RESUMEN
Intravenous infusion of sodium-channel blockers (SCB) with either ajmaline, flecainide, procainamide, or pilsicainide to unmask the ECG of Brugada syndrome is the drug challenge most commonly used for diagnostic purposes when investigating cases possibly related to inherited arrhythmia syndromes. For a patient undergoing an SCB challenge, the impact of a positive result goes well beyond its diagnostic implications. It is, therefore, appropriate to question who should undergo a SCB test to diagnose or exclude Brugada syndrome and, perhaps more importantly, who should not. We present a critical review of the benefits and drawbacks of the SCB challenge when performed in cardiac arrest survivors, patients presenting with syncope, family members of probands with confirmed Brugada syndrome, and asymptomatic patients with suspicious ECG.
Asunto(s)
Síndrome de Brugada , Electrocardiografía , Bloqueadores de los Canales de Sodio , Humanos , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/fisiopatología , Síncope/diagnóstico , Síncope/etiologíaRESUMEN
Genetic arrhythmia disorders are rare diseases; however, they are a common cause of sudden cardiac death in children, adolescents, and young adults. In principle, a distinction can be made between channelopathies and cardiomyopathies in the context of genetic diseases. This paper focuses on the channelopathies long and short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia (CPVT). Early diagnosis of these diseases is essential, as drug therapy, behavioral measures, and if necessary, implantation of a cardioverter defibrillator can significantly improve the prognosis and quality of life of patients. This paper highlights the pathophysiological and genetic basis of these channelopathies, describes their clinical manifestations, and comments on the principles of diagnosis, risk stratification and therapy.
Asunto(s)
Arritmias Cardíacas , Síndrome de Brugada , Canalopatías , Humanos , Arritmias Cardíacas/genética , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/terapia , Arritmias Cardíacas/fisiopatología , Canalopatías/genética , Canalopatías/diagnóstico , Canalopatías/terapia , Síndrome de Brugada/genética , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/fisiopatología , Síndrome de Brugada/terapia , Taquicardia Ventricular/genética , Taquicardia Ventricular/terapia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatología , Adolescente , Niño , Síndrome de QT Prolongado/genética , Síndrome de QT Prolongado/diagnóstico , Síndrome de QT Prolongado/terapia , Síndrome de QT Prolongado/fisiopatología , Muerte Súbita Cardíaca/prevención & control , Muerte Súbita Cardíaca/etiología , Adulto , Desfibriladores Implantables , ElectrocardiografíaRESUMEN
Brugada Syndrome Type 1 is an arrhythmogenic disorder triggered by various etiologies, including febrile illness, pregnancy, and certain medications. This paper describes the electrocardiographic (ECG) manifestation of the Brugada pattern in a patient who developed ventricular arrhythmia after undergoing general anesthesia for pituitary surgery.
Asunto(s)
Anestesia General , Síndrome de Brugada , Electrocardiografía , Humanos , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/fisiopatología , Anestesia General/efectos adversos , Masculino , Femenino , Hipófisis/cirugía , Hipófisis/diagnóstico por imagen , AdultoRESUMEN
Brugada syndrome (BrS) is a cardiac electrophysiological disease with unknown etiology, associated with sudden cardiac death. Symptomatic patients are treated with implanted cardiac defibrillator, but no risk stratification strategy is effective in patients that are at low to medium arrhythmic risk. Cardiac computational modeling is an emerging tool that can be used to verify the hypotheses of pathogenesis and inspire new risk stratification strategies. However, to obtain reliable results computational models must be validated with consistent experimental data. We reviewed the main electrophysiological and structural variables from BrS clinical studies to assess which data could be used to validate a computational approach. Activation delay in the epicardial right ventricular outflow tract is a consistent finding, as well as increased fibrosis and subclinical alterations of right ventricular functional and morphological parameters. The comparison between other electrophysiological variables is hindered by methodological differences between studies, which we commented. We conclude by presenting a recent theory unifying electrophysiological and structural substrate in BrS and illustrate how computational modeling could help translation to risk stratification.
Asunto(s)
Potenciales de Acción , Síndrome de Brugada , Simulación por Computador , Modelos Cardiovasculares , Humanos , Síndrome de Brugada/fisiopatología , Síndrome de Brugada/diagnóstico , Valor Predictivo de las Pruebas , Frecuencia Cardíaca , Factores de Riesgo , Técnicas Electrofisiológicas Cardíacas , Pronóstico , Medición de Riesgo , Muerte Súbita Cardíaca/prevención & control , Muerte Súbita Cardíaca/etiología , Electrocardiografía , Función Ventricular Derecha , FibrosisRESUMEN
Brugada phenocopies are conditions that have an electrocardiography (ECG) pattern that mimics typical patterns seen in Brugada syndrome (BS). We report a rare case of a patient who had a Brugada-like ECG pattern caused by ischemia due to strangulation of the septal artery. The patient was treated with thrombolytic therapy after a probable diagnosis of ST-elevation myocardial infarction (STEMI), which resulted in hematologic complications.
Asunto(s)
Síndrome de Brugada , Electrocardiografía , Humanos , Síndrome de Brugada/diagnóstico , Masculino , Persona de Mediana Edad , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/etiologíaAsunto(s)
Síndrome de Brugada , Modelos Animales de Enfermedad , Síndrome de Brugada/fisiopatología , Síndrome de Brugada/genética , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/terapia , Animales , Ratones , Humanos , Canal de Sodio Activado por Voltaje NAV1.5/genética , Canales de Sodio/genéticaRESUMEN
BACKGROUND: Brugada syndrome (BrS) has been associated with sudden cardiac death in otherwise healthy subjects, and drug-induced BrS accounts for 55% to 70% of all patients with BrS. This study aims to develop a deep convolutional neural network and evaluate its performance in recognizing and predicting BrS diagnosis. METHODS AND RESULTS: Consecutive patients who underwent ajmaline testing for BrS following a standardized protocol were included. ECG tracings from baseline and during ajmaline were transformed using wavelet analysis and a deep convolutional neural network was separately trained to (1) recognize and (2) predict BrS type I pattern. The resultant networks are referred to as BrS-Net. A total of 1188 patients were included, of which 361 (30.3%) patients developed BrS type I pattern during ajmaline infusion. When trained and evaluated on ECG tracings during ajmaline, BrS-Net recognized a BrS type I pattern with an AUC-ROC of 0.945 (0.921-0.969) and an AUC-PR of 0.892 (0.815-0.939). When trained and evaluated on ECG tracings at baseline, BrS-Net predicted a BrS type I pattern during ajmaline with an AUC-ROC of 0.805 (0.845-0.736) and an AUC-PR of 0.605 (0.460-0.664). CONCLUSIONS: BrS-Net, a deep convolutional neural network, can identify BrS type I pattern with high performance. BrS-Net can predict from baseline ECG the development of a BrS type I pattern after ajmaline with good performance in an unselected population.
Asunto(s)
Ajmalina , Síndrome de Brugada , Aprendizaje Profundo , Electrocardiografía , Humanos , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/fisiopatología , Síndrome de Brugada/inducido químicamente , Electrocardiografía/efectos de los fármacos , Masculino , Femenino , Ajmalina/efectos adversos , Persona de Mediana Edad , Adulto , Valor Predictivo de las Pruebas , Estudios RetrospectivosRESUMEN
The risk of arrhythmia and its management become increasingly complex as kidney disease progresses. This presents a multifaceted clinical challenge. Our discussion addresses these specific challenges relevant to patients as their kidney disease advances. We highlight numerous opportunities for enhancing the current standard of care within this realm. Additionally, this review delves into research concerning early detection, prevention, diagnosis, and treatment of various arrhythmias spanning the spectrum of kidney disease.
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Arritmias Cardíacas , Humanos , Arritmias Cardíacas/etiología , Arritmias Cardíacas/fisiopatología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/fisiopatología , Fibrilación Atrial/complicaciones , Síndrome de Brugada/complicaciones , Síndrome de Brugada/fisiopatología , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/terapia , Síndrome de QT Prolongado/complicaciones , Síndrome de QT Prolongado/diagnóstico , Fibrilación Ventricular/etiología , Fibrilación Ventricular/terapia , Fibrilación Ventricular/fisiopatologíaRESUMEN
Molecular autopsy has recently been gaining attention as a means of postmortem diagnosis; however, it is usually performed using the victim's blood sample at the time of death. Here, we report the first case of a deceased infant with Brugada syndrome whose diagnosis was made with banked cord blood. A seemingly healthy 1-year-old male infant collapsed while having a fever; this collapse was witnessed by his mother. Despite cardiopulmonary resuscitation, he died of ventricular fibrillation. No abnormalities of cardiac structure were identified on autopsy. Genomic samples were not stored at the time because of a lack of suspicion for familial arrhythmia. Five years later, his sister showed Brugada electrocardiogram pattern while febrile from Kawasaki disease. Their father showed a spontaneous type 1 Brugada electrocardiogram pattern. A heterozygous SCN5A p.R893C variant was found by genetic testing in the proband's father and sister. Furthermore, the proband's genetic testing was performed using his banked cord blood, which identified the same variant. Family history of Brugada syndrome with an SCN5A-R893C variant and clinical evidence led to a postmortem diagnosis of Brugada syndrome in the proband. Identification of this variant in this case later contributed to verifying SCN5A-R893C as a pathogenic variant through data accumulation. Banked cord blood may prove useful for conducting molecular autopsies in previously undiagnosed cases of sudden death in which genomic samples were not stored.
Asunto(s)
Autopsia , Síndrome de Brugada , Sangre Fetal , Canal de Sodio Activado por Voltaje NAV1.5 , Humanos , Síndrome de Brugada/genética , Síndrome de Brugada/diagnóstico , Masculino , Canal de Sodio Activado por Voltaje NAV1.5/genética , Lactante , Electrocardiografía , Muerte Súbita/etiologíaRESUMEN
Inherited cardiovascular diseases are rare diseases that are difficult to diagnose by non-expert professionals. Genetic analyses play a key role in the diagnosis of these diseases, in which the identification of a pathogenic genetic variant is often a diagnostic criterion. Therefore, genetic variant classification and routine reinterpretation as data become available represent one of the main challenges associated with genetic analyses. Using the genetic variants identified in an inherited cardiovascular diseases unit during a 10-year period, the objectives of this study were: 1) to evaluate the impact of genetic variant reinterpretation, 2) to compare the reclassification rates between different cohorts of cardiac channelopathies and cardiomyopathies, and 3) to establish the most appropriate periodicity for genetic variant reinterpretation. All the evaluated cohorts (full cohort of inherited cardiovascular diseases, cardiomyopathies, cardiac channelopathies, hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic cardiomyopathy, Brugada syndrome, long QT syndrome and catecholaminergic polymorphic ventricular tachycardia) showed reclassification rates above 25%, showing even higher reclassification rates when there is definitive evidence of the association between the gene and the disease in the cardiac channelopathies. Evaluation of genetic variant reclassification rates based on the year of the initial classification showed that the most appropriate frequency for the reinterpretation would be 2 years, with the possibility of a more frequent reinterpretation if deemed convenient. To keep genetic variant classifications up to date, genetic counsellors play a critical role in the reinterpretation process, providing clinical evidence that genetic diagnostic laboratories often do not have at their disposal and communicating changes in classification and the potential implications of these reclassifications to patients and relatives.
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Enfermedades Cardiovasculares , Humanos , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/diagnóstico , Canalopatías/genética , Canalopatías/diagnóstico , Pruebas Genéticas/métodos , Variación Genética , Cardiomiopatías/genética , Cardiomiopatías/diagnóstico , Síndrome de QT Prolongado/genética , Síndrome de QT Prolongado/diagnóstico , Síndrome de Brugada/genética , Síndrome de Brugada/diagnósticoRESUMEN
BACKGROUND Brugada syndrome is characterized by specific electrocardiographic changes predisposing individuals to ventricular arrhythmias and sudden cardiac death. Cases of coexisting Brugada syndrome and ischemic stroke are seldom documented, and an underlying pathophysiological link is yet unknown. This article presents a case in which a patient exhibited both Brugada syndrome patterns and an ischemic stroke, prompting a comprehensive literature review to explore the potential association between Brugada syndrome and ischemic stroke. CASE REPORT A 49-year-old man, previously healthy, was admitted to the hospital after being discovered unconscious at his workplace. Physical exam showed low oxygen saturation, fever, and abnormal neurological findings. Head computed tomography revealed a significant posterior circulation ischemic stroke. An electrocardiogram revealed Brugada syndrome type II initially, progressing to type III pattern. Despite efforts, the patient's condition rapidly deteriorated, leading to death within 24 hours. As far as we're aware, Brugada patterns following a posterior circulation ischemic stroke have only been documented in 1 other instance, in which the patient was also diagnosed with atrial fibrillation. CONCLUSIONS Both our literature review and the presented case indicate that Brugada patterns may coexist with and even be associated with ischemic stroke. More extensive research is required to shed light on this potential association. The question of whether Brugada syndrome is a precursor to or a result of ischemic stroke remains unanswered. We propose that patients with ischemic stroke should undergo an evaluation for electrocardiographic signs indicative of Brugada syndrome, particularly if no clear causes, like cardioembolism, are evident.
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Síndrome de Brugada , Electrocardiografía , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Síndrome de Brugada/complicaciones , Síndrome de Brugada/diagnóstico , Persona de Mediana Edad , Accidente Cerebrovascular Isquémico/etiología , Accidente Cerebrovascular Isquémico/complicaciones , Resultado FatalRESUMEN
AIMS: Brugada syndrome (BrS) diagnosis and risk stratification rely on the presence of a spontaneous type 1 (spT1) electrocardiogram (ECG) pattern; however, its spontaneous fluctuations may lead to misdiagnosis and risk underestimation. This study aims to assess the role for repeat high precordial lead (HPL) resting and ambulatory ECG monitoring in identifying a spT1, and evaluate its prognostic role. METHODS AND RESULTS: HPL resting and ambulatory monitoring ECGs of BrS subjects were reviewed retrospectively, and the presence of a spT1 associated with ventricular dysrhythmias and sudden cardiac death (SCD). Three-hundred and fifty-eight subjects (77 with spT1 pattern at presentation, Group 1, and 281 without, Group 2) were included. In total, 1651 resting HPL resting and 621 ambulatory monitoring ECGs were available for review, or adequately described. Over a median follow-up of 72 months (interquartile range - IQR - 75), 42/77 (55%) subjects in Group 1 showed a spT1 in at least one ECG. In Group 2, 36/281 subjects (13%) had a newly detected spT1 (1.9 per 100 person-year) and 23 on an HPL ambulatory recording (8%). Seven previously asymptomatic subjects, five of whom had a spT1 (four at presentation and one at follow-up), experienced arrhythmic events; survival analysis indicated that a spT1, either at presentation or during lifetime, was associated with events. Univariate models showed that a spT1 was consistently associated with increased risk [spT1 at presentation: hazard ratio (HR) 6.3, 95% confidence interval (CI) 1.4-28, P = 0.016; spT1 at follow-up: HR 3.1, 95% CI 1.3-7.2, P = 0.008]. CONCLUSION: Repeated ECG evaluation and HPL ambulatory monitoring are vital in identifying transient spT1 Brugada pattern and its associated risk.
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Síndrome de Brugada , Muerte Súbita Cardíaca , Electrocardiografía Ambulatoria , Humanos , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/fisiopatología , Masculino , Femenino , Electrocardiografía Ambulatoria/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Adulto , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/prevención & control , Medición de Riesgo , Valor Predictivo de las Pruebas , Factores de Riesgo , Frecuencia Cardíaca , AncianoRESUMEN
Brugada syndrome (BrS) is a genetic disorder known for its characteristic electrocardiogram (ECG) patterns and increased risk of sudden cardiac death. Brugada phenocopy (BrP) presents similar ECG patterns but is distinguished by its reversible nature when the underlying conditions are resolved. This article delineates the intricacies of BrP, emphasizing its etiology, clinical presentation, diagnosis, treatment, and prognosis. The article categorizes BrP based on various underlying causes, including metabolic disturbances, myocardial infarction, and mechanical compression, among others. It also underscores the critical importance of differentiating BrP from BrS to avoid misdiagnosis and inappropriate treatment, such as unnecessary implantation of cardioverter-defibrillators. The reversible aspect of BrP underlines the necessity for an etiology-specific approach to treatment, which not only prevents cardiac death but also highlights the significance of understanding the dynamic nature of ECG patterns. Through an exploration of case studies and current research, this review advocates for increased awareness and further investigation into BrP. It aims to enhance the diagnostic accuracy and management strategies, thereby improving the prognosis for patients presenting with Brugada-like ECG patterns. The review culminates in a call for further research to close existing knowledge gaps and improve patient outcomes.
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Síndrome de Brugada , Electrocardiografía , Fenotipo , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/terapia , Síndrome de Brugada/fisiopatología , Humanos , Diagnóstico Diferencial , Pronóstico , Muerte Súbita Cardíaca/prevención & control , Muerte Súbita Cardíaca/etiología , Desfibriladores ImplantablesRESUMEN
BACKGROUND: A pathogenic/likely pathogenic variant can be found in 20% to 25% of patients with Brugada syndrome (BrS) and a pathogenic/likely pathogenic variant in SCN5A is associated with a worse prognosis. The aim of this study is to define the diagnostic yield of a large gene panel with American College of Medical Genetics and Genomics variant classification and to assess prognosis of SCN5A and non-SCN5A variants. METHODS: All patients with BrS, were prospectively enrolled in the Universitair Ziekenhuis Brussel registry between 1992 and 2022. Inclusion criteria for the study were (1) BrS diagnosis; (2) genetic analysis performed with a large gene panel; (3) classification of variants following American College of Medical Genetics and Genomics guidelines. Patients with a pathogenic/likely pathogenic variant in SCN5A were defined as SCN5A+. Patients with a reported variant in a non-SCN5A gene or with no reported variants were defined as patients with SCN5A-. All variants were classified as missense or predicted loss of function. RESULTS: A total of 500 BrS patients were analyzed. A total of 104 patients (20.8%) were SCN5A+ and 396 patients (79.2%) were SCN5A-. A non-SCN5A gene variant was found in 75 patients (15.0%), of whom, 58 patients (77.3%) had a missense variant and 17 patients (22.7%) had a predicted loss of function variant. At a follow-up of 84.0 months, 48 patients (9.6%) experienced a ventricular arrhythmia (VA). Patients without any variant had higher VA-free survival, compared with carriers of a predicted loss of function variant in SCN5A+ or non-SCN5A genes. There was no difference in VA-free survival between patients without any variant and missense variant carriers in SCN5A+ or non-SCN5A genes. At Cox analysis, SCN5A+ or non-SCN5A predicted loss of function variant was an independent predictor of VA. CONCLUSIONS: In a large BrS cohort, the yield for SCN5A+ is 20.8%. A predicted loss of function variant carrier is an independent predictor of VA.