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The conus artery (CA) supplies the right ventricular outflow tract (RVOT). ST-segment elevation in leads V1-3, which can resemble Brugada electrocardiogram (EKG) patterns, has been reported due to occlusion of the CA. A 68-year-old male was admitted to the hospital with a diagnosis of non-ST-elevation myocardial infarction. A coronary angiogram revealed a dissection in the conus artery, most likely caused by the catheter. Due to the small caliber of the CA, medical therapy was chosen as the course of action. However, after the procedure, an EKG showed changes consistent with features of both type-1 and type-2 Brugada patterns, with ST-segment elevations in leads V1-4. Subsequent coronary imaging revealed that the CA had progressed to total occlusion. Despite multiple attempts to gain reentry into the true lumen, they were unsuccessful. Based on the risk-benefit ratio, the decision was made to continue with medical therapy. This is the first reported case of CA occlusion induced by catheter dissection, which manifested as anteroseptal ST-segment elevation. The patient did not report any anginal symptoms or arrhythmic events, which contrasts with conventional knowledge. Not all CA obstructions or RVOT infarcts cause Brugada-like patterns. When they do, ST elevations tend to be less than those in true Brugada syndrome.

We present a clinical case of a teenager in whom a Brugada syndrome electrical pattern was found which was finally diagnosed as a Brugada phenocopy due to a wrong setup of the high-pass filter on the electrocardiogram.

No real-world data are available about the complications rate in drug-induced type 1 Brugada Syndrome (BrS) patients with an implantable cardioverter-defibrillator (ICD). Aim of our study is to compare the device-related complications, infections, and inappropriate therapies among drug-induced type 1 BrS patients with transvenous- ICD (TV-ICD) versus subcutaneous-ICD (S-ICD). Data for this study were sourced from the IBRYD (Italian BRugada sYnDrome) registry which includes 619 drug-induced type-1 BrS patients followed at 20 Italian tertiary referral hospitals. For the present analysis, we selected 258 consecutive BrS patients implanted with ICD. 198 patients (76.7%) received a TV-ICD, while 60 a S-ICD (23.4%). And were followed-up for a median time of 84.3 [46.5-147] months. ICD inappropriate therapies were experienced by 16 patients (6.2%). 14 patients (7.1%) in the TVICD group and 2 patients (3.3%) in S-ICD group (log-rank P = 0.64). ICD-related complications occurred in 31 patients (12%); 29 (14.6%) in TV-ICD group and 2 (3.3%) in S-ICD group (log-rank P = 0.41). ICD-related infections occurred in 10 patients (3.88%); 9 (4.5%) in TV-ICD group and 1 (1.8%) in S-ICD group (log-rank P = 0.80). After balancing for potential confounders using the propensity score matching technique, no differences were found in terms of clinical outcomes between the two groups. In a real-world setting of drug-induced type-1 BrS patients with ICD, no significant differences in inappropriate ICD therapies, device-related complications, and infections were shown among S-ICD vs TV-ICD. However, a reduction in lead-related complications was observed in the S-ICD group. In conclusion, our evidence suggests that S-ICD is at least non-inferior to TV-ICD in this population and may also reduce the risk of lead-related complications which can expose the patients to the necessity of lead extractions., (© 2022. The Author(s).)

A 23-year-old man with no significant medical history was rushed to a hospital due to transient loss of consciousness with incontinence. The patient had developed a fever after his second dose of coronavirus disease 2019 (COVID-19) vaccine, and the patient was found groaning in bed approximately 40 hours after the vaccination in the early morning. The patient was diagnosed with Brugada syndrome (BrS) based on a drug-provocation test. His father had been diagnosed with BrS and died suddenly at 51 years of age. Young adults with a family history of BrS should be cautioned about fever following COVID-19 vaccination.

A 35-year-old male patient with no specific history visited an emergency medical center with a chief complaint of facial swelling accompanied by fever (38.3°C). Contrast-enhanced facial computed tomography confirmed diffuse soft tissue swelling and facial infiltration of inflammation. Additional laboratory findings revealed elevated white blood cell count and C-reactive protein level. The patient also complained of chest pain; therefore, electrocardiography was performed, which confirmed a curved pattern-like ST-segment elevation (≥2 mm) of V2 without elevated cardiac enzyme levels. Based on various test results, the patient was diagnosed with Brugada syndrome. He was administered intravenous empirical antibiotics and intravenous ibuprofen as an antipyretic for the treatment of facial cellulitis and Brugada syndrome. After the resolution of the symptoms, his body temperature normalized. A subsequent electrocardiogram confirmed a normal sinus rhythm pattern. This case report shows that Brugada syndrome, a rare but life-threatening disease, can be unmasked by facial cellulitis. Because antipyretics can immediately reduce the critical rate of sudden cardiac death, Brugada syndrome should be differentially diagnosed, with an evaluation of facial cellulitis, to prevent sudden cardiac death., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Background: Brugada syndrome (BrS) is a severe inherited arrhythmia syndrome that can be unmasked by fever., Methods: A multicentre clinical analysis was performed in 261 patients diagnosed with fever-induced BrS, including 198 (75.9%) and 27 (10.3%) patients who received next-generation genetic sequencing and epicardial arrhythmogenic substrate (AS) mapping, respectively., Findings: In fever-induced BrS patients, pathogenic or likely pathogenic (P/LP) SCN5A variant carriers developed fever-induced BrS at a younger age, and more often in females and those of Caucasian descent. They exhibited significant electrophysical abnormalities, including a larger epicardial AS area, and more prolonged abnormal epicardial electrograms. During a median follow-up of 50.5 months (quartiles 32.5-81.5 months) after the diagnosis, major cardiac events (MCE) occurred in 27 (14.4%) patients. Patients with P/LP SCN5A variants had a higher ratio of MCE compared with the rest. Additionally, history of syncope, QRS duration, and Tpe interval could also predict an increased risk for future MCE according to univariate analysis. Multivariate analysis indicated that only P/LP SCN5A variants were independent significant predictors of MCE. Computational structural modelling showed that most variants are destabilizing, suggesting that Nav1.5 structure destabilization caused by SCN5A missense variants may contribute to fever-induced BrS., Interpretation: In our cohort, P/LP SCN5A variant carriers with fever-induced BrS are more prevalent among patients of Caucasian descent, females, and younger patients. These patients exhibit aggressive electrophysiological abnormalities and worse outcome, which warrants closer monitoring and more urgent management of fever., Funding: The current work was supported by the National Natural Science Foundation Project of China (Nos. 82270332 & 81670304), The Fundamental Research Funds for the Central Universities of China - Independent Research Project of Wuhan University (No. 2042022kf1217) from China; the National Institutes of Health of USA [NIH R56 (HL47678), NIH R01 (HL138103), and NIH R01 (HL152201)], the W. W. Smith Charitable Trust and the Wistar and Martha Morris Fund, Sharpe-Strumia Research Foundation, the American Heart Association Postdoctoral Fellowship (20POST35220002) from United States; the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation, Dutch Federation of University Medical Centers, the Netherlands Organization for Health Research and Development, and the Royal Netherlands Academy of Sciences (PREDICT2) from the Netherlands., Competing Interests: Declaration of interests Dr. Antzelevitch served as a consultant and received grant funds from Novartis and Trevena Inc. Dr. Wilde served as a consultant for LQTtherapeutics. All other authors report no relationships to disclose., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Competing interests: None declared.

Brugada syndrome and early repolarization syndrome are both classified as J-wave syndromes, with a similar mechanism of arrhythmogenesis and with the same basis for genesis of the characteristic electrocardiographic features. The Brugada syndrome is now considered a conduction disorder based on subtle structural abnormalities in the right ventricular outflow tract. Recent evidence suggests structural substrate in patients with the early repolarization syndrome as well. We propose a unifying mechanism based on these structural abnormalities explaining both arrhythmogenesis and the electrocardiographic changes. In addition, we speculate that, with increasing technical advances in imaging techniques and their spatial resolution, these syndromes will be reclassified as structural heart diseases or cardiomyopathies.

A diagnosis of Brugada pattern in paediatric or adolescent patients is rare. COVID-19 is characterised by fevers and a pro-inflammatory state, which may serve as inciting factors for Brugada pattern. Recently described in two adult patients, we report the first case of Brugada pattern in an adolescent with COVID-19.

Context: Excess cardiovascular morbidity and an increased prevalence of sudden cardiac death (SCD) contributes to premature mortality in schizophrenia. Brugada syndrome (BrS) is an important but underrecognized cause of SCD. It is more commonly seen in schizophrenia than in general population controls., Methods: We conducted a scoping review to describe the pathogenesis of BrS in schizophrenia and to identify the psychotropic medications that increase the risk of unmasking BrS and associated ventricular arrhythmias resulting in SCD., Findings: Schizophrenia and BrS share similar calcium channel abnormalities, which may result in aberrant myocardial conductivity. It remains uncertain if there is a genetic pre-disposition for BrS in a subset of patients with schizophrenia. However, the unmasking of Brugada ECG patterns with the use of certain antipsychotics and antidepressants increases the risk of precipitating SCD, independent of QT prolongation., Conclusions and Future Directions: Specific cardiology assessment and interventions may be required for the congenital or unmasked Brugada ECG pattern in schizophrenia. The current long-term standard of care for BrS is an implantable cardioverter defibrillator (ICD), but post-implantation psychological effects must be considered. Careful use of antipsychotic and other psychotropic medications is necessary to minimize proarrhythmic effects due to impact on cardiac sodium and calcium ion channels. When prescribing such drugs to patients with schizophrenia, clinicians should be mindful of the potentially fatal unmasking of Brugada ECG patterns and how to manage it. We present recommendations for psychiatrists managing this patient population., (Copyright © 2020. Published by Elsevier Inc.)

Importance: The true incidence of sudden unexplained death in childhood (SUDC), already the fifth leading category of death among toddlers by current US Centers for Disease Control and Prevention estimates, is potentially veiled by the varied certification processes by medicolegal investigative offices across the United States., Objective: To evaluate the frequency of SUDC incidence, understand its epidemiology, and assess the consistency of death certification among medical examiner and coroner offices in the US death investigation system., Design, Setting, and Participants: In this case series, 2 of 13 forensic pathologists (FPs) conducted masked reviews of 100 cases enrolled in the SUDC Registry and Research Collaborative (SUDCRRC). Children who died aged 11 months to 18 years from 36 US states, Canada, and the United Kingdom had been posthumously enrolled in the SUDCRRC by family members from 2014 to 2017. Comprehensive data from medicolegal investigative offices, clinical offices, and family members were reviewed. Data analysis was conducted from December 2014 to June 2020., Main Outcomes and Measures: Certified cause of death (COD) characterized as explained (accidental or natural) or unexplained, as determined by SUDCRRC masked review process., Results: In this study of 100 cases of SUDC (mean [SD] age, 32.1 [31.8] months; 58 [58.0%] boys; 82 [82.0%] White children; 92 [92.0%] from the United States), the original pathologist certified 43 cases (43.0%) as explained COD and 57 (57.0%) as unexplained COD. The SUDCRRC review process led to the following certifications: 16 (16.0%) were explained, 7 (7.0%) were undetermined because of insufficient data, and 77 (77.0%) were unexplained. Experts disagreed with the original COD in 40 cases (40.0%). These data suggest that SUDC incidence is higher than the current Centers for Disease Control and Prevention estimate (ie, 392 deaths in 2018)., Conclusions and Relevance: To our knowledge, this is the first comprehensive masked forensic pathology review process of sudden unexpected pediatric deaths, and it suggests that SUDC may often go unrecognized in US death investigations. Some unexpected pediatric deaths may be erroneously attributed to a natural or accidental COD, negatively affecting surveillance, research, public health funding, and medical care of surviving family members. To further address the challenges of accurate and consistent death certification in SUDC, future studies are warranted.

BACKGROUND Brugada phenocopies (BrP) are clinical and electrocardiographic (ECG) entities elicited by reversible medical conditions speculated to have pathogenesis rooted in ion current imbalances or conduction delays within the myocardial wall. During an inciting pathologic condition, it produces ECG patterns identical to those of congenitally-acquired Brugada syndrome and subsequently returns to normal ECG patterns upon resolution of the medical condition. This case report describes a 26-year-old man presenting to the Emergency Department (ED) for suspected heroin overdose with a rare ECG consistent with BrP secondary to acute hyperkalemia. CASE REPORT A 26-year-old man with a history of substance abuse and a seizure disorder presented to the ED for acute encephalopathy secondary to a heroin overdose complicated by severe rhabdomyolysis and acute renal failure. Laboratory investigations showed acute hyperkalemia (potassium of 7.2 mmol/L) in addition to an elevated creatine kinase, severe transaminitis, and elevated creatinine. His ECG on admission revealed Brugada-like changes in leads V1-V2, with subsequent resolution upon bicarbonate administration and normalization of potassium. After initial stabilization, the patient was admitted to the Intensive Care Unit (ICU). His rhabdomyolysis and acute kidney injury improved after copious rehydration. He was found to have community-acquired pneumonia, with a negative infectious disease workup, that improved with antibiotics. Upon resolution of his hypoxemic respiratory failure and improvement in mentation, he was discharged from the hospital. CONCLUSIONS Our case report adds to the growing literature on BrP and highlights the importance of recognizing its characteristic ECG pattern as a unique presentation of a common electrolyte derangement.

Background: 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)., Methods: 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., Results: 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 5 hours. 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., Conclusions: 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., (© 2019 Wiley Periodicals, Inc.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Brugada syndrome is an inherited, rare cardiac arrhythmogenic disease, associated with sudden cardiac death. It accounts for up to 20% of sudden deaths in patients without structural cardiac abnormalities. The majority of mutations involve the cardiac sodium channel gene SCN5A and give rise to classical abnormal electrocardiogram with ST segment elevation in the right precordial leads V1 to V3 and a predisposition to ventricular fibrillation. The pathophysiological mechanisms of Brugada syndrome have been investigated using model systems including transgenic mice, canine heart preparations, and expression systems to study different SCN5A mutations. These models have a number of limitations. The recent development of pluripotent stem cell technology creates an opportunity to study cardiomyocytes derived from patients and healthy individuals. To date, only a few studies have been done using Brugada syndrome patient-specific iPS-CM, which have provided novel insights into the mechanisms and pathophysiology of Brugada syndrome. This review provides an evaluation of the strengths and limitations of each of these model systems and summarizes the key mechanisms that have been identified to date., Competing Interests: The authors declare no conflict of interest.

We present a patient with fever-induced Brugada syndrome, a rare cardiac disease caused by an inherited ion channelopathy and associated with malignant arrhythmias. ECG findings normalized after the fever resolved. As Brugada syndrome can be confused with anterior myocardial ischemia, right bundle branch block and intoxication with tricyclic antidepressants, ECG recognition is important. Patients with Brugada syndrome are instructed to avoid contraindicated substances, and fever should be treated aggressively.

Background: Spontaneous type 1 electrocardiogram (ECG) in the right precordial lead is a dominant predictor of ventricular fibrillation (VF) in Brugada syndrome (BrS). In some BrS patients with VF, however, spontaneous type 1 ECG is undetectable, even in repeated ECG and immediately after VF. This study investigated differences between BrS patients with spontaneous or drug-induced type 1 ECG. Methods and Results: We evaluated 15 BrS patients with drug-induced (D-BrS) and 29 with spontaneous type 1 ECG (SP-BrS). All patients had had a previous VF episode. In each D-BrS patient, ECG was recorded more than 15 times (mean, 46±34) during 7.2±5.1 years of follow-up. Age and family history were comparable between groups. Inferolateral early repolarization (ER) was observed in 13 D-BrS (87%) at least once but in only 3 SP-BrS (10%, P<0.01). Immediately after VF, inferolateral ER was accentuated in 9 of 10 D-BrS, while type 1 ECG was accentuated in 12 of 16 SP-BrS. Fragmented QRS in the right precordial lead and aVR sign were absent in D-BrS but present in 20 (69%, P<0.01) and 11 (38%, P<0.01) SP-BrS, respectively. There was no prognostic difference between groups., Conclusions: Although having similar clinical profiles, there are obvious ECG differences between VF-positive BrS patients with spontaneous or drug-induced type 1 ECG. The inferolateral lead rather than the right precordial lead on ECG may be particularly crucial in some BrS patients.

Background Several 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 Results We 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. Conclusions In 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.

Background Epicardial mapping can reveal low-voltage areas on the right ventricular outflow tract in patients with Brugada syndrome with several ventricular fibrillation ( VF ) episodes. A type 1 ECG is associated with an abnormal electrogram on right ventricular outflow tract epicardium. This study investigated the clinical significance of the amplitude of type 1 ECGs in patients with Brugada syndrome. Methods and Results In 209 patients with Brugada syndrome with a spontaneous type 1 ECG (26 resuscitated from VF , 54 with syncope, and 129 asymptomatic), the amplitude of the ECG in leads exhibiting type 1 was measured among V1 to V3 leads positioned in the standard and upper 1 and 2 intercostal spaces. The number of ECG leads exhibiting type 1 did not differ among groups. The averaged amplitude of type 1 ECG was, however, significantly smaller in the group resuscitated from VF than in the asymptomatic group ( P<0.05). Moreover, the minimum amplitude of type 1 ECG was significantly smaller in the group resuscitated from VF than in the group with syncope and the asymptomatic group ( P<0.05 and P<0.01, respectively). During follow-up (56±48 months), VF occurred in 29 patients. Kaplan-Meier analysis revealed that patients with the minimum amplitude of type 1 ECG lower than or at the median value had a higher incidence of VF (log-rank test, P<0.01). In multivariate analysis, syncope, past VF episode, and minimum amplitude of type 1 ECG ≤0.8 mV were independent predictors of VF events during follow-up. Conclusions Low-voltage type 1 ECG is highly and independently related to fatal ventricular tachyarrhythmia in patients with Brugada syndrome.

BACKGROUND Brugada syndrome is a cardiac disorder associated with sudden death due to sodium channelopathy, most commonly the SCN5a mutation. There are 3 different patterns of electrocardiogram (ECG) changes characterized as type I, II, and III. ECG patterns consist of variations of incomplete RBBB and ST elevation in anterior precordial leads only. Treatment, if warranted, consists of implantable cardioverter-defibrillator. CASE REPORT A 63-year-old male presented with abdominal pain for 4 days that was persistent, and after further imaging, he was found to have hepatic metastases from a stage IV small cell carcinoma of the lung. The patient was started on chemotherapy with carboplatin and VP-16. The patient decompensated, developed septic shock secondary to post-obstructive pneumonia, and eventually required intubation. He became tachycardic, and an ECG was ordered to evaluate the heart rhythm. It was determined that the patient had Brugada wave/syndrome. The patient's condition deteriorated with worsening septic shock, suspected type II NSTEMI, and multiorgan failure. The patient was designated DNR ("do not resuscitate") and passed away. CONCLUSIONS This case represents how channelopathies can be provoked with fever. It is believed that this occurs due to denaturing of the ion channel leading to abnormal ST segment changes typically seen on ECG and an increased risk of developing lethal arrhythmias. Spontaneous presentation of nondrug-induced Brugada syndrome carries an increased risk of deadly arrhythmia, for which this patient would have required electrophysiological studies. Unfortunately, this patient was unable to undergo genetic testing or electrophysiological studies, as he passed away.

The Brugada syndrome is an inherited disorder associated with risk of ventricular fibrillation and sudden cardiac death in a structurally normal heart. Diagnosis is based on a characteristic electrocardiographic pattern (coved type ST-segment elevation ≥2 mm followed by a negative T-wave in ≥1 of the right precordial leads V 1 to V 2 ), observed either spontaneously or during a sodium-channel blocker test. The prevalence varies among regions and ethnicities, affecting mostly males. The risk stratification and management of patients, principally asymptomatic, still remains challenging. The current main therapy is an implantable cardioverter-defibrillator, but radiofrequency catheter ablation has been recently reported as an effective new treatment. Since its first description in 1992, continuous achievements have expanded our understanding of the genetics basis and electrophysiological mechanisms underlying the disease. Currently, despite several genes identified, SCN5A has attracted most attention, and in approximately 30% of patients, a genetic variant may be implicated in causation after a comprehensive analysis., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Brugada syndrome (BrS) is an inherited electroclinical syndrome and can be occasionally precipitated by fever. The prevalence of Brugada-type electrocardiographic patterns (BTEP) due to febrile illnesses have not been previously studied in India., Materials and Methods: Between June 2014 and December 2015, 525 consecutive patients admitted to a government hospital with acute febrile illness were retrospectively enrolled. In addition to their investigations for workup of fever, ECGs were analyzed and BTEP types 1 and 2 were noted. Daily ECGs if available were perused to document reversal., Results: BTEP was seen in 23 (4% 95%CI: 2.9-6.5%): BTEP type 1 (Brugada syndrome) in 11 patients (2%; 95%CI 1.2-3.7%) and BTEP type 2 in 12. All patients with BrS (BTEP type1) were males; mean age and temperature were 37.7 years (SD: 17.6) and 38.8°C (SD: 0.6), respectively. There were no significant differences in age, temperature or ECG parameters between patients with BTEP and those without. These patients neither had cardiac symptoms nor family history of sudden cardiac deaths. Bacterial infections were the commonest cause of fever in patients with BrS. All BTEP changes resolved with defervesence of fever except in one., Conclusion: The prevalence of the fever induced BrS is higher in our study group and is comparable to estimates in Southeast Asian populations. An ECG should be considered in all febrile patients. Further studies are required for better characterization and risk stratification of these patients., (Copyright © 2017 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Competing Interests: None

Background: Loperamide has been increasing in popularity recently for its effects separate from treatment of diarrhea. In large doses or in combination with other agents, it can lead to desirable effects in the central nervous system. However, cardiotoxicity has been reported with its abuse., Case Report: A 49-year-old male who had been chronically abusing loperamide was found to have Brugada-like changes on his electrocardiogram (ECG). He had no other clinical symptoms associated with Brugada syndrome and did not have similar findings on previous ECGs. After abstaining from further loperamide use during hospitalization, this pattern slowly resolved without clinically significant dysrthymias. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: A patient with a history of loperamide abuse is at risk for cardiotoxicity. While other dysrhythmias are reported more commonly with loperamide abuse, Brugada-like ECG changes can occur and warrant appropriate consultation and prompt follow-up., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Two patients without cardiac history demonstrated type 1 Brugada pattern during hospitalization for diabetic ketoacidosis (DKA). Both patients had normalization of their ECGs after treatment of marked electrolyte abnormalities and metabolic acidosis. In this report, we describe two cases of Brugada phenocopy associated with DKA in children., (Copyright © 2017 Elsevier Inc. All rights reserved.)

A Brugada phenocopy has been defined as a clinical situation that presents with an abnormal electrocardiogram identical to any of the electrocardiographic patterns found in Brugada syndrome in the absence of the characteristic congenital genetic abnormalities. The first confirmed case of type 1 Brugada phenocopy associated with severe left pneumothorax is presented. A provocative test with ajmaline, which proved to be negative, was performed to confirm the diagnosis. The presence of ST-segment elevation in the context of pneumothorax is most infrequent., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Rationale: Vasospastic angina is caused by sudden occlusive vasoconstriction of a segment of an epicardial artery, with transient ST-segment elevation on electrocardiography. Brugada Syndrome is an inherited arrhythmogenic cardiac disorder with a diagnostic electrocardiography characterized by coved-type ST-segment elevation in right precordial leads (V1-V3). Those two diseases usually have no correlation. In this report, we discuss an interesting case of a patient who was diagnosed as vasospastic angina according to his coronary angiography, but his electrocardiography showed a Brugada-like ST-segment elevation., Patient Concerns: Our patient had a 9-month history of temporary but progressive substernal burning sensation with acid bilges of shoulders and arms, as well as profuse sweating at night., Diagnoses: Although he had no abnormal laboratory test result, no dysfunctional recorded echocardiogram or documented arrhythmia after being admitted to the hospital, his electrocardiography showed a Brugada-like ST-segment elevation. The coronary angiography result confirmed a diagnosis of vasospastic angina., Interventions: The patient was prescribed diltiazem, aspirin, isosorbide mononitrate and rosuvastatin and was strongly advised to quit cigarettes and alcohol., Outcomes: Follow-up at half a year turned out well., Lessons: This case links Brugada syndrome to coronary vasospasm. They may share similar mechanisms. Provocation test and gene test needs to be ran to distinguish both. Long-term follow-up is essential for it may bring a warning sign for life threatening ventricular arrhythmias.

Long QT syndrome, short QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia are inherited primary electrical disorders that predispose to sudden cardiac death in the absence of structural heart disease. Also known as cardiac channelopathies, primary electrical disorders respond to mutations in genes encoding cardiac ion channels and/or their regulatory proteins, which result in modifications in the cardiac action potential or in the intracellular calcium handling that lead to electrical instability and life-threatening ventricular arrhythmias. These disorders may have low penetrance and expressivity, making clinical diagnosis often challenging. However, because sudden cardiac death might be the first presenting symptom of the disease, early diagnosis becomes essential. Genetic testing might be helpful in this regard, providing a definite diagnosis in some patients. Yet important limitations still exist, with a significant proportion of patients remaining with no causative mutation identifiable after genetic testing. This review aims to provide the latest knowledge on the genetic basis of cardiac channelopathies and discuss the role of the affected proteins in the pathophysiology of each one of these diseases., Competing Interests: The authors declare no conflict of interest.

BACKGROUND Brugada pattern on electrocardiogram (ECG) is seen when there are at least 2 mm J-point elevation and 1 mm ST-segment elevation in two or more of the right precordial leads, with right bundle-branch block (RBBB)-like morphology. Elevation of a coved-type shape in leads V1 and V2 is consistent with type I Brugada pattern, whereas elevation of a saddle-back configuration distinguishes type II Brugada. If accompanied by life-threatening arrhythmias or sudden cardiac death, Brugada syndrome (BrS) is diagnosed. The presence of Brugada ECG pattern in absence of the syndrome has come to be known as Brugada phenocopy (BrP). CASE REPORT We introduce a case of both Brugada type I and II patterns unmasked in a 28-year-old female with fever secondary to mastitis. Though fever-induced BrP is a universally known phenomenon, the presentation of both type I and II patterns presenting in a patient during a single hospitalization makes this case unique from others. The patient was brought to the emergency department after experiencing a syncopal episode that appeared classically vasovagal in nature. Once her fever resolved, her baseline ECG showed no abnormalities. CONCLUSIONS Though Brugada ECG pattern may be very alarming, especially after syncope, appropriate management in the case of a fever-induced event would consist of observation with cardiac monitoring, immediate treatment of fever with antipyretics, and antibiotics for suspected infection. Close follow-up by a cardiologist as an outpatient is imperative to further ascertain if the patient is at high risk of life-threatening arrhythmias, significant for BrS.

Metabolic alteration, either through the ketogenic diet (KD) or by genetic alteration of the BAD protein, can produce seizure protection in acute chemoconvulsant models of epilepsy. To assess the seizure-protective role of knocking out (KO) the Bad gene in a chronic epilepsy model, we used the Kcna1 -/- model of epilepsy, which displays progressively increased seizure severity and recapitulates the early death seen in sudden unexplained death in epilepsy (SUDEP). Beginning on postnatal day 24 (P24), we continuously video monitored Kcna1 -/- and Kcna1 -/- Bad -/- double knockout mice to assess survival and seizure severity. We found that Kcna1 -/- Bad -/- mice outlived Kcna1 -/- mice by approximately 2 weeks. Kcna1 -/- Bad -/- mice also spent significantly less time in seizure than Kcna1 -/- mice on P24 and the day of death, showing that BadKO provides seizure resistance in a genetic model of chronic epilepsy., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

The voltage-gated cardiac sodium channel (Na v 1.5) is a mega-complex comprised of a pore-forming α subunit and 4 ancillary β-subunits together with numerous protein partners. Genetic defects in the form of rare variants in one or more sodium channel-related genes can cause a loss- or gain-of-function of sodium channel current (I Na ) leading to the manifestation of various disease phenotypes, including Brugada syndrome, long QT syndrome, progressive cardiac conduction disease, sick sinus syndrome, multifocal ectopic Purkinje-related premature contractions, and atrial fibrillation. Some sodium channelopathies have also been shown to be responsible for sudden infant death syndrome (SIDS). Although these genetic defects often present as pure electrical diseases, recent studies point to a contribution of structural abnormalities to the electrocardiographic and arrhythmic manifestation in some cases, such as dilated cardiomyopathy. The same rare variants in SCN5A or related genes may present with different clinical phenotypes in different individuals and sometimes in members of the same family. Genetic background and epigenetic and environmental factors contribute to the expression of these overlap syndromes. Our goal in this chapter is to review and discuss what is known about the clinical phenotype and genotype of each cardiac sodium channelopathy, and to briefly discuss the underlying mechanisms.

Besli GE, Yıldırım S, Akalın İ, Ayhan Yİ, Kısıoğlu M, Berdeli A. Fever-induced Brugada syndrome in a 9-year-old boy presenting with acute chest pain. Turk J Pediatr 2018; 60: 571-575. Brugada syndrome, an arrhythmogenic disease, occurs due to mutations involving cardiac sodium channels. It is characterized by persistent or transient ST-segment elevation in the right precordial electrocardiogram leads that could be unmasked by several circumstances, with fever particularly. Molecular and cellular mechanisms leading to Brugada syndrome have not been completely elucidated. Mutations of the SCN5A gene encoding the pore-forming α-subunit of the cardiac sodium channel protein have been attributed in the molecular diagnosis. Although this syndrome is well-known in adults, it is less frequently reported in infants and children. We describe a 9-year-old Turkish boy with a family history of sudden cardiac death, who presented with chest pain and fever-induced expression of the Brugada syndrome phenotype that might be associated with a mutation in SCN5A gene.

Brugada syndrome is an inherited cardiac condition with the potential for development of life-threatening arrhythmias in relatively young individuals without significant structural cardiac abnormalities. The condition is characterized by a distinct coved-type ST segment elevation in the right precordial leads (V1-V3). This hallmark pattern (type 1) is often dynamic and sometimes concealed, and may be unmasked in certain conditions or under the effect of certain agents, which include variation of sympathovagal balance, hormones, metabolic factors and drugs. These factors may not only modulate electrocardiographic morphology and induce the characteristic type 1 pattern, but also predispose to ventricular arrhythmias. The risk of malignant arrhythmias in acute events with induced type 1 pattern may be imminent, particularly if the patient in fact has Brugada syndrome. The physician should be aware of the modulating factors that may underlie a Brugada pattern, and be able to recognize, identify and promptly correct them. The mechanisms responsible for the type 1 pattern and possible associated ventricular arrhythmias induced by these modulating factors have attracted growing attention and interest. Furthermore, not all induced Brugada ECG patterns are observed in patients with Brugada syndrome, existing the possibility for acquired Brugada patterns/syndrome and Brugada phenocopies. This paper reviews the modulating factors associated with induced type 1 pattern as possible causes of arrhythmogenesis, particularly in Brugada syndrome patients, describes some of the probable underlying mechanisms, and discusses the concepts of acquired Brugada syndrome and Brugada phenocopies., (Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Case Presentation: A 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., Discussion: Brugada 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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Brugada syndrome is an inherited arrhythmogenic disease that may cause sudden cardiac death due to ventricular fibrillation in young adults. Brugada syndrome caused by propafenone intoxication has been noted rarely in the literature. We report a rare case, Brugada phenocopy due to propafenone intoxication and its treatment., Case Report: A 15-year-old girl having a seizure was brought to the emergency room. She took 1.5 g propafenone (Rythmol, Abbott, Chicago, IL, USA) for suicidal intention. She had metabolic acidosis. Long QRS interval and ST elevation in leads V1 through V3 were seen on electrocardiography. After bicarbonate infusion for 4 hours, haemodynamic and neurologic findings were recovered, and all electrocardiography abnormalities disappeared. The Brugada-like electrocardiography pattern was not recognized in her surface and 24-hour Holter electrocardiography at follow-up. Ajmaline challenge test was negative 2 weeks later., Conclusion: Absence of symptoms and documented ventricular tachycardia, negative challenge test, and a negative family history demonstrated that the Brugada phenocopy was a transient finding in this case and related to propafenone intoxication.

Background: Syncope is considered a risk factor for life-threatening arrhythmias in Brugada patients. Distinguishing a benign syncope from one due to ventricular arrhythmias is often difficult, unless an ECG is recorded during the episode. Aim of the study was to analyze the characteristics of syncopal episodes in a large population of Brugada patients and evaluate the role of electrophysiological study (EPS) and the prognosis in the different subgroups., Methods and Results: One hundred ninety-five Brugada patients with history of syncope were considered. Syncope were classified as neurally mediated (group 1, 61%) or unexplained (group 2, 39%) on the basis of personal and family history, clinical features, triggers, situations, associated signs, concomitant therapy. Most patients underwent EPS; they received ICD or implantable loop-recorder on the basis of the result of investigations and physician's judgment. At 62±45months of mean follow-up, group 1 showed a significantly lower incidence of arrhythmic events (2%) as compared to group 2 (9%, p<0.001). Group 2 patients with positive EPS showed the highest risk of arrhythmic events (27%). No ventricular events occurred in subjects with negative EPS., Conclusion: Etiological definition of syncope in Brugada patients is important, as it allows identifying two groups with different outcome. Patients with unexplained syncope and ventricular fibrillation induced at EPS have the highest risk of arrhythmic events. Patients presenting with neurally mediated syncope showed a prognosis similar to that of the asymptomatic and the role of EPS in this group is unproven., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Since its recognition as a clinical entity in 1992, the Brugada Syndrome (BrS), a hereditary disease characterized by a typical electrocardiogram (ECG) pattern potentially predisposing to sudden cardiac death (SCD), has attracted the attention of many physicians for its circadian pattern of ventricular arrhythmias (VA), mostly occurring at rest. Exercise may potentially worsen the ECG abnormalities in BrS patients, resulting in higher peak J-point amplitudes during the vasovagal reaction of the recovery period, possibly leading to an increased risk of cardiac events. Moreover, the enhanced vagal tone in athletes could be both a BrS risk factor and an exercise effect. Therefore, the true risk of a BrS patient during exercise is still unclear. This review summarizes current knowledge, shortcomings and open questions on BrS and exercise. The paper, in particular, underlines specific considerations including BrS diagnostic criteria and differential diagnosis in athletes, the genetic basis, the autonomic imbalance during exercise practice and the recommendations for athletic participation in this patient group., Competing Interests: Conflict of interest: The Authors have no conflict of interest to declare., (© Georg Thieme Verlag KG Stuttgart · New York.)