2008BNP Alan Maisel MD, FACC, ACP

, , CCUHF

2008BNP 2, 1, 1, and 15 9, 2, 5, 2, 1

BNP:BNP BNP ( HF)BNP BNP ( & )BNP 2004 BNP

Alan Maisel

Prof. Shanghai Ruijin hospital Department of NephrologyProf. General Hospital of the Chinese People's Liberation Army Clinical laboratoryProf. Peoples Hospital of Jiangsu province Department of CardiologyProf. Peoples Hospital of Jiangsu province Department of CardiologyProf. First affiliated hospital, Sun yat-sen university Emergency DepartmentProf. First Hospital of Peking University Department of Gerontology Prof. Peoples Hospital of Peking University Department of CardiologyMr. Chinese Journal of CardiologyEditorial Department Prof. Shanghai Ruijin hospital Department of CardiologyMs. Chinese Journal of Laboratory Editorial DepartmentProf. Peoples Hospital of Peking University Department of Cardiology Prof. China-Japan Friendship Hospital Clinical laboratoryProf. Beijing FuWai Hospital Department of CardiologyProf. Beijing FuWai Hospital Department of CardiologyProf. Shanghai Ruijin Hospital Department of NephrologyProf. Peoples Hospital of Peking University Emergency Department

P 1.1% 0.8% 0.054

P 1.4% 0.5% < 0.01

P 1.0% 0.7% < 0.05

Chin J Cardiol. 2003;31:3-6.

Sample data were collected from 10 province in China.GU Dongfeng et al. Chin J Cardiol. 2003;31:3-6. (%) n=7,518P

1980, 1990 2000HFSample data were collected from 10 province in China.GU Dongfeng et al. Chin J Cardiol. 2003;31:3-6.

1980, 1990 2000 Sample data were collected from 10 province in China.GU Dongfeng et al. Chin J Cardiol. 2003;31:3-6.

1980, 19902000%Mortality19801990200015.412.36.20510152025198020001990Percent(%)Sample data were collected from 10 province in China.GU Dongfeng et al. Chin J Cardiol. 2003;31:3-6.

3.06.0Data were taken from 42 hospitals in different city in China in 2000Chin J Cardiol, 2002; 30: 450-454%

Chin J Cardiol, 2002; 30: 450-454N=92, follow-up 47 months(37-71)

Framingham - SOLVD* Total African-American White Hypertension 77% 32% 4%CAD 39%50% 36% 73%Rheumatic/Valvular 2%20% 11% 10%Idiopathic 5%15% 13% 12%Framingham Heart Study.*Bourassa et al. J Am Coll Cardiol. 1993;22:14A-19A.

Data were taken from 42 hospitals in different city in ChinaChin J Cardiol, 2002; 30: 450-454N=10,71436.833.845.68.010.412.934.434.318.618.718.920.505101520253035404550198019902000

45.6%18.6%12.9%20.5%CAD: Coronary Artery Disease; HT: Hypertension; RVHD: Rheumatic valvular heart disease; Others including congenital heart disease, non-rheumatic valvular heart disease, cadiomyopathy, etc.2000

BNP 80%BNPHF 50%BNPHF 400BNPHF

BNP: +++ Iwanaga Y et al. JACC. 2006;47:742-8.

Adapted from Dzau V et al. Am Heart J.1991;121:1244-63.: () () () BNPBNP = 0

BNP Daniels LB & Maisel AS. Heart Failure Clin. 2006;2(3):299-309.

BNPN=56N=94Dao, Q., Maisel, A. et al. J. American College of Cardiology, Vol 37, No. 2, 2001

BNP

CHF (BNP)CHF Adapted with permission from McCullough P et al. Circulation. 2002;106:416422.050100150200250300350010.020.030.040.050.060.070.080.090.0100.0

Maisel AS et al. N Engl J Med. 2002;347:161-167.BNP,,0.0 0.2 0.4 0.6 0.8 1.0

& BNP0%5%10%15%20%25%30%35%40%45% BNP 43%11%*P

BNPROC

BNP

BNP(BASEL)Mueller C et al. N Engl J Med 2004;350:647-54.

(n=227) + BNP (n=225) P (minutes, median, interquartile range)90 (20-205)63 (16-153)0.03 (days, median, interquartile range)11.0 (5.0-18.0)8.0 (1.0-16.0)0.001(%)85750.008ICC (%)24150.01 (S. median, 95% )7264 (6301-8227)5410 (4516-6304)0.006 (%)960.2130 (%)12100.45

BNPSilver M., Maisel AS et al. BNP Consensus Panel 2004 (Heart Failure 2004; (suppl. 3) S3-S14)

BNPMaisel A, et al. Annals of Emergency Medicine 2001 (in press)0204060801001201401601800%5%10%15%20%25%30%35%40%45%BNP < 230 pg/mlBNP 230-480 pg/mlBNP > 480 pg/ml

BNPADHF BNP 77,467 48,629 (63%)BNP.ADHERE 3.3% BNP 100 pg/mLFonarow et al, JACC 2007 in press pg/mL

BNP BNP(< 200 pg/mL) BNP(> 1700 pg/mL)

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1000500300200100503020105BNP (pg/mL) CHF n=844 n=165 n=287=34 pg/ml=821 pg/ml=413 pg/mlBNPJ Am Coll Cardiol 2003;410(11):2010-17.

BNPLubien and Maisel, Circulation. 2002; 105:595-601

BNP 800 pg/ml vs. 400 pg/mlBNPBNP20-40 pg/ml

BNPPAW* 24Msaisel, A. et al. J Cardiac Failure, Vol. 7, No. 1, 2001*.

: BNP= BNP() +()BNP level (pg/ml)NYHA Class - Euvolemic (Dry) BNP

BNP Logeart D. et al. J Am Coll Cardiol. 2004 Feb 18;43(4):635-41 ()Hazard ratiosof 2nd and 3rdversus 1st BNP range (%)10075502500306090120150180 BNP >700ng/ln =41, events =38BNP 350 - 700ng/ln =50, events =30 BNP

BNP 20, BNPBNPBNP

BNPBNP BNPBNP 3BNP24 BNP

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BNPNT-BNPRCV % OHanlon R et al. J Card Fail. 2007. Feb;13(1):50-5. 020406080100120140Wu BruinO'HanlonSchouBNPNT-BNP

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ROC Lewin J. Eur J Heart Fail. 2005 Oct;7(6):953-7.

BNPLewin J. Eur J Heart Fail. 2005 Oct;7(6):953-7.

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70605040302010010BNP (pg/mL)n=137n=148n=1850n=51n=50n=340n=343ALOFT3 monthsA-HeFT6 monthsVal-HeFT4 monthsRALES3 months126134+2n=1890 615839- BNP (pg/mL)p=0.016p

: BNPBNPBNPCHF, BNPBNP (100- 300 pg/ml)BNPBNP BNP

ACShs-CRP, Ox LDLMCP-1, MPO, IL18PAI-1, sCD40LvWF, D dimerBNP, NEsICAM, pSelectinMMPs, PAPPsCD40L, PIGFcTnT, cTnI, Myo, CKMB, FABPIMA, uFFA

BNPACS ()STSTACSN=327 Nov,2006Dec,2007,in PUPH

BNP by Triage BNP Test (Biosite, Inc., San Diego, CA)

4.28%Data not published

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BNPBNP European Heart J. 2005;26:385-6.

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***0.9%,0.7%,1.0%,3574 400 , ; , , ,*HF , 56 Framingham 40 , 525%,38%199020005HF

*198020004***** , 1980 34.4 % 2000 18.6 % , 1980 44.8 % 2000 58 .5%, , 90 % , *1.0.9%,0.7%,1.0%,14.4/102.3.4.20

(Note to reviewer: This is the second part of a building slide. This version shows the reviewer how the slide will appear once the build of BNP squares is completed.)

This diagram illustrates how patients progress from high risk, to microscopic disease, to clinical disease, and eventually to death. There are other pathways to heart failure but this (atherosclerosis and ischemic disease) is the most common representation of myocardial injury. Throughout these stages the BNP levels are increasing up to the point of death whereby it falls to zero. BNP may be useful for identification of patients at earlier stages of this continuum in whom clinical intervention may be the most beneficial in slowing and halting disease progression.Figure 1. B-type natriuretic peptide (BNP) rises with age over the course of a lifetime, but generally stays under 20 pg/mL in the absence of left ventricular (LV) dysfunction or structural heart disease. BNP > 100 pg/mL is the cut-off for diagnosing congestive heart failure (CHF) in symptomatic patients.The ability to differentiate dyspnea due to COPD vs. CHF is a major diagnostic dilemma in the E.D. The rapid whole blood assay provides a strong indication of symptom origin. Patients who presented with dyspnea from pulmonary origin without cardiac involvement had normal BNP levels in the blood, whereas patients with dyspnea as a symptom of congestive heart failure had markedly elevated BNP levels.

The Triage BNP Test is indicated for use as an aid in the diagnosis of congestive heart failure.**

Slide 18In 325 patients presenting to the ED with dyspnea, BNP levels were determined. Patients were then followed for 6 months looking for the following endpoints: death (cardiac and non-cardiac), hospital admissions (cardiac), and repeat ED visits for CHF. Using Kaplan-Meyer plots for all CHF events, patients who left the emergency department with BNP levels >480 pg/ml had a 6-month cumulative probability of a CHF event of (43%). On the other hand, patients who left the emergency department with BNP levels 230 was 46. BNP levels measured in patients presenting with dyspnea to the ED are highly predictive of future cardiac events. Utilization of BNP levels in patients presenting with symptoms of CHF should prove to be a cost-effective way to risk-stratify patients with HF. From April 2003 through December 2004 there were 48,629 eligible acute HF hospitalization episodes in the ADHERE Registry with documented BNP level and LVEF (LVEF > 40%, N = 18,164; LVEF < 40%, N = 19,544). BNP levels were < 100 in only 3.3% of the total cohort hospitalized with a primary discharge diagnosis of HF.

*This graph shows the take home points of the predischarge BNP study. At BNP levels over 700 there is a significant increase in risk of death or readmission. Levels less than 350 confer a significantly lower risk. The hazard ratios are on the right, and the results are statistically significant. These data are from the validation and derivation (whole population). *