Brugada syndrome: updated perspectives
TL;DR: An in-depth review sheds light on the most important literature to date on Brugada syndrome, highlighting insights that shifted the global perspective on the disease.
Abstract: Jagdeep Walia Christian Steinberg Zachary Laksman 1Heart Rhythm Services, Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada; 2Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, Universite Laval, Québec, Canada Abstract: Since the first reported descriptions of Brugada syndrome, there has been a growing awareness and appreciation of the disease and its implications. From the diagnostic criteria, to risk stratification and management, there is an ongoing evolution, reclassification and re-thinking of Brugada syndrome as basic science, registry and clinical trial data shape our understanding of the pathophysiology and its clinical implications. This in-depth review sheds light on the most important literature to date, highlighting insights that shifted the global perspective on the disease. Current clinical paradigms and guidelines are presented, along with their justification, and possible opportunities for future research are explored.
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Journal Article•
TL;DR: Quinidine prevented VF induction in 22 of the 25 patients (88%) and after a follow-up period of 6 months to 22.2 years, all patients are alive.
Abstract: Background— Automatic implantable cardioverter-defibrillator therapy is considered the only effective treatment for high-risk patients with Brugada syndrome. Quinidine depresses Ito current, which may play an important role in the arrhythmogenesis of this disease. Methods and Results— The effects of quinidine bisulfate (mean dose, 1483±240 mg) on the prevention of inducible and spontaneous ventricular fibrillation (VF) were prospectively evaluated in 25 patients (24 men, 1 woman; age, 19 to 80 years) with Brugada syndrome. There were 15 symptomatic patients (including 7 cardiac arrest survivors and 7 patients with unexplained syncope) and 10 asymptomatic patients. All 25 patients had inducible VF at baseline electrophysiological study. Quinidine prevented VF induction in 22 of the 25 patients (88%). After a follow-up period of 6 months to 22.2 years, all patients are alive. Nineteen patients were treated with quinidine for 6 to 219 months (mean±SD, 56±67 months). None had an arrhythmic event, although 2 h...
67 citations
Dissertation•
01 Jan 2014
26 citations
TL;DR: In this paper, a Cox regression analysis revealed novel risk markers in Brugada syndrome (BrS) patients, and a weighted score based on dichotomized values provided good predictive performance.
Abstract: Background: Patients suffering from Brugada syndrome (BrS) are at an increased risk of life-threatening ventricular arrhythmias. Whilst electrocardiographic (ECG) variables have been used for risk stratification with varying degrees of success, automated measurements have not been tested for their ability to predict adverse outcomes in BrS. Methods: BrS patients presenting in a single tertiary center between 2000 and 2018 were analyzed retrospectively. ECG variables on vector magnitude, axis, amplitude and duration from all 12 leads were determined. The primary endpoint was spontaneous ventricular tachycardia/ventricular fibrillation (VT/VF) on follow-up. Results: This study included 83 patients [93% male, median presenting age: 56 (41-66) years old, 45% type 1 pattern] with 12 developing the primary endpoint (median follow-up: 75 (Q1-Q3: 26-114 months). Cox regression showed that QRS frontal axis > 70.0 degrees, QRS horizontal axis > 57.5 degrees, R-wave amplitude (lead I) 50.0 ms, S-wave amplitude (lead I) 35.5 ms, QRS duration (lead V3) > 96.5 ms, QRS area in lead I 31.5 deg, T-wave area (lead V1) 157 ms were significant predictors. A weighted score based on dichotomized values provided good predictive performance (hazard ratio: 1.59, 95% confidence interval: 1.27-2.00, P-value<0.0001, area under the curve: 0.84). Conclusions: Automated ECG analysis revealed novel risk markers in BrS. These markers should be validated in larger prospective studies.
10 citations
TL;DR: In this paper , a review of the latest findings addressing the genetic architecture of Brugada syndrome and to provide novel perspectives into its molecular underpinnings and novel models of risk stratification is presented.
Abstract: Brugada syndrome (BrS) is a rare hereditary arrhythmia disorder, with a distinctive ECG pattern, correlated with an increased risk of ventricular arrhythmias and sudden cardiac death (SCD) in young adults. BrS is a complex entity in terms of mechanisms, genetics, diagnosis, arrhythmia risk stratification, and management. The main electrophysiological mechanism of BrS requires further research, with prevailing theories centered on aberrant repolarization, depolarization, and current-load match. Computational modelling, pre-clinical, and clinical research show that BrS molecular anomalies result in excitation wavelength (k) modifications, which eventually increase the risk of arrhythmia. Although a mutation in the SCN5A (Sodium Voltage-Gated Channel Alpha Subunit 5) gene was first reported almost two decades ago, BrS is still currently regarded as a Mendelian condition inherited in an autosomal dominant manner with incomplete penetrance, despite the recent developments in the field of genetics and the latest hypothesis of additional inheritance pathways proposing a more complex mode of inheritance. In spite of the extensive use of the next-generation sequencing (NGS) technique with high coverage, genetics remains unexplained in a number of clinically confirmed cases. Except for the SCN5A which encodes the cardiac sodium channel NaV1.5, susceptibility genes remain mostly unidentified. The predominance of cardiac transcription factor loci suggests that transcriptional regulation is essential to the Brugada syndrome’s pathogenesis. It appears that BrS is a multifactorial disease, which is influenced by several loci, each of which is affected by the environment. The primary challenge in individuals with a BrS type 1 ECG is to identify those who are at risk for sudden death, researchers propose the use of a multiparametric clinical and instrumental strategy for risk stratification. The aim of this review is to summarize the latest findings addressing the genetic architecture of BrS and to provide novel perspectives into its molecular underpinnings and novel models of risk stratification.
4 citations
TL;DR: Cardiac MRI is useful in highlighting myocardial fibrosis, fatty replacement or wall movement with high accuracy, thus guiding not only the depiction, but also the patient’s stratification and management.
Abstract: Arrhythmogenic right ventricular dysplasia (ARVD) is a rare genetic condition of the myocardium, with a significantly high risk of sudden death. Recent genetic research and improved understanding of the pathophysiology tend to change the ARVD definition towards a larger spectrum of myocardial involvement, which includes, in various proportions, both the right (RV) and left ventricle (LV), currently referred to as ACM (arrhythmogenic cardiomyopathy). Its pathological substrate is defined by the replacement of the ventricular myocardium with fibrous adipose tissue that further leads to inadequate electrical impulses and translates into varies degrees of malignant ventricular arrythmias and dyskinetic myocardium movements. Particularly, the cardio-cutaneous syndromes of Carvajal/Naxos represent rare causes of ACM that might be suspected from early childhood. The diagnostic is sometimes challenging, even with well-established rTFC or Padua criteria, especially for pediatric patients or ACM with LV involvement. Cardiac MRI gain more and more importance in ACM diagnostic especially in non-classical forms. Furthermore, MRI is useful in highlighting myocardial fibrosis, fatty replacement or wall movement with high accuracy, thus guiding not only the depiction, but also the patient’s stratification and management.
2 citations
References
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TL;DR: Common clinical and ECG features define a distinct syndrome in this group of patients with recurrent episodes of aborted sudden death unexplainable by currently known diseases, not explainable by electrolyte disturbances, ischemia or structural heart disease.
3,075 citations
"Brugada syndrome: updated perspecti..." refers background in this paper
...Brugada syndrome (BrS) was first described in 1992 within a group of patients presenting with ST elevation in the anterior precordial leads, right bundle branch block, and recurrent aborted sudden cardiac death (SCD).(1) It has since been recognized to predispose patients to malignant cardiac events leading to ventricular fibrillation (VF) and sudden cardiac arrest (SCA)....
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TL;DR: The present report elaborates further on the diagnostic criteria and examines risk stratification schemes and device and pharmacological approaches to therapy on the basis of the available clinical and basic science data.
Abstract: Since its introduction as a clinical entity in 1992, the Brugada syndrome has progressed from being a rare disease to one that is second only to automobile accidents as a cause of death among young adults in some countries Electrocardiographically characterized by a distinct ST-segment elevation in the right precordial leads, the syndrome is associated with a high risk for sudden cardiac death in young and otherwise healthy adults, and less frequently in infants and children Patients with a spontaneously appearing Brugada ECG have a high risk for sudden arrhythmic death secondary to ventricular tachycardia/fibrillation The ECG manifestations of Brugada syndrome are often dynamic or concealed and may be unmasked or modulated by sodium channel blockers, a febrile state, vagotonic agents, α-adrenergic agonists, β-adrenergic blockers, tricyclic or tetracyclic antidepressants, a combination of glucose and insulin, hypo- and hyperkalemia, hypercalcemia, and alcohol and cocaine toxicity In recent years, an exponential rise in the number of reported cases and a striking proliferation of articles defining the clinical, genetic, cellular, ionic, and molecular aspects of the disease have occurred The report of the first consensus conference, published in 2002, focused on diagnostic criteria The present report, which emanated from the second consensus conference held in September 2003, elaborates further on the diagnostic criteria and examines risk stratification schemes and device and pharmacological approaches to therapy on the basis of the available clinical and basic science data
1,730 citations
New York University1, University of Amsterdam2, Shiga University of Medical Science3, Kyungpook National University4, St George's, University of London5, Children's National Medical Center6, Leiden University7, University of Barcelona8, University of Oulu9, Vanderbilt University10, University of British Columbia11, University of Paris12, University of Rochester13, University of Pavia14, Nippon Medical School15, Johns Hopkins University16, Washington University in St. Louis17
TL;DR: Developed in partnership with the Heart Rhythm Society (HRS), the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology, and the Asia Pacific Heart Rhythm society (APHRS).
1,569 citations
TL;DR: In the largest series of Brugada syndrome patients thus far, event rates in asymptomatic patients were low and gender, familial history of SCD, inducibility of ventricular tachyarrhythmias during electrophysiological study, and the presence of an SCN5A mutation were not predictive of arrhythmic events.
Abstract: BACKGROUND: Brugada syndrome is characterized by ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death (SCD). Fundamental questions remain on the best strategy for assessing the real disease-associated arrhythmic risk, especially in asymptomatic patients. The aim of the present study was to evaluate the prognosis and risk factors of SCD in Brugada syndrome patients in the FINGER (France, Italy, Netherlands, Germany) Brugada syndrome registry. METHODS AND RESULTS: Patients were recruited in 11 tertiary centers in 4 European countries. Inclusion criteria consisted of a type 1 ECG present either at baseline or after drug challenge, after exclusion of diseases that mimic Brugada syndrome. The registry included 1029 consecutive individuals (745 men; 72%) with a median age of 45 (35 to 55) years. Diagnosis was based on (1) aborted SCD (6%); (2) syncope, otherwise unexplained (30%); and (3) asymptomatic patients (64%). During a median follow-up of 31.9 (14 to 54.4) months, 51 cardiac events (5%) occurred (44 patients experienced appropriate implantable cardioverter-defibrillator shocks, and 7 died suddenly). The cardiac event rate per year was 7.7% in patients with aborted SCD, 1.9% in patients with syncope, and 0.5% in asymptomatic patients. Symptoms and spontaneous type 1 ECG were predictors of arrhythmic events, whereas gender, familial history of SCD, inducibility of ventricular tachyarrhythmias during electrophysiological study, and the presence of an SCN5A mutation were not predictive of arrhythmic events. CONCLUSIONS: In the largest series of Brugada syndrome patients thus far, event rates in asymptomatic patients were low. Inducibility of ventricular tachyarrhythmia and family history of SCD were not predictors of cardiac events.
754 citations
TL;DR: The underlying electrophysiological mechanism that causes abnormal ECG pattern and ventricular tachycardia/ventricular fibrillation (Vt/VF) in patients with Brugada syndrome (BrS) remains unelucidated.
Abstract: Background—The underlying electrophysiological mechanism that causes an abnormal ECG pattern and ventricular tachycardia/ventricular fibrillation (Vt/VF) in patients with the Brugada syndrome (BrS) remains unelucidated. However, several studies have indicated that the right ventricular outflow tract (RVOT) is likely to be the site of electrophysiological substrate. We hypothesized that in patients with BrS who have frequent recurrent VF episodes, the substrate site is the RVOT, either over the epicardium or endocardium; abnormal electrograms would be identified at this location, which would serve as the target site for catheter ablation. Methods and Results—We studied 9 symptomatic patients with the BrS (all men; median age 38 years) who had recurrent VF episodes (median 4 episodes) per month, necessitating implantable cardioverter defibrillator discharge. Electroanatomic mapping of the right ventricle, both endocardially and epicardially, and epicardial mapping of the left ventricle were performed in all...
650 citations