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.     

Two-year case collection of the Brugada syndrome electrocardiogram pattern at a large teaching hospital

BACKGROUND: Recommendations have recently emerged suggesting that the presence of the Brugada electrocardiographic (ECG) pattern in an otherwise asymptomatic individual warrants electrophysiologic testing for inducible ventricular arrhythmias. However, the prevalence of this pattern in the general population and its specificity for identifying those likely to develop the true Brugada syndrome are not known. HYPOTHESIS: The purpose of this study was to collect ECGs that displayed the Brugada pattern from unselected, noncardiac patients at a single institution to determine whether the implied prevalence in the literature may represent a significant underestimation of the true prevalence. METHODS: We performed a prospective case collection of Brugada-patterned ECGs over a 2-year time period from unselected, noncardiac patients at a large urban teaching hospital. RESULTS: Of approximately 12,000 noncardiac patients, 52 were found to have an ECG pattern fully consistent with the Brugada sign. CONCLUSIONS: The Brugada type ECG pattern is much more prevalent than previously reported when rigorously searched for in a prospective manner. More data are needed on its specificity for predicting future arrhythmic events in asymptomatic individuals before recommendations are made for extensive evaluation in this group.     

Risk stratification of individuals with the Brugada electrocardiogram: a meta-analysis

OBJECTIVES: We performed a meta-analysis of prognostic studies of patients with a Brugada ECG to assess predictors of events. BACKGROUND: The Brugada syndrome is an increasingly recognized cause of idiopathic ventricular fibrillation; however, there is wide variation in the prognosis of patients with the Brugada ECG. METHODS AND RESULTS: We retrieved 30 prospective studies of patients with the Brugada ECG, accumulating data on 1,545 patients. Summary estimates of the relative risk (RR) of events (sudden cardiac death [SCD], syncope, or internal defibrillator shock) for a variety of potential predictors were made using a random-effects model. The overall event rate at an average of 32 months follow-up was 10.0% (95% CI 8.5%, 11.5%). The RR of an event was increased (P < 0.001) among patients with a history of syncope or SCD (RR 3.24 [95% CI 2.13, 4.93]), men compared with women (RR 3.47 [95% CI 1.58, 7.63]), and patients with a spontaneous compared with sodium-channel blocker induced Type I Brugada ECG (RR 4.65 [95% CI 2.25, 9.58]). The RR of events was not significantly increased in patients with a family history of SCD (P = 0.97) or a mutation of the SCN5A gene (P = 0.18). The RR of events was also not significantly increased in patients inducible compared with noninducible by electrophysiologic study (EPS) (RR 1.88 [95% CI 0.62, 5.73], P = 0.27); however, there was significant heterogeneity of the studies included. CONCLUSIONS: Our findings suggest that a history of syncope or SCD, the presence of a spontaneous Type I Brugada ECG, and male gender predict a more malignant natural history. Our findings do not support the use of a family history of SCD, the presence of an SCN5A gene mutation, or EPS to guide the management of patients with a Brugada ECG.     

Differences in 12-lead electrocardiogram between symptomatic and asymptomatic Brugada syndrome patients

Introduction: Brugada syndrome (BrS) is an inherited disorder that predisposes some subjects to sudden cardiac death (SCD). It is not well established which BrS patients are at risk of severe arrhythmias. Our aim was to study whether standard 12-lead electrocardiogram (ECG) would give useful information for this purpose.
Methods: This study included 200 BrS probands (142 male, 62%; mean age 42 ± 16 years). Symptoms related to BrS were defined as syncope, documented ventricular tachyarrhythmia, or SCD. We determined PR, QRS, QTc, T_peak, and T_end interval from leads II and V₂ and QRS from lead V₅, R'/S ratio from lead aVR (aVR sign), QRS axis, and J-point elevation amplitude from right precordial leads from the baseline ECGs.
Results: Sixty-six subjects (33%) had experienced symptoms related to BrS. The only significant difference between the symptomatic and asymptomatic BrS subjects was the QRS duration measured from lead II or lead V₂, for example, the mean QRS in V₂ was 115 ± 26 ms in symptomatic versus 104 ± 19 ms in asymptomatic patients (P < 0.001). The optimized cut-off point of V₂ QRS ≥120 ms gave an odds ratio (OR) of 2.5 (95% CI: 1.4–4.6, P = 0.003) for being symptomatic. In a multivariate analysis adjusted with gender, age, and SCN5A mutation, the OR was 2.6 (95% CI: 1.4–4.8, P = 0.004).
Conclusion: Prolonged QRS duration, measured from standard 12-lead ECG, is associated with symptoms and could serve as a simple noninvasive risk marker of vulnerability to life-threatening ventricular arrhythmias in BrS.     

Identification of electrocardiographic risk markers for the initial and recurrent episodes of ventricular fibrillation in patients with Brugada syndrome

1 Introduction

New onset of ventricular fibrillation (VF) in asymptomatic patients with Brugada‐type ECG is not frequent, but it cannot be negligible. Risk markers for predicting VF are usually based on results of analysis in symptomatic patients, and they have not been determined for asymptomatic patients. We analyzed ECG markers in patients with Brugada syndrome to differentiate the risk factors for VF in both symptomatic and asymptomatic patients.

2 Methods

The subjects were 471 patients with Brugada syndrome and we divided the subjects into two groups: Asymptomatic group (n = 326) and Symptomatic group (syncope: n = 122, VF: n = 23). We analyzed the following ECG markers: RR, PQ, QRS, QT and Tpeak‐Tend (Tpe) intervals, ST level, atrial fibrillation (AF), atrioventricular block, spontaneous type 1 ECG, early repolarization (ER) and fragmented QRS (fQRS).

3 Results

During follow‐up (91 ± 64 months), 41 patients experienced VF (Asymptomatic: n = 10, Symptomatic: n = 31). Univariable analysis showed that spontaneous type 1 ECG, Tpe interval (≥95 milliseconds), high ST level (≥0.52 mV) and fQRS were common predictors for VF in both the Asymptomatic and Symptomatic groups. In addition to the common risk factors, wide QRS (≥107 milliseconds), long QT interval (≥420 milliseconds), ER and AF were predictors for VF in Symptomatic group. Multivariable analysis of the Symptomatic group showed fQRS, Tpe and ER were independent predictors of prognosis.

4 Conclusions

fQRS and Tpe interval are common risk factors for VF in both asymptomatic and symptomatic patients, whereas ER is a predictor for recurrent VF.     

Low prevalence of Brugada-type electrocardiogram in a prospective large cohort of Egyptians

BackgroundBrugada syndrome is a cardiac channelopathy that is associated with a high risk of VF and SCD and characterized by ECG pattern of transient or persistent, coved type ST-segment elevation in leads V₁–V₃.AimTo prospectively determine the prevalence of Brugada-type ECG pattern (Brugada sign) among unselected non cardiac individuals served at Cairo university teaching-hospital.MethodsThis study was conducted from October 2011 to September 2012, and included 4000 unselected noncardiac individuals (2078 males 52%, mean age 39 ± 14.44 years) admitted or presented to our hospital for different reasons. A 12-lead ECG was recorded for each of them; these ECGs were reviewed independently by two electrophysiologists for criteria of the three types of Brugada ECG pattern, and diagnosis of Brugada sign was made when both investigators agreed on the classification of the ECG findings according to the criteria of the Consensus Report of the Study Group of the Molecular Basis of Arrhythmia of the European Society of Cardiology.ResultsTwenty-two (0.55%) subjects had Brugada ECG pattern. All of them were of Mediterranean ethnic group. 18 males (0.45%), and 4 females (0.1%). No subjects showed type-1, while 11 (0.275%) of the 22 subjects had type-2, and the other 11 had type-3 Brugada ECG pattern. Eight cases (0.2%) among the 22 subjects were between 10 and 24 years old. Of the 22 subjects, 4 cases (18.2%) were symptomatic (palpitation and syncope), and 3 cases (13%) had positive F.H of SCD.ConclusionThe frequency of type-1 Brugada-type ECG pattern was 0%, while type-2 and type-3 (saddleback type) was 0.55% among Egyptian hospital-based population, and it was more prevalent in middle-aged males.     

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     

Baseline fragmented QRS increases the risk of major arrhythmic events in Brugada syndrome: Systematic review and meta‐analysis

Background

Fragmented QRS reflects disturbances in the myocardium predisposing the heart to ventricular tachyarrhythmias. Recent studies suggest that fragmented QRS (fQRS) is associated with major arrhythmic events in Brugada syndrome. However, a systematic review and meta‐analysis of the literature has not been done. We assessed the association between fQRS and major arrhythmic events in Brugada syndrome by a systematic review of the literature and a meta‐analysis.

Methods

We comprehensively searched the databases of MEDLINE and EMBASE from inception to May 2017. Included studies were published prospective or retrospective cohort studies that compared major arrhythmic events (ventricular fibrillation, sustained ventricular tachycardia, sudden cardiac arrest, or sudden cardiac death) in Brugada syndrome with fQRS versus normal QRS. Data from each study were combined using the random‐effects, generic inverse variance method of DerSimonian and Laird to calculate risk ratios and 95% confidence intervals.

Results

Nine studies from January 2012 to May 2017 were included in this meta‐analysis involving 2,360 subjects with Brugada syndrome (550 fQRS and 1,810 non‐fQRS). Fragmented QRS was associated with major arrhythmic events (pooled risk ratio =3.36, 95% confidence interval: 2.09‐5.38, p < .001, I² = 50.9%) as well as fatal arrhythmia (pooled risk ratio =3.09, 95% confidence interval: 1.40‐6.86, p = .005, I² = 69.7%).

Conclusions

Baseline fQRS increased major arrhythmic events up to 3‐fold. Our study suggests that fQRS could be an important tool for risk assessment in patients with Brugada syndrome.

     

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.     

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.     

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。     

Role of programmed ventricular stimulation in patients with Brugada syndrome: a meta-analysis of worldwide published data.

AIMS: Brugada syndrome (BS) is an ion channelopathy with the risk of sudden cardiac death. The role of programmed ventricular stimulation (PVS) in risk stratification has been controversially discussed. Therefore, we performed a meta-analysis on the prognostic role of PVS in BS. METHODS AND RESULTS: A Medline search until July 2006 documented 822 entries for BS. Only English publications with > 10 patients and a follow-up period were considered (n = 15). Patients [n = 1217; 974 males (80%)] were divided into three groups: survived sudden cardiac arrest (SCA) [n = 222 (18%)], syncope (Syncope) [n = 275 (23%)], and asymptomatic patients (Asympt) [n = 720 (59%)]. PVS was conducted in 1036 patients (85%). In 548 patients (53%), sustained ventricular tachyarrhythmias (VT) or ventricular fibrillation (VF) was inducible. During follow-up (34 +/- 40 months), VT/VF occurred in 141 patients. SCA bore the highest chance for a VT/VF occurrence during follow-up [odds ratio (OR) 14.4 compared with asymptomatic patients; P < 0.0005]. However, except for one study, the OR for VT/VF during follow-up in relation to VT/VF inducibility was non-significant (OR 1.5; P = ns). CONCLUSION: The main finding is that we were unable to identify a significant role of PVS with regard to arrhythmic events during follow-up in BS, thus questioning the role of PVS for risk stratification in patients with BS. Patients with BS and survived SCA show the highest chance for VT/VF occurrence during follow-up.     

Risk stratification of sudden cardiac death in asymptomatic female Brugada syndrome patients: A literature review

Background and Objectives

Risk stratification in Brugada syndrome remains a difficult problem. Given the male predominance of this disease and their elevated risks of arrhythmic events, affected females have received less attention. It is widely known that symptomatic patients are at increased risk of sudden cardiac death (SCD) than asymptomatic patients, while this might be true in the male population; recent studies have shown that this association might not be significant in females. Over the past few decades, numerous markers involving clinical symptoms, electrocardiographic (ECG) indices, and genetic tests have been explored, with several risk-scoring models developed so far. The objective of this study is to review the current evidence of clinical and ECG markers as well as risk scores on asymptomatic females with Brugada syndrome.

Findings

Gender differences in ECG markers, the yield of genetic findings, and the applicability of risk scores are highlighted.

Conclusions

Various clinical, electrocardiographic, and genetic risk factors are available for assessing SCD risk amongst asymptomatic female BrS patients. However, due to the significant gender discrepancy in BrS, the SCD risk amongst females is often underestimated, and there is a lack of research on female-specific risk factors and multiparametric risk scores. Therefore, multinational studies pooling female BrS patients are needed for the development of a gender-specific risk stratification approach amongst asymptomatic BrS patients.     

Long-term follow-up in patients with presumptive Brugada syndrome treated with implanted defibrillators

Long‐Term Follow‐Up in Patients with Brugada Syndrome. Introduction: Risk stratification for patients with suspected Brugada syndrome (BS) remains difficult. Implantation of cardioverter‐defibrillators (ICDs) in high‐risk patients provides continuous long‐term arrhythmia protection . Methods: Data of 33 consecutive patients undergoing ICD implantation after BS evaluation between 1995 and 2008 were reviewed. Results: There were 30 (91%) men and 3 (9%) women (46.4 ± 11.7 years). Type I Brugada was noted in 18 (54.5%), type II in 12 (36.4%) patients, and ST elevation after drug challenge in 3 patients (9.1%). Three patients had prior cardiac arrest; 70% a history of syncope; and 56% ventricular arrhythmias at the electrophysiology study. During 7.9 ± 3.6 years of follow‐up, 2 patients with prior arrest received appropriate ICD shocks. None of the 30 patients without prior arrest had a sustained arrhythmia detected. ICD‐related adverse effects occurred in 11 (33%) patients, including inappropriate shocks in 5 (15%). Eight patients (24%) developed 11 major device‐related complications including subclavian vein thrombosis (1), pericardial effusion (1), lead fracture (2), and infection (2); in 4 patients the only complication was premature battery depletion that required early ICD replacement; however, some of these complications such as lead fractures and early battery depletion may not be specific for this patient cohort and may not repeat in the future. Conclusion: Risk stratification for patients with BS for primary prevention remains challenging. The low risk of arrhythmic events that is exceeded by ICD‐related adverse effects should inform discussions with patients who do not have a prior history of cardiac arrest . (J Cardiovasc Electrophysiol, Vol. 22, pp. 1115‐1119, October 2011)