BNP is originally isolated from the porcine brain, although the highest concentration of BNP is actually found in the heart rather than in the brain. It is a cardiac hormone released by ventricular myocytes in response to ventricular dysfunction and wall stress . Probrain natriuretic peptide is a 108 amino-acid propeptide synthesized by myocytes, predominantly from the left ventricle, in response to the increased wall stretch. When released, it is cleaved into 2 fragments: the active brain peptide (BNP) which has the function of natriuresis, diuresis and vasorelaxation , and the N-terminal amino acid sequence (NT-proBNP). In rapid time, both BNP and NT-proBNP have emerged as established cardiovascular biomarkers, especially in heart failure, hypertension, acute coronary syndrome or stable ischemic cardiac disease . The main objective of our study was to find out the factors which influence preoperative plasma NT-proBNP levels, then to assess the predictive value of BNP in cardiac surgery.
Steady-state levels of NT-proBNP are as much as four-to six-fold higher than BNP. We used NT-proBNP instead of BNP because of its longer plasma half-life (60-120 min).The longer half-life of NT-proBNP suggests it is more independent of inter- and intra-individual variations . Furthermore, molecules of BNP are unstable at room temperature and start degrading immediately after blood draw if not processed. And in their relation to clinical characteristics and prognostic performance in a large population of patients with heart failure, BNP and NT-proBNP showed subtle differences . This is why we decided to use NT-proBNP in our study.
There is a wide individual variation in plasma NT-proBNP values. As a general guideline, in young, healthy adults, 90% will have BNP <25 pg/ml and NTproBNP ≤70 pg/ml . Our study showed that the preoperative NT-proBNP ranged from 19.3 pg/mL to 35000 pg/mL (median 728.4, IQR 213.5 to 2551 pg/mL). Univariate analysis showed that preoperative atrial fibrillation, NYHA class III/IV, LVEF, pulmonary pressure, LVEDD, preoperative creatinine, preoperative cTnT were significantly associated with preoperative NT-proBNP levels. NT-proBNP had a significant positive correlation with LVEDD, pulmonary pressure, and a significant negative correlation with LVEF and NYHA classification, respectively. This indicates that NT-proBNP is released increasingly from the left ventricle when wall tension or stretch increased as a consequence of volume overload or as left ventricular function deteriorates . Also high NT-proBNP levels are associated with increased creatinine levels and kidney failure. Besides of a reduced renal clearance of NTproBNP, increased cardiac afterload caused by fluid retention is a possible explanation . Experimental and clinical studies have suggested that atrial volume, pressure and wall stretch are the main determinants of the activation of these peptides and are all potentially altered in atrial fibrillation , so atrial fibrillation is also a risk factor of increased NT-proBNP. Furthermore, our research found that patients undergoing valvular surgery had higher NT-proBNP levels compared to patients undergoing CABG. We think that patients with valvular diseases had higher heart overload and wall tension than patients with coronary artery diseases.
The postoperative NT-proBNP ranged from 132.1 pg/mL to 35000 pg/mL (median 1940.5, IQR 995.9 to 3892 pg/mL). The difference between the preoperative and postoperative NT-proBNP level was statistically significant (p = 0.015). Previous studies demonstrated that BNP decreases when the aortic clamp is applied and the heart is isolated from circulation. Then there is a minor increase in BNP concentrations following cardiac reperfusion . 24 h post-CPB it arrived its peak value, and returned to the preoperative baseline values 3 weeks after surgery . The postoperative peak concentration of plasma NT-proBNP correlated with the preoperative plasma NT-proBNP concentration (r = 0.526, p < 0.001) in our research. This finding offers a possible explanation why the outcomes after cardiac surgery can be predicted by the preoperative plasma concentration.
A variety of multifactorial risk indexes have been described to help preoperative risk assessment of patients undergoing cardiac surgery. Some studies had focused on the predictive value of preoperative NT-proBNP [12, 13]. Hutfless et al. considered that BNP levels > 385 pg/ml could predict the postoperative complications and one-year mortality after heart surgery . Sodeck’s research showed increased levels of NT-proBNP (>647 pg/ml) indicated unfavorable outcome . Grescenzi et al. showed that postoperative NT-proBNP levels are associated with in-hospital mortality and prolonged ICU stay after CABG surgery . Our study demonstrated that a NT-proBNP of 2773.5 pg/ml was the best cutoff (sensitivity of 63.6% and specificity of 80.8%) to predict the mortality within 30d of surgery. In our analysis, median NT-proBNP level in patients with unfavorable clinical end points had significantly higher NT-proBNP level than those without(1998.5 pg/ml Vs. 630.5 pg/ml, p = 0.016). At the same time, the preoperative NT-proBNP showed a significant influence on the ICU LOS, hospital LOS and ventilation time. So NT-proBNP may be become a clinical routine biomarker capable of predicting patients’ perioperative and early postoperative risk because of it is convenient, quick and not expensive. The quantitative cut-off values may be used by physicians in their decision to delay heart surgery in order to further ameliorate the patient. This might be through diuresis, and NT-proBNP level could be quantitatively followed until it reaches more reassuring levels.