Mitral Regurgitation Severity at LVAD Implantation is Associated with Distinct Myocardial Transcriptomic Signatures

Objectives We examined for differences in pre-left ventricular assist device (LVAD) myocardial transcriptome between patients with different degrees of MR. Methods From 1/2018 to 10/2019, we collected left ventricular cores during durable LVAD implantation (n=72). Retrospective chart review was performed. Total RNA was isolated from LV cores and used for the construction of cDNA sequence libraries. The libraries were sequenced in nova seq with data quantified using Kallisto. Gene Set Enrichment Analysis (GSEA) or Gene Ontology (GO) analyses were performed with FDR Results Comparing patients with preoperative mild or less MR (n=30) versus moderate-severe MR (n=42), the moderate-severe MR group weighted less (P=0.004), and had more tricuspid valve repairs (P=0.043) without differences in demographics or comorbidities. We then compared both groups to human donor hearts without heart failure (n=8). Compared to donor hearts, there were 3985 differentially expressed genes (DEGs) for mild or less MR and 4587 DEGs for moderate-severe MR. Specifically altered genes included 448 DEGs for specific for mild or less MR and 1050 DEGs for moderate-severe MR. On GSEA, common regulated genes showed increased immune gene expression and reduced expression of contraction and energetics genes. Of the 1050 genes specific for moderate-severe MR, there were additional upregulated genes related to inflammation and reduced expression of genes related to cellular proliferation. Conclusions Patients undergoing durable LVAD implantation with moderate-severe MR had increased activation of genes related to inflammation and reduction of cellular proliferation genes. This may have important implications for myocardial recovery.