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Interact CardioVasc Thorac Surg 2009;9:662-666. doi:10.1510/icvts.2008.189837
© 2009 European Association of Cardio-Thoracic Surgery
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ESCVS article - Cardiac general

Brain natriuretic peptide a predictive marker in cardiac surgery{star}

Saina Attarana,*, Roy Sherwoodb, Jatin Desaia, Rachel Langworthyb, Peter Mhandua, Lindsay Johna and Ahmed El-Gamela

a Department of Cardiothoracic, King's College NHS Foundation Trust, London, UK
b Department of Clinical Biochemistry, King's College NHS Foundation Trust, London, UK

Received 1 August 2008; received in revised form 15 June 2009; accepted 16 June 2009

{star} Presented at the 57th International Congress of the European Society for Cardiovascular Surgery, Barcelona, Spain, April 24–27, 2008.

*Corresponding author. 46 Queen of Denmark Court, Finland Street, SE16 7TB London, UK. Tel.: +44-79-73435452; fax: +44-2072314421.

E-mail address: saina.attaran{at}kcl.ac.uk (S. Attaran).


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Statistics
 4. Results
 5. Discussion
 References
 
Background: BNP which stands for B-type natriuretic peptide is a cardiac neurohormone and is secreted in response to myocardial stress and causes natriuresis and vasodilatation. Studies have reported close correlation between a high concentration of BNP in blood and worse short-term and long-term prognosis following myocardial infarction and heart failure. In this study, we have tested its usefulness and predictive value in the outcome post cardiac surgery. Methods: Between March 2006 and June 2007, 141 patients, undergoing cardiac surgery, were enrolled in this study. Their BNP concentration was measured prior to the operation and their comorbidities were examined against their BNP levels. Postoperatively their outcome was closely monitored. Main clinical endpoints were atrial fibrillation (AF), inotrope use, renal impairment, early deaths and hospital stay. Results: Some preoperative comorbidities, such as renal impairment, peripheral vascular disease (PVD) and low ejection fraction (EF) were associated with higher BNP level. Statistically, EuroSCORE and Parsonnet score showed significant correlation with preoperative BNP concentration (P<0.0001). Postoperatively, high-BNP concentration predicted inotropic use, higher than baseline creatinine level, longer ventilation time, longer hospital stay and early mortality (P<0.05) but our study did not reveal any predictive value for BNP in identifying those developing AF or infection postoperatively. Conclusions: BNP is a valuable biochemical marker, which is easy to measure and can be beneficial in predicting the operative outcome.

Key Words: Coronary artery bypass graft; Valve cardiopulmonary bypass


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Statistics
 4. Results
 5. Discussion
 References
 
BNP stands for B-type natriuretic peptide. It is a neurohormone that was originally isolated from porcine brain in 1988 [1]. In human, it is synthesized in ventricular myocardium, as well as atria in response to increased wall stress [2–4]. BNP modulates plasma volume and myocardial stretch through its diuretic and vasoconstrictive properties, as well as sympathetic inhibition and renin-angiotensin-aldosterone system antagonism [5, 6].

BNP has diagnostic and prognostic values in congestive heart failure and acute myocardial infarction [7–10]. It has been shown previously that BNP concentration increases after the initiation of cardiopulmonary bypass [11–13]. It can also predict the severity of aortic stenosis and is a valuable factor in monitoring the progression of valvular heart disease [14, 15]. The predictive value of BNP in cardiac surgery has only been assessed in a small number of studies, and has shown some promising results. Furthermore, BNP is easy to detect and is becoming available in some centres [16–21].

The main objective of this study was to assess the predictive value of BNP in cardiac surgery. We also analysed the preoperative comorbidities against BNP concentration in plasma sample of patients assigned for cardiac surgery.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Statistics
 4. Results
 5. Discussion
 References
 
This study was conducted prospectively and after obtaining permission from the Research Ethics Committee of our hospital. One hundred and forty-one consecutive patients undergoing any first-time open-heart surgery and agreed to the study were recruited (Table 1). Informed consent was obtained from each individual. The exclusion criteria for the study were: intubated patients and patients who did not agree to the study.


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  		Table 1 Patient characteristics

 
Twenty-four hours prior to the operation, 5 ml of venous blood was obtained from each patient and collected into a Trazylol pre-filled EDTA (ethylenediamine-tetra-acetic acid) bottles, centrifuged at 3000 rpm for 10 min, and subsequently stored at –20 °C until analysis. For analysis, Siemens ADVIA Centaur BNP assay (Siemens, USA) was used. This is a two-site sandwich immunoassay using direct chemiluminescent technology for the measurement of BNP in human plasma. It utilises an acridinium ester labelled monoclonal mouse anti-human BNP F(ab')2 fragment specific to the ring structure of BNP. The second antibody, in the solid phase, is a biotinylated monoclonal mouse anti-human antibody specific to the C-terminal portion of BNP, which is coupled to a streptavidin magnetic bead.

The result range was reported between 2 and 5000 ng/l. Any results above 5000 ng/l were reported as >5000 ng/l. If necessary the samples were diluted 1:5 using the sample diluents on-board and repeated. Samples with results below this range were reported as ‘<2 ng/l’ by the Centaur. Functional sensitivity was defined as the lowest BNP concentration determined at a coefficient of variation of 20% and was determined as 2.5 ng/l.

Postoperatively all patients had routine postoperative care with close monitoring of the cardiovascular system, renal output and development of arrhythmia. No change in the management of the patients was applied and no treatment was withheld.

Clinical endpoints included: 1) atrial fibrillation; 2) use of inotropic agents or intra-aortic balloon pump on first postoperative day; 3) creatinine level of 20 µmol/l than the baseline on day 3 postoperatively; 4) infection; 5) cardiac events; 6) hospital stay and 7) deaths within 30 days of surgery.

Additionally, correlation between preoperative BNP concentration and patient characteristics, some laboratory results, cardiac pathology, EuroSCORE and Parsonnet score were examined.


   3. Statistics
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistics
4. Results
 5. Discussion
 References
 
Statistical analysis was performed with Analyse-It software version 2.08 (Analyse-It, Leeds, UK). Data were tested for normal distribution using the Shapiro–Wilk test. Mann–Whitney U-test was used to compare the results between groups of numerical data and Spearman rank was used for correlations between continuous variables. For categorical data {chi}2 was used. A P<0.05 was considered to be statistically significant.


   4. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistics
 4. Results
5. Discussion
 References
 
BNP was detectable and measured in all 141 patients. As previously reported, BNP had a statistically significant correlation with the age (P<0.0001) [22] but no difference of the level between men and women was observed (P=0.2). There was also no correlation between BNP and body mass index (BMI). Patients with a higher grade of New York Heart Association (NYHA) had higher concentration of BNP (P<0.0001), however, severity of chest pain (Canadian Cardiovascular Society) did not have any association with preoperative BNP concentration. Patients with diabetes, hypertension (HTN), or with a history of myocardial infarction did not have significant higher BNP concentration compared to those without these risk factors (P>0.05). Conversely, high-BNP concentrations had a statistically significant association with preoperative AF and preoperative history of peripheral vascular disease (PVD), such as carotid artery stenosis, aortic aneurysm and low ankle brachial blood pressure index (ABPI) (P=0.0009). High-BNP concentrations were also associated with impaired renal function. BNP showed a statistically significant correlation with glomerular filtration rate (GFR) when GFR was <90 ml/min (P=0.0003) and preoperative creatinine when this was >120 µmol/l (P=0.016). BNP concentration also correlated indirectly with the haemoglobin (Hb) concentration (P=0.001) but was not associated with platelet count or other biochemical markers (Table 2).


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  		Table 2 Correlation between preoperative patient characteristics and BNP level

 
In view of cardiac morphological problems, BNP concentration was not associated with left main stem (LMS) disease, but high-BNP concentrations were associated with low ventricular ejection fractions (EFs) and impaired left ventricular function (P<0.0001). Patients undergoing emergency or urgent operation also had a higher level of BNP preoperatively compared to the elective patients (P=0.0017). Furthermore, patients with valvular conditions had higher BNP concentrations compared to patients who underwent CABG only (P=0.0018) (Table 3).


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  		Table 3 Correlation between operative and postoperative variables and preoperative BNP concentration

 
To assess the predictive value of BNP, its concentration was compared to the two main risk calculation indices; the EuroSCORE and Parsonnet score. This showed significant correlations between BNP concentration, EuroSCORE and Parsonnet score (P<0.0001). High-BNP concentration, also predicted the requirement for inotropic agents postoperatively (Fig. 1), significant increases from baseline creatinine concentration, as well as longer ventilation time and longer hospital stay (P<0.05). High preoperative BNP also correlated with mortality within 30 days of the operation (P=0.019, Fig. 2). Our study did not predict value for BNP in predicting the development of postoperative AF or infection (Table 3).


Figure 1
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  		Fig. 1. Correlation between preoperative BNP and postoperative inotropic use.

 

Figure 2
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  		Fig. 2. Correlation between preoperative BNP level and early postoperative mortality.

 

   5. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistics
 4. Results
 5. Discussion
References
 
Since the discovery of natriuretic peptides and the endocrine activity of the heart two decades ago, many studies have reported different practical uses for the family of natriuretic peptides. In this study, we have assessed whether BNP measurement as part of the routine blood tests carried out before cardiac surgery could provide information regarding the outcome of the operation or the risk of developing common postoperative complications, such as AF, infection, longer intubation time or longer hospital stay.

Wazani et al. reviewed the association between preoperative plasma BNP concentration and postoperative development of AF. Reviewing 187 patients retrospectively, they concluded that raised BNP was a strong predictor of developing AF postoperatively [20]. However, our results failed to find a similar correlation between preoperative BNP and postoperative AF incidence. A recent study by Jogia et al. showed that patients with preoperative AF have significantly higher NT-pro BNP compared to patients in sinus rhythm (SR). In our study, this correlation was statistically insignificant. Jogia's study failed to prove the predictive value of BNP in occurrence of postoperative AF or mortality. Despite their findings of association between preoperative BNP and slow postoperative recovery, the authors were still unclear about the role of BNP in predicting the outcome after cardiac surgery [19].

Chello et al. measured plasma ANP and BNP in a small group of patients with poor left ventricular function undergoing CABG. They showed that BNP is a significant predictor of left ventricular recovery after cardiac surgery. However, they did not include a control group with preserved left ventricular function [17]. Hutfless et al. achieved similar results in almost 100 male patients undergoing heart surgery. They concluded that high concentrations of BNP pre- and postoperatively were associated with longer hospital stay and higher mortality rates within one year post-cardiac surgery. They also advocated following BNP-guided therapy for a better outcome after cardiac surgery [18]. In a study by Provenchère et al., BNP was measured for the assessment of outcome up to one year post-cardiac surgery. This study showed an elevation in plasma BNP that correlated with a 12-fold increase in potential risk of developing postoperative heart failure, however, in their multivariate analysis, only left ventricular EF was shown to be significantly associated with one-year survival [21]. In another study by Weber et al., BNP was assessed as an indicator of severity of aortic stenosis, the progression of the disease and as an indication for the optimal timing for aortic valve replacement [14]. Furthermore, in neonates undergoing atrial switch operation for transposition of great arteries, BNP was measured preoperatively and was found to have a high-predictive value for postoperative complications and outcome [16].

Our study is not the first to assess the predictive value of BNP in cardiac surgery, but it did include a number of variables which are associated with certain complications post-cardiac surgery, such as inotropic requirement, renal impairment and increased ventilation time which had not been investigated before. The statistically strong correlation between the preoperative BNP concentration and risk stratification calculators, such as EuroSCORE and Parsonnet score, demonstrates the value of preoperative testing of BNP in cardiac surgery. BNP measurement is not expensive and can give us an idea of ventricular function if ventriculogram or echocardiogram is not readily available. Furthermore, correlation between low-Hb and high-BNP concentration has not been reported previously and may suggest optimisation of Hb prior to the surgery, however, this requires further investigations.

There are several methods and scoring systems used by cardiac surgeons to predict the outcome. Each method has been developed from large databases of cardiac surgical patients, however, the performance of each system has been investigated in several publications due to differences observed in various patient populations. These studies have suggested that each method may be better suited for some analyses but not for others as expected from formal risk quantitation; some underestimate or over estimate mortality risk. Therefore, using a simple blood test is more objective and can potentially apply to all patients, however, many cases are required to enable us to calculate the risk of postoperative morbidity and mortality with different values of plasma BNP preoperatively.

BNP measurement is not expensive and can give us an idea of ventricular function if ventriculogram or echocardiogram is not readily available. Furthermore, correlation between low-Hb and high-BNP level has not been reported previously and may suggest optimisation of Hb prior to the surgery, this, however, requires further investigations.

This study has its own limitations; higher number of patients is required to prove the significance of preoperative BNP measurement. Furthermore, our study is also lacking the results of the long-term follow-up of our patients. This study concentrated only on preoperative BNP concentration and postoperative complications. We did not measure postoperative BNP, which increases after cardiopulmonary bypass, to analyse its increase against developing complications.

More importantly, in this study we are unable to offer a cut-off value BNP level that would be able to predict postoperative complications due to the low incidence of complications post-cardiac surgery and requires the study to be carried out on a large number of cases and in several centres. This will be possible with routine measurement of BNP in cardiac surgery.

In conclusion, we strongly believe that BNP is a valuable, inexpensive, reliable, simple and strong predictor of the outcome post-cardiac surgery and should be measured alongside the routine blood tests preoperatively.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistics
 4. Results
 5. Discussion
 References
 

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eComment: Re: Brain natriuretic peptide a predictive marker in cardiac surgery
Leo A. Bockeria, Olga L. Bockeria, and Uliana A. Kolesnikova
Interactive CardioVascular and Thoracic Surgery 2009 9: 666. [Full Text] [PDF]



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eComment: Re: Brain natriuretic peptide a predictive marker in cardiac surgery
Interactive CardioVascular and Thoracic Surgery, October 1, 2009; 9(4): 666 - 666.
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