Abstract 11858: A Metabolomic Study of Thrombosis After Cardiac Surgery in Children With Congenital Heart Disease

Abstract

Background: Thrombosis is a major complication after cardiac surgery in children with congenital heart disease (CHD), and it significantly increases the risk of mortality and other complications and prolongs hospital stay. The underlying mechanisms for the development of thrombosis after cardiac surgery in children with CHD remain poorly understood. Aim: To identify novel circulating metabolites before cardiac surgery that are associated with the development of thrombosis in children with CHD after surgery. Methods: Untargeted metabolomic data on 1,006 metabolites were measured in plasma from 100 children (age range: 0 days-18 years) with CHD undergoing cardiac surgery. A total of 740 metabolites met quality control criteria (call rate>70% and Spearman correlation coefficient between blind duplicates>0.5). Kruskal Wallis test was used to examine the difference in concentrations of individual metabolites between those who developed thrombosis and those who did not. Results: In total, 16 children (16%) developed thrombosis. Among the 740 metabolites, 170 showed differences at a false discovery rate (FDR) of less than 0.01. The top three metabolites showing the strongest associations with thrombosis were 5-methylthioadenosine (MTA), cytidine, and eicosapentaenoate (EPA; 20:5n3) with an FDR of 0.003. Pathway analysis showed that pathways of Arginine biosynthesis (P=7.67х10 -4 ), nicotinate and nicotinamide metabolism (P=0.001), and aminoacyl-tRNA biosynthesis (P=0.008) were significantly enriched. Conclusion: We have identified promising novel metabolites associated with thrombosis in children with CHD who have undergone cardiac surgery. Replication studies are ongoing.