A Pilot Serum Metabolomics Reveals Mitochondrial Dysfunction and Identifies Methylguanidine as a Potential Diagnostic Biomarker for ATAAD with Mesenteric Malperfusion Syndrome

Background: Acute type A aortic dissection complicated by mesenteric malperfusion syndrome (ATAAD-MMPS) is a highly lethal emergency with diagnostic challenges due to rapid progression and non-specific symptoms. This pilot study aimed to characterize the serum metabolomic and lipidomic alterations specific to ATAAD-MMPS and identify potential early diagnostic biomarkers. Methods: Serum samples from healthy controls, patients with uncomplicated ATAAD, and patients with ATAAD-MMPS were analyzed using targeted metabolomics and lipidomics. Multivariate statistical analyses were performed to discriminate between groups and identify differentially abundant metabolites and lipids. Pathway analysis was conducted to explore underlying pathological mechanisms. Results: Metabolomic profiles clearly distinguished ATAAD-MMPS from uncomplicated ATAAD, whereas lipidomic changes were primarily associated with ATAAD itself rather than the presence of mesenteric malperfusion. Metabolic pathway analysis revealed significant perturbations in the citric acid cycle, suggesting mitochondrial involvement as a potential pathological feature. Notably, methylguanidine was uniquely and markedly elevated in the ATAAD-MMPS group, demonstrating potential diagnostic value in distinguishing this lethal complication from uncomplicated ATAAD in this exploratory cohort (AUC = 0.923). Conclusions: This pilot study identifies distinct metabolic signatures associated with mesenteric malperfusion in ATAAD, with mitochondrial metabolic perturbations emerging as a potential contributing mechanism. Methylguanidine represents a candidate early diagnostic biomarker for ATAAD-MMPS, warranting validation in larger prospective studies. These findings provide a foundation for improved diagnostic strategies for this devastating condition.