Mechanisms and clinical management of inherited channelopathies: long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and short QT syndrome

Abstract

The following briefly reviews features and management of long QT syndrome (LQTS), Brugada Syndrome, catecholaminergic polymorphic ventricular tachycardia (CPVT), and short QT syndrome (SQTS). LQTS is marked by QT prolongation, syncope and sudden death due to torsades de pointes. Risk stratification is based on age, gender, history of symptoms, QT interval, and genetic subtype of LQTS. In addition to avoidance QT-prolonging drugs and high intensity sports, standard treatment for LQTS involves anti-adrenergic therapy, with implantable cardioverter-defibrillator (ICD) use in high risk subgroups. Brugada Syndrome is associated with right ventricular conduction delay and ST elevation in the right precordial leads, syncope, and sudden death from ventricular fibrillation. The electrocardiographic abnormality can be accentuated by sodium channel blocker, vagal stimulation or fever. Patients with aborted cardiac arrest and those with syncope and a spontaneous or sodium channel blocker-inducible type I Brugada ECG pattern are at high risk and should receive an ICD. The role of electrophysiologic testing is controversial. Although there is no reliable drug therapy for Brugada Syndrome, quinidine, which suppresses I(to) current, can reduce the incidence of arrhythmias. Patients with CPVT present with exercise-induced syncope and sudden cardiac death but normal resting electrocardiograms. Exercise or isoproterenol infusion may cause increased ventricular ectopy or bidirectional ventricular tachycardia. Treatment modalities include anti-adrenergic therapy and ICD implantation. Congenital SQTS is a relatively recently described disorder characterized by a very short QT interval and by susceptibility to atrial and ventricular fibrillation. ICD implantation is the primary therapy; quinidine may be a useful adjunctive therapy.