bnp testing and the accuracy of heart failure diagnosis...

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 [email protected]

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

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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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-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

contrast, the

studydydydy condddductedededed in

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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

admission.

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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

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

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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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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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%.

nosis of no HF. IIIIn n n n t

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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

of gender. Half ththththe

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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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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.

et allll19191919, iinii tttthhehh orrrryyyy, w

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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

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

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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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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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Reference

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ype natriuretic pepepeeptppptttt-c-c-c-carararare e e e sesesesettttttttinininingg.g.g. JJ J J AmAmAmAm

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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

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.

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