Changes in Metabolomic Profile on End-Stage Heart Failure Patients Before and After Durable Left Ventricular Support Device

Document Type

Conference Proceeding - Restricted Access

Publication Date

5-9-2025

Abstract

Left ventricular assist device (LVAD) support helps reverse the hemodynamic derangements seen in end-stage heart failure and can promote reverse remodeling. Our aim was to evaluate the changes in metabolomic profiles of myocardial tissue and peripheral blood in patients receiving LVAD support.

Paired blood and tissue samples were collected at LVAD implantation and heart transplantation. Metabolomic profiling of blood (n=8) and tissue samples (n=12) was conducted using the Biocrates Quant 500 XL assay which integrates targeted liquid chromatography-mass spectrometry (LC-MS) with proton nuclear magnetic resonance spectroscopy (¹H NMR). To identify changes in biochemical pathways related to durable circulatory support, linear modeling, metabolic pathway enrichment, metabolite functional analysis, and machine learning approaches were applied.

We measured 638 metabolites in serum and 529 in tissue. Linear modeling showed few differences in metabolite concentration. Metabolomic pathway enrichment analysis showed significant upregulation of glycerolphosphoserines, phosphoglycerate hydrogenase deficiency, oxoadipic aciduria, and hydroxy-3-methylglutaryl CoA lyase pathways in blood. Pathways related to obesity and the phosphosphingolipid subclass were found to be significantly upregulated in tissue after LVAD implantation. Mixed-effects analysis of metabolite functional groups shows an upregulation of phosphatidylglycerols, phosphatidic acids, and phosphatidylethanolamines, and downregulation of triglycerides in both tissue and blood.

LVAD support is associated with metabolic alterations at both the local and systemic levels. Our findings demonstrate upregulation of specific lipid pathways in blood and in myocardium following LVAD implantation. These metabolic shifts during LVAD support could provide information about new potential pathways in reverse remodeling.

Comments

2025 Research Day Corewell Health West, Grand Rapids, MI, May 9, 2025. Abstract 1700

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