PLATELET MIRNA PROFILE IN PATIENTS WITH LVAD: A NEW MARKER TO PREDICT BLEEDING EVENTS?

Objectives: MicroRNAs (miRs) emerged as promising diagnostic and therapeutic markers in heart failure. To date, few studies investigated miR patterns in LVAD patients, but none focused on the association between platelet miRs and the development of adverse events. We investigated for the first time the potential clinical utility of platelet miRs in the setting of durable LVAD support. Methods: We prospectively determined by quantitative real-time polymerase chain reaction the expression levels of selected platelet miRs known to be involved in platelet activation, coagulation, and cardiovascular diseases in consecutive LVAD patients. Data were longitudinally measured before LVAD implant and after 1, 6, and 12 months of LVAD support. Data were compared with those measured in healthy volunteers (controls). In silico analysis was also performed to identify pathways related to differentially expressed miRs. Results: Data from 15 consecutive LVAD patients and 5 controls were analyzed. The pre-implant expression levels of platelet miR-126, miR-374b, miR-223 and miR-320a were significantly different in patients vs. controls. Following LVAD implantation, the expression levels of platelet miR-25, miR-144, miR-320 and miR-451a changed significantly over the course of LVAD support. In silico analysis revealed that these miRs are implicated in both cardiac- and coagulation-associated pathways. Of note, patients who suffered from bleeding (n=5, 33%) had significantly higher pre-implant expression levels of platelet miR-151a and miR-454 with respect to patients who did not. The same miRs were also differentially expressed in bleeders following LVAD implantation early before the clinical manifestation of the events. Conclusions: This study provides proof-of-concept evidence of significant modulation of platelet miRs expression driven by LVADs. Importantly, our data suggest the possible existence of a platelet miRs signature predictive of bleeding events and open the perspective for the development of novel therapeutic strategies targeted to platelet miRs modulation in patients identified at high risk of LVAD-related adverse events.