analysed in all patients and subsequent clinical decisions were made if indicated. RESULTS: During an average observation time of 27 months, 46 alerts were received from 32 different patients. Five patients (9%) received appropriate therapies for life-threatening arrhythmias and four patients (8%) inappropriate therapies because ofT wave oversensing or supraventricular tachycardias. Three patients had alerts due to electrical noise (two on the atrial, one on the ventricular channel). Overall, 18 alerts (39%) required a modification of the pharmacological therapy or the programming of the device. Mean anticipation of clinical visits based on the alerts was 92.6 +/- 56 days (median 97, interquartile range 50-150). CONCLUSION: HM substantially improves the clinical management of patients with cardiac arrhythmogenic disease by early recognition of device-related inappropriate therapies and subsequent anticipation of treatment adaptation.

BACKGROUND: Sustained ventricular arrhythmias (sVA), such as polymorphic ventricular tachycardia or ventricular fibrillation, can complicate ajmaline challenge in patients with Brugada syndrome (BS). OBJECTIVE: Aim of this study was to assess the incidence of life-threating sVA during ajmaline administration in a large series of patients with BS. In addition, clinical characteristics as well as prognosis of these patients were evaluated. METHODS: All consecutive patients with ajmaline-induced diagnosis of BS were eligible for this study. RESULTS: A total of 503 patients were included. Nine patients (1.8%) (44% male, mean age: 26±18 years) experienced a life-threating sVA during ajmaline challenge. Three patients were children and 2 individuals (22%) experienced sVA refractory to the first external defibrillation. One patient underwent veno-arterial extracorporeal membrane oxygenation to restore the sinus rhythm. Age at the time of ajmaline challenge was significantly lower in the group of patients developing sVA as compared to patients without sVA (26±18 vs 41±18 years, p=0.01). Moreover, patients with sVA presented more frequently with sinus node dysfunction as compared to patients with normal response to ajmaline (22.2% vs 1.4%, P=0.01). After a mean follow-up time of 29±8 months, none of the patients having experienced sVA during ajmaline challenge died suddenly or experienced further life-threating ventricular arrhythmias. CONCLUSION: Sustained VA during ajmaline challenge is not a rare event in BS occurring in 1.8% of patients. Despite its challenging acute treatment, the occurrence of ajmaline-induced sVA in patients with BS might not identify a category at higher risk for further arrhythmic events.

ObjectivesThe goal of this study was to investigate the clinical features, management, and long-term follow-up of children with drug-induced Brugada syndrome (BS).BackgroundPatients with BS