Ventricular tachycardia circuits in healed myocardial infarction scars uniquely exhibit upregulation of KCNE3 and KCNE4, creating a distinct pattern of repolarization heterogeneity that supports reentry.
Does repolarization heterogeneity driven by specific ion channel expression create the substrate for ventricular tachycardia circuits in healed myocardial infarction scar?
This study identifies a novel mechanism for post-infarct ventricular tachycardia, demonstrating that localized repolarization heterogeneity driven by KCNE3 and KCNE4 upregulation creates the necessary substrate for reentry.
Arrhythmias originating in scarred ventricular myocardium are a major cause of death, but the underlying mechanism allowing these rhythms to exist remains unknown. This gap in knowledge critically limits identification of at-risk patients and treatment once arrhythmias become manifest. Here we show that potassium voltage-gated channel subfamily E regulatory subunits 3 and 4 (KCNE3, KCNE4) are uniquely upregulated at arrhythmia sites within scarred myocardium. Ventricular arrhythmias occur in areas with a distinctive cardiomyocyte repolarization pattern, where myocyte tracts with short repolarization times connect to myocytes tracts with long repolarization times. We found this unique pattern of repolarization heterogeneity only in ventricular arrhythmia circuits. In contrast, conduction abnormalities were ubiquitous within scar. These repolarization heterogeneities are consistent with known functional effects of KCNE3 and KCNE4 on the slow delayed-rectifier potassium current. We observed repolarization heterogeneity using conventional cardiac electrophysiologic techniques that could potentially translate to identification of at-risk patients. The neutralization of the repolarization heterogeneities could represent a potential strategy for the elimination of ventricular arrhythmia circuits.
Kelemen et al. (Fri,) conducted a other in Post-infarct ventricular tachycardia (n=25). Molecular and electrophysiological mapping of VT circuits vs. Non-VT scarred myocardium and healthy remote myocardium was evaluated on Repolarization heterogeneity and KCNE3/KCNE4 expression in VT circuits. Ventricular tachycardia circuits in healed myocardial infarction scars uniquely exhibit upregulation of KCNE3 and KCNE4, creating a distinct pattern of repolarization heterogeneity that supports reentry.