腦鈉肽(bnp)與心力衰竭的研究進展-教學課件幻燈

1、腦鈉肽(BNP)與心力衰竭的研究進展北京世紀壇醫(yī)院北京大學第九臨床醫(yī)學院 楊水祥 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在美國，因心衰入院人數(shù)=每年一百萬。總費用=560億美元住院治療花費中，70-75%直接用于患者護理心衰住院治療后再入院=6個月內(nèi)達45% 心衰的治療負擔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水平和院內(nèi)死亡率 BN

9、P水平的分布(pg/mL)在初期評估中，77,467例患者中有 48,629 例 (63%)作了BNP評估.在ADHERE工程中僅 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.連續(xù)BNP測定能指導住院治療嗎? Courtesy of Damien Logeart.住院期間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 住院治療和結(jié)果評價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)和住院時間(天)121086420BNP onadmissionBNP ondischargeLength of stay39812348112710377292.26.86.9020040060080010001200BNP1BNP

13、2LOSpg/mlBNP 250 pg/ml on clinical stabilityBNP 250 pg/ml根據(jù)出院前 BNP水平作出的Kaplan-Meier曲線顯示累積死亡率和再入院率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小時治療期間 BNP 和PAW*水平的變化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