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B-Type Natriuretic Peptide Testing, Clinical Outcomes, and Health Services Use in Emergency Department Patients With Dyspnea: A Randomized Trial

Hans-Gerhard Schneider, MBBS, MD; Louisa Lam, MPH; Amaali Lokuge, MBBS; Henry Krum, MBBS, PhD; Matthew T. Naughton, MBBS; Pieter De Villiers Smit, MBBS; Adam Bystrzycki, MBBS; David Eccleston, MBBS, PhD; Jacob Federman, MBBS; Genevieve Flannery, MBBS; and Peter Cameron, MBBS, MD
[+] Article and Author Information

ClinicalTrials.gov registration number: NCT00163709.


From Alfred Health, Prahran, and Royal Melbourne Hospital, Parkville, Victoria, Australia.


Grant Support: By an unrestricted educational grant from Janssen-Cilag to Drs. Schneider and Krum.

Potential Financial Conflicts of Interest:Grants received: H.G. Schneider (Janssen-Cilag), H. Krum (Janssen-Cilag).

Reproducible Research Statement:Study protocol: Available from Dr. Schneider (e-mail, schneiderh@alfred.org.au). Statistical code and data set: Not available.

Requests for Single Reprints: Hans-Gerhard Schneider, MBBS, MD, Alfred Pathology Service, PO Box 315, Commercial Road, Prahran, Victoria 3181, Australia; e-mail, schneiderh@alfred.org.au.

Current Author Addresses: Dr. Schneider: Alfred Pathology Service, Alfred Health, PO Box 315, Commercial Road, Prahran, Victoria 3181, Australia.

Drs. Lam, Krum, and Cameron: Department of Epidemiology and Preventive Medicine, Monash University, Alfred Hospital, 89 Commercial Road, Melbourne, Victoria 3004, Australia.

Drs. Lokuge, De Villiers Smit, and Bystrzycki: Emergency Department, Alfred Health, PO Box 315, Commercial Road, Prahran, Victoria 3181, Australia.

Dr. Naughton: Department of Allergy, Immunology and Respiratory Medicine, Alfred Health, PO Box 315, Commercial Road, Prahran, Victoria 3181, Australia.

Dr. Eccleston: Department of Cardiology, Royal Melbourne Hospital, Gratton Street, Parkville, Victoria 3052, Australia.

Dr. Federman: Cardiology Department, Alfred Health, PO Box 315, Commercial Road, Prahran, Victoria 3181, Australia.

Dr. Flannery: Professional General Medicine Unit, Alfred Health, PO Box 315, Commercial Road, Prahran, Victoria 3181, Australia.

Author Contributions: Conception and design: H.G. Schneider, L. Lam, H. Krum, M.T. Naughton, A. Bystrzycki, P. Cameron.

Analysis and interpretation of the data: H.G. Schneider, L. Lam, A. Lokuge, H. Krum, M.T. Naughton, P. De Villiers Smit, A. Bystrzycki, D. Eccleston, J. Federman, G. Flannery, P. Cameron.

Drafting of the article: H.G. Schneider, L. Lam, H. Krum, M.T. Naughton, P. De Villiers Smit, D. Eccleston, G. Flannery, P. Cameron.

Critical revision of the article for important intellectual content: H.G. Schneider, L. Lam, H. Krum, M.T. Naughton, P. De Villiers Smit, A. Bystrzycki, D. Eccleston, J. Federman, G. Flannery, P. Cameron.

Final approval of the article: H.G. Schneider, L. Lam, A. Lokuge, H. Krum, M.T. Naughton, P. De Villiers Smit, A. Bystrzycki, D. Eccleston, G. Flannery, P. Cameron.

Provision of study materials or patients: H.G. Schneider, L. Lam, P. De Villiers Smit, A. Bystrzycki, D. Eccleston, P. Cameron.

Statistical expertise: L. Lam, D. Eccleston.

Obtaining of funding: H.G. Schneider, H. Krum, P. Cameron.

Administrative, technical, or logistic support: H.G. Schneider, L. Lam, A. Lokuge, P. Cameron.

Collection and assembly of data: H.G. Schneider, L. Lam, A. Lokuge, P. De Villiers Smit, D. Eccleston.


Ann Intern Med. 2009;150(6):365-371. doi:10.7326/0003-4819-150-6-200903170-00004
Text Size: A A A

Background: B-type natriuretic peptide (BNP) is used to diagnose heart failure, but the effects of using the test on all dyspneic patients is uncertain.

Objective: To assess whether BNP testing alters clinical outcomes and health services use of acutely dyspneic patients.

Design: Randomized, single-blind study. Patients were assigned to a treatment group through randomized numbers in a sealed envelope. Patients were blinded to the intervention, but clinicians and those who assessed trial outcomes were not.

Setting: 2 Australian teaching hospital emergency departments.

Patients: 612 consecutive patients who presented with acute severe dyspnea from August 2005 to March 2007.

Intervention: BNP testing (n = 306) or no testing (n = 306).

Measurements: Admission rates, length of stay, and emergency department medications (primary outcomes); mortality and readmission rates (secondary outcomes).

Results: There were no between-group differences in hospital admission rates (85.6% [BNP group] vs. 86.6% [control group]; difference, −1.0 percentage point [95% CI, −6.5 to 4.5 percentage points]; P = 0.73), length of admission (median, 4.4 days [interquartile range, 2 to 9 days] vs. 5.0 days [interquartile range, 2 to 9 days]; P = 0.94), or management of patients in the emergency department. Test discrimination was good (area under the receiver-operating characteristic curve, 0.87 [CI, 0.83 to 0.91]). Adverse events were not measured.

Limitation: Most patients were very short of breath and required hospitalization; the findings might not apply for evaluating patients with milder degrees of breathlessness.

Conclusion: Measurement of BNP in all emergency department patients with severe shortness of breath had no apparent effects on clinical outcomes or use of health services. The findings do not support routine use of BNP testing in all severely dyspneic patients in the emergency department.

Primary Funding Source: Janssen-Cilag.

Figures

Grahic Jump Location
Figure 1.
Study flow diagram.

BNP = B-type natriuretic peptide; ED = emergency department.

Grahic Jump Location
Grahic Jump Location
Figure 2.
BNP values in patients who presented to the emergency department with shortness of breath and had a final diagnosis of HF or no HF.

BNP = B-type natriuretic peptide; HF = heart failure.

Grahic Jump Location

Tables

References

Letters

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Comments

Submit a Comment
IGNORING BNP RESULTS WILL NOT IMPROVE OUTCOME OF CHF THERAPY
Posted on March 19, 2009
Mihály Tapolyai
Louisiana State University Health Scieneces Center - Shreveport
Conflict of Interest: None Declared

To the Editor: Schneider HG et al. describe how Australian emergency room physicians treat patients with severe shortness of breath. They evaluate their patients based on their symptoms and promptly institute therapy based on their clinical impression.

This study contrasted this practice with the same except that "physicians (were advised) that a BNP level less than 100 ng/L made the diagnosis of heart failure unlikely, whereas a BNP level greater than 500 ng/L made heart failure likely (1)." No other decision methodology nor decision tree nor decision algorithm was instituted. The results show no difference between being informed and not being informed.

This comparison contrasts physician behavior not the utility of BNP testing. Why patients were blinded to the B-type natriuretic peptide value is unclear but it appears that physicians also blinded themselves to this. The results clearly show no difference between ignoring the test result versus not being aware of the test result. This study is not about the utility of BNP but the bravery of Australian emergency room physicians who can march on with their decisions despite of clear, objective, laboratory-proven evidence!

References

1. Schneider HG, Lam L, Lokuge A, Krum H, Naughton MT, De Villiers Smit P, et al. B-type natriuretic peptide testing, clinical outcomes, and health services use in emergency department patients with dyspnea: a randomized trial. Ann Intern Med. 2009;150:365-71. [PMID: 19293069]

Conflict of Interest:

None declared

BNP testing might be useful in selected cases
Posted on March 24, 2009
P Dileep Kumar
Port Huron Hospital
Conflict of Interest: None Declared

Schneider et al's report (1) points to the fact that indiscriminate testing might not result in better outcomes or cost savings. B-type natriuretic peptide (BNP) is touted as a universal test in the emergency rooms with questionable validity. A plethora of research links BNP to several clinical settings ranging from pneumonia to pulmonary embolism, thus partially limiting its usefulness.

In evaluating dyspnea in the emergency room, straightforward cases of exacerbations of chronic obstructive pulmonary disease and congestive heart failure could be diagnosed by judiciously employing a combination of history, physical findings and chest X-ray. BNP testing might have a useful role in the rest of the difficult cases of dyspnea when a diagnosis is not certain.

Reference:

1. Schneider HG, Lam L, Lokuge A, et al. B-type natriuretic peptide testing, clinical outcomes, and health services use in emergency department patients with dyspnea: a randomized trial. Ann Intern Med. 2009;150:365-71.

Conflict of Interest:

None declared

BNP testing in acutely dyspneic patients presenting to Emergency Department: Does it impact outcome?
Posted on March 31, 2009
Ajay Pachika
Crozer Chester Medical Center
Conflict of Interest: None Declared

The article by Schneider et al (1) is a well-conducted randomized trial on the impact of B-type Natriuretic Peptide (BNP) testing on management of dyspneic patients presenting to Emergency Department. The study looks at the impact of BNP measurement on clinical outcomes among acutely dyspneic patients. It is a well-powered study given the large sample size.

In this article, authors noted that compared to those without heart failure, the BNP group with final diagnosis of heart failure had markedly elevated BNP values and BNP accurately discriminated between the groups. However, it would be very important to know what the initial diagnosis was, how BNP was utilized in arriving at it and how well it correlated with the final diagnosis. This distinction may be very crucial because outcome and length of stay may be affected by accuracy of initial diagnosis and initiation of appropriate treatment. BNP is a valuable tool in establishing or excluding diagnosis of congestive heart failure in patients presenting with acute dyspnea with a diagnostic accuracy of 83% at a cut off of 100pg/ml (2). Furthermore, addition of BNP to clinical judgment improves the evaluation of acute dyspnea (3). Authors recommended use of Heart failure nomogram (3) but did not provide further information on how well it was utilized in decision-making, especially in view of the limited experience of the ED physicians at the participating hospitals, as the test was ordered by Cardiologists or performed only with approval from chemical pathologists.

It is difficult to conclude that BNP testing does not alter clinical outcomes without knowing how well BNP was incorporated in arriving at initial diagnosis and also if there was any discordance between initial and final diagnosis.

References:

1. Schneider H, Lam L, Lokuge A et al. B-Type Natriuretic Peptide Testing, Clinical Outcomes, and Health Services Use in Emergency Department Patients With Dyspnea: A Randomized Trial. Annals of Internal Medicine 2009 Mar 17;150 (6): 365-371

2. Maisel AS, Krishnaswamy P; Nowak RM, McCord J, et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med 2002 Jul 18;347(3):161-7

3. McCullough PA, Nowak RM, McCord J, Hollander JE et al. B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study. Circulation. 2002;106:416-22.

Conflict of Interest:

None declared

The clinical use of B-type natriuretic peptide
Posted on April 7, 2009
Yu Han
Xijing Hospital, Fourth Military Medical University
Conflict of Interest: None Declared

To the editor:

We read with great interest the excellent paper by Schneider HG and colleagues (1). They concluded that measurement of BNP in emergency department patients with severe shortness of breath had no apparent effects on clinical outcomes or use of health services.

Although the study was potentially clinically directive, we would like to express 2 concerns. First, the study has excluded patients under the age of 40 years, which left clinicians with a dilemma. We assumed that the practice of excluding patients from clinical trials on the basis of age alone limited the application of the trials' findings and should be reviewed. Second, not included in the report was a discussion about initiating and monitoring B-type natriuretic peptide use, or about potential risks, which might be unique among these patients. It was weel known that the adverse events associated with B-type natriuretic peptide were dependent on the dose and route of administration. We suggested to develop a treatment protocol to optimize safety.

References

1. Schneider HG, Lam L, Lokuge A, Krum H, Naughton MT, De Villiers Smit P, et al. B-type natriuretic peptide testing, clinical outcomes, and health services use in emergency department patients with dyspnea: a randomized trial. Ann Intern Med. 2009;150:365-71.

Conflict of Interest:

None declared

Does BNP knowledge affect intermediate dyspnea-severity patients management?
Posted on April 15, 2009
Franca Dipaola
Gruppo di Autoformazione Metodologica
Conflict of Interest: None Declared

We read with interest the article by Schneider et al. regarding the use of B-Type Natriuretic Peptide (BNP) in Emergency Department (ED) patients with dyspnea (1). However, we believe that several key issues deserve clarification.

The authors have reported no significant differences between BNP and control groups in ED use of medications. It would be interesting to analyse how BNP and non BNP groups were treated on the basis of final diagnosis in order to evaluate if knowledge of BNP results (<100 or >500 ng/L, used as exclusion or confirmatory heart failure (HF) diagnosis cut-off (2)) have influenced therapeutic approach. If no differences are found between HF BNP and control group patients, weÆd like to propose three possible interpretations. First, as the authors suggest, the results of BNP analysis, could have been available too late to influence physician decision making. Second, BNP testing was a new technique for ED physicians, and, though knowing its theoretical meaning, they could have been insufficiently used to it to be influenced by its results. Third, as shown in a previous study, BNP is useful especially for intermediate-risk patients (pre-test probability of HF between 21 and 79%), which amount to 28% of dyspneic subjects enrolled (2). Supposing a similar patientÆs distribution in the present study, probably intermediate -risk patients were too little to reach statistical significance.

Finally, since in clinical practice BNP is used for the differential diagnosis of dyspnea, we think that having enrolled patients either with a low dyspnea severity (which are discharged without doubt) or with a serious respiratory impairment (which are admitted regardless of the cause of dyspnea) could have masked a significant reduction in admission rates, which would have been obtained enrolling only intermediate-respiratory compromised patients. At this regard, it would be interesting to stratify patients in three severity subgroups according to respiratory rate or oxygen saturation and analyze if BNP is useful in the intermediate severity subgroup.

REFERENCES

1. Schneider H, Lam L, Lokuge A et al. B-Type Natriuretic Peptide Testing, Clinical Outcomes, and Health Services Use in Emergency Department Patients With Dyspnea: A Randomized Trial. Ann of Intern Med. 2009;150:365-371

2. McCullough PA, Nowak RM, McCord J et al. B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study. Circulation 2002;106:416-422

Conflict of Interest:

None declared

In Response
Posted on May 12, 2009
Hans-Gerhard Schneider
No Affiliation
Conflict of Interest: None Declared

Tapolyai questions, whether the ED physicians ignored the BNP results as they provide μclear, objective, laboratory-proven evidence╞. BNP levels are elevated in a range of conditions that are not heart failure, such as pulmonary embolism, acute coronary syndromes and AMI and increase with atrial fibrillation, radiographic cardiomegaly, decreased blood hemoglobin concentration, decreased body mass index, and increasing age (1) and our population was older than some other studies. The diagnostic accuracy of our physicians was  overall 80.5%. 74% accuracy was described for clinicians in the ⌠Breathing Not Properly÷ study in patients with a high likelihood of HF(2). In that study addition of BNP in a mathematical model increased diagnostic accuracy to 81%. At the optimal BNP cut-point the diagnostic accuracy for BNP in our study was 82% (manuscript submitted).

 

Pachika wonders, how the emergency physicians incorporated the BNP value into their assessment and whether there were differences in the initial and final diagnosis. BNP is mainly used to exclude HF as the cause of shortness of breath. In our study the accuracy of the BNP value at 101 pg/ml was 71% (92% sensitivity, 51% specificity). In the BNP group there were 89 patients with BNP <100 pg/ml. 74 of these were clinically judged not to have HF as cause of the SOB, while 15 were judged to have HF. Subsequent to the laboratory and other results this reduced to 10 patients, a relatively small change.

 

DiPaola queries, whether the management of patients in the BNP group, who were ultimately identified as having HF was better than in the control group. We have analysed according to subgroups and see no difference apart from non-invasive ventilation, which is of benefit both in HF and in COPD (see table 1).  Therefore the knowledge of BNP did not markedly improve patient management. It is important to remember that the studies looking at combining BNP and clinical assessment for HF diagnosis commonly are posthoc analysis of results that are mathematically modelled (2,3), and not a randomised controlled trial like this study. We will do further modelling to identify intermediate risk patients, who might benefit from BNP measurement and perhaps age stratified BNP values might be helpful. In summary the knowledge of BNP in our study did not improve management or length of stay in our study, perhaps partly explained by the high level of diagnostic accuracy of the clinicians.

 

References

 

1. Knudsen CW, Clopton P, Westheim A, et al. Predictors of elevated B-type natriuretic peptide concentrations in dyspneic patients without heart failure: an analysis from the breathing not properly multinational study. Ann Emerg Med. 2005 Jun;45(6):573-80.

 

2. McCullough PA, Nowak RM, McCord J, et al. B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study. Circulation. 2002 Jul 23;106(4):416-22.

 

3. Januzzi JL Jr, Camargo CA, Anwaruddin S, et al. The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study. Am J Cardiol. 2005 Apr 15;95(8):948-54.

 

Table 1

 

Use of medication in ED for patient diagnosed with and without heart failure between the BNP group and the control group

            HF (n=274) No HF (n=338)

Medication,

n (%)           BNP

148 (48.4)   Control

126 (41.2)   p-value            BNP

158 (46.7)   Control

180 (53.3)   p-value

Bronchodilator 39 (26.4)     32 (25.4)     0.86     83 (52.5)     80 (44.4)     0.14

Diuretic            94 (63.5)     87 (69.1)     0.34     16 (10.1)     22 (12.2)     0.54

Vasodilator      42 (28.4)     38 (30.2)     0.75     10 (6.3)       9 (5)            0.6

Antibiotic         41 (27.7)     32 (25.4)     0.67     59 (37.3)     80 (44.4)     0.19

Steroid 17 (11.5)     11 (8.7)       0.45     63 (39.9)     54 (30)        0.06

Morphine         10 (6.8)       7 (5.6)         0.68     7 (4.4)         10 (5.6)       0.64

Digoxin            6 (4.1)         6 (4.8)         0.75     2 (1.3)         2 (1.1)         0.9

Amiodarone    0          2 (1.6)         0.12     0          0         

ACE* inhibitor 3 (2)            3 (2.4)         0.84     0          0         

NIV*     32 (21.6)     14 (11.1)     0.02     11 (7)          16 (8.89)     0.12

 

*ACE angiotensin converting enzyme

*NIV: Non-invasive ventilation including BiPAP and CPAP

Conflict of Interest:

None declared

 

 

Conflict of Interest:

None declared

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