aVR sign as a risk factor for life-threatening arrhythmic events in patients with Brugada syndrome

BACKGROUND: Risk stratification in Brugada syndrome (BS) is controversial, especially in asymptomatic individuals. OBJECTIVE: The aim of this study was to evaluate the significance of lead aVR in patients with BS. METHODS: Twenty-four patients with the electrocardiogram pattern of BS (24 male, mean age 32.1 +/- 13.6 years) and 24 healthy age- and gender-matched controls were studied. RESULTS: Thirteen patients were symptomatic. The R-wave amplitude or R/q ratio in lead aVR was significantly greater in patients experiencing a recurrence compared with those who did not. The aVR sign was defined as R wave >/= 0.3 mV or R/q >/= 0.75 in lead aVR. Most of the recurrences (78%) were in patients with present aVR sign; 84% of BS patients with present aVR sign had events during follow-up. In contrast, only 27% of BS patients with absent aVR sign had events during follow-up. CONCLUSION: Our study shows significant correlation between a prominent R wave in lead aVR (aVR sign) and risk for development of arrhythmic events in BS. In the presence of BS, prominent R wave in lead aVR may reflect more right ventricular conduction delay and subsequently more electrical heterogeneity, which in turn is responsible for a higher risk of arrhythmia.     

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.     

Intravenous drug challenge using flecainide and ajmaline in patients with Brugada syndrome

OBJECTIVES: The purpose of this study was to compare the effect of intravenous flecainide and ajmaline with respect to their ability to induce or accentuate the typical ECG pattern of Brugada syndrome. BACKGROUND: Brugada syndrome is associated with a high incidence of sudden cardiac death. The typical ECG pattern of ST-segment elevation in the right precordial leads often is concealed, but it can be unmasked with sodium channel blockers such as flecainide and ajmaline. Little is known about the relative effectiveness of these provocative agents in unmasking Brugada syndrome. METHODS: Intravenous pharmacologic challenge with flecainide and ajmaline was performed. Whole-cell patch clamp techniques were used to assess the relative potency of ajmaline and flecainide to inhibit the transient outward current (I(to)). RESULTS: A coved-type ST-segment elevation in the right precordial leads was induced or enhanced in 22 of 22 patients following ajmaline administration. Among the 22 patients, only 15 patients showed positive response to flecainide, resulting in a positive concordance of 68%. Both drugs produced equivalent changes in QRS and PQ intervals, suggesting similar effects on sodium channel current. Whole-cell patch clamp experiments revealed a reduction of the total charge provided by I(to) with an IC(50) of 216 and 15.2 microM for ajmaline and flecainide, respectively. CONCLUSIONS: Our data demonstrate disparate response of Brugada patients to flecainide and ajmaline, with a failure of flecainide in 7 of 22 cases (32%). Greater inhibition of I(to) by flecainide may render it less effective. These observations have important implication for identification of patients at risk for sudden death.     

Prevalence of the Brugada sign in idiopathic ventricular fibrillation and healthy controls

OBJECTIVE—To determine the prevalence of the Brugada sign (right bundle branch block with ST elevation in V1-V3) in idiopathic ventricular fibrillation and in an age matched healthy population.DESIGN—ECGs from 39 consecutive patients with idiopathic ventricular fibrillation and 592 healthy controls were reviewed. They were classified as definite, questionable, and no Brugada sign (according to predetermined criteria) by four investigators blinded to the subjects'' status.RESULTS—Eight patients (21%) with idiopathic ventricular fibrillation but none of the 592 controls had a definite Brugada sign (p < 0.005). Thus the estimated 95% confidence limits for the prevalence of a definite Brugada sign among healthy controls was less than 0.5%. A questionable Brugada sign was seen in two patients with idiopathic ventricular fibrillation (5%) but also in five controls (1%) (p < 0.05). Normal ECGs were found following resuscitation and during long term follow up in 31 patients with idiopathic ventricular fibrillation (79%). Patients with idiopathic ventricular fibrillation and a normal ECG and those with the Brugada syndrome were of similar age and had similar spontaneous and inducible arrhythmias. However, the two groups differed in terms of sex, family history, and the incidence of sleep related ventricular fibrillation.CONCLUSIONS—A definite Brugada sign is a specific marker of arrhythmic risk. However, less than obvious ECG abnormalities have little diagnostic value, as a "questionable" Brugada sign was observed in 1% of healthy controls. In this series of consecutive patients with idiopathic ventricular fibrillation, most had normal ECGs.     

Brugada Syndrome with atypical characteristics: Case report

The Brugada Syndrome (BrS) is a heterogeneous genetic disease characterized by persistent or transient ST-segment elevation in the right precordial electrocardiography (ECG) leads and a high incidence of sudden death and life-threatening ventricular tachyarrhythmias in patients with structurally normal hearts. The syndrome generally manifests in men during adulthood. The ECG manifestations can be overt or concealed. We report a case of BrS whose type 1 ECG pattern during febrile state converted to type 2 ECG after alleviation of fever with atypical characteristics (78-year-old woman with monomorphic ventricular tachycardia on holter monitoring, a history of the sudden infant death of her child, and without inducible ventricular arrhythmia by programed ventricular stimulation [PVS]).     

国人Brugada综合征特点探讨(附三例报道)

目的：探讨国人Brugada综合征的特点。方法 报道3例Brugada综合征，并复习国内文献报道的20例，分析其特点。结果 (1)共23例Brugada综合征中男20例，女3例，发病年龄为9—73岁，平均40岁。(2)临床表现为晕厥14例，其中4例死亡，单纯阵发性心悸、胸闷3例，无症状6例；18个家系中有5个家系有明确或可疑家族史。(3)所有病例心电图Vl—V3导联ST段呈尖峰状和／或马鞍状抬高，大多ST段抬高程度多变，同时15例伴典型右束支传导阻滞，11例发生室速或室颤，其他还可见阵发性房颤、早博、房室传导阻滞、窦房传导阻滞等心律失常。结论：(1)国人Brugada综合征临床和心电图特点与国外文献报道相似。(2)诊断Brugada综合征主要应根据Vl—V3导联ST段尖峰状和／或马鞍状抬高的特征性改变，晕厥及典型右束支传导阻滞并非必需。(3)Vl—V3导联段抬高幅度多变是Brugada综合征的一个重要特点，ST段抬高程度可能与晕厥发作有关。     

Electrocardiographic characteristics of premature ventricular contractions in subjects with type 1 pattern of Brugada syndrome

Background

The ECG characteristics of premature ventricular contractions (PVCs) in subjects with Brugada syndrome (BrS) phenotype were investigated.

Methods and results

A total of 96 patients with type 1 ECG pattern of BrS were screened for PVCs. The study population consisted of 10 male individuals (mean age 41.9 ± 5.6 years) with spontaneous (n = 2) or drug-induced (n = 8) type 1 ECG phenotype of BrS and PVCs. Twenty patients (11 males, age 44.6 ± 15.1 years) with idiopathic right ventricular outflow tract (RVOT) PVCs (LBBB/inferior axis morphology with a negative QRS complex in lead aVL) successfully ablated from an endocardial site were also included in the study, and served as comparative controls. Six subjects with BrS phenotype (five during drug challenge) displayed PVCs with LBBB/inferior axis morphology and negative QRS complex in aVL lead which indicates an RVOT origin. The ECG characteristics of PVCs with LBBB/inferior axis in subjects with BrS and idiopathic RVOT arrhythmia were subsequently compared. QRS duration in inferior (p = 0.001) and right precordial leads (p < 0.001) was significantly longer in subjects with BrS phenotype. The RS interval in lead V2 was also significantly prolonged in individuals with BrS phenotype (p = 0.016). Subjects with BrS phenotype exhibited an increased intrinsicoid deflection time measured in right precordial leads compared to those with idiopathic RVOT PVCs (46.0 ± 7.6 vs. 27.2 ± 9.5 ms, p < 0.001). Finally, a pseudo-delta wave in precordial leads was more commonly observed in subjects with BrS ECG pattern (p = 0.029).

Conclusions

PVCs in BrS usually originate from the RVOT and display specific ECG characteristics that might be indicative of an epicardial origin. The prolonged interval criteria may be related to a localized epicardial conduction delay.     

Long-term follow-up in patients with Brugada Syndrome in South China

ObjectiveTo evaluate the presence of Brugada electrocardiogram (ECG) pattern, clinical characteristics, treatment, and long‐term prognosis of Brugada syndrome in southern Chinese population.MethodsThis prospective study consisted of a consecutive series of patients with diagnostic coved type I Brugada ECG pattern at baseline between January 2007 and February 2020. Histories of symptoms including ventricular tachycardia (VT)/ventricular fibrillation (VF) episode, syncope, and family history of Brugada Syndrome (BrS) or unexplained sudden cardiac death were collected. Electrophysiological study and implantable cardioverter‐defibrillator (ICD) were performed. All patients included in this study were followed up in the outpatient department every 6 months after baseline evaluation. Occurrences of syncope, VF, and sudden death were independently analyzed by two cardiologists.Results45 (56.3%) patients were diagnosed with BrS. During a mean follow‐up of 7.9 ± 3.6 years, six patients had experienced documented VF/sudden cardiac death (SCD) or recurrent syncope. Two patients experienced episodes of syncope more than once. Two patients experienced onset of electrical storm with a total of 11 episodes of VF. There were 50% of these events occurring in fever status. One of patient with BrS died of SCD.ConclusionThere was a very low prevalence of Brugada syndrome in southern Chinese population. The risk of arrhythmic events was low in asymptomatic patients. ICD was high effective in preventing SCD without adverse device outcome in long‐term follow‐up. Fever can lead to predispose to malignant arrhythmia, and aggressive treatment of febrile state in Brugada syndrome was recommended.     

Indications for automatic implantable defibrillators in patients with the Brugada syndrome

Brugada syndrome is a primary electrical cardiac disease characterized by an ST segment elevation in V1-V2 leads on surface ECG and an increased risk of polymorphic ventricular tachyarrhythmia (ventricular tachycardia and/or ventricular fibrillation). The objective of the treatment is to prevent sudden death and it therefore includes in some cases the implantation of an automatic implantable cardiac defibrillator (AICD). In secondary prevention (i.e. after a first episode of resuscitated ventricular fibrillation), the implantation of AICD is mandatory (indication of class 1 level A). In primary prevention (i.e. in patients without documented ventricular fibrillation), the guidelines are not definitively established. We may consider two different clinical situations. First, the patient complains from syncope and this justifies the implantation of an AICD. Second, the patient is asymptomatic and the physician has to discuss the implantation of an AICD. Two parameters should be analysed: the pattern of ECG and the result of right programmed ventricular stimulation. An evident ST segment elevation (>2 mm) is associated with a high risk of sudden death. Likewise, the inducibility of a ventricular tachycardia or fibrillation is considered at the present time as a factor linked to sudden death and justifies the implantation of an AICD. On the other hand, a normal resting ECG only associated with a provoked ST segment elevation by class I antiarrhythmic drug (flecainide) defines a group of patients with a low risk of sudden death, and these patients do not require the implantation of an AICD.     

经导管射频消融术后心悸原因的分析与处理

目的：了解阵发性心动过速(PT)患者经导管射频消融术(RFCA)后心悸的原因,提出相应的处理对策。方法：对680例行 RFCA 的 PT 患者进行随访,根据心悸的临床特点,选择相应的检查以明确诊断。结果：随访2月～4 年(平均0.6±1.1年),RFCA 后114例(16.8%)仍有心悸症状,其中心律失常53例(包括 RFCA 不成功15例,复发13例,合并阵发性房颤17例,多机制心动过速4例,房室传导阻滞4例),冠心病12例,高血压病15例,心神经官能症10例,15例原因不明。术后并发症13例,均不严重,经处理后恢复。结论：RFCA 后心悸的发生率并不低,其原因除心律失常(包括手术失败和复发)外,原发病是常见原因,应作相应检查和治疗。     

中国人Brugada综合征分子遗传学研究发现一个新的SCN5A基因突变

目的 研究探索中国人Brugada综合征是否存在基因突变及突变类型。并分析突变可能的致病机制。方法 以SCN5A作为候选基因。应用PCR-SSCP技术对4例患及其家系成员进行突变检测，并用DNA直接测序验证。结果 SSCP分析在一个家系内发现SCN5A基因第8外显子PCR产物出现异常带型，而在200例正常对照中均未发现此改变，DNA直接测序显示SCN5A编码区第317位密码子的第三位碱基G→C的错义突变，并导致位于DⅠS5与DⅠS6节段之间与钠通道蛋白“孔”区相关的第一个P-Loop结构上一个赖氨酸（K）被天冬酰胺（N）取代（K317N）。一个家系调查表明，21例家系成员中共有10例携带，其中有症状（4例）均为携带，2例无症状携带有心电图改变，隐性携带占40%，结论 在中国人中发现了Brugada综合征一个新的SCN5A基因突变。     

An Unusual Case of Brugada Syndrome in a 10-year-old Child with Fevers

Brugada syndrome is an arrhythmogenic disease characterized by a pattern of ST segment elevation in the right precordial leads on an electrocardiogram with an increased risk of sudden cardiac death. It is primarily reported in adults with limited data about the prevalence, prognosis, and long-term management in children. We describe a 10-year-old boy with a family history of sudden cardiac death, who had near syncope associated with a febrile illness. A screening electrocardiogram revealed ST segment elevation in the right precordial leads consistent with Type-1 Brugada syndrome. An electrocardiogram after recovery from his illness showed Type-2 “saddle-back” ST segment changes. An echocardiogram and a cardiac magnetic resonance imaging revealed a normal heart without myocardial fibrofatty infiltration, scar, or ischemia. A tilt-table test was negative. Implantable cardioverter-defibrillator placement remains the only effective treatment for patients with symptomatic Brugada syndrome; however, risk stratification of asymptomatic patients continues to remain a challenge. Although some investigators have reported the use of electrophysiological studies for distinguishing between high and low risk patients with Brugada syndrome, there are no precise predictors of risk for sudden cardiac death in pediatric patients. After careful discussion, this patient was considered intermediate to high risk for sudden cardiac death and had successful implantation of a transvenous defibrillator. Although Brugada syndrome is a rare diagnosis in the pediatric population, such patients should be referred for further evaluation and management.     

Intra day ECG variation after general anesthesia in Brugada syndrome

ECG variations of characteristic coved-type patterns are a common finding in subjects with Brugada syndrome. Few data are available about patients with Brugada syndrome undergoing major surgery and requiring general anesthesia. We reported ECG serial variations in a patient with Brugada syndrome who underwent surgery for tibial fracture. Relevant variations of ST patterns in V1–V2 leads over 24-h ECG monitoring were detectable, albeit these modifications were not associated with incidence of arrhythmias.     

Brugada syndrome with atypical ECG: downsloping ST-segment elevation in inferior leads

We present an unusual case of a young Thai immigrant, symptomatic, who had suffered prior episodes of syncope with strong family background: male, first-degree relatives, younger than 45 years old who had died suddenly. The rest ECG, with the patient asymptomatic at the time, showed persistent ST-segment elevation, in inferior leads and "mirror" image in the anterior wall, which were not modified with sublingual nitrates, in absence of demonstrable structural heart disease by chest X-rays and echocardiogram, hypothermia, ischemia, or electrolytic disorders. Holter monitoring revealed at dawn, a short episode of polymorphic ventricular tachycardia of short onset extrasystole coupling, which evolved into asystole and sudden cardiac death. We believe this is a sudden unexplained death syndrome, although we did not have a chance to conduct a genetic study.     

Negative flecainide test in Brugada syndrome patients with previous positive response.

Class I antiarrhythmic drug infusion has been established as the standard test to unmask Brugada syndrome. This report presents two patients with Brugada syndrome with positive flecainide response which was not reproducible in a subsequent test.     

Low-dose isoproterenol for repetitive ventricular arrhythmia in patients with Brugada syndrome.

AIMS: Arrhythmic storm or repetitive ventricular arrhythmia (VA) has been occasionally observed in Brugada syndrome (BS). A beta-adrenergic stimulator [isoproterenol (ISP)] has been reported to suppress this arrhythmic storm in sporadic cases. Accordingly, we investigated the antiarrhythmic effects of ISP infusion in consecutive BS patients with arrhythmic storm or repetitive VA. METHODS AND RESULTS: Seven BS patients with arrhythmic storm were studied. Intravenous ISP was administered as a bolus injection (1-2 microg), followed by continuous infusion (0.15 microg/min). Arrhythmic storm or repetitive VA was suppressed immediately after the bolus administration of ISP, which was followed by continuous infusion of low-dose ISP for 1-3 days. In all patients, ST-elevation decreased in right precordial leads. In six of the seven patients, VA subsided after the discontinuance of ISP. RR interval was shortened and ST-elevation in right precordial leads was decreased after ISP bolus injection. ST-elevation in right precordial leads remained decreased during continuous ISP infusion, whereas the RR interval returned to the control level. CONCLUSION: Continuous administration of low-dose ISP may be effective for the suppression of repetitive VA occurrence in patients with BS.