Elevação Enganosa do Segmento ST Ântero-Septal e Padrão de Brugada Causado por Oclusão Isolada da Artéria do Cone / Deceptive Anteroseptal ST-segment Elevation and Brugada Pattern Caused by Isolated Conus Artery Occlusion

Resumo A artéria do cone (AC) irriga a via de saída do ventrículo direito (VSVD). A elevação do segmento ST nas derivações V1-3, que pode assemelhar-se aos padrões de eletrocardiograma (ECG) de Brugada, foi relatada devido à oclusão da AC. Um paciente do sexo masculino, 68 anos de idade, foi internado no hospital com diagnóstico de infarto do miocárdio sem supradesnivelamento do segmento ST. Uma angiografia coronária revelou uma dissecção na AC, provavelmente causada pelo cateter. Devido ao pequeno calibre da AC, a terapia medicamentosa foi escolhida como curso de ação. No entanto, após o procedimento, um ECG mostrou alterações consistentes com características dos padrões de Brugada tipo 1 e tipo 2, com elevações do segmento ST nas derivações V1-4. A imagem coronariana subsequente revelou que a AC havia progredido para oclusão total. Apesar das diversas tentativas de obter a reentrada no lúmen verdadeiro, não houve êxito. Com base na relação risco-benefício, foi tomada a decisão de continuar com a terapia medicamentosa. Este é o primeiro caso relatado de oclusão da AC induzida por dissecção por cateter, que se manifesta como elevação ântero-septal do segmento ST. O paciente não relatou sintomas anginosos ou eventos arrítmicos, o que contrasta com o conhecimento convencional. Nem todas as obstruções da AC ou infartos da VSVD causam padrões semelhantes aos de Brugada. Quando isso ocorre, as elevações de ST tendem a ser menores do que as da verdadeira síndrome de Brugada.

Abstract 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.

Evaluation of a new treadmill exercise protocol to unmask type 1 Brugada electrocardiographic pattern: can we improve diagnostic yield?

AIMS: High precordial leads (HPL) on the resting electrocardiogram (ECG) are widely used to improve diagnostic detection of type 1 Brugada ECG pattern (Br1ECGp). A parasympathetic activation marks the initial recovery phase of treadmill stress testing (TET), and this can be useful for detecting the typical ECG pattern. Our study aimed to evaluate the role of a new HPL-treadmill exercise testing (TET) protocol in detecting Br1ECGp fluctuation compared to resting HPL-ECG. METHODS AND RESULTS: 74 out of 163 patients of a Brugada syndrome (BrS) Brazilian cohort (GenBra Registry) underwent exercise testing with HPL-TET protocol. Precordial leads were displayed in strategic positions in the right and left parasternal spaces. The step-by-step analysis included ECG classification (as presence or absence of Br1ECGp) in standard vs. HPL leads placement in the following sequences: resting phase, maximal exercise, and the passive recovery phase (including 'quick lay down'). For heart rate recovery (HRR) measurements and comparisons, a Student's t-test was applied. McNemar tests compared the detection of Br1ECGp. The significance level was defined as P < 0.05. Fifty-seven patients (57/74; 77%) were male, the mean age was 49.0 ± 14, 78.4% had spontaneous BrS, and the mean Shanghai score was 4.5. The HPL-TET protocol increased Br1ECGp detection by 32.4% against resting HPL-ECG (52.7% vs. 20.3%, P = 0.001) alone. CONCLUSION: Stress testing using HPL with the passive recovery phase in the supine position offers an opportunity to unmask the type 1 Br1ECGp, which could increase the diagnostic yield in this population.

Síndrome de Brugada: 30 Anos de Aventura Científica / Brugada Syndrome: 30 Years of Scientific Ventures

Resumo Trinta anos atrás, uma nova síndrome clínico-eletrocardiográfica distinta foi descrita, agora conhecida como síndrome de Brugada (SBr). Típico para essa síndrome é o eletrocardiograma com supradesnivelamento do segmento ST nas derivações precordiais direitas. A apresentação clínica da doença é altamente variável: os pacientes podem permanecer completamente assintomáticos, mas também podem desenvolver episódios de síncope, fibrilação atrial (FA), síndrome do nódulo sinusal (SNS), distúrbios de condução, assistolia e fibrilação ventricular (FV). A doença é causada por mutações nos genes responsáveis pelo potencial de ação das células do coração. O gene mais frequentemente envolvido é o SCN5A, que controla a estrutura e função do canal de sódio cardíaco. A descrição dessa nova síndrome teve implicações muito positivas em todos os campos da medicina.

Abstract Thirty years ago, a distinctly new clinical-electrocardiographic syndrome was described, today known as Brugada Syndrome (BrS). Typical treatment for this type of syndrome is electrocardiography with ST-segment elevation in the direct precordial derivations. The clinical presentation of the disease is highly variable: the patients can remain completely asymptomatic, but they can also develop episodes of syncope, atrial fibrillation (AF), sinus node dysfunction (SNF), conduction disorders, asystole, and ventricular fibrillation (VF). This disease is caused by mutations in the genes responsible for the potential action of cardiac cells. The most commonly involved gene is SCN5A, which controls the structure and function of the heart's sodium channel. The description of this new syndrome has shown highly positive implications in all fields of medicine.

Exercise Stress Test in The Assessment of Brugada Syndrome Patients

Abstract Brugada syndrome (BS) is a genetic channelopathy, clinically characterized by an increased risk of sudden cardiac death. The diagnosis requires a typical electrocardiographic pattern, and data on risk stratification are limited in the literature. The aim of this study was to conduct a review on the importance of exercise stress test (EST) in risk stratification in BS. Articles were searched in the PubMed, Scielo and Google Scholar databases. From the 200 articles retrieved, eight were included, with a total of 712 patients (95% men) aged between 35 and 60 years. Severe symptoms and ventricular arrhythmias were reported by 256 patients before the EST, with syncope being reported in 70% of cases. The reviewed articles suggest that the EST is a safe method that can help in the diagnosis and risk stratification for malignant arrhythmias in patients with BS. Potential predictors of poor prognosis were: augmentation in ST-segment elevation > 0.5 mV in V1, V2 or V3 in early recovery; J-point elevation in lead > 2mm in aVR in late recovery; heart rate reduction < 40% from maximum heart rate in late recovery and occurrence of ventricular extrasystoles in early recovery.

Genetic variants in Colombian patients with inherited cardiac conditions.

BACKGROUND: Clinical and molecular diagnosis of inherited cardiac conditions is key to find at-risk subjects and avoid preventable deaths. This study aimed to identify genetic variants in a sample of Colombian patients diagnosed with inherited cardiac conditions. METHODS: Next-generation sequencing (Illumina platform) using a 231 gene panel was performed in blood samples of 25 unrelated patients with age disease onset between 9 and 55 years. RESULTS: Genetic testing yield was 52%. Two novel likely pathogenic/ pathogenic variants were found: a DSP nonsense variant in a patient with arrhythmogenic cardiomyopathy and a KCNE1 frameshift variant in two patients with long QT syndrome. Younger individuals (<18 years) had the highest genetic testing yield (66.6%) compared to 50% and 20% in young adults and patients over 40 years, respectively. All subjects affected with long QT syndrome with a severe event while exercising had a positive genetic test. They also had four times more loss of consciousness events and, resuscitated sudden cardiac arrest was more representative. CONCLUSION: This study is the first one undertaken in Colombia to evaluate inherited cardiac conditions. It highlights the need to perform mutational analysis to provide adequate genetic counseling and to be able to identify patients at risk of severe events.

Brugada syndrome unmasked by fever and paradoxical lower degree of dromotropic disturbance in the right ventricular outflow tract

Brugada syndrome (BrS) is an inherited clinical-electrocardiographic arrhythmic entity with an autosomal dominant genetic pattern of inheritance or de novo variant. The syndrome has low worldwide prevalence, but is endemic in Southeast Asian countries (Thailand, Philippines and Japan). The BrS is a subtle structural heart disease (SHD), and the diagnosis is only possible when the so-called type 1 Brugada ECG pattern is spontaneously present or induced for example with fever. Repolarization-depolarization disturbances in BrS patients can be caused by genetic mutations, abnormal neural crest cell migration, low expression of connexin-43 gap junction protein, or connexome disturbances. A recent autopsy study revealed increase in biventricular collagen with myocardial fibrosis when compared with control subjects although the main affected cardiac territory is the right ventricular outflow tract (RVOT). In this location, there is abnormally low expression of significant connexin-43 gap junction responsible for the electro-vectorcardiographic manifestations of terminal QRS conduction delay in the right standard precordial leads (V1-V2), high right precordial leads (V1H-V2H), as well as in the unipolar aVR lead ("the forgotten lead"). Based on their location, these leads reflect the electrical activity of the RVOT.

A síndrome de Brugada (SBr) é uma entidade arrítmica clínico-eletrocardiográfica hereditária com padrão genético autossômico dominante de herança ou variante de novo. A síndrome tem baixa prevalência mundial, porém sendo endêmica no Sudeste Asiático (Tailândia, Filipinas e Japão). A SBr é uma doença cardíaca minimamente estrutural, sendo o diagnóstico só possível na presença do chamado padrão ECG de Brugada tipo 1 espontâneo ou induzido, por exemplo, a febre. Os distúrbios de repolarização-despolarização em pacientes com SBr podem ser causados por mutações genéticas responsáveis pela migração anormal de células da crista neural, baixa expressão "gap junctions" conexina-43 ou distúrbios do conexoma. Um estudo recente de autópsia revelou aumento do colágeno biventricular com fibrose miocárdica quando comparado aos controles, embora o principal território cardíaco afetado seja a via de saída do ventrículo direito (VSVD). Nessa área, há menor expressão da conexina-43, o que se traduz no ECG-VCG por atraso final de condução do QRS nas derivações precordiais direitas (V1-V2), precordiais direitas altas (V1H-V2H), bem como na derivação unipolar aVR ("a derivação esquecida"). Com base em sua localização, esses eletrodos refletem a atividade elétrica da VSVD

Brugada pattern unmasked during COVID-19 infection -:A case report.

The current pandemic caused by the coronavirus disease 2019 (COVID-19) continues affecting millions of people worldwide. Various cardiovascular manifestations have been associated with COVID-19 but only a few case reports of Brugada syndrome in acute respiratory syndrome by SARS-CoV-2 were published. The diagnosis, prognosis, and treatment remain a challenge and represent a concern in terms of management in this population. We describe a case of a 66-year-old patient with COVID-19 presenting a coved type-1 Brugada pattern in electrocardiogram. Drug challenge was performed for the diagnosis of Brugada syndrome and electrophysiological study for risk stratification. .

Transient ascending ST-segment depression and widening of the S wave in 3-channel Holter monitoring-A sign of dromotropic disturbance in the right ventricular outflow tract in the Brugada syndrome: A report of five cases.

BACKGROUND: Brugada syndrome (BrS) is somewhat a challenging diagnosis, due to its dynamic pattern. One of the aspects of this disease is a significant conduction disorder located in the right ventricular outflow tract (RVOT), which can be explained as a consequence of low expression of Connexin-43. This decreased conduction speed is responsible for the typical electrocardiographic pattern. Opposite leads located preferably in inferior leads of the electrocardiogram may show a deep and widened S wave associated with ascending ST segment depression. Holter monitoring electrocardiographic (ECG) aspects is still a new frontier of knowledge in BrS, especially in intermittent clinical presentations. METHODS: We describe, as an exploratory analysis, five case series of intermittent type 1 BrS to demonstrate the appearance of ascending ST segment depression and widening of the S wave, during 3-channel 24h-Holter monitoring (C1, C2 and C3) with bipolar leads. RESULTS: In the five cases described, the ST segment depression was observed mainly in C2, but in some cases also in C1 and C3. Only case 1 presented concomitant intermittent elevation of the ST segment in C1. All cases were intermittent. CONCLUSION: The recognition of an ECG pattern with ascending ST-segment depression and widening of the S wave in 3-channel Holter described in this case series should raise a suspicion of the BrS and suggests the counterpart of a dromotropic disturbance registered in the RVOT and/or reciprocal changes.

Bloqueo del plano transverso abdominal para control del dolor intra y posoperatorio en herniorrafia inguinal en paciente con síndrome de Brugada / Block of transverse abdominal pain for intra-and posoperative pain control in inguinal herniorrhaphy in patient with Brugada syndrome

Los pacientes con síndrome de Brugada suponen un reto desde el punto de vista anestésico ya que son muchas las circunstancias perioperatorias y los fármacos que pueden desencadenar una crisis arritmogénica, los cuales pueden llegar a tener un fatal desenlace. Las implicaciones anestésicas en estos pacientes son múltiples por lo que se debe ser muy cuidadoso y tener en cuenta muchos factores. Se exponen las consideraciones y el manejo anestésico que se realizó en un paciente con síndrome de Brugada sometido a una herniorrafía inguinal izquierda en la que se opta por la realización de una anestesia general junto con un bloqueo ecoguiado del plano transverso abdominal para control de dolor(AU)

Patients with Brugada syndrome are a challenge from the anesthetic point of view, since there are many perioperative circumstances and drugs that can trigger an arrhythmogenic crisis, which can have a fatal outcome. Anesthetic implications in these patients are multiple, a reason why one must be very careful and take into account many factors. The considerations and anesthetic management are described for the case of a patient with Brugada syndrome who underwent left inguinal herniorrhaphy, in which general anesthesia was chosen together with ultrasound-guided block of transverse abdominal plane for pain control(AU)

Prevalência e características relacionadas de pacientes com eletrocardiograma com padrão de brugada em Santa Catarina, Brasil / Prevalence and related characteristics of patients with brugada pattern electrocardiogram in Santa Catarina, Brazil

Resumo Fundamento: A síndrome de Brugada é um distúrbio arritmogênico hereditário caracterizado pela presença de características eletrocardiográficas específicas com ou sem sintomas. Os pacientes apresentam risco aumentado de morte súbita por fibrilação ventricular. A prevalência desse padrão eletrocardiográfico difere de acordo com a região estudada. Porém, informações epidemiológicas, incluindo a população brasileira, são escassas. Objetivo: Avaliar a prevalência do padrão eletrocardiográfico da síndrome de Brugada e o perfil epidemiológico associado a ela. Métodos: Estudo transversal que incluiu 846.533 registros ECG de 716.973 pacientes do banco de dados de eletrocardiograma (ECG) da Rede de Telemedicina de Santa Catarina por um período de quatro anos. Todos os exames foram ECG de 12 derivações convencionais (sem V1 e V2 em posições altas). Os exames identificados com o diagnóstico de "Síndrome de Brugada" (tipos 1 e 2) foram revisados por um eletrofisiologista. Foram considerados significativos valores de p<0,05. Resultados: Apresentavam padrão potencialmente consistente com ECG do tipo Brugada 83 pacientes. Destes, 33 foram confirmados com padrão de Brugada tipo 1, e 22 com tipo 2, após reavaliação. A prevalência de ECG do tipo 1 de Brugada foi de 4,6 por 100.000 pacientes. O ECG do tipo Brugada 1 foi associado ao sexo masculino (81,8% vs. 41,5%, p<0,001) e menor prevalência de obesidade (9,1% vs. 26,4%, p=0,028). Conclusões: Este estudo mostrou baixa prevalência de ECG do tipo Brugada no sul do Brasil. A presença de ECG com padrão Brugada tipo 1 esteve associada ao sexo masculino e menor prevalência de obesidade que a população geral.

Abstract Background: Brugada Syndrome is an inherited arrhythmogenic disorder characterized by the presence of specific electrocardiographic features with or without clinical symptoms. The patients present increased risk of sudden death due to ventricular fibrillation. The prevalence of this electrocardiographic pattern differs according to the studied region. However, epidemiological information including the Brazilian population is scarce. Objectives: To assess the prevalence of the electrocardiographic pattern of Brugada syndrome and the epidemiological profile associated with it. Methods: Cross-sectional study that included 846,533 ECG records of 716,973 patients from the electrocardiogram (ECG) database from the Santa Catarina Telemedicine Network over a 4-year period. All tests were 12-lead conventional ECG (without V1 and V2 in high positions). The tests revealing "Brugada Syndrome" diagnosis (Types 1 and 2) were reviewed by a cardiac electrophysiologist. The level of significance was set at p<0.05. Results: In total, 83 patients had a pattern potentially consistent with Brugada-type pattern ECG. Of these, 33 were confirmed having Brugada-type 1, and 22 with type 2 ECG after reevaluation. The prevalence of Brugada-type 1 ECG was 4.6 per 100,000 patients. Brugada-type 1 ECG was associated with the male gender (81.8% vs. 41.5%, p<0.001) and a lower prevalence of obesity diagnosis (9.1% vs. 26.4%, p=0.028). Conclusions: This study showed low prevalence of Brugada-type ECG in Southern Brazil. The presence of Brugada-type 1 ECG was associated with the male gender and lower prevalence of obesity diagnosis comparing to the general population.

Peculiaridade dos pacientes com arritmias hereditárias na pandemia pela COVID-19 / Peculiar aspects of patients with Inherited arrhythmias during the COVID-19 pandemic

Resumo Desde dezembro de 2019, observamos o rápido avanço da síndrome respiratória aguda grave causada pelo coronavírus 2019 (SARS-CoV-2). O impacto da evolução clínica de uma infecção respiratória é pouco conhecido em pacientes portadores de arritmias hereditárias, devido à baixa prevalência dessas doenças. Os pacientes que apresentam quadros infecciosos podem exacerbar arritmias primárias ocultas ou bem controladas, por diversos fatores, tais como febre, distúrbios eletrolíticos, interações medicamentosas, estresse adrenérgico e, eventualmente, o próprio dano miocárdico do paciente séptico. O objetivo desta revisão é destacar os principais desafios que podemos encontrar durante a pandemia pela Covid 19, especificamente nos pacientes com arritmias hereditárias, com destaque para a síndrome do QT longo congênito (SQTL), a síndrome de Brugada (SBr), a taquicardia ventricular polimórfica catecolaminérgica (TVPC) e a cardiomiopatia arritmogênica do ventrículo direito.

Abstract Since December 2019 we have observed the rapid advance of the severe acute respiratory syndrome caused by the new coronavirus (SARS-CoV-2). The impact of the clinical course of a respiratory infection is little known in patients with hereditary arrhythmias, due to the low prevalence of these diseases. Patients who present with infectious conditions may exacerbate hidden or well-controlled primary arrhythmias, due to several factors, such as fever, electrolyte disturbances, drug interactions, adrenergic stress and, eventually, the septic patient's own myocardial damage. The aim of this review is to highlight the main challenges we may encounter during the Covid 19 pandemic, specifically in patients with hereditary arrhythmias, with emphasis on the congenital long QT syndrome (LQTS), Brugada syndrome (SBr), ventricular tachycardia polymorphic catecholaminergic (CPVT) and arrhythmogenic right ventricular cardiomyopathy.

Muerte súbita por fibrilación ventricular en deportista: una presentación inusual del Síndrome de Brugada. Caso Clínico / Sudden cardiac death during exercise due to Brugada syndrome. report of one case

We report a 20-year-old male athlete who while running, presented a sudden death due to ventricular fibrillation. He was successfully rescued by cardiopulmonary resuscitation maneuvers and an automatic external defibrillator. Without evidence of structural heart disease, Brugada syndrome was diagnosed as the cause, after which a subcutaneous implantable cardioverter defibrillator was indicated. We discuss the subject of sudden cardiac death in athletes and its unusual relationship with exercise in this channelopathy.

SCN5A compound heterozygosity mutation in Brugada syndrome: Functional consequences and the implication for pharmacological treatment.

AIMS: SCN5A gene encodes the α-subunit of Nav1.5, mainly found in the human heart. SCN5A variants are the most common genetic alterations associated with Brugada syndrome (BrS). In rare cases, compound heterozygosity is observed; however, its functional consequences are poorly understood. We aimed to analyze the functional impact of de novo Nav1.5 mutations in compound heterozygosity in distinct alleles (G400R and T1461S positions) previously found in a patient with BrS. Moreover, we evaluated the potential benefits of quinidine to improve the phenotype of mutant Na+ channels in vitro. MATERIALS AND METHODS: The functional properties of human wild-type and Nav1.5 variants were evaluated using whole-cell patch-clamp and immunofluorescence techniques in transiently expressed human embryonic kidney (HEK293) cells. KEY FINDINGS: Both variants occur in the highly conservative positions of SCN5A. Although all variants were expressed in the cell membrane, a significant reduction in the Na+ current density (except for G400R alone, which was undetected) was observed along with abnormal biophysical properties, once the variants were expressed in homozygosis and heterozygosis. Interestingly, the incubation of transfected cells with quinidine partially rescued the biophysical properties of the mutant Na+ channel. SIGNIFICANCE: De novo compound heterozygosis mutations in SNC5A disrupt the Na+ macroscopic current. Quinidine could partially reverse the in vitro loss-of-function phenotype of Na+ current. Thus, our data provide, for the first time, a detailed biophysical characterization of dysfunctional Na+ channels linked to compound heterozygosity in BrS as well as the benefits of the pharmacological treatment using quinidine on the biophysical properties of Nav1.5.

Brugada syndrome: current concepts and genetic background / Síndrome de Brugada: conceitos atuais e antecedentes genéticos

BACKGROUNG: Brugada syndrome (BrS) is a hereditary clinical-electrocardiographic arrhythmic entity with low worldwide prevalence. The syndrome is caused by changes in the structure and function of certain cardiac ion channels and reduced expression of Connexin 43 (Cx43) in the Right Ventricle (RV), predominantly in the Right Ventricular Outflow Tract (VSVD), causing electromechanical abnormalities. The diagnosis is based on the presence of spontaneous or medicated ST elevation, characterized by boost of the J point and the ST segment ≥2 mm, of superior convexity "hollow type" (subtype 1A) or descending rectilinear model (subtype 1B). BrS is associated with an increased risk of syncope, palpitations, chest pain, convulsions, difficulty in breathing (nocturnal agonal breathing) and/or Sudden Cardiac Death (SCD) secondary to PVT/VF, unexplained cardiac arrest or documented PVT/VF or Paroxysmal atrial fibrillation (AF) in the absence of apparent macroscopic or structural heart disease, electrolyte disturbance, use of certain medications or coronary heart disease and fever. In less than three decades since the discovery of Brugada syndrome, the concept of Mendelian heredity has come undone. The enormous variants and mutations found mean that we are still far from being able to concretely clarify a genotype-phenotype relationship. There is no doubt that the entity is oligogenetic, associated with environmental factors, and that there are variants of uncertain significance, especially the rare variants of the SCN5A mutation, with European or Japanese ancestors, as well as a spontaneous type 1 or induced pattern, thanks to gnomAD (coalition) researchers who seek to aggregate and harmonize exome and genome sequencing data from a variety of large-scale sequencing projects and make summary data available to the scientific community at large). Thus, we believe that this in-depth analytical study of the countless mutations attributed to BrS may constitute a real cornerstone that will help to better understand this intriguing syndrome.

INTRODUÇÃO: A Síndrome de Brugada (SBr) é uma entidade arrítmica clínico-eletrocardiográfica hereditária com baixa prevalência mundial. A síndrome é causada por alterações na estrutura e função de certos canais iônicos cardíacos e redução da expressão da Connexina 43 (Cx43) no Ventrículo Direito (VD), predominantemente no Trato de Saída do Ventricular Direito (VSVD), causando anormalidades eletromecânicas. O diagnóstico é baseado na presença de supradesnivelamento de ST espontâneo ou medicamentoso caracterizado por supradesnivelamento do ponto J e do segmento ST ≥2 mm, de convexidade superior "tipo covado" (subtipo 1A) ou modelo retilíneo descendente (subtipo 1B). A SBr está associado a um risco aumentado de síncope, palpitações, dor precordial, convulsões, dificuldade em respirar (respiração agonal noturna) e/ou Morte Cardíaca Súbita (MSC) secundária a PVT/VF, parada cardíaca inexplicada ou PVT/VF documentado ou Fibrilação atrial paroxística (FA) na ausência de doença cardíaca macroscópica ou estrutural aparente, distúrbio eletrolítico, uso de certos medicamentos ou coração coronário e febre. Em menos de três décadas desde a descoberta da síndrome de Brugada, o conceito de hereditariedade mendeliana se desfez. As enormes variantes e mutações encontradas significam que ainda estamos longe de sermos capazes de esclarecer concretamente uma relação genótipo-fenótipo. Não há dúvida de que a entidade é oligogenética associada a fatores ambientais, e que há variantes de significado incerto, principalmente as raras variantes da mutação SCN5A, com ancestrais europeus ou japoneses, bem como padrão espontâneo tipo 1 ou induzido, graças ao gnomAD (coalizão de pesquisadores que buscam agregar e harmonizar dados de sequenciamento de exoma e genoma de uma variedade de projetos de sequenciamento em grande escala e disponibilizar dados resumidos para a comunidade científica em geral). As enormes variantes e mutações encontradas significam que ainda estamos longe de sermos capazes de esclarecer concretamente uma relação genótipo-fenótipo. Assim, acreditamos que este estudo analítico em profundidade das inúmeras mutações atribuídas à BrS pode constituir uma verdadeira pedra angular que ajudará a compreender melhor esta síndrome intrigante.

Clinical Spectrum of SCN5A Channelopathy in Children with Primary Electrical Disease and Structurally Normal Hearts.

Sodium voltage-gated channel α subunit 5 (SCN5A)-mutations may cause an array of arrhythmogenic syndromes most frequently as an autosomal dominant trait, with incomplete penetrance, variable expressivity and male predominance. In the present study, we retrospectively describe a group of Mexican patients with SCN5A-disease causing variants in whom the onset of symptoms occurred in the pediatric age range. The study included 17 patients with clinical diagnosis of primary electrical disease, at least one SCN5A pathogenic or likely pathogenic mutation and age of onset <18 years, and all available first- and second-degree relatives. Fifteen patients (88.2%) were male, and sixteen independent variants were found (twelve missense, three truncating and one complex inframe deletion/insertion). The frequency of compound heterozygosity was remarkably high (3/17, 17.6%), with early childhood onset and severe disease. Overall, 70.6% of pediatric patients presented with overlap syndrome, 11.8% with isolated sick sinus syndrome, 11.8% with isolated Brugada syndrome (BrS) and 5.9% with isolated type 3 long QT syndrome (LQTS). A total of 24/45 SCN5A mutation carriers were affected (overall penetrance 53.3%), and penetrance was higher in males (63.3%, 19 affected/30 mutation carriers) than in females (33.3%, 5 affected/15 carriers). In conclusion, pediatric patients with SCNA-disease causing variants presented mainly as overlap syndrome, with predominant loss-of-function phenotypes of sick sinus syndrome (SSS), progressive cardiac conduction disease (PCCD) and ventricular arrhythmias.