P3605ADMA/nitrite ratio: possible marker of early post-operative adverse events in HFrEF patients undergoing CABG

Abstract

Introduction: Stable plasma nitric oxide (NO) metabolites (nitrate and nitrite) and asymmetric dimethylarginine (ADMA) has shown to be attractive predictors of left ventricular remodeling and heart failure. Previously we studied the dynamics of NO metabolites and ADMA during coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) in patients with heart failure with reduced ejection fraction (HFrEF) and found that decline of nitrite level by the end of CPB is avaluable predictor of complicated postoperative period. Still this finding is not useful in pre-operative risk assessment in this cohort, since the value is obtained after the surgery. Purpose: To identify endothelial dysfunction marker(s) useful for risk scoring and strategy choice in pre-operative period of patients with HFrEF scheduled to CABG and also to estimate their significance as predictors of acute heart failure (AHF) and multiple organ dysfunction syndrome (MODS) in postoperative period. Methods: The study included 88 patients with HFrEF (prior MI, LVEF<35%, left ventricle ESV index >60 mL/m2) scheduled for CABG. All patients had undergone CABG with CPB for multivessel coronary artery disease in 2015-2017. We determined the concentration of ADMA and NO metabolites: total content, nitrite and nitrate in plasma before the surgery, at the end of the surgery and 24 hours after the surgery. The following outcomes were recorded postoperatively: AHF, MODS,total ventilation time, ICU stay length. Results: Retrospective analysis identified 11 patients (12,5%) with complicated postoperative period (combined endpoint: AHF + MODS). The pre-operative nitrite level was higher in uncomplicated (n=77) than in the complicated group (1.26±0.24 μmol/L vs. 0.66±0.21, p=0.031) and ADMA level was significantly lower (0.71±0.17μmol/L vs. 1.03±0.19, p<0.001). Among all the parameters the baseline ADMA level had the highest correlation with the complications (r=0.48, p=0.001), while baseline nitrite level had shown week correlation (r=0.34, p=0.013); baseline nitrate level had no correlation with investigated parameters. This finding potentiated the search of new parameter that would have a better predictive value, and finally led to identification of ADMA/nitrite ratio as a potent predictor of complication (r=0.64, p<0.001), ventilation time (r=0.58, p=0.08) and total ICU stay (r=0.62, p=0.011). Moreover, for a threshold value of 2.5 the ADMA/nitrite ratio predicted significantly better than the other parameters (receiver operating characteristic curves) the presence of AHF and MODS in early postoperative period (sensitivity and specificity of 83% and 77%, respectively, AUC=0.801). Conclusion: Baseline ADMA/nitrite ratio can be used as a marker of complicated course of postoperative period in HFrEF patients undergoing CABG; its calculation would be helpful for a better pre-operative risk assessment in this cohort.