LVAD-Induced Improvement in Myocardial Function Is Associated with a Unique Pattern of Circulating microRNAs

Purpose MicroRNAs (miRNAs,) are small non-coding molecules that negatively regulate gene transcription.MiRNAs show unique patterns of expression both in the myocardium and blood of chronic heart failure (HF) patients.A subset of HF patients experience myocardial functional improvement following mechanical unloading induced by left ventricular assist device (LVAD).The aim of this study was to determine whether functional improvement is associated with measurable changes in circulating miRNAs. Methods and Materials LVAD- induced myocardial functional response was defined as a relative increase in left ventricular (LV) ejection fraction >50% and a relative decrease in LV end- systolic volumes >25% (LVAD Responders).Peripheral blood samples were collected after continuous flow LVAD unloading from two patients’ groups: LVAD Responders (n=7) and LVAD- Non Responders (n=11).Profiling of 14 circulating miRNAs previously shown to be abnormally expressed in HF (miRNAs -15b,-208;-499;-205;-133a;-133b;-145;-21;-29a;-9;-195,-23a,-200b) was performed in serum samples and normalized to the level of miR 16 that was used as an endogenous control. Results Average duration LVAD support was 157± 87 days. MiRNAs- 15b and- 133b were present at significantly higher levels in serum of LVAD Non -Responders compared to LVAD Responders (15.78 fold, p Conclusions Functional myocardial response to LVAD unloading was associated with lower circulating levels of miRs -15b and – 133b, which may increase expression of their correspondingly regulated genes.The full biological significance of this finding and the contribution of these specific miRNAs to HF recovery as well as the potential use of these molecules to predict myocardial improvement in LVAD recipients warrants further investigation.