Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease (Mar 2022)

Increased Circulating Endothelin 1 Is Associated With Postoperative Hypoxemia in Infants With Single‐Ventricle Heart Disease Undergoing Superior Cavopulmonary Anastomosis

  • Benjamin S. Frank,
  • Ludmila Khailova,
  • Lori Silveira,
  • Max B. Mitchell,
  • Gareth J. Morgan,
  • Michael V. DiMaria,
  • Jesse A. Davidson

DOI
https://doi.org/10.1161/JAHA.121.024007
Journal volume & issue
Vol. 11, no. 6

Abstract

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Background Inadequate pulmonary vascular growth results in morbidity for many children with single‐ventricle heart disease (SVHD). Endothelin 1 (ET1) is a potent vasoconstrictor and stimulator of pulmonary artery smooth muscle proliferation. Circulating ET1 levels and their association with outcomes have not been studied during early SVHD palliation. We aimed to define circulating levels of ET1 in patients with SVHD undergoing stage 2 palliation and evaluate their relationship to postoperative hypoxemia. We hypothesized that patients with SVHD with higher ET1 concentration would have a greater post–stage 2 hypoxemia. Methods and Results Prospective cohort study of 55 subjects with SVHD undergoing stage 2 palliation and 50 controls. Samples for ET1 analysis were collected at preoperation (systemic and pulmonary vein) and 2, 24, and 48 hours postoperation for cases and a single time point for controls. The primary outcome was percentage of first 48 postoperative hours with clinically significant hypoxemia (saturation, <70%). ET1 concentration was lower in preoperative cases than controls (2.2 versus 2.7 pg/mL; P=0.0015) and in the pulmonary vein than systemic vein (1.7 versus 2.2 pg/mL; P<0.001). ET1 level increased by 2 hours postoperation and trended back to baseline by 48 hours. Higher preoperative pulmonary vein ET1 and 2 hours postoperative ET1 were associated with larger hypoxemia burden (10.6% versus 2.7% [P=0.0081]; and 7.6% versus 3.2% [P=0.01], respectively). Multivariable testing demonstrated ET1 concentration and cardiopulmonary bypass time were associated with hypoxemia, whereas catheterization measurements and clinical variables were not. Conclusions Infants with SVHD with higher perioperative ET1 concentration experience more post–stage 2 hypoxemia. ET1 activity may be a modifiable risk factor of pulmonary vascular inadequacy for stage 2 palliation.

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