The circular RNA (circRNA) hsa_circ_0003416 might have diagnostic value in pulmonary arterial hypertension (PAH) secondary to congenital heart disease (CHD), according to a new study published in the Journal of Clinical Laboratory Analysis.

Patients with PAH-CHD (n=50) presented with lower levels of hsa_circ_0003416 in the plasma compared to those of CHD patients (n=50) and healthy individuals (n=20). Moreover, hsa_circ_0003416 levels were found to be negatively associated with those of B-type natriuretic peptide (BNP), a blood biomarker currently used for screening in PAH patients.

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The area under the curve of plasma hsa_circ_0003416 was 0.721 (95% CI, 0.585-0.857; P =.004), with a cutoff value of 0.99. The sensitivity and specificity were 0.66 and 0.7, respectively. Moreover, the results suggested that hsa_circ_0003416 might be an independent predictor of PAH-CHD (odds ratio, 0.015, 95% CI, 0.000-0.597; P =.025).

Early diagnosis of PAH-CHD is currently limited due to the lack of specific symptoms in the early stages. “Patients with CHD have been reported to be diagnosed with PAH approximately 6 years after symptom onset; occurrence of PAH increases the mortality rate of patients with CHD more than twofold compared with that of patients without PAH,” the authors said. Therefore, it is essential to identify novel biomarkers that could improve early diagnosis.

Improvements in Screening for and Diagnosing PAH

CircRNAs have emerged as potential biomarkers for PAH. Several have been implicated in PAH pathogenesis by promoting vascular remodeling.

Though promising, the results presented in this study require further validation in a larger cohort. “Exploring a new biomarker is a long and difficult process, from its discovery to validation and clinical application,” the authors recognized.


Huang Y, Su D, Ye B, et al. Expression and clinical significance of circular RNA hsa_circ_0003416 in pediatric pulmonary arterial hypertension associated with congenital heart disease. J Clin Lab Anal. Published online February 15, 2022. doi:10.1002/jcla.24273