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

Journal OF MILITARY PHARMACO - MEDICINE N04 - 2021  
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  
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,  
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 -  
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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Journal OF MILITARY PHARMACO - MEDICINE N04 - 2021  
mainly due to coronary artery disease Hanoi Heart Hospital from October 2016  
(CHD) [3]. Myocadial ischemia in chronic to January 2021  
coronary syndrome leads to functional  
* Selection criteria:  
impairment of an area of the left  
Patients with a diagnosis or a history of  
ventricular heart muscle, disorders of left  
acute myocardial infarction; Patients with  
ventricular  
increased passive stiffness promotes  
diastolic filling, hypertrophy  
relaxation,  
and  
then  
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.  
and  
myocardial fibrosis. Cardiac ischemia in  
cardiovascular  
disease  
can  
trigger  
and  
electrophysiological  
arrhythmias.  
changes  
When myocardial ischemia and  
hypoxia occur, the release of NT-proBNP  
is stimulated. Other factors in myocardial  
ischemia include increased heart rate,  
- Patient was diagnosed with heart  
failure by ESC 2016 [6].  
* Exclusion criteria:  
proinflammatory  
neurotransmitters  
vasoconstriction,  
cytokines  
such  
and  
as  
Patients had chronic kidney disease,  
severe arrhythmia, pericardial disease,  
antidiuretic,  
rapidly  
myocarditis,  
infectious  
endocarditis,  
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].  
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.  
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.  
* 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, ...).  
SUBJECTS AND METHODS  
1. Subjects  
136 patients with chronic heart failure  
were diagnosed as ischemic heart  
disease at Military Hospital 103 and  
* Data processing: By SPSS statistical  
software version 21.0. The statistical  
significance level is 95% with p < 0.05.  
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Journal OF MILITARY PHARMACO - MEDICINE N04 - 2021  
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  
34 (25.0)  
Females (n, %)  
Age ( SD)  
70.0 10.483  
X
Hypertension (n, %)  
Smoke (n, %)  
105 (77.2)  
25 (18.4)  
Chest pain (n, %)  
Edema (n, %)  
118 (86.8)  
19 (3.7)  
Rale in the lungs (n, %)  
25 (18.4)  
Enlarged liver, jugular vein (n, %)  
5 (3.7)  
88.49 25.212  
Diastolic blood pressure (mmHg) (  
X
SD)  
SD)  
135.10 25.568  
Systolic blood pressure (mmHg) (  
X
Ejection fraction (%)  
54.689 17.839  
2540.846 5486.735  
NT-proBNP before treatment (pg/mL) (  
NT-proBNP after treatment (pg/mL) (  
X
SD)  
SD)  
1162.268 2085.617  
X
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  
-0.065  
0.108  
0.141  
-0.083  
0.302  
0.322  
-0.315  
0.023  
0.454  
0.209  
0.102  
0.335  
< 0.001  
< 0.001  
< 0.001  
Gender  
Body mass index (BMI)  
Edema  
Chest pain  
Heart rate  
Creatinine  
Ejection fraction (%)  
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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Journal OF MILITARY PHARMACO - MEDICINE N04 - 2021  
Table 3: Correlation between NT-proBNP and heart failure by NYHA classification  
NYHA classification  
NT-proBNP pre-treatment (  
1235.36 4118.46  
4552.371 8280.329  
4167.684 5811.875  
2453.262 2820.500  
0.02  
SD)  
X
NYHA I  
NYHA II  
NYHA III  
NYHA IV  
p (medium)  
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  
Lown 0  
Before treatment n (%)  
68 (50.0)  
After treatment n (%)  
69 (50.7)  
50 (36.8)  
6 (4.4)  
p
Lown 1  
Lown 2  
Lown 3  
Lown 4  
Lown 5  
34 (25.0)  
9 (6.6)  
0.027  
7 (5.1)  
2 (1.5)  
18 (13.2)  
9 (6.6)  
0 (0.0)  
0 (0.0)  
There was a dramatical change between the ratio ofPVCs 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  
SD  
Post-treatment NT-proBNP  
SD  
Lown  
p
X
X
Lown 0  
2132.715 4244.692  
4370.759 8862.632  
1652.645 2234.545  
1675.567 1194.475  
988.613 1738.441  
1670.962 3129.067  
890.963 1042.746  
756.012 820.785  
0.008  
0.013  
0.256  
0.084  
Lown 1  
Lown 2  
Lown 3  
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Journal OF MILITARY PHARMACO - MEDICINE N04 - 2021  
Lown 4-5  
p (medium)  
r
1647.107 1787.532  
1151.074 1459.703  
0.048  
0.251  
0.046  
0.595  
0.578  
0.048  
0.583  
p (correlation)  
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.  
2. Relationship between NT-proBNP  
DISCUSSION  
and characteristics of heart failure and  
1. General characteristics of the patient  
premature ventricular complex  
Patients’ median age was 70.0 10.483.  
Clinical manifestations of heart failure  
Previous studies showed that men had a  
include chest pain, edema and enlarged  
higher risk of ischemic heart disease,  
liver with the corresponding rates of  
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].  
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].  
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.  
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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Journal OF MILITARY PHARMACO - MEDICINE N04 - 2021  
systolic function (EF%) had a moderately  
The degree of PVCs according to  
negative correlation with the NT-proBNP 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].  
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  
correlation  
a
moderately positive  
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).  
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.  
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].  
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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Journal OF MILITARY PHARMACO - MEDICINE N04 - 2021  
acute and chronic heart failure: The task force  
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