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Relationship between B-type natriuretic peptide levels and echocardiographic indices of left ventricular filling pressures in post-cardiac surgery patients
© Salustri et al; licensee BioMed Central Ltd. 2009
Received: 4 September 2009
Accepted: 28 October 2009
Published: 28 October 2009
B-type natriuretic peptide (BNP) is increased in post-cardiac surgery patients, however the mechanisms underlying BNP release are still unclear. In the current study, we aimed to assess the relationship between postoperative BNP levels and left ventricular filling pressures in post-cardiac surgery patients.
We prospectively enrolled 134 consecutive patients referred to our Center 8 ± 5 days after cardiac surgery. BNP was sampled at hospital admission and related to the following echocardiographic parameters: left ventricular (LV) diastolic volume (DV), LV systolic volume (SV), LV ejection fraction (EF), LV mass, relative wall thickness (RWT), indexed left atrial volume (iLAV), mitral inflow E/A ratio, mitral E wave deceleration time (DT), ratio of the transmitral E wave to the Doppler tissue early mitral annulus velocity (E/E').
A total of 124 patients had both BNP and echocardiographic data. The BNP values were significantly elevated (mean 353 ± 356 pg/ml), with normal value in only 17 patients (13.7%). Mean LVEF was 59 ± 10% (LVEF ≥50% in 108 pts). There was no relationship between BNP and LVEF (p = 0.11), LVDV (p = 0.88), LVSV (p = 0.50), E/A (p = 0.77), DT (p = 0.33) or RWT (p = 0.50). In contrast, BNP was directly related to E/E' (p < 0.001), LV mass (p = 0.006) and iLAV (p = 0.026). At multivariable regression analysis, age and E/E' were the only independent predictors of BNP levels.
In post-cardiac surgery patients with overall preserved LV systolic function, the significant increase in BNP levels is related to E/E', an echocardiographic parameter of elevated LV filling pressures which indicates left atrial pressure as a major determinant in BNP release in this clinical setting.
B-type natriuretic peptide (BNP), a cardiac hormone synthesized by ventricular myocytes in response to left ventricular (LV) dysfunction and wall stress, has been shown to be increased in patients with cardiovascular disease such as heart failure, cardiac hypertrophy, and acute coronary syndromes . Although in most of these situations the increase in BNP is related to systolic LV dysfunction , recent evidences suggest that, at least in patients with heart failure, elevated LV filling pressures may also act as a trigger for BNP release [5, 6] and are likely to reduce exercise capacity . More recently, high levels of BNP have also been reported early after cardiac surgery, with prognostic implications for prolonged hospital stay and 1-year mortality . However, it is worth noting that in post-cardiac surgery patients, as compared to patients with heart failure, LV ejection fraction does not correlate as much as expected with BNP levels . Thus, in this clinical setting, factors other than LV systolic function, such as myocardial damage during aortic cross clamping, have been advocated; however the results of these studies are still controversial and the mechanisms underlying BNP release remain unclear.
We hypothesized that elevated LV filling pressures in post-cardiac surgery patients may account for the increase in plasma BNP. Thus, we designed this prospective study with the aims of assessing the relationship between postoperative BNP levels and LV filling pressures as evaluated by transthoracic two-dimensional and Doppler echocardiography.
We prospectively enrolled 134 consecutive in-hospital patients admitted to our Centre for a cardiac rehabilitation program 8 ± 5 days after a cardiac surgery procedure. No patients required urgent cardiac surgery due to acute myocardial infarction or acute heart failure. Patients in haemodialysis were excluded. All patients were clinically stable and followed the medical therapy prescribed by the referring physicians.
Participants in the study had complete data on age, sex, diabetes mellitus (glucose level >126 mg/dl or hypoglicemic drugs), renal insufficiency (serum creatinine value ≥1.5 mg/dl), type of cardiac surgery, and length of hospitalization. The investigation conforms with the principles outlined in the Declaration of Helsinki. The hospital institutional review board approved the study and written informed consent to participate in the study was obtained from all patients.
Blood samples (5 ml) were obtained 24 hours after patient admission. In all patients, blood was sampled from an antecubital vein after 15 minutes of supine rest and collected into a sampling tube containing potassium EDTA. Samples were analyzed for BNP levels using a microparticle enzyme immunoassay (Abbott Laboratories, Abbott Park, Illinois, USA). The precision and sensitivity of this kit have been previously described by Rawlins et al .
All the patients underwent a comprehensive echocardiographic study within 24 hours after admission at our Center using a commercially available ultrasound equipment (Philips Sonos 5500, Andover, Massachusetts, USA). All measurements were made according to the recommendations of the American Society of Echocardiography/European Association of Echocardiography .
The left ventricular (LV) assessment included measurement of the diastolic (DV) and systolic (SV) volumes with derived ejection fraction (LVEF) using the modified biplane Simpson's method, mass, and relative wall thickness (RWT). Left atrial volume was derived using the modified biplane Simpson's method and the value was indexed by body surface area. Mitral inflow was assessed from the apical 4-chamber view using pulsed-wave Doppler. Early-to-late diastolic velocities (E/A) ratio was calculated, as well as the deceleration time (DT) of the E wave. The early diastolic velocities at the septal and lateral mitral annulus were obtained from the apical 4-chamber view using Doppler tissue imaging, and the values were averaged (E'). LV filling pressure was estimated by the E/E' ratio .
All analyses were performed by using SPSS for Windows (version 12.0.1, Chicago Ill.). Continuous variables are expressed as mean ± SD. Categorical variables are expressed as number of subjects and percentages. Since plasma concentrations of BNP did not follow a Gaussian distribution, the values were log-transformed before statistical analysis. We used the independent Student's t test for univariate comparison of log-transformed BNP [ln(BNP)] value within dichotomic variables. Correlations between continuous variables were tested by Pearson's correlation test. Multiple regression analysis was used to clarify the contribution of each independent variable to BNP having ln(BNP) as the dependent variable. Statistical significance was assumed at p < 0.05.
Clinical characteristics of the study population.
Number of patients
Male, nr (%)
Age, mean ± SD (yrs)
67 ± 10
Days after cardiac surgery, mean ± SD
8 ± 5
Type of surgery, nr (%)
- Valve surgery
- CABG + valve surgery
- Aorta replacement
Renal failure, nr (%)
Diabetes, nr (%)
Medical therapy, nr (%)
BNP after cardiac surgery
Mean value of ln(BNP) according to female gender, presence of renal failure, diabetes mellitus, and coronary artery by-pass surgery (CABG).
Diabetes mellitus, yes
Diabetes mellitus, no
Renal failure, yes
Renal failure, no
Other cardiac surgery
BNP and echocardiographic parameters
Mean value of ln(BNP) and E/E' according to the presence or absence of left ventricular systolic dysfunction.
(n = 16)
(n = 108)
5.4 ± 0.5
5.5 ± 0.8
9.6 ± 3.7
9.4 ± 2.9
Echocardiographic parameters in the study group.
Mean ± SD
80.4 ± 32.3
34.8 ± 21.3
59 ± 10
LV mass (g/m2.7)
57.3 ± 18.3
0.48 ± 0.10
iLA volume (ml/m2)
31.2 ± 10.7
1.06 ± 0.34
203 ± 52
9.48 ± 3.07
Multivariable linear regression for ln(BNP) as dependent variable (covariates: E/E', age, LV mass, LVEF, iLAV, gender).
R2 = 0.222
Elevated BNP levels have been previously reported both prior to and immediately after cardiac surgery. Such findings have been associated with cardiac complications, prolonged hospital stay, and 1-year mortality [8, 14, 15]. However, the reasons for BNP increase in this clinical setting have not been clarified yet, with BNP inconsistently associated with a variety of factors related to surgery, such as biomarkers of myocardial damage, anaesthesia, sternotomy, etc . Since BNP increase reflects hemodynamic changes, we believe that the ultimate reason for BNP increase in these patients could be the loading changes that occur during and after cardiac surgery. Thus, we hypothesized that elevated LV filling pressures might be the trigger for BNP release.
the vast majority of post-cardiac surgery patients show a significant increase in BNP levels;
the increase in BNP levels does not correlate with LV systolic function;
E/E' ratio, an echocardiographic marker of filling pressures, is strongly associated with elevated BNP levels.
BNP and ventricular function
In patients with heart failure, plasma BNP levels are inversely related to LV systolic function . In contrast, in our study population we did not find any correlation between BNP levels and systolic LV function as evaluated by echocardiographic ejection fraction. This finding is not surprising, since in the study group, which represents consecutive patients admitted to our Center, the prevalence of LV systolic dysfunction is rather low (only 3 patients had a LVEF <40%). Although our population was not selected, this might not represent the whole spectrum of post cardiac surgery patients.
More recently, in patients with heart failure, an increase in BNP levels has also been related to diastolic (dys)function [4, 18]. To this aim, most studies have used conventional echocardiographic parameters, such as mitral inflow diastolic velocities. However, in patients with preserved LV systolic function, i.e. the vast majority of those included in our study, the diagnostic value of these parameters is rather limited and newer echocardiographic modalities are warranted for a comprehensive categorization of the patient's hemodynamic profile. Doppler myocardial velocities at the mitral annulus are widely used for a (relatively) load-independent evaluation of diastolic properties, and left atrial volume is increasingly considered as a long-term biomarker of average LV diastolic pressure .
BNP and newer echocardiographic parameters of diastolic dysfunction
E/E' ratio as an index of LV filling pressures
Several studies have evaluated the relationship between BNP levels and the E/E' ratio in different clinical settings (ambulatory patients, heart failure), with consistent results that demonstrate a relationship between BNP levels and echocardiographic indices of LV filling pressures. The findings of the present study obtained in post-cardiac surgery patients are in line with those from previous reports in different clinical settings: we observed a significant correlation between BNP levels and the E/E' ratio, indicating elevated filling pressures as the major determinant of BNP release.
Left atrium as an index of chronic diastolic dysfunction
During diastole, the left atrium is directly exposed to LV pressures. Abnormal LV diastolic function causes an elevation of filling pressures, which may lead to left atrial dilatation over time. In the present study, iLAV is associated with BNP values, however when entered into a multivariable regression analysis this parameter did not retain its statistical power as predictor of BNP levels.
Additional factors affecting BNP levels
Age, female gender, and renal failure are all variables related to BNP levels [22, 23]. In our study, a statistically significant direct relationship between BNP levels and patient age was observed. In contrast, the difference in BNP values according to renal function, although present, was not significant perhaps because of the small sample size of our study population and the exclusion of patients on haemodialysis.
There are several limitations of our study. First, BNP levels before cardiac surgery were not sampled. Thus, we cannot exclude that at least in some patients BNP levels had been elevated before surgery. Secondly, we did not perform any invasive hemodynamic tests to evaluate the relationship between hemodynamic status and BNP levels. Previous studies have already shown a close correlation between BNP levels and LV end-diastolic pressure. Thirdly, we did not evaluate the impact of cardioplegic arrest on BNP levels. Finally, follow-up data that may show if elevated BNP levels are associated with worse clinical outcome are lacking. Although length in-hospital stay was independent from BNP levels, the potential role of BNP levels for long-term prognostication of post cardiac surgery patients remains to be assessed.
What is, then, the clinical relevance of this study? We believe that early after cardiac surgery an increase in LV filling pressure is very likely to occur, independent from LV systolic function, and is a trigger for a significant BNP release. In this clinical setting Doppler echocardiogram is a good alternative to BNP samples for assessing LV filling pressures, and E/E' in particular is a practical and more convenient parameter for detecting and monitoring haemodynamic imbalance.
We thank Mrs Paola Luciolli for her help and support to reviewing the English manuscript.
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