Abstract 13104: Differential Expression of Serum MicroRNAs is Associated with Recovery from Heart Failure
Objective: Recovery of left ventricular (LV) function in nonischemic cardiomyopathy is variable and unpredictable. Our aim was to test the hypothesis that serum microRNAs (miRs) expression profiling from heart failure (HF) patients with resent onset severe nonischemic cardiomyopathy would identify the potential for LV recovery.
Methods: We studied 24 nonischemic HF patients, aged 48±14, with onset <6 months and ejection fraction (EF) <25%, enrolled in the Intervention in Myocarditis and Acute Cardiomyopathy II (IMAC 2) trial. Serum collected at entry was compared for miR expression between patients with LV recovery (EF >50% after 6 months; Recovered group) vs. clinically matched HF patients with no EF improvement [Persistent Heart Failure group] (Combined Data: Age: 48±14, Males: 100%, EF: 17±4%, LV size: 6.5±0.7cm; p=ns between groups). Serum expression of 376 miRs was compared by PCR-based array in a test cohort (n=6 each), and confirmed by additional real-time PCR in a validation cohort (n=12 each, including 6 each from the test cohort).
Results: Combined baseline EF was 17±4%, p=ns between groups. After 6 months, EF was 53±2% (Recovered) and 18±0.6% (Persistent HF), p<0.01. 10 miRs were differentially expressed between the Recovered and Persistent HF groups when measured by PCR array. Of these, miRs-16, 25 and -92a demonstrated significantly higher expression in the Recovered group (p<0.04; Fig 1) when confirmed by individual RT-PCR analyses. Pathway analysis revealed intersection of inhibitory effects of all 3 miRs on E2F transcription factor-1 (shown to promote cardiomyocyte hypertrophy), and MAPK8 (modulates cardiomyocyte hypertrophy and TNF-α mediated apoptosis).
Conclusions: Increased expression of serum miRs -16, -25 and 92a at presentation of recent onset cardiomyopathy is associated with LV recovery. Serum miR expression is a novel and convenient means to assess potential for LV recovery in HF patients with recent onset cardiomyopathy.
- © 2011 by American Heart Association, Inc.