Metabolomic Profiling of Adults with Congenital Heart Disease

Abstract

Metabolomic analysis may provide an integrated assessment in genetically and pathologically heterogeneous populations. We used metabolomic analysis to gain mechanistic insight into the small and diverse population of adults with congenital heart disease (ACHD). Consecutive ACHD patients seen at a single institution were enrolled. Clinical variables and whole blood were collected at regular clinical visits. Stored plasma samples were analyzed for the concentrations of 674 metabolites and metabolic markers using mass spectrometry with internal standards. These samples were compared to 28 simultaneously assessed healthy non-ACHD controls. Principal component analysis and multivariable regression modeling were used to identify metabolites associated with clinical outcomes in ACHD. Plasma from ACHD and healthy control patients differed in the concentrations of multiple metabolites. Differences between control and ACHD were greater in number and in degree than those between ACHD anatomic groups. A metabolite cluster containing amino acids and metabolites of amino acids correlated with negative clinical outcomes across all anatomic groups. Metabolites in the arginine metabolic pathway, betaine, dehydroepiandrosterone, cystine, 1-methylhistidine, serotonin and bile acids were associated with specific clinical outcomes. Metabolic markers of disease may both be useful as biomarkers for disease activity and suggest etiologically related pathways as possible targets for disease-modifying intervention.

Circular Network of Coregulated Sphingolipids Dictates Chronic Hypoxia Damage in Patients With Tetralogy of Fallot

“…Metabolomics has revealed metabolic changes in the plasma or serum of patients with CHD. Cedars et al (8) reported that the amino acid metabolic pathway was significantly changed in adult CHD, which is consistent with the results of another study (9). Cao et al (10) showed that uric acid and sphingolipid were increased in the serum of patients with VSD.…”

Amino Acid and Phospholipid Metabolism as an Indicator of Inflammation and Subtle Cardiomyopathy in Patients with Marfan Syndrome

“…In addition, as we did not know on exactly which distinct single metabolites to focus, we elected the relatively broad (albeit targeted) approach provided by the kit that we used. In concert with our metabolomics studies in patients with complex CHD, the results of our current study and the finding that the metabolomics approach is feasible in adult MFS patients may help configure a metabolomics approach methodologically adapted to requirements for patients with CHD and connective tissue disorders [24][25][26].…”

“…Biomarkers for the evaluation of the risk of the development of myocardial abnormalities are not reported in this patient group. In biventricular heart failure patients and in patients with congenital heart disease (CHD), candidate biomarkers derived from the metabolism of amino acids and lipids indicate not only general chronic low-level inflammation, oxidative stress and nitric oxide (NO) pathway alterations but also subtle myocardial dysfunction [22][23][24][25][26]. Thus, the study of amino acids and lipid metabolism offers promise, focusing on potential mechanisms of subtle alteration of myocardial function in patients with MFS.…”

Metabolomics Signatures and Subsequent Maternal Health among Mothers with a Congenital Heart Defect-Affected Pregnancy

“…There are strong lines of evidence demonstrating that fundamental role of glutamine in maintaining cardiovascular health [71], and altered D-glutamine and D-glutamate metabolisms were identified as significantly impacted pathways among adults with congenital heart disease when compared with healthy controls [72]. Furthermore, glutamine supplements have also been shown to improve the cardiac function of patients with chronic heart failure [73].…”