True Congenital Brugada Syndrome Research Articles

Captagon-induced Brugada phenocopy: A report of two cases.

Brugada phenocopies (BrP) represent electrocardiogram changes identical to those of true congenital Brugada syndrome but are induced by reversible clinical conditions. Previous cases have been reported in patients following recreational drug use. This report presents two cases of type 1B BrP associated with Fenethylline abuse, a recreational drug known by its trade name, Captagon.

A Rare Case of Brugada Phenocopy in A Patient With Takotsubo Cardiomyopathy Masquerading as an Acute Coronary Syndrome

Brugada phenocopies (BrP) are clinical entities that are etiologically distinct from true congenital Brugada syndrome. BrP are characterized by type 1 or 2 Brugada electrocardiogram (ECG) patterns in precordial leads V1-V3. However, BrP is elicited by various underlying clinical conditions such as myocardial ischemia, pulmonary embolism, electrolyte abnormalities, or poor ECG filters. Upon resolution of the inciting underlying pathological condition, the BrP ECG subsequently normalizes. Takotsubo (octopus fishing pot) cardiomyopathy (TCM) also known as stress cardiomyopathy is an acute cardiac condition characterized by transient systolic dysfunction of the left ventricular apex and mid-ventricle with depressed LV function mimicking acute coronary syndrome (ACS) and recovers within a few weeks. TCM is most commonly seen in postmenopausal women with intense physical and or emotional stress. We are reporting a rare case of BrP in a patient with TCM masquerading as ACS posing a diagnostic and therapeutic challenge.

Brugada Phenocopy Induced by a Lethal Methanol Intoxication.

Brugada phenocopies (BrP) are clinical entities that present with an ECG pattern identical to either the type 1 or type 2 Brugada pattern without true congenital Brugada syndrome. This ECG pattern is associated with an identifiable condition and normalizes upon resolution or treatment of the underlying cause. We present a case of a 54-year-old man with extreme metabolic acidosis, hyperkalaemia and a Brugada type 1 ECG pattern in the setting of a suicidal methanol (MeOH) poisoning. Upon correction of these metabolic derangements with bicarbonate infusions and continuous veno-venous haemodiafiltration (CVVH), the Brugada type 1 ECG pattern normalized. Unfortunately, the patient developed signs of cerebral herniation followed by brain death and died on the first day of ICU admission.LEARNING POINTSBrugada-like ECG patterns are described in several metabolic conditions such as extreme hyperglycaemia, glucose/insulin challenge, isolated hyperkalaemia or in association with hyponatraemia and acidosis.Until now, there have been no published case reports of BrP in association with methanol intoxication.Correction of hyperkalaemia and acidosis and specific therapy for methanol intoxication leads to a complete resolution of a Brugada type 1 ECG pattern.

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.

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.

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.

Brugada phenocopy: A new electrocardiogram phenomenon

Brugada phenocopies (BrP) are clinical entities that are etiologically distinct from true congenital Brugada syndrome. BrP are characterized by type 1 or type 2 Brugada electrocardiogram (ECG) patterns in precordial leads V1-V3. However, BrP are elicited by various underlying clinical conditions such as myocardial ischemia, pulmonary embolism, electrolyte abnormalities, or poor ECG filters. Upon resolution of the inciting underlying pathological condition, the BrP ECG subsequently normalizes. To date, reports have documented BrP in the context of singular clinical events. More recently, recurrent BrP has been demonstrated in the context of recurrent hypokalemia. This demonstrates clinical reproducibility, thereby advancing the concept of this new ECG phenomenon. The key to further understanding the pathophysiological mechanisms behind BrP requires experimental model validation in which these phenomena are reproduced under strictly controlled environmental conditions. The development of these validation models will help us determine whether BrP are transient alterations of sodium channels that are not reproducible with a sodium channel provocative test or alternatively, a malfunction of other ion channels. In this editorial, we discuss the conceptual emergence of BrP as a new ECG phenomenon, review the progress made to date and identify opportunities for further investigation. In addition, we also encourage investigators that are currently reporting on these cases to use the term BrP in order to facilitate literature searches and to help establish this emerging concept.

Terminological clarification of Brugada Phenocopy, Brugada Syndrome, and the Brugada ECG pattern: Re. Early repolarization pattern in patients with provocable Brugada Phenocopy: A marker of additional arrhythmogenic cardiomyopathy

We read the recent paper by Dr. Peters [1] with great interest and noted that the term Brugada Phenocopy (BrP) was used in the title; however, the discussion focuses on early repolarization pattern (ERP) in the context of arrhythmogenic right ventricular cardiomyopathy and provocable Brugada ECG pattern with sodium channel blockers. We have been publishing extensively on the subject of BrP [2–9] and would like to suggest a clarification on terminology so as to facilitate future research on BrP and avoid confusion with other forms of ERP. As previously described, Bayes de Luna et al. articulated the ECG criteria for type 1 and type 2 Brugada ECG patterns in the most recent consensus report [10]. In our recent publications [2–9], we have established the diagnostic criteria for BrP and would like to identify salient features that differentiate BrP from true congenital Brugada Syndrome (BrS). First, patients with BrP and BrS both have identical type 1 or type 2 ECG patterns in precordial leads V1–V3. Second, patients with BrP have an identifiable underlying condition that elicits the Brugada ECG pattern and once this underlying condition resolves, the ECG normalizes. Additionally, patients with BrS have a high clinical pretest probability of true congenital BrS, while patients with BrP have a low clinical pretest probability of true congenital BrS suggested by lack of symptoms, medical history, or family history. Most importantly, patients with BrP have a negative provocative challenge with sodium channel blockers such as procainamide, flecainide, or ajmaline while patients with true congenital BrS have a positive provocative challenge. As such, right ventricular outflow tract sodium channel dysfunction in patients with BrS may have a different pathophysiological basis compared to patients with BrP; however, the underlying mechanisms have yet to be elucidated. We thank Dr. Peters for incorporating the relatively new term Brugada Phenocopy into his literature but we would like to emphasize that this term should not be used for cases where the Brugada ECG pattern is provoked by the use of sodium channel blockers [2]. We are developing an international online registry at www.brugadaphenocopy.com and encourage all investigators working on BrP to submit their cases online in order to provide long-term follow-up and insight into the clinical evolution of this emerging phenomenon. The authors of this manuscript certify that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.

Brugada Phenocopy Clinical Reproducibility Demonstrated by Recurrent Hypokalemia

Brugada phenocopies (BrP) are clinical entities that are etiologically distinct from true congenital Brugada syndrome (BrS). BrP are characterized by type 1 or type 2 Brugada electrocardiogram (ECG) patterns in precordial leads V1 -V3 ; however, BrP are elicited by various underlying clinical conditions such as electrolyte disturbances, myocardial ischemia, or poor ECG filters. In this report, we describe the first case of clinically reproducible BrP which is important to the conceptual evolution of BrP.

Possible Brugada Phenocopy Induced by Hypokalemia in a Patient with Congenital Hypokalemic Periodic Paralysis

5. Anselm DD, Baranchuk A. Brugada Phenocopy Emerging as a New Concept. Rev Esp Cardiol. 2013;66(9):755. References DOI: 10.5935/abc.20130249 Dear Editor, We read with great interest the case report by Gazzoni et al1 regarding a Brugada ECG pattern induced by hypokalemia. This paper is important because it contributes to the growing body of literature describing Brugada Phenocopies (BrP)2-5. Briefly, BrP are characterized by ECG patterns that are identical to type-1 or type-2 Brugada ECG patterns despite the absence of true congenital Brugada Syndrome (BrS). BrP are induced by various clinical circumstances including: hypokalemia, hyperkalemia, hypothermia, myocardial ischemia, and pulmonary embolism. We have established six etiological categories of BrP2-4 along with a systematic approach to diagnose BrP3 by excluding sodium channel dysfunction in the myocardium. The presented case by Gazzoni et al1 would possibly qualify under category (i) metabolic conditions; however, further analysis of this case report is required. Specifically, this is the first report of a possible BrP induced by hypokalemia in association with hypokalemic periodic paralysis (HPP). Patients with HPP are known to have gene mutations resulting in abnormalities of either dihydropyridine-sensitive calcium channels or sodium channels (SCN4A) in skeletal muscles. Patients with true congenital BrS have mutations in the myocardial sodium channels (SCN5A) and the association in this patient is most intriguing and remains speculative. The type-1 “coved” Brugada ECG pattern observed in this patient could have been induced by the transient serum hypokalemia (which would qualify this as a BrP) or there may be a congenital dysfunction in this patient’s sodium channels in both his skeletal muscles (HPP) and myocardium resulting in the ECG abnormalities. Therefore, we recommend to the authors that a myocardial provocative challenge with a sodium channel blocker such as procainamide, ajmaline, or flecainide be performed to rule out myocardial sodium channel dysfunction. In addition, we also suggest that future reports use the established term Brugada Phenocopy to provide consistency in the literature and facilitate future research.