Acute Metabolomic Changes after Implantation of a Left Ventricular Assist Device

Abstract

Purpose Implantation of a left ventricular assist device (LVAD) is associated with a significant change in cardiac output for patients with severe heart failure. We hypothesized that this abrupt change circulatory flow would be associated with acute metabolic changes related to tissue oxygen delivery. Methods We enrolled 32 patients in a prospective observational cohort study undergoing elective LVAD placement at the University of Colorado from 2013 to 2017 and collected blood immediately before surgery and 24 hours post-operatively and performed clinical follow up for a minimum of 1 year. We performed UHPLC-MS based metabolomics to quantify 24 metabolites with heavy isotope labelled standards and measured an additional 91,413 features with a minimum signal to noise ratio of 3 and minimum relative ion intensity of 1000. We performed the statistical analysis with JMP v14 and for the metabolomics analysis we report false discovery rate corrected p values. Results Subsequent heart transplantation significantly increased survival in patients undergoing elective LVAD placement (Table 1). After surgery, we noted significant changes in patients’ metabolomic profile with glutamate decreasing and kynurenine and leucine/isoleucine increasing. We also identified 6941 out of 91,413 features with an FDR corrected p value less 0.05 that were significantly different between the pre-surgery and post-surgery samples (Figure 1) Conclusion LVAD placement resulted in significant metabolomic changes after 24 hours. Subsequent analyses have the potential to identify metabolomic profiles that predict clinical outcomes or guide therapies.