Clinical and Mechanistic Issues in Early Repolarization

Abstract

Early repolarization, involving ST-segment elevation and, sometimes, prominent J waves at the QRS-ST junction, has been considered a normal electrocardiographic variant for over 60 years. A growing number of case reports and case-control studies indicate that in some instances, early repolarization patterns are associated with increased risk of idiopathic ventricular fibrillation. Epidemiological evidence indicates a dose effect for the risk of cardiac and sudden death with the extent of J-point elevation. This paper reviews present knowledge regarding the epidemiology, presentation, therapeutic response, and mechanisms characteristic of early repolarization. We highlight major unanswered questions relating to our limited ability to determine which individuals with this common electrocardiographic variant are at risk for sudden death, our incomplete understanding of underlying mechanisms, the inadequate information regarding genetic determinants and therapeutic responses, and the unclear relationship between early repolarization and other conditions involving accelerated repolarization and sudden arrhythmic death such as Brugada and short-QT syndromes. This review paper intends to inform the practicing physician about important clinical issues and to stimulate investigators to address the many unresolved questions in this rapidly evolving field.

Electrocardiographic Early Repolarization

“…16,23,[33][34][35] Some controversy exists as to whether the electrocardiographic findings represent ER, late depolarization, or neither. 36,37 The repolarization hypothesis suggests that the presence of the ERP reflects regional heterogeneity in the dispersion gradient of myocardial refractoriness prompted by a net outward shift in repolarizing current.…”

Ventricular Arrhythmias in the Absence of Structural Heart Disease

“…Such a pattern in the anterior precordial leads (V 1 to V 3 ) was excluded from the studies as it could occur in disease states such as Brugada syndrome and arrhythmogenic right ventricular cardiomyopathy/dysplasia. Further, early repolarization pattern in the anterior precordial leads is considered to have a benign prognosis (116). Recent data suggest the KCNJ8 gene may be involved in early repolarization syndrome (117).…”

“…Recent data suggest the KCNJ8 gene may be involved in early repolarization syndrome (117). Early repolarization pattern is not uncommon and has for years been considered a normal ECG variant with a benign prognosis (116). The mechanism of VT or VF that can occur with it is not well understood (116).…”

Management of Ventricular Arrhythmias in Suspected Channelopathies

“…β-adrenergic activation with isoproterenol is effective in suppressing ER arrhythmias by enhancing inward calcium current (Figures 2 and 5). 53 Quinidine via its effects to inhibit I to is effective as well. 53 A multicenter observational cohort study has demonstrated that isoproterenol in acute cases and quinidine in chronic cases is effective for suppression of VF related to ERS.…”

“…53 Quinidine via its effects to inhibit I to is effective as well. 53 A multicenter observational cohort study has demonstrated that isoproterenol in acute cases and quinidine in chronic cases is effective for suppression of VF related to ERS. 54 In this study (n=122; 90 male patients; mean age, 37±12 years), patients with ER in the inferolateral leads with >3 episodes of idiopathic VF (including those with electrical storms) had empirical antiarrhythmic drug therapy prescribed by the treating physicians.…”