NGS PBMC Transcriptome Analysis Identifies More Pronounced Activation of the Inflammatory Response in Advanced INTERMACS Class Before MCSD Implantation

s S39 on immune system function in relationship to INTERMACS class prior to MCSD-implantation is virtually non-existent. We hypothesized that preMCSD peripheral blood mononuclear cell (PBMC) gene expression profiling (GEP) by next-generation sequencing (NGS) identifies a subgroup of patients with higher risk of post MCSD MODS. Methods: PBMC samples from 8 AdHF patients (53±25 years old) undergoing MCSD implantation included in the prospective MultiOrgan Dysfunction Expression (MOD-E) profiling study between August 2012 2013. Obtained 1 day before surgery, and at days 1, 3, 5 and 8 postoperatively were collected for 3 INTERMACS level 3 patients (n= 3) and 5 patients (n= 5) INTERMACS level 1-2. Purified mRNA was subjected to whole-genome NGS analysis. Differentially expressed genes where identified by Two-way ANOVA and Benjamini-Hochberg correction. Only those with fold change of at least 1.5 were included in the analysis. Hierarchically clustering was used for visualization. Biological significance was assessed by gene ontology and pathway analysis. Results: Compared to INTERMACS level 3, patients in the higher risk categories had dramatic differences in their gene expression profiles before and across all 5 time points (Figure 1). Over 3100 different genes were identified and mechanistically linked to the systemic inflammatory response by their biological significance. Gene ontology and pathway analysis revealed significant enrichment of immune related categories and pathways. Conclusion: In AdhF patient facing MCSD-implantation, NGS-based PBMC GEP correlates with clinical severity as assessed by INTERMACS class prior to as well as early after MCSD-implantation and may be further develop to assist in improved patient selection.