Benjamin S. Frank, Sierra Niemiec, Ludmila Khailova, Christopher A. Mancuso, Max B. Mitchell, Gareth J. Morgan, Mark Twite, Michael V. DiMaria, Carmen C. Sucharov, Jesse A. Davidson
University of Colorado. University of Michigan.
United States
Journal of the American College of Cardiology Advances
JACC Adv 2025; 4:
DOI: 10.1016/j.jacadv.2025.101672
Abstract
Background: Endothelin-1 (ET1) is a potent vasoconstrictor and stimulator of pulmonary artery smooth muscle cell proliferation. We previously demonstrated that failure to suppress ET1 is associated with morbidity in infants with single ventricle heart disease (SVHD) undergoing stage 2 palliation.
Objectives: The aim of this study is to evaluate whether persistent failure to suppress ET1 is associated with impaired recovery among children with SVHD undergoing the stage 3 (Fontan) operation.
Methods: A prospective cohort study that includes 84 children with SVHD undergoing stage 3 palliation and 50 controls. Samples for ET1 analysis were collected at preoperation (systemic and pulmonary vein), 2, 24, and 48 hours postoperation for SVHD cases and a single timepoint for controls. Primary outcomes were Fontan pressure and systemic oxygen saturation at 24 hours postoperation.
Results: SVHD cases showed higher ET1 in the systemic vein than pulmonary vein (1.0 vs 0.7 pg/mL, P < 0.001) and lower systemic vein levels than controls (1.0 vs 1.4 pg/mL, P = 0.001). Among cases, ET1 concentration peaked at 2 hours postoperation, decreased by 24 hours, and was stable but not back to baseline by 48 hours. Adjusting for clinical covariates, higher preoperative ET1 was associated with higher 24-hour Fontan pressure. Higher 24-hour postoperative ET1 was associated with lower systemic oxygen saturation at 24 hours postoperation, higher 24-hour Fontan pressure, more pleural drainage, and longer length of stay.
Conclusions: SVHD children with higher peri-operative ET1 experience more post-stage 3 morbidity. Failure to suppress ET1 may be a modifiable risk factor for intolerance of SVHD palliation.
Category
Class I. Pulmonary Hypertension Associated with Congenital Cardiovascular Disease
Potential Biomarkers Associated with Pulmonary Vascular Disease
Symptoms and Findings Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes