Potential biomarkers of pulmonary arterial hypertension (PAH) and congenital heart disease (CHD), which can be used alone or in combination to distinguish patients with PAH-CHD from those with CHD, have been identified with the use of nuclear magnetic resonance (NMR)-based metabolomic analyses, according to the results of a recently published study in Metabolites.

Recognizing that patients with unrepaired CHD are prone to the development of PAH, the investigators sought to assess metabolic alterations in patients with CHD and associated PAH for use in noninvasive diagnosis, severity, and prognosis evaluation by conducting NMR-based metabolomic analyses. They hoped the results of the current study might help in the clinical management of patients with PAH-CHD.

A prospective study was conducted among adult patients with CHD who were admitted to the Guangdong Provincial People’s Hospital in Guangzhou, China, and had undergone cardiac catheterization between May 8, 2020, and December 31, 2020, along with a group of healthy controls. Participants were divided into 3 groups: (1) PAH-CHD group: n=24; (2) CHD group: n=38; and (3) control group: n=29. Plasma from each study participant was prepared for NMR detection.


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Twenty-eight metabolites were identified from the NMR spectra, with their relative concentrations calculated and examined. Potential biomarkers and their roles in clinical evaluation were performed via receiver operating characteristic curve analysis.

Results showed that the levels of 26 metabolites were increased significantly in patients with CHD (all P <.01), with 4 metabolites (glutamine, lysine, methanol, and glucose) identified as being characteristic metabolites. Further, the accumulation of essential amino acids (ie, leucine, isoleucine, valine, lysine, threonine, serine, and phenylalanine) was observed among participants with CHD.

Read more about the etiology of PAH

When PAH developed, participants with PAH-CHD exhibited a metabolic profile that differed markedly from that of patients with CHD only and healthy controls. Compared with those of healthy controls, 18 metabolites were increased in participants with PAH-CHD, all of which were also increased in those with CHD only, with the exception of lactate.Increased lactate, along with 7 other metabolites (glutamine, citrate, lysine, methanol, glucose, threonine, and serine), were identified as the characteristic metabolites. Participants with PAH-CHD presented with more severe metabolic disorders than those with CHD only.

The potential biomarkers identified from characteristic metabolites were correlated significantly with the critical parameters of PAH, including mean pulmonary arterial pressure, pulmonary vascular resistance, and N-terminal pro-B-type natriuretic peptide level—all of which are closely associated with the diagnosis and prognosis of PAH-CHD. Thus, 5 metabolites—lactate, alanine, threonine, glucose, and glycine—might have the potential to act as novel biomarkers for the diagnosis of patients with PAH-CHD.

The researchers concluded that these findings that address the “metabolic alterations of a particular PAH subtype may advance our understanding of the metabolic impairments in PAH, from which some promising potential biomarkers could be identified to improve the management of patients with PAH-CHD.”

Reference 

Xu B, Huang C, Zhang C, Lin D, Wu W. NMR-based metabolomic analysis of plasma in patients with adult congenital heart disease and associated pulmonary arterial hypertension: a pilot study. Metabolites. 2022;12(9):845. doi:10.3390/metabo12090845