Relationship between the plasma nt-Probnp concentration and characteristics of heart failure and premature ventricular complexes in stable ischemic heart disease

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RELATIONSHIP BETWEEN THE PLASMA NT-proBNP 
CONCENTRATION AND CHARACTERISTICS OF HEART 
FAILURE AND PREMATURE VENTRICULAR COMPLEXES 
IN STABLE ISCHEMIC HEART DISEASE 
 Doan Thinh Truong1,2, Nguyen Oanh Oanh2, Nguyen Quang Toan3 
SUMMARY 
Objectives: To investigate the relationship between plasma NT-proBNP levels and 
characteristics of heart failure and premature ventricular complexes (PVCs) in patients with 
chronic ischemic heart disease. 
Subjects and methods: A cross-sectional descriptive study on 136 patients with chronic 
heart failure who were diagnosed as stable ischemic heart disease at Military Hospital 103 and 
Hanoi Heart Hospital from October 2016 to January 2021. Participants were eligible for 
inclusion and exclusion criteria. NT-proBNP was taken at the admission and after treatment. 
Medical statistical algorithm was used to determine the correlation between symptoms of heart 
failure, PVCs and plasma NT-proBNP. 
Results: Patients’ median age was 70.0 ± 10.483. NT-proBNP concentrations pre- and post - 
treatment were 2540.846 ± 470.484 and 1162.268 ± 178.840 pg/mL. Patient's age, heart rate, 
and creatinine levels were positively correlated with NT-proBNP concentration whereas left 
ventricular systolic function (EF%) was inversely correlated with NT-proBNP levels (r = -0.315, 
p < 0.001). There was a positive correlation between NT-proBNP concentrations and heart 
failure degree according to New York Heart Association (NYHA) (r = 0.406, p < 0.001). The 
severity of the post-treatment PVCs significantly decreased, with significant difference (p = 0.027). 
But there was no correlation between PVCs and the plasma NT-proBNP concentrations. 
Conclusion: Plasma NT-proBNP concentrations are correlated with several features of 
heart failure. But there is no correlation between PVCs and plasma NT-proBNP concentrations 
in patients with heart failure due to ischemic heart disease. 
* Keywords: NT-proBNP; Heart failure; Premature ventricular complexes; Stable ischemic 
heart disease. 
INTRODUCTION 
Chronic ischemic heart disease or 
chronic coronary syndrome is a condition 
that relates to the stability of atherosclerotic 
plaques, when there is not sudden 
rupture or after the acute phase or post - 
surgery/intervention. When the atheroma 
progresses, the coronary is narrowed 
significantly [2]. According to the 
statistics, cardiovascular diseases cause 
4 million deaths annually in Europe and 
1.9 million deaths in the European Union, 
1Hoai Duc General Hospital, Hanoi 
2Military Hospital 103, Vietnam Military Medical University 
3Thai Nguyen National General Hospital 
Corresponding author: Doan Thinh Truong (bsdoanthinhtruong@gmail.com) 
 Date received: 20/02/2020 
 Date accepted: 25/4/2021 
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 173 
mainly due to coronary artery disease 
(CHD) [3]. Myocadial ischemia in chronic 
coronary syndrome leads to functional 
impairment of an area of the left 
ventricular heart muscle, disorders of left 
ventricular relaxation, and then 
increased passive stiffness promotes 
diastolic filling, hypertrophy and 
myocardial fibrosis. Cardiac ischemia in 
cardiovascular disease can trigger 
electrophysiological changes and 
arrhythmias. 
When myocardial ischemia and 
hypoxia occur, the release of NT-proBNP 
is stimulated. Other factors in myocardial 
ischemia include increased heart rate, 
proinflammatory cytokines and 
neurotransmitters such as 
vasoconstriction, antidiuretic, rapidly 
increasing left ventricular pressure and 
cell proliferation. Birth also stimulates NT-
proBNP synthesis [4]. Studies show that 
NT-proBNP test plays a pivotal role in 
screening, diagnosing, and predicting 
cardiovascular events such as heart 
failure, arrhythmia, etc. in patients with 
chronic coronary syndrome [5]. 
Therefore, we conducted this project 
with the following objectives: To investigate 
the relationship between NT-proBNP 
levels and characteristics of heart failure 
and PVCs in patients with chronic ischemic 
heart disease. 
SUBJECTS AND METHODS 
1. Subjects 
136 patients with chronic heart failure 
were diagnosed as ischemic heart 
disease at Military Hospital 103 and 
Hanoi Heart Hospital from October 2016 
to January 2021 
* Selection criteria: 
Patients with a diagnosis or a history of 
acute myocardial infarction; Patients with 
significant coronary lesions (one coronary 
artery stenosis of at least 50% by 
coronary angiography at the time of the 
study or before; Patients undergoing 
coronary revascularization or without 
intervention; Patients undergoing coronary 
bypass surgery; Patients with stable angina 
or unstable angina. 
- Patient was diagnosed with heart 
failure by ESC 2016 [6]. 
* Exclusion criteria: 
Patients had chronic kidney disease, 
severe arrhythmia, pericardial disease, 
myocarditis, infectious endocarditis, 
or other severe chronic disease, or those 
who did not agree to participate in 
the study. 
2. Method 
A cross-sectional descriptive study. 
* Sampling method: 
Convenient sample, including all patients 
who met the inclusion criteria. 
* Research target: 
Age, sex, clinical symptoms (blood 
pressure, pulse, breathing rate, edema, 
heart failure degree according to NYHA, 
degree of chest pain according to CCS, ...), 
subclinical features (plasma NT-ProBNP, 
EF, Dd, ...). 
* Data processing: By SPSS statistical 
software version 21.0. The statistical 
significance level is 95% with p < 0.05. 
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RESULTS 
Through a study on 136 heart failure patients with chronic ischemic heart disease, 
we obtained the following results: 
Table 1: General characteristics of study subjects. 
Characteristics Parameters 
Females (n, %) 34 (25.0) 
Age ( X ± SD) 70.0 ± 10.483 
Hypertension (n, %) 105 (77.2) 
Smoke (n, %) 25 (18.4) 
Chest pain (n, %) 118 (86.8) 
Edema (n, %) 19 (3.7) 
Rale in the lungs (n, %) 25 (18.4) 
Enlarged liver, jugular vein (n, %) 5 (3.7) 
Diastolic blood pressure (mmHg) ( X ± SD) 88.49 ± 25.212 
Systolic blood pressure (mmHg) ( X ± SD) 135.10 ± 25.568 
Ejection fraction (%) 54.689 ± 17.839 
NT-proBNP before treatment (pg/mL) ( X ± SD) 2540.846 ± 5486.735 
NT-proBNP after treatment (pg/mL) ( X ± SD) 1162.268 ± 2085.617 
Male/female ratio: 3/1. Hypertension accounted for the highest percentage (77.2%). 
The mean age was 70.0 ± 10.483. Mean values of NT-proBNP pre- and post-treatment 
were different. 
Table 2: Relationship between plasma NT-proBNP concentrations and heart failure 
characteristics. 
Before treatment 
Correlation index 
r p 
Age 0.195 0.023 
Gender -0.065 0.454 
Body mass index (BMI) 0.108 0.209 
Edema 0.141 0.102 
Chest pain -0.083 0.335 
Heart rate 0.302 < 0.001 
Creatinine 0.322 < 0.001 
Ejection fraction (%) -0.315 < 0.001 
Patient's age, heart rate, creatinine level were positively correlated with NT-proBNP 
concentration, left ventricular systolic function (EF%) was inversely correlated with 
NT-proBNP concentration. In this study, we found no correlation between gender, BMI, 
chest pain level, edema and NT-proBNP levels. 
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Table 3: Correlation between NT-proBNP and heart failure by NYHA classification 
NYHA classification NT-proBNP pre-treatment ( X ± SD) 
NYHA I 1235.36 ± 4118.46 
NYHA II 4552.371 ± 8280.329 
NYHA III 4167.684 ± 5811.875 
NYHA IV 2453.262 ± 2820.500 
p (medium) 0.02 
r 0.406 
p (correlation ) < 0.001 
Plasma NT-proBNP concentration differs based on the severity of heart failure 
according to NYHA. The higher the NYHA level, the higher NT-proBNP concentration, 
the difference was significant with p = 0.02. There was a moderately positive 
correlation between plasma NT-proBNP concentrations and NYHA-based heart failure 
levels with r = 0.406 (p < 0.001). 
Table 4: Characteristics of ventricular premature complex on the 24-hour Holter 
monitoring by Lown grading system. 
24-hour Holter Before treatment n (%) After treatment n (%) p 
Lown 0 68 (50.0) 69 (50.7) 
Lown 1 34 (25.0) 50 (36.8) 
Lown 2 9 (6.6) 6 (4.4) 
Lown 3 7 (5.1) 2 (1.5) 
Lown 4 18 (13.2) 9 (6.6) 
Lown 5 0 (0.0) 0 (0.0) 
0.027 
There was a dramatical change between the ratio of PVCs pre- and post-treatment, the 
number of Lown 3-4 PVCs decreased significantly after treatment, the difference was 
statistically significant, p < 0.05. 
Table 5: Correlation between NT-proBNP and premature ventricular complex. 
Pre-treatment NT-proBNP Post-treatment NT-proBNP 
Lown 
X ± SD X ± SD 
p 
Lown 0 2132.715 ± 4244.692 988.613 ± 1738.441 0.008 
Lown 1 4370.759 ± 8862.632 1670.962 ± 3129.067 0.013 
Lown 2 1652.645 ± 2234.545 890.963 ± 1042.746 0.256 
Lown 3 1675.567 ± 1194.475 756.012 ± 820.785 0.084 
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Lown 4-5 1647.107 ± 1787.532 1151.074 ± 1459.703 0.048 
p (medium) 0.251 0.578 
r 0.046 0.048 
p (correlation) 0.595 0.583 
The plasma NT-proBNP concentration according to Lown grading system for PVCs 
did not differ between groups (p > 0.05). There was also no correlation for plasma 
NT-proBNP concentrations between the groups of PVCs as classified by Lown. 
DISCUSSION 
1. General characteristics of the patient 
Patients’ median age was 70.0 ± 10.483. 
Previous studies showed that men had a 
higher risk of ischemic heart disease, 
stroke and other cardiovascular diseases 
than women. In our study, male 
accounted for 75.0%, female only 25.0%. 
The pathogenesis of later development of 
atherosclerosis in women is due to the 
protective role hormone estrogen [7]. 
The mean values of plasma NT-proBNP 
concentrations pre- and post- treatment 
were 2540.846 ± 470.484 and 1162.268 ± 
178.840. The study by Nuria Farre et al. 
on 3,580 chronic heart failure patients, of 
whom ischemic heart disease was the 
leading cause with the rate of 44.7% and 
mean NT-proBNP concentration was 
1.638 pg/mL [8]. It is suggested that the 
group of heart failure patients with chronic 
ischemic heart disease had higher plasma 
NT-proBNP concentrations than those 
with chronic heart failure due to other 
causes, and myocardial ischemia contributes 
to increase the levels of NT-proBNP. 
2. Relationship between NT-proBNP 
and characteristics of heart failure and 
premature ventricular complex 
Clinical manifestations of heart failure 
include chest pain, edema and enlarged 
liver with the corresponding rates of 
86.8%, 3.7% and 3.7%. The incidence of 
edema in our study was lower because 
these patients were followed up regularly 
at an outpatient clinic. 
In this study, we found no correlation 
between sex, BMI, chest pain level, 
edema and NT-proBNP levels. According 
to Nguyen Thi Thu Dung et al, when 
studying 202 heart failure patients by 
stages, there was no correlation between 
NT-proBNP and BMI, glomerular filtration 
rate, hemoglobin, and left ventricular 
systolic [1]. 
Patient's age, heart rate, and creatinine 
level were positively correlated with 
NT-proBNP levels (mean r > 0.3). 
It means that the older the patients are, 
the faster the heart rate is, leading to an 
increased NT-proBNP levels. When 
tachycardia causes myocardial ischemia 
resulting in an increased myocardial 
contractility, which, in turn, stimulates 
release of NT-proBNP. Left ventricular 
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systolic function (EF%) had a moderately 
negative correlation with the NT-proBNP 
concentration with r = -0.315 (p < 0.001). 
It means that when left ventricular systolic 
function decreases, the concentration of NT-
proBNP increases, when left ventricular 
function decreases, ventricular relaxation, 
myocardial atony loss increases, leading 
to the release of NT-proBNP. In this 
study, we found no correlation between 
sex, BMI, chest pain level, and edema 
with NT-proBNP concentration (table 3). 
According to Richards M's study on 1,049 
patients with heart failure undergoing 
coronary intervention in Australia - New 
Zealand (ANZ), the author revealed that 
there was a moderately positive 
correlation between NT-proBNP 
concentration and age r = 0.44 (p < 0.001), 
and moderately negative correlation with 
left ventricular systolic function r = -0.46 
(p < 0.001) [9]. 
The plasma NT-proBNP concentration 
differs according to NYHA classification of 
heart failure, the higher the NYHA level, 
the higher the NT-proBNP concentrations, 
the difference was significant (p = 0.02). 
There was a moderately positive 
correlation between plasma NT-proBNP 
concentrations and NYHA-based heart 
failure levels with r = 0.406 (p < 0.001). 
Nguyen Thi Thu Dung et al studied on 
202 heart failure patients in different 
stages, the study results showed that 
there was a fairly strong correlation 
between the concentration of NT-proBNP 
and the degree of heart failure according 
to NYHA with r = 0.67 (p < 0.0001) [1]. 
The degree of PVCs according to 
Lown's classification on 24-hour Holter 
pre- and post-treatment was significantly 
different (p = 0.027). It means that after 
treatment, the number and the degree of 
severe PVCs decreased significantly 
compared to pre-treatment. However, 
there was no significant correlation between 
plasma NT-proBNP concentrations in the 
Lown-classified PVCs, indicating that 
NT-proBNP levels did not vary significantly 
between PVCs according to Lown 
classification with p (correlation) > 0.05 
and p (general) > 0.05. Lucian M. studied 
40 neuropathic patients undergoing 
24-hour electrocardiographic Holter to 
detect PVCs, the results revealed an 
NT-proBNP < 125 pg/mL in 16 patients 
and NT-proBNP > 125 pg/mL in 24 patients. 
The results showed that there was a great 
number of patients with PVCs in the 
NT-proBNP group, the presence of PVC 
was positively correlated with NT-proBNP 
with r = 0.445 (p = 0.006) [10]. 
Our study found no association 
between NT-proBNP levels and the 
presence of PVCs, which may be due to 
high degree of heart failure among our 
patients. Because NT-proBNP is elevated, 
we do not define NT-proBNP's cut-off for 
ventricular arrhythmias. 
CONCLUSION 
Plasma NT-proBNP concentrations in 
patients with chronic ischemic heart was 
correlated with several clinical and 
subclinical features of heart failure. But 
there was no correlation between plasma 
NT-proBNP levels and the presence 
of PVCs. 
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REFERENCES 
1. Nguyen Thi Thu Dung, Dang Van 
Phuoc. Correlation between NT-proBNP and 
stages in the progression of heart failure 
according to the School of Cardiology/ 
American Heart Association. Proceedings of 
the 9th Southern Conference on Cardiology 
2010:29-35. 
2. Knuuti J, et al. ESC guidelines for the 
diagnosis and management of chronic coronary 
syndromes. European Heart Journal 2019:1-71. 
3. Nichols M, Townsend N, Luengo-
Fernandez R, et al. European Cardiovascular 
Disease Statistics 2012. European Heart 
Network, Brussels and European Society of 
Cardiology. Sophia Antipolis 2012. 
4. Omland T, De Lemos JA. Amino-
terminal pro-b-type natriuretic peptides in 
stable and unstable ischemic heart disease. 
Am J Cardiol 2008; 101[suppl]:61A-66A. 
5. Radosavljevic-Radovanovic M, 
Radovanovic N, Vasiljevic Z, et al. Usefulness 
of NT-proBNP in the follow-up of patients after 
myocardial infarction. J Med Biochem 2016; 
35(2):158-165. 
6. Ponikowski P, et al. 2016 ESC 
Guidelines for the diagnosis and treatment of 
acute and chronic heart failure: The task force 
for the diagnosis and treatment of acute and 
chronic heart failure of the European Society 
of Cardiology (ESC). Developed with the 
special contribution of the Heart Failure 
Association (HFA) of the ESC. Eur J Heart 
Fail 2016; 18(8):891-975. 
7. Maas AH, Appelman YE. Gender 
differences in coronary heart disease. Neth 
Heart J 2010; 18 (12):598-602. 
8. Farré N, Lupon J, Roig E, et al. Clinical 
characteristics, one-year change in ejection 
fraction and long-term outcomes in patients 
with heart failure with mid-range ejection 
fraction: A multicentre prospective observational 
study in Catalonia (Spain). BMJ Open 2017; 
7(12):e018719. 
9. Richards M, Nicholls MG, Espiner EA, et 
al. Comparison of B-tupe natriuretic peptide 
for assessment of cardiac function and 
prognosis in stable ischemic heart disease. 
J Am Coll Cardioj 2006; 47(1):52-60. 
10. Lucian M, Ana P, Crina M, et al. The 
role of NT-proBNP in the diagnosis of 
ventricular arrhythmias in patients with 
systemic sclerosis. Iran J Public Health 2017; 
46(7):906-916.