Exploring Biomarkers in Congenital Heart Disease: A Case-Control Study of ST2 in Children with Atrial Septal Defects

Soluble growth stimulation protein form of interleukin-1 receptor-like 1 (ST2) may signal myocardial stress, and elevated ST2 blood levels are associated with adverse outcomes in adult heart disease. Data on ST2 in children with congenital heart disease (CHD) is limited. This study explored ST2 in newborns and older children with atrial septal defect (ASD), as this represents a common CHD type that remains clinically challenging to recognize in childhood with slowly evolving symptoms. A case-control study was carried out in newborn ASD cases versus controls measuring ST2 on dried blood spot samples and additionally in pediatric ASD cases versus controls on venous blood together with cardiac magnetic resonance before and after treatment. ST2 was higher in newborns with ASD (n = 19) compared to controls (n = 93); (p < 0.01). Receiver operating characteristics to diagnose newborn ASD by ST2 showed an area under the curve of 0.848. Levels of ST2 decreased in pediatric ASD (n = 16) after treatment (p = 0.014). Lower left ventricular ejection fraction correlated with higher ST2 levels before (r = -0.348) and after treatment (r = -0.497). Elevated ST2 in newborns may aid early ASD diagnosis. Levels of ST2 in pediatric ASD decrease after treatment, and higher levels are associated with lower left ventricular ejection fraction, warranting further study.