脑钠肽(bnp)与心力衰竭的研究进展-教学课件幻灯

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2021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)Natriuretic PeptidesAdapted from Burnett JC. J Hypertens. 2000;17(Suppl 1):S37-S43.ANP = Atrial Natr

6、iuretic PeptideBNP = B-type Natriuretic PeptideCNP = C-type Natriuretic PeptidePeptidePrimary OriginStimulus of ReleaseANPCardiac atriaAtrial distensionBNPVentricular myocardium Ventricular overloadCNPEndothelium Endothelial stressNatriuretic Peptides:Origin and Stimulus of ReleaseH2NH2NCOOHCOOHCOOH

7、pro-BNP (aa1 - aa108)CleavageBNP (aa77 - aa108)NT-proBNP (aa1 - aa76)HPLGSPGSASYTLRAPRSPKMVQGSGCFCRKMDRISSSSGLCCKVLRRHHPLGSPGSASYTLRAPRSPKMVQGSGCFCRKMDRISSSSGLCCKVLRRHH2N110707680901001081107076MyocardBloodpre-proBNP 1 - 134(134 Aa)Signal peptide(26 Aa)28171463kDa Rec. A B C D E blank Rec. Clinical

8、BNP Results pg/mL: A BCDEMaisel3920 3720 4010 2090 127in-house Triage 1140 1440 1260 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)ADHF中的BNP水平和院内死亡率 BN

9、P水平的分布(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工程中仅 3.3%的患者 初始 BNP水平 100 pg/mLFonarow et al, JACC 2007 in pressBaseline 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)BNP Levels Independen

10、tly Predict Mortality in Patients with ESRD on Hemodialysis246 patients on hemodialysis without clinical CHF diagnosisJ Am Soc Nephr. 2001;12:1508-1515.7ortality ORBNP tertile 1BNP tertile 2BNP tertile 3Mortality OR 7.14 (95% CI 2.83-18.0)P0.000013.201.00BNP Predicts Sudden Death in Pat

11、ients 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.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05

12、001000150020002500admission 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入院和出院前BNP值(pg/mL)和住院时间(天)121086420BNP onadmissionBNP ondischargeLength of stay39812348112710377292.26.86.9020040060080010001200BNP1BNP

13、2LOSpg/mlBNP 250 pg/ml on clinical stabilityBNP 250 pg/ml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 Engl J Med. 2001. Vol 345, No. 14.BNP to

14、 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 (orofiban vs placebo) BNP level at averag

15、e 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 x-ray, ECG,BNP levelBNP 400 pg/mLCHF ver

16、y 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 + 286 II389 + 374 III640 + 447 IV817 + 4

17、35NesiritideIdentical 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 with fewer adverse effects than intraven

18、ous 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 = 92Nesiritiden = 154*P0.05 vs placeboP0.05 vs IV N

19、TG 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 (responders)PAW (mm Hg)HoursBNP (pg/ml)15171921

20、232527293133baseline48121620246007008009001000110012001300PAWBNP*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* (n = 143)Nesiritide* (n = 204)Placebo*

21、 (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 Cardiothoracic Surgery &International C

22、enter 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 cardiopulm