A Multicenter External Validation of a Score Model to Predict Risk of Events in Patients With Brugada Syndrome.

A multivariate risk score model was proposed by Sieira et al in 2017 for sudden death in Brugada syndrome; their validation in 150 patients was highly encouraging, with a C-index of 0.81; however, this score is yet to be validated by an independent group. A total of 192 records of patients with Brugada syndrome were collected from 2 centers in the United Kingdom and retrospectively scored according to a score model by Sieira et al. Data were compiled summatively over follow-up to mimic regular risk re-evaluation as per current guidelines. Sudden cardiac death survivor data were considered perievent to ascertain the utility of the score before cardiac arrest. Scores were compared with actual outcomes. Sensitivity in our cohort was 22.7%, specificity was 57.6%, and C-index was 0.58. In conclusion, up to 75% of cardiac arrest survivors in this cohort would not have been offered a defibrillator if evaluated before their event. This casts doubt on the utility of the score model for primary prevention of sudden death. Inherent issues with modern risk scoring strategies decrease the likelihood of success even in robustly designed tools such as the Sieira score model.

Electrocardiographic imaging of the arrhythmogenic substrate of Brugada syndrome: Current evidence and future perspectives.

Brugada syndrome is responsible for about 20% of sudden cardiac deaths in patients with apparently normal hearts. Basic and clinical research has elucidated some of the mechanisms that are responsible for life-threatening ventricular arrhythmias in this syndrome. Delays in activation and repolarization over the right ventricular outflow tract are the most likely cause of the ECG typical pattern and arrhythmogenesis. Invasive epicardial and endocardial mapping has identified the epicardium as the principal region of interest for these anomalies, and areas of fragmented potentials at invasive mapping are a target for epicardial ablation. Noninvasive mapping systems have been developed to study the epicardial depolarization and repolarization and may be particularly useful in assessing the epicardial arrhythmogenic substrate of Brugada syndrome for both clinical and research purpose. This review focuses on recent advances in this field.

Restitution metrics in Brugada syndrome: a systematic review and meta-analysis.

BACKGROUND: Brugada syndrome (BrS) is an ion channelopathy that predisposes affected subjects to ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death. Restitution analysis has been examined in BrS patients but not all studies have reported significant differences between BrS patients and controls. Therefore, we conducted a systematic review and meta-analysis to investigate the different restitution indices used in BrS. METHODS: PubMed and Embase were searched until April 7, 2019, identifying 20 and 27 studies. RESULTS: A total of ten studies involving 178 BrS (mean age 38 years old, 63% male) and 102 controls (mean age 31 years old, 42% male) were included in this systematic review. Pacing was carried out at the right ventricular outflow tract (RVOT)/right ventricular apex (RPA) (n = 4), RPA (n = 4), or right atrium (RA) (n = 1). Basic cycle lengths of 400 (n = 4), 500 (n = 2), 600 (n = 6) and 750 ms (n = 1) were used. Recording methods include electrograms (n = 4), monophasic action potentials (n = 5), and electrocardiograms (n = 1). Signals were obtained from the RVOT (n = 8), RVA (n = 3), RA (n = 1), or the body surface (n = 1). The maximum restitution slope for endocardial repolarization at the RVOT was 0.87 for BrS patients (n = 5; 95% confidence interval [CI] 0.68-1.07) compared with 0.74 in control subjects (n = 4; 95% CI 0.42-1.06), with a significant mean difference of 0.40 (n = 4; 95% CI 0.11-0.69; P = 0.007). CONCLUSIONS: Steeper endocardial repolarization restitution slopes are found in BrS patients compared with controls at baseline. Restitution analysis can provide important information for risk stratification in BrS.

Clinical characteristics and long-term clinical course of patients with Brugada syndrome without previous cardiac arrest: a multiparametric risk stratification approach.

AIMS: Risk stratification in Brugada syndrome (BrS) still represents an unsettled issue. In this multicentre study, we aimed to evaluate the clinical characteristics and the long-term clinical course of patients with BrS. METHODS AND RESULTS: A total of 111 consecutive patients (86 males; aged 45.3 ± 13.3 years) diagnosed with BrS were included and followed-up in a prospective fashion. Thirty-seven patients (33.3%) were symptomatic at enrolment (arrhythmic syncope). An electrophysiological study (EPS) was performed in 59 patients (53.2%), and ventricular arrhythmias were induced in 32 (54.2%). A cardioverter defibrillator was implanted in 34 cases (30.6%). During a mean follow-up period of 4.6 ± 3.5 years, appropriate device therapies occurred in seven patients. Event-free survival analysis (log-rank test) showed that spontaneous type-1 electrocardiogram pattern (P = 0.008), symptoms at presentation (syncope) (P = 0.012), family history of sudden cardiac death (P < 0.001), positive EPS (P = 0.024), fragmented QRS (P = 0.004), and QRS duration in lead V2 > 113 ms (P < 0.001) are predictors of future arrhythmic events. Event rates were 0%, 4%, and 60% among patients with 0-1 risk factor, 2-3 risk factors, and 4-5 risk factors, respectively (P < 0.001). Current multiparametric score models exhibit an excellent negative predictive value and perform well in risk stratification of BrS patients. CONCLUSIONS: Multiparametric models including common risk factors appear to provide better risk stratification of BrS patients than single factors alone.

Characterization and Management of Arrhythmic Events in Young Patients With Brugada Syndrome.

BACKGROUND: Information on young patients with Brugada syndrome (BrS) and arrhythmic events (AEs) is limited. OBJECTIVES: The purpose of this study was to describe their characteristics and management as well as risk factors for AE recurrence. METHODS: A total of 57 patients (age ≤20 years), all with BrS and AEs, were divided into pediatric (age ≤12 years; n = 26) and adolescents (age 13 to 20 years; n = 31). RESULTS: Patients' median age at time of first AE was 14 years, with a majority of males (74%), Caucasians (70%), and probands (79%) who presented as aborted cardiac arrest (84%). A significant proportion of patients (28%) exhibited fever-related AE. Family history of sudden cardiac death (SCD), prior syncope, spontaneous type 1 Brugada electrocardiogram (ECG), inducible ventricular fibrillation at electrophysiological study, and SCN5A mutations were present in 26%, 49%, 65%, 28%, and 58% of patients, respectively. The pediatric group differed from the adolescents, with a greater proportion of females, Caucasians, fever-related AEs, and spontaneous type-1 ECG. During follow-up, 68% of pediatric and 64% of adolescents had recurrent AE, with median time of 9.9 and 27.0 months, respectively. Approximately one-third of recurrent AEs occurred on quinidine therapy, and among the pediatric group, 60% of recurrent AEs were fever-related. Risk factors for recurrent AE included sinus node dysfunction, atrial arrhythmias, intraventricular conduction delay, or large S-wave on ECG lead I in the pediatric group and the presence of SCN5A mutation among adolescents. CONCLUSIONS: Young BrS patients with AE represent a very arrhythmogenic group. Current management after first arrhythmia episode is associated with high recurrence rate. Alternative therapies, besides defibrillator implantation, should be considered.

Coexistence of Brugada and Wolff Parkinson White syndromes: A case report and review of the literature.

A 31-year-old male patient presented with complaints of palpitations, dizziness, and recurrent episodes of syncope. A 12-lead electrocardiogram (ECG) revealed manifest ventricular preexcitation, which suggested Wolff Parkinson White syndrome. In addition, an incomplete right bundle branch block and a 3-mm ST segment elevation ending with inverted T-waves in V2 were consistent with coved-type (type 1) Brugada pattern. An electrophysiological study was performed, and during the mapping, the earliest ventricular activation with the shortest A-V interval was found on the mitral annulus posterolateral site. After successful radiofrequency catheter ablation of the accessory pathway, the Brugada pattern on the ECG changed, which prompted an ajmaline provocation test. A type 1 Brugada ECG pattern occurred following the administration of ajmaline. Considering the probable symptom combinations of these 2 coexisting syndromes and the presence of recurrent episodes of syncope, programmed ventricular stimulation was performed and subsequently, ventricular fibrillation was induced. An implantable cardioverter-defibrillator was implanted soon after.

Arritmias ventriculares sustentadas: a tempestade chegou / Sustained ventricular arrhythmias: the storm has arrived

Um dos grandes desafios no atendimento dos pacientes nas unidades de emergência é o tratamento das arritmias ventriculares, principalmente, quando sustentadas e recorrentes, pois são de difícil tratamento e estão associadas à alta mortalidade. O principal mecanismo envolvido na sustentação das taquicardias ventriculares é o mecanismo de reentrada, devido às cicatrizes miocárdicas secundárias a diversas cardiopatias estruturais. A tempestade elétrica pode ser séria quando ocorre em portadores de desfibriladores automáticos, provocando múltiplos choques correspondentes fora do ambiente hospitalar. Nesses casos é necessária a internação hospitalar, onde medidas específicas e escalonadas de tratamento são realizadas, indo desde o manejo clínico até intervenções específicas, como programação de dispositivos eletrônicos, intervenções eletrofisiológicas ou cirúrgicas

One of the biggest challenges in the care of patients in emergency units is the treatment of ventricular arrhythmias, particularly when sustained and relapsing, as they are difficult to treat and are associated with high mortality. The main mechanism involved in the maintenance of ventricular tachycardias is the mechanism of reentry, due to myocardial scars secondary to various structural heart diseases. The electrical storm may be serious when it occurs in patients with automatic defibrillators, causing multiple corresponding shocks outside the hospital setting. In these cases, admission to hospital is necessary, where specific and stepwise treatment measures are performed, ranging from clinical management to specific interventions, such as programming of electronic devices, and electrophysiological or surgical interventions

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.

Brugada syndrome: Diagnosis, risk stratification and management.

Brugada syndrome is a rare inherited arrhythmia syndrome leading to an increased risk of sudden cardiac death, despite a structurally normal heart. Diagnosis is based on a specific electrocardiogram pattern, observed either spontaneously or during a sodium channel blocker test. Among affected patients, risk stratification remains a challenge, despite recent insights from large population cohorts. As implantable cardiac defibrillators - the main therapy in Brugada syndrome - are associated with a high rate of complications in this population, the main challenge is risk stratification of patients with Brugada syndrome. Aside from the two main predictors of arrhythmia (symptoms and spontaneous electrocardiogram pattern), many risk factors have been recently suggested for stratifying risk of sudden cardiac death in Brugada syndrome. We have reviewed these data and discuss current guidelines in light of recent progress in this complex field.

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.

Predictors of Ventricular Arrhythmias and Sudden Death in a Québec Cohort With Brugada Syndrome.

BACKGROUND: Patients with Brugada syndrome (BrS) are at risk for ventricular arrhythmias (VAs) and sudden death. Identification of high-risk individuals beyond those with syncope or resuscitated sudden death remains a major challenge. METHODS: We assessed the value of clinical, electrophysiological, and electrocardiographic (ECG) features, including depolarization and repolarization metrics, in predicting arrhythmic events and sudden death in consecutive patients with BrS diagnosed between 2002 and 2013 in Quebec, Canada. Qualifying electrocardiograms with the highest type 1 ST-segment elevations were reviewed and analyzed by 2 electrophysiologists who were blinded to clinical history. Survival analyses were adjusted for Firth bias correction and left truncation. RESULTS: A total of 105 patients, 79.8% of whom were men, were diagnosed with BrS at a mean age of 46.2 ± 13.3 years and were followed for 59.6 ± 16.4 months. Ten (9.5%) had a history of cardiac arrest, 37 (35.2%) had syncope, and 7 (6.7%) experienced 20 arrhythmic events during follow-up, all consisting of appropriate ICD therapy (7 antitachycardia pacing; 13 shocks). In multivariate Cox regression analyses, a spontaneous type 1 electrocardiographic (ECG) pattern (hazard ratio [HR], 10.80; 95% confidence interval [CI], 1.03-113.87; P = 0.0476), maximal T peak-end (Tp-e) duration ≥ 100 ms (HR, 29.73; 95% CI, 1.33-666.37; P = 0.0325), and QRS duration in lead V6 > 110 ms (HR, 15.27; 95% CI, 1.07-217.42; P = 0.0443) were independently associated with VAs or aborted sudden cardiac death. CONCLUSIONS: In a multicentre cohort with BrS from Quebec, Canada, VAs and sudden death were independently associated with standard 12-lead ECG features, including a spontaneous type 1 pattern, depolarization (QRS in lead V6), and repolarization (maximal Tp-e duration) criteria.

Prognostic value of programmed electrical stimulation in Brugada syndrome: 20 years experience.

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

Diagnosis and management of pediatric brugada syndrome: a survey of pediatric electrophysiologists.

BACKGROUND: Brugada syndrome (BrS) can be difficult to diagnose and treat, especially in the young patient. As there is currently no consensus on the evaluation and treatment of BrS in the pediatric population, we sought to describe the current practice for the diagnosis and treatment of BrS among pediatric electrophysiologists. METHODS: A web-based survey was distributed to 204 physician members (MDs) of The Pediatric and Adult Congenital Electrophysiology Society (PACES). Practice characteristics, BrS patient attributes, and diagnostic and therapeutic preferences were collected. RESULTS: Responses were obtained from 83 pediatric electrophysiologists. The most common initial presentation was family history. There is a large variation in testing, particularly in the use of electrophysiology (EP) studies, drug challenge testing, and genetic testing. Despite limited treatment options, there is only consensus in the therapeutic approach to the pediatric patient with symptomatic BrS with 97% of physicians recommending an implantable cardioverter defibrillator (ICD). In the asymptomatic patient, a wide variation in therapy was seen with only 27% of physicians recommending an ICD CONCLUSIONS: Significant practice variation exists among pediatric electrophysiologists with deviation from accepted diagnostic and therapeutic practices for adult BrS patients. Further studies are necessary to establish best practice guidelines for BrS in the pediatric EP community.

Dual phenotypic transmission in Brugada syndrome.

BACKGROUND: Brugada syndrome is a genetic heart disease with autosomal dominant inheritance. Family screening commonly detects one parent responsible for transmission of the disease. AIMS: To describe atypical transmission of Brugada syndrome. METHODS: Between 2001 and 2007, systematic screening, including an electrocardiogram, ajmaline challenge and DNA sequencing of the SCN5A gene, of the first-degree relatives of 62 probands with Brugada syndrome was performed (Programme Hospitalier de Recherche Clinique). RESULTS: In two families, both parents transmitted Brugada syndrome to their offspring. In the first family, the proband presented Brugada electrocardiogram features with ajmaline challenge and carried a new SCN5A mutation (p.V1281F). The mutation was also identified in the mother, who had a type 1 aspect on inferior leads with ajmaline. The proband's father presented a typical Brugada electrocardiogram pattern on lead V2 with ajmaline and no SCN5A gene mutation. In the second family, the proband was a boy aged 2.5 years who had been resuscitated from sudden cardiac death. Ajmaline challenge revealed a typical Brugada electrocardiogram pattern in both parents but with no mutation in the genes studied. CONCLUSION: Family studies should always be exhaustive and discovery of one parent with Brugada syndrome does not eliminate the need for screening of the other parent.