Global Lipidomic and Metabolomic Uncovers Blood Signatures of Left Ventricular Assist Devices for Heart Failure

Abstract

Background: The left ventricular-assist device (LVAD) significantly improves the health of patients with chronic advanced heart failure (HF); however, its underlying molecular mechanisms remain unclear. This study aimed to develop an integrated plasma pseudo-targeted lipidomic and untargeted metabolomic strategy to provide insight into the early postoperative changes that occur in the global blood metabolome profile and determine whether these changes can be used to screen patients for LVAD installation. Methods: Data was collected from 20 pairs of patients with HF before and after LVAD surgery and compared with 36 healthy subjects. Plasma metabolomic and lipidomic profiles were established by liquid chromatography-mass spectrometry and analyzed by multivariate statistics. Results: A total of 49 lipids showed significant recovery after LVAD pump loading compared with before pump loading. Moreover, 144 differential metabolites and 21 pathways were identified from healthy control and patients with HF. Among which, 33 metabolites were differentially regulated between pre and post-LVAD samples (p < 0.05, FC > 2). Further analysis revealed differential regulation in two key pathways: fatty acid metabolism and methionine metabolism. Simultaneously, we identified S-adenosylmethionine, L-methionine, FFA (14:1), and FFA (16:1) as potential diagnostic markers for the prediction of LVAD efficacy in HF. In three postLVAD patients who died within one year, we observed a decrease in SM (24:0) and SM (22:0) immediately before LVAD implantation, indicating that these metabolites may predict a poor outcome. Furthermore, we demonstrated that PS (18:1/20:4) and canavaninosuccinate were significantly attenuated in postLVAD patients. Conclusions: Our findings provide preliminary evidence that LVAD therapy is associated with changes in the metabolomic and lipidomic profiles of patients with HF. It highlights the potential use of metabolomics as a tool to stratify LVAD patients based on the risk of adverse events. These findings may help to guide patient selection for advanced HF therapies and identify new HF therapeutic targets.