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BNP for the Diagnosis of BNP for the Diagnosis of Acute Decompensated Acute Decompensated

CHFCHFWashington University in St. LouisWashington University in St. Louis

Emergency Medicine Journal ClubEmergency Medicine Journal Club

November 18, 2009November 18, 2009

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NT-proBNP for Diagnosis NT-proBNP for Diagnosis CHFCHF

80 year old female 2 days shortness of breath

Risk factors for CAD PMH: CHF, COPD - 40 pack years BP 180/90, Pulse 80 (NSR), RR 18,

afebrile, pulse ox 92% (2L nasal canula)

Exam reveals symmetric lower extremities 2+ pitting edema

What is her pre-BNP What is her pre-BNP probability of probability of

decompensated CHF?decompensated CHF?

a) Low (≤ 20%)b) Intermediate (21% to 79%)c) High (≥ 80%)

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CHF Disease BurdenCHF Disease Burden

In Canada, CHF is #2 for total number of hospital days and #3 for total number of patients affected with 15.8% in-hospital mortality rate and 32.7% re-admission rates among 106,130 annual CHF admissions*

In the US, 2.3% of population are living with CHF with annual death rate 18.7% costing $27.9 billion annually.†*Can J Cardiology 2003; 19(4): 436*Can J Cardiology 2003; 19(4): 436

††ACEP Clinical Policy on CHF, Annals EM 2007; 49(5): 627ACEP Clinical Policy on CHF, Annals EM 2007; 49(5): 627

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H2N—

H2N—

—COOH

—COOH

—COOH

Enzymatic Cleaving of Enzymatic Cleaving of proBNPproBNP

proBNP(aa1 - aa108)

BNP(aa77 - aa108)NT-proBNP

(aa1 - aa76)

H P L G S P G S A S

Y T L R A P R SP

KM

VQ

GS G

CF

C

RK

MD R I S

SS

S

GLC

CK

VL

RR

H

H P L G S P G S A S Y T L R A P R

SP

KM

VQ

GS G

CF

C

RK

MD R I S

SS

S

GLC

CK

VL

RR

H

H2N—

1

10 7

0

76

80

90

100

108

1 10

70

76

blood

J. de Lemos et al., Lancet online 2003

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NT-proBNP for Diagnosis NT-proBNP for Diagnosis of CHFof CHF

Negative LRs: Battaglia meta-analysis of ELISA BNP:

0.12 Januzzi meta-analysis of NT-proBNP

0.12 Tung study

0.15Januzzi et al. NT-proBNP testing for diagnosis and short-term Januzzi et al. NT-proBNP testing for diagnosis and short-term prognosis in acute destabilized heart failure. European Heart J prognosis in acute destabilized heart failure. European Heart J 2006; 27: 330-337.2006; 27: 330-337.

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NT-proBNP for Diagnosis NT-proBNP for Diagnosis of CHFof CHF

Positive LRs: Battaglia meta-analysis of ELISA BNP:

8.2 Januzzi meta-analysis of NT-proBNP

5.6 Tung study

5.4

Januzzi et al. NT-proBNP testing for diagnosis and short-term Januzzi et al. NT-proBNP testing for diagnosis and short-term prognosis in acute destabilized heart failure. European Heart J 2006; prognosis in acute destabilized heart failure. European Heart J 2006; 27: 330-337.27: 330-337.

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BNP vs NT-proBNPBNP vs NT-proBNP

BNP AUC = 0.916 (95% CI: 0.874, 0.947)

NT-proBNP AUC = 0.903 (95% CI: 0.859, 0.939)

Nearly identical ROC curvesMueller T, et al. Diagnostic accuracy of B type natriuretic peptide and amino terminal proBNP in the emergency diagnosis of heart failure. Heart. 2005 May;91(5):606-12.

Diagnostic TestsDiagnostic Tests

Sensitivity (Se) and Specificity (Sp) are the most commonly used measures of diagnostic test performance.

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Diagnostic TestsDiagnostic Tests

Sensitivity 70% Given that a patient has influenza,

there is a 70% probability that the rapid test will be positive

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FP

DISEASE STATUS

PRESENT (D+) ABSENT (D-)

TEST RESULT

POSITIVE (T+)

NEGATIVE (T-)

TP

FN TN

a bc d

FP

Sp = TN/TN+FPSp = d / d + b

Se = TP/TP+FNSe = a / a + c

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Diagnostic TestsDiagnostic Tests

Disadvantages of Se & Sp must dichotomize results (2x2 table) difficult to apply in clinical practice

Se applies only to patients with disease Sp applies only to healthy patients Clinician does not know disease status,

only test result

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Diagnostic TestsDiagnostic Tests

What we really want to know:

What is the probability of disease in my patient given a particular test result?

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Diagnostic TestsDiagnostic Tests

prob (test result) with disease

prob (test result) without disease

LR (test result) =LR (test result) =

Effect on Post-test Effect on Post-test ProbabilityProbability

LR+ LR- Effect on prob

> 10 <0.1 large

5-10 0.1-0.2 moderate 2-5 0.5-0.2 small 1 1 no effect

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proBNP for Diagnosis CHFproBNP for Diagnosis CHF

80 year old female 2 days shortness of breath

PMH: COPD, CHF Exam consistent with neither CHF nor

COPD Pre-test probability 50% (?)

Her NT-proBNP results is 500 pg/mL LR neg = 0.15

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Does This Patient Have Does This Patient Have CHF?CHF?

FindingFinding LR+LR+ LR-LR-

GestaltGestalt 9.99.9 0.650.65

Prior CHFPrior CHF 5.85.8 0.450.45

OrthopneaOrthopnea 1.31.3 0.680.68

EdemaEdema 2.72.7 0.410.41

RalesRales 2.62.6 0.390.39

WheezeWheeze 0.850.85 1.21.2

From JAMA 2005; 294: 1944-1956From JAMA 2005; 294: 1944-1956

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Pretest Probability Pretest Probability 50%50%

LR- = 0.15LR- = 0.15

Posttest Probability 10%Posttest Probability 10%

Wheeze LR- 1.2Wheeze LR- 1.2

Edema LR+ 2.7Edema LR+ 2.7

Prior CHF LR+ 5.8Prior CHF LR+ 5.8

What is her post-BNP What is her post-BNP probability of probability of

decompensated CHF?decompensated CHF?

a) Low (≤ 20%)b) Intermediate (21% to 79%)c) High (≥ 80%)

Excel FileExcel File