脑钠肽bnp与心力衰竭研究进展幻灯PPT课件

1、第1页/共39页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页/共39页 在美国，因心衰入院人数=每年一百万。总费用=560亿美元 住院治疗花费中，70-75%直接用于患者护理 心衰住院治疗后再入院=6个月内达45% 心衰的治疗负担心衰的治疗负担第3页/共39页Increased morbidityand mortalityDiuretic therapyImpaired renalfunctionDecreased renal perfusionDiuretic resistanceDiminishedblood flowNeurohormonalactivationPotential Deleterious Effects of Diuretic

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

4、LGFCCSSGSGQVMKVLRRHKPSCardiac llusitropiclantifibroticlanti-remodeling第5页/共39页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页/共39页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页/共39页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页/共39页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页/共39页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页/共39页All55-6465-7475+AgeAll non-CHFNon-CHF MaleNon-CHF FemaleBNP Levels in Non-CHF PatientsBNP (pg/mL)050100(n=478)第11页/共39页(pg/mL)在初期评估中，77,467例患者中有 48,629 例 (63%)作了BNP评估.在ADHERE项目中仅 3.3%的患者 初始 BNP水平 100 pg/mLFonarow et al, JACC 2007 in press第12页/共39页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页/共39页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页/共39页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页/共39页连续BNPBNP测定能指导住院治疗吗? ? Courtesy of

13、 Damien Logeart.第16页/共39页住院期间BNP值Logeart D, et al, JACC, 18 February 2004, Volume 43, Issue 4 Pages 635-641第17页/共39页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页/共39页1210864

14、20BNP onadmissionBNP ondischargeLength of stay39812348112710377292.26.86.9020040060080010001200BNP1BNP2LOSpg/mlBNP 250 pg/ml on clinical stabilityBNP 250 pg/ml第19页/共39页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页/共39页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页/共39页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页/共39页BNP levels and NYHA class of HFNYHA ClassBNP level (pg/ml) I244 + 286 II389 + 374 III640 + 447 IV817 + 435第24页/共39页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页/共39页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页/共39页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页/共39页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页/共39页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页/共39页NAPA TRIAL DESIGNMulti-center (54 centers)RandomizedDouble-blindPlacebo-controlledIntroductionMethodsResultsSummary第30页/共39页NAPA TRIAL DESIGNLV dysfunction (EF40%)NYHA Class II - IVundergoing CABG MVS using cardiopulmonary bypassIntroductionMethodsResultsSummary第31页/共39页EXCLUSION CRITERIAPlanned AVR/rOff-pumpOngoing or chronic d