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Central Society for Clinical and Translational Research and Midwestern Section of American Federation for Medical Research

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2015 Combined Annual Meeting April 23 – 24, 2015 Chicago, IL

Hotel Chicago

333 N. Dearborn

Chicago, IL 60654

Combined Annual Meeting Abstracts

Cardiology/Cardiovascular Disease

ID: 2 MICRORNA EXPRESSION PATTERN IN PATIENTS WITH VENTRICULAR ARRHYTHMIAS AND END STAGE HEART FAILURE

T. Calway, T. Bak, K. Furlough, G. Kim. Medicine, University of Chicago, Chicago, IL.

Introduction: Patients with heart failure (Hf) are among those at greatest risk for sudden cardiac death. Despite the advancement in medical and device therapy for Hf, there remains a high incidence of cardiac arrhythmias with a highly unpredictable nature. Ventricular tachyarrhythmias (VA) occur frequently in Hf, irrespective of the etiology, identifying an inseparable relationship between the arrhythmogenic and failing heart substrate. MicroRNAs (miRs) are critical regulators of diverse biological processes; however, studies of miRs and arrhythmia remain sparse, particularly in humans. Given their inherent pleiotropic actions to repress multiple gene targets simultaneously, microRNAs (miRNAs) are well poised to play a comprehensive and integrative role coordinating the interplay among electrical, contractile, and structural components that drive Hf-induced ventricular tacharrhythmias. We recently reported on the role of miR-130a in regulation of the gap junction protein, connexin43 (Cx43) and arrhythmogenesis in HF. Induction of miR-130a expression in murine heart in a cardiomyocyte-specific manner is sufficient to induce both atrial and ventricular tachyarrhythmias. We sought to determine whether elevated levels of miR-130a in explanted heart tissue from human patients was associated with the presence of VAs.

Methods: A prospective study of miR levels in myocardium was performed to determine the association between miR-130a levels and VAs. Subjects were enrolled between January 2013 and June 2014. Patients with high VA burden were defined as: 1) history of VA storm within the preceding 3 months, or 2) greater than five defibrillator shocks at the time of admission. Subjects with ischemic heart disease were excluded. Controls in this study were subjects listed for transplantation with a diagnosis of non-ischemic dilated cardiomyopathy with: 1) no prior history of VAs, or 2) not receiving antiarrhythmic medication …

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