Abstract 20568: Increased MicroRNA-130a in Patients With Ventricular Tachycardia and End-Stage Heart Failure
Introduction: MicroRNAs (miRs) are endogenous ~22 nucleotide RNA molecules that are critical regulators of diverse biological processes; however, studies of miRs and arrhythmia remain sparse in human hearts. Cardiac arrhythmias result in extensive morbidity and mortality and significantly affect the quality of life of patients. We recently reported on the role of miR-130a in regulation of the gap junction protein, connexin43 (Cx43). Increased expression of miR-130a in mice resulted in both atrial arrhythmias and ventricular tachycardia (VT) via a loss of cardiac Cx43. We aimed to determine whether levels of miR-130a in explanted heart tissue from human patients correlated with the presence of ventricular tachyarrhythmias.
Methods: A prospective study was performed to determine the association between miR-130a levels and VT. Subjects were enrolled at the time of listing for transplantation at the University of Chicago between June 2013 and June 2014. Patients with high arrhythmia burden were defined as: 1) history of VT storm within the preceding 3 months, or 2) greater than five defibrillator shocks at the time of admission. Controls in this study were subjects listed for transplantation with a diagnosis of non-ischemic dilated cardiomyopathy with: 1) no prior history of ventricular tachycardia, or 2) not receiving antiarrhythmic medication at the time of admission. Subjects with atrial fibrillation were excluded from the analysis.
Results: Six patients with a history of VT were identified and compared to six patients with non-ischemic cardiomyopathy. In both groups, the ejection fraction (EF) was equally reduced (21.5 ± 1.4% (nonVT) vs. 21.9 ± 2.3% (VT), p=0.9). All patients were supported with an intra-aortic balloon pump at the time of transplantation. Using quantitative PCR, we found that miR-130a levels were increased by 2.9 fold in patients with VT storm compared to non-VT controls (p=0.0012). Cx43 protein levels were reduced by 53% in patients with VT compared to those who did not.
Conclusions: Myocardial miR-130a levels are increased by nearly 3-fold in patients with VT and end-stage heart failure. These results provide important mechanistic insight into the possible role of miRs and ventricular tachyarrhythmias in human hearts.
Author Disclosures: T. Calway: None. T. Bak: None. G. Kim: None.
- © 2014 by American Heart Association, Inc.