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.
Khan
Ijaz A
IA
Division of Cardiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. ikhan@medicine.umaryland.edu
Nair
Chandra K
CK
D002037:Bundle-Branch Block / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D016757:Death, Sudden, Cardiac / Q000209:etiology / Q000517:prevention & control; D017147:Defibrillators, Implantable; D004562:Electrocardiography; D006801:Humans; D008133:Long QT Syndrome / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010641:Phenotype; D011379:Prognosis; D015222:Sodium Channels / Q000235:genetics; D013577:Syndrome
D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels