The Brugada Syndrome

In 1992 a syndrome was described consisting of syncopal episodes and/or (resuscitated) sudden death in patients with a structurally normal heart and a characte ristic electrocardiogram (ECG) displaying a pattern resembling a right bundle branch block with ST segment elevation in leads V1 to V3. The disease is genetically determined with an autosomal dominant pattern of transmission in 50% of the familial cases. Several different mutations have been identified affecting the structure, function and trafficking of the sodium channel. The syndrome is ubiquitous. Its incidence and prevalence are difficult to estimate, but this disease may cause 4 to 10 sudden deaths per 10,000 inhabitants per year representing the most frequent cause of natural death in males younger than 50 in South Asia. The disease has been linked to the sudden infant death syndrome (SIDS) and to the sudden unexpected death syndrome (SUDS) by showing that the electrocardiogram and mutations are the same as in Brugada syndrome. The diagnosis is easily made by means of the ECG when it is typical. There exist, however, patients with concealed and intermittent electrocardiographic forms that make the diagnosis difficult. The ECG can be modulated by changes in autonomic balance, body temperature, glucose level and the administration of antiarrhythmic, neuroleptic and antimalaria drugs. Beta adrenergic stimulation normalizes the ECG. Loss of the action potential dome in right ventricular epicardium but not in endocardium underlies the ST segment elevation. Electrical heterogeneity within right ventricular epicardium leads to the development of closely coupled extrasystoles via phase 2 reentry that precipitate ventricular ,fibrillation. Antiarrhythmic drugs do not prevent sudden death in symptomatic or asymptomatic individuals. Implantation of an automatic cardioverter-defibrillator is the only currently proven effective therapy. Patients with frequent electrical storms may even need cardiac transplantation as last resort.