Brugada ECG Pattern Research Articles

Clinical approach to the patient with Brugada Syndrome: risk stratification and optimal management.

The Brugada Syndrome (BrS) is an inherited cardiac ion channel disorder associated with increased risk of ventricular arrhythmias and mortality. Diagnosis is based on a characteristic electrocardiographic (ECG) pattern of coved type ST-segment elevation >2 mm followed by a negative T-wave in ≥1 of the right precordial leads V1 to V3. Since the first description of BrS, the definition of disease and underlying pathophysiological mechanisms have been significantly improved in recent years. Also, significant progress has been made in the field of genetic testing in these patients. Still, there are several open questions regarding the management and outcome of these patients. There is more information about patients who would need an implantable cardiac defibrillator for the primary prevention of sudden cardiac death (that is, those with spontaneous Type I Brugada ECG pattern and arrhythmia-related syncope), but currently published data concerning asymptomatic patients with Brugada ECG pattern and other less-well defined presentations are conflicting. Whereas the role of cardiac defibrillator in patients with Brugada Syndrome is clear, optimal use of catheter ablation and antiarrhythmic drug therapy needs to be further investigated. In this review, we summarize current evidence and contemporary management of patients with BrS.

Link between Brugada phenocopy and myocardial ischemia: Results from the International Registry on Brugada Phenocopy.

Brugada phenocopies clinical entities that have indistinguishable electrocardiographic (ECG) patterns from true congenital Brugada syndrome. However, they are induced by other clinical circumstances such as myocardial ischemia. The purpose of our study was to examine the clinical features and pathogenesis of ischemia-induced Brugada phenocopy (BrP). Data from 17 cases of ischemia-induced BrP were collected from the International Registry (www.brugadaphenocopy.com). Data were extracted from these publications and authors were contacted to provide further insight into each case. Of the patients included in this study, 71% were male. Mean age was 59 ± 11 years (range: 38-76). Type-1 Brugada ECG pattern occurred in 15/17 (88%) of the cases, while a type-2 Brugada ECG pattern was observed in the other 2/17 (12%). In all cases, the Brugada ECG pattern resolved upon correction of the ischemia, indicating ischemia as the inducing circumstance. No arrhythmic events have been detected acutely or during the follow-up. Reported time to resolution ranged from 2 minutes to 5hours. Provocative challenges using sodium channel blocking agents were performed in 7/17 cases (41%), and all failed to induce a Brugada ECG pattern (BrP Class A). The remaining 10/17 cases (59%) did not undergo provocative testing due to various clinical reasons. Myocardial ischemia is a commonly reported etiology of BrP. Importantly, this study found no association between BrP induced by myocardial ischemia and sudden cardiac death or malignant ventricular arrhythmias.

A novel prediction model for risk stratification in patients with a type 1 Brugada ECG pattern

BackgroundRisk stratification in Brugada syndrome remains a controversial and unresolved clinical problem, especially in asymptomatic patients with a type 1 ECG pattern. The purpose of this study is to derive and validate a prediction model based on clinical and ECG parameters to effectively identify patients with a type 1 ECG pattern who are at high risk of major arrhythmic events (MAE) during follow-up. MethodsThis study analysed data from 103 consecutive patients with Brugada Type 1 ECG pattern and no history of previous cardiac arrest. The prediction model was derived using logistic regression with MAE as the primary outcome, and patient demographic and electrocardiographic parameters as potential predictor variables. The model was externally validated in an independent cohort of 42 patients. ResultsThe final model (Brugada Risk Stratification [BRS] score) consisted of 4 independent predictors (1 point each) of MAE during follow-up (median 85.3 months): spontaneous type 1 pattern, QRS fragments in inferior leads≥3,S wave upslope duration ratio ≥ 0.8, and T peak – T end ≥ 100 ms. The BRS score (AUC = 0.95,95% CI 0.0.92–0.98) stratifies patients with a type 1 ECG pattern into low (BRS score ≤ 2) and high (BRS score ≥ 3) risk classes, with a class specific risk of MAE of 0–1.1% and 92.3–100% across the derivation and validation cohorts, respectively. ConclusionsThe BRS score is a simple bed-side tool with high predictive accuracy, for risk stratification of patients with a Brugada Type 1 ECG pattern. Prospective validation of the prediction model is necessary before this score can be implemented in clinical practice.

Syncope in a patient with acute pulmonary embolism and Brugada Type-2 ECG pattern: Brugada phenocopy or Brugada syndrome?

Brugada phenocopies are clinical entities characterized by electrocardiographic patterns that are identical to true Brugada syndrome, but are elicited by a number of clinical circumstances. ECG normalizes upon resolution of underlying condition, family history of arrhythmic syncope or ventricular arrhythmias is strictly absent and provocative tests with sodium channel blockers have to be negative. We describe herein the case of type-2 ECG Brugada pattern in a patient with acute pulmonary embolism presenting with recurrent syncope but negative provocative test with sodium channel blockers. Transthoracic echocardiography and transcranial Doppler did not show atrial septal defect. In conclusion, to the best of our knowledge no other cases excluded atrial septal defect and paradoxical embolism as a possible cause of acute pulmonary embolism related Type-2 Brugada ECG pattern. Therefore in our case right ventricle transmural myocardial ischemia due to acute pulmonary embolism, mainly secondary to right ventricle stretch, could explain Brugada ECG pattern.

BRUGADA PATTERN: AN UNUSUAL PRESENTATION OF TRICYCLIC ANTIDEPRESSANT OVERDOSE

Brugada electrocardiographic pattern (BEP) can be found in conditions other than Brugada syndrome (BrS). Precise history is relevant to determine etiology and treatment. A 34-year-old woman was found convulsing at home. Upon arrival, she had a cardiac arrest with monomorphic VT (Panel A). Direct

BRUGADA SYNDROME: DEATH REVEALS ITS PERPETRATOR

Brugada syndrome is an inherited channelopathy that conveys an increased risk of sudden cardiac death (SCD). Baseline ECG may be normal, confounding the diagnosis. Provoking factors may be required to unmask the Brugada ECG pattern. A 50 year old woman with HTN and HLD presented with fever and

Clinical Characteristics and Electrophysiological Mechanisms Underlying Brugada ECG in Patients With Severe Hyperkalemia.

BackgroundSeveral metabolic conditions can cause the Brugada ECG pattern, also called Brugada phenotype (BrPh). We aimed to define the clinical characteristics and outcome of BrPh patients and elucidate the mechanisms underlying BrPh attributed to hyperkalemia.Methods and ResultsWe prospectively identified patients hospitalized with severe hyperkalemia and ECG diagnosis of BrPh and compared their clinical characteristics and outcome with patients with hyperkalemia but no BrPh ECG. Computer simulations investigated the roles of extracellular potassium increase, fibrosis at the right ventricular outflow tract, and epicardial/endocardial gradients in transient outward current. Over a 6‐year period, 15 patients presented severe hyperkalemia with BrPh ECG that was transient and disappeared after normalization of their serum potassium. Most patients were admitted because of various severe medical conditions causing hyperkalemia. Six (40%) patients presented malignant arrhythmias and 6 died during admission. Multiple logistic regression analysis revealed that higher serum potassium levels (odds ratio, 15.8; 95% CI, 3.1–79; P=0.001) and male sex (odds ratio, 17; 95% CI, 1.05–286; P=0.045) were risk factors for developing BrPh ECG in patients with severe hyperkalemia. In simulations, hyperkalemia yielded BrPh by promoting delayed and heterogeneous right ventricular outflow tract activation attributed to elevation of resting potential, reduced availability of inward sodium channel conductance, and increased right ventricular outflow tract fibrosis. An elevated transient outward current gradient contributed to, but was not essential for, the BrPh phenotype.ConclusionsIn patients with severe hyperkalemia, a BrPh ECG is associated with malignant arrhythmias and all‐cause mortality secondary to resting potential depolarization, reduced sodium current availability, and fibrosis at the right ventricular outflow tract.

Relation of the Brugada Phenocopy to Hyperkalemia (From the International Registry on Brugada Phenocopy)

Brugada phenocopies (BrPs) are clinical entities that differ in etiology from true congenital Brugada syndrome but have identical electrocardiographic (ECG) patterns. Hyperkalemia is known to be one of the causes of BrP. The aim of this study was to determine the clinical characteristics and evolution of hyperkalemia-induced BrP. Data from 27 cases of hyperkalemia-induced BrP were collected from the International Registry at www.brugadaphenocopy.com . Data were extracted from publications. Of the 27 patients included in the analysis, 18 (67%) were male; mean age was 53 ± 15 years (range 31 to 89). Mean serum potassium concentration was 7.45 ± 0.89 mmol/L. Type-1 Brugada ECG pattern was observed in 21 cases (78%), whereas 6 cases (22%) showed a type-2 Brugada ECG pattern. The Brugada ECG pattern resolved once the hyperkalemia was corrected, with no arrhythmic events. Estimated time to resolution was 7 ± 3 hours. In 4 cases (16%), a concurrent metabolic abnormality was detected: 3 (11%) presented with acidosis, 2 (7%) with hyponatremia, 1 (4%) with hypocalcaemia, 1 (4%) with hyperphosphatemia, and 1 (4%) with hyperglycemia. In 7 cases (26%), provocative testing using sodium channel blockers was performed, and all failed to reproduce a BrS ECG pattern (BrP class A). Additionally, no sudden cardiac death or malignant ventricular arrhythmias were detected. Hyperkalemia was found a common cause of BrP in our International Registry. The Brugada ECG pattern appears to occur at high serum potassium concentrations (>6.5 mmol/L). The ECG normalizes within hours of correcting the electrolyte imbalance. Importantly, hyperkalemia-induced BrP has not been associated with sudden cardiac death or ventricular arrhythmia.

Cardiac events occurred commonly among apparently healthy Filipinos with the Brugada ECG pattern in the LIFECARE cohort

BackgroundBrugada syndrome is the mechanism for sudden unexplained death. The Brugada ECG pattern is found in 2% of Filipinos. There is a knowledge gap on the clinical outcome of these...

Risk Stratification in Brugada Syndrome: Current Status and Emerging Approaches.

Brugada syndrome (BrS) is one of the most common inherited channelopathies associated with an increased risk of sudden cardiac death. Appropriate use of an ICD in high-risk patients is life-saving. However, there remains a lack of consensus on risk stratification, and even on the diagnosis of BrS itself. Some argue that people with a type 1 Brugada ECG pattern but no symptoms should not be diagnosed with BrS, and guidelines recommend observation without therapy in these patients. Others argue that the presence of a spontaneous (rather than drug-induced) type 1 ECG pattern alone is enough to label them as high-risk for arrhythmic events, particularly if syncope is also present. Syncope and a spontaneous type 1 ECG pattern are the only factors that have consistently been shown to predict ventricular arrhythmic events and sudden cardiac death. Other markers have yielded conflicting data. However, in combination they may have roles in risk scoring models. Epicardial catheter ablation in the right ventricular outflow tract has shown promise in studies as an alternative management option to an ICD, but longer follow-up is required to ensure that the ablation effect is permanent.

Relation of the Brugada Phenocopy to Hyperkalemia (from the International Registry on Brugada Phenocopy)

Brugada phenocopies (BrPs) are clinical entities that differ in etiology from true congenital Brugada syndrome but have identical electrocardiographic (ECG) patterns. Hyperkalemia is known to be one of the causes of BrP. The aim of this study was to determine the clinical characteristics and evolution of hyperkalemia-induced BrP. Data from 27 cases of hyperkalemia-induced BrP were collected from the International Registry at www.brugadaphenocopy.com. Data were extracted from publications. Of the 27 patients included in the analysis, 18 (67%) were male; mean age was 53 ± 15 years (range 31 to 89). Mean serum potassium concentration was 7.45 ± 0.89 mmol/L. Type-1 Brugada ECG pattern was observed in 21 cases (78%), whereas 6 cases (22%) showed a type-2 Brugada ECG pattern. The Brugada ECG pattern resolved once the hyperkalemia was corrected, with no arrhythmic events. Estimated time to resolution was 7 ± 3 hours. In 4 cases (16%), a concurrent metabolic abnormality was detected: 3 (11%) presented with acidosis, 2 (7%) with hyponatremia, 1 (4%) with hypocalcaemia, 1 (4%) with hyperphosphatemia, and 1 (4%) with hyperglycemia. In 7 cases (26%), provocative testing using sodium channel blockers was performed, and all failed to reproduce a BrS ECG pattern (BrP class A). Additionally, no sudden cardiac death or malignant ventricular arrhythmias were detected. Hyperkalemia was found a common cause of BrP in our International Registry. The Brugada ECG pattern appears to occur at high serum potassium concentrations (>6.5 mmol/L). The ECG normalizes within hours of correcting the electrolyte imbalance. Importantly, hyperkalemia-induced BrP has not been associated with sudden cardiac death or ventricular arrhythmia.

Prevalence of spontaneous Brugada ECG pattern recorded at standard intercostal leads: A meta-analysis

ObjectiveTypical Brugada ECG pattern is the keystone in the diagnosis of Brugada syndrome. However, the exact prevalence remains unclear, especially in Asia. The present study was designed to systematically evaluate the prevalence of spontaneous Brugada ECG pattern recorded at standard leads. MethodsWe searched the Medline, Embase and Chinese National Knowledge Infrastructure (CNKI) for studies of the prevalence of Brugada ECG pattern, published between Jan 1, 2003, and September 1, 2016. Pooled prevalence of type 1 and type 2-3 Brugada ECG pattern were estimated in a random-effects model, and group prevalence data by the characteristic of studies. Meta-regression analyses were performed to explore the potential sources of heterogeneity, and sensitivity analyses were conducted to assess the effect of each study on the overall prevalence. ResultsThirty-nine eligible studies involving 558,689 subjects were identified. Pooled prevalence of type 1 and 2-3 Brugada ECG pattern was 0.03% (95%CI, 0.01%–0.06%), and 0.42% (95%CI, 0.28%–0.59%), respectively. Regions, sample size, year of publication were the main source of heterogeneity. The prevalence of type 1 Brugada ECG pattern was higher in male, Asia, adult, patient, and fever subjects; but the relation between fever and type 2-3 Brugada ECG pattern was not significant. Sensitivity analysis showed that each study did not lonely affect the prevalence of type 1 and type 2-3 Brugada ECG pattern. ConclusionBrugada ECG pattern is not rare, especially preponderant in adult Asian males, and fever subjects. Clinical screening and further examination of Brugada syndrome in potential population need to be highlighted.

Abstract 21344: Mutations in CACNA1C and KCNE2 Genes are Associated With Brugada Syndrome and Epilepsy

Introduction: Cardiac arrhythmias are generally associated with abnormal mutations in ion channel genes. Epilepsy is a disorder of neuronal function, which also involves abnormal channel function. Our Hypothesis: now increasing by demonstration that the etiologies of Brugada syndrome (BrS) and epilepsy may partly overlap. However, only a few genetic studies have addressed a possible link between cardiac and neural channelopathies. Methods: The suspected case and family were underwent thorough medical examination. Fifteen candidate genes were screened for ion channels by direct sequencing. Ion channel variants were cloned by site-directed mutagenesis and studied using patch clamp and confocal microscopy techniques in TSA201 cells. Results: A 36 y/o male with epilepsy showing typical type 1 Brugada pattern ECG during flecainide challenge test and under antiepileptic medication (valproic acid). Cardiac evaluation included a normal echocardiogram and exercise stress test. We identified two mutations (D2130N and A1717G) in CACNA1C and one in KCNE2 (T10M). All mutations are highly conserved. The variants in CACNA1C were located in C terminal and the one in KCNE2 was in N terminal. Functional studies in CACNA1C mutants were co-expressed with CACNB2b and CACNA2D1 . At 0 mV, peak ICa densities were reduced by 85% and 70% in D2130N and A1717G vs. WT respectively. Significant kinetic alterations included a negative shift in V1/2 of inactivation, and positive shift in V1/2 of activation, for D2130N and A1717G, respectively. Confocal study showed D2130N and A1717G conjugated to YFP trafficked normally to the cell membrane. We found a gain-of-function in Ito current when T10M- KCNE2 was co-expressed with KCND3 channels by 55% relative to WT. Conclusion: Our results suggest for the first time that several mutations in CACNA1C leads to a loss of function in ICa and thus can contribute to the development of BrS phenotype. T10M- KCNE2 produces a gain of function in Ito, which further aggravates BrS. Meanwhile, as previously reported, T10M- KCNE2 also produces a loss-of-function of IKr, so it is reasonable to deduce that the mutation is probably responsible for the epilepsy. It once again provides the evidence that anti-epilepsy drug could unmask potential Brugada ECG.

An unusual presentation of asymptomatic Type 2 Brugada pattern

Patients with asymptomatic Type 2 Brugada ECG patterns are not often associated with the sinister cardiac presentations that are more often related to the Type 1 Brugada pattern. The use of implantable cardiac defibrillators (ICDs) are not recommended in this patient group.We present the case of a 56year old male whom was brought following a witnessed out of hospital cardiac arrest. His background included a drug-induced type 1 Brugada pattern following a flecanide challenge. He has been asymptomatic until this event. In the absence of other causes for a cardiac arrest, he received an implantable cardiac defibrillator.This case highlights an uncommon presentation of a patient with a Drug Induced Type 1 Brugada pattern. These situations pose challenges to clinicians in surveillance of patients, and highlights the need for further research into predictive markers for sudden cardiac death.

Ten questions on Brugada syndrome

Brugada syndrome is a possible cause of sudden cardiac death in subjects with characteristic ECG pattern (type 1 Brugada ECG pattern). Brugada ECG pattern is not infrequent in the general population and the challenge is to identify within a large population those patients who are really at risk. Unfortunately, this is a partially unresolved problem and this uncertainty determines an inhomogeneous behavior among doctors. Some of them overestimate the risk extensively indicating cardioverter-defibrillator implantation, others apply restrictive indications of guidelines, many are not able to decide without doubts.In this paper we will try to clarify some doubts, to give some certain points, and to draw some perspectives for the future.

Yellow phosphorus-induced Brugada phenocopy

BackgroundMetallic phosphides (of aluminum and phosphide) and yellow phosphorus are commonly used rodenticide compounds in developing countries. Toxicity of yellow phosphorus mostly pertains to the liver, kidney, heart, pancreas and the brain. Cardiotoxicity with associated Brugada ECG pattern has been reported only in poisoning with metallic phosphides. Methods and resultsBrugada phenocopy and hepatic dysfunction were observed in a 29-year-old male following yellow phosphorus consumption. He had both type 1 (day1) and type 2 (day2) Brugada patterns in the electrocardiogram, which resolved spontaneously by the third day without hemodynamic compromise. ConclusionToxins such as aluminum and zinc phosphide have been reported to induce Brugada ECG patterns due to the generation of phosphine. We report the first case of yellow phosphorus-related Brugada phenocopy, without hemodynamic compromise or malignant arrhythmia.

Comparisons of clinical impacts on individuals with Brugada electrocardiographic patterns defined by ISHNE criteria or EHRA/HRS/APHRS criteria: a nationwide community-based study

Introduction: Identifying Brugada electrocardiographic pattern (BrP) early is crucial to prevent sudden cardiac death. Two different diagnostic criteria proposed by International Society for Holter and Noninvasive Electrocardiography (ISHNE) and Heart Rhythm Society/European Heart Rhythm Association/Asia-Pacific Heart Rhythm Society (HRS/EHRA/APHRS) were widely used in clinical practice. The difference in prevalence and prognosis of BrP by applying the two different criteria was never studied before.Methods: This study was prospectively conducted in a nationwide large-scale stratified random sampling community-based cohort (HALST) from Han Chinese population in Taiwan from December 2008 to December 2012. We compared the prevalence and prognosis of BrP defined by the two diagnostic criteria.Results: A total of 5214 adults were enrolled (2530 men) with mean age of 69.3 years. Four had spontaneous type 1 BrP (0.077%). By the HRS/EHRA/APHRS criteria, 68 individuals have type 2 BrP (1.30%) and 101 have type 3 BrP (1.94%) whereas by the ISHNE criteria, 46 individuals exhibited type 2 BrP (0.88%). When applying the ISHNE criteria, the number of individuals with BrP decreased by 71%. However, all-cause mortality and cardiovascular mortality were not different between individuals with or without BrP, irrespective of the criteria used.Conclusions: The two different criteria may impact the diagnostic yield of individuals with BrP, but do not affect the prognosis of the individuals with BrP.Key messagesComparing with the use of HRS/EHRA/APHRS criteria, the number of individuals with Brugada ECG patterns was decreased by 71% when applying the ISHNE criteria.The prognosis of individuals with Brugada ECG patterns defined by 2012 ISHNE or 2013 HRS/EHRA/APHRS criteria were not different.

Brugada phenocopy during right coronary artery dissection

Case presentationA 68-year-old female presented with non-ST-segment elevation myocardial infarction, and urgency coronary angiography was performed. The procedure was complicated with right coronary artery dissection leading to type-1 Brugada ECG pattern. DiscussionBrugada phenocopies (BrP) are clinical entities that present with electrocardiograms identical to those found in Brugada Syndrome (BrS) but are the result of different medical conditions. This report provides evidence that atypical causes of myocardial ischemia may induce BrP. Appropriate electrocardiogram and clinical differentiation of Brugada phenocopy from true Brugada syndrome may prevent unnecessary treatments. Although patients with true high-risk BrS are candidates for ICD therapy, the natural history of BrP remains unknown and seems to be more benign, depending on the severity of the underlying condition.

Late gadolinium enhancement in Brugada syndrome: A marker for subtle underlying cardiomyopathy?

There is increasing evidence that the Brugada ECG pattern is a marker of subtle structural heart disease. The purpose of this study was to characterize patients with Brugada syndrome (BrS) using cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). BrS was diagnosed according to international guidelines. Twenty-six percent of patients with BrS carried SCN5A mutations. CMR data from 78 patients with BrS were compared with 78 healthy controls (44 ± 15 vs 42 ± 14 years; P = .434; and 64% vs 64% male; P = 1). Right ventricular (RV) ejection fraction was slightly lower (61 ± 8% vs 64 ± 5%; P = .004) and RV end-systolic volume slightly greater (31 ± 10 mL/m2 vs 28 ± 6 mL/m2; P = .038) in BrS compared with controls. These values remained within the normal range. LGE was demonstrated in 8% of patients with BrS (left ventricular midwall LGE in 5%) but not in controls (P = .028). In patients with BrS with midwall LGE there were no other features of cardiomyopathy at the time of CMR, but genetic testing and follow-up revealed a desmoplakin mutation in 1 patient and evolution of T-wave inversion throughout all precordial ECG leads in another. Neither patient fulfils diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy. Some patients with BrS have left ventricular midwall LGE consistent with an underlying cardiomyopathic process. Even cases without LGE show greater RV volumes and reduced RV function. These findings lend further support to the presence of subtle structural abnormalities in BrS. The BrS pattern with LGE may serve as early markers for evolution of a cardiomyopathic phenotype over time. CMR is a potentially useful adjunct investigation in the clinical evaluation of BrS.

A meta-analytic review of prevalence for Brugada ECG patterns and the risk for death.

Background:The prevalence of Brugada ECG pattern (BrEP) is different in different regions, and its mean prevalence over the world is unknown. The risk of people with BrEP for death remains unknown. We performed a meta-analysis to determine the prevalence of BrEP and risk ratio (RR) for death.Methods:Relevant studies published between July 1, 2000 and August 20, 2016, which contain prevalence and RR for all-cause death and cardiac death, were included. The prevalence and RR are analyzed using meta-analysis.Results:We finally retrieved 24 studies of the prevalence for BrEP and 5 studies of the RR for all-cause death and cardiac death. The worldwide mean prevalence of BrEP is 0.4%, with highest in Asia (0.9%) and lowest in North America (0.2%). Additionally, the mean prevalence in male is 0.9%, whereas it is 0.1% in female. The RR of BrEP for all-cause death is 0.78 (95% confidence interval 0.45–1.37), and for cardiac death it is 0.92 (95% confidence interval 0.23–3.66).Conclusion:The prevalence of BrEP is about 0.4% around the world with different prevalence in region and sex. Our study shows that BrEP may not be taken as a predictor of all-cause death and cardiac death.