Le dosage du peptide natriurétique B est - il

intéressant aux Urgences ?

Jérôme ALLARDET-SERVENTDESC Réanimation MédicaleMARSEILLE – Décembre 2004

Introduction

La Famille des Peptides Natriurétiques ...

Levin et al.NEJM.1998.

Biosynthèse

proBNP

NT-proBNPBNP

pre-proBNP1341

1

1 7677 108

108

Stretch activated

ion channelsVoltage dependant

Ca ++ channels

Furin

Wall Stretch

Physiologie

Levin et al.NEJM.1998.

GFR

Na+ reabsorption

Tonus veineux Tonus artériel

Antiprolifératif

Lusitropie +

AntifibrotiqueAntiprolifératif

Tonus vagal Activité SNS Aldostérone Rénine

HOMEOSTASIE

BNP ou NT-proBNPCharacteristic BNP NT-proBNP

Molecular weight 3,5 KDa 8,5 KDa

Hormonally active Yes No

Genesis from NT-proBNP

Release by myocytes

Half-life 20 min 120 min

Clearance mechanism NEP - NPR Renal Clearance

Increases with normal aging + +++

Correlation with estimated GFR - 0,20 - 0,60

Approved cutoff(s) for CHF diagnosis > 100 pg/mL < 75 ans : 125> 75 ans : 450

McCullough et al.2003.

Triage BNP assay

Maisel et al. JACC.2003.

-Tube EDTA-Analyse dans les 4 heures (stable pendant < 24 heures)-Echantillon 250 µL-SandwichImmunoassay-Signal fluorescent-Résultats : 15 min-Range : 5 – 1300 pg/mL

Physiopathologie

20 -

50 -

100 -

250 -

Age

BNP

(pg/

mL)

Normal

Symptomatic CHF

Asymptomatic LV

dysfunction

30 -

60 -

90 -

McCullough et al.2003.

Quel Rôle ?

Diagnostic

Pronostic Thérapeutique

Monitorage

Quelles pathologies ?

Urgences

Syndrome coronarien aigu

Dyspnée aiguë Pleurésie

ACR EP

IVG

HTAP

Dyspnée aiguë

Morrison et al. JACC.2002.

321 patients. Diagnostic rétrospectif par deux experts.

Dyspnée aiguë

Morrison et al. JACC.2002.

Receiver Operating Characteristic Curve

Dyspnée aiguë

Morrison et al. JACC.2002.

BNP Levels

(pg/mL)

Sensitivity%

Specificity%

Positive Predictive

value%

Negative Predictive

Value%

Accuracy%

94 86 (80-90) 98 (94-99) 98 (95-99) 83 (76-88) 91

105 86 (80-90) 94 (89-97) 95 (91-98) 83 (76-88) 89

135 90 (85-94) 90 (84-94) 93 (88-96) 87 (80-92) 90

195 94 (89-96) 85 (78-90) 90 (85-93) 90 (84-95) 90

240 96 (92-98) 79 (71-85) 86 (81-91) 93 (87-97) 89

321 patients. Diagnostic rétrospectif par deux experts.

Dyspnée aiguë

Morrison et al. JACC.2002.

321 patients. Diagnostic rétrospectif par deux experts.

Dyspnée aiguë

Morrison et al. JACC.2002.

321 patients. Diagnostic rétrospectif par deux experts.

Dyspnée aiguë

Morrison et al. JACC.2002.

Variable 276 Cases Chi-Square

Significance

Sensitivity%

Specificity %

Accuracy%

History of CHF 94,3 < 0,001 76 81 79

Chest X ray enlarged

33 < 0,001 89 76 82

Jugular Venous Pressure

12,9 < 0,001 81 81 81

Pulmonary venous hypertension

6,4 0,011 68 91 80

Rales 4,3 0,038 74 88 82

BNP 119,6 < 0,001 87 95 91

Multivariate Analysis of factors used for differentiating between patients with and those without Congestive Heart

Failure

Dyspnée aiguë

Maisel et al. NEJM.2002.

1586 patients. Diagnostic rétrospectif par deux experts.

Dyspnée aiguë

Maisel et al. NEJM.2002.

1586 patients. Diagnostic rétrospectif par deux experts.

Dyspnée aiguë

Maisel et al. NEJM.2002.

Receiver Operating Characteristic Curve

Dyspnée aiguë

Maisel et al. NEJM.2002.

BNP Levels

(pg/mL)

Sensitivity%

Specificity%

Positive Predictive

value%

Negative Predictive

Value%

Accuracy%

50 97 (96-98) 62 (59-66) 71 (68-74) 96 (94-97) 79

80 93 (91-95) 74 (70-77) 77 (75-80) 92 (89-94) 83

100 90 (88-92) 76 (73-79) 79 (76-81) 89 (87-91) 83

125 87 (85-90) 79 (76-82) 80 (78-83) 87 (84-89) 83

150 85 (82-88) 83 (80-85) 83 (80-85) 85 (83-88) 84

Operating caracteristics for various cutoff levels of BNP in differentiating between Dyspnea due to Congestive Heart Failure and Dyspnea due to

other cause

Dyspnée aiguë

Maisel et al. NEJM.2002.

Predictor P Value Odds Ratio (95 % CI)

Age 0,04 1,02 (1,00 - 1,03)

History of congestive heart failure

< 0,001 11,08 (6,55 – 18,77)

History of myocardial infarction < 0,001 2,72 (1,63 – 4,54)

Rales < 0,001 2,24 (1,41 – 3,58)

Cephalization of vessels < 0,001 10,69 (5,32 – 21,47)

Edema < 0,001 2,88 (1,81 – 4,57)

Jugular venous distension 0,04 1,87 (1,04 – 3,36)

BNP > 100 pg/mL < 0,001 29,60 (17,75 – 49,37)

Multiple Logistic regression Analysis of factors used for differentiating between patients with and those without Congestive

Heart Failure

Dyspnée aiguë

Maisel et al. JACC.2003.

36,5 % 63,5 %

452 patients avec diagnostic rétrospectif de CHF. FEVG réduite ( < 45 % ) vs FEVG conservée ( > 45 %)

Dyspnée aiguë

Maisel et al. JACC.2003.

ROC curve : Dysfonction Systolique vs Diastolique.

OAP

Ray et al. ICM.2004.

388 patients > 65 ans avec diagnostic rétrospectif d’expert.

Usefulness of BNP in elderly patients with acute dyspnea

0

100

200

300

400

500

600

BNP

(pg/

mL)

CPE no CPE n=141 n=167

OAP

Ray et al. ICM.2004.

Usefulness of BNP in elderly patients with acute dyspnea

Comparison of the efficiency of various threshold values of BNP in the diagnosis of cardiogenic pulmonary edema in acute dyspnea in patients

older than 65 years

BNP Levels

(pg/mL)

Sensitivity%

Specificity%

Positive Predictive

value%

Negative Predictive

Value%

Accuracy%

100 90 59 65 88 72

150 85 71 71 85 78

200 82 84 81 85 83

250 78 90 87 83 84

300 72 92 88 80 82

350 67 92 88 77 80

400 60 95 90 74 79

OAP

Ray et al. ICM.2004.

Usefulness of BNP in elderly patients with acute dyspnea

Multiple forward logistic regression analysis of factors used for differentiating between patients with cardiogenic pulmonary edema (CPE)

and those without CPE

Predictor P Value Odds Ratio (95 % CI)

BNP 250 pg/mL < 0,001 24,4 (12 - 49,6)

Lower extremity edema < 0,001 4,6 (2 – 10,6)

Rales 0,001 3,1 (1,6 – 6)

History of cardiac disease 0,005 2,9 (1,4 – 6,1)

OAP

Ray et al. ICM.2004.

Usefulness of BNP in elderly patients with acute dyspnea

Comparison of the efficiency of the emergency physician and BNP level (value 250 pg/ml)

Emergency Physician

BNP Level

Sensitivity, % 0.74 (0.66–0.80) 0.78 (0.71–0.84)

Specificity, % 0.80 (0.73–0.85) 0.90 (0.84–0.93)*

Positive predictive value, % 0.75 (0.68–0.82) 0.87 (0.80–0.91)*

Negative predictive value, % 0.78 (0.71–0.84) 0.83 (0.77–0.88)

Accuracy, % 0.77 (0.72–0.81) 0.84 (0.80–0.88)*

Positive likelihood ratio 3.62 (2.64–4.97) 7.66 (4.84–12.12)

Negative likelihood ratio 0.33 (0.25–0.44) 0.24 (0.18–0.33)

Dyspnée aiguë

Mueller et al. NEJM.2004.

456 patients randomisés en deux groupes de stratégie diagnostique

Age, sexe et race

Maisel et al. Am Heart J.2003.

1586 patients. Diagnostic rétrospectif par deux experts.

BNP et GFR B-type natriuretic peptide and renal function in the diagnosis of heart

failure.

McCullough et al. Am J Kidney Dis. 2003.

0100200300400500600700800900

> 90 89 - 60 59 - 30 < 30

CHFno CHF

BNP

(pg/

mL)

GFR (mL/min/1,73m²)

1452 patients avec diagnostic retrospectif CHF. Exclusion Hemodialysé et GFR < 15 mL/min/1,73m²

BNP et GFR B-type natriuretic peptide and renal function in the diagnosis of heart

failure.

McCullough et al. Am J Kidney Dis. 2003.

1452 patients avec diagnostic retrospectif CHF. Exclusion Hemodialysé et GFR < 15 mL/min/1,73m²

GFRmL/min/1,73m²

BNPCutoff

AUC

> 90 70,7 0,91

89 - 60 104,3 0,9

59 – 30 201,2 0,81

< 30 225 0,86

BNP en pratique

Maisel et al.2003.

BNP en pratique

Maisel et al.2003.