Rise in Angiopoietin-2 Following Neonatal Cardiac Surgery Is Associated With Adverse Clinical Outcomes

Abstract

Objectives: Neonatal cardiac surgery for congenital cardiac defects is associated with significant morbidity and mortality, and there is a need for early identification of patients at highest risk of adverse outcomes. Because vascular endothelial injury mediates damage across organ systems, we measured serum biomarkers of endothelial injury in neonates following cardiopulmonary bypass and examined their associations with short-term outcomes. Design: Prospective cohort study. Setting: Pediatric cardiac ICU. Patients: Thirty neonates less than 2 weeks old undergoing repair of congenital cardiac defects with cardiopulmonary bypass. Interventions: None. Measurements and Main Results: Biomarkers of endothelial integrity, angiopoietin-1 and angiopoietin-2, were measured preoperatively and at 24 hours postoperatively. A composite adverse outcome was defined as any of the following: stroke, need for renal replacement therapy, extracorporeal membrane oxygenation support, cardiac arrest, or death. Associations of biomarkers with adverse outcomes were examined using Wilcoxon rank-sum test. There was an increase in angiopoietin-2 from preoperatively to 24 hours postoperatively (p < 0.0001) and a decrease in angiopoietin-1 from preoperatively to 24 hours postoperatively (p < 0.0001). Patients with greater rise in angiopoietin-2 from preoperatively to 24 hours postoperatively had greater risk of composite adverse outcome (p = 0.04). They had a trend toward higher Vasoactive-Inotropic Score (p = 0.06) and a higher prevalence of low cardiac output syndrome (p = 0.06). Twenty-four hour postoperative angiopoietin-2 level was associated with the composite adverse outcome (p = 0.03). The rise in angiopoietin-2 level from preoperatively to 24 hours postoperatively directly correlated with cardiopulmonary bypass duration (r = 0.47; p = 0.01). Conclusions: In neonatal cardiac surgery, longer duration of cardiopulmonary bypass is directly associated with greater endothelial injury as measured by increased serum levels of angiopoietin-2. Angiopoietin-2 levels 24 hours postoperatively were significantly associated with a composite adverse outcome. Postoperative angiopoietin-2 level may serve as an early indicator of patients in need of closer monitoring and protective intervention. Further research into endothelial protective strategies is warranted.

Angiopoietin-2 is associated with capillary leak and predicts complications after cardiac surgery

“…In a study of 21 post-CPB patients, the increase in postoperative Ang-2 was higher in patients who developed AKI [ 31 ] and an altered Ang-2/Ang-1 ratio was correlated with higher odds for prolonged mechanical ventilation [ 10 ]. In 30 neonates less than two weeks of age undergoing congenital cardiac repair, patients with a greater rise in Ang-2 showed a higher chance for a composite of adverse outcomes after cardiac surgery [ 32 ]. Secondary analyses from our cohort further highlight the predictive relevance of CLS for hemodynamic, renal, and pulmonary complications.…”