脑钠肽(bnp)与心力衰竭的研究进展-教学幻灯课件

1、脑钠肽(BNP)与心力衰竭的研究进展北京世纪坛医院北京大学第九临床医学院 杨水祥 教授2009年8月20日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% COPE

2、RNICUS DATANYHA class II HF-7% SCD-HeFT DATA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Increased morbidityand mortalityDiuretic therapyImpaired renalfunctionDecreased renal perfusionDiuretic resistanceDiminishedblood flowNeurohormonalactivationPotential Deleterious

3、Effects of Diuretics and Cardiorenal Syndrome of HFNeurohormonalactivationVasoconstrictionCongestionPathologicremodelingHemodynamic(balanced vasodilation)veinsarteriescoronary arteriesB-Type Natriuretic Peptide (BNP)Neurohumoral aldosterone endothelin norepinephrineRenal diuresis natriuresis GFRDRIM

4、KRGSSSSGLGFCCSSGSGQVMKVLRRHKPSCardiac lusitropicantifibroticanti-remodelingJamieson and Palade. J Cell Biol. 1964;23:151.Natriuretic Peptides:The Heart as a Secretory OrganAtrial stretch receptors link blood volume to renal functionDistension of a balloon catheter in atria of dogs resulted in diures

5、isHenry 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)H2NH2NCOOHCOOHCOOHpro-BNP (aa1 - aa108)CleavageBNP (aa77 - aa108)NT-proBNP (aa1 - aa76)HPLGSPGSASYTL

6、RAPRSPKMVQGSGCFCRKMDRISSSSGLCCKVLRRHHPLGSPGSASYTLRAPRSPKMVQGSGCFCRKMDRISSSSGLCCKVLRRHH2N110707680901001081107076MyocardBloodpre-proBNP 1 - 134(134 Aa)Signal peptide(26 Aa)28171463kDa Rec. A B C D E blank Rec. Clinical BNP Results pg/mL: A BCDEMaisel3920 3720 4010 2090 127in-house Triage 1140 1440 12

7、60 1570 584在心衰患者中BNP主要的形式是proBNPproBNP BNP5 CHF patients:Liang, Maisel et al., JACC 2007All55-6465-7475+AgeAll non-CHFNon-CHF MaleNon-CHF FemaleBNP Levels in Non-CHF PatientsBNP (pg/mL)050100(n=478)BNP Predicts Sudden Death in Patients with Chronic Heart Failure452 pts with HF, LVEF 13 0 pg/mL only

8、multivariate predictor of SD (P=0.0006)Berger. Circulation. 2002;105:2392-2397.连续BNP测定能指导住院治疗吗? Courtesy of Damien Logeart.住院期间BNP值Logeart D, et al, JACC, 18 February 2004, Volume 43, Issue 4 Pages 635-641BNP在急性充血性心力衰竭 住院治疗和结果评价05001000150020002500admission follow-up(pg/mL)n=22Endpoints:13 deaths 9

9、re-admissions (30d)n=50No EndpointsBNP +233 pg/mLBNP -215 pg/mLCheng,Maisel. JACC 2001;37:386-91根据出院前 BNP水平作出的Kaplan-Meier曲线显示累积死亡率和再入院率BNP 250 pg/mlBNP 250 pg/ml after“intensive” treatmentTarone-Wares test 80 pg/mL (n=1274)Percent of Patients (%) Death 30 daysP0.005 for each comparisonBraunwald. N

10、Engl J Med. 2001. Vol 345, No. 14.BNP to Risk Stratify Patients withAcute Coronary Syndromes10 monthsCHFMI DeathCHFMI0481216Q1Q2Q3Q4 ST Elevation Non-ST Elevation Unstable AnginaMyocardial Infarction Myocardial Infarctionn= 825 565 113310-month Mortality (%) P0.0012525 patients with ACS in TIMI-16 (

11、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 SyndromesMaisel A. Rev Cardiovasc Med. 2002;3(suppl 4):S13.Patient presenting with dyspneaPhysical examination,chest

12、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(95%)Heart Failure Diagnostic AlgorithmBNP levels and NYHA class of HFNYHA ClassBNP level (pg/ml) I244

13、+ 286 II389 + 374 III640 + 447 IV817 + 435NesiritideIdentical to human BNPCausing vasodilation and decrease LV filling pressureDecrease pulmonary capillary wedge pressureImproves patients symptomsnesiritide resulted in improvement in hemodynamics and some self-reported symptoms more effectively and

14、with fewer adverse effects than intravenous nitroglycerin (VMAC trial )Hemodynamic Effects of Nesiritide vs Placebo vs IV NTG*Publication Committee for the VMAC Investigators. JAMA. 2002;287:1531During 3-hr placebo periodPlacebon = 62 IV NTGn = 60Nesiritiden = 124After 3-hr periodIV NTGn = 92Nesirit

15、iden = 154*P0.05 vs placeboP0.05 vs IV NTG PCWP Placebo PCWP IV NTG PCWP NesiritideEnd of Placebo-Controlled PeriodTime on Study Drug (hr)00.250.512369122436489876543210*Change From Baseline in PCWP (mm Hg)24小时治疗期间 BNP 和PAW*水平的变化Msaisel, A. et al. J Cardiac Failure, Vol. 7, No. 1, 2001N = 15 (respon

16、ders)PAW (mm Hg)HoursBNP (pg/ml)15171921232527293133baseline48121620246007008009001000110012001300PAWBNP*Pulmonary artery wedge.VMAC: Dyspnea Improvement *Added to standard carePublication Committee for the VMAC Investigators. JAMA. 2002;287:1531Dyspnea at 3 hrProportion of Subjects (%)Nitroglycerin

17、* (n = 143)Nesiritide* (n = 204)Placebo* (n = 142)403020100102030405060708090100P=0.191P=0.034Markedly betterModerately betterMinimally betterNo changeMinimallymarkedly worseTHE NAPA TRIAL:Nesiritide Administered Peri-Anesthesia in Patients Undergoing Cardiac Surgery Mark J. Russo, MD, MSDivision of

18、 Cardiothoracic Surgery &International Center for Health Outcomes and Innovation ResearchCollege of Physicians and Surgeons, Columbia University, New York, NYNAPA TRIAL DESIGNMulti-center (54 centers)RandomizedDouble-blindPlacebo-controlledIntroductionMethodsResultsSummaryNAPA TRIAL DESIGNLV dysfunction (EF40%)NYHA Class II - IVundergoing CABG MVS using cardiopulmonary bypassIntroductionMethodsResultsSummaryEXCLUSION CRITERIAPlanned AVR/rOff-pumpOngoing or chronic dialysis Hemody