Electrophysiological Basis and Genetics of Brugada Syndrome

Brugada syndrome is a primary arrhythmic syndrome arising in the structurally normal heart. Any proposed mechanism should account for the major features of the syndrome: localization of the ST segment and T-wave changes to the right precordial leads, association of conduction slowing at several levels, precipitation or aggravation of the major ECG changes by sodium channel-blocking drugs and the occurrence of ventricular fibrillation. Heterogeneity of repolarization across the ventricle wall plays a major role. Any agency that shifts the net current gradient during phase I outward would exaggerate the normal heterogeneity of repolarization and result in the ST segment and T-wave changes characteristic of the syndrome. When the outward current shift is marked, premature repolarization may occur in epicardial zone and the resulting gradient may precipitate reentry. The syndrome is inherited as an autosomal dominant. However, 75% of clinically affected individuals are males. In 20% of cases, the syndrome is associated with mutations of the cardiac sodium channel gene SCN5A. The mutations result in a loss-of-function as a result of the synthesis of a non-functional protein, altered protein trafficking, or change in gating. Agencies that reduce the sodium current may precipitate the characteristic ECG changes, for example, sodium channel blockers and membrane depolarization by hyperkalemia. Sympathetic stimulation may reverse the ECG changes and reduce arrhythmia recurrence. By its nonspecific potassium channel blocking action, quinidine may also reduce arrhythmia recurrence. We still do not know the basis for defect in the majority of patients with Brugada syndrome.     

Spontaneous Fluctuations between Diagnostic and Nondiagnostic ECGs in Brugada Syndrome Screening: Portuguese Family with Brugada Syndrome

Background: All family members of patients with Brugada syndrome (BS) should be screened. Fluctuations between diagnostic and nondiagnostic electrocardiogram (ECG) patterns in patients with BS are recognized, but systematic studies are lacking. The objective of this work was to prospectively evaluate the spontaneous changes between diagnostic and nondiagnostic ECG patterns in a family screened for BS. Methods: One hundred twenty‐nine family members were possibly affected plus the index case were screened with two ECGs with an interval of 6 months. Only coved‐type ECG pattern was defined as diagnostic; type 2 and 3 ECGs were considered suggestive. Results: The first ECG series made six diagnostics and the second 11, but only three patients maintained the diagnostic ECG. Patients with basal diagnostic ECG were older and more frequently symptomatic. Body mass index (BMI) was significantly lower in adults with diagnostic plus suggestive ECG when compared with the others. No significant gender difference was found among relatives with or without diagnostic ECG. Conclusion: Spontaneous phenotypic manifestation of BS was more frequent in older symptomatic patients, absent in children, and related with low BMI. ECG manifestations were intermittent in more than 3/4 of the affected patients. Fluctuations between diagnostic and nondiagnostic ECGs may have an implication on the correct phenotyping in family screening so several ECGs with drug challenging are mandatory. Ann Noninvasive Electrocardiol 2010;15(4):337‐343     

Brugada综合征患者的心电图及临床特点分析

目的分析Brugada综合征患者的心电图及临床特点。方法对我院近5年诊断的8例Brugada综合征住院患者的心电图及临床情况进行长期随访观察。结果8例Brugada综合征患者均为男性，年龄平均（40±13）岁。心电图Ⅰ型Brugada波者3例，Ⅱ型4例，Ⅲ型1例；Brugada波具有多变性，提高肋间描记右胸导联心电图可显现Brugada波或使其更明显。8例中4例有猝死家族史，5例有晕厥史，3例在住院期间发生室速／室颤，随访期间2例猝死。结论心电图Brugada波（尤其Ⅰ型）是诊断Brugada综合征的必要条件，明确诊断Brugada综合征尚需联合其他几项临床指标；Brugada综合征患者猝死的风险高，消除晕厥或室速／室颤的诱因是预防的关键。     

Tp—e时间及离散度对Brugada综合征患者预后的分析

目的探讨T波峰-末时间（Tp—e时间）及离散度与Brugada综合征患者预后的关系。方法采用动态心电图分析仪测量31例Brugada综合征患者的Tp—e时间及离散度。随访2～6年，每年2次，心脏事件为猝死幸存和（或）发生室性心动过速／心室颤动。结果无症状者发生心脏事件的Tp—e时间及离散度分别为（116．00±8．94）ms、（3300±1150）ms；未发生心脏事件者分别为（8666±1000）ms、（22．00±6．30）ms，差异有显著统计学意义（均P〈0．01）。有症状者再发生心脏事件的Tp—e时间及离散度分别为（108．50±10．69）ms、（3420±1060）ms；未发生心脏事件者分别为（85．45±9．34）ms、（18．10±12．60）ms，差异有显著统计学意义（均P〈0．01）。Tp—e时间及其离散度预测心脏事件发生的ROC曲线下面积分别为0947、0703。结论Tp—e时间及离散度可作为一种无创手段用于预测Brugada综合征患者发生心脏事件。     

Prevalence of Supraventricular Tachyarrhythmias in a Cohort of 115 Patients with Brugada Syndrome

Background : The Brugada syndrome is characterized by ST segment elevation in leads V₁ to V₃ and a right bundle branch block like pattern. It is associated with an increased risk of syncope and sudden cardiac death. Initial reports in small numbers of patients suggest an association between supraventricular tachycardias and Brugada syndrome with a prevalence varying between 13% and 40%. Objective : Aim of this study was to evaluate the prevalence of AV nodal reentrant tachycardia, AV reentry tachycardia, and/or atrial fibrillation in a large cohort of patients diagnosed as Brugada syndrome. Methods and Results : From three different European centers 115 consecutive patients with a Brugada syndrome were evaluated noninvasively and invasively (mean age 45 ± 12 years, n = 82 men, n = 33 women). Nineteen of 115 patients (17%) had a history of previous cardiac arrest. Syncope was reported by 58 patients (50%), 33 patients had a positive family history of sudden cardiac death (29%). Supraventricular tachycardias were documented in 26 of the patients (23%): Eight patients (7%) had AV‐nodal reentrant tachycardias and two patients had AV‐reentry tachycardias; atrial tachycardias were documented in three patients, and another 13 patients (11%) suffered from atrial fibrillation/atrial flutter. Additionally, atrial fibrillation was inducible by programmed atrial stimulation in nine patients (8%). Conclusions : Supraventricular tachycardias occur in 23% of patients with Brugada syndrome. Documentation of atrial fibrillation especially in the young or supraventricular tachycardias associated with syncope should give reason to screen for Brugada syndrome.     

Brugada Syndrome: Current Clinical Aspects and Risk Stratification

Brugada syndrome is a primary electrical disease of the heart that causes sudden cardiac death or life‐threatening ventricular arrhythmias, especially in younger men. Genetic analysis supports that this syndrome is a cardiac ion channel disease. A typical electrocardiographic finding consists of a right bundle branch block pattern and ST‐segment elevation in the right precordial leads. The higher intercostal space V₁ to V₃ lead electrocardiogram could be helpful in detecting Brugada patients. Although two types of the ST‐segment elevation are present, the coved type is more relevant to the syndrome than the saddle‐back type. These patterns can be present permanently or intermittently. Recent data suggest that the Brugada‐type electrocardiogram is more prevalent than the manifest Brugada syndrome. Asymptomatic individuals have a much lower incidence of future cardiac events than the symptomatic patients. Although risk stratification for the Brugada syndrome is still incomplete, the inducibility of sustained ventricular arrhythmias has been proposed as a good outcome predictor in this syndrome. In noninvasive techniques, some clinical evidence supports that late potentials detected by signal‐averaged electrocardiography are a useful index for identifying patients at risk. The available data recommend prophylactic implantation of an imptantabie cardioverter defibrillator to prevent sudden cardiac death. This review summarizes recent information of the syndrome by reviewing most of new clinical reports and speculates on its risk stratification. A.N.E. 2002;7(3):251–262     

常规心电图检查发现的Brugada波发生率与临床

目的初步调查Brugada波与Brugada综合征的发生率及与临床的关系。方法通过回顾调查近3年我院心电图室常规检查的52291份心电图，严格按诊断标准筛选有Brugada波的心电图，并对部分患者进行随访。结果共筛选出17例Brugada波患者，占总数的0．33％o，其中男性16例，女性1例，符合Brugada综合征的患者4例。结论Brugada波在临床上并非少见，但符合Brugada综合征即伴有反复晕厥、猝死的相对较少，是潜伏在体格健康的正常人群中的危险疾病。     

T Wave Alternans Does not Assess Arrhythmic Risk in Patients with Brugada Syndrome

Background: Brugada syndrome is associated with a risk for sudden death, but the arrhythmic risk in an individual Brugada syndrome patient is difficult to predict. Pathologic changes in the early repolarization phase of the ventricular action potential probably constitute part of the arrhythmogenic substrate in Brugada syndrome. Microvolt T wave alternans (TWA) assesses dynamic beat‐to‐beat changes in repolarization and has been suggested as a marker for repolarization‐related sudden death. We therefore tested whether TWA is an indicator for arrhythmias in Brugada syndrome with a focus on right precordial ECG leads. Methods: We assessed TWA in nine symptomatic, inducible patients with established Brugada syndrome and in seven healthy controls. TWA was assessed at rest and during exercise using both standard methods and an algorithm that assesses TWA in the early ST segment and the right precordial leads. Results : None of the Brugada patients developed TWA in this study irrespective of analysis at rest or during exercise, neither using standard methods nor when the early ST segment was included in the analysis. When the early ST segment was included in the analysis, nonsustained TWA was found in three out of seven, and sustained TWA in one control. Conclusion: T wave alternans is not an appropriate test to detect arrhythmic risk in patients with Brugada syndrome.     

发热诱发Brugada综合征的临床及心电图特征

目的 探究发热诱发Brugada综合征的临床及心电图特点.方法 选择2000年1月-2019年1月武汉大学人民医院收治Brugada综合征患者112例,根据诱发因素将全部病例分为发热组(34例)和非发热组(78例),比较分析两组临床特点及药物激发试验结果.结果 发热组在主要不良心血管事件发生率及家族史比例方面均显著大于...     

Conduction Delay in Right Ventricle as a Marker for Identifying High‐Risk Patients With Brugada Syndrome

Conduction Delay as a Marker for Brugada Syndrome. Objectives: To evaluate the significance of conduction delay (CD) in the right ventricle (RV) in Brugada syndrome (BS) as a marker for risk stratification of sudden death. Methods: Twenty‐five patients with BS (7 with documented ventricular fibrillation (VF), 8 with syncope, and 10 without symptoms) and 10 control subjects were paced from the RV apex using 8 beats of drive pacing and a single extra‐stimulus. CDs in the right ventricular outflow tract (RVOT) (CD‐RV) and in the lateral left ventricle (L‐LV) (CD‐LV), and the local electrogram durations at a single extra‐stimulus in RVOT (D‐RV) and L‐LV (D‐LV) were calculated. We also evaluated changes in 12‐lead ECG parameters in 16 patients with BS after pilsicainide challenge test (Pilsicainide‐test). Results: Maximal CD‐RV and maximal D‐RV were significantly larger than maximal CD‐LV and maximal D‐LV in BS (26 ± 10 and 105 ± 15 vs 20 ± 6 and 92 ± 15 ms, P < 0.05, respectively). Maximal CD‐RV and maximal D‐RV in patients with documented VF were the largest among the 3 groups. There was a significant positive correlation between maximal CD‐RV or maximal D‐RV and changes in QRS duration in leads V2 and V5 and in S wave duration in lead II and V5 after Pilsicainide‐test (CD‐RV; r = 0.54, 0.51, 0.56, and 0.53: D‐RV; r = 0.55, 0.5, 0.57, and 0.53, P < 0.05, respectively). In control subjects, there were no significant differences. Conclusions: CD in RV was a useful marker for identifying high‐risk patients with BS. CD in the RV, especially in the RVOT epicardium, may be related to arrhythmias in BS. (J Cardiovasc Electrophysiol, Vol. 21, pp. 688‐696, June 2010)     

Typical ECG Changes Unmasked by Ajmaline in a Patient with Brugada Syndrome and Left Bundle Branch Block

Brugada syndrome is a channelopathy associated with right bundle branch block and ST segment elevation in the right precordial leads. These electrocardiographic signs may not be apparent most of the time but can be unmasked by certain antiarrhythmic agents. Until now, all of the reports on this syndrome have focused on patients with no significant intraventricular conduction delay at baseline electrograms. In this report, we describe a patient with Brugada syndrome with left bundle branch block at baseline ECG. After intravenous ajmaline, the patient developed right bundle branch block and ST segment elevations in the right precordial leads.     

Transient Local Changes in Right Ventricular Monophasic Action Potentials Due to Ajmaline in a Patient with Brugada Syndrome

A 48-year-old patient with recurrent episodes of palpitations and syncope presented with transient ST segment elevation in the right precordial ECG leads. Structural heart disease was excluded. No arrhythmias were inducible by programmed ventricular stimulation. Parallel to ST elevation after intravenous ajmaline, a gradual and reversible delay in the upstroke of right ventricular (RV) monophasic action potentials (MAPs) occurred that was most marked in the RV outflow tract and nearly absent at right free-wall recordings. Ajmaline led to a cycle length-dependent increase in RV dispersion of repolarization. Thus, right endocardial MAPs may demonstrate regionally different action potential changes that may contribute to the ECG changes in Brugada syndrome.     

Electrocardiographic pattern of Brugada syndrome disclosed by a febrile illness: clinical and therapeutic implications.

BACKGROUND: Recent studies have identified a direct link between the ionic mechanisms responsible for the electrocardiographic (ECG) pattern of the Brugada syndrome (BS) and the in vitro experimental temperature, pointing to the possibility that some BS patients may display the ECG phenotype only during a febrile state, being in this setting at risk of lethal arrhythmias. CASE REPORT: A 53-year-old man referred to the emergency room for abdominal pain and fever. The ECG showed dome-shaped ST-segment elevation in V1-V3, as in the typical BS. The personal and family history were unremarkable for syncope and sudden death and physical, laboratory and ultrasound examinations were negative. On day 3, at normal body temperature, the patient's ECG returned to normal and the ECG abnormalities were later reproduced with intravenous flecainide. The patient refused the implantation of a loop recorder and was discharged after 6 days. He has remained asymptomatic during 2 years of follow-up. CONCLUSIONS: The typical ECG phenotype of BS disclosed by a febrile illness confirms the in vitro experimental data that previously established a correlation between ECG pattern of BS and temperature variations. The clinical and therapeutic implications of these findings are discussed.     

Study of the Extent of the Information of Cardiologists from São Paulo City,Brazil, Regarding a Low‐Prevalence Entity: Brugada Syndrome

Objective: To determine the degree of knowledge that cardiologists from São Paulo, Brazil, have regarding a low‐prevalent entity associated with a high rate of sudden death—Brugada syndrome. Methods: Two hundred forty‐four cardiologists were interviewed by an instrument divided in two parts: in the first, we recorded gender, age, and data related to academic profile. The second—answered only by the professionals that manifested having some degree of knowledge on the syndrome—had 28 questions that evaluated their knowledge. The answers were spontaneous and they did not have a chance to consult. We used uni‐ and multivariate analysis on the average percentage of right and wrong answers, and the influence of the academic profile. Results: The predominant gender was the male gender (61.1%), the average age was 44.32 ± 10.83 years, 40% with more than 20 years after obtaining their degree, 44% were educated in public institutions, 69% had a residency in cardiology, 20% had overseas practice, 12% had postdegree, 41% were linked to an educational institution, 24% with publication(s) in an indexed journal, 17.2% were authors of chapters in books, 2.5% had edited books, and 10% were linked to the Brazilian Society of Cardiac Arrhythmias. The average percentage of right answers was 45.7%. Conclusion: The sample studied revealed a little knowledge on the entity. A residency in cardiology was the factor of greater significance in the percentage of right answers. Other significant factors were the link of the interviewed person to an educational institution, or the Brazilian Society of Cardiac Arrhythmias, and having a specialist degree.     

New Electrocardiographic Features in Brugada Syndrome

Brugada syndrome is a genetically determined familial disease with autosomal dominant transmission and variable penetrance, conferring a predisposition to sudden cardiac death due to ventricular arrhythmias. The syndrome is characterized by a typical electrocardiographic pattern in the right precordial leads. This article will focus on the new electrocardiographic features recently agreed on by expert consensus helping to identify this infequent electrocardiographic pattern.