Preoperative Serum NT-proBNP levels; Can it be a Clue About Postoperative Clinical Outcome of Patients Undergoing to Coronary Artery Bypass Surgery?-Juniper Publishers
JUNIPER PUBLISHERS-OPEN ACCESS JOURNAL OF CARDIOLOGY & CARDIOVASCULAR THERAPY
Abstract
Introduction:Brain natriuretic peptid (BNP) is a ventricular hormone that is sensitive and specific marker of changes in ventricular function. It is sample screening test for symptomless left ventricular failure. The aim of this study was examine there is a corelation between the preoperative plasma level of BNP and early morbidity in patients undergoing to coronary artery bypass.Materials and Method:During the 11 month period, we retrospectively evaluated 22 consecutive patients who was operated on for coronary artery bypass. Patients had not have other system and cardiac disease and had not EF ≤ 50. Preoperative plasma BNP values was statisticaly compired with early postoperative morbidity findings. BNP analysis was made by Electrohemoluminescent immunassay method and Roche Diagnostic Indianapolis, Indiana proBNP Elecsys 1010 autoanalyzer with tecnique and ≥125 pg/ml was accepted sign for cardiac function disorder. Postoperative morbidity criterias were accepted as; staying longer than 4 day in intensive care unit and longer than 10 days in hospital, mechanic ventilatory support longer than 48 hours, necessity for inotrops or IABP(intra aortic baloon pump) support. All analysies were done by using SPSS 9.0 statistical software pocket. One or more of above criterias for morbidity are established in 12 of 22(%54) patients.
Results:There were no significant differance for demografic findings between the patients who morbidity were established and was not. Preoperative plasma BNP level was 763±53 pg/ml in 12 patients with morbidity while 113±47 pg/ml among 10 patients with no morbidity(P <0.05).
Conclusion:With the results it is concluded that preoperative plasma BNP levels is a reliable indicator for early postoperative morbidity in patients undergoing coronary artery bypass.
Keywords: Cardiopulmonarybypass; BNP(Brain Natriuratic Peptid); Postoperative morbidity
Abbreviations: ANP: Atrial Natriuretic Peptide; BNP: Brain Natriuretic Peptide; CNP: C-type Natriuretic Peptidine; EF: Ejection Fraction
Introduction
It was raised about 50 years ago that heart had a
natriuretic endocrine effect and in fact, it was stated that heart was
an endocrine organ. Attention was drawn that this effect appeared as a
result of the distention of atria [1], it was determined that there were
intracellular granules similar to endocrine cells on the walls of atria
by electron microscope [2], that the active substance was a peptide and
this substance, which had the characteristics of a hormone, was named
the “atrial natriuretic peptide” (ANP) [3]. Subsequently, in 1988, Sudoh
et al. [4] demonstrating the existence of an ANP like natriuretic
peptide
have called it “brain natriuretic peptide” (BNP). In subsequent studies,
it was demonstrated that BNP was a homologue of ANP, was synthesized in
the ventricular myocard cells and shared the same periphery receptors
as ANP [5].
“C-type natriuretic peptidine (CNP), on the other
hand, which is yet another natriuretic peptide is believed to have a
minimum effect on cardiac functions and operates by a different
mechanism [5]. It has been demonstrated that natriuretic peptides
decreased myocardial “preload” and “afterload”,
improved ventricular functions, expanded the coronary arteries,
reducing myocardial ischemia originating from exercise and
that they had a protective effect on myocardial “remodeling”
post-myocardial infarctus [5]. In consequence, it is known that
myocardial origin peptides achieve natriuresis by an endocrine
function and they have an effect on cardiac functions. Specifically,
this effect of BNP which is secreted from ventricular myocardium
has been proven. Still, the significance of the serum levels of this
peptide, pre and post arterial bypass grafting is not yet clear.
The purpose of this retrospective study is to investigate
whether the preoperative serum BNP level may be an indicator
in terms of adverse clinical findings (morbidity) which may be
faced in the early postoperative period in patients to undergo
coronary bypass surgery, employing a pump. The values
assumed to be normal for serum BNP level varies depending on
the type of natriuretic peptide and the selected patient group. In
cases where the measured serum NTproBNP value is under 125
pg/ml in patients evaluated in respect of chronic heart failure,
the diagnosis of heart failure is doubtful and in great probability,
cardiac dysfunction will be excluded (negative diagnostic value
≥% 97)[6,7]. (cardiac dysfunction must be considered if NTproBNP
value is over 125 pg/ml) [6,7].
While for patients presenting to emergency units with
shortness of breath, the diagnosis of heart failure is considered
under 300 pg/ml, looking at the NT-proBNP serum level for
diagnosis of acute heart failure, heart failure must be considered
between 300-1800 pg/ml and the diagnosis of heart failure
becomes conclusive over 1800 pg/ml [8]. There are certain cases
where BNP is high although there is no chronic heart failure.
These are advanced age, female gender, kidney failure, acute
myocard infarctus, lung diseases affecting right heart functions
and pulmonary embolism. However, there are times when the
serum BNP level is normal despite the existence of heart failure.
These conditions are flash lung eudema, NYHA class 1 patients
with low EF and mitral stenosis, atrial myxoma and acute mitral
failure which cause heart failure without ventricular dysfunction
[9].
Currently, there are three different laboratory tests
recommended for heart failure by FDA. The first one is the Triage
BNP test determining BNP concentration in human plasma
implemented in 2000 (Biosite Diagnostics, San Diego, CA). Result
is achieved in 15 minutes by the Florescene method. This test
was used in certain recent studies. The second test is Shionogi
BNP test. This test has been used in previous studies but time of
essay is as long as 20 hours. This method has been FDA approved
in 2003 (Bayer Diagnostics)[10]. FDA has approved a new test
measuring BNP’s N-terminal fragment in 2002 (Elecsys®
proBNP, Roche Diagnostics). Under this measuring system, the
NT-proBNP (1-76) reading is taken.
In studies performed, NT-proBNP reading and BNP reading
have given similar results. BNP is eliminated rapidly from the serum with the aid of natriuretic peptide receptor-C and
endopeptidase. NT-proBNP, on the other hand, has a longer
lasting and stable serum level with no variations in day or night
time. Furthermore, this test may be run quite rapidly. However,
the most important problem with this test is that it is less useful
compared to BNP in patients with poor kidney functions since
NT-proBNP is mostly eliminated through the renal tract.
Patient group:Twenty-two patients who underwent
coronary bypass surgery due to coronary arterial disease
between April 2004-March 2005 at Çukurova University School
of Medicine Cardiovascular Surgery Main Scientific Discipline
were included in the study; 16 patients were male, 6 patients
werefemale with an average age of 58.7 ± 7.9 years. From
amongst patients admitted for coronary bypass procedure, 22
patients with;
- Left ventricular ejection fraction (EF) is over 50%
- No advanced renal failure (serum creatinine<2.0mg/ dl)
- No thyroid dysfunction (hyperthyroidism, hypothyroidism)
- No chronic obstructive pulmonary disease, Chronic Bronchitis, no pulmonary embolism history, no primary pulmonary hypertension (normal respiratory function tests)
- no right or left heart failure or functional capacity restricting valve disease alongside of coronary arterial disease and no arrhythmia like atrial fibrillation or frequent ventricular ectopic beats were included in the study.
Routine procedures were implemented in the preoperative
period for all coronary artery patients: The medical histories
of patients were compiled and their physical exams were
performed. Risk factors like hypertension, diabetes mellitus,
hyperlipidemia, smoking and history of heart disease in the
family were noted, electrocardiograms, telecardiograms and
echocardiograms (M mode and tissue Doppler) of patients were
taken and full blood count, urine analysis, fasting blood sugar,
serum electrolytes, serum lipids and renal and liver function
tests were performed.
For identifying any adverse clinical findings (morbidity) after
operation, the patients were monitored 30 ± 5 days on the average
during the post-operative period. In the study, the preoperative
BNP values were compared to the preoperative echocardiogram
findings and surgery data (cardiopulmonary bypass time spans,
cross clamp period and number of anastomosis). In this study,
morbidity was taken as stay over 4 days in intensive care and
more than 10 days in hospital, mechanical ventilator need over
2 days, inotropic support, intra-aortic balloon pump need and
recurring hospital admission. From all patients after a resting period of twenty minutes, 10 ml blood specimen was taken from
the antecubital vein into EDTA tubes for measuring NT-proBNP.
Right after the conclusion of symptom limited stress test
(within first 1-2 minutes), blood specimens were taken once
again similarly for measurement of NT-proBNP. Specimens were
centrifuged for 5 minutes at + 4 Co at 1500 rpm and the upper
phase plasma segment was transferred into another tube for
NTproBNP measurement. The NT-proBNP level was measured
from the separated serum by the electrochemoluminescent
immunoassay method and Roche Diagnostics (Indianapolis,
Indiana) proBNP commercial kits using Elecsys® 1010
autoanalyzer. All patients and controls were advised about the
study and their approved consent forms were collected. The
study was certified by Çukurova University School of Medicine
Board of Ethics.
anaesthesia procedure, after EKG, pulse oximeter, peripheric vein
and invasive arterial monitorization, induction was performed
and intubation carried out with 0.1 mg/kg diazepam, 0.1 mg/
kg pancuronium ve 8-10 μg/kg fentanyl and a central venous
catheter was placed in V. Jugularis Interna. Maintenance of
anaesthesia was achieved by 60% 02 and air mixture sevoflurane,
pancuronium and where necessary, fentanyl. After 3 mg/kg
heparin was given, CPB was started. Following application of the
aortic cross clamp, heart was stopped by blood cardioplegia (30
mEq K+, 10 mEq NaHCO3, 12 mEq Mg++ in 1000 cc blood). Slight
hypothermia was achieved. Myocardial protection was provided
by antegrade isothermic blood cardioplegy. Neutralization was
done by protamine during exit from CPB. The patients were
taken to the intensive care unit in intubated state.
Statistical analyses:All analyses were performed using the
SPSS 9.0 statistical software package. The continuous variables
in group data were expressed as average ± standard deviation
(avg. ± SS). Categorical variables, on the other hand, were
given in numbers and percentages. In intergroup univariate
comparisons, in independent groups, parametric tests, t tests
and variance analyses and non-parametric tests Mann Whitney
U test and Kruskall Wallis tests were employed depending
on the distribution of continuous variables. In comparison of
categorical variables, the Chi-Square test was employed.
In determining the factors affecting morbidity, multivariate
logistic regression analysis was performed with variables found
to be significant as a result of univariate analyses. The increase or
decrease in the risk was stated with Odds Ratio according to the
unit increase in the variables found to be significant as a result of
this analysis. ROC analysis was used for determining the “cut off”
for parameters identifying the progression of cardiac incident
independently. p<0.05 was used for statistical significance.
Morbidity related findings:In the postoperative 30 ± 5 day
monitoring of the 22 patients who underwent coronary arterial
by-pass, postoperative morbidity and incidents were observed
in 12 patients (54.5%). IABP need was 2, need for mechanical ventilator over 2 days was 4, positive inotropic support need was
2, discharge after 10 days was 7, and more than 4 day intensive
care stay was in 8 patients. In more than one patient, two or
three parameters were observed together.
Clinical and demographic characteristics of patients
with and without morbidity:No significant difference could
be found between the clinical and demographic characteristics
of patients with and without morbidity. Upon evaluation of
medications received by patients in the preoperative period, it
was found that use of beta blockers and statin was low in patients
in whom morbidity was observed and that inotropic support
need was greater although this was not significant. It was
found that only the rate of use of beta blockers was statistically
significant between the two groups out of these parameter.
Upon evaluation of the preoperative laboratory data of
the patients, it was found that in patients with morbidity, the
urea and creatinine values were significantly higher than that
of the control group and the hemoglobin, hemotocrite and
HDL cholesterol values were significantly lower. Evaluation of
the postoperative laboratory data of the patients showed that
similarly to preoperative values, in patients with morbidity;
urea, creatinine and CRP values were significantly higher
compared to the control group and hemoglobin, hemotocrite
and HDL cholesterol values were significantly lower.
In comparison of the NT-proBNP values of patients with
and without morbidity, it was found that in the patient group
with morbidity, the preoparative NTproBNP levels were found
to be significantly higher statistically compared to those with no
morbidity. Postoperative NT-proBNP, absolute and relative NTproBNP
difference values, on the other hand, were found to be
similar in the two groups. The preoperative and postoperative
values of patients with and without morbidity and the absolute
and relative NTproBNP difference values derived from such
value differences are shown (Table 1).
coronary bypass patients by logistic regression analysis, it was
found that only the preoperative NT-proBNP level was related
to morbidity independent of other parameters (Table 2). Based
on Odds ratios, it was determined that each 100 pg/ml increase
in preoperative NT-proBNP increased the morbidity risk of the
individual by 62.1%. In the ROC analysis performed for the relationship between the preoperative NT-proBNP level and
morbidity of coronary bypass patients, it was found that the
area under the line in the ROC curve was 75.7%. In this analysis,
it was found that the “cut-off” value of 180 pg/ml which is the
average NT-proBNP value of all patients predicted morbidity at
73% sensitivity and 69% specificity. No significant relationship
could be determined between the coronary by-pass CPC and ACC
times and the Nt-proBNP serum levels. There was a negative and
significant relationship between the number of anastomosis
and all three NT-proBNP levels other than the preoperative NTproBNP.
Positive significant relationship was found between
the time of stay in hospital and intensive care and only the
preoparative NT-proBNP level (Table 3).
After it was established that the heart also has an endocrine
function, playing a role in secretion of natriuretic peptide, broad
studies were performed on the effects of natriuretic peptides.
Chello et al. [11] have stated that in patients with left ventricular
dysfunction, the preoperative BNP values are correlated with
the severety of the left ventricular dysfunction and were the
predictors of to what level the left ventricular functions can
improve after a coronary artery by-pass procedure. In this
study, a reduction in parallel with the improvement in the left
ventricular function has been determined in the BNP levels in
the postoperative period.
It was stated that the preoperative BNP plasma level is an
indicator for the postoperative left ventricular systolic function
in patients who will undergo coronary artery by-pass, in other
words, that the high preoperative BNP values are indicators of
high risk for patients to undergo coronary by-pass [3,12-15].
In our study, it was found that in patients to undergo coronary
artery bypass, the preoperative BNP values will indicate
postoperative morbidity at 73% sensitivity and 69% specificity
with a cutoff value of 180 mg/dl and furthermore, that each
increase of 100pg/dl in BNP raise morbidity by 62.1%.
It was posited that high preoperative BNP values may be an
indication of the pervasiveness of the disease and whether there
was a significant relationship between the preoperative BNP level and the cross clamp and perfusion times was investigated
by Saribülbül et al. [15]; Avidan et al. [16]; Georges et al. [9],
Morimoto et al. [17] who found data giving support to this
hypothesis. It was hypothesized that both the preoparative high
BNP level and also extended cross clamp times are related to the
pervasiveness of the coronary arterial disease. Yet, in our study,
no relationship could be established between the cross clamp
and cardiopulmonary bypass durations and the preoperative
BNP level in coronary bypass operations.
A negative and significant relationship was found between
the number of anastomosis and all three NT-proBNP levels other than the preoperative NTproBNP. Song et al. [14], in their
study on patients on whom they performed open heartsurgery,
have published that in case of coronary by-pass, BNP levels
were significant indicators for pleural effusion. Although the
relationship between BNP and pleural effusion has not yet
been figured out entirely, progression of pleural effusion as
a complication of myocard failure may be considered (Figure
1). In our study, since there was no pleural effusion requiring
thoracentesis, this finding could not be evaluated. Development
of postoperative atrial fibrillation in patients undergoing heart
surgery and therefore, coronary artery by-pass increases the
time of stay in hospital and the risk of onset of morbidity. Wazni
OM et al. [18] have published that high preoperative values in
heart surgery patients constitute an independent risk factor for
onset of postoperative atrial fibrillation.
The incidents of atrial fibrillation in coronary artery by-pass
surgery are 16-33% with the etiology not yet fully resolved. Song
et al. [14], in their study, have found the BNP peak to be over 450
pgr/mL in all patients in whom atrial fibrillation developed. In
the study by Albage et al. [19], statistically significant decrease
was determined in BNP levels in patients they administered
the isolated Maze procedure. The drop in BNP levels is an
indicator of the development of ventricular function post Maze
operation. At the same time, high BNP levels are also indicators
of thromboembolic incidents as atrial fibrillation increases such
thromboembolic incidents. However, no post-operative atrial
fibrillation was observed in our series of 22 subjects.
We believe based on our clinical study that preoperative
BNP levels is a useful parameter in determining the morbidity
and prognosis in the early postoperative period of patients with
no left ventricular dysfunction to undergo cardiopulmonary
bypass or coronary artery bypass graft surgery. However, we are
also aware that a much greater number of findings and clinical
studies are needed.
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