Mitral regurgitation severity at left ventricular assist device implantation is associated with distinct myocardial transcriptomic signatures.

Abstract

OBJECTIVES\nWe examined for differences in pre-left ventricular assist device (LVAD) implantation myocardial transcriptome signatures among patients with different degrees of mitral regurgitation (MR).\n\n\nMETHODS\nBetween January 2018 and October 2019, we collected left ventricular (LV) cores during durable LVAD implantation (n\xa0=\xa072). A retrospective chart review was performed. Total RNA was isolated from LV cores and used to construct cDNA sequence libraries. The libraries were sequenced with the NovaSeq system, and data were quantified using Kallisto. Gene Set Enrichment Analysis (GSEA) and Gene Ontology analyses were performed, with a false discovery rate <0.05 considered significant.\n\n\nRESULTS\nComparing patients with preoperative mild or less MR (n\xa0=\xa030) and those with moderate-severe MR (n\xa0=\xa042), the moderate-severe MR group weighted less (P\xa0=\xa0.004) and had more tricuspid valve repairs (P\xa0=\xa0.043), without differences in demographics or comorbidities. We then compared both groups with a group of human donor hearts without heart failure (n\xa0=\xa08). Compared with the 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 energetic genes. Of the 1050 genes specific for moderate-severe MR, there were additional up-regulated genes related to inflammation and reduced expression of genes related to cellular proliferation.\n\n\nCONCLUSIONS\nPatients 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.