ST-segment elevation in the early repolarization syndrome, idiopathic ventricular fibrillation, and the Brugada syndrome: cellular and clinical linkage

ST-segment elevation in a structurally normal heart is associated with an electrocardiographic (ECG) J wave, which can be observed in the early repolarization syndrome (ERS), idiopathic ventricular fibrillation (VF), and the Brugada syndrome. Animal studies have demonstrated that the J wave is the consequence of a transmural voltage gradient resulting from an Ito-mediated action potential notch (spike and dome) in epicardium but not endocardium. Ito-mediated spike and dome morphology predisposes loss or depression of the dome in epicardium, leading to ST-segment elevation. Despite the fact that 3 clinical syndromes share many common ECG features, their clinical consequences are remarkably different. The ERS is a benign ECG finding characterized by a distinct J wave and ST segment in left precordial leads V4 through V6. In contrast, idiopathic VF and the Brugada syndrome, characterized by a J wave and ST-segment elevation in the inferior and right precordial leads, respectively, are the leading causes for sudden cardiac death in young Southeast Asian males. The underlying mechanism for such a difference in clinical consequences among these syndromes is due to a difference in Ito density and Ito-mediated epicardial spike and dome. When Ito is prominent, complete loss of the dome may occur due to either a decrease in inward currents or an increase in outward currents, leading to phase 2 reentry capable of initiating VF as in idiopathic VF and the Brugada syndrome. When Ito is relatively small as in the ERS, partial depression of the dome occurs without the development of phase 2 reentry.