Plasma Metabolomics in Perioperative Period of Defect Repair in Patients with Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

Background The pathophysiological alterations in response to shunt correction in patients with pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) is still not clear. Purpose To explore the dynamic plasma metabolite profiling and its relationship with clinical characteristics in patients with CHD-PAH during the perioperative period of defect repair. Methods Plasma samples from 13 patients with CHD-PAH were harvested at four time points: before cardiopulmonary bypass (CPB) after anesthesia (Pre), immediately after CPB (T0), 24 h (T24), and 48 h (T48) after defect repair. The untargeted metabolomics strategy based on UPLC Q-TOF MS was used to detect the metabolites. Clinical measures were recorded at indicated time points. Results The sample distribution at four time points was well separated (Figure 1A, B). 193 metabolites were distinguished at different time points according to Variable Important in Projection (VIP) score (Figure 1C), enriched in pathways such as carnitine synthesis, phospholipid biosynthesis and oxidation of branched chain fatty acids (Figure 2A). 17 metabolites alterations were significantly correlated with gradients in mean pulmonary arterial pressure (mPAP) at T48 versus Pre, indicative of the response to defect correction (Figure 2B). Intriguingly, 4 out of the 17 (23.5%) metabolites including propionylcarnitine, butenylcarnitine, isobutyryl-L-carnitine and hexanoylcarnitine were enriched in oxidation of branched chain fatty acids. They were increased at both T24 and T48 (all P<0.05 except propionylcarnitine with P<0.05 at T24) (Figure 2C). Conclusions This is the first study to show the altered metabolic profiles of CHD-PAH patients in perioperative period of defect repair. Metabolites that respond to shunt correction could be a suitable non-invasive marker and would be of great value in disease monitoring and evaluating future therapeutic interventions. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): 13th Five-Year Plan–Precise Medicine–Key Research and Development Program–Clinical Cohort of Rare Disease; National Natural Science Foundation of China Figure 1. Overall analysis of metabolitesFigure 2. Shunt correction associated metabolites