A new study has determined that a series of 3 metabolites in serum, S-adenosyl methionine (SAM), guanine, and N-terminal pro-brain natriuretic peptide (NT-proBNP), can serve as useful biomarkers to identify pulmonary arterial hypertension (PAH) associated with congenital heart disease (PAH-CHD) in children.

“If CHD is not treated in a timely manner, the decrease in cardiac output, the increase in cardiac load, and the increase in pulmonary blood flow lead to an increase in mean pulmonary arterial pressure, resulting in PAH and the loss of surgical opportunities in advanced irreversible PAH,” the authors wrote. “Therefore, it is of great clinical significance to screen suitable non- invasive biomarkers for early diagnosis of PAH-CHD from CHD in infants and young children.”

The research team screened serum from 329 children at a single center in China and divided them into three groups based on pulmonary pressure: CHD (n=132), PAH-CHD (n=97), and healthy controls (n=100).

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Nuclear magnetic resonance spectroscopy was employed to identify 22 metabolites of CHD and PAH-CHD. These metabolites were further analyzed using ultra-high-performance liquid chromatography–tandem mass spectroscopy-based metabolomics.

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The results revealed that 8 metabolites were significantly altered in the PAH-CHD group: betaine, choline, SAM, acetylcholine, xanthosine, guanosine, inosine, and guanine. Binary logistic regression showed that of those, the combination of SAM, guanine, and NT-proBNP had the best diagnostic yield: of 92 cases of CHD and 65 cases of PAH-CHD, the accuracy of the serum samples was 92.7%. The area under the receiver operating characteristic curve was 0.9455.

Given these encouraging results, the authors recommend further validation of this 3-biomarker panel with a larger number of samples, along with an assessment of stability and metabolite flux to help confirm its usefulness in screening and early diagnosis of PAH-CHD.


Jin N, Yu M, Du X, et al. Identification of potential serum biomarkers for congenital heart disease children with pulmonary arterial hypertension by metabonomics. BMC Cardiovasc Disord. Published online March 24, 2023. doi.10.1186/s12872-023-03171-5