Abstract 17607: MicroRNA Expression Profiles in Endomyocardial Biopsies From Patients With Myocarditis - Association With Left Ventricular Function and Clinical Events

Abstract

Background: Myocarditis represents an important cause of chronic dilated cardiomyopathy. Predicting the clinical course of patients with myocarditis is difficult and the prognostic value of current histological markers remains controversial. We tested whether expression of selected microRNAs (miRNAs) in endomyocardial biopsies is related to left ventricular (LV) function and clinical events in patients with myocarditis. Methods: Endomyocardial biopsies were obtained from patients with non-inflammatory dilated cardiomyopathy (n=22) and histologically proven myocarditis (n=81). Based on literature search, we predefined a set of 6 miRNAs implicated in inflammation (miR-155, miR-146b), heart failure (miR-21, miR-133a), endothelial cell (miR-126) and skeletal muscle function (miR-206). Expression of these miRNAs in endomyocardial biopsies was quantified by RT-PCR. Results: Expression of miR-133a, miR-206 and miR-155 was markedly upregulated in endomyocardial biopsies from patients with myocarditis as compared to patients with dilated cardiomyopathy, irrespective of viral or non-viral etiology. Levels of miR-133a (R=0,68, P<0,01) and miR-155 (R=0,65, P<0,01) significantly correlated with CD68 cell count in endomyocardial biopsies from patients with myocarditis. Patients with myocarditis and preserved LV function at study entry displayed higher endomyocardial expression of miR-133a than patients with reduced LV function. Higher expression levels of miR-133a were associated with improved LV function during a mean follow-up of 3,1 years. Importantly, in a Kaplan-Meier estimate, patients with myocarditis and miR-133a levels above median showed longer survival free of death and malignant arrhythmias. Conclusion: The present study demonstrates that in a predefined set of miRNAs, relevant to cardiovascular pathology, endomyocardial miR-133a levels correlate with macrophage infiltration, improved LV function and clinical outcome in a comparatively large cohort of patients with histologically proven myocarditis. miR-133a may serve as a potential novel biomarker and therapeutic target in human myocarditis.