The syndrome of right bundle branch block ST segment elevation in V-1 to V-3 and sudden death - the Brugada syndrome

In 1992 a new syndrome was described consisting of syncopal episodes and/or sudden death in patients with a structurally normal heart and an electroca rdiogram (ECG) characteristic of right bundle branch block with ST segment elevation in leads V-1 to V-3. The disease is genetically determined, with an autosomal dominant pattern of transmission. Three different mutations th at affect the structure and function of the cardiac sodium channel gene SCN 5A have been identified. Two mutations result in total loss of function of the sodium channel. The other mutation results in acceleration of the recov ery of the sodium channel from inactivation. The incidence of the disease i s difficult to estimate, but it causes 4 to 10 sudden deaths per 10 000 inh abitants per year in areas like Thailand and Laos. In these countries, the disease represents the most frequent cause of death in young adults. Up to 50% of the yearly sudden deaths in patients with a structurally normal hear t are caused by this syndrome. The diagnosis is easily made by means of the EGG. The presence of concealed and intermittent forms, however, make the d iagnosis difficult in some patients. The ECG can be modulated by changes in autonomic balance and the administration of antiarrhythmic drugs. Beta-adr energic stimulation normalizes the EGG, while intravenous ajmaline flecaini de or procainamide accentuate ST segment elevation and are capable of unmas king concealed and intermittent forms of the disease. Recent data suggest t hat loss of the action potential dome in the right ventricular epicardium b ut not the endocardium underlies ST segment elevation seen in the Brugada s yndrome. Also, electrical heterogeneity within the right ventricular epicar dium leads to the development of closely coupled extrasystoles via a phase 2 reentrant mechanism, which then precipitates ventricular tachycardia-vent ricular fibrillation. Right ventricular epicardium is preferentially affect ed because of the predominance of transient outward current iu this tissue. Antiarrhythmic drugs like amiodarone and beta-blockers do not prevent sudd en death in symptomatic or asymptomatic individuals. Gene therapy may offer a cure in future years. Implantation of an automatic cardioverter-defibril lator is the only currently proven effective therapy.