Abstract 12083: A Novel MicroRNA Signature Associated with Recovery of Left Ventricular Function in Patients with Severe Heart Failure on Mechanical Circulatory Support
Objective: To test the hypothesis that expression profiling of cardiac microRNAs (miRs) in tissues obtained at ventricular assist device (VAD) placement (VAD cores) would differentiate hearts that remained VAD-dependent (D) from those which eventually recovered ventricular function (R).
Methods: VAD cores from patients with severe nonischemic cardiomyopathy who demonstrated > 6 months heart failure-free survival after VAD removal (R; n=6) were compared to VAD cores from clinically matched (age:40±12 years; 50% male, heart failure duration: 70±68 days; left ventricular (LV) ejection fraction(EF): 16±5% LV dimension: 6.1±0.8 cm; % of pulsatile VAD: 100%) patients who remained VAD-dependent (D; n=6). Myocardial expression of 376 miRs was assessed by PCR-based array, and confirmed by additional real-time PCR. miRs found to be differentially expressed between the two groups were tested in a validation cohort of samples from R and D patients (n=7 each) from a second institution, with baseline characteristics distinct from the initial cohort (age:31±9 years; 71% male, heart failure duration: 726±968 days, LV EF: 17±5% LV dimension: 7.0±1.0 cm; % of pulsatile VAD: 43% p<0.03 (except EF) compared with initial cohort) .
Results: Ten miRs were differentially expressed (p<0.002–0.05) between the R and D groups. Additional PCR methods confirmed significant fold change (R/D, with — values being lower in R) differences for 4 of these 10 miRs (miR-15b, -1.5, p<0.04; miR-23a, -2.2, p<0.04; miR-26a, -1.4, p<0.04; and miR-195, -1.8, p<0.01). Of these, miRs -23a and -195 were shown to also be differentially expressed between the R and D groups in the validation cohort (Fig 1).
Conclusions: A novel miR signature at time of VAD implantation consisting of low expression of miRs -23a and -195 was associated with LV functional recovery. Differential expression of miRs may provide markers to assess recovery potential at the time of VAD placement.
- © 2010 by American Heart Association, Inc.