Download Plasma Levels of B - Type Natriuretic Peptide (BNP

Plasma Levels of B - Type Natriuretic Peptide (BNP) and
Non-Invasive Cardiac Index in Diagnosing Congestive
Heart Failure in the Emergency Department
Radmila Kazanegra, Erin A. Barcarse, Amelia J. Chen, Alan S. Maisel
Cardiology, School of Medicine, UCSD, San Diego, CA; Cardiology, SDVAHCS, San Diego, CA
Presented at the 6th Scientific Meeting of the Heart Failure Society of America, September 22 - 25, 2002.
Abstract Published in Journal of Cardiac Failure, August 2002, Vol.8, No. 4., Suppl.
Background
B-type natriuretic peptide (BNP) is a cardiac
neurohormone secreted primarily from the left
ventricle in response to volume expansion and
pressure overload and is elevated in both systolic
and diastolic dysfunction.
While elevated BNP levels in dyspneic patients can
help to diagnose congestive heart failure (CHF), BNP
levels alone cannot differentiate systolic from diastolic
dysfunction. We propose that the combination of a
BNP level with various non-invasive cardiodynamic
parameters will help physicians more quickly and
accurately diagnose CHF.
Methods
Impedance Cardiography (ICG) is a non-invasive
method for measuring various hemodynamic
parameters. Changes in electrical impedance
(resistance) of the thorax are due primarily to changes
in the velocity and volume of the blood in the aorta.
Monitoring ICG involves injecting a high frequency
(70 kHz), low amplitude (2.5 mA) alternating
electrical current through the thorax and detecting
the resulting current with sensors. Measuring
changes in ICG as a function of time allows cardiac
output, systemic vascular resistance, acceleration
index, and many other hemodynamic parameters to
be calculated non-invasively.
98 patients seen in the the emergency department
(ED) of the VA San Diego hospital with acute
dyspnea enrolled in the study.
Plasma concentration of BNP quantified using the
Triage BNP Test (Biosite Diagnostics, Inc).
Non-invasive hemodynamic monitoring done using
the BioZ ICG monitor (CardioDynamics Corp).
Data sheets completed include health history,
physical exam findings, lab results, and medications.
Final CHF diagnosis made by cardiologist reviewing
patient charts.
Cardiologist blinded to hemodynamic parameters
but not to BNP level.
Statistical analyses: Mann-Whitney Test, Logistic
Regression, ROC curves.
Table 1. Patient Demographics
Characteristics
Age
Gender: male/female
Race
White
African-American
Hispanic
Asian
Height (inches)
Weight (lbs)
Habits
Smoking
Ethanol abuse
% of
Total
Patients
64.6 ± 1.2
100
79.6
10.2
6.1
4.1
69.1 ± 0.3
204.1 ± 5.4
72.4
58.2
Characteristics
History
Congestive heart failure
Hypertension
Diabetes mellitus
COPD
Asthma
Pulmonary embolism
Myocardial infarction
CAD / Angina
Atrial fibrillation
Any cardiac surgery
Stroke
% of
Total
Patients
59.2
74.5
41.8
37.8
13.3
3.1
40.8
44.9
13.6
33.7
14.3
Table 2. Signs and Symptoms
Characteristics
Symptoms
Dyspnea
Lethargy
Ankle/peripheral edema
Cough
Orthopnea
Chest pain
Recent weight gain
Paroxysmal nocturnal dyspnea
% of
Total
Patients
100
65.3
59.2
54.1
43.9
41.8
35.7
30.6
Characteristics
Physical Exam
Pulmonary rales
JVP > 6 cm
Wheezing
Abnormal heart sounds
S3 Gallop
Murmurs
Diffuse/lateral PMI
Ascites
% of
Total
Patients
48
44.9
36.7
27.6
9.2
19.4
4.1
4.1
ROC curves for CI and BNP: Determining Systolic
Dysfunction in Patients with BNP > 100 pg/ml
Results
Plasma BNP Levels in All Patients
Plasma BNP Level (pg/ml)
900
*p<0.001
800
1.0
400
2.6
496
550
0.6
590
0.4
BNP (pg/ml)
670
2.3
725
BNP: AUC = 0.640 (0.487-0.793)
p < 0.078
0.2
CI: AUC = 0.735 (0.598-0.871)
p < 0.003
0.0
0.0
0.2
0.4
0.6
0.8
1.0
1 - Specificity
Table 3. CI in Determining Systolic Dysfunction in Patients
with BNP > 100
Positive
Negative
CI
Sensitivity Specificity
Accuracy
Predictive Predictive
2
(%)
(%)
(%)
(l/min m )
Value (%) Value (%)
*
700
3.0
2
CI (L/min m )
0.8
Sensitivity
Regardless of their cardiac index (CI) (N=37), patients
with a BNP < 100 pg/ml had no evidence of CHF 97%
of the time. In those with a BNP > 100 pg/ml (601 ± 55
pg/ml, N = 61), a CI of 2.6 L/min m2 is 71% sensitive
and 69% specific in distinguishing systolic from diastolic
heart failure. In patients with a BNP > 100 pg/ml, a
multivariate model consisting of thoracic fluid content
(TFC), acceleration index (ACI), and left cardiac work
index (LCWI) measurements was able to predict cardiac
deaths, re-admissions, and ED visits within 90 days with
an 80% accuracy.
< 2.3
29
92
82
50
56
< 2.6
65
88
87
66
75
< 3.0
84
50
68
71
69
600
500
698 ± 73
630 ± 57
535 ± 88
400
300
200
*
Table 4. A Multivariate Model of LCWI, ACI, and TFC for
Predicting Endpoints in Patients with BNP >100 pg/ml
44 ± 9
100
0
Non-CHF All CHF 1 Systolic
(N=41)
(N=57)
Diastolic
(N=33)
(N=24)
Hemodynamic
Parameters
CI Measurements in All Patients
*
3
LCWI
31
89
56
74
71
LCWI + ACI
45
88
62
78
74
LCWI + ACI + TFC
59
89
71
83
80
*p<0.003
2.9
2.8
2.7
2.94 ± 0.10
2.88 ± 0.12
Conclusion
*
2.6
2.71 ± 0.08
2.5
2.54 ± 0.11
2.4
Plasma BNP level is a sensitive and specific test for
identifying patients with CHF in an emergency setting.
A CI of 2.6 l/min m2 is 75% accurate in determining the
type of LV dysfunction in CHF patients.
A multivariate model of LCWI, ACI, and TFC in patients
with BNP > 100 pg/ml is 80% accurate in predicting
cardiac death, re-admission, and ED visits within 90 days.
In patients presenting to the ED with dyspnea, the
addition of non-invasive hemodynamic measurements
to a BNP level more effectively diagnoses CHF by:
2.3
2.2
Non-CHF All CHF
(N=41)
1
(N=57)
Systolic
Diastolic
(N=33)
(N=24)
ROC curves for CI and BNP:
Determining CHF versus Non-CHF in all patients
1.0
110
BNP (pg/ml)
0.8
Sensitivity
Cardiac Index (l/min m2)
3.1
Positive Negative
Sensitivity Specificity Predictive Predictive Accuracy
(% )
(% )
(% )
Value
Value
(% )
(% )
170
2
CI (L/min m )
3.0
300
0.6
2.8
0.4
- Differentiating between systolic and diastolic
dysfunction in a rapid and inexpensive manner.
2.6
2.5
2.4
0.2
BNP: AUC = 0.979 (0.956-1.002)
p < 0.001
- Determining the severity of illness.
CI: AUC = 0.577 (0.460-0.693)
p < 0.196
0.0
0.0
0.2
0.4
0.6
1 - Specificity
0.8
1.0
M357 Rev. A