A micro-ribonucleic acid signature associated with recovery from assist device support in 2 groups of patients with severe heart failure

Abstract

Objectives: This study was conducted to test the hypothesis that cardiac micro-ribonucleic acid (miR) profiling in severe heart failure patients at the time of ventricular assist device (VAD) placement would differentiate those who remained VAD-dependent from those with subsequent left ventricular (LV) recovery.

Background: The relationship of myocardial miR expression to ventricular recovery is unknown.

Methods: We studied 28 patients with nonischemic cardiomyopathy requiring VAD support consisting of test and validation cohorts from 2 institutions: 14 with subsequent LV recovery and VAD removal and 14 clinically matched VAD-dependent patients. Apical core myocardium was studied for expression of 376 miRs by polymerase chain reaction (PCR) array and real-time-PCR methods. Samples from 7 nonfailing hearts were used in confirmatory studies.

Results: By PCR array, 10 miRs were differentially expressed between LV recovery and VAD-dependent patients in the test cohort. The real-time PCR confirmed lower expression in LV recovery patients for 4 miRs (15b, -1.5-fold; 23a, -2.2-fold; 26a, -1.4-fold; and 195, -1.8-fold; all p < 0.04 vs. VAD dependent). The validation cohort similarly showed lower miRs expression in LV recovery patients (23a, -1.8-fold; and 195, -1.5-fold; both p < 0.03). Furthermore, miR 23a and 195 expression in nonfailing hearts was similar to LV recovery patients (both p < 0.04 vs. VAD dependent). The LV recovery patients also had significantly smaller cardiomyocytes by quantitative histology in both cohorts.

Conclusions: Lower cardiac expression of miRs 23a and 195 and smaller cardiomyocyte size at the time of VAD placement were associated with subsequent LV functional recovery. Differential expression of miRs at VAD placement may provide markers to assess recovery potential.