Methods for Improving the Diagnosis of a Brugada ECG Pattern

Brugada syndrome (BrS) is an inherited channelopathy that predisposes individuals to malignant arrhythmias and can lead to sudden cardiac death. The condition is characterized by two electrocardiography (ECG) patterns: the type‐1 or “coved” ECG and the type‐2 or “saddleback” ECG. Although the type‐1 Brugada ECG pattern is diagnostic for the condition, the type‐2 Brugada ECG pattern requires differential diagnosis from conditions that produce a similar morphology. In this article, we present a case that is suspicious but not diagnostic for BrS and discuss the application of ECG methodologies for increasing or decreasing suspicion for a diagnosis of BrS.     

Brugada Phenocopy in Concomitant Ethanol and Heroin Overdose

Brugada phenocopy describes conditions with Brugada‐like ECG pattern but without true congenital Brugada syndrome. We report a case of 44‐year‐old man with no known medical history who presented with loss of consciousness. Toxicology screening was positive for opiates and high serum alcohol level. His initial ECG showed Brugada type 1 pattern which resolved after several hours of observation and treatment with continuous naloxone infusion. Patient regained his consciousness and disclosed heroin abuse and drinking alcohol. This case highlights the heroin overdose as a possible cause of Brugada phenocopy.     

Brugada phenocopy secondary to extensive inferior wall ischemia induced by coronary steal effect

The diagnosis of Brugada syndrome is usually made with a typical ECG pattern. However, different disorders can emulate this pattern (Brugada phenocopies). Pathophysiologic mechanisms underlying this phenomenon remain controversial. We describe the development of type‐1 Brugada ECG pattern associated with extensive coronary steal effect during myocardial perfusion scintigraphy. Proximal occlusion of the right coronary artery and severe proximal stenosis in distally occluded left circumflex artery were confirmed by coronary angiogram. Brugada ECG pattern can be a reversible sign associated with inferior left ventricular and right ventricular ischemia. Its presence during acute ischemia deserves appropriate risk stratification.     

Relationship Between ST‐Segment Morphology and Conduction Disturbances Detected by Signal‐Averaged Electrocardiography in Brugada Syndrome

Background: Although arrhythmogenesis of Brugada syndrome is still unknown, it has been reported to be associated with conduction disturbances. Two ST‐segment morphologies (coved and saddle‐back patterns) have been described in this syndrome. No study has sought to determine which morphology has stronger conduction disturbances, thereby associating with life‐threatening events. Methods: Forty‐six patients who presented the Brugada‐type ECG with either of a characteristic coved (n = 25) or saddle‐back (n = 21) pattern of ST‐segment morphology underwent signal‐averaged ECG (SAECG). SAECG parameters, and the history of life‐threatening events defined as syncope or aborted sudden death, were compared between groups. Results: Although filtered QRS duration did not differ between groups, the incidence of late potentials in the coved group was higher than in the saddle‐back group (22 patients (88%) versus 4 patients (19%); P < 0.01), showing lower RMS₄₀ and longer LAS₄₀. Life‐threatening events occurred in 17 patients (68%) in the coved group and 7 patients (33%) in the saddle‐back group (P = 0.02) . Conclusion: The coved pattern of ST segment was more closely related to conduction disturbances than the saddle‐back pattern in patients with Brugada‐type ECG. Life‐threatening events were more common in patients with the coved ST‐segment elevation. Conduction disturbances in the coved pattern of ST segment may reflect a substrate of arrhythmogenesis in Brugada syndrome.     

Brugada Phenocopy Induced by Electrolyte Disorder: A Transient Electrocardiographic Sign

Brugada syndrome (BrS) is an important cause of sudden cardiac death (SCD) with well‐defined ST‐segment elevation patterns on V₁–V₃. Observation of BrS‐Type‐electrocardiogram (ECG) patterns in medical conditions without true BrS is called “Brugada Phenocopy” (BrP). We present a case of 61‐year‐old male patient with hyperkalemia, hyponatremia, and BrS‐Type‐1 ECG pattern in the setting of acute postrenal failure. He was denying any syncope or family history of SCD. With normalization of electrolyte levels, BrS‐Type‐1‐ECG resolved. Electrolyte disturbances are one of the most common reasons of BrP. Being aware of BrPs and differentiating from an unmasked BrS‐ECG pattern could prevent patients from lethal consequences and unnecessary treatments.     

Brugada phenocopy in a patient with unstable angina and three-vessel coronary artery disease

A 52-year-old male was admitted with unstable angina and three-vessel coronary artery disease. Electrocardiography (ECG) changes consistent with type-1 Brugada ECG pattern were noted during admission. The patient was asymptomatic for syncope and had no family history of sudden cardiac death, ICD implantation, and Brugada syndrome. After coronary by-pass graft the Brugada ECG pattern resolved, and ajmaline test did not elicit type-1 ECG pattern, confirming the suspicion of Brugada phenocopy.     

Padrão de Brugada em doente medicada com lamotrigina

The authors report the case of a 52-year-old woman with depressive syndrome, treated with lamotrigine for about five months, who went to the emergency department for atypical precordial pain. The electrocardiogram (ECG) revealed a 2-mm downsloping ST-segment elevation and negative T waves in V1 and V2. Due to suspicion of ST-elevation acute coronary syndrome, cardiac catheterization was performed, which revealed normal coronary arteries. The initial ECG was suggestive of type 1 Brugada pattern, but subsequent serial ECGs were less typical. A flecainide test showed the same pattern.After discontinuation of lamotrigine reversal of the typical Brugada ECG pattern was observed.Although not currently contraindicated in Brugada syndrome, the antidepressant lamotrigine blocks sodium channels, which are usually inactivated in heart cell membranes in Brugada syndrome, and may be responsible for the expression of type 1 Brugada pattern.     

Propranolol intoxication revealing a Brugada syndrome

This is the first report of Brugada syndrome revealed by beta-blocker intoxication. A 24-year-old healthy man ingested propranolol (2.28 g) to commit suicide. After early gastric lavage, electrolytes, cardiac enzymes, chest X-ray, and echocardiography were normal. Dosages of psychotropic drugs were negative. ECG showed a typical coved-type pattern of Brugada syndrome. Follow-up showed partial ECG normalization of the discrete saddleback-type pattern. The ajmaline- test confirmed Brugada syndrome. These ECG modifications may be explained by the stabilizing membrane effect of high concentration of propranolol and/or inhibition of ICaL. This case illustrates the possible deleterious effects of beta-blockers in patients with Brugada syndrome.     

Current electrocardiographic criteria for diagnosis of Brugada pattern: a consensus report

Brugada syndrome is an inherited heart disease without structural abnormalities that is thought to arise as a result of accelerated inactivation of Na channels and predominance of transient outward K current (I(to)) to generate a voltage gradient in the right ventricular layers. This gradient triggers ventricular tachycardia/ventricular fibrillation possibly through a phase 2 reentrant mechanism. The Brugada electrocardiographic (ECG) pattern, which can be dynamic and is sometimes concealed, being only recorded in upper precordial leads, is the hallmark of Brugada syndrome. Because of limitations of previous consensus documents describing the Brugada ECG pattern, especially in relation to the differences between types 2 and 3, a new consensus report to establish a set of new ECG criteria with higher accuracy has been considered necessary. In the new ECG criteria, only 2 ECG patterns are considered: pattern 1 identical to classic type 1 of other consensus (coved pattern) and pattern 2 that joins patterns 2 and 3 of previous consensus (saddle-back pattern). This consensus document describes the most important characteristics of 2 patterns and also the key points of differential diagnosis with different conditions that lead to Brugada-like pattern in the right precordial leads, especially right bundle-branch block, athletes, pectus excavatum, and arrhythmogenic right ventricular dysplasia/cardiomyopathy. Also discussed is the concept of Brugada phenocopies that are ECG patterns characteristic of Brugada pattern that may appear and disappear in relation with multiple causes but are not related with Brugada syndrome.     

Cibenzoline induced Brugada ECG pattern.

We report a case of a 61-year-old female patient who presented with palpitations. The baseline electrocardiogram showed incomplete right bundle branch block with saddle back pattern of the ST segment in one precordial lead, but without any significant ST elevation. She was treated with oral cibenzoline. The subsequent ECG showed a coved Brugada ECG (type I) pattern, which resolved following the discontinuation of cibenzoline. An ajmaline test reproduced the coved type Brugada ECG pattern. Our case is the first report of oral cibenzoline therapy unmasking the diagnostic coved Brugada ECG pattern in a patient with a baseline normal ECG. Cibenzoline, a class I sodium channel blocker antiarrhythmic drug, should probably be avoided in the treatment of patients with Brugada syndrome.     

New electrocardiographic leads and the procainamide test for the detection of the Brugada sign in sudden unexplained death syndrome survivors and their relatives.

AIMS: Sudden unexplained death syndrome occurs in previously healthy South-east Asian young adults without any structural cause of death. The common electrocardiographic (ECG) change in sudden unexplained death syndrome survivors is right bundle branch block and ST elevations in leads V(1) to V(3), which are similar to the ECG pattern in the Brugada syndrome (Brugada sign). It is difficult to diagnose the Brugada sign with the 12-lead ECG in sudden unexplained death syndrome survivors and their family members because the ECG could be transiently normalized. We proposed using the higher intercostal space V(1) to V(3) lead ECG, together with procainamide to detect the Brugada sign. METHODS AND RESULTS: Among 20 ventricular fibrillation cardiac arrest patients, 13 sudden unexplained death syndrome survivors and their relatives (n=88) were studied using the single standard 12-lead ECG and the new six higher intercostal space V(1) to V(3) lead ECG (-V(1) to -V(3) and -2V(1) to -2V(3)). Ten sudden unexplained death syndrome survivors and relatives (n=48) who had a normalized ECG were also infused with procainamide (10 mg x kg(-1)i.v.) to unmask the Brugada sign and both ECG methods were recorded. Forty healthy individuals and 13 spouses served as the control group. Prior to the procainamide infusion, the Brugada sign could be detected in nine sudden unexplained death syndrome survivors (69.2%) and three (3.4%) relatives with the standard ECG and in 12 (92.3%) and nine (10.2%) with the new six-lead ECG. After the procainamide infusion, the Brugada sign could be demonstrated in seven sudden unexplained death syndrome survivors (70%) and seven (14.6%) relatives with the standard ECG and in nine (90%) (P=0.26) and 23 (47.9%) (P=0.0004) with the new six-lead ECG, respectively. All the controls were negative for the Brugada sign. CONCLUSIONS: Our data suggest that the new higher intercostal space lead ECG, with or without the procainamide test is helpful in detecting the Brugada sign in sudden unexplained death syndrome survivors and their relatives.     

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.     

Prevalence of Brugada sign in patients presenting with palpitation in southern Iran.

AIMS: Brugada syndrome is a cardiac channel abnormality that is associated with a high risk of ventricular fibrillation and sudden cardiac death and characterized by an electrocardiographic pattern of right bundle branch block and transient or persistent ST-segment elevation in leads V1-V3. No data regarding the frequency of Brugada syndrome exist in an Iranian population. The aim of this study was to determine the frequency of Brugada-type ECG pattern in southern Iran. METHODS AND RESULTS: All patients presenting with palpitation were enrolled in the study. A Brugada-type ECG pattern was determined according to the criteria recommended by European Heart Association Molecular Basis of Arrhythmias Study Group. A total of 3895 patients (mean age 38.2 +/- 11.9 years, 54% women) met all study criteria. One hundred patients (2.56%) had Brugada-type ECG pattern. Of these, 21 patients (0.54%) had definite Brugada sign (Type 1 or Types 2 and 3 with conversion to Type 1 following procainamide test). Of 21 patients with definite Brugada sign, eight had Brugada syndrome, four had history of syncope, two had coved-type ECG in the family, one had polymorphic ventricular tachycardia, and one had history of sudden cardiac death in the family. Five patients underwent ICD implantation. The incidence of a Brugada-type ECG pattern was 2.43% in subjects between 17 and 30 years and 0.13% in subjects >30 years (P = 0.01). CONCLUSION: Frequency of Brugada sign in an Iranian population presenting with palpitation is greater than some European countries and lower than a Japanese urban population.     

Phenotypic characterization of a large European family with Brugada syndrome displaying a sudden unexpected death syndrome mutation in SCN5A:

INTRODUCTION: Brugada syndrome is characterized by sudden death secondary to malignant arrhythmias and the presence of ST segment elevation in leads V(1) to V(3) of patients with structurally normal hearts. This ECG pattern often is concealed but can be unmasked using potent sodium channel blockers. Like congenital long QT syndrome type 3 (LQT3) and sudden unexpected death syndrome, Brugada syndrome has been linked to mutations in SCN5A. METHODS AND RESULTS: We screened a large European family with Brugada syndrome. Three members (two female) had suffered malignant ventricular arrhythmias. Ten members showed an ECG pattern characteristic of Brugada syndrome at baseline, and eight showed the pattern only after administration of ajmaline (total 12 female). Haplotype analysis revealed that all individuals with positive ECG at baseline shared the SCN5A locus. Sequencing of SCN5A identified a missense mutation, R367H, previously associated with sudden unexpected death syndrome. Two of the eight individuals who displayed a positive ECG after the administration of ajmaline, but not before, did not have the R367H mutation, and sequencing analysis failed to identify any other mutation in SCN5A. The R367H mutation failed to generate any current when heterologously expressed in HEK cells. CONCLUSION: Our results support the hypothesis that (1) sudden unexpected death syndrome and Brugada syndrome are the same disease; (2) male predominance of the phenotype observed in sudden unexpected death syndrome does not apply to this family, suggesting that factors other than the specific mutation determine the gender distinction; and (3) ajmaline may provide false-positive results. These findings have broad implications relative to the diagnosis and risk stratification of family members of patients with the Brugada syndrome.     

Brugada electrocardiographic pattern due to tricyclic antidepressant overdose

The Brugada syndrome is an arrhythmogenic disease with characteristic coved ST-segment elevation 2 mm or greater in the right precordial leads (type 1 Brugada electrocardiogram [ECG] pattern or “Brugada sign”] and is estimated to be responsible for at least 20% of sudden deaths in patients with structurally normal hearts [Circulation 2005;111(5):659-70]. The Brugada sign has been described in asymptomatic patients after exposure to various drugs. As published reports of the drug-induced Brugada sign have become increasingly prevalent, there is growing interest in the mechanisms responsible for this acquired ECG pattern and its clinical significance.We report a case of a patient who developed the type 1 Brugada ECG pattern after intentional overdose of a tricyclic antidepressant agent, review the literature concerning tricyclic antidepressant agent-induced Brugada sign, discuss potential mechanisms, and evaluate the clinical significance of this ECG abnormality.     

Brugada Phenocopy: New Terminology and Proposed Classification

Brugada syndrome is a channelopathy characterized on ECG by coved ST‐segment elevation (≥2 mm) in the right precordial leads and is associated with an increased risk of malignant ventricular arrhythmias. The term Brugada phenocopy is proposed to describe conditions that induce Brugada‐like ECG manifestations in patients without true Brugada syndrome. An extensive review of the literature identified case reports that were classified according to their suspected etiological mechanism. Future directions to learn more about these intriguing cases is discussed.     

A prospective study on spontaneous fluctuations between diagnostic and non-diagnostic ECGs in Brugada syndrome: implications for correct phenotyping and risk stratification.

AIMS: Fluctuations between the diagnostic ECG pattern and non-diagnostic ECGs in patients with Brugada syndrome are known, but systematic studies are lacking. The purpose of this study was to prospectively evaluate the spontaneous ECG changes between diagnostic and non-diagnostic ECG patterns in patients diagnosed with Brugada syndrome. METHODS AND RESULTS: In 43 patients with Brugada syndrome (27 males; mean age 45+/-11 years), 310 resting ECGs were obtained during a median follow-up of 17.7 months. The ECGs were analysed for the presence of coved type, saddle-back type or no, respectively unspecific, changes. A coved-type ECG pattern with more than 2 mm ST-segment elevation in at least two right precordial leads was defined as diagnostic. The patients were compared for different clinical characteristics with respect to the pattern of fluctuations. Out of a total of 310 ECGs, 102 (33%) revealed a coved type, 91 (29%) a saddle-back type, and 117 (38%) a normal ECG. Fifteen patients (35%) initially presented with a diagnostic coved-type ECG. Fourteen patients (33%) with an initially coved-type ECG exhibited intermittently non-diagnostic ECGs during follow-up. Only one patient (2%) presented constantly with a coved-type ECG. Out of 28 patients (65%) with an initially non-diagnostic ECG, eight (19%) patients developed a diagnostic coved-type ECG during follow-up. Twenty patients (47%) revealed a coved-type ECG during ajmaline challenge, but never had a baseline coved-type ECG recorded. No significant differences were found in gender and clinical characteristics among patients with or without fluctuations between diagnostic and non-diagnostic basal ECGs. The rate of inducible ventricular fibrillation was significantly higher in patients with more than 50% coved-type ECGs than in patients with less than 50% diagnostic ECGs. CONCLUSION: The prevalence of fluctuations between diagnostic and non-diagnostic ECGs in patients with Brugada syndrome is high and may have an implication on the correct phenotyping and on the risk stratification in patients with Brugada syndrome without aborted sudden cardiac death. For correct phenotyping and risk stratification, repetitive ECG recordings seem to be mandatory.     

A Deep Learning–Enabled Electrocardiogram Model for the Identification of a Rare Inherited Arrhythmia: Brugada Syndrome

BackgroundBrugada syndrome is a major cause of sudden cardiac death in young people and has distinctive electrocardiographic (ECG) features. We aimed to develop a deep learning–enabled ECG model for automatic screening for Brugada syndrome to identify these patients at an early point in time, thus allowing for life-saving therapy.MethodsA total of 276 ECGs with a type 1 Brugada ECG pattern (276 type 1 Brugada ECGs and another randomly retrieved 276 non-Brugada type ECGs for 1:1 allocation) were extracted from the hospital-based ECG database for a 2-stage analysis with a deep learning model. After trained network for identifying right bundle branch block pattern, we transferred the first-stage learning to the second task to diagnose the type 1 Brugada ECG pattern. The diagnostic performance of the deep learning model was compared with that of board-certified practicing cardiologists. The model was further validated in an independent ECG data set collected from hospitals in Taiwan and Japan.ResultsThe diagnoses by the deep learning model (area under the receiver operating characteristic curve [AUC] 0.96, sensitivity 88.4%, specificity 89.1%) were highly consistent with the standard diagnoses (kappa coefficient 0.78). However, the diagnoses by the cardiologists were significantly different from the standard diagnoses, with only moderate consistency (kappa coefficient 0.63). In the independent ECG cohort, the deep learning model still reached a satisfactory diagnostic performance (AUC 0.89, sensitivity 86.0%, specificity 90.0%).ConclusionsWe present the first deep learning–enabled ECG model for diagnosing Brugada syndrome, which appears to be a robust screening tool with a diagnostic potential rivalling trained physicians.     

Coexisting early repolarization pattern and Brugada syndrome: recognition of potentially overlapping entities

The Brugada type 1 electrocardiographic (ECG) pattern and the early repolarization pattern (ERP) are 2 ECG patterns characterized by the appearance of J waves. Although Brugada type 1 ECG pattern in the context of the Brugada syndrome (BrS) is well known for predisposing to life-threatening ventricular arrhythmias, it has only recently come to light that ERP, which was previously believed to be benign, may also be a marker for arrhythmogenic potential. ERP and BrS share many remarkable cellular, ionic, and ECG similarities and behave comparably in terms of their response to heart rate, pharmacologic agents, and neuromodulation. The extent to which ERP and BrS may overlap remains unclear. Here, we present an illustrated case of a symptomatic patient whose ECG signature evolved spontaneously from ERP alone to ERP with a concomitant Brugada type 1 ECG pattern over a short number of days. This case lends further strength to the notion that these 2 ECG patterns may be more closely related than had been initially thought.