Three-molecule panel may help detect PAH in children with CHD
Combination of SAM, guanine, and NT-proBNP yielded best results
Measuring blood levels of three molecules — SAM, guanine, and NT-proBNP — could help identify pulmonary arterial hypertension (PAH) in children with congenital heart diseases (CHD), a study suggests.
“This 3-marker panel has the potential to be used in clinical practice for the early diagnosis and screening of PAH-CHD,” the researchers wrote in “Identification of potential serum biomarkers for congenital heart disease children with pulmonary arterial hypertension by metabonomics,” which was published in BMC Cardiovascular Disorders.
CHD refers to a group of disorders affecting the structure and function of the heart that are present from birth. In some cases, abnormal heart function in CHD can contribute to PAH, where the pressure in the lungs’ blood vessels is abnormally high. This puts further strain on the heart and is generally associated with poorer clinical outcomes, so early detection and care is critical.
The gold standard for detecting PAH in children with CHD is right heart catheterization, which involves inserting a tube called a catheter to the right ventricle and pulmonary artery to measure pressure. Due to its invasive nature, researchers are exploring alternatives to help diagnose PAH — for example, by measuring levels of disease-impaired molecules (biomarkers) that can be collected with a simple blood draw.
Scientists in China screened blood samples to identify biomarkers that could help detect PAH in children with CHD. The study included samples from 329 children — 132 with CHD, 97 with PAH associated with CHD (referred to as PAH-CHD), and 100 without heart disease.
The researchers used a technique called proton nuclear magnetic resonance spectroscopy to screen for potential markers, then used ultra-high-performance liquid chromatography-tandem mass spectroscopy to confirm levels of preselected molecules. They noted that prior research with these technologies suggested markers to help detect CHD, but they haven’t “been employed to screen and identify biomarkers of PAH-CHD in children.”
The biochemical analysis identified eight molecules — betaine, choline, S-Adenosyl methionine (SAM), acetylcholine, xanthosine, guanosine, inosine, and guanine — that were significantly altered in the PAH-CHD children, compared to those with CHD, but not PAH.
The researchers also noted that two well-established disease biomarkers were also elevated in PAH-CHD children — urea nitrogen (BUN), a marker of kidney damage, and NT-proBNP, a marker of heart damage.
Analyses to see which of these 10 potential markers best detect PAH-CHD were conducted.
The team calculated a statistical measure called the area under the receiver operating characteristic curve (AUROC), which assesses how well a given measure can distinguish between two groups, in this case, CHD or PAH-CHD. AUROC values range from 0.5 to 1, with higher values reflecting a better ability to differentiate.
Results showed a combination of three molecules — SAM, guanine and NT-proBNP — yielded the best power to identify PAH-CHD, with an AUROC of 0.9455 and an overall accuracy of 92.7%.
Based on these findings, the scientists concluded that blood levels of “SAM, guanine and NT-proBNP are expected to be [a] potential biomarker combination for the differential diagnosis of PAH-CHD. More research was need to validate the findings, they said.
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