Platelet Transcriptomics Following Mechanical Unloading

Purpose End-stage heart failure (HF), including patients supported by left ventricular assist devices (LVAD), is associated with dysregulated thrombo-inflammatory responses which are mediated, in part, by platelets. While functional studies of platelet activation have been undertaken in HF patients, changes in the platelet transcriptome in LVAD patients have not previously been investigated. Methods We prospectively enrolled 32 patients receiving durable continuous flow LVADs and 20 donors without HF. We longitudinally measured platelet transcriptional changes by next-generation RNA-sequencing in patients prior to and following LVAD implantation. Results Patients were followed for a mean of 57 months post-LVAD implantation. Platelets were hyperactive in HF patients, pre-LVAD, as evidenced by significantly increased formation of circulating platelet-monocyte aggregates. Transcriptional profiling identified numerous genes (n=588) that were significantly (FDR Conclusion In this first report of longitudinal changes in platelet gene expression prior to and following LVAD support, we found that HF is associated with marked alterations in the platelet transcriptome. While mechanical circulatory support results in significant resolution in the majority of differentially expressed genes, a subset of the platelet transcriptome remains persistently activated. Further studies will delineate whether or not this latter group is involved with and potentially predictive of LVAD-related adverse events.