Abstract 15556: Effects of Left Ventricular Assist Device Support on microRNA Levels

Objectives: To examine changes in a broad panel of circulating microRNAs (miRs) following left ventricular assist device (LVAD) support in advanced heart failure (HF). Background: LVAD therapy unloads the failing heart and may result in partial reversal of the end stage HF phenotype; however, molecular changes with support have not been well defined. MicroRNAs are small nucleotide RNAs involved in the pathogenesis of HF and have been postulated to have a potential role as circulating biomarkers or as therapeutic modalities. Human studies of the role of miRs in end stage HF have been limited. Methods: 23 distinct miRs, previously shown to play a role in the pathogenesis of HF, were measured in frozen plasma collected from 40 individuals prior to continuous flow LVAD implantation, and at a median of 96.5 (interquartile range, IQR: 72.25-149.75) days after implantation. Quantitative real-time PCR was performed for miR amplification. Ultimately, 19 miRs (miR-15b, -16, -21, -24, -27a, -29a, -92a, -103, -126, -133a, -146a, -146b, -155, -159a, -195, -221, -222, -320, -423) were expressed in >80% of patient samples. Wilcoxon Rank Sum Tests were used to compare median relative quantification values pre- and post-LVAD placement. Results: The median age of patients was 67 years, and 60% were INTERMACS 1-2 prior to LVAD implantation. Following LVAD implantation, seven miRs (miR-21, -92a, -103, -159a, -195, -320, -423) were downregulated while 12 miRs (miR-15b, -16, -24, -27a, -29a, -126, -133a, -146a, -146b, -155, -221, -222) were up-regulated. After correction for multiple testing, only miR-155 was associated with significant up-modulation in plasma expression levels with LVAD support. Conclusions: While most plasma levels of miRs associated with cardiovascular pathophysiology remained unchanged with LVAD support, miR-155, which has been shown to play a role in cardiac hypertrophy, was up-regulated. The biological relevance of miR-155 in this setting requires further study.