An untargeted metabolic profiling of myocardium and serum in patients with left ventricular assist devices

Background: Mechanical unloading via left ventricular assist devices (LVADs) is an established therapy for end-stage heart failure (ESHF). Although LVAD support improves hemodynamics and can promote structural reverse remodeling, the accompanying metabolic changes within the myocardium and systemic circulation remain insufficiently defined. The objective of this study was to describe metabolic signatures associated with LVAD support in ESHF using an unbiased, untargeted profiling approach. Methods: Paired serum (N = 8) and myocardial tissue (N = 12) samples were collected from ESHF patients at two timepoints: at LVAD implantation and at heart transplantation. Global metabolic profiling was conducted using untargeted liquid chromatography-mass spectrometry (LC-MS). Differential abundance analysis was carried out to identify metabolites with significant changes between time points, with filtering applied to exclude pharmaceutical metabolites and metabolites lacking annotations. Results: In myocardial tissue, LVAD support was associated with lower levels of adenosine-5-diphosphate (logFC -0.58, FDR q < 0.05) and octanoic acid (logFC -0.32, FDR q < 0.05), metabolites related to cellular energetics and fatty acid oxidation pathways. In contrast, androsterone glucuronide (logFC 1.44, FDR q < 0.05) and estrone (logFC 0.9, FDR q < 0.05) increased following LVAD support, indicating shifts in steroid-related metabolic pathways. Serum profiles differed from tissue findings and were characterized primarily by reduced pyruvic acid levels (logFC -0.65, FDR q < 0.05) post-LVAD support, consistent with a reduction in systemic anaerobic glycolysis and improved peripheral perfusion. Conclusion: We show that LVAD support is accompanied by measurable tissue-specific metabolic differences. While systemic changes appear to reflect the clearance of glycolytic byproducts due to improved perfusion, the myocardium is characterized by changes in energetic substrates and steroid metabolites. These findings suggest that mechanical unloading may facilitate a re-regulation of cardiomyocyte metabolism, offering further insight into the physiology of reverse remodeling. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.