EXERCISE SHEET:
Evidence table: The data below were extracted from Appendix J of the NICE Heart Failure Guideline, Section 6: Diagnosing Heart Failure
Key question: Which natriuretic peptide measuremnt is best for diagnosing congestive heart failure?
Study/Give level of
evidence!
Type of
study
Number of
patients
Diagnostic Outcomes
test
Davis, K. et al. 1992
Atrial natriuretic peptide
levels in the prediction of
congestive heart failure
risk in frail elderly
JAMA, vol. 267, no. 19, pp.
2625-2629.
Cohort
310
plasma ANP
Presence of
congestive heart
failure, no
congestive heart
failure, death
Results

Non congestive heart failure group had lower ANP
level (207+/- 15 pmol/l) than the CHf group (493 +/55 pmol/l) (p<0.001)

ANP >200 pmol/l has sensitivity of 85% and
specificity of 66% as a predictor of coronary heart
failure


No significant difference in hypertension to control
Cardiac impairment tests and both BNP tests higher
than for controls
Both tests inversely correlated with left ventricular
ejection fraction (p<0.001), and exercise test time
(particularly NT-proBNP)
Results higher in NYHA class I than controls, and
higher in classes II-III than class I
Comments
Specialist care setting
may detect more
coronary heart failure
cases, or may treat
patients better.
LEVEL OF EVIDENCE:.........
Hunt, P. J. et al. 1997
Immunoreactive aminoterminal pro-brain
natriuretic peptide (NTPROBNP): a new marker
of cardiac impairment",
Clin.Endocrinol.(Oxf), vol.
47, no. 3, pp. 287-296.
Casecontrol
157
Hypertension
and cardiac
impairment
vs control
Levels of BNP in
blood plasma. NTproBNP, and
BNP-32


New Zealand study
Source of NT-proBNP
appears to be the heart
as shown by significant
gradients in levels
sampled from femoral
artery and coronary
sinus
LEVEL OF EVIDENCE:.........
Cowie, M. R. et al. 1997
Value of natriuretic
peptides in assessment of
patients with possible new
heart failure in primary
care Lancet, vol. 350, no.
9088, pp. 1349-1353.
LEVEL OF EVIDENCE:.........
Diagnostic
study
122
Diagnostic
value of
natriuretic
peptides
(ANP and
BNP)
Against clinical
diagnosis of HF
by physical
assessment,
Chest X-ray and
echocardiography
Peptide levels higher in HF patients than in non-HF
patients diagnosed for all test types:

ANP 29.2 Vs 12.4

BNP 63.9 Vs 13.9

NT-ANP 1187.0 Vs 410.6

(pmol/l) (p<0.001)
No significant association with age and sex
At negative predictive value of 98% (BNP =22.2 pmol/l) a
sensitivity of 97% and specificity of 84%
BNP only independently predictive value for HF with other
peptides and chest X-ray, by logistic regression
Possible systematic
loss of assays due to
high or low
concentrations
Patients from referral
of 81 GPs
Possibly more HF
aware population of
GPs from participation
in Hillingdon study
1
Study/Give level of
evidence!
Type of
study
Number of
patients
Diagnostic
test
Outcomes
Results
Comments
Maisel, A. S. et al. 2002
Rapid measurement of Btype natriuretic peptide in
the emergency diagnosis
of heart failure.
New England Journal of
Medicine., vol. 347, no.3,
pp. 161-167.
Diagnostic
study
n=1586
Age =64yrs,
Male: 56%,
History of HF:
33%,
MI: 27%,
COPD: 41%,
DM: 25%
USA, France,
Norway
Multinational
trial to assess
the utility of
BNP in
diagnosis of
CHF in
patients with
dyspnoea.
Reference
standard: clinical
assessment of HF
cause by two
independent
cardiologists
(agreement not
stated) using
patient
records, chest Xray and cardiac
function test
results. Ref. std.
measured in all
patients
regardless of the
test result

All patients were
classified as to
whether dyspnoea due
to HF or otherwise
blind to test result,
other tests of cardiac
function such as
echocardiogram were
strongly encouraged
but not undertaken in
all patients.
Multivariate analysis of
diagnostic use of
natriuretic assay using
historical, clinical , and
roentgenographic
parameters in a
stepwise logistic
regression using
factors that had a
significance at p=0.05
in bivariate analysis.
This test may be useful
if echocardiography is
difficult or where there
is a co-existing
condition such as
obesity or lung disease
147
Diagnostic
value of
natriuretic
peptides
(ANF and
BNP)
LEVEL OF EVIDENCE:.........
Selvais, P. L. et al. 1998
Cardiac natriuretic
peptides for diagnosis and
risk stratification in heart
failure: influences of left
ventricular dysfunction and
coronary artery disease on
cardiac hormonal
activation. Eur J Clin Invest,
vol. 28, no. 8, pp. 636-642.
Diagnostic
study
BNP Test:
fluorescence
immunoassay
kit.
Against Left
ventricular
ejection fraction
by echocard. and
NYHA class
Final diagnosis was of HF in 774 patients (47%), non
cardiac causes inpatients with history of LV
dysfunction 72 patients (5%) , and no finding of HF in
770 patients (49%).

In 97% of patients with HF the final diagnosis was
confirmed by the use of other tests

Patients with final diagnosis of HF had a natriuretic
peptide level of 675 pg/ml, those without HF had a
level of 110 pg/ml, and those who had baseline LV
dysfunction and had Dyspnoea without an
exacerbation of HF had a peptide level of 346 pg/ml.
The difference between each of these groups was
significant at p<0.001for each comparison

A B-type natriuretuc cut-off value of 100 pg/ml had a
sensitivity of 90% a sensitivity of 76% and an
accuracy of 83% fro differentiating congestive HF
from other causes of dyspnoea

B-type natriueretic values varied significantly with
patient NYHA class as determined by cardiologists,
with the level in class I averaging 144 pg/ml, in class
II it was 389 pg/ml. In class III the reading was 640
pg/ml, and in class IV the level was 817 pg/ml
(p<0.0010 for comparison of groups

In a multiple logistic regression analysis the addition
of B=type natriuretic peptide added to the combined
explanatory power of history, symptoms, signs,
radiological studies, and laboratory findings. A value
of 100pg/ml or higher was the strongest independent
predictor of congestive HF with an OR 29.60 (95% CI
17.75 to 49.37)
Significant correlation of the three peptide measures and
left ventricular dysfunction

BNP r=-0.59

N-proANF r=-0.53

ANF r=-0.30

(p<0.001)
BNP performed better than others at grading severity of
congestive heart failure (p<0.05)
Larger proportion of
women in control
group.
Used NYHA class
rather than ejection
fraction for receiveroperating analysis.
LEVEL OF EVIDENCE:.........
2
Study/Give level of
evidence!
Type of
study
Number of
patients
Diagnostic Outcomes
test
Yamamoto, K. et al. 1996
Superiority of brain
natriuretic peptide as a
hormonal marker of
ventricular systolic and
diastolic dysfunction and
ventricular hypertrophy.",
Hypertension, vol. 28, no.
Diagnostic
study
94
Diagnostic
ability of
BNP, CANP, and NANP
6, pp. 988-994
Against Left
ventricular
ejection fraction
and mass by
echocardiography,
and end diastolic
pressure , and
time constant of
left ventricular
relaxation by
catheterisation
Results
Comments

For each physiological variable BNP showed the
strongest correlation (ejection fraction, left ventricular
mass, relaxation time) and was significantly better
than C-ANP or N-ANP, no significant difference in
Left ventricular end diastolic pressure
Sensitivity 73% and specificity 83% to detect any
abnormality of left ventricular structure or function at
BNP= 14.7 pmol/l
Significant structural and functional abnormalities in
patients without clinical evidence of heart failure
All test interpreted
blind Minnesota study.
Age: 62 yrs, 57% male.
Used control patients
to define baseline
peptide levels and the
elevated level set at
this plus 3 SD.
42% of patients presenting with dyspnoea had HF as
their final diagnosis, and 26% had a final diagnosis of
pulmonary disease
Of the patients with the final diagnosis of HF the
mean BNP level was 759 pg/ml compared to 61
pg/ml in the pulmonary patients (p<0.001)
BNP level of 94 pg/ml had a sensitivity of 86%, a
specificity of 98%, and an accuracy of 91%
The best clinical predictors of final diagnosis for
dyspnoea were history of HF, and heart size and
venous hypertension on chest X-ray
The addition of BNP levels to the multivariate
regression substantially increased the explanatory
power of the model and was a significant
independent variable (p<0.001)
All tests were
conducted on all
patients, with two
independent
cardiologists
determining whether
dyspnoea was relating
to HF (according to
Framingham criteria),
or to other conditions.
The coefficient of
variation at 28.8ng/l is
9.5% for intra-assay
precision and 10% for
inter-assay precision.
The lowest conc. of
BNP distinguishable is
<5.0 ng/l.
Patients who are on
dialysis or have endstage renal failure may
have elevated BNP
levels and would need
standard diagnostic
criteria to be assessed.


LEVEL OF EVIDENCE:.........
Morrison, L. K. 1996
Utility of a rapid Bnatriuretic peptide assay in
differentiating congestive
heart failure from lung
disease in patients
presenting with dyspnea",
Journal of the American
College of Cardiology., vol.
39, no. 2, pp. 202-209
LEVEL OF EVIDENCE:.........
Diagnostic
study
321
USA
Test
compared
with
duplicated
cardiologist
defined
evaluation as
to whether
the patients
presented
with HF or
other causes
of dyspnoea
A multivariate
model was used
to assess the
additive predictive
value of BNP over
clinical findings





3
Extract the data from the two papers appraised in the previous small group session!
Study/Give level of
evidence!
Type of
study
Number of
patients
Diagnostic Outcomes
test
Results
Comments
Landray et al. 2000.
Measuring brain natriuretic
peptide in suspected left
ventricular systolic
dysfunction in general
practice: cross-sectional
study. BMJ 320:985–6.
LEVEL OF EVIDENCE:.........
Smith et al. 2000
Biochemical diagnosis
of ventricular
dysfunction in elderly
patients in general
practice: observational
study. BMJ 320:906–8.
LEVEL OF EVIDENCE:.........
Summarize conclusions:
4