腦鈉肽bnp與心力衰竭研究進(jìn)展幻燈PPT課件

1、第1頁(yè)/共39頁(yè)Outcomes in Patients Hospitalized With HFJong P et al. Arch Intern Med. 2002;162:1689025507510020%50%30days6moHospital Readmissions025507510012%50%30days12moMortality33%5yrMedian hospital LOS: 6 daysAnnual mortality rate-NYHA class III HF-12% COPERNICUS DATANYHA class II HF-7% SCD-HeFT DATA第

2、2頁(yè)/共39頁(yè) 在美國(guó)，因心衰入院人數(shù)=每年一百萬(wàn)?？傎M(fèi)用=560億美元 住院治療花費(fèi)中，70-75%直接用于患者護(hù)理 心衰住院治療后再入院=6個(gè)月內(nèi)達(dá)45% 心衰的治療負(fù)擔(dān)心衰的治療負(fù)擔(dān)第3頁(yè)/共39頁(yè)Increased morbidityand mortalityDiuretic therapyImpaired renalfunctionDecreased renal perfusionDiuretic resistanceDiminishedblood flowNeurohormonalactivationPotential Deleterious Effects of Diuretic

3、s and Cardiorenal Syndrome of HFNeurohormonalactivationVasoconstrictionCongestionPathologicremodeling第4頁(yè)/共39頁(yè)Hemodynamic(balanced vasodilation)lveinslarterieslcoronary arteriesB-Type Natriuretic Peptide (BNP)Neurohumoral aldosterone endothelin norepinephrineRenal diuresis natriuresis GFRDRIMKRGSSSSG

4、LGFCCSSGSGQVMKVLRRHKPSCardiac llusitropiclantifibroticlanti-remodeling第5頁(yè)/共39頁(yè)Jamieson and Palade. J Cell Biol. 1964;23:151.Natriuretic Peptides:The Heart as a Secretory Organ Atrial stretch receptors link blood volume to renal function Distension of a balloon catheter in atria of dogs resulted in d

5、iuresisHenry et al (1956) Secretory granules discovered in the atriaKisch (1956)Jamieson and Palade (1964) BNP was characterized by amino acid sequence and DNA clones Sudoh et al (1988)Seilhamer et al (1989)第6頁(yè)/共39頁(yè)ANPNH 2N-COOH-NH2HOOC-UrodilatinBNPCNPH2N-H2N-HOOC-HOOC-ANPNH 2N-SerLeuArgArgSerSerCy

6、sPheGlyGlyArgCysGlyArgTyrAsnPheSerGlyLeuSerGinAlaGlyIIeArgAspMetCOOH-SSNH2HOOC-ThrAlaProArgSerLeuArgArgTyrArgPheSerAsnCysGlyLeuGlySerGinAlaGlyIIeArgAspMetArgGlyGlyPheCysSerSerSSUrodilatinBNPCNPSSSSH2N-H2N-HOOC-HOOC-SerProLysMetValGinGlyCysGlySerPheGlyLeuSerLysGlyCysPheHisArgArgLeuValLysCysGlyLeuGlyS

7、erGlyArgLysMetAspIIeSerSerSerCysGlyLeuGly SerMetSerGlyIIeArgAspLeuLysLeuGlyArgNatriuretic Peptides第7頁(yè)/共39頁(yè)Adapted from Burnett JC. J Hypertens. 2000;17(Suppl 1):S37-S43.ANP = Atrial Natriuretic PeptideBNP = B-type Natriuretic PeptideCNP = C-type Natriuretic PeptidePeptidePrimary OriginStimulus of Re

8、leaseANPCardiac atriaAtrial distensionBNPVentricular myocardium Ventricular overloadCNPEndothelium Endothelial stressNatriuretic Peptides:Origin and Stimulus of Release第8頁(yè)/共39頁(yè)H2NH2NCOOHCOOHCOOHpro-BNP (aa1 - aa108)CleavageBNP (aa77 - aa108)NT-proBNP (aa1 - aa76)HPLGSPGSASYTLRAPRSPKMVQGSGCFCRKMDRISS

9、SSGLCCKVLRRHHPLGSPGSASYTLR APRSPKMVQGSGCFCRKMDRISSSSGLCCKVLRRHH2N110707680901001081107076pre-proBNP 1 - 134(134 Aa)Signal peptide(26 Aa)第9頁(yè)/共39頁(yè)28171463kDa Rec. A B C D E blank Rec. Clinical BNP Results pg/mL: A BCDEMaisel3920 3720 4010 2090 127in-house Triage 1140 1440 1260 1570 584proBNP BNP5 CHF

10、patients:Liang, Maisel et al., JACC 2007第10頁(yè)/共39頁(yè)All55-6465-7475+AgeAll non-CHFNon-CHF MaleNon-CHF FemaleBNP Levels in Non-CHF PatientsBNP (pg/mL)050100(n=478)第11頁(yè)/共39頁(yè)(pg/mL)在初期評(píng)估中，77,467例患者中有 48,629 例 (63%)作了BNP評(píng)估.在ADHERE項(xiàng)目中僅 3.3%的患者 初始 BNP水平 100 pg/mLFonarow et al, JACC 2007 in press第12頁(yè)/共39頁(yè)Base

11、line BNP and Mortality in HF:Val-HeFT Study1.00.80.60.50024123648SurvivalMonthQ1 238P0.0001RR 95% CI1.01.47 (1.15-1.89)2.27 (1.80-2.86)3.95 3.18-4.92)第13頁(yè)/共39頁(yè)246 patients on hemodialysis without clinical CHF diagnosisJ Am Soc Nephr. 2001;12:1508-1515.7ortality ORBNP tertile 1BNP tertil

12、e 2BNP tertile 3Mortality OR 7.14 (95% CI 2.83-18.0)P0.000013.201.00第14頁(yè)/共39頁(yè)BNP Predicts Sudden Death in Patients with Chronic Heart Failure452 pts with HF, LVEF 13 0 pg/mL only multivariate predictor of SD (P=0.0006)Berger. Circulation. 2002;105:2392-2397.第15頁(yè)/共39頁(yè)連續(xù)BNPBNP測(cè)定能指導(dǎo)住院治療嗎? ? Courtesy of

13、 Damien Logeart.第16頁(yè)/共39頁(yè)住院期間BNP值Logeart D, et al, JACC, 18 February 2004, Volume 43, Issue 4 Pages 635-641第17頁(yè)/共39頁(yè)05001000150020002500admission follow-up(pg/mL)n=22Endpoints:13 deaths 9 re-admissions (30d)n=50No EndpointsBNP +233 pg/mLBNP -215 pg/mLCheng,Maisel. JACC 2001;37:386-91第18頁(yè)/共39頁(yè)1210864

14、20BNP onadmissionBNP ondischargeLength of stay39812348112710377292.26.86.9020040060080010001200BNP1BNP2LOSpg/mlBNP 250 pg/ml on clinical stabilityBNP 250 pg/ml第19頁(yè)/共39頁(yè)Days1801501209060300Event-free Survival1,0,8,6,4,20,0BNP 250 pg/mlBNP 250 pg/ml after“intensive” treatmentTarone-Wares test 80 pg/mL

15、 (n=1274)Percent of Patients (%) Death 30 daysP0.005 for each comparisonBraunwald. N Engl J Med. 2001. Vol 345, No. 14.BNP to Risk Stratify Patients withAcute Coronary Syndromes10 monthsCHFMI DeathCHFMI第21頁(yè)/共39頁(yè)0481216Q1Q2Q3Q4 ST Elevation Non-ST Elevation Unstable AnginaMyocardial Infarction Myocar

16、dial Infarctionn= 825 565 113310-month Mortality (%) P0.0012525 patients with ACS in TIMI-16 (orofiban vs placebo) BNP level at average 40 hours.Braunwald. N Engl J Med. 2001;345(14).BNP Level (pg/mL) 5-44 44-81 82-138 139-1456 BNP to Risk Stratify Patients withAcute Coronary Syndromes第22頁(yè)/共39頁(yè)Maise

17、l A. Rev Cardiovasc Med. 2002;3(suppl 4):S13.Patient presenting with dyspneaPhysical examination,chest x-ray, ECG,BNP levelBNP 400 pg/mLCHF very unlikely(2%)Baseline LV dysfunction,underlying cor pulmonale oracute pulmonary embolism?YesNoPossibleexacerbation of CHF(25%)CHF likely(75%)CHF very likely

18、(95%)Heart Failure Diagnostic Algorithm第23頁(yè)/共39頁(yè)BNP levels and NYHA class of HFNYHA ClassBNP level (pg/ml) I244 + 286 II389 + 374 III640 + 447 IV817 + 435第24頁(yè)/共39頁(yè)Nesiritide Identical to human BNP Causing vasodilation and decrease LV filling pressure Decrease pulmonary capillary wedge pressure Impro

19、ves patients symptoms nesiritide resulted in improvement in hemodynamics and some self-reported symptoms more effectively and with fewer adverse effects than intravenous nitroglycerin (VMAC trial )第25頁(yè)/共39頁(yè)Hemodynamic Effects of Nesiritide vs Placebo vs IV NTG*Publication Committee for the VMAC Inve

20、stigators. JAMA. 2002;287:1531During 3-hr placebo periodPlacebon = 62 IV NTGn = 60Nesiritiden = 124After 3-hr periodIV NTGn = 92Nesiritiden = 154*P 0.05 vs placeboP 0.05 vs IV NTG PCWP Placebo PCWP IV NTG PCWP NesiritideEnd of Placebo-Controlled PeriodTime on Study Drug (hr)00.250.5 12369 12 24 36 4

21、89876543210*Change From Baseline in PCWP (mm Hg)第26頁(yè)/共39頁(yè)Msaisel, A. et al. J Cardiac Failure, Vol. 7, No. 1, 2001N = 15 (responders)PAW (mm Hg)HoursBNP (pg/ml)15171921232527293133baseline48121620246007008009001000110012001300PAWBNP*Pulmonary artery wedge.第27頁(yè)/共39頁(yè)VMAC: Dyspnea Improvement *Added to

22、 standard carePublication Committee for the VMAC Investigators. JAMA. 2002;287:1531Dyspnea at 3 hrProportion of Subjects (%)Nitroglycerin* (n = 143)Nesiritide* (n = 204)Placebo* (n = 142) 40 30 20 100102030405060708090100P=0.191P=0.034Markedly betterModerately betterMinimally betterNo changeMinimall

23、y markedly worse第28頁(yè)/共39頁(yè)THE NAPA TRIAL:Nesiritide Administered Peri-Anesthesia in Patients Undergoing Cardiac Surgery Mark J. Russo, MD, MSDivision of Cardiothoracic Surgery &International Center for Health Outcomes and Innovation ResearchCollege of Physicians and Surgeons, Columbia University,

24、 New York, NY第29頁(yè)/共39頁(yè)NAPA TRIAL DESIGNMulti-center (54 centers)RandomizedDouble-blindPlacebo-controlledIntroductionMethodsResultsSummary第30頁(yè)/共39頁(yè)NAPA TRIAL DESIGNLV dysfunction (EF40%)NYHA Class II - IVundergoing CABG MVS using cardiopulmonary bypassIntroductionMethodsResultsSummary第31頁(yè)/共39頁(yè)EXCLUSION CRITERIAPlanned AVR/rOff-pumpOngoing or chronic d