Sudden Cardiac Death: A Review Focused on Cardiovascular Imaging

Sudden cardiac death (SCD) is defined as natural death due to cardiac causes, heralded by abrupt loss of consciousness within 1 h of the onset of acute symptoms; pre-existing heart disease may have been known to be present but the time and mode of death are unexpected. Prediction and prevention of SCD is an area of active investigation, but considerable challenges persist that limit the efficacy and cost-effectiveness of available methodologies. It was well-recognized that optimization of SCD risk stratification would require integration of multi-disciplinary efforts at the bench and bedside, with studies in the general population. This integration has yet to be effectively accomplished. There is also increasing awareness that more investigation needs to be directed toward the identification of early predictors of SCD. Significant advancements have recently occurred for risk prediction in the inherited channelopathies and other inherited conditions that predispose to SCD, but there is much to be accomplished in this regard for the more common complex phenotypes, such as SCD among patients with coronary artery disease. A multimodality imaging approach is actually the most important tool to provide comprehensive information on different pathophysiological mechanisms related to SCD.     

离子通道调整与新药研制——胃肠离子通道病研究最新进展

本文概述近年来尤其是最近5年,胃肠平滑肌和肠神经细胞离子通道及其与消化道疾病关系研究的最新进展,总结了可能用于新疗法、新药研制的新靶点,提出离子通道调整及修饰,应是今后与离子通道特性改变密切相关的功能性胃肠道疾病的诊治的方向。     

Epilepsy surgery for patients with genetic refractory epilepsy: a systematic review

Aims. In recent years, many different DNA mutations underlying the development of refractory epilepsy have been discovered. However, genetic diagnostics are still not routinely performed during presurgical evaluation and reports on epilepsy surgery outcome for patients with genetic refractory epilepsy are limited. We aimed to create an overview of the literature on seizure outcome following epilepsy surgery in patients with different genetic causes of refractory epilepsy. Methods. We systematically searched PubMed and Embase prior to January 2017 and included studies describing treatment outcome following epilepsy surgery in patients with genetic causes of epilepsy. We excluded studies in which patients were described with epilepsy due to Tuberous Sclerosis Complex or Sturge‐Weber syndrome (since this extensive body of research has recently been described elsewhere) and articles in which surgery was aimed to be palliative. Results. We identified 24 eligible articles, comprising a total of 82 patients who had undergone surgery for (mainly childhood‐onset) refractory epilepsy due to 15 different underlying genetic causes. The success rate of surgery varied widely across these different genetic causes. Surgery was almost never effective in patients with epilepsy due to mutations in genes involved in channel function and synaptic transmission, whereas surgery was significantly more successful regarding seizure control in patients with epilepsy due to mutations in the mTOR pathway. Patients with a lesion on MRI tended to have higher seizure freedom rates than those who were MRI‐negative. Conclusion. Although the evidence is still scarce, this systematic review suggests that studying genetic variations in patients with refractory epilepsy could help guide the selection of surgical candidates.     

Brugada and Long QT‐3 Syndromes: Two Phenotypes of the Sodium Channel Disease

Brugada and long QT‐3 syndromes are two allelic diseases caused by different mutations in SCN5A gene inherited by an autosomal dominant pattern with variable penetrance. Both of these syndromes are ion channel diseases of the heart manifest on surface electrocardiogram by ST‐segment elevation in the right precordial leads and prolonged QT_c interval, respectively, with predilection for polymorphic ventricular tachycardia and sudden death, which may be the first manifestation of the disease. Brugada syndrome usually manifests during adulthood with male preponderance, whereas long QT3 syndrome usually manifests in teenage years, although it can also manifest in adulthood. Class IA and IC antiarrhythmic drugs increase ST‐segment elevation and predilection for polymorphic ventricular tachycardia and ventricular fibrillation in Brugada syndrome, whereas these agents shorten the repolarization and QT_c interval, and thus may be beneficial in long QT‐3 syndrome. Beta‐blockade also increases the ST‐segment elevation in Brugada syndrome but decreases the dispersion of repolarization in long QT‐3 syndrome. Mexiletine, a class IB sodium channel blocker decreases QT_c interval as well as dispersion of repolarization in long QT‐3 syndrome but has no effect on Brugada syndrome. The only effective treatment available at this time for Brugada syndrome is implantable cardioverter defibrillator, although repeated episodes of polymorphic ventricular tachycardia can be treated with isoproterenol. In symptomatic patients of long QT‐3 syndrome in whom the torsade de pointes is bradycardia‐dependent or pause‐dependent, a pacemaker could be used to avoid bradycardia and pauses and an implantable cardioverter defibrillator is indicated where arrhythmia is not controlled with pacemaker and beta‐blockade. However, the combination of new devices with pacemaker and cardioverter‐defibrillator capabilities appear promising in these patients warranting further study.     

Association of congenital, diffuse electrical disease in children with normal heart: sick sinus syndrome, intraventricular conduction block, and monomorphic ventricular tachycardia

Introduction: Rhythm disturbances in children with structurally normal hearts are usually associated with abnormalities in cardiac ion channels. The phenotypic expression of these abnormalities ("channelopathies") includes: long and short QT syndromes, Brugada syndrome, congenital sick sinus syndrome, catecholaminergic polymorphic ventricular tachycardia, Lènegre-Lev disease, and/or different degrees of cardiac conduction disease.
Methods: The study group consisted of three male patients with sick sinus syndrome, intraventricular conduction disease, and monomorphic sustained ventricular tachycardia. Clinical data and results of electrocardiography, Holter monitoring, electrophysiology, and echocardiography are described.
Results: In all patients, the ECG during sinus rhythm showed right bundle branch block and long QT intervals. First-degree AV block was documented in two subjects, and J point elevation in one. A pacemaker was implanted in all cases due to symptomatic bradycardia (sick sinus syndrome). Atrial tachyarryhthmias were observed in two patients. The common characteristic ventricular arrhythmia was a monomorphic sustained ventricular tachycardia, inducible with ventricular stimulation and sensitive to lidocaine. In one patient, radiofrequency catheter ablation was successfully performed. No structural abnormalities were found in echocardiography in the study group.
Conclusion: Common clinical and ECG features suggest a common pathophysiology in this group of patients with congenital severe electrical disease.     

Inherited arrhythmia syndromes leading to sudden cardiac death in the young: A global update and an Indian perspective

Inherited primary arrhythmias, namely congenital long QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia, account for a significant proportion of sudden cardiac deaths in young and apparently healthy individuals. Genetic testing plays an integral role in the diagnosis, risk-stratification and treatment of probands and family members. It is increasingly obvious that collaborative efforts are required to understand and manage these relatively rare but potentially lethal diseases. This article aims to update readers on the recent developments in our knowledge of inherited arrhythmias and to lay the foundation for a national synergistic effort to characterize them in the Indian population.