Right ventricular electrocardiographic leads for detection of Brugada syndrome in sudden unexplained death syndrome survivors and their relatives

BACKGROUND: Sudden unexplained death syndrome (SUDS) is a sudden death syndrome in previously healthy Southeast Asian young adults without any structural causes of death. Many SUDS survivors show electrocardiographic (ECG) evidence of RSR' and ST elevation in leads V1 to V3, which is similar to the ECG pattern in Brugada syndrome. However, in many cases transient normalization of the ECG does not make diagnosis with standard 12-lead ECG possible. HYPOTHESIS: To overcome this problem, we utilized the new right ventricular ECG leads to detect the Brugada syndrome in SUDS survivors. METHODS: The subject was a Thai male patient who presented with a SUDS-like syncopal attack. He had cardiac arrest due to idiopathic ventricular fibrillation. RESULTS: Post-resuscitation standard 12-lead ECG showed no diagnostic features of Brugada syndrome. However, ECG patterns of RSR' and ST elevations typical for Brugada syndrome could be detected at the higher intercostal space leads V1 to V3. We observed similar findings in 2 of the other 10 SUDS survivors and 4 of 23 healthy family members. CONCLUSIONS: Our data suggest that these new right ventricular leads ECG may be helpful in detecting Brugada syndrome in SUDS survivors and their relatives.     

中国人群青壮年猝死综合征的流行现状——广东省东莞市、深圳龙岗区及宝安区青壮年猝死综合征的流行病学调查

目的了解中国人群不明原因夜间睡眠猝死综合征(SUNDS)的流行现状。方法采用描述性研究方法,对广东省东莞市、深圳市宝安区及龙岗区975例SUNDS案件资料进行回顾性分析。结果中国人SUNDS主要发生于劳动强度较高、文化素质较低的生产作业工人,年发病率约为1.0人/10万;男性病例占93.23%,80.56%的病例集中在21~40岁;4、5月份异常高发,SUNDS病例与急诊发热病例的月份分布呈正相关(r=0.785,P<0.05);64.96%的病例籍贯属于北纬30度以南地区;目击病例的临床症状集中表现为睡眠中突发呼吸障碍。结论本研究首次勾勒了中国人群SUNDS的流行现状并初步提出与其发生可能相关的危险因素,为后继的病因探索奠定了基础。     

Dynamic electrocardiographic changes after aborted sudden death in a patient with Brugada syndrome and rate-dependent right bundle branch block

A 37-year-old man with Brugada syndrome and dynamic changes of the ST-segment morphology observed after an episode of aborted sudden death is described. On admission, after 3 syncopal episodes during nighttime, his electrocardiogram showed right bundle branch block (RBBB) with a J-point elevation of 0.6 mV in lead V 2 . Changes observed in the following days included a diminished J-point elevation and intermittent "saddle-back" type of morphology. During a previous 2-year follow-up, intermittent, complete, acceleration-dependent RBBB was documented. Right ventricular intracavitary tracings showed an RS pattern with a broad S wave in the unipolar electrogram; the time of onset of intrinsic deflection in this electrogram was 60 milliseconds. To our knowledge, this is the first report of an intracavitary demonstration of complete RBBB in Brugada syndrome.     

Heart rate variability in patients with Brugada syndrome in Thailand.

AIMS: Since patients with Brugada syndrome usually have symptoms at nighttime, we hypothesize that changes in autonomic modulation have an important role in the occurrence of the ventricular fibrillation episodes. The objective of this study was to determine the changes in heart rate variability (HRV) in patients with Brugada syndrome compared to asymptomatic subjects with Brugada ECG and controls. METHODS AND RESULTS:We studied 17 patients with Brugada syndrome, 10 asymptomatic subjects with Brugada ECG and 45 controls. Patients with Brugada syndrome and asymptomatic subjects with Brugada ECG underwent echocardiography, exercise stress testing, 24-h Holter monitoring, signal-averaged ECG. Patients with Brugada syndrome also underwent coronary angiography and electrophysiologic study. Time domain and frequency domain HRV analysis were performed at daytime and nighttime. The results of this study showed that patients with Brugada syndrome had lower HRV or lower vagal tone at night compared to the controls. They also had lower heart rate during the day and higher during the night compared to asymptomatic subjects and the controls. CONCLUSION: Patients with Brugada syndrome had low heart rate variability at night which may predispose to the occurrence of VF episodes.     

A balanced translocation disrupting SCN5A in a family with Brugada syndrome and sudden cardiac death

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SCN5A基因突变与青壮年猝死综合征

青壮年猝死综合征(SUNDS)的病因迄今不明。随着分子遗传学和心脏离子通道研究的深入,SCN5A基因突变已被确定为Brugada综合征、3型长QT间期综合征的最重要病因。本文综述文献,结合项目组研究,介绍SCN5A基因突变与SUNDS发生的相关性。     

高位右侧胸前导联对诊断Brugada综合征心电图的价值

目的观察加做高位右侧胸前导联对揭示Brugada综合征心电图的有效性。方法对有猝死家族史、心电图胸前导联ST段抬高的3例患者进行家系调查，对3个家系中的10个成员进行了体格检查、X线胸片、超声心动图检查，将30例20～50岁的健康体检者作为对照，描记常规及高位右侧胸前导联心电图。结果加做高位右侧胸前导联可提高Brugada综合征心电图诊断的阳性率，且极为简便、安全。结论与常规心电图相比高位右侧胸前导联心电图能有效地提高Brugada综合征心电图诊断的阳性率。     

Prevalence of Brugada sign in a Greek tertiary hospital population.

AIMS: The purpose of the present study was to determine for the first time the prevalence of Brugada-type electrocardiographic (ECG) pattern (Brugada sign) in unselected individuals served by an urban Greek tertiary hospital during a 4-year time period. METHODS AND RESULTS: Among 11,488 individuals (6640 males, 4848 females), 25 (23 males, 2 females, aged 36.8 +/- 19.2 years) were found to display the Brugada sign (0.22%). Two cases exhibited the diagnostic type 1 ECG pattern (0.02%) and 23 subjects fulfilled the ECG criteria for type 2 or 3 patterns (0.2%). The incidence of Brugada sign was higher among men (0.34%) than in women (0.04%). Structural heart disease was established in four cases (one of them exhibiting a type 1 ECG pattern). Twenty-one individuals (19 males, 2 females, aged 29.7 +/- 10.7 years) without structural heart disease displaying Brugada-type ECG features (4 cases with spontaneous or procainamide-induced type 1 ECG pattern) were subsequently selected and closely followed up for 24 +/- 12 months. No mortality or life-threatening ventricular arrhythmias were recorded during this period. CONCLUSION: The Brugada-type ECG pattern is infrequently seen in a Greek hospital-based population. All subjects with Brugada sign and structurally normal hearts displayed a benign clinical course without arrhythmic events during a relatively long follow-up period.     

Long-term follow-up of primary prophylactic implantable cardioverter-defibrillator therapy in Brugada syndrome.

AIMS: To analyse the follow-up data of implantable cardioverter-defibrillator (ICD) therapy in Brugada syndrome (BS). METHODS AND RESULTS: We conducted a retrospective, single centre study of 47 patients (mean age: 44.5 +/- 15 years) with BS, who underwent primary prophylactic ICD implantation. All patients had baseline spontaneous (23 patients) or drug-induced (24 patients) coved type I ECG pattern. All patients were judged to be at high risk because of syncope (26 patients) and/or a positive family history of sudden death (26 patients). During a median follow-up of 47.5 months, seven patients had appropriate shocks. The presence of spontaneous type I ECG and non-sustained ventricular tachyarrhythmia in the ICD datalog suggested a trend towards shorter appropriate shock-free survival by Kaplan-Meier analysis (P = 0.037 and P = 0.012, respectively). Seventeen patients received inappropriate shocks (IS); eight patients for sinus tachycardia; six patients for new onset atrial arrhythmias; and five patients for noise oversensing. In multivariable Cox-regression analysis, new onset atrial fibrillation (AF) and less than 50 years of age were independent predictors of significantly shorter IS-free survival (P = 0.04 and P = 0.036, respectively). CONCLUSION: In high-risk patients with BS, primary prophylactic ICD therapy is an effective treatment. In this, young and otherwise healthy patient population, the IS rate is high.     

Beat-to-beat variations of the electrocardiogram in survivors of sudden death without structural heart disease

Aim

We sought to determine whether survivors of sudden death without structural heart disease have beat-to-beat electrocardiographic (ECG) characteristics at the microvolt and at the millisecond level that differ from normal subjects.

Methods

We studied patients at our implantable cardioverter defibrillator clinic who had been resuscitated from ventricular fibrillation with no evidence of underlying structural heart disease. Continuous 10-minute high-resolution unfiltered digital surface ECGs at 1000-Hz sampling rate were acquired in these subjects and in a group of healthy volunteers. We then analyzed different parameters of beat-to-beat variations in duration, amplitudes and vectors of the QRS complex, and the T wave using a locally developed program (Comparative Analysis of ECGs, Vectocardiograms, and their Interpretation with Auto-Reference to the patient) and compared them between the 2 groups.

Results

Thirteen patients (7 men; age, 46 ± 16 years) were studied. Standard ECGs were unremarkable in 7 patients and suggestive of Brugada syndrome in the 6 others. The control group consisted of 23 age- and sex-matched subjects (13 men; age, 41 ± 10 years). Although the QRS parameters showed only few differences between the 2 groups, there were several differences in parameters evaluating repolarization.

Conclusion

High-resolution ECGs show distinct beat-to-beat variations in parameters of repolarization in survivors of sudden death without structural heart disease, as compared with normal subjects. These findings may reflect increased electrical instability and should be evaluated for stratifying arrhythmic risk in asymptomatic individuals.     

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。     

Cardiac ion channel mutations in the sudden infant death syndrome

Sudden infant death syndrome (SIDS) is characterized by the sudden death of an infant that occurs during sleep and remains unexplained despite thorough examination. In addition to clinical associations such as prone sleeping and exposure to cigarette smoke, several genetic factors have been identified with regard to SIDS, including autonomic disorders, immunologic polymorphisms and metabolic disorders. In the past decade, postmortem genetic analysis (‘molecular autopsy’) of SIDS cases has revealed a number of cardiac ion channel mutations that are associated with arrhythmia syndromes, including the long QT syndrome, Brugada syndrome and short QT syndrome. Mutations have been found in genes encoding (subunits of) cardiac potassium, sodium and calcium channels, as well as in genes involved in the trafficking or regulation of these channels. Here, we review the literature on cardiac ion channel mutations in relation to SIDS. Combining data from population-based cohort studies, we conclude that at least one out of five SIDS victims carries a mutation in a cardiac ion channel-related gene and that the majority of these mutations are of a known malignant phenotype. Genetic analysis is therefore recommended in cases of sudden infant death. More research is required to further elucidate the pathophysiology of SIDS and to determine whether genetic or electrocardiographic screening of apparently healthy infants should be pursued.     

Cardiac genetic investigation of young sudden unexplained death and resuscitated out of hospital cardiac arrest

Nearly 30% of young sudden deaths have negative autopsies and these sudden unexplained deaths (SUDs) are presumed to be due to heritable cardiac arrhythmias attributed to cardiac ion channel disorders. Comprehensive cardiac and genetic testing of families of SUD is helpful in the detection of inherited cardiac genetic conditions. It frequently provides a clue to the cause of death in SUD victims and allows early diagnosis and opportunities to prevent SUD in other family members. Out of Hospital Cardiac Arrest (OHCA) victims and their families also require similar assessment, although the role of genetic testing in this group should be reserved to patients where a clinical diagnosis is established. A team approach with multidisciplinary specialised clinics and increased access to genetic analysis is very helpful in achieving these goals.     

新胸导联在诊断Brugada综合征中的应用

目的 评价自行设计的新胸导联在Brugada综合征诊断中的应用价值。方法 4例Brugada综合征先证者和9例家族成员接受新胸导联和普罗帕酮药物试验。11例无晕厥史和无猝死家族史的房室结折返性室上性心动过速患者作为新胸导联检查对照组。自行设计的心电图新胸导联包括A-G(7)列、0-5(6)行,共42个导联,记录方法同标准胸导联。普罗帕酮试验:普罗帕酮70 mg(体重>70kg者用105 mg)加入生理盐水10 ml于5 min内静脉注射,用药前、后记录标准12导联心电图;用药后标准V1-V3导联J点或ST段抬高超过2 mm(或ST段抬高由BrugadaⅡ或Ⅲ型转变成Ⅰ型),称为药物试验阳性。结果 先证者1～3均有晕厥史,先证者1和3有家族猝死史,先证者2和3晕厥发作时记录到心室颤动,先证者3猝死;除先证者4标准胸导联心电图呈Brugada典型下斜型改变外,先证者1-3标准胸导联心电图不能明确诊断为Brugada综合征。新胸导联发现先证者1-3呈典型Brugada综合征心电图改变,位于标准胸导联以外区域。新胸导联同时发现,5例家族成员在标准胸导联以外区域有典型的Brugada心电图改变。新胸导联阳性者亦被普罗帕酮试验证实。对照组11例新胸导联检查均为阴性。结论 新胸导联有助于发现Brugada综合征典型心电图改变位于标准V1-V3导联以外的病例,且应用安全,方法较简单     

Identification of a SCN5A founder mutation causing sudden death,Brugada syndrome,and conduction blocks in Southern Italy

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一个Brugada综合征合并先天性长QT综合征的家系及临床研究

目的 1例Brugada综合征合并先天性长QT综合征的家系的临床研究。方法 对夜间反复发作性晕厥的先证者进行冠状动脉，左、右心室造影和电生理检查及药物试验(异丙肾上腺素和普罗帕酮)；对其家族成员进行病史询问、体格检查、超声心动图、动态心电图和药物试验，同时记录右侧胸前导联(V1～V3)上两个肋间的心电图。结果 家族中有两例猝死，均发生在睡眠中。家族成员未被发现器质性心脏病。先证者心电图表现为右侧胸前和下壁导联ST段抬高，住院期再次发生夜间晕厥记录到心电图为多形室性心动过速(室速)。冠状动脉及左、右心室造影正常，电生理检查诱发多形室速。异丙肾上腺素试验时ST段正常，QTc间期明显延长；普罗帕酮试验阳性。另两例家族成员，右侧胸前导联上一或二肋间心电图呈典型Brugada综合征改变，异丙肾上腺素试验QTc间期亦明显延长，1例普罗帕酮试验阳性。结论 结果表明可能是由于一种新的钠通道基因(SCN5A)突变类型同时引起Brugada综合征和先天性长QT综合征。     

The syndrome of right bundle branch block ST segment elevation in V1 to V3 and sudden death--the Brugada syndrome.

In 1992 a new syndrome was described consisting of syncopal episodes and/or sudden death in patients with a structurally normal heart and an electrocardiogram (ECG) characteristic of right bundle branch block with ST segment elevation in leads V1 to V3. The disease is genetically determined, with an autosomal dominant pattern of transmission. Three different mutations that affect the structure and function of the cardiac sodium channel gene SCN5A have been identified. Two mutations result in total loss of function of the sodium channel. The other mutation results in acceleration of the recovery of the sodium channel from inactivation. The incidence of the disease is difficult to estimate, but it causes 4 to 10 sudden deaths per 10000 inhabitants per year in areas like Thailand and Laos. In these countries, the disease represents the most frequent cause of death in young adults. Up to 50% of the yearly sudden deaths in patients with a structurally normal heart are caused by this syndrome. The diagnosis is easily made by means of the ECG. The presence of concealed and intermittent forms, however, make the diagnosis difficult in some patients. The ECG can be modulated by changes in autonomic balance and the administration of antiarrhythmic drugs. Beta-adrenergic stimulation normalizes the ECG, while intravenous ajmaline, flecainide or procainamide accentuate ST segment elevation and are capable of unmasking concealed and intermittent forms of the disease. Recent data suggest that loss of the action potential dome in the right ventricular epicardium but not the endocardium underlies ST segment elevation seen in the Brugada syndrome. Also, electrical heterogeneity within the right ventricular epicardium leads to the development of closely coupled extrasystoles via a phase 2 reentrant mechanism, which then precipitates ventricular tachycardia-ventricular fibrillation. Right ventricular epicardium is preferentially affected because of the predominance of transient outward current in this tissue. Antiarrhythmic drugs like amiodarone and beta-blockers do not prevent sudden death in symptomatic or asymptomatic individuals. Gene therapy may offer a cure in future years. Implantation of an automatic cardioverter-defibrillator is the only currently proven effective therapy.