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Circulation. 2002
Published online before print July 1, 2002, doi: 10.1161/01.CIR.0000025242.79963.4C
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© American Heart Association, Inc.

Clinical Investigation and Reports

B-Type Natriuretic Peptide and Clinical Judgment in Emergency Diagnosis of Heart Failure

Analysis From Breathing Not Properly (BNP) Multinational Study

Peter A. McCullough, MD, MPH; Richard M. Nowak, MD, MBA; James McCord, MD; Judd E. Hollander, MD; Howard C. Herrmann, MD; Philippe G. Steg, MD; Philippe Duc, MD; Arne Westheim, MD, PhD; Torbjørn Omland, MD, PhD, MPH; Cathrine Wold Knudsen, MD; Alan B. Storrow, MD; William T. Abraham, MD; Sumant Lamba, MD; Alan H.B. Wu, PhD; Alberto Perez, MD; Paul Clopton, MS; Padma Krishnaswamy, MD; Radmila Kazanegra, MD Alan S. Maisel, MD, for the BNP Multinational Study Investigators

From the University of California (P.C., P.K., R.K., A.S.M.), Veteran’s Affairs Medical Center, San Diego; Henry Ford Hospital (R.M.N., J.M.), Detroit, Mich; University of Pennsylvania (J.E.H., H.C.H.), Philadelphia; Hopital Bichat (P.G.S., P.D.), Paris, France; Ullevål University Hospital (A.W., T.O., C.W.K.), Oslo, Norway; University of Cincinnati College of Medicine (A.B.S.), Cincinnati, Ohio; University of Kentucky College of Medicine (W.T.A., S.L.), Lexington; Hartford Hospital (A.H.B.W., A.P.), Hartford, Conn; and University of Missouri–Kansas City School of Medicine (P.A.M.), Truman Medical Center, Kansas City, Mo.

Correspondence to Peter A. McCullough, MD, MPH, University of Missouri–Kansas City School of Medicine, Truman Medical Centers, 2301 Holmes St, Kansas City, MO 64108. E-mail mcculloughp{at}umkc.edu

Background— We sought to determine the degree to which B-type natriuretic peptide (BNP) adds to clinical judgment in the diagnosis of congestive heart failure (CHF).

Methods and Results— The Breathing Not Properly Multinational Study was a prospective diagnostic test evaluation study conducted in 7 centers. Of 1586 participants who presented with acute dyspnea, 1538 (97%) had clinical certainty of CHF determined by the attending physician in the emergency department. Participants underwent routine care and had BNP measured in a blinded fashion. The reference standard for CHF was adjudicated by 2 independent cardiologists, also blinded to BNP results. The final diagnosis was CHF in 722 (47%) participants. At an 80% cutoff level of certainty of CHF, clinical judgment had a sensitivity of 49% and specificity of 96%. At 100 pg/mL, BNP had a sensitivity of 90% and specificity of 73%. In determining the correct diagnosis (CHF versus no CHF), adding BNP to clinical judgment would have enhanced diagnostic accuracy from 74% to 81%. In those participants with an intermediate (21% to 79%) probability of CHF, BNP at a cutoff of 100 pg/mL correctly classified 74% of the cases. The areas under the receiver operating characteristic curve were 0.86 (95% CI 0.84 to 0.88), 0.90 (95% CI 0.88 to 0.91), and 0.93 (95% CI 0.92 to 0.94) for clinical judgment, for BNP at a cutoff of 100 pg/mL, and for the 2 in combination, respectively (P<0.0001 for all pairwise comparisons).

Conclusions— The evaluation of acute dyspnea would be improved with the addition of BNP testing to clinical judgment in the emergency department.


Key Words: heart failure • diagnosis • natriuretic peptides • lung • tests




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Crit Care NurseHome page
N. M. Albert, C. A. Eastwood, and M. L. Edwards
Evidence-Based Practice for Acute Decompensated Heart Failure
Crit. Care Nurse, December 1, 2004; 24(6): 14 - 29.
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Clin. Chem.Home page
S. Bruins, M. R. Fokkema, J. W.P. Romer, M. J.L. DeJongste, F. P.L. van der Dijs, J. M.W. van den Ouweland, and F. A.J. Muskiet
High Intraindividual Variation of B-Type Natriuretic Peptide (BNP) and Amino-Terminal proBNP in Patients with Stable Chronic Heart Failure
Clin. Chem., November 1, 2004; 50(11): 2052 - 2058.
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Arch Intern MedHome page
J. A. Doust, P. P. Glasziou, E. Pietrzak, and A. J. Dobson
A Systematic Review of the Diagnostic Accuracy of Natriuretic Peptides for Heart Failure
Arch Intern Med, October 11, 2004; 164(18): 1978 - 1984.
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Eur Heart JHome page
A. Gackowski, R. Isnard, J.-L. Golmard, F. Pousset, A. Carayon, G. Montalescot, J.-S. Hulot, D. Thomas, W. Piwowarska, and M. Komajda
Comparison of echocardiography and plasma B-type natriuretic peptide for monitoring the response to treatment in acute heart failure
Eur. Heart J., October 2, 2004; 25(20): 1788 - 1796.
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J Am Coll CardiolHome page
A. Maisel, J. E. Hollander, D. Guss, P. McCullough, R. Nowak, G. Green, M. Saltzberg, S. R. Ellison, M. A. Bhalla, V. Bhalla, et al.
Primary results of the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT): A multicenter study of B-type natriuretic peptide levels, emergency department decision making, and outcomes in patients presenting with shortness of breath
J. Am. Coll. Cardiol., September 15, 2004; 44(6): 1328 - 1333.
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J Am Coll CardiolHome page
T. Omland
Heart failure in the emergency department: Is B-type natriuretic peptide a better prognostic indicator than clinical assessment?
J. Am. Coll. Cardiol., September 15, 2004; 44(6): 1334 - 1336.
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Evid. Based Med.Home page
P. Henriksson
Chest radiographs and BNP levels provided complementary information beyond clinical findings for diagnosing heart failure
Evid. Based Med., September 1, 2004; 9(5): 152 - 152.
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J Am Coll CardiolHome page
S. Sadanandan, C. P. Cannon, K. Chekuri, S. A. Murphy, P. M. DiBattiste, D. A. Morrow, J. A. de Lemos, E. Braunwald, and C. M. Gibson
Association of elevated B-type natriuretic peptide levels with angiographic findings among patients with unstable angina and non-ST-segment elevation myocardial infarction
J. Am. Coll. Cardiol., August 4, 2004; 44(3): 564 - 568.
[Abstract] [Full Text] [PDF]


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Br J AnaesthHome page
M. Kemp, J. Donovan, H. Higham, and J. Hooper
Biochemical markers of myocardial injury
Br. J. Anaesth., July 1, 2004; 93(1): 63 - 73.
[Abstract] [Full Text] [PDF]


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CirculationHome page
J. L. Januzzi, A. S. Maisel, R. W. Troughton, A. M. Richards, T. G. Yandle, M. G. Nicholls, T. Nishikimi, H. Matsuoka, and M. Packer
Routine Measurement of Natriuretic Peptide to Guide the Diagnosis and Management of Chronic Heart Failure * Response
Circulation, June 29, 2004; 109(25): e325 - e326.
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J Am Coll CardiolHome page
P. de Groote, J. Dagorn, B. Soudan, N. Lamblin, E. McFadden, and C. Bauters
B-type natriuretic peptide and peak exercise oxygen consumption provide independent information for risk stratification in patients with stable congestive heart failure
J. Am. Coll. Cardiol., May 5, 2004; 43(9): 1584 - 1589.
[Abstract] [Full Text] [PDF]


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CirculationHome page
C. Mueller, P. Huber, G. Laifer, B. Mueller, and A. P. Perruchoud
Procalcitonin and the Early Diagnosis of Infective Endocarditis
Circulation, April 13, 2004; 109(14): 1707 - 1710.
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Eur J Heart FailHome page
M. Vanderheyden, J. Bartunek, and M. Goethals
Brain and other natriuretic peptides: molecular aspects
Eur J Heart Fail, March 15, 2004; 6(3): 261 - 268.
[Abstract] [Full Text] [PDF]


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Eur J Heart FailHome page
T.A. McDonagh, S. Holmer, I. Raymond, A. Luchner, P. Hildebrant, and H.J. Dargie
NT-proBNP and the diagnosis of heart failure: a pooled analysis of three European epidemiological studies
Eur J Heart Fail, March 15, 2004; 6(3): 269 - 273.
[Abstract] [Full Text] [PDF]


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Eur J Heart FailHome page
Y. Seino, A. Ogawa, T. Yamashita, M. Fukushima, K.-i. Ogata, H. Fukumoto, and T. Takano
Application of NT-proBNP and BNP measurements in cardiac care: a more discerning marker for the detection and evaluation of heart failure
Eur J Heart Fail, March 15, 2004; 6(3): 295 - 300.
[Abstract] [Full Text] [PDF]


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Eur J Heart FailHome page
A. Bayes-Genis, M. Santalo-Bel, E. Zapico-Muniz, L. Lopez, C. Cotes, J. Bellido, R. Leta, P. Casan, and J. Ordonez-Llanos
N-terminal probrain natriuretic peptide (NT-proBNP) in the emergency diagnosis and in-hospital monitoring of patients with dyspnoea and ventricular dysfunction
Eur J Heart Fail, March 15, 2004; 6(3): 301 - 308.
[Abstract] [Full Text] [PDF]


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HeartHome page
A F L Schinkel, E C Vourvouri, J J Bax, F Boomsma, M Bountioukos, V Rizzello, E Biagini, E Agricola, A Elhendy, J R T C Roelandt, et al.
Relation between left ventricular contractile reserve during low dose dobutamine echocardiography and plasma concentrations of natriuretic peptides
Heart, March 1, 2004; 90(3): 293 - 296.
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NEJMHome page
C. Mueller, A. Scholer, K. Laule-Kilian, B. Martina, C. Schindler, P. Buser, M. Pfisterer, and A. P. Perruchoud
Use of B-Type Natriuretic Peptide in the Evaluation and Management of Acute Dyspnea
N. Engl. J. Med., February 12, 2004; 350(7): 647 - 654.
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NEJMHome page
D. B. Mark and G. M. Felker
B-Type Natriuretic Peptide -- A Biomarker for All Seasons?
N. Engl. J. Med., February 12, 2004; 350(7): 718 - 720.
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CirculationHome page
S. D. Wiviott, C. P. Cannon, D. A. Morrow, S. A. Murphy, C. M. Gibson, C. H. McCabe, M. S. Sabatine, N. Rifai, R. P. Giugliano, P. M. DiBattiste, et al.
Differential Expression of Cardiac Biomarkers by Gender in Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A TACTICS-TIMI 18 (Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction 18) Substudy
Circulation, February 10, 2004; 109(5): 580 - 586.
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Eur Heart JHome page
R. Latini, S. Masson, I. Anand, M. Salio, A. Hester, D. Judd, S. Barlera, A. P Maggioni, G. Tognoni, J. N Cohn, et al.
The comparative prognostic value of plasma neurohormones at baseline in patients with heart failure enrolled in Val-HeFT
Eur. Heart J., February 2, 2004; 25(4): 292 - 299.
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ChestHome page
S. de Denus, C. Pharand, and D. R. Williamson
Brain Natriuretic Peptide in the Management of Heart Failure: The Versatile Neurohormone
Chest, February 1, 2004; 125(2): 652 - 668.
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Am J Crit CareHome page
A. Prahash and T. Lynch
B-Type Natriuretic Peptide: A Diagnostic, Prognostic, and Therapeutic Tool in Heart Failure
Am. J. Crit. Care., January 1, 2004; 13(1): 46 - 53.
[Abstract] [Full Text] [PDF]


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Eur J Heart FailHome page
C. W. Knudsen, J. S. Riis, A. V. Finsen, L. Eikvar, C. Muller, A. Westheim, and T. Omland
Diagnostic value of a rapid test for B-type natriuretic peptide in patients presenting with acute dyspnoe: effect of age and gender
Eur J Heart Fail, January 1, 2004; 6(1): 55 - 62.
[Abstract] [Full Text] [PDF]


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Clin. Chem.Home page
A. Clerico and M. Emdin
Diagnostic Accuracy and Prognostic Relevance of the Measurement of Cardiac Natriuretic Peptides: A Review
Clin. Chem., January 1, 2004; 50(1): 33 - 50.
[Abstract] [Full Text] [PDF]


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Eur J Heart FailHome page
E. C. Vourvouri, A. F.L. Schinkel, J. R.T.C. Roelandt, F. Boomsma, G. Sianos, M. Bountioukos, F. B. Sozzi, V. Rizzello, J. J. Bax, H. I. Karvounis, et al.
Screening for left ventricular dysfunction using a hand-carried cardiac ultrasound device
Eur J Heart Fail, December 1, 2003; 5(6): 767 - 774.
[Abstract] [Full Text] [PDF]


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Arch SurgHome page
E. Berendes, C. Schmidt, H. Van Aken, M. G. Hartlage, S. Wirtz, H. Reinecke, M. Rothenburger, H. H. Scheld, B. Schluter, G. Brodner, et al.
Reversible Cardiac Sympathectomy by High Thoracic Epidural Anesthesia Improves Regional Left Ventricular Function in Patients Undergoing Coronary Artery Bypass Grafting: A Randomized Trial
Arch Surg, December 1, 2003; 138(12): 1283 - 1290.
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J. Thorac. Cardiovasc. Surg.Home page
Y. Ootaki, M. Yamaguchi, N. Yoshimura, S. Oka, M. Yoshida, and T. Hasegawa
Secretion of A-type and B-type natriuretic peptides into the bloodstream and pericardial space in children with congenital heart disease
J. Thorac. Cardiovasc. Surg., November 1, 2003; 126(5): 1411 - 1416.
[Abstract] [Full Text] [PDF]


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HeartHome page
T H Marwick
Techniques for comprehensive two dimensional echocardiographic assessment of left ventricular systolic function
Heart, November 1, 2003; 89(90003): iii2 - 8.
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Eur Respir JHome page
P. Pruszczyk, M. Kostrubiec, A. Bochowicz, G. Styczynski, M. Szulc, M. Kurzyna, A. Fijalkowska, A. Kuch-Wocial, I. Chlewicka, and A. Torbicki
N-terminal pro-brain natriuretic peptide in patients with acute pulmonary embolism
Eur. Respir. J., October 1, 2003; 22(4): 649 - 653.
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Eur Heart JHome page
M.R Cowie, P Jourdain, A Maisel, U Dahlstrom, F Follath, R Isnard, A Luchner, T McDonagh, J Mair, M Nieminen, et al.
Clinical applications of B-type natriuretic peptide (BNP) testing
Eur. Heart J., October 1, 2003; 24(19): 1710 - 1718.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
B. M. Massie
Natriuretic peptide measurements for the diagnosis of "nonsystolic" heart failure: Good news and bad
J. Am. Coll. Cardiol., June 4, 2003; 41(11): 2018 - 2021.
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Endocr. Rev.Home page
H. Ruskoaho
Cardiac Hormones as Diagnostic Tools in Heart Failure
Endocr. Rev., June 1, 2003; 24(3): 341 - 356.
[Abstract] [Full Text] [PDF]