Predicting and Recognizing Drug-Induced Type I Brugada Pattern Using ECG-Based Deep Learning.

BACKGROUND: Brugada syndrome (BrS) has been associated with sudden cardiac death in otherwise healthy subjects, and drug-induced BrS accounts for 55% to 70% of all patients with BrS. This study aims to develop a deep convolutional neural network and evaluate its performance in recognizing and predicting BrS diagnosis. METHODS AND RESULTS: Consecutive patients who underwent ajmaline testing for BrS following a standardized protocol were included. ECG tracings from baseline and during ajmaline were transformed using wavelet analysis and a deep convolutional neural network was separately trained to (1) recognize and (2) predict BrS type I pattern. The resultant networks are referred to as BrS-Net. A total of 1188 patients were included, of which 361 (30.3%) patients developed BrS type I pattern during ajmaline infusion. When trained and evaluated on ECG tracings during ajmaline, BrS-Net recognized a BrS type I pattern with an AUC-ROC of 0.945 (0.921-0.969) and an AUC-PR of 0.892 (0.815-0.939). When trained and evaluated on ECG tracings at baseline, BrS-Net predicted a BrS type I pattern during ajmaline with an AUC-ROC of 0.805 (0.845-0.736) and an AUC-PR of 0.605 (0.460-0.664). CONCLUSIONS: BrS-Net, a deep convolutional neural network, can identify BrS type I pattern with high performance. BrS-Net can predict from baseline ECG the development of a BrS type I pattern after ajmaline with good performance in an unselected population.

Genetic Testing in Brugada Syndrome: A 30-Year Experience.

BACKGROUND: A pathogenic/likely pathogenic variant can be found in 20% to 25% of patients with Brugada syndrome (BrS) and a pathogenic/likely pathogenic variant in SCN5A is associated with a worse prognosis. The aim of this study is to define the diagnostic yield of a large gene panel with American College of Medical Genetics and Genomics variant classification and to assess prognosis of SCN5A and non-SCN5A variants. METHODS: All patients with BrS, were prospectively enrolled in the Universitair Ziekenhuis Brussel registry between 1992 and 2022. Inclusion criteria for the study were (1) BrS diagnosis; (2) genetic analysis performed with a large gene panel; (3) classification of variants following American College of Medical Genetics and Genomics guidelines. Patients with a pathogenic/likely pathogenic variant in SCN5A were defined as SCN5A+. Patients with a reported variant in a non-SCN5A gene or with no reported variants were defined as patients with SCN5A-. All variants were classified as missense or predicted loss of function. RESULTS: A total of 500 BrS patients were analyzed. A total of 104 patients (20.8%) were SCN5A+ and 396 patients (79.2%) were SCN5A-. A non-SCN5A gene variant was found in 75 patients (15.0%), of whom, 58 patients (77.3%) had a missense variant and 17 patients (22.7%) had a predicted loss of function variant. At a follow-up of 84.0 months, 48 patients (9.6%) experienced a ventricular arrhythmia (VA). Patients without any variant had higher VA-free survival, compared with carriers of a predicted loss of function variant in SCN5A+ or non-SCN5A genes. There was no difference in VA-free survival between patients without any variant and missense variant carriers in SCN5A+ or non-SCN5A genes. At Cox analysis, SCN5A+ or non-SCN5A predicted loss of function variant was an independent predictor of VA. CONCLUSIONS: In a large BrS cohort, the yield for SCN5A+ is 20.8%. A predicted loss of function variant carrier is an independent predictor of VA.

Patient-reported outcome measures on mental health and psychosocial factors in patients with Brugada syndrome.

AIMS: Brugada syndrome (BrS) is a hereditary arrhythmic disease, associated with sudden cardiac death. To date, little is known about the psychosocial correlates and impacts associated with this disease. The aim of this study was to assess a set of patient-reported psychosocial outcomes, to better profile these patients, and to propose a tailored psychosocial care. METHODS AND RESULTS: Patients were recruited at the European reference Centre for BrS at Universitair Ziekenhuis Brussel, Belgium. Recruitment was undertaken in two phases: phase 1 (retrospective), patients with confirmed BrS, and phase 2 (prospective), patients referred for ajmaline testing who had an either positive or negative diagnosis. BrS patients were compared to controls from the general population. Two hundred and nine questionnaires were analysed (144 retrospective and 65 prospective). Collected patient-reported outcomes were on mental health (12 item General Health Questionnaire; GHQ-12), social support (Oslo Social Support Scale), health-related quality of life, presence of Type-D personality (Type-D Scale; DS14), coping styles (Brief-COPE), and personality dimensions (Ten Item Personality Inventory). Results showed higher mental distress (GHQ-12) in BrS patients (2.53 ± 3.03) than in the general population (P < 0.001) and higher prevalence (32.7%) of Type D personality (P < 0.001) in patients with confirmed Brugada syndrome (BrS +). A strong correlation was found in the BrS + group (0.611, P < 0.001) between DS14 negative affectivity subscale and mental distress (GHQ-12). CONCLUSION: Mental distress and type D personality are significantly more common in BrS patients compared to the general population. This clearly illustrates the necessity to include mental health screening and care as standard for BrS.

Atrial Abnormalities in Brugada Syndrome: Evaluation With ECG Imaging.

BACKGROUND: Patients with Brugada syndrome (BrS) have an increased risk of arrhythmias, including atrial tachyarrhythmias (ATas). OBJECTIVES: The purpose of this study was to assess underlying atrial cardiomyopathy in BrS and the effect of ajmaline (AJM) test on the atrium of BrS patients using electrocardiogram imaging (ECGI). METHODS: All consecutive patients diagnosed with BrS in a monocentric registry were screened and included if they met the following criteria: 1) BrS diagnosed following current recommendations; and 2) ECGI map performed before and after AJM with a standard protocol. Consecutive patients with no structural heart disease or BrS who had undergone ECGI were included as a control group. Genetic analysis for SCN5A was performed in all BrS patients. Total atrial conduction time (TACT) and local atrial conduction time (LACT) were calculated from atrial ECGI. The primary endpoint was ATas during follow-up. RESULTS: Forty-three consecutive BrS patients and 40 control patients were included. Both TACT and LACT were significantly prolonged in BrS patients compared with control patients. Furthermore, TACT and LACT were significantly higher after AJM administration and in BrS patients who were carriers of a pathogenic/likely pathogenic SCN5A variant. After a mean follow-up of 40.9 months, 6 patients experienced a first ATa occurrence (all in the BrS group, 13.9%). TACT was the only independent predictor of ATas with a cutoff of >138.5 ms (sensitivity 0.92 [95% CI: 0.83-0.98], specificity 0.70 [95% CI: 0.59-0.81]). CONCLUSIONS: ECGI-calculated TACT and LACT are significantly prolonged in BrS patients compared with control patients, and in BrS patients after AJM. This may be consistent with a concealed atrial cardiomyopathy in BrS.

Genetic testing in children with Brugada syndrome: results from a large prospective registry.

AIMS: A pathogenic/likely pathogenic (P/LP) variant in SCN5A is found in 20-25% of patients with Brugada syndrome (BrS). However, the diagnostic yield and prognosis of gene panel testing in paediatric BrS is unclear. The aim of this study is to define the diagnostic yield and outcomes of SCN5A gene testing with ACMG variant classification in paediatric BrS patients compared with adults. METHODS AND RESULTS: All consecutive patients diagnosed with BrS, between 1992 and 2022, were prospectively enrolled in the UZ Brussel BrS registry. Inclusion criteria were: (i) BrS diagnosis; (ii) genetic analysis performed with a large gene panel; and (iii) classification of gene variants following ACMG guidelines. Paediatric patients were defined as ≤16 years of age. The primary endpoint was ventricular arrhythmias (VAs). A total of 500 BrS patients were included, with 63 paediatric patients and 437 adult patients. Among children with BrS, 29 patients (46%) had a P/LP variant (P+) in SCN5A and no variants were found in 34 (54%) patients (P-). After a mean follow-up of 125.9 months, 8 children (12.7%) experienced a VA, treated with implanted cardioverter defibrillator shock. At survival analysis, P- paediatric patients had higher VA-free survival during the follow-up, compared with P+ paediatric patients. P+ status was an independent predictor of VA. There was no difference in VA-free survival between paediatric and adult BrS patients for both P- and P+. CONCLUSION: In a large BrS cohort, the diagnostic yield for P/LP variants in the paediatric population is 46%. P+ children with BrS have a worse arrhythmic prognosis.

Heart rate variability and microvolt T wave alternans changes during ajmaline test may predict prognosis in Brugada syndrome.

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 between control 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) ms2 versus 129.5 (52.7-286) ms2, 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.

Case report: Coexistence of myotonia congenita and Brugada syndrome in one family.

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.

Hybrid-Approach Ablation in Drug-Refractory Arrhythmogenic Right Ventricular Cardiomyopathy.

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.

SCN5A mutation in Brugada syndrome is associated with substrate severity detected by electrocardiographic imaging and high-density electroanatomic mapping.

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.

Ajmaline-Induced Abnormalities in Brugada Syndrome: Evaluation With ECG Imaging.

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

High-density epicardial mapping in Brugada syndrome: Depolarization and repolarization abnormalities.

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

Ajmaline Testing and the Brugada Syndrome.

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

Abnormally high risk of stroke in Brugada syndrome.

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 ±â€Š17.0 years; men 63%) with a diagnosis of BrS were retrospectively analysed over a mean follow-up period of 10.8 ±â€Š5.5 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 < 0.0001) and older (59.4 ±â€Š11.2 vs. 43.9 ±â€Š16.7; P = 0.004) as compared with those without cerebrovascular events. CONCLUSION: The incidence of cardioembolic stroke in patients with BrS and atrial fibrillation was unexpectedly high. The cerebrovascular accidents were often the presenting clinical manifestation and were significantly associated with asymptomatic atrial fibrillation and older age. CHADS2 and CHA2DS2Vasc scores did not predict the unexpectedly high risk of thromboembolic events in this group of patients. The use of more invasive diagnostic tools might be useful in order to increase the rate of atrial fibrillation detection.

Implantable Cardioverter-Defibrillators in Children and Adolescents With Brugada Syndrome.

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 ≤20 years, were studied. RESULTS: The study included 35 consecutive patients. The mean age at ICD placement was 13.9 ± 6.2 years. Ninety-two percent were symptomatic; 29% presented with aborted sudden cardiac death and 63% with syncope. During a mean follow-up period of 88 months, sustained ventricular arrhythmias were treated by the ICD in 9 patients (26%), including shocks in 8 patients (23%) and antitachycardia pacing in 1 patient (3%). Three patients (9%) died in an electrical storm. Seven patients (20%) experienced inappropriate shocks, and 5 patients (14%) had device-related complications. Aborted sudden cardiac death and spontaneous type I electrocardiogram were identified as independent predictors of appropriate shock occurrence. CONCLUSIONS: ICD therapy is an effective strategy in young patients with symptomatic Brugada syndrome, treating potentially lethal arrhythmias in >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.

Role of Electrocardiographic Tpeak-Tend for the Prediction of Ventricular Arrhythmic Events in the Brugada Syndrome.

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.

A Clinical Score Model to Predict Lethal Events in Young Patients (≤19 Years) With the Brugada Syndrome.

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 ≤19 years. The median age at diagnosis was 12.9 years. The clinical presentation was sudden cardiac death in 7% and syncope in 21%. The remaining 72% were asymptomatic at diagnosis. Electrical abnormalities were present in 36%, including spontaneous type I electrocardiogram (12%), sinus node dysfunction (9%), atrioventricular block (17%), intraventricular conduction delay (16%), and atrial arrhythmias (8%). An electrophysiologic study was performed in 75%; ventricular arrhythmias were induced in 3%. An implantable cardioverter-defibrillator was placed in 25%. During a mean follow-up of 59 months, 9 patients presented with arrhythmic events (event rate: 1.9% per year). Variables significantly associated with events were: presentation with sudden cardiac death or syncope, spontaneous type I electrocardiogram, sinus node dysfunction and/or atrial tachycardia, conduction abnormality, and induction of ventricular arrhythmias during programmed ventricular stimulation. A model including the previous 4 main clinical variables (1, sudden cardiac death or syncope; 2, spontaneous type I electrocardiogram; 3, sinus node dysfunction and/or atrial tachycardia; and 4, conduction abnormality) had a high predictive power (C: 0.93) for the risk of lethal events. A score of ≥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.

Long-term prognosis of drug-induced Brugada syndrome.

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

A score model to predict risk of events in patients with Brugada Syndrome.

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.

Long-Term Follow-Up of Probands With Brugada Syndrome.

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.

Brugada syndrome in the young: an assessment of risk factors predicting future events.

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 (≤25 years old at diagnosis) was analysed. Eighty-eight patients (69%) were asymptomatic, whereas 40 (31%) presented with clinical manifestations of BS. Markers of prognosis and risk were identified upon comparison of these two groups. A history of malignant syncope was strong predictors of ventricular arrhythmic events. Family history of sudden cardiac death (SCD) and mutations in the SCN5A gene did not associate with increased risk. Symptomatic patients presented with significantly abnormal baseline electrical characteristics when compared with the asymptomatic cohort, including spontaneous type I electrocardiograph (ECG) patterns, sinus node dysfunction (SND), first-degree atrioventricular (AV) block, and intra-ventricular conduction delay. The symptomatic group more frequently exhibited atrial arrhythmias. Electrophysiological studies resulted positive more frequently in symptomatic patients, but no risk association for future events could be determined. During the follow-up period (mean: 65 months), 10 arrhythmic events occurred in nine symptomatic patients (event rate: 4.5% per year). No events occurred in the asymptomatic group. Variables significantly associated with arrhythmic events during follow-up were presence of symptoms at diagnosis and spontaneous type I ECG. The presence of atrial arrhythmias and conduction abnormalities was also associated with the risk of arrhythmic events during follow-up. CONCLUSION: Symptomatic BS in the young age is a rare but malignant condition that can manifest with a spectrum of electrical abnormalities (i.e. SND, atrial tachycardias, AV block, and infra-nodal conduction delay) and result in the extreme cases in lethal arrhythmic events and SCD.