Pseudo-targeted metabolic profile differences between emergency patients with type 1 and type 2 myocardial infarction diagnosed by optical coherence tomography

It is difficult to distinguish type 2 myocardial infarction (T2MI) from type 1 myocardial infarction (T1MI), although their management varies. Using optical coherence tomography (OCT) and pseudo-targeted metabolomics to identify biomarkers, investigate metabolic differences, and establish a T2MI subclassification. Among 1519 patients with MI, 97 T2MI patients are identified who are 1:1 matched with 97 T1MI patients after considering age, gender, ST-segment elevation, time from onset to coronary angiography, and hs-cTnI on admission by propensity score matching. Plasma pseudo-targeted metabolomics at baseline was determined. The clinical characteristics of the two groups were comparable, while the T1MI showed more severe coronary lesions than T2MI according to OCT imaging. 90 differential metabolites were identified between the two groups, among 1027 endogenous metabolites in 20 classes. N-Acetyl-L-Leucine, free fatty acid (15:1), Thymidine-5′-triphosphate, Mevalonic acid 5-pyrophosphate, and five oligopeptides were candidate biomarkers (AUC ≥ 0.85) distinguishing T2MI from T1MI. 12 KEGG pathways showed significant differences, mainly involving amino acid, nucleotide, and their derivatives metabolism, and signaling pathways such as mTOR, cGMP-PKG, and cAMP. Other differences were observed in TCA cycle (P = 0.08) and ROS (P = 0.05). Proteolysis and coronary heart disease risk lipid level were lower in T2MI. T2MI had a decrease of differential abundance score in almost all the KEGG enrichment pathways. Furthermore, T2MI can be subdivided into three subtypes by hierarchical cluster analysis of AUCs with causes/triggers of T2MI. There are significant metabolic profile differences between T1MI and T2MI. Several candidate metabolic biomarkers can effectively distinguish the two groups. Clinical trial registration: ClinicalTrials. gov NCT03297164.