A danger of induction of Brugada syndrome during pill-in-the-pocket therapy for paroxysmal atrial fibrillation

Rhythm control therapy by sodium channel blockers is widely performed for the treatment of paroxysmal atrial fibrillation. Here, we present a case of acquired Brugada syndrome by pill-in-the-pocket treatment using pilsicainide. It is important that this therapy should be applied only after confirming the drug safety to the patients

Truncated KCNQ1 mutant, A178fs/105, forms hetero-multimer channel with wild-type causing a dominant-negative suppression due to trafficking defect

AbstractWe identified a novel mutation Ala178fs/105 missing S3–S6 and C-terminus portions of KCNQ1 channel. Ala178fs/105-KCNQ1 expressed in COS-7 cells demonstrated no current expression. Co-expression with wild-type (WT) revealed a dominant-negative effect, which suggests the formation of hetero-multimer by mutant and WT. Confocal laser microscopy displayed intracellular retention of Ala178fs/105-KCNQ1 protein. Co-expression of the mutant and WT also increased intracellular retention of channel protein compared to WT alone. Our findings suggest a novel mechanism for LQT1 that the truncated S1–S2 KCNQ1 mutant forms hetero-multimer and cause a dominant-negative effect due to trafficking defect

Electrical Storm in Idiopathic Ventricular Fibrillation Is Associated With Early Repolarization

ObjectivesThis study sought to characterize patients with idiopathic ventricular fibrillation (IVF) who develop electrical storms.BackgroundSome IVF patients develop ventricular fibrillation (VF) storms, but the characteristics of these patients are poorly known.MethodsNinety-one IVF patients (86% male) were selected after the exclusion of structural heart diseases, primary electrical diseases, and coronary spasm. Electrocardiogram features were compared between the patients with and without electrical storms. A VF storm was defined as VF occurring ≥3 times in 24 h and J waves >0.1 mV above the isoelectric line in contiguous leads.ResultsFourteen (15.4%) patients had VF storms occurring out-of-hospital at night or in the early morning. J waves were more closely associated with VF storms compared to patients without VF storms: 92.9% versus 36.4% (p < 0.0001). VF storms were controlled by intravenous isoproterenol, which attenuated the J-wave amplitude. After the subsidence of VF storms, the J waves decreased to the nondiagnostic level during the entire follow-up period. Implantable cardioverter-defibrillator therapy was administered to all patients during follow-up. Quinidine therapy was limited, but the patients on disopyramide (n = 3), bepridil (n = 1), or isoprenaline (n = 1) were free from VF recurrence, while VF recurred in 5 of the 9 patients who were not given antiarrhythmic drugs.ConclusionsThe VF storms in the IVF patients were highly associated with J waves that showed augmentation prior to the VF onset. Isoproterenol was effective in controlling VF and attenuated the J waves, which diminished to below the diagnostic level during follow-up. VF recurred in patients followed up without antiarrhythmic agents

Clinical characteristics and electrophysiologic properties of SCN5A variants in fever-induced Brugada syndrome

Brugada syndrome (BrS) is a severe inherited arrhythmia syndrome that can be unmasked by fever. 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. 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. 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. None. [Abstract copyright: Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

Clinical characteristics and electrophysiologic properties of SCN5A variants in fever-induced Brugada syndrome

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

Clinical Characteristics and Electrophysiologic Properties of SCN5A Variants in Fever-Induced Brugada Syndrome

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: None