NT-proBNP as a marker of postoperative heart failure in adult cardiac surgery

Postoperative heart failure (PHF) remains the major cause of mortality after cardiac surgery. Unfortunately, generally accepted diagnostic criteria for PHF are lacking. This may explain why the evidence for the efficacy and safety of current treatment of PHF with inotropes is insufficient. In cardiology practice N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an established biomarker for heart failure. However, the association between NT-proBNP and PHF after cardiac surgery needs further clarification. Glutamate is a key intermediate in myocardial metabolism, which may improve myocardial tolerance to ischemia and facilitate post-ischemic recovery. Glutamate was associated with a reduced risk of developing severe PHF in high-risk patients undergoing coronary artery bypass surgery (CABG). The aim of this thesis was to study the role of NT-proBNP for prediction and assessment of PHF in cardiac surgery (Paper I-III) and the impact of intravenous glutamate infusion on postoperative NTproBNP after CABG (Paper IV). Paper I: We retrospectively studied the role of underlying heart disease for preoperative NT-proBNP in patients admitted for first time CABG (n=2226), aortic valve surgery (AVR) for aortic stenosis (AS) (n=406) and mitral valve surgery for mitral valve regurgitation (MR) (n=346) by adjusting for non-cardiac confounders (age, gender, obesity and renal function). The level of NT-proBNP in AS or MR was 1.67 (p<0.0001) and 1.41 times (p<0.0001) higher respectively than in coronary artery disease (CAD) after adjusting for confounders. Preoperative NT-proBNP was predictive of severe PHF in CAD and MR patients but less so in AS patients. Preoperative NT-proBNP emerged as an independent risk factor for severe PHF and postoperative mortality in CAD patients. Paper II-III: We prospectively studied the association between postoperative NT-proBNP and PHF in two cohorts, patients undergoing AVR for AS (n=203) and patients undergoing isolated CABG for acute coronary syndrome (ACS) from the GLUTAMICS-trial (n=382). NT-proBNP was measured preoperatively, on the first (POD1) and third postoperative morning (POD3). An end-points committee blinded to NT-proBNP used prespecified criteria to diagnose PHF and its severity. After AVR for AS only NT-proBNP level on POD1 provided good discrimination of PHF. PHF with NT-proBNP POD1 ≥ 5290 ng•L-1 emerged as an independent risk factor for long-term mortality (Paper II). After isolated CABG for ACS both absolute postoperative levels on POD1 and POD3 and postoperative increases of NT-proBNP were associated with PHF and the levels reflected the severity of PHF (Paper III). Paper IV: We prospectively studied the impact of intravenous glutamate infusion on postoperative NT-proBNP in a randomized double-blind study on patients undergoing CABG for ACS from the GLUTAMICS-trial (n=399). Patients were randomly allocated to intravenous infusion of L-glutamate (n=200) or saline (n=199). No effect of glutamate on postoperative NT-proBNP levels was detected in the whole cohort. According to post-hoc analysis glutamate was associated with less increase of NT-proBNP from preoperative level to POD3 and significantly lower absolute levels on POD3 among high risk patients with EuroSCORE II ≥4.15 (upper quartile). Conclusion: Patients with AS or MR have higher preoperative NT-proBNP than CAD patients after adjusting for confounders. The predictive value of NT-proBNP with regard to severe PHF and postoperative mortality was confirmed in CAD patients. Postoperative NTproBNP may prove a useful tool for assessment of PHF after AVR for AS and isolated CABG. NT-proBNP POD1 identifies patients with PHF at risk of a poor long-term survival after AVR for AS. Intravenous infusion of glutamate may prevent or mitigate PHF in highrisk patients undergoing CABG but these results need to be confirmed