Manifestation of Brugada syndrome after pacemaker implantation in a patient with sick sinus syndrome

A 49-year-old woman experienced syncope 10 months after DDD pacemaker implantation for sick sinus syndrome. ECG revealed abnormal ST elevation in leads V1 to V3 during a paced rhythm. Multifocal premature ventricular contractions followed by ventricular fibrillation were documented. Saddleback-type ST elevation was confirmed after a mode change to AAI. The diagnosis of Brugada syndrome was made, and the DDD pacemaker was upgraded to an implantable cardioverter defibrillator. Brugada syndrome can be easily overlooked if the classic ECG findings are not initially noted but may be observed even during pacing therapy.     

Is There a Role for Implantable Cardioverter Defibrillators in Long QT Syndrome?

ICDs in Long QT Syndrome. The congenital familial long QT syndrome (LQTS) is characterized by QT interval prolongation on ECG and potentially life‐threatening polymorphic ventricular arrhythmias. Antiadrenergic therapy, i.e., beta‐adrenoceptor blockade, left cardiac sympathetic denervation, and occasionally pacemaker therapy, sufficiently protects most LQTS patients. Implantable cardioverter defibrillator treatment, with some specific problems and setting requirements in LQTS patients, should at least be considered or implanted in patients with recurrent arrhythmias despite adequate antiadrenergic therapy. Some genetic subtypes, such as LQTS3, may not respond as well (or even adversely) to antiadrenergic therapy and, thus, benefit more from implantable cardioverter defibrillator therapy.     

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     

The Brugada Syndrome

The Brugada syndrome is a genetically determined disease caused by mutations of the cardiac sodium channel. The disease affects mainly males in their forties and causes sudden cardiac death because of polymorphic ventricular tachycardia. These patients have a structurally normal heart. The electrocardiogram of this syndrome shows, spontaneously or after Class 1 antiarrhythmic drugs, ST segment elevation in leads V₁ to V₃ and a pattern resembling a right bundle branch block. Phase 2 reentry between epi‐ and endocardiac layers is responsible for the arrhythmias. The only effective treatment at present is implantation of a cardioverter defibrillator. A.N.E. 2000;5(1):88–91     

Brugada syndrome in a patient with accessory pathway.

Brugada syndrome in a patient with Wolff-Parkinson-White syndrome. We report a 32-year-old man with orthodromic atrioventricular (AV) reciprocating tachycardia using a right posterior accessory pathway. However, his ECG showed ST segment elevation in leads V1 to V3. After successful radiofrequency ablation of his accessory pathway a cardioverter defibrillator was implanted.     

Does early repolarization in the athlete have analogies with the Brugada syndrome?

AIMS: To re-examine the prevalence and presentation of early repolarization in athletes and to compare it with electrocardiographic abnormalities observed in patients with the Brugada syndrome. METHODS: Electrocardiograms of 155 male athletes and 50 sedentary controls were studied. Early repolarization was considered present if at least two adjacent precordial leads showed elevation of the ST segment > or =1 mm. Amplitude and morphology of ST elevation, the leads where it was present and the lead in which it showed its maximum value were analysed together with QRS duration, the presence of right ventricular activation delay, QT and QTc duration. Data were compared with those obtained by electrocardiograms of 23 patients with the Brugada syndrome. RESULTS: Early repolarization was found in 139 athletes (89%) and 18 controls (36%, P< or =0.025), being limited to right precordial leads in 42 (30%) athletes and 13 (72%) controls (P< or =0.001). Only 12 (8.6%) athletes and one control (5.5%) with early repolarization had an ST elevation 'convex toward the top' in right precordial leads, similar to that seen in the Brugada syndrome. In athletes the maximum ST elevation was greater (2.3+/-0.6 mm) than in the controls (1.2+/-0.8 mm; P< or =0.004) but significantly lower than in patients with the Brugada syndrome (4.4+/-0.7 mm; P< or =0.0001). Patients with the Brugada syndrome also had a greater QRS duration (0.11+/-0.02 s) than athletes (0.090+/-0.011 s; P< or =0.0001) with early repolarization. CONCLUSIONS: Early repolarization is almost always the rule in athletes but it is also frequent in sedentary males. Tracings somewhat simulating the Brugada syndrome were observed in only 8% of athletes without a history of syncope or familial sudden death. Significant differences exist between athletes with early repolarization and patients with the Brugada syndrome as regards the amplitude of ST elevation and QRS duration.     

Ionic and cellular mechanisms underlying the development of acquired Brugada syndrome in patients treated with antidepressants

Antidepressant‐Induced Brugada Syndrome. Introduction: Tricyclic antidepressants are known to induce cardiac arrhythmias at therapeutic or supratherapeutic doses. The tricyclic antidepressant, amitriptyline, is reported to induce ST segment elevation in the right precordial electrocardiogram (ECG) leads, thus unmasking Brugada syndrome (BrS). The mechanism by which antidepressants induce the BrS phenotype and associated sudden death is not well established. Methods and Results: Action potentials (AP) were simultaneously recorded from epicardial and endocardial sites of isolated coronary‐perfused canine right ventricular wedge preparations, together with a transmural pseudo‐ECG. Amitriptyline alone (0.2 μM–1 mM) failed to induce a BrS phenotype. NS5806 (8 μM), a transient outward potassium channel current (I_to) agonist, was used to produce an outward shift of current mimicking a genetic predisposition to BrS. In the presence of NS5806, a therapeutic concentration of amitriptyline (0.2 μM) accentuated the epicardial AP notch leading to ST‐segment elevation of the ECG. All‐or‐none repolarization at some epicardial sites but not others gave rise to phase‐2‐reentry and polymorphic ventricular tachycardia (VT) in 6 of 9 preparations. Isoproterenol (100 nM) or quinidine (10 μM) reversed the effects of amitriptyline aborting phase 2 reentry and VT (4/4). Using voltage‐clamp techniques applied to isolated canine ventricular myocytes, 0.2 μM amitriptyline was shown to produce use‐dependent inhibition of sodium channel current (I_Na), without significantly affecting I_to (n = 5). Conclusions: Our data suggest that amitriptyline‐induced inhibition of I_Na unmasks the Brugada ECG phenotype and facilitates development of an arrhythmogenic substrate only in the setting of a genetic predisposition by creating repolarization heterogeneities that give rise to phase 2 reentry and VT.     

Brugada综合征快速心律失常的发病机理与射频消融治疗

目的探讨Brugada综合征ST-T抬高与快速心律失常的发病机理和射频消融治疗。方法选择体表心电图V1~V3相邻2个导联ST-T下斜或马鞍型抬高≥0.2mV,且有心律失常者按常规行心脏电生理检查和射频消融。结果38例患者,男31例,女7例,年龄38.27±13.91岁。17例有晕厥或黑矇,3例经历心肺复苏。23例为Ⅰ型Brugada图形,10例为Ⅱ型,5例为Ⅰ、Ⅱ、Ⅲ型交替,均合并不同类型的心脏传导异常。10例为单形(2例)或多形(8例)室性心动过速,1例为心室颤动电风暴,5例为室性与房性心律失常并存,5例为单纯室上性心动过速(4例为显性预激综合征),3例为室上性心动过速和心房扑动,14例为房性早搏、房性心动过速和心房颤动。射频消融即刻成功32例(成功率84%),失败6例,未发生并发症。消融成功者心律失常消失后即刻,ST-T抬高未见改变。而室性早搏、房性早搏伴差传、His束传导阻滞、间歇预激旁道、心室起搏与静脉滴注异丙肾上腺素可使ST-T抬高幅度改变或逆转。随访5.72±2.03年,1例失访,5例心律失常复发,1例猝死,3例安装心脏永久起搏器,1例安装心脏转复除颤器。结论Brugada综合征常见心脏传导异常,ST-T抬高继发于心脏传导系统疾病与除极顺序改变,而非原发心内、外膜复极离散与2相折返,射频消融可有效防治Brugada综合征的多种快速心律失常。     

Heterogeneity and cardiac arrhythmias: An overview

This lecture examines the hypothesis that amplification of spatial dispersion of repolarization in the form of transmural dispersion of repolarization (TDR) underlies the development of life-threatening ventricular arrhythmias associated with inherited ion channelopathies, including the long QT, short QT, and Brugada syndromes as well as catecholaminergic polymorphic ventricular tachycardia. In the long QT syndrome, amplification of TDR often is secondary to preferential prolongation of the action potential duration of M cells, whereas in Brugada syndrome, it is thought to be due to selective abbreviation of the action potential duration of right ventricular epicardium. In the short QT syndrome, preferential abbreviation of action potential duration of either endocardium or epicardium appears to be responsible for amplification of TDR. In catecholaminergic polymorphic ventricular tachycardia, reversal of the direction of activation of the ventricular wall is responsible for the increase in TDR. Thus, the long QT, short QT, Brugada, and catecholaminergic ventricular tachycardia syndromes are pathologies with very different phenotypes and etiologies. However, these syndromes share a common final pathway in their predisposition to sudden cardiac death.     

与猝死有关的遗传性心律失常的研究进展

随着分子生物学及功能性研究的不断进展，遗传性心律失常的病因逐渐明晰，心脏离子通道或调节蛋白的基因突变已经在遗传决定的多形性室性心动过速如长QT综合征、Brugada综合征、短QT综合征和儿茶酚胺源性多形性室性心动过速中被证实，现就这些综合征的遗传学基础、临床特征和目前的治疗作一回顾。     

Concurrent long QT and Brugada syndrome in a single patient]

We present a 61-year-old patient with previous cardiac arrest and frequent syncopal spells. ECG showed a typical Brugada pattern and a QTc interval of 425 ms. During programmed ventricular stimulation a self-limited syncopal polymorphic ventricular tachycardia was induced. On diagnosis of the Brugada syndrome an implantable cardioverter defibrillator was implanted. Two days later two episodes of polimorphic ventricular arrhythmia were converted by the device. The ECG at this time showed a prolonged QTc of 500 ms in addition to a typical Brugada pattern. Atenolol was started and after a 36-month follow-up the patient has remained asymptomatic without arrhythmic events. In conclusion, this patient has the Brugada syndrome and also fulfills the clinical and ECG characteristics of the Long QT syndrome. These findings suggest a genetic link between the two syndromes.     

Primär elektrische Herzerkrankungen im Erwachsenenalter—

Sudden cardiac death accounts for 100,000 victims in Germany per year. Predominantly, patients with structural heart disease such as coronary artery disease or dilated cardiomyopathy are affected. However, approximately 5-10% of sudden deaths hit patients without structural disease of the heart. The proportion of young patients (< 40 years of age) in this group is even higher (10-20%). In younger patients significantly more diseases like hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia and primary electrical diseases of the heart could be observed such as long QT syndrome, short QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia. The primary electrical diseases are different concerning their electrocardiographical pattern, clinical triggers of arrhythmias, results of invasive diagnostics and therapy. Meanwhile, molecular genetic screening can reveal specific mutations of ion channels and can identify consecutive functional defects. The significance of programmed ventricular stimulation is at present unclear concerning risk stratification in patients with Brugada syndrome and short QT syndrome and of no significance in long QT syndrome and catecholaminergic polymorphic ventricular tachycardias. The implantable cardioverter defibrillator is the therapy of choice in most symptomatic patients. With increasing knowledge as a result of sophisticated molecular genetic screening, identification of underlying ion channel defects and new details of the mechanisms of arrhythmogenesis, a potential genotype-guided therapy will gain more importance in the future.     

Effects of glucose-induced insulin secretion on ST segment elevation in the Brugada syndrome

INTRODUCTION: ST segment elevation in patients with Brugada syndrome is known to fluctuate occasionally, influenced by multiple factors. Insulin has been shown to affect QT dispersion in healthy volunteers, as well as result in abnormality of ventricular repolarization in patients with congenital long QT syndrome. METHODS AND RESULTS: To assess a possible role of insulin in ST segment elevation in patients with Brugada syndrome, an oral glucose tolerance test (OGTT) was administered to 20 patients with Brugada syndrome and 20 normal patients without ST-T changes as a control group. Plasma glucose and potassium levels, immunoreactive insulin concentration (IRI), and ST segment elevation and ST-T wave changes on 12-lead ECG during OGTT were analyzed. Augmentation (>1 mm) of ST elevation or morphologic changes in ST-T waves were observed frequently in response to increased IRI during OGTT [15/20 cases (75%)] in patients with Brugada syndrome but in none of the patients in the control group [0/20 cases (0%), P < 0.01]. The changes returned to baseline 180 minutes after the glucose load in 9 of 15 patients. Patients who showed coved-type ST elevation before the glucose load exhibited positive ECG changes more frequently than patients with saddleback-type elevation or transiently normalized ST segment [8/8 cases (100%) vs 7/12 (58%), P < 0.05]. There was no significant difference between the two groups in terms of glucose, IRI, and potassium levels during OGTT. CONCLUSION: The findings suggest that glucose-induced insulin secretion is one of the contributing factors to fluctuation of ST segment elevation in patients with Brugada syndrome.     

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.     

Brugada syndrome unmasked by pneumonia

A 69-year-old white woman presented at our emergency room with right-side pleuritic chest pain, fever, and tachycardia. Results of the physical examination, routine laboratory tests, and chest radiography were unexceptional. An electrocardiogram showed ST elevation in leads V(1) through V(3) with T-wave inversion. Because of the chest pain and the ST elevation, the patient underwent emergency cardiac catheterization, which showed no coronary artery stenosis. A computed tomographic scan of the chest showed pulmonary infiltration in the right middle lobe and the lingula of the left upper lobe; pneumonia was diagnosed, and appropriate antibiotic therapy was started. The electrocardiographic changes met the criteria for type-1 Brugada pattern. Brugada syndrome is an arrhythmogenic disease caused in part by mutations in the cardiac sodium channel gene SCN5A. When the sodium current is disrupted, the outward transient current at the end of phase 1 of the action potential becomes unopposed. This creates a voltage gradient between the epicardium and endocardium, especially in the right ventricular wall, which leads to J-point elevation in leads V(1) through V(3). Fever exaggerates this defect in sodium channels. In our patient, the pleuritic chest pain was caused by the pneumonia, and the ST elevation was probably related to Brugada syndrome, unmasked by the febrile episode. Brugada syndrome can be associated with ventricular tachycardia or fibrillation; the only treatment proven to prevent sudden death is placement of an implantable cardioverter defibrillator, which is recommended in symptomatic patients or in those with ventricular tachycardia induced during electrophysiologic studies.     

Early Repolarization Syndrome: Electrocardiographic Signs and Clinical Implications

Early repolarization syndrome (ERS) was previously considered as a benign variant, but it has recently emerged as a risk marker for idiopathic ventricular fibrillation (VF) and sudden death. As measured by electrocardiogram (ECG), early repolarization is characterized by an elevation of the J point and/or ST segment from the baseline by at least 0.1 mV in at least two adjoining leads. In particular, early repolarization detected by inferior ECG leads was found to be associated with idiopathic VF and has been termed as ERS. This condition is mainly observed in young men, athletes, and blacks. Also, it has become evident that electrocardiographic territory, degree of J‐point elevation, and ST‐segment morphology are associated with different levels of risk for subsequent ventricular arrhythmia. However, it is unclear whether J waves are more strongly associated with a depolarization abnormality rather than a repolarization abnormality. Several clinical entities can cause ST‐segment elevation. Therefore, clinical and ECG data are essential for differential diagnosis. At present, the data set is insufficient to allow risk stratification in asymptomatic individuals. ERS, idiopathic VF, and Brugada syndrome (known as J‐wave syndromes) are three clinical conditions that share many common ECG features; however, their clinical consequences are remarkably different. This review summarizes the current electrocardiographic data concerning ERS with clinical implications.     

早复极和早复极综合征与心脏性猝死

早复极是临床常见的心电图表现,当具有早复极心电图表现的患者出现恶性心律失常甚至猝死时称为早复极综合征.早复极综合征患者10％可以检测到基因学改变,发生猝死的危险性与ST段抬高部位波及下壁和侧壁、抬高幅度≥0.2 mV,具有心律失常或猝死家族史等相关.诊断需除外器质性心脏病和Brugada综合征等,临床应注意心电图早复极与早复极综合征的区别和危险分层.对有心脏骤停史者应植入植入式心脏复律除颤器,异丙肾上腺素可用于早复极综合征合并的电风暴,奎尼丁对植入式心脏复律除颤器植入后患者可能预防复发.     

Association of congenital, diffuse electrical disease in children with normal heart: sick sinus syndrome, intraventricular conduction block, and monomorphic ventricular tachycardia

Introduction: Rhythm disturbances in children with structurally normal hearts are usually associated with abnormalities in cardiac ion channels. The phenotypic expression of these abnormalities ("channelopathies") includes: long and short QT syndromes, Brugada syndrome, congenital sick sinus syndrome, catecholaminergic polymorphic ventricular tachycardia, Lènegre-Lev disease, and/or different degrees of cardiac conduction disease.
Methods: The study group consisted of three male patients with sick sinus syndrome, intraventricular conduction disease, and monomorphic sustained ventricular tachycardia. Clinical data and results of electrocardiography, Holter monitoring, electrophysiology, and echocardiography are described.
Results: In all patients, the ECG during sinus rhythm showed right bundle branch block and long QT intervals. First-degree AV block was documented in two subjects, and J point elevation in one. A pacemaker was implanted in all cases due to symptomatic bradycardia (sick sinus syndrome). Atrial tachyarryhthmias were observed in two patients. The common characteristic ventricular arrhythmia was a monomorphic sustained ventricular tachycardia, inducible with ventricular stimulation and sensitive to lidocaine. In one patient, radiofrequency catheter ablation was successfully performed. No structural abnormalities were found in echocardiography in the study group.
Conclusion: Common clinical and ECG features suggest a common pathophysiology in this group of patients with congenital severe electrical disease.     

Recommendations for participation in leisure-time physical activity and competitive sports of patients with arrhythmias and potentially arrhythmogenic conditions. Part II: ventricular arrhythmias, channelopathies and implantable defibrillators.

This consensus paper on behalf of the Study Group on Sports Cardiology of the European Society of Cardiology follows a previous one on guidelines for sports participation in competitive and recreational athletes with supraventricular arrhythmias and pacemakers. The question of imminent life-threatening arrhythmias is especially relevant when some form of ventricular rhythm disorder is documented, or when the patient is diagnosed to have inherited a pro-arrhythmogenic disorder. Frequent ventricular premature beats or nonsustained ventricular tachycardia may be a hallmark of underlying pathology and increased risk. Their finding should prompt a thorough cardiac evaluation, including both imaging modalities and electrophysiological techniques. This should allow distinguishing idiopathic rhythm disorders from underlying disease that carries a more ominous prognosis. Recommendations on sports participation in inherited arrhythmogenic conditions and asymptomatic gene carriers are also discussed: congenital and acquired long QT syndrome, short QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular cardiomyopathy and other familial electrical disease of unknown origin. If an implantable cardioverter defibrillator is indicated, it is no substitute for the guidelines relating to the underlying pathology. Moreover, some particular recommendations for patients/athletes with an implantable cardioverter defibrillator are to be observed.