Le dosage du peptide natriurétique B est - il intéressant aux Urgences ? Jérôme ALLARDET-SERVENT DESC Réanimation Médicale MARSEILLE – Décembre 2004

Introduction La Famille des Peptides Natriurétiques ... Levin et al.NEJM.1998.

Biosynthèse Wall Stretch pre-proBNP proBNP Furin BNP NT-proBNP 1 134 1 Stretch activated ion channels Voltage dependant Ca ++ channels 1 134 pre-proBNP 1 108 proBNP Furin 77 108 1 76 BNP NT-proBNP

Physiologie HOMEOSTASIE  Tonus veineux  Tonus artériel Antiprolifératif  GFR  Na+ reabsorption HOMEOSTASIE Lusitropie + Antifibrotique Antiprolifératif  Tonus vagal  Activité SNS  Aldostérone  Rénine Levin et al.NEJM.1998.

BNP ou NT-proBNP BNP NT-proBNP Characteristic McCullough et al.2003. 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 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 Maisel et al. JACC.2003.

Physiopathologie BNP (pg/mL) Age Symptomatic CHF Asymptomatic LV 250 - Symptomatic CHF 100 - Asymptomatic LV dysfunction BNP (pg/mL) 50 - 20 - Normal 30 - 60 - 90 - Age McCullough et al.2003.

Quel Rôle ? Thérapeutique Pronostic Diagnostic Monitorage

Quelles pathologies ? Urgences IVG Dyspnée aiguë Pleurésie ACR EP HTAP Syndrome coronarien aigu

Dyspnée aiguë 321 patients. Diagnostic rétrospectif par deux experts. Morrison et al. JACC.2002.

Dyspnée aiguë Receiver Operating Characteristic Curve Morrison et al. JACC.2002.

Dyspnée aiguë 321 patients. Diagnostic rétrospectif par deux experts. BNP Levels (pg/mL) Sensitivity % Specificity Positive Predictive value Negative Value Accuracy 94 86 (80-90) 98 (94-99) 98 (95-99) 83 (76-88) 91 105 94 (89-97) 95 (91-98) 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) 240 96 (92-98) 79 (71-85) 86 (81-91) 93 (87-97) Morrison et al. JACC.2002.

Dyspnée aiguë 321 patients. Diagnostic rétrospectif par deux experts. Morrison et al. JACC.2002.

Dyspnée aiguë 321 patients. Diagnostic rétrospectif par deux experts. Morrison et al. JACC.2002.

Jugular Venous Pressure Pulmonary venous hypertension Dyspnée aiguë Multivariate Analysis of factors used for differentiating between patients with and those without Congestive Heart Failure Variable 276 Cases Chi-Square Significance Sensitivity % Specificity % Accuracy History of CHF 94,3 < 0,001 76 81 79 Chest X ray enlarged 33 89 82 Jugular Venous Pressure 12,9 Pulmonary venous hypertension 6,4 0,011 68 91 80 Rales 4,3 0,038 74 88 BNP 119,6 87 95 Morrison et al. JACC.2002.

Dyspnée aiguë 1586 patients. Diagnostic rétrospectif par deux experts. Maisel et al. NEJM.2002.

Dyspnée aiguë 1586 patients. Diagnostic rétrospectif par deux experts. Maisel et al. NEJM.2002.

Dyspnée aiguë Receiver Operating Characteristic Curve Maisel et al. NEJM.2002.

Dyspnée aiguë Operating caracteristics for various cutoff levels of BNP in differentiating between Dyspnea due to Congestive Heart Failure and Dyspnea due to other cause BNP Levels (pg/mL) Sensitivity % Specificity Positive Predictive value Negative 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) 125 87 (85-90) 79 (76-82) 80 (78-83) 87 (84-89) 150 85 (82-88) 83 (80-85) 85 (83-88) 84 Maisel et al. NEJM.2002.

Dyspnée aiguë Multiple Logistic regression Analysis of factors used for differentiating between patients with and those without Congestive Heart Failure 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 2,72 (1,63 – 4,54) Rales 2,24 (1,41 – 3,58) Cephalization of vessels 10,69 (5,32 – 21,47) Edema 2,88 (1,81 – 4,57) Jugular venous distension 1,87 (1,04 – 3,36) BNP > 100 pg/mL 29,60 (17,75 – 49,37) Maisel et al. NEJM.2002.

Dyspnée aiguë 452 patients avec diagnostic rétrospectif de CHF. FEVG réduite ( < 45 % ) vs FEVG conservée ( > 45 %) 36,5 % 63,5 % Maisel et al. JACC.2003.

Dyspnée aiguë ROC curve : Dysfonction Systolique vs Diastolique. Maisel et al. JACC.2003.

OAP Usefulness of BNP in elderly patients with acute dyspnea 388 patients > 65 ans avec diagnostic rétrospectif d’expert. n=141 n=167 Ray et al. ICM.2004.

OAP 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 Value Accuracy 100 90 59 65 88 72 150 85 71 78 200 82 84 81 83 250 87 300 92 80 350 67 77 400 60 95 74 79 Ray et al. ICM.2004.

History of cardiac disease OAP 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 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) Ray et al. ICM.2004.

OAP 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, % 0.83 (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) Ray et al. ICM.2004.

Dyspnée aiguë 456 patients randomisés en deux groupes de stratégie diagnostique Mueller et al. NEJM.2004.

Age, sexe et race 1586 patients. Diagnostic rétrospectif par deux experts. Maisel et al. Am Heart J.2003.

BNP et GFR B-type natriuretic peptide and renal function in the diagnosis of heart failure. 1452 patients avec diagnostic retrospectif CHF. Exclusion Hemodialysé et GFR < 15 mL/min/1,73m² BNP (pg/mL) GFR (mL/min/1,73m²) McCullough et al. Am J Kidney Dis. 2003.

BNP et GFR B-type natriuretic peptide and renal function in the diagnosis of heart failure. 1452 patients avec diagnostic retrospectif CHF. Exclusion Hemodialysé et GFR < 15 mL/min/1,73m² GFR mL/min/1,73m² BNP Cutoff AUC > 90 70,7 0,91 89 - 60 104,3 0,9 59 – 30 201,2 0,81 < 30 225 0,86 McCullough et al. Am J Kidney Dis. 2003.

BNP en pratique Maisel et al.2003.

BNP en pratique Maisel et al.2003.