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BNP TESTING AND THE ACCURACY OF HEART FAILURE DIAGNOSIS
IN THE EMERGENCY DEPARTMENT
Amaali Lokuge* MBBS1, Louisa Lam* MPH2, Peter Cameron MBBS, MD1,2, Henry
Krum MBBS, PhD2,3, de Villiers Smit MBBS1,6, Adam Bystrzycki MBBS1, Matthew T
Naughton MD2,4, David Eccleston MBBS, PhD7, Genevieve Flannery MBBS2,3, Jacob
Federman MBBS4, Hans-Gerhard Schneider MBBS, MD2,5
* Joint first author, contributed equally 1Emergency and Trauma Centre, 2Monash University, Melbourne, Victoria, Australia 3Clinical Pharmacology Department, 4Department of Allergy, Immunology and Respiratory Medicine, 5Alfred Pathology Service, Alfred Hospital, Melbourne, Victoria, Australia, 6Emergency Department and 7Cardiology Department, Northern Hospital, Victoria, Australia
Correspondence to:
Professor Peter Cameron Head Victorian State Trauma Registry Department Epidemiology Preventive Medicine Director Research Emergency and Trauma Centre Alfred Hospital Commercial Road Melbourne, Victoria 3004 AustraliaFax 0392762699 ph 03 99030581 mob 0405 500 397 email peter.cameron@med.monash.edu.au
Total Word Count: 5931
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Abstract
Background: It is often difficult to diagnose heart failure (HF) accurately in patients
presenting with dyspnoea to the emergency department (ED). This study assessed
whether B-type Natriuretic Peptide (BNP) testing in these patients improved the
accuracy of HF diagnosis.
Methods and Results: Patients presenting to The Alfred and The Northern Hospital
EDs with a chief complaint of dyspnoea were enrolled prospectively from August
2005 to April 2007. Patients were randomly allocated to have BNP levels tested or
not. The diagnostic “gold” standard for HF was determined by one cardiologist and
one emergency or respiratory physician who, blinded to the BNP result,
independently reviewed all available information.
The ED diagnosis of HF in the non BNP group, showed a sensitivity, specificity and
accuracy of 65%, 92% and 81% respectively. The BNP group had a similar
sensitivity, specificity and accuracy of 66%, 90% and 78% respectively for the
diagnosis of HF in the ED. There was no significant difference between the BNP and
non BNP groups in any of the measures of diagnostic accuracy for HF.
Conclusion: In the clinical setting of emergency departments, availability of BNP
levels did not significantly improve the accuracy of a diagnosis of HF.
Key words: heart failure, BNP, dyspnoea, emergency, diagnosis
Clinical Trial Registration Information: www.clinicaltrial.gov, Identifier:
NCT00163709
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y of 65%, 92% and 81% respectively. The BNP group had a s
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dently reviewed all available information.
diagnosis of HF in the non BNP group, showed a sensitivity, specificity
y of 65%, 92% and 81% respectively. The BNP group had a s
y, specificity and accuracy of 66%, 90% and 78% respectively fof
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Introduction
The incidence of heart failure (HF) is reaching epidemic proportions in the
Western world1. With an ageing population and greater survival from disease
processes leading to HF, the burden of this disease on the health care system will
only increase in the future2.
Most patients with acute HF syndromes present to hospital through the ED3.
Their most common presenting complaint is dyspnoea4. However, the differential
diagnosis of dyspnoea is myriad and includes pulmonary diseases which often co-
exist in patients with HF5. Studies examining the accuracy of ED diagnosis of HF
using traditional means such as history, examination, ElectroCardioGraphy (ECG)
and Chest X-ray (CXR) have found varying levels of accuracy resulting in
misdiagnosis, delays to treatment and increased morbidity and mortality6-9.
B-type Natriuretic peptide (BNP) is a cardiac neurohormone primarily secreted
from cardiac ventricles10. BNP levels rise in patients with HF11-13. Since the
development of rapid bedside investigations to test BNP levels, BNP has been
studied widely as a potential tool to enhance the accuracy of HF diagnosis14-16.
These studies show that BNP levels are significantly higher in patients with
dyspnoea due to HF than from another cause. Further, BNP levels show a higher
accuracy in diagnosing HF than clinical judgement17-19. Consequently, several of
these studies have extrapolated through statistical analysis that theoretically, adding
a BNP test to other clinical measures could improve the accuracy of HF diagnosis17-
20. However, as yet no study has assessed the impact of real time BNP
measurement on the accuracy of HF diagnosis in the ED in a randomised clinical
trial.
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EDEEE diaii gngngngnosooo iss oooof f f f HFHHH
CardiiioGoGoGoGraraaphphphphy y y y (E(E(E(ECG
s
-type Natriuretic peptide (BNP) is a cardiac neurohormone primarily sec
d
st X-ray (CXR) have found varying levels of accuracy resulting in
osis, delays to treatment and increased morbidity and mortality6-9.
-type Natriuretic peptide (BNP) is a cardiac neurohormone primarily sec
diac ventricles10. BNP levels rise in patients with HF11-13. Since the
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The European Society of Cardiology guidelines for heart failure recommend
use of the BNP test to rule out HF21 and the American College of Cardiology
suggests use of the BNP test in the urgent care setting where the diagnosis of HF is
uncertain22. Recently, BNP testing for HF diagnosis in the emergency setting
received government funding in Australia23. Most available literature suggests a cut
off point of 100pg/ml for the BNP test, so that at a value <100pg/ml HF is unlikely14-
18. Mueller et al showed that in Switzerland, patients who had BNP testing in ED had
earlier initiation of appropriate treatment, decreased hospital and ICU admission
rates, earlier discharge and decreased cost of treatment24. In contrast, the
randomised controlled trial BNP in shortness of breath (SOB) study conducted in
Australia by Schneider et al showed that BNP testing in dyspnoeic patients
presenting to the ED did not improve hospital admission rates, length of hospital stay
or management in ED25.
This study analyses data from the BNP in SOB multicentre study25. With
several studies demonstrating a theoretical improvement to the accuracy of HF
diagnosis in the ED with BNP testing17-20, we hypothesised that real time BNP testing
in the ED would improve the accuracy of the clinical diagnosis of HF.
Methods
Study Setting
A prospective, randomised, controlled, single blind study “The BNP in SOB
Study” conducted in the EDs of The Alfred Hospital (tertiary referral centre, 45 000
patient attendances per year) and The Northern Hospital (metropolitan hospital, 70
000 patient attendances per year) Victoria, Australia was undertaken between
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contrast, the
studydydydy condddductedededed in
n
g
h
by Schneider et al showed that BNP testing in dyspnoeic patients l
ng to the ED did not improve hospital admission rates, length of hospita
gement in ED25.
his study analyses data from the BNP in SOB multicentre study25. With
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August 2005 and April 200725. Data from this study was retrospectively reviewed for
this paper.
Study Design and Consent
Eligible patients were enrolled in the study by ED staff at presentation. They
were randomised either to the BNP group (BNP levels were tested) or the non BNP
group (BNP levels not tested – control group) before consent. Randomisation was by
random numbers (from computer generated random number tables) concealed in an
envelope. The randomisation was stratified by site. A trained research assistant
gained from the patient or their next of kin within 24 hours of admission.
Entry criteria included an Australian Triage Scale of 1-3 (illness acuity
requiring assessment by a doctor immediately to within 30 minutes of arrival), in
patients with a primary presenting complaint of dyspnoea. Exclusion criteria were:
<40 years, a traumatic cause of dyspnoea, cardiogenic shock, a serum creatinine
>250 mol/L and patients who were transferred to another hospital within 24 hours of
presentation.
All patients underwent routine clinical examination by a doctor (ED registrar or
consultant, or ED resident supervised by a registrar or consultant) and routine
investigations including blood tests, CXR and ECG. When possible, a TransThoracic
Echo (TTE) and a Pulmonary Function Test (PFT) were performed within 30 days of
presentation.
Doctors and nurses involved in patient care in the ED were given four
education sessions during the study period by emergency doctors involved in the
study. These education sessions familiarised staff with BNP, its role in the diagnosis
of HF and the current literature in the field. Further, each treating doctor of an
enrolled patient received a written guideline on the treatment of acute HF and
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admission.
3 (illness acuiiiti y y y
n
w r
s n
o u
assessment by a doctor immediately to within 30 minutes of arrival), in
with a primary presenting complaint of dyspnoea. Exclusion criteria wer
s, a traumatic cause of dyspnoea, cardiogenic shock, a serum creatinin
ol/L and patients who were transferred to another hospital within 24 hou
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chronic obstructive pulmonary disease and the BNP nomogram (developed by
McCullough et al17) with an explanation on how to use it. Doctors were educated
that dyspnoeic patients with a BNP value <100pg/ml were unlikely to have HF as the
primary diagnosis and that dyspnoeic patients with a BNP value >500pg/ml were
likely to have HF as the primary diagnosis.
Probability of HF
The treating emergency doctor for each patient was asked to assign a
probability of HF as the cause of dyspnoea after initial assessment of the patient and
preliminary investigations, but without the BNP test. The probabilities were divided
into 5 categories: 0%, 1-25%, 26-50%, 51-75% and 76-100%.
Disposition Diagnosis
The disposition diagnosis (the diagnosis at the time of discharge from the ED;
after all investigations, including the BNP test, and treatment in the ED) was
recorded for the BNP and non BNP groups. Where the patient was admitted, the
disposition diagnosis was that recorded by the admitting unit registrar or resident
derived from the emergency doctor’s diagnosis. Where the patient was discharged
from the ED, the disposition diagnosis was the emergency doctor’s final diagnosis.
Baseline demographics, clinical information from the current and relevant
previous presentations and follow-up investigations (TTE and PFT) were gathered by
trained research assistants.
BNP Testing
All patients had a 10ml sample of blood collected in an EDTA tube upon
presentation to the ED. Only patients who were randomised to the BNP group had a
BNP level tested and the result available on the computer. The BNP level was
measured on plasma using the Abbott AxSYM MEIA Automated immunoassay
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abilities were divvvvidididi
.
h e
n
e
ion Diagnosis
he disposition diagnosis (the diagnosis at the time of discharge from the
nvestigations, including the BNP test, and treatment in the ED) was
for the BNP and non BNP groups. Where the patient was admitted, the
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(Abbott, USA). The measurable range of the BNP assay is 15 – 4,000pg/ml with an
on-board 1 in 5 dilution to take the upper limit to 20,000pg/ml. The BNP levels were
available to medical staff within one hour of collection. This test is calibrated against
the Triage B-Type Natriuretic Peptide test (Biosite Inc., San Diego, California). It
performs well in the clinical setting with an area under the curve comparable to
published data26.
Reviewer Adjudicated Diagnosis (Final Diagnosis)
The final diagnosis of HF was made by one emergency physician and one
cardiologist who independently reviewed all available information including case
notes, blood tests, ECG and CXR reports, response to treatment, TTE and PFT
results. The reviewing physician was blinded to the BNP result. The reviewers
received a definition of HF based on the European Society of Cardiology Working
Group on HF diagnostic criteria27 and an algorithm for the diagnosis of HF. Patients
were classified into 3 categories for the main cause of dyspnoea: 1) HF in isolation,
2) HF in conjunction with another diagnosis and 3) no HF. For this analysis, patients
in categories 1 and 2 were grouped together so that the two categories for the final
diagnosis were HF and no HF. Where the two reviewers agreed, the diagnosis was
taken as the final diagnosis for the patient. Where they disagreed, a third physician
(cardiology, respiratory or emergency) reviewed all available data (blinded to the
BNP test) and made a diagnosis, which was then used as the final diagnosis.
Data and Statistical Analysis
Statistical analyses were performed using Stata version 9.0 (Stata
Corporation, College Station, Tx, USA). A p value less than 0.05 was considered to
indicate statistical significance. Baseline characteristics are reported in counts and
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tion including casasasase
ent, TTTTTETETETE a dddnd PPPPFTFTFTFT
T
a definition of HF based on the Eur ean Societ of Cardiol Workin
n e
ssified into 3 categories for the main cause of dyspnoea: 1) HF in isolat
The reviewing physician was blinded to the BNP result. The reviewers
a definition of HF based on the European Society of Cardiology Workin
n HF diagnostic criteria27 and an algorithm for the diagnosis of HF. Patie
ssified into 3 categories for the main cause of dyspnoea: 1) HF in isolat
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proportions or mean SD as appropriate. Univariate comparisons were made with 2
test, 2-sample t test, or the Wilcoxon 2-sample test as appropriate.
The disposition diagnosis and final diagnosis were divided into 2 groups: HF
or no HF. Statistics were computed from 2x2 tables and reported as accuracy (true
positive and true negative cases as a proportion of the total), sensitivity and
specificity.
Receiver-operating characteristic (ROC) curve analysis was performed for
BNP levels and the emergency doctors’ assessment of the probability of HF with the
final diagnosis as the reference standard. These ROC curves were compared using
the area under the curve (AUC). An ROC curve was generated through logistic
regression using the BNP group doctors’ assessment of the probability of HF and the
BNP values as predictors of a final diagnosis of HF. This combined ROC curve was
compared to the ROC curves of the probability of HF and BNP values to determine
whether the BNP test would significantly improve the diagnostic quality of the
doctor’s assessment of the probability of HF.
Agreement between the two reviewers for the final diagnosis was quantified
using Cohen’s statistic.
Ethics
Ethics approval for this study was granted by The Alfred Ethics Committee,
The Northern Hospital Ethics Committee and The Monash University Standing
Committee on Ethics in Research Involving Humans. The investigation conforms to
the principles outlined in the Declaration of Helsinki. This study was registered on the
Registry of the US National Institutes of Health (www.clinicaltrial.gov), registration
number NCT00163709.
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were compared d d d usuuu
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o n
u
d m
t
on using the BNP group doctors’ assessment of the probability of HF an
ues as predictors of a final diagnosis of HF. This combined ROC curve
d to the ROC curves of the probability of HF and BNP values to determ
the BNP test would significantly improve the diagnostic quality of the
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Results
Study Cohort and Baseline Characteristics
799 patients were recruited. 187 patients were excluded due to refusal of
consent (n=135), exclusion criteria (n=20), transfer within 24 hours (n=19) or
incomplete sample collection (n=13). Of the final cohort of 612 patients, 306 patients
were randomised to have the BNP test (BNP group) and 306 patients not to have
BNP test (non BNP group).
The baseline demographic and clinical characteristics for the BNP and non
BNP groups were similar except patients in the BNP group were more likely to have
a history of orthopnoea and a past history of HF and hypertension (p=0.005, p=0.03
and p=0.01 respectively; table 1). Adjusting for a past history of HF through logistic
regression did not significantly alter the results.
Of the study cohort of 612 patients, 45% (n = 274) had a final diagnosis of HF:
48% (n = 148) in the BNP group and 41% (n = 126) in the non BNP group.
Reviewers 1 and 2 agreed on the final diagnosis in 553 (90%) patients. A third
reviewer assessed the remaining 59 patients’ data to determine the final diagnosis.
Exclusion of these patients from the final analysis did not significantly alter the
results. Agreement for the final diagnosis between reviewer 1 and reviewer 2 in the
BNP and non BNP groups was = 0.79 (95%CI: 0.78-0.83) and = 0.82 (95%CI:
0.78-0.86) respectively. Table 2 shows characteristics of patients with a final
diagnosis of HF and no HF.
In the BNP group, 10 patients did not have BNP levels tested due to
laboratory error. We included these patients in the analysis. Their exclusion did not
significantly alter the results.
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eeeerer mmmmore lilll kelylylyy t t tto o o o hhhh
nsion ((((p=ppp 0.0.0 00000005,5,5,5, p ppp=0
0 s
o
f o
=
01 respectively; table 1). Adjusting for a past history of HF through logis
on did not significantly alter the results.
f the study cohort of 612 patients, 45% (n = 274) had a final diagnosis o
= 148) in the BNP group and 41% (n = 126) in the non BNP group.
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Impact of the BNP Test on the Accuracy of the Disposition Diagnosis
In the BNP group, the accuracy of the disposition diagnosis of HF was 78%,
with a sensitivity of 66% (95% Confidence Interval (CI): 57%-73%) and a specificity
of 90% (95%CI: 84%-94%). In the non BNP group, the accuracy of the disposition
diagnosis of HF was 81% with a sensitivity of 65% (95%CI: 56%-73%) and a
specificity of 92% (95%CI: 87%-96%) (Figure 1).
In the BNP group, analysis of the disposition diagnosis against the final
diagnosis of the subgroup of patients with a BNP value <100pg/ml (n=89) shows that
a majority (n=75, 84%) received an accurate disposition diagnosis of no HF. In the
subgroup with a BNP value >500pg/ml (n=127), 74 patients had an accurate
disposition diagnosis of HF and 18 had an accurate disposition diagnosis of no HF.
However, 31 patients (24%) were under-diagnosed as having no HF and only 4
patients over-diagnosed as having HF.
The accuracy of the disposition diagnosis in patients given an intermediate
probability of HF (26-75%) by the emergency doctor (n = 131) was similar in the BNP
and non BNP groups. In the BNP group (n = 69), the disposition diagnosis had an
accuracy, sensitivity and specificity of 64%, 66% and 58% respectively and in the
non BNP group (n = 62), the disposition diagnosis had an accuracy, sensitivity and
specificity of 65%, 67% and 58% respectively.
Accuracy of the BNP Test
At a cut off of 101pg/ml the accuracy, sensitivity and specificity of the BNP
test was 71%, 92%, 51% respectively. The optimum cut off point for the BNP test in
our study, derived from the ROC curve of the BNP test against the final diagnosis of
HF was 265pg/ml: accuracy 82%, sensitivity 83% and specificity 81%.
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nosis of no HF. IIIIn n n n t
ad an accuratet
o H
o
h t
on diagnosis of HF and 18 had an accurate disposition diagnosis of no H
, 31 patients (24%) were under-diagnosed as having no HF and only 4
over-diagnosed as having HF.
he accuracy of the disposition diagnosis in patients given an intermediat
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The overall diagnostic accuracy of the BNP test in the two groups with a BNP
value <100pg/ml (HF unlikely) and >500pg/ml (HF likely) was 84%. These two
groups combined encompassed 71% of the study cohort.
Reference Range of the BNP Test and the BNP levels of our participants.
In our study, the range of BNP values was 4-10565pg/ml. The cohort with a
final diagnosis of HF (n=148) had a median BNP value of 830pg/ml (interquartile
range: 391-1425pg/ml). 92% (n = 136) of these patients had a BNP value
>100pg/ml. Patients with a final diagnosis of HF and a BNP value <100pg/ml (n = 12)
had a mean age of 66 (range 55-80) with an even distribution of gender. Half the
patients had a past history of ischaemic heart disease and hypertension and more
than half had a past history of heart failure. TTE was available in 8 patients and of
these 7 patients had a normal ejection fraction, however, interestingly half of these
patients (n = 4) had evidence of diastolic dysfunction on TTE.
The cohort of patients with a final diagnosis of no HF (n=158) had a median
BNP value of 99pg/ml (interquartile range: 46-180pg/ml). Only 49% (n = 77) of these
patients had a BNP value <100pg/ml.
The probability of HF
A probability of HF was recorded by the emergency doctor after initial
assessment but prior to the BNP result for 593 patients. The ROC curves of the
probability of HF for the whole group had an AUC of 0.86 (95%CI: 0.83-0.89). The
BNP values ROC curve had an AUC of 0.87 (95%CI: 0.83-0.91). There was no
significant difference between the BNP group probability of HF ROC curve AUC
(0.88, 95%CI: 0.84-0.92) and the AUC of the BNP values (p = 0.73).
The ROC curves of the BNP values and the BNP group probability of HF were
combined statistically and had an AUC of 0.93 (95%CI: 0.90-0.96) significantly better
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of gender. Half ththththe
pertett nsioiii n and ddd mmmmo
p e
(
h i
had a past history of heart failure. TTE was available in 8 patients and
patients had a normal ejection fraction, however, interestingly half of the
(n = 4) had evidence of diastolic dysfunction on TTE.f
he cohort of patients with a final diagnosis of no HF (n=158) had a medi
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than the AUCs of the BNP values or the BNP group probability of HF ROC curves
individually, p < 0.001 (figure 2).
Discussion
This is the first randomised controlled study to assess the impact of real time
BNP testing on the accuracy of HF diagnosis in the clinical setting within two busy
Australian EDs. Although our study found that BNP values were significantly higher
in patients with a final diagnosis of HF and that the BNP test had a high level of
accuracy for the diagnosis of HF, in the real life setting, adding the BNP test to
clinical judgement did not significantly add to the accuracy of the disposition
diagnosis of HF.
Consistent with other studies, we found that patients with a final diagnosis of
HF had significantly higher BNP levels than patients with a final diagnosis of no HF14-
16. However, the median BNP value of our patients with a final diagnosis of HF and
patients with a final diagnosis of no HF was higher than previously reported at
830pg/ml and 99pg/ml respectively14-16. Also we found that in our study population,
the recommended cut off point of 100pg/ml had a much lower specificity than
reported in other studies17,18. We found similar accuracy, sensitivity and specificity
levels to those reported by Maisel et al18 at the optimum cut off point of 265pg/ml.
This reflects the findings by Edmin et al28 that BNP cut off concentrations are greatly
dependent on the study population and the type of BNP assay used.
There are three main characteristics of our study population which may have
led to higher BNP levels. 1) Although BNP levels have been shown to be higher in
patients with myocardial ischaemia29, we did not exclude these patients from the
study population as acute HF may often co-exist with myocardial ischaemia in
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gggg theeee BNPNPPP tesest t t t totototo
the dididd spspsppososositittioioioon n n n
s
o s
s
v a
s of HF.
onsistent with other studies, we found that patients with a final diagnosis
significantly higher BNP levels than patients with a final diagnosis of no
ver, the median BNP value of our patients with a final diagnosis of HF a
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patients presenting to the ED. 2) Our cohort of patients had a significant level of co-
morbidity and was generally older and more acutely unwell than the patients
investigated in other studies. It is well known that BNP levels increase with age. 3) In
the group with a final diagnosis of no HF, patients who had a past history of HF were
not separated out. Patients with a past history of HF have been shown to have
higher baseline BNP levels18. However, this is a confounder that is frequently
encountered in the real life setting. This variability in BNP concentrations between
different patient populations may be detrimental to the usefulness of the test in aiding
diagnosis in the clinical setting.
Similar to the studies by McCullough et al17 and Green et al19, in theory, when
the BNP test is statistically combined with the emergency doctors’ assessment of the
probability of HF, the accuracy of the doctors’ assessment improves significantly. In
our study, if the emergency doctor had adhered strictly to the diagnostic
recommendations and diagnosed all patients with a BNP value <100pg/ml as no HF
and >500pg/ml as having HF, the disposition diagnosis accuracy would not have
improved greatly (84%) and approximately 30% of patients would not have been
classified. However, in the subgroup with a BNP value >500pg/ml, more patients with
HF would have been identified.
In the real life clinical setting, this randomised controlled study, found that
there was no significant difference in accuracy, sensitivity or specificity of the
disposition diagnosis with or without the BNP test. This is consistent with the
primary results of the BNP in SOB study which showed that BNP testing did not alter
hospital admission rates, length of stay or 30day mortality25.
The study cohort of patients was drawn from EDs staffed by senior doctors
experienced in emergency medicine with a high level of supervision of junior doctors.
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et allll19191919, iinii tttthhehh orrrryyyy, w
o
t y
y
e o
test is statistically combined with the emergency doctors’ assessment o
ty of HF, the accuracy of the doctors’ assessment improves significantly
y, if the emergency doctor had adhered strictly to the diagnostic
endations and diagnosed all patients with a BNP value <100pg/ml as no
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Consistent with this, the assessment of the probability of HF by the emergency
doctor and the disposition diagnosis had a higher accuracy than described by
McCullough et al17. Further, BNP levels may be elevated in several conditions such
as a past history of heart failure, chronic renal failure, myocardial ischaemia,
pulmonary embolus and rapid atrial fibrillation30-32. Some of these conditions may co-
exist with HF in a patient presenting with dyspnoea to the ED.
The main strength of this study is that the impact of the BNP test on the
accuracy of the diagnosis of HF was assessed in the clinical setting in real time
through a randomised controlled trial. In this way, it was possible to elucidate
whether the BNP test improves the accuracy of HF diagnosis in the ED. Further, this
study was able to define an optimum cut off point for the BNP test in the diagnosis of
HF in an Australian population of patients presenting to a tertiary referral and a
metropolitan hospital.
One of the limitations of our study is that there were more patients in the BNP
group with a past history of hypertension and HF and a symptom of orthopnoea.
However, adjusting for these patients did not alter the results of the study. Another
limitation is that there is no definitive test or robust clinical definition of HF: it is a
syndrome characterised by a constellation of symptoms and signs27. However, we
counteracted this by providing each reviewer with a standardised definition and an
algorithm for the diagnosis of acute HF. Reviewers were blinded to the BNP result.
There was a high level of agreement between reviewers.
BNP levels would have been influenced by acute myocardial ischemia and a
past history of HF. These have been excluded in some studies. As these problems
are encountered in the real life setting we did not attempt to control for these
Page 14
ible to elucidate
in thehhh EEEED.DDD FFF Furththththeeeer
s able to define an optimum cut off point for the BNP test in the diagnos
i
n
s able to define an optimum cut off point for the BNP test in the diagnos
Australian population of patients presenting to a tertiary referral and a
itan hospital.
ne of the limitations of our study is that there were more patients in the
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confounders. Similarly, we did not use age adjusted partition values given that the
BNP nomogram by McCullough et al17 does not stratify the BNP values by age.
Conclusions
This study showed that BNP levels were significantly higher in patients with
HF and the BNP test had a high level of accuracy in the diagnosis of HF. In the
clinical setting, however, BNP testing did not add to the accuracy of the disposition
diagnosis of HF in patients presenting with dyspnoea to the ED.
In the future, the development of more specific BNP nomograms adjusted to
variables affecting BNP values such as age, gender, ethnicity and a past history of
HF, may make the BNP test more useful in HF diagnosis in the ED.
Funding source
The study was supported by an unrestricted educational grant from Janssen-
Cilag. The study sponsor had no influence on the study design and reporting of the
data.
Disclosures
There is no conflict to disclose.
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omommm grgrgrgramms s ss addjujujuuststststedededed
and aaa p pppasasast t t hihihihistststs oro y
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h s
make the BNP test more useful in HF diagnosis in the ED.
g source
he study was supported by an unrestricted educational grant from Janss
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lure: An Analysisisisis F mmmmererererg g g g MeMeMeMed.d.d.d.
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cCullough PA, Torbjørn PD, McCord OJ, Nowak RM, Hollander JE, errmann HC, Steg PG, Westheim A, Knudsen CW, Storrow AB, AbrahaT, Lamba S, Wu AHB, Perez A, Clopton P, Krishnaswamy P, Kazanegraisel AS. B-type natriuretic peptide and renal function in the diagnosis oeart failure: An analysis from the breathing not properly multinational stumerican Journal of Kidney Diseases 2003;41:9.
orrison LK, Harrison A, Krishnaswamy P, Kazanegra R, Clopton P, and
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Figure Legends
Table 1: Patient Baseline Characteristics
Table 2: Clinical Characteristics of Patients with a Final Diagnosis of HF and No HF
Figure 1: Accuracy of the Disposition Diagnosis for HF against the Final Diagnosis in
the BNP and non BNP groups
Figure 2: ROC curves for the BNP values (bnpvalue), the BNP group doctors’
assessment of the probability of HF (ccfprob0), and the combined ROC
curve
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Table 1 Patient Baseline Characteristics
*COPD: Chronic Obstructive Pulmonary Disease
Characteristics BNP group n=306
Non BNP group n=306
Age (years) Mean ± SD 74 ± 11 73 ± 11 Range 42-98 49-98
Sex, n (%) Male 166 (54) 162 (53) Female 140 (46) 144 (47)
History, n (%) COPD*/Asthma 202 (66) 186 (61) Hypertension 170 (56) 138 (45) Ischaemic HeartDisease
129 (42) 124 (41)
HF 123 (40) 97 (32) Atrial Fibrillation 93 (30) 79 (26) Diabetes Mellitus 61 (20) 60 (20)
Renal failure 32 (10) 37 (12) Symptoms, n (%)
Cough 153 (50) 152 (50) Sputum 79 (26) 81 (26) Orthopnoea 76 (25) 48 (16)
Swelling of ankles 41 (13) 54 (18) Fever 36 (12) 44 (14)
Signs, n (%) Crackles 168 (55) 173 (57) Wheeze 84 (27) 86 (28) Raised JVP† 81 (28) 88 (30) Displaced Apex Beat 54 (19) 39 (13) Third Heart Sound 5 (2) 11 (4)
Vital signs, mean ± SD(range)
Systolic blood pressure 143 ± 30 (70-269) 141 ± 28 (70-240) Diastolic blood pressure 73 ± 18(30-155) 73 ± 18 (23-140) Heart rate, bpm‡ 95 ± 24 (46-178) 97 ± 23 (50-175) Respiratory rate 25 ± 6 (6-46) 25 ± 8 (12-62)
Investigations, n (%)Chest X ray 283 (92) 282 (92) Electrocardiogram 236 (77) 236 (77)
Final diagnosis of HF, n (%) 148 (48) 126 (41) Number of admission: Admitted, n (%) 262 (86) 265 (87)
† JVP: Jugular Venous Pressure‡ bpm: beats per minute
Page 21
9797977 ( ( ((3232322) ) ) )79797979 ( ( ((26262626) ) ) )60000 ( ( ( (20202020) )))
173 (57)168 (55)kl
nal failure 32 (10) 37 (12)mopree
kl 168 (55) 173 (57)
nal failure 32 (10) 37 (12) ms, n (%)ough 153 (50) 152 (50) putum 79 (26) 81 (26) rthopnoea 76 (25) 48 (16) elling of ankles 41 (13) 54 (18)ever 36 (12) 44 (14)
(%)
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Table 2Clinical Characteristics of Patients with a Final Diagnosis of HF and No HF
Characteristics HF group No HF group p-value
Patient number (%) 274 (45) 338 (55) Age, mean ± SD, (range), years 77± 11
(45-98)71±11(40-94)
< 0.001
BNP pg/ml, median (IQR) 830 (391-1425)
99 (46-180) <0.001
Medical History, n (%) Hypertension 173 (63) 135 (40) <0.001Heart Failure 163 (60) 57 (17) <0.001Ischaemic Heart Disease 162 (59) 91 (27) <0.001Atrial Fibrillation 110 (40) 62 (18) <0.001COPD* 156 (57) 232 (69) 0.003Diabetes Mellitus 63 (23) 58 (17) 0.072Renal Failure 49 (18) 20 (6) <0.001
Symptoms, n (%) Orthopnoea 86 (32) 38 (11) <0.001Cough 111 (41) 194 (57) <0.001Sputum 49 (18) 111 (34) <0.001Fever 24 (9) 56 (17) 0.004Swelling of Ankles 63 (23) 32 (9) <0.001
Signs, n (%) Crackles on auscultation 209 (74) 137 (40) <0.001
Raised JVP† 136 (52) 33 (10) <0.001Wheeze on auscultation 64 (24) 106 (32) 0.028 Displaced Apex Beat 68 (27) 22 (7) <0.001
CXR findings, n (%) Pulmonary Venous Congestion
114 (42) 13 (4) <0.001
Kerley B lines 10 (4) 1 (0.3) 0.002ECG findings, n (%)
Atrial fibrillation 64 (24) 27 (8) <0.001Sinus tachycardia 37 (14) 86 (25) <0.001
Statistical analysis by Pearson chi-square test * Chronic Obstructive Pulmonary Disease † JVP: Jugular Venous Pressure
(((1717171 ) ) )) 0.0.00 07070772222(6) <0<0<0<0.0.0.0.0010100
rthopnoea 86 (32) 38 (11) <0 001opew
rsh lt ti 0 028106 (32)64 (24)
rthopnoea 86 (32) 38 (11) <0.001ough 111 (41) 194 (57) <0.001putum 49 (18) 111 (34) <0.001ever 24 (9) 56 (17) 0.004welling of Ankles 63 (23) 32 (9) <0.001(%)
rackles on auscultation 209 (74) 137 (40) <0.001 sed JVP† 136 (52) 33 (10) <0.001h lt ti 64 (24) 106 (32) 0 028
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Figure 1Accuracy of the Disposition Diagnosis for HF against the Final Diagnosis in the BNP and non BNP groups
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Figure 2ROC curves for the BNP values (bnpvalue), the BNP group doctors’ assessment of the probability of HF (ccfprob0), and the combined ROC curve
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SchneiderMatthew T. Naughton, David Eccleston, Genevieve Flannery, Jacob Federman and Hans G.
Amaali Lokuge, Louisa L. Lam, Peter Cameron, Henry Krum, de Villiers Smit, Adam Bystrzycki,BNP Testing and the Accuracy of Heart Failure Diagnosis in the Emergency Department
Print ISSN: 1941-3289. Online ISSN: 1941-3297 Copyright © 2009 American Heart Association, Inc. All rights reserved.
75231is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TXCirculation: Heart Failure
published online November 20, 2009;Circ Heart Fail.
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