Myocardial and Circulating microRNA Expression Profile and Biomarker Potential in LVAD-Supported End-Stage Heart Failure Patients – a Comprehensive Review and Update of the Literature

Left ventricular assist devices (LVAD) have been widely adopted for the treatment of both pediatric and adult patients with end-stage heart failure. By unloading the failing ventricle, maintaining sufficient end-organ perfusion, and improving the heart's functional capacity, they are increasingly used as bridges to recovery, cardiac transplantation, or destination therapy, thus improving patients' overall survival rate and life quality. However, beyond their life-sustaining functions, these devices pumping total cardiac output may have a range of short and long-term harmful effects initiated by interactions of blood cells with artificial surfaces at the LVAD/Host interface or by non-physiological flow conditions generated by these devices. One of the major challenges in LVAD therapy is the lack of satisfactory sensitivity and specificity of the currently available biomarkers, making it difficult to differentiate the patients who will benefit from LVAD placement from those at high risk for adverse events and poor outcomes. To this end, myocardial miRNAs have emerged as promising targets for investigating heart failure-related molecular pathways. In addition, extracellular circulatory miRNAs whose concentrations change with pathological state and disease progression may also mediate intercellular signaling pathways that are important in the functional and structural changes associated with the development and progression of HF. Herein, we provide a comprehensive overview of the currently known cardiac miRNAs involved in LVAD-induced myocardial reverse remodeling, remission, and recovery, and circulatory cell-free and platelet-enriched miRNAs that may serve as potential non-invasive biomarkers for pre-LVAD decision-making or monitoring and predicting patient response to LVAD therapy.