Micro-RNA-451 and Measures of Hemolysis Associated with Left Ventricular Assist Device Implantation

Abstract

Purpose Hemolysis is a well-known complication of left ventricular assist device (LVAD) implantation that contributes to hemodynamic derangement and end-organ damage. Micro-RNAs (miRs) are non-coding RNA species that control gene expression by targeting specific messenger RNAs for degradation. MiR-451 is specifically expressed in erythrocyte precursors and mature red blood cells. The goal of this study was to evaluate changes in circulating miR-451 levels before and after LVAD implantation and whether these changes associate with measures of hemolysis. Methods and Materials Blood samples were obtained from healthy volunteers and from patients with advanced heart failure at the time of LVAD implantation and at the time of explantation. Absorbance at 414 nm (ABS 414 ), the maximum absorbance of hemoglobin, was measured in plasma. RNA was extracted from plasma and RT-PCR specific for miR-451 was performed. Results The mean duration of LVAD therapy was 488 ± 179 days. Plasma ABS 414 correlated with the degree of hemolysis of blood that was mechanically disrupted in vitro. The mean plasma ABS 414 was increased 3.4-fold after LVAD implantation compared to paired pre-implantation samples (P=0.05), which had a mean plasma ABS 414 comparable to non-hemolyzed control samples. Lactate dehydrogenase and bilirubin, commonly used tests for hemolysis, each correlated poorly with plasma ABS 414 among these patients (R2=0.20 and 0.22, respectively; each P nonsignificant) and did not differ between pre- and post-LVAD samples. Compared to control plasma, miR-451 levels were roughly 40% higher in samples from heart failure patients before LVAD placement. Plasma miR-451 levels increased 164-fold after LVAD implantation compared to paired pre-implant samples (Mann-Whitney P= 0.002). Conclusions Micro-RNAs hold promise as biomarkers in heart failure. MiR-451 may be a new marker of hemolysis related to LVAD implantation that performs favorably compared to traditional markers.