Oksana Trębacz, Patrycja Florek, Jacek Podlewski, Teresa Iwaniec, Wojciech Tarała, Piotr Weryński, Łukasz Niemiec, Bernadeta Szewczyk
St. Jadwiga the Queen Clinical Regional Hospital. Polish Academy of Science. Dover Fueling Solutions. Jagiellonian University Medical College.
Poland
Pharmacological Reports
Pharmacol Rep 2026;
DOI: 10.1007/s43440-026-00883-1
Abstract
Background: Children with complex cyanotic congenital heart disease (CHD) and with pulmonary hypertension (PH) commonly experience hypoxia. Hypoxia-inducible factor-1α (HIF-1α) is a key regulator of cellular responses to low oxygen, and its levels are elevated in these conditions. However, HIF-1α concentrations in non-cyanotic CHD, such as patent ductus arteriosus (PDA), remain largely unknown. This study aimed to evaluate circulating serum HIF-1α levels in patients with PDA and compare them with those in healthy children and in patients with complex CHD after Fontan palliation.
Methods: Eighty children were assigned to three groups: PDA group (n = 34), Fontan group (n = 23), and healthy controls (n = 23). Complete blood counts, serum HIF-1α levels, and baseline clinical characteristics were collected. Multiple regression analysis was performed to identify predictors of HIF-1α variability. Receiver operating characteristic (ROC) curves were analyzed to evaluate the ability of selected variables to predict increased HIF-1α levels.
Results: Patients with PDA exhibited the highest median [IQR] HIF-1α levels (0.62 [0.41-1.18] ng/mL), compared to patients in the Fontan group (0.52 [0.34-0.73] ng/mL), and healthy controls (0.48 [0.33-0.63] ng/mL) (p = 0.03). In the combined CHD cohort, hemoglobin, age, and red blood cell count formed the best predictive model, explaining 53.9% of HIF-1α variance (p < 0.01). Hematocrit < 36.6% and hemoglobin < 12.9 g/dL showed the best diagnostic accuracy for identifying HIF-1α > 1.1 ng/mL.
Conclusions: Children with PDA, even without PH, exhibit elevated circulating HIF-1α. Further research is needed to clarify the clinical relevance of HIF-1α in non-cyanotic CHD.
Category
Class I. Pulmonary Hypertension Associated with Congenital Cardiovascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
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