Related Experiment Video
Updated: May 21, 2025
Author Spotlight: A Neonatal Heterotopic Rat Heart Transplantation Model for the Study of Endothelial-to-Mesenchymal Transition
Published on: July 21, 2023
Increased Endothelin-1 Is Associated With Morbidity in Single Ventricle Heart Disease in Children Undergoing Fontan
Benjamin S Frank1, Sierra Niemiec2, Ludmila Khailova1
1Section of Cardiology, Department of Pediatrics, University of Colorado, Aurora, Colorado, USA.
Insights
Persistent high levels of endothelin-1 (ET1) in children with single ventricle heart disease (SVHD) undergoing the Fontan operation are linked to increased post-operative complications and impaired recovery. Managing ET1 may improve outcomes for these complex patients.
Area of Science:
- Pediatric Cardiology
- Cardiovascular Surgery
- Critical Care Medicine
Background:
- Endothelin-1 (ET1) is a critical mediator of vasoconstriction and smooth muscle cell proliferation.
- Previous research linked suppressed ET1 levels to adverse outcomes in infants with single ventricle heart disease (SVHD) post-stage 2 palliation.
- The role of ET1 in recovery following stage 3 palliation (Fontan operation) in SVHD patients remains unclear.
Purpose of the Study:
- To investigate the association between persistent failure to suppress ET1 and impaired recovery in children with SVHD undergoing the Fontan operation.
- To evaluate peri-operative ET1 levels in relation to clinical outcomes after stage 3 palliation.
Main Methods:
- Prospective cohort study of 84 children with SVHD undergoing stage 3 palliation and 50 controls.
- Serial ET1 measurements (pre-op, 2, 24, 48 hours post-op) in SVHD cases.
- Primary outcomes: Fontan pressure and systemic oxygen saturation at 24 hours post-operation.
Main Results:
- SVHD patients exhibited higher systemic venous ET1 than pulmonary venous ET1 and lower levels than controls pre-operatively.
- ET1 levels peaked at 2 hours post-operation and remained elevated at 48 hours.
- Higher pre-operative and 24-hour post-operative ET1 levels correlated with increased Fontan pressure, lower systemic oxygen saturation, greater pleural drainage, and longer hospital stay.
Conclusions:
- Elevated peri-operative ET1 levels in children with SVHD undergoing the Fontan operation are associated with increased post-operative morbidity.
- Failure to adequately suppress ET1 may represent a modifiable risk factor for poor outcomes in SVHD palliation.
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.
