Cardiology Section
DOI: 10.7860/JCDR/2017/29173.10801
Original Article
Usefulness of B-Type Natriuretic
Peptide in Predicting the Involvement
of Right Ventricle in Acute Inferior Wall
Myocardial Infarction
RAMALINGAM AROUTSELVAN1, VICTOR ASHOK2, SETHUMADHAVAN RAGHOTHAMAN3, HANNAH SUGIRTHABAI RAJILARAJENDRAN4
ABSTRACT
Introduction: Cardiovascular Disease (CVD) is the leading cause
of deaths globally as the death rate due to CVD has increased
from 26% in 1990 to 29.5% in 2010. The Acute Coronary
Syndrome (ACS) includes acute Myocardial Infarction (MI) with
ST segment elevation, Non-ST Segment Elevation Myocardial
Infarction (NSTEMI) and Unstable Angina (UA). Isolated infarction
of the right ventricle is rare and is commonly associated with
Inferior Wall MI (IWMI) or Posterior Wall MI (PWMI). B-type
Natriuretic Peptide (BNP) is one of the biomarkers which has
been evaluated during acute MI.
Aim: In this study, the usefulness of BNP in predicting the
involvement of Right Ventricle (RV) in acute ST elevation with
IWMI and PWMI was assessed.
Materials and Methods: The study was a prospective observational
study, done on 64 patients less than 60 years of age. The study was
conducted over a period of four months at Rajiv Gandhi General
Hospital, Madras Medical College, Chennai., Tamil Nadu, India.
The patients with diagnosis of IWMI, IW with RVMI, IW with PWMI,
IW and PW with RVMI were included. BNP levels, Left Ventricular
Ejection Fraction (LVEF) and troponin I were measured. Killip class
was also observed and patients were classified and compared
against different levels of BNP.
Results: When IWMI is associated with RV, PW or RV with PW
involvement, BNP level was increased to more than 900 pg/ml,
than in isolated IWMI. This increment was statistically significant.
There was severe increase in BNP in those having LVEF ≤30%,
and majority of patients were in the range of 30-50%. All the
patients in Killip class III and IV had severe BNP increase as did
those patients with cardiac troponin levels between the range
of 2-4 ng/ml.
Conclusion: All the findings are statistically significant and
prove that severe BNP increase in acute IWMI is definitely a
predictor of associated RV, PW or RV with PW involvement.
LVEF has a significant inverse correlation with BNP levels, as
the BNP rises, LVEF shows a steady decline. Killip class also
shows a poor prognosis with elevated BNP. Troponin I levels are
higher with increase in BNP.
Keywords: Cardiovascular disease, Left Ventricular Ejection Fraction, Predictor
INTRODUCTION
MATERIALS AND METHODS
Cardiovascular Disease (CVD) has emerged as one of the major
fatal diseases, its mortality percentage increasing from 26% in 1990
to 29.5% in 2010 [1]. Acute MI with ST segment elevation, NSTEMI
and UA are all parts of ACS. Isolated infarction of the RV is rare
and Right Ventricular Myocardial Infarction (RVMI) occurs in about
50% of the cases of IWMI [2,3] or with PWMI. The latest biomarkers
include Heart-type Fatty Acid Binding Protein (H-FABP), serum
amyloid A, myeloperoxidase, interleukin-6 and ischaemia modified
albumin.
The study was a prospective observational study, done during
the period between November 2014 to February 2015. The study
population were 64 patients, less than 60 years of age, with acute
IW ST elevation MI with no history of cardiac disease. The patients
with diagnosis of IWMI, IW with RVMI, IW with PWMI, IW and PW
with RVMI were included. The patients aged more than 60 years,
with AWMI, NSTEMI/UA, history of MI, valvular heart disease, renal
failure, liver cirrhosis, other causes of pulmonary hypertension,
anaemia and other infections were excluded. Ethical clearance and
informed consent of the patients were obtained.
BNP is a natriuretic peptide that is mainly released from the cardiac
myocytes in the left ventricular wall in reaction to stress and tension
of myocardial wall [4]. There is a n-terminal prohormone natriuretic
peptide of brain (NT-proBNP) which is an inactive remnant of
hormonically active BNP. BNP and NT-proBNP will be secreted into
circulation after the cleavage of prohormone pro BNP and BNP. The
BNP has a protective mechanism in the body that causes diuresis,
sodium excretion and dilation of vessel and the sympathetic nervous
system inhibition. Half-life of BNP is nearly 20 minutes but of NTproBNP is 120 minutes.
In this study, the usefulness of BNP in predicting the involvement of
RV in acute ST elevation with IWMI and PWMI was assessed. The
LVEF was also assessed and correlated with the different levels of
BNP. In this study, BNP levels were compared with cardiac troponin
I and Killip class, in predicting the prognosis after acute MI.
Journal of Clinical and Diagnostic Research. 2017 Nov, Vol-11(11): OC01-OC04
The study population was divided into three major groups.
Group 1: Mild BNP increase
301-600 pg/mL
Group 2: Moderate BNP increase
601-900 pg/mL
Group 3: Severe BNP increase
more than 900 pg/mL
With ECG & ECHO they were further divided into four sub-groups
Sub-group 1: IWMI
15 patients
Sub-group 2: IW and PWMI
13 patients
Sub-group 3: IW with RVMI
22 patients
Sub-group 4: IW and PWMI with RVMI
14 patients
The LVEF was measured for all 64 patients and tabulated for different
BNP levels. Killip class was recorded for all these patients and TIMI
scoring for STEMI was also calculated. Detailed ECG assessment
was done to localise MI. The BNP levels and troponin I levels were
1
Ramalingam Aroutselvan et al., BNP as Predictor of RVMI
measured in blood by rapid quantitative test in the first 24 hours,
using a Alere Triage cardio three panel. This panel is a single use
fluorescence immunoassay device to simultaneously determine
the concentration of CK-MB, troponin I and BNP in EDTA anticoagulated whole blood or plasma concentrations.
www.jcdr.net
ECG-MI/
Localisation
IWMI
8
80
5
83
2
4
STATISTICAL ANALYSIS
IW/RVMI
2
20
0
0
20
42
Descriptive statistics were done for all data and suitable statistical
tests for comparison were used. Continuous variables were
analysed with ANOVA and categorical variables were analysed
with Chi-square test or Fisher-exact test. Statistical significance
was taken as p<0.05. Epi Info software (7.1.0.6 version; Center for
disease control, USA) was used to analyse the obtained data from
the study.
IW/PWMI
0
0
0
0
13
27
IW/RV/
PWMI
0
0
1
17
13
27
Total
10
100
6
100
48
100
[Table/Fig-1]: MI localisation and BNP levels.
ECG - Electrocardiogram, MI - Myocardial Infarction, BNP - B-type natriuretic peptide
Chi-square Test
p-value=0.00001
RESULTS
The study was done on 64 patients, hailing from in and around
Chennai. All patients less than 60 years of age were included in the
study. Most of the patients were from low socioeconomic group
and were included in the study irrespective of gender, habits like
smoking or drinking and any associated diseases like diabetes and
hypertension.
The localisation of MI with ECG along with the number of cases in
each category, namely, IWMI - 15, IW/RVMI - 22, IW/PWMI - 13, IW/
RV/PWMI - 14 was recorded and labelled as in [Table/Fig-1]. The
BNP levels were divided into mild, moderate and severe categories.
The LVEF was measured, and the sample division was done as
follows: ≤30%, 31-40%, 41-50% and 51-60%. The values for the
different categories of BNP were as seen in [Table/Fig-2]. The Killip
classification was recorded and the patients were divided into class
I, II, III and IV and the number of patients in each BNP category
was found to be as in [Table/Fig-3]. The levels of cardiac troponin I
was also recorded and tabulated against different BNP levels as in
[Table/Fig-4]. Upto a maximum of 4 ng/mL was recorded starting
from 0.01 ng/mL, being the lowest. Higher the cardiac troponin
level, the BNP severity also increased.
LVEF %
Number
Number of
Number
of patients
patients with
of patients
PerPerPerwith Mild
Moderate
with Severe
centage
centage
centage
BNP
BNP
BNP
increase
increase
increase
≤ 30%
0
0
0
0
11
23
31-40%
1
10
1
17
18
37.5
41-50%
4
40
2
33
19
39.5
51-60%
5
50
3
50
0
0
Total
10
100
6
100
48
100
[Table/Fig-2]: LVEF and BNP levels.
LVEF - Left ventricular ejection fraction, BNP - B-type natriuretic peptide
ANOVA
p-value=0.0001
KILLIP
Classification
Number of
Number of
Number of
patients
patients
patients
Perwith
Perwith
Perwith Mild
centage Moderate centage
Severe
centage
BNP
BNP
BNP
increase
increase
increase
Class I
8
80
4
67
8
17
Class II
2
20
2
33
18
37.5
DISCUSSION
Class III
0
0
0
0
21
43.5
The prognosis in MI can be predicted by scoring system like TIMI
scoring system and Killip classification. The other enzymes like
troponin I and CK-MB are also used for prognostic implications. BNP
is one of the most sensitive biomarkers of cardiac muscle strain.
This study evaluates its use as a prognostic marker in patients with
acute IWMI with RVMI.
Class IV
0
0
0
0
1
2
Total
10
100
6
100
48
100
In acute IW MI with right ventricular involvement, RV involvement
is sometimes a misnomer, as RV infarction leads to temporary RVdysfunction and indicates viable myocardium which recovers with
early reperfusion. LV is a thick walled pressure pump. RV is a thin
walled volume pump which ejects into a low resistance pulmonary
circulation. Factors responsible for RV systolic pressure and
flow include shortening of the RV free walls, contraction towards
the septum (APEX to RVOT) and LV septal contraction. Nearly
50% of the patients with IW MI have associated right ventricular
involvement. In most of the cases LV systolic function is preserved.
Clinical features of RVMI are severe right heart failure, clear lungs
and low output hypotension. So RV involvement is associated with
increased, mortality and mobility.
BNP has usefulness as a prognostic marker among patients with
ACS, including those with STEMI/NSTEMI/UA [5,6]. IW STEMI has
raised BNP values; however, anterior wall STEMI has comparatively
raised BNP values. IWMI with RV involvement has increased BNP
levels compared to isolated IWMI [7]. In OPUS-TIMI 16, the 10
months mortality rate was increased to two to three folds in patients
whose BNP was significantly higher [8]. TIMI II and TACTICSTIMI 18 trials confirmed this [9,10]. The ESI guidelines and AHA
guidelines suggest that BNP assays are useful adjunct to clinical
2
Number
Number of
Number
of patients
patients with
of patients
PerPerPerwith Mild
Moderate
with Severe
centage
centage
centage
BNP
BNP
BNP
increase
increase
increase
[Table/Fig-3]: Killip classification and BNP levels.
BNP - B-type natriuretic peptide
Fisher’s Exact Test
p-value=0.002
Cardiac
Troponin I
Number of
Number of
Number of
patients
patients
patients
Perwith
Perwith
Perwith Mild
centage Moderate centage
Severe
centage
BNP
BNP
BNP
Increase
Increase
Increase
≤ 1 ng/ml
7
70
4
67
8
17
1.01-2 ng/ml
3
30
2
33
22
46
2.01-3 ng/ml
0
0
0
0
13
27
3.01-4 ng/ml
0
0
0
0
5
10
Total
10
100
6
100
48
100
[Table/Fig-4]: Cardiac troponin I and BNP levels.
BNP - B-type natriuretic peptide
ANOVA*
p-value= 0.004153
assessment. Levels of BNP differentiated whether shortness of
breath is due to heart failure or a respiratory cause in a multinational
study “Breathing not properly” [11]. In addition BNP cut-off value
was 100 pg/mL as normal. The diagnostic accuracy of BNP is
81.2%, compared to 74% for clinical judgments alone. The role of
BNP in diagnosing dyspnoea as a cause for heart failure in acute
conditions was established in the above study. In these trials BNP
value of 100 pg/mL had a negative predictive value. More than 400
Journal of Clinical and Diagnostic Research. 2017 Nov, Vol-11(11): OC01-OC04
www.jcdr.net
pg/mL has a positive predictive value. Values of 100 to 400 pg/mL
is grey area.
The infarct size [12,13] and regional wall motion abnormalities
correlate well with BNP levels. Patients with AWMI, low cardiac
index and heart failure have increased levels of BNP and have the
worst prognosis. Patients with increased levels of BNP in the first
six hours have increased risk of mortality. Patients with increased
levels in the third to fourth week have increased cardiac related
complications in the next five to ten years. BNP is an independent
marker of myocardial inflammation and necrosis. This was not
proved in TACTICS-TIMI-18 [10]. Dynamic risk profile can be
done by serial BNP measurements. When BNP levels are very
low and troponin levels, normal patients are at very low risk of
cardiovascular events.
In our study, patients with IW MI were divided into only IWMI, IW with
RV involvement, IW with PW involvement and IW with PW and RV
involvement as in [Table/Fig-1]. In simple terms, mild BNP increase
is seen in isolated IWMI patients; whereas, severe BNP increase is
seen in patients with IWMI associated RV and PWMI. Among the
three groups showing severe BNP increase, the patients with IW/
RV MI have the highest incidence [Table/Fig-1]. The cut-off value
for this significant BNP level is 900 pg/mL. The difference between
groups was significant with a p-value of 0.00001 according to Chisquare test. This indicates that there is a true difference among the
study groups and the difference is significant and has not occurred
by chance. Hence, severe BNP increase levels correlates with
incidence of IW/RV/PWMI and mild BNP increase levels correlate
with incidence of IWMI in ECG.
In studies done by Kaya MG et al., it was found that PWMI with
RV involvement had higher BNP values than isolated PW infarction.
The study was conducted on 49 patients who were admitted with
first attack of IWMI, with and without RV involvement. As per the
study, plasma BNP levels were higher in IWMI with RVMI compared
to isolated IW MI alone [7]. In the present study also, the same was
true, though along with this finding, it was found that the higher
levels of BNP is found in IWMI associated with PW alone as well as
in PW with RV involvement when compared to isolated IWMI. So,
we can conclude that BNP levels correlate with higher incidence of
RV involvement.
According to Gunes Y et al., the basal BNP level is an indicator of
LVEF [14]. It is a prognostic indicator as well. In a study conducted
by Kallistratos MS et al., It was found that plasma BNP levels were
related to LVEF. In patients with impaired LVEF, it was observed
that the exercise capacity was lower [15]. In the present study,
by conventional criteria the association between ECHO LVEF%
findings and BNP increase was found to be statistically significant
(p<0.05). In simple terms, the incidence of lowest LVEF ≤ 30% was
highest in severe BNP increase group [Table/Fig-2]. The difference
between groups was significant with a p-value of 0.0001 according
to ANOVA test. The higher mean LVEF levels, being 51.5%, was
measured in mild BNP increase group and the lower mean LVEF
being 40.04%, was measured in severe BNP increase group. This
indicates that there is a true difference among the study groups
and the difference is significant and has not occurred by chance.
Hence, severe BNP increase is associated with decreased LVEF%
levels. There was a reverse correlation between BNP level and LVEF
and the p-value was very significant. The increase in BNP levels
inversely correlates with LVEF.
After acute MI, BNP has been identified as an important indicator
of prognosis. It has been a prognostic indicator for early and
delayed complication of MI and also Killip class [16]. In a study
conducted by Grabowski M et al., in patients with STEMI, 126
patients were included [17]. With higher Killip class BNP level was
severely increased. In this study, the incidence of Killip classification
class I is 80% in mild BNP increase group compared to 67% in
moderate BNP increase and 17% in severe BNP increase group.
Journal of Clinical and Diagnostic Research. 2017 Nov, Vol-11(11): OC01-OC04
Ramalingam Aroutselvan et al., BNP as Predictor of RVMI
Whereas, the incidence of Killip classification class IV was 0% in
mild and moderate BNP increase and 2% in severe BNP increase
group [Table/Fig-3]. The major part of patients in class II and III,
belonged to the severe BNP increase group, indicating a strong
link between Killip classification and BNP increase. The difference
between groups was significant with a p-value of 0.002 according
to Fisher’s exact test. This indicates that there is a true difference
among the study groups and the difference was significant and has
not occurred by chance. We can hence, conclude that severe BNP
increase is associated with higher Killip class.
In our study, the cardiac troponin I levels are significantly high. This is
statistically significant. In a study it was proved that for each additional
biomarker that was positive the mortality rate doubled [18]. In our
study significant increase in Troponin I levels were associated with
increase in BNP levels. The incidence of cardiac troponin I levels
≤1 ng/mL is 70% in mild BNP Increase group compared to 67% in
moderate BNP Increase and 17% in severe BNP increase group.
Similarly, the incidence of cardiac troponin I levels 3.01-4 ng/mL
range is 0% in mild and moderate BNP increase and 10% in severe
BNP Increase group [Table/Fig-4]. The difference between groups
is significant with a p-value of 0.004153 according to ANOVA test.
The lowest mean cardiac troponin I levels (0.80 ng/mL) is measured
in Mild BNP Increase group and the highest mean cardiac troponin I
levels (2.00 ng/mL) is measured in severe BNP Increase group.
LIMITATION
Major limitation of the study was lesser number of patients. The
use of ECHO and ECG in the first 24 hours can still be difficult in
diagnosing RVMI as RV dysfunction and stunning is frequently
transient. Effect of type of treatment on BNP levels was not assessed
in this study. Newer biomarkers like NT-proBNP could have been
used but it was not used because of its higher cost.
CONCLUSION
Plasma BNP levels are significantly higher in IWMI, when right ventricle
is involved. In patients with IWMI right ventricular involvement may be
suspected when BNP levels are significantly higher. Severe increase
in BNP levels correlate with higher incidence of right ventricular
involvement as indicated by occurrence of significant increase in
BNP levels in IW/RV/PWMI diagnosed by ECG and ECHO. Isolated
IWMI is associated with mild BNP increase. We conclude that
severe BNP increase is associated with decreased LVEF. Severe
BNP elevations in higher KILLIP classification strongly confirmed
prognostic value of BNP.
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PARTICULARS OF CONTRIBUTORS:
1. Assistant Professor, Department of Cardiology, Government Chengalpattu Medical College, Chengalpattu, Tamil Nadu, India.
2. Associate Professor, Department of Cardiology, Government Chengalpattu Medical College, Chengalpattu, Tamil Nadu, India.
3. Assistant Professor, Department of Cardiology, Government Chengalpattu Medical College, Chengalpattu, Tamil Nadu, India.
4. Professor, Department of Anatomy, Chettinad Hospital and Research Institute, Kelambakkam, Chennai, Tamil Nadu, India.
NAME, ADDRESS, E-MAIL ID OF THE CORRESPONDING AUTHOR:
Dr. Victor Ashok,
7D, KG Towers, 100 Feet Bypass Road, Velachery, Chennai-600042, Tamil Nadu, India.
E-mail: drashokcardio@yahoo.co.in
FINANCIAL OR OTHER COMPETING INTERESTS: None.
4
Date of Submission: Apr 09, 2017
Date of Peer Review: May 26, 2017
Date of Acceptance: Sep 06, 2017
Date of Publishing: Nov 01, 2017
Journal of Clinical and Diagnostic Research. 2017 Nov, Vol-11(11): OC01-OC04