Summary of medical doctoral thesis: study of the changes of serum nt probnp level and the association with low cardiac output syndrome after coronary artery bypass grafting surgery

MINISTRY OF EDUCATION

MINISTRY OF DEFENCEANDTRAINING

108 INSTITUTE OF CLINICAL MEDICINE AND PHARMACY
--------------------------------------------------------

BUI DUC THANH

STUDY OF THE CHANGES OF SERUM NT-proBNP LEVEL
AND THE ASSOCIATION WITH LOW CARDIAC OUTPUT
SYNDROME AFTER CORONARY ARTERY BYPASS
GRAFTING SURGERY
Specialty: Anesthesiology
Code: 62.72.01.46

SUMMARY OF MEDICAL DOCTORAL THESIS

Ha Noi – 2020


The work was completed at:
108 INSTITUTE OF CLINICAL MEDICINE AND
PHARMACY

Full name of supervisor:
1. Nguyen Hong Son. Assoc. Prof.
2. Nguyen Thi Quy. Assoc. Prof.

The Objections:
1.

2.
3.

The thesis will be protected at the Board of Insitute doctoral thesis
evaluation at 108 Institue of Clinical Medicine and Pharmacy
At the time:
/ 2020

Can be found the thesis in:
1. National Library.
2. The library of 108 Institue of Clinical Medicine and
Pharmacy.


1

BACKGROUND
Low cardiac output syndrome (LCOS) is a clinical condition
caused by a transient decrease in systemic perfusion due to cardiac
dysfunction, resulting in an imbalance between supply and demand for
cellular oxygen level that le led to metabolic acidosis. LCOS is common
in elderly patients, patients with reduced systolic and diastolic left
ventricular function, the longer time of aortic cross-clamp
orextracorporeal circulation, re-surgery, valve replacement surgery, and
coronary artery bypass grafting (CABG) surgeries.
The causes of LCOS including reducing myocardial contraction,
etiology of pre-load, and afterload. Factors leading to impair left
ventricular function after LCOS include inflammatory response,
myocardial anemia, hypothermia, reperfusion damage, inadequate
cardioprotection, and ventricular surgery. Reduced cardiac output in

heart failure after surgery is a common condition accounting for 30% of
CABG cases.
In recent years, the role of diuretic peptides (natriuretic peptide)
was got attention. Many studieshave shown the role of NT-proBNP (NTerminal pro-B-Type Natriuretic Peptide) in early diagnosis of heart
failure, assessment of severity, evaluation of the efficacy of treatment
efficacy prognosis of heart failure. NT-proBNP is also used to determine
the factors associated with heart failure.
In Vietnam, the study of NT-pro BNP was mainly internal
medicine. From a surgical perspective, there has not been any study
about NT-pro BNP in patients with CABG surgery. For theabove
reasons,wehavecarriedout the thesis:“Study of the changes of serum
NT-proBNP level and the association with low cardiac output syndrome
after coronary artery bypass grafting surgery”withthefollowing
objectives:
1. Investigate the changes in serum NT-proBNP level in patients
undergoing CABG with extracorporeal circulation.
2. Evaluate the association between serum NT-proBNP level and
LCOS after CABG.


2

Chapter 1
OVERVIEW
1.1. Coronary artery bypass grafting surgery with extracorporeal
circulation.
After coronary artery bypass grafting surgery with extracorporeal
circulation, the patient underwent the recovery process of an important
organ such as a cardiopulmonary organ with an average time was 2-7
days.This period was called the early stage after heart surgery. The

common complications were seen in this period:
-Blood pressure: Hypotension during the first hours after surgery.
- Arrhythmias: bradycardia, sinus tachycardia, atrial fibrillation.
- Low cardiac output syndrome: common in about 6-8 hours after
surgery.
- Right ventricular failure and pulmonary hypertension.
- Diastolic dysfunction.
- Distribution shock.
- Myocardial anemia and myocardial infarction.
1.2. Low cardiac output syndrome after heart surgery caused by
heart failure
1.2.1. Cardiac Output and Cardiac Index
The activity of the heart is reflected through cardiac output (CO). It is
an average of blood volume that the heart pumps per minute to demand
the metabolic needs.
CO = Stroke volumex Heart rate
Mean of CO: 5 – 6l/min.
The Cardiac Index (CI) is another presentation of cardiac output,
defined as CO per skin area. This index is not depending on the height,
weight, and feasibility to apply in clinical practice.
CI = CO / S
Mean ofCI: 2.5 – 3.5 l/min/m2.
1.2.2. Low cardiac output syndrome caused by heart failure
Low cardiac output syndrome caused by heart failure is a clinical
condition resulted from decreasing in systemic perfusion pressure,which
led to a decrease in myocardial function with imbalance cellular oxygen
supply and consumption and formed metabolic acidosis.
There is no definition consensus of LCOS after cardiac surgery
with extracorporeal circulation. According to many authors, LCOS after

3

cardiac surgery with extracorporeal circulation is a condition that patient
needs to used post-operative intra-aortic balloon pumpe or
cardiovascular medication such as vasomotor (dopamine dose > 5
µg/kg/min or dobutamine, adrenalin, noradrenalin, milrinone at any
doses) from ≥ 30 minutes after surgery to maintain systolic blood
pressure> 90 mmHg and CI > 2.2 L/min/m2, after optimizing the
preload, afterload, and hemostatic condition (electrolyte and blood gas).
Recommendation of Vela aboutLCOS after cardiac surgery with
extracorporeal circulation:
- Cardiac index <2.2 L/min/ m2 without reducing blood volume.
The etiology maybe are the failure of right, left, or both ventricles with
or without pulmonary congestion. Blood pressure maybe normal or
decreased.
-The clinical manifestations of LCOS: using when unable to
monitor cardiac output: oliguria (urine <0.5 ml/kg/h), central venous
oxygen saturation <60% (with normal arterial oxygen saturation), and/or
lactate > 3 mmol/l, without the insufficiency blood volume.
- In severe cases: cardiac index <2 L/min/m2, systolic blood
pressure <90 mmHg, oliguria, and sufficient blood volume.
1.2.3.Hemodynamic monitoring in cardiac surgery from an
anesthesiologist.
- Invasive arterial blood pressure measures.
- Swan-Ganz Catheter: measuring pulmonary pressure, cardiac
output, and other values.
-Echocardiography:Trans-thoracicortrans-esophageal
echocardiography.
- Monitor cardiac output using a PiCCO or Flotrac system.

1.3. N-Terminal pro-B-type natriuretic peptide (NT-proBNP)
1.3.1. Structure and formation of NT-proBNP
Formation of NT-proBNP: In cardiomyocytes, preproBNP divide
into proBNP (108 amino acid) and signal peptide (26 amino acids).
ProBNP secreted into the blood by ventricles of the heart in response to
myocardial injury or excessive stretching of the heart muscle cell
(pressure or volume). In blood, undergoing the catalysis process
ofcorin/furin enzyme, proBNP divide into BNP (32 amino acid) and NTproBNP (76 amino acid).


4

1.3.2. Serum NT-proBNP level
The value 125 pg/ml ofNT-proBNP is considered a baseline in
patients at risk for heart failure with a very high negative predictive
value. However, It is useful when dividing by age:Under 50 years old:
50 pg/ml; From 50 to 75 years: 75 - 125 pg/ml; Over 75 years: 125
pg/ml.
The US Food and Drug Administration (FDA) certified a value of
250-300 pg/ml for people  75 years old.
1.3.3. Identify the serum NT-proBNP level
NT-proBNPwas performed by luminescent electrochemical
immunization according to the principle of sandwich onCobase601
(Roche Elecsys 2010) using ECLIA (Electro chemiluminescence
immunoassay).Analyzing the immunological test by MODULAR
ANALYTICS E170. The principleof luminescentelectrochemical
immunization. Principle of sandwiches:
- The first incubation period: the antigen in the test specimen
sandwiched between a biotinized NT-proBNP-specific monoclonal
antibody and a ruthenium-marked NT-proBNP-specific monoclonal

antibody forming a sandwich complex (sandwich).
- The second incubation period: After adding the microparticles
coated with Streptavidin, the sandwich complex becomes cohesive and
converts to the solid phase by the reaction of Biotin and Streptavidin.
This mixture is sucked into the measuring chamber, where the particles
are magnetically attracted to the surface of the electrode. The unbound
substances will then be rejected with the procell solution. Applying
voltage to the electrode produces chemical luminescence. The
luminescent signal is received and measured with a magneto-optical
amplifier. The results are determined based on a standard machine
curve.
*ReagentM: microparticles surrounded by streptavidin; R1:
biotinized monoclonal anti-NT-proBNP (from mouse) antibody; R2:
NT-proBNP (sheep) monoclonal antibody labeled with a ruthenium
complex.
* Specimen tube and storage: Blood tubes that contain K2- or K3EDTA plasma. The blood is centrifuged and serous. Blood samples were
stable for 3 days at a temperature of 200C – 250C, 6 days at 20C – 80C,
24 months at –200C


5

CHAPTER 2
MATERIALS AND METHODS
2.1.Study subjects
We conducted this prospective study on 107 patients who
underwent CABG surgery withextracorporeal circulationat Ho Chi Minh
Heart Institute from October 2012 to June 2014.
2.1.1. Inclusion criteria
- Aged 18 and older regardless of gender.

- Indication for CABG surgery with extracorporeal circulation.
2.1.2. Exclusion criteria:
- Aged <18
- Concomitant cardiac surgery.
- Renal function insufficiency (Creatinin > 1.6 mg/dl).
- Myocardial infarction.
- Severe COPD.
- Do not agree to participate in the study.
2.1.3. Discontinuation from study
- Death within 24h after surgery.
- Do not agree to participate in the study.
2.2. Methodology
2.2.1. Study design:Prospective, longitudinal descriptivestudy with
comparison.
2.2.2. Materials
- The arterial catheter (20G, Vygon, French).
- Central venous catheter (7Fr B.Braun, Germany).
- Colour Echocardiography(Philips Bothel.WA, USA).
- Flotrac/Vigileo System USA).
- Monitor (Philips MP40, USA).
- Immunology test (Cobas e602, Roche).
-Dobutamine (Bivid Co, Germany): 250 mg/20ml
- Noradrenalin (Levonor, Poland): 1mg/ml.
- Adrenalin (Minh Dan, Viet Nam): 1mg/ml.
2.2.3. Study process
2.2.3.1. Before surgery:
Recording the patient history and general characteristic, diagnosis
of chronic heart failure according to Framingham, heart failure

6

classification according to NYHA, EuroSCORE scale, taking blood
tests, X-ray, electrocardiography, Doppler echocardiography, coronary
artery image, consultation decision on CABG surgery with
cardiopulmonary bypass.
2.2.3.2. In surgery:
- Setup monitor to follow the vital signs.
- Arterial catheter to monitor arterial blood pressure.
- Monitoring central venous pressure using catheter: Central-line
catheter number 16 was placed through the internal jugular vein. The
position of the catheter was the position of the aortic vein in the right
atrium (depth of the catheter about 15 cm). Central venous pressure
measured by Truwave sensor (mmHg), The zero point is the intersection
of the medial axillary line and the 4th intercostal space.
- Using Flotrac System to monitor cardiovascular indexes: Cardiac
Output (CO), Cardiac Index (CI), Stroke Volume (SV), Stroke Volume
Index (SVI), Stroke Volume Variations (SVV), Stroke Volume
Resistants (SVR).
- Testing NT-proBNP before going to the operative room, before
the procedure.
2.2.3.3. After surgery (in ICU)
- Continous following vital signs on monitoring: heart rate, invasive
blood pressure, respiratory rate, respiratory pattern, SpO2, central
venous pressure CVP, and temperature.
- Following CI, CO, SVI through Flotrac System.
- Following LCOS after cardiac surgery.
- Transthoracic echocardiography: assessment of left ventricular
function (EF), systolic pulmonary arterial pressure (PAPs), regional
movement disorders, pleural effusion, and pericardium effusion (if any).

- Monitoring and treatment LCOS after heart surgery.
- Serum NT-proBNP test at postoperative days:
+ Sample preparation: Taking 1ml of blood from the vein into a
tube containing K2- or K3-EDTA plasma. Tubes are marked with the
full name and age of the study patient and are barcoded. After taking the
blood, the specimen tube was put in an icebox and bring it to the
laboratory. The maximum time from taking blood to putting the tube in
the machine is 30 minutes. The assay was performed on Roche Cobas
e602 automated immunoassay.


7

+ Performing test: Using pipettes Roche CARDIAC to take blood
from a sample tube with a rubber lid. Before removing the blood sample
from the tube, press the piston completely and then pierce the needle
through the rubber tube cap. Always ensure homogeneity of blood
specimens before inserting the test strip (by gently shaking the tube
several times before taking the sample). Taking exactly 150 ml of blood
from the tube into the pipette (according to the mark on the pipette) and
ensure that there are no bubbles.
+ The analyzer automatically calculates the analyte concentration
of each sample (either in pmol/ L or pg/mL).
2.2.3.4. Data collection
The results were collected at the time points:
- No: the day before surgery(NT-proBNP and hemodynamic index
using Flotrac system were evaluated before going to the operating room
to operate).
- N1: Postoperative day 1 (2 hours after surgery).
- N2: Postoperative day 2(8 a.m.).

- N3: Postoperative day 3(8 a.m.).
- N4: Postoperative day 4(8 a.m.).
- N5: Postoperative day 5(8 a.m.).
Besides,we also recorded data about clinical characteristics,
cardiovascular indexes, NT-proBNP,and dosage of cardiovascular
medication at a time when patients showed cardiac impairment or when
LCOS occurred.
2.2.4. Criteria in our research
2.2.4.1. Criteria in general characteristics:
- Age (years) divided into three groups : < 50 years, from 50 – 75
years and > 75 years.
- Gender: Male, female and % male/ female ratio.
- Height (cm), wieght (kg).
- Body Mass Index (BMI):
BMI (kg/m2 ) = Weight/(Height)2.
According to WHO:
BMI < 18,5
Underweight
BMI = 18,5 – 24,99 Normal
BMI ≥ 25
Overweight
- Diagnosing chronic heart failure before surgery according to
Framingham.


8

- Classification by NYHA: NYHAI; NYHAII; NYHAIII,
NYHAIV.
2.2.4.2.Criteria for the changes of NT-proBNP level with clinical and

subclinical characteristics
- Maximum and minimum blood pressure (mmHg): Diagnosis of
hypotension according to the Vietnam Heart Association: systolic blood
pressure <90 mmHg and/or diastolic blood pressure<60 mmHg.
- Central venous pressure (CVP): Using Flotrac.
+ Normal CVP: CVP = 5-12 cmH2O
+ High CVP: CVP > 12 cmH2O
- Evaluating left ventricular function: Based on Ejection fraction
(EF) on Doppler Echocardiography.
+ Normal EF: EF = 55 - 70%.
+ Decreased EF: EF < 55%.
In our study, we used the index of EF ≤ 50% as left ventricular
dysfunction.
- Evaluating Systolic Pulmonary Artery Pressures (PAPs):
+ Normal PAPs: < 30 mmHg
+ High PAPs: ≥ 30 mmHg
- Evaluating hemodynamics index: Using monitor to follow
continuous cardiac output (CCO) through Flotrac system:
+ Cardiac index (CI):
Normal CI: 2.5 – 4.0 L/min/m2
Decreased CI:
≤ 2.4 L/min/m2
+ Cardiac output (CO):
Normal CO: 4.0 – 8.0 L/min
Decreased CO:
< 4.0 L/min
+ Stroke volume index (SVI):
Normal SVI: 33 – 47 ml/m2
Decreased SVI:
≤ 32 ml/m2

2.2.4.3. Criteria in the association between NT-proBNP and LCOS after
surgery:
- The association between NT-proBNP and the prognosis ability of
LCOS.
Criteria for diagnosing LCOS after surgery:
+ Cardiac index <2.2 L/min/ m2 without reducing blood volume.
The etiology maybe are the failure of right, left, or both ventricles with


9

or without pulmonary congestion. Blood pressure maybe normal or
decreased.
+ In severe cases: cardiac index <2 L/min/m2, systolic blood
pressure <90 mmHg, oliguria, and sufficient blood volume.
- Recommendation the cut-off value of NT-proBNP to diagnose
acute heart failure:
Table 2.1. The cut-off value for diagnosing heart failure by age

Diagnosing heart
failure

Optimal cut-off value
(pg/ml)
< 50
 450
Confirmed diagnosis
50 – 75
 900
> 75

 1800
Excluding at any ages
< 300
The cut-off value was determined as the value that the NT-proBNP
level had the maximal sensitivity and specificity, calculated by maximal
J index (Youden Index). J = max (Sensitivity + Specificity -1).
- The association between NT-proBNP and the ability of profnosis
of LCOS after cardiac surgery.
In our study, we used EuroSCOREto prognose the risk of acute
heart failure after CABG surgery. This is quite simple based on 17 index
according to patients, heart or surgery. It has three level of EuroSCORE:
 EuroSCORE 0-2 score: low risk
 EuroSCORE 2-5 score: moderate risk
 EuroSCORE > 5 score: high risk
- The association betweenNT-proBNP level with Vasoactive
Inotropic Score (VIS) after surgery:
IS = dopamin dosage (µg/kg/min) + dobutamin dosage (µg/kg/min) +
100 x epinephrin dosage (µg/kg/min).
VIS = IS + 10 x milrinon dosage (µg/kg/min) + 10000 x vasopressin
dosage (UI/kg/min) + 100 x norepinephrin dosage (µg/kg/min).
The medication did not use, its dosage was calculated as 0.We
evaluated VIS at N1, N2, N3, N4, N5. VIS > 15 was considered as high
value and VIS ≤ 15 was considered as low value.
Age


10

2.3. Statistical analysisData collected using Epi Data 6 and using
STATA14.0 to analyze.

Indication for CABG
surgery
Excluded

Included
N0: Clinical characteristics,
Echocardiography, NT-proBNP
Hemodynamic indexes
CABG

ICU

N1

N2

N3

N4

N5

Clinical characteristics,
Echocardiography, NT-proBNP
Hemodynamic indexes

No LCOS

Objective 1
Figure 2.1. Study design

LCOS

Objective2


11

Chapter 3
RESULTS
3.1. Demographic characteristics
- The mean age in the research group is 60.7 ± 9.4. Patients aged
50-75 years were major with 87.8%. The percentage of males was
higher than females (72 male versus 35 female).
- There were 36/107 cases (33.64%) diagnosed with chronic heart
failure before surgery. NYHA II and NYHA III were dominant in
classification accounting for 55.6% and 33.3% respectively.
- Patients with EuroScore 3-5 were mainly with 58% before
surgery.
- CABG with 3 and 4 bridges was mainly with 48.6% and 33.6%.
The mean of ECMO and clipped aorta artery time were 126.8 ± 27.1
minutes and 87.7 ± 23.4 minutes, respectively.
3.2.Evaluating the changes in the level of serum NT-proBNP in
patients with CABG.
Table 3.11. Level of serum NT-proBNP at time points

Time
N0

NT-proBNP (pg/ml)

Median
± SD
491.2 ± 601.1
364.7

N1

972.5 ± 1608.05

838.5

N2

1915.1 ± 2513

1792.4

N3

4057.26 ± 4458.12

3766.2

N4

3981.78 ± 4549.03

3157.1

N5

3457.81 ± 4110.98

2845.3

p
< 0.05
Comment:After surgery, the mean of NT-proBNP level increased
slightly at N1 with 972.5 pg/ml, then increased fastly and peaked at N3
with 4057.26 pg/ml, and then tending decreased gradually at N5 with
3457.81 pg/ml. The difference in the NT-proBNP level between preand post-operative time was statistically significant with a p-value
<0.05.


12
Table 3.14. Level of serum NT-proBNP and EF after surgery

Time

EF%

NT-proBNP (pg/ml)
Median
± SD
571.65 ± 2196.71
949.15
447 ± 609.45
195.4
< 0.001
4450.07 ± 4417.48

2964
1514.91 ± 1384.37
1063
< 0.001
6026.43 ± 5597.83
4819
2301.03 ± 2081.84
1816
< 0.001
5958.9 ± 5865.69
5066
2600.93 ± 2608.74
1873
< 0.001
5202.64 ± 5311.8
4069
2285.5 ± 2480.12
1743
< 0.001

r

≤ 50 (n=50)
> 50 (n=57)
-0.396; > 0.05
p
≤ 50 (n=49)
N2
> 50 (n=58)
-0.49; > 0.05

p
≤ 50 (n=50)
N3
> 50 (n=57)
-0.489; > 0.05
p
≤ 50 (n=44)
N4
> 50 (n=63)
-0.408; > 0.05
p
≤ 50 (n=43)
N5
-0.392; > 0.05
> 50 (n=64)
p
Comment:
At time points of N1, N2, N3, N4, and N5 after surgery, the
mean of NT-proBNP level in the group with EF ≤ 50% was higher than
in the group with EF> 50%. The difference was statistically significant
with a p-value <0.001. However, there was a negative correlation
between the NT-proBNP level and EF.
N1


13
Table 3.16. Level of serum NT-proBNP and CI after surgery

NT-proBNP (pg/ml)
CI

r
(l/min/m2)
Median
± SD
< 2.4 (n=14)
2589.95 ± 1535
2731.5
N1
≥ 2.4 (n=93)
729.1 ± 1539.95
255
-0.35; > 0.05
p
< 0.001
< 2.4 (n=11)
8376 ± 8321.13
5370
N2
≥ 2.4 (n=96)
2472.86 ± 2525.27
1529
-0.516; > 0.05
p
< 0.01
< 2.4 (n=3)
10118 ± 3659.22
10758
N3
≥ 2.4 (n=104)
3881.8 ± 4428.38

2431
-0.436; > 0.05
p
< 0.05
< 2.4 (n=0)
N4
≥ 2.4 (n=107) 3981.78 ± 4549.03
2430
-0.309; > 0.05
p
< 2.4 (n=0)
N5
≥ 2.4 (n=107) 3457.81 ± 4110.98
2079
-0.289; > 0.05
p
Comment: At the time points of N1, N2, N3, N4, and N5 after surgery,
the mean of NT-proBNP level in the group with CI <2.4l/min/m2 was
higher than in the group with CI≥2.4l/min/m2 (p-value<0.05). There
was a negative correlation between the NT-proBNP level and CI.
3.3. The relationship between serum NT-proBNP with low cardiac
output syndrome after CABG.
3.3.1.The correlation between serum NT-proBNP with the
predictability about LCOS

Time

Table 3.19. The rate of LCOS after heart surgery(n=107)

Time

POD 1
POD 2
POD 3
POD 4
POD 5
POD(ingeneral)

Low cardiac output
syndrome(No)
n
%
94
87.9
98
91.6
104
97.2
107
100.0
107
100.0
82
76.6

Low cardiac output
syndrome(Yes)
n
%
13
12.1

9
8.4
3
2.8
0
0.0
0
0.0
25
23.4

pvalue
< 0.05
< 0.05
< 0.05
< 0.05


14

0.00

0.00

0.25

Sensitivity
0. 50

0.75

Sensitivity/Specificit y
0. 25
0.50
0.75

1.00

1.00

Comment:The patients with LCOS at postoperative day 1 (POD 1),
POD 2, POD 3 were 13 cases (12.1%), 9 cases (8.4%), 3 cases (2.8%).
The patients with low cardiac output syndrome after surgery was 25
cases (23.4%). The difference between the group with low cardiac
output syndrome and the group without low cardiac output syndrome
was statistically significant with a p-value <0.05.

0.00

0.00

0.25

0.50
1 - Sp ecifici ty

0.75

0.25

1.00

0.50
Probabil ity cutoff
Sens itiv ity

Area u nder ROC c urve = 0.8650

0.75

1.00

Speci fici ty

Figure 3.1. Cut-off NT-proBNP and the predictability about LCOSPOD 1

0.00

0.0 0

0.2 5

Sensitivity
0.50

0.7 5

Se nsitivity/Specificity
0.2 5
0.5 0

0.7 5

1.0 0

1.00

- Cut-off value of serum NT-proBNP POD 1: 951.5 pg/ml.
- Sensitivity (Se): 92.3%; Specificity (Sp): 78.7%.
- J index (Youden Index): 0.71
- AUC (CI95%): 0.865 (0.72 – 1) with p<0.05.

0.00

0 .00

0 .25

0.5 0
1 - Spe cificity

0.7 5

0.2 5

1.0 0

0 .50
P ro bab ilit y cuto ff
S ensit ivity

Area u nder R OC curve = 0 .8 549

0 .75

1.00

S pecif icity

Figure 3.2. Cut-off NT-proBNP and the predictability about LCOS POD 2

0.00

0.00

0.25

Sensitivity
0.50

Sensitivity/Specific ity
0.25
0.50
0.75

0.75

1.00

1.00

- Cut-off value of serum NT-proBNP POD 2: 2018 pg/ml.
- Sensitivity (Se): 100.0%;Specificity (Sp): 65.3%.
- J index (Youden Index): 0.65
- AUC (CI95%): 0.855(0.75-0.95) with p<0.05.

0.00

0.00

0. 25

Area und er R OC cu rve = 0.8 479

0. 50
1 - Spec if icit y

0.75

1.0 0

0.25

0 .50
Probability cutoff
Sensitivity

0.75

1.00

Specifi city

Figure 3.3. Cut-off NT-proBNP and the predicility about LCOS POD 3

- Cut-off point of serum NT-proBNP POD 3: 4601 pg/ml.
- Sensitivity (Se): 100.0%;Specificity (Sp): 74.8%.
- J index (Youden Index): 0.748
- AUC (CI95%): 0.848(0.72-0.98) with p<0.05.


15

3.3.2. The correlation between serum NT-proBNP with the
predictability of low cardiac output syndrome according to
EuroSCORE.
Table 3.1. Analyzing the diagnosis accuracy in low cardiac output syndrome
according to EuroSCORE and cut-off value NT-proBNP at POD 1

Index
≤5
>5
Se. Sp. Acc
≤871.8pg/ml
>871.8pg/ml
Se. Sp. Acc

EuroSCORE
Cut-off value
NT-proBNP

Low cardiac output syndromeat POD 1
No
Yes
Total
(n=94)
(n=13)
n
%
n
%
n
%
73
77.7
4
30.8 77 72.0
21
22.3
9
69.2 30 28.0
Se: 77.7%; Sp 69.2%; Acc: 76.64%
70
74.5
1
7.7
71 66.4
24
25.5 12 92.3 36 33.6
Se: 74.5%; Sp 92.3%; Acc: 76.64%

p

<0.01

<0.001

Table 3.24.Analyzing the diagnosis accuracy in low cardiac output syndrome
according to EuroSCORE and cut-off value NT-proBNP at POD 2

Index

EuroSCORE
Cut-off value
NT-proBNP

≤5
>5
Se. Sp. Acc
≤2516pg/ml
>2516pg/ml
Se. Sp. Acc

Low cardiac output syndrome at POD 2
No (n=98)
Yes (n=9)
Total
n
%
n
%

n
%
74
75.5
3
33.3 77 72.0
24
24.5
6
66.7 30 28.0
Se: 75.5%; Sp 66.7%; Acc: 74.8%
68
69.4
2
22.2 70 65.4
30
30.6
7
77.8 37 34.6
Se: 69.4%; Sp 77.8%; Acc: 70.1%

p

<0.05

<0.01


16
Table 3.26. Analyzing the diagnosis accuracy in low cardiac output syndrome

according to EuroSCORE and cut-off value NT-proBNP at POD 3

Low cardiac output syndrome POD 3
No (n=104)
Yes (n=3)
Total
n
%
n
%
n
%
76
73.1
1 33.3 77 72.0
28
26.9
2 66.7 30 28.0
Se: 73.1%; Sp 66.7%; Acc: 72.9%
74
71.8
0
0
74 69.8
29
28.2
3 100 32 30.2
Se: 71.8%; Sp: 100%; Acc: 72.6%

Index

EuroSCORE
Cut-off
NT-proBNP

≤5
>5
Se. Sp. Acc
≤.3556pg/ml
>3556pg/ml
Se. Sp. Acc

p

>0.05

<0.05

0

20

40

60

80

100

Comment:
- Table 3.22 showed at POD 1, the sensitivity (Se) and specificity
(Sp) of the cut-off value NT-proBNP was higher when compared to the
EuroSCORE 5 score. However, accuracy was equivalent to 76.64%.
- Table 3.24 showed at POD 2, the accuracy of the cut-off value
NT-proBNP was higher when compared to the EuroSCORE 5 score.
- Table 3.26 showed at POD 3, the accuracy of the cut-off value
NT-proBNP was higher when compared to EuroSCORE 5 score.
3.3.3. Correlation between serum NT-ProBNP and VIS

0

500 0

10000

15000

NT-ProBNP - N1
VIS - N 1

Fitt ed val ues

VIS POD 1 = 0.002 x NT-ProBNP POD 1 + 12.15; r =0.175; p>0.05

0

50

100

150

200

Figure 3.4. Correlation between serum NT-ProBNP and VIS in POD1.

0

50 00

10000
15000
NT-ProBNP - N2
VIS - N 2

2000 0

25000

Fitt ed val ues

VIS POD 2 = 0.001 x NT-ProBNP POD 2 + 9.44; r= 0.193; p>0.05
Figure 3.5. Correlation between serum NT-ProBNP and VIS in (POD 2).


0

50

100

17

0

100 00

200 00
NT-ProBNP - N3

VIS - N 3

300 00

Fitted val ues

VIS POD 3 = 0.001 x NT-ProBNP POD 3 + 5.58; r= 0.257; p>0.05

0

20

40

60

80

100

Figure 3.6. Correlation between serum NT-ProBNP and VIS inPOD3.

0

1000 0

20000
NT-ProBNP - N4
VIS - N 4

3000 0

40000

Fitt ed val ues

0

20 0

400

600

VIS POD 4 = 0.0008 x NT-ProBNP POD4 + 5.69; r=

0

10000

2000 0
NT-ProBNP - N5

VIS - N 5

300 00

Fitt ed val ues

0.203;p>0.05Figure 3.7. Correlation between serum NT-ProBNP and VIS in
POD4.

VIS POD 5 = 0.001 x NT-ProBNP POD 5 + 8.42; r= 0.09; p>0.05
Figure 3.8. Correlation between serum NT-ProBNP and VIS inPOD5.

Comment:
The figure above showed the correlation between NT-proBNP and
VIS was a weak positive correlation and not statistically significant (p>
0.05).


18

Chapter 4
DISCUSSION
4.1. General characteristics
In our study, the average age was 60.7 ± 9.4 years, mostly from 5075 years old with 94 patients. We categorized the age into three groups:
under 50 years old, 50 to 75 years old, and over 75 years old. This
division is in line with Januzzi JL in choosing the age cutoff for NTproBNP evaluation.

Regarding the distribution of patients by gender, our results showed
that male subjects made up the majority with 72 patients, accounting for
67.3%. As for Nguyen Thi Quy's study on 330 patients undergoing
coronary artery bypass grafting, the ratio of men to women was 2.75: 1.
Our research showed an almost similar result when the ratio of men to
women was 2.1.
In our study, the average cardiopulmonary bypass time was 126.8 ±
27.1 minutes, the average aortic cross-clamp time was 87.7 ± 23.4
minutes. This result was similar to the study of Nguyen Thi Quy and
Duong Ngoc Dinh. Our research, as well as some other author in our
country, showed that the cardiopulmonary bypass time and the average
aortic cross-clamp time were longer than those of some authors from
other countries, such as Mustafa Cerrahoglu's study with the result: 101
± 36.41 minutes for the cardiopulmonary bypass time, 57.23 ± 20.66
minutes for the aortic cross-clamp time; the study of Guillermo Reyes
has the cardiopulmonary bypass time of 101.8 ± 35.3 minutes and the
aortic cross-clamp time of 66.4 ± 27.8 minutes.
4.2. Investigation of changes in the serum NT-proBNP level in
patients undergoing CABG.
4.2.1. Changes in the NT-proBNP level on postoperative days
After surgery, the average serum NT-proBNP level tended to
increase slightly from 491.2 ± 601.1 pg/ml before surgery (N0) to 972.8
± 1608.05 pg/ml on N1 (2 hours after treatment at ICU). On the second
postoperative day, the serum NT-proBNP level increased markedly with
an average of 1915.1 ± 2513 pg/ml. On the third postoperative day, the
serum NT-proBNP level continued to increase and peaked at 4057.26 ±
4458.12 pg/ml. The fourth postoperative day witnessed a marginal
decrease in the serum NT-proBNP level, standing at 3981.78 ± 4549.03
pg/ml. Then, it decreased rapidly to 3457.81 ± 4110.98 pg/ml on the

19

fifth postoperative day. The study of Guillermo Reyes et al. on 83 heart
surgery patients also showed similar variation in serum NT-proBNP in 7
days after surgery.
4.2.2 Changes in the NT-proBNP level by blood pressure after surgery
The study showed that: on N1, N2, and N3, the NT-proBNP level
in the group of patients with MAP <90 mmHg was higher than that in
the group with MAP ≥ 90 mmHg, the difference was statistically
significant with p <0.05. Correlation analysis showed that there was a
weak inverse correlation between NT-proBNP level and MAP, while
blood pressure decreased, the NT-proBNP level increased. On N4, N5,
there was no patient with low blood pressure. The study of Dang Duc
Hoan on 123 patients with acute myocardial infarction receiving PCI
also showed a moderate inverse correlation between blood pressure and
NT-proBNP level (r = -0,381 and -0,338; p <0.0001). And the study of
Nguyen Thi Tuong Van et al. also showed that serum BNP and systolic
and diastolic blood pressure in patients with MI had a moderate inverse
correlation (r = -0,41 and -0.46; p <0.01).
4.2.3 Changes in the NT-proBNP level by EF on postoperative days
The results showed that: on N1, N2, N3, N4, and N5, the NTproBNP level in the group of patients with EF ≤ 50% higher than that in
the group with EF> 50%, the difference is statistically significant with
p<0.05. Correlation analysis showed that there is a moderate inverse
correlation between the NT-proBNP level and EF. Research by Omland
et al. showed an increase in NT-proBNP level (>545 pmol /L) associated
with decreased left ventricular function. Serum NT-ProBNP level is a
useful marker to assess the recovery of left ventricular ejection function
(LVEF), especially in patients with a high-risk factor after CABG; And
it had an inverse correlation with LVEF. If the NT-proBNP level

increased, LVEF would decrease.
4.2.4Changes in the NT-proBNP level by cardiac index (CI) after
surgery
The result showed that there were 28 patients with decreased
cardiac index (CI <2.4 L / min / m2) after surgery. These cases all
happened at the times N1, N2, and N3 after surgery. No patient had a
decrease in CI on the fourth and fifth postoperative days. In patients
with decreased CI, the NT-proBNP level increased twofold to threefold
higher than that of the group with normal CI. The difference is


20

statistically significant with p <0.05. There is a moderate inverse
correlation between the NT-proBNP level and CI. A study by Mustafa
on 52 patients undergoing CABG showed that the variables, including
left ventricular ejection fraction (LVEF), cardiac output (CO), and
cardiac index (CI), in the group with increased levels of NT-proBNP,
were lower than those in the group with normal NT-proBNP level (NTproBNP <220 pg /ml).
4.3. The association between serum NT-proBNP and LCOS after
CABG
4.3.1 The role of serum NT-proBNP in the diagnosis of LCOS after
CABG
The NT-proBNP assay was highly valuable in detecting LCOS with
AUC (CI95%): 0.865 (0.72-1) with p <0.05. At the level of 951.5 pg
/ml, the serum NT-proBNP had a sensitivity of 92.3% and a specificity
of 78.7%. The AUC of serum NT-proBNP level of the group with
LCOS on N2 was AUC (CI95%): 0.855 (0.75-0.95) with p <0.05,
indicating that NT-proBNP assay was also valuable in detecting LCOS.
At the level of 2018 pg /ml, the serum NT-proBNP had 100.0%

sensitivity and 65.3% specificity. The AUC of serum NT-proBNP level
of the group with LCOS on N3 was AUC (CI95%): 0.848 (0.72-0.98)
with p <0.05, indicating that NT- proBNP was also valuable in detecting
LCOS. At the level of 4601 pg /ml, serum NT-proBNP had a sensitivity
of 100.0% and a specificity of 74.8%.
To diagnose LCOS after cardiac surgery, we found the cut-off with
the highest sensitivity and specificity, and the highest J (Youden Index).
Therefore, the cut-off was determined to be the level of NT-proBNP on
N1, standing at 951.5 pg /ml with a sensitivity of 92.3% and a
specificity of 78.7%, the J (Youden Index) of 0.71, which were highest
among postoperative days.
In the PRIDE study, the 300 pg/ml cutoff gave excellent application
in excluding the diagnosis of acute heart failure, the negative predictive
value (99%) was significantly higher than that of 100 pg/ml individual
BNP cut-off (89%). The 900 pg /ml cutoff for the diagnosis of acute
heart failure had a positive predictive value similar to that of the 100
pg/ml BNP cutoff (76% versus 79%).


21

4.3.2. The correlation between serum NT-proBNP with the
predictability of low cardiac output syndrome according to
EuroSCORE.
The results show that the threshold of NT-proBNP on the first day after
surgery is 871.8 pg/ml and in combination with EuroSCORE before
surgery, the accuracy of diagnosing LCOS with EuroSCORE lowmoderate risk (mostly medium risk) is 80.5%, with the EuroSCORE
high risk 70%.With a threshold of NT-proBNP on the second day after
surgery is 2516 pg/ml and and in combination with EuroSCORE before
surgery, the accuracy of diagnosing LCOS with EuroSCORE lowmoderate risk (mostly medium risk) is 77.9%, with the EuroSCORE

high risk 66.7%. With a threshold of NT-proBNP on the third day after
surgery is 3556 pg/ml and and in combination with EuroSCORE before
surgery, the accuracy of diagnosing LCOS with EuroSCORE lowmoderate risk (mostly medium risk) is 81.6 %, with the EuroSCORE
high risk 60%.Holm's retrospective study showed that the combination
of predictive evaluation of postoperative heart failure between the
EuroSCORE point and the preoperative NT-proBNP showed efficacy.
4.3.4. The association between NT-proBNP level and vasoactive
inotropic score (VIS) after surgery
The result showed that: basically, the correlation between NT-proBNP
and VIS at times N1, N2, N3, N4, and N5 was positive, weak, and not
statistically significant. This result is also in line with the study of
Yanqin Cui and the study of Ibarra-Sarlat M. The study of Yanqin Cui et
al. showed that there was a correlation between NT-proBNP and MIS
(Maximum Inotropic Score) at 1, 12, and 36 hours after surgery (p
<0.01). The study of Ibarra Sarlat M et al. on 40 patients after heart
surgery showed a weak positive correlation (r = 0.26) and there was no
statistical significance (p = 0.09) between NT-proBNP and VIS at 24
hours after surgery.


22

CONCLUSION
1. Changes in serum NT-proBNP level in patients undergoing
CABGwith extracorporeal circulation.
- After CABG, the serum NT-proBNP level increased gradually
from N1(972,5 ± 1608,05 pg/ml), increased andpeaked on N3 (4057,26
± 4458,12 pg/ml), and then tended to decrease gradually at N5(3457,81
±4110,98 pg/ml), (p<0,05).
- On N1, N2 and N3, there was weak inverse correlation ((r1 = 0.207; r2 = -0.033; r3 = -0.027) between the serum NT-proBNP level and

low blood pressure ( MAP < 90 mmHg).
- At pre- and post-operative times, the average NT-proBNP level in
patients with EF ≤ 50was higher than that in patients with EF> 50%
(p<0.05). NT-proBNP levels were in moderate inverse correlation with
the average with LVEF at postoperative times (r1 = -0.396; r2 = -0.49;
r3 = -0.489; r4 = -0.408; r5 = -0.392).
- At the times N1, N2, and N3, the average NT-proBNP level in
the group of patients with low cardiac output (CI <2.4 l /min /m2; CO
<4.0 l /min) was higher than that in the group with normal cardiac
output (CI ≥ 2.4 l /min /m2; CO ≥ 4.0 l /min), the difference was
statistically significant with p <0.05. There is a moderate inverse
correlation between the NT-proBNP level and CI (r1 = -0.35; r2 = 0.516; r3 = -0.436), and with CO (r1 = -0.32; r2 = -0.451; r3 = -0.434).
2. The association between serum NT-proBNP level and LCOS after
CABG.
- To diagnose LCOS after CABG, the cut-off value was determined
based on the level of NT-proBNP with the highest sensitivity and
specificity, the highest J index, on N1 with 951,5 pg/ml: sensitivity of
92.3%, the specificity of 78.7%; J index (Youden Index) of 0.71; AUC
(CI95%) of 0.865 (0.72-1) with p <0.05.
-The combination of preoperative EuroSCORE and postoperative
serum NT-proBNP showed prognostic effects of LCOS: the cut-off of
NT-proBNP level for detecting LCOS on N1, N2, N3 by the
EuroSCORE was: 871.8 pg/ml, 2516 pg/ml, and 3556 pg/ml,
respectively. The correlation between NT-proBNP level and
EuroSCORE was a weak positive correlation (p> 0.05).
- Serum NT-proBNP level has prognostic significance in LCOS by
VIS:


23

The cut-off of NT-proBNP levelmay predict acute heart failure in
the group with high VIS (VIS ≥ 15) on the first postoperative day was
1682 pg/ml (with a sensitivity of 93.7% and a specificity of 72.7 %; J
index of 0.664); on the second postoperative day was 8844 pg/ml(with
90% sensitivity and 60% specificity; J index of 0.5);on the third
postoperative day was 7152 pg/ml (with 63.2% sensitivity and 100%
specificity; J index of 0.63). The correlation between serum NT-proBNP
level and VIS was a weak positive correlation(p> 0.05).