RNA Sequencing Identifies Novel Genes That Could Modulate Bleeding Risk in Heart Failure Patients after LVAD Placement

Abstract

Purpose The overall success of modern left ventricular assist devices (LVADs) has been mitigated by the complication of gastrointestinal (GI) bleeding. While evidence suggests that anticoagulation and acquired von Willebrand factor deficiency contribute, these two factors do not fully explain all bleeding events. Methods and Materials To identify new targets contributing to bleeding risk in patients with mechanical support we performed whole blood RNA sequencing on 9 patients before LVAD placement, then 7 days and 180 days postoperatively. A paired t-test and false discovery rate method were used to identify statistically significant changes in expression. Transcripts unique to patients with GI bleeding events were identified by comparing the transcriptome of those with GI bleeding (n = 3) to those without bleeding (n = 6) 7 days after LVAD placement. Results Bleeding events occurred between 12 and 202 days after LVAD implant (median 18 days). Glutaredoxin (GLRX) and glutaredoxin 2 (GLRX2) decreased in patients with bleeding 7 days after LVAD implant, but increased in those without bleeding events at 7 days (p = 0.0004 and p = 0.004, respectively). Furthermore, a family of RAB genes were differentially expressed in patients with bleeding compared to non-bleeders 7 days following LVAD implant. These genes include RAB18, RAB1A, RAB21, RAB11A, and RABEP1. Other genes of interest that were significantly and differentially expressed in bleeders versus non-bleeders included transmembrane protein 54 (TMEM54) and family with sequence similarity 26, member F (FAM26F). Conclusions We have identified novel genes that are differentially expressed in LVAD patients who develop GI bleeding. These findings provide an initial step towards uncovering mechanisms that may affect GI bleeding in patients with LVADs.