The Brugad syndrome: clinical, electrophysiologic and genetic aspects

This review deals with the clinical, basic and genetic aspects of recently highlighted form of idiopathic ventricular fibrillation known as the Brugad syndrome. Our primary objective in this review is to identify the full scope of the syndrome and attempt to correlate the electrocardiographic manifestations of the Brugad syndrome with cellular and ionic heterogeneity known to exist within the heart under normal and pathophysiologic conditions so as to identify the cellular basis and thus potential diagnostic and therapeutic approaches. The available dat suggest that the Brugad syndrome is primary electrical disease resulting in abnormal electrophysiologic activity in right ventricular epicardium. Recent genetic dat linking the Brugad syndrome to an ion channel gene mutation (SCN5A) provides further support for the hypothesis. The electrocardiographic manifestations of the Brugad syndrome show transient normalization in many patients, but can be unmasked using sodium channel blockers such as flecainide, ajmaline or procainamide, thus identifying patients at risk. The available dat suggest that loss of the action potential dome in right ventricular epicardium but not endocardium underlies the ST segment elevation seen in the Brugad syndrome and that electrical heterogeneity within right ventricular epicardium leads to the development of closely coupled premature ventricular contractions vi phase 2 reentrant mechanism that then precipitates ventricular tachycardia/ventricular fibrillation (VT/VF). Currently, implantable cardiac defibrillator implantation is the only proven effective therapy in preventing sudden death in patients with the Brugad syndrome and is indicated in symptomatic patients and should be considered in asymptomatic patients in whom VT/VF is inducible at time of electrophysiologic study.