Angiogenic factors and their soluble receptors predict organ dysfunction and mortality in post-cardiac arrest syndrome

Takeshi Wada, Subrina Jesmin, Satoshi Gando, Yuichiro Yanagida, Asumi Mizugaki, Sayeeda N Sultana, Sohel Zaedi, Hiroyuki Yokota

ABSTRACT: INTRODUCTION: Post-cardiac arrest syndrome (PCAS) often leads to multiple organ dysfunction syndrome (MODS) with a poor prognosis. Endothelial and leukocyte activation after whole-body ischemia/reperfusion following resuscitation from cardiac arrest is a critical step in endothelial injury and related organ damage. Angiogenic factors, including vascular endothelial growth factor (VEGF) and angiopoietin (Ang), and their receptors play crucial roles in endothelial growth, survival signals, pathological angiogenesis and microvascular permeability. The aim of this study was to confirm the efficacy of angiogenic factors and their soluble receptors in predicting organ dysfunction and mortality in patients with PCAS. METHODS: A total of 52 resuscitated patients were divided into two subgroups: 23 survivors and 29 non-survivors. The serum levels of VEGF, soluble VEGF receptor (sVEGFR)1, sVEGFR2, Ang1, Ang2 and soluble Tie2 (sTie2) were measured at the time of admission (Day 1) and on Day 3 and Day 5. The ratio of Ang2 to Ang1 (Ang2/Ang1) was also calculated. This study compared the levels of angiogenic factors and their soluble receptors between survivors and non-survivors, and evaluated the predictive value of these factors for organ dysfunction and 28-day mortality. RESULTS: The non-survivors demonstrated more severe degrees of organ dysfunction and a higher prevalence of MODS. Non-survivors showed significant increases in the Ang2 levels and the Ang2/Ang1 ratios compared to survivors. A stepwise logistic regression analysis demonstrated that the Ang2 levels or the Ang2/Ang1 ratios on Day 1 independently predicted the 28-day mortality. The receiver operating characteristic curves of the Ang2 levels, and the Ang2/Ang1 ratios on Day 1 were good predictors of 28-day mortality. The Ang2 levels also independently predicted increases in the Sequential Organ Failure Assessment (SOFA) scores. CONCLUSIONS: We observed a marked imbalance between Ang1 and Ang2 in favor of Ang2 in PCAS patients, and the effect was more prominent in non-survivors. Angiogenic factors and their soluble receptors, particularly Ang2 and Ang2/Ang1, are considered to be valuable predictive biomarkers in the development of organ dysfunction and poor outcomes in PCAS patients.