脑钠肽(bnp)与心力衰竭的研究进展教学课件幻灯PPT.ppt

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 HF,Jong P et al.Arch Intern Med.2002;162:1689,0,25,50,75,100,20%,50%,30days,6mo,Hospital Readmissions,0,25,50,75,100,12%,50%,30days,12mo,Mortality,33%,5yr,Median hospital LOS:6 days,Annual mortality rate-NYHA class III HF-12%COPERNICUS 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 mortality,Diuretic therapy,Impaired renalfunction,Decreased renal perfusion,Diuretic resistance,Diminishedblood flow,Neurohormonalactivation,Potential Deleterious Effects of Diuretics and Cardiorenal Syndrome of HF,Neurohormonalactivation,Vasoconstriction,Congestion,Pathologicremodeling,Hemodynamic(balanced vasodilation)veinsarteriescoronary arteries,B-Type Natriuretic Peptide(BNP),Neurohumoral aldosterone endothelin norepinephrine,Renal diuresis natriuresis GFR,Cardiac lusitropicantifibroticanti-remodeling,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 functionDistension of a balloon catheter in atria of dogs resulted in diuresisHenry 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 Peptides,Adapted from Burnett JC.J Hypertens.2000;17(Suppl 1):S37-S43.,ANP=Atrial Natriuretic PeptideBNP=B-type Natriuretic PeptideCNP=C-type Natriuretic Peptide,PeptidePrimary OriginStimulus of ReleaseANPCardiac atriaAtrial distensionBNPVentricular myocardium Ventricular overloadCNPEndothelium Endothelial stress,Natriuretic Peptides:Origin and Stimulus of Release,H2N,H2N,COOH,COOH,COOH,pro-BNP(aa1-aa108),Cleavage,BNP(aa77-aa108),NT-proBNP(aa1-aa76),P,L,G,S,P,G,S,A,S,Y,T,L,R,A,P,R,S,P,K,M,V,Q,G,S,G,C,F,C,R,K,M,D,R,I,S,S,S,S,G,L,C,C,K,V,L,R,R,H,P,L,G,S,P,G,S,A,S,Y,T,L,R,A,P,R,S,P,K,M,V,Q,G,S,G,C,F,C,R,K,M,D,R,I,S,S,S,S,G,L,C,C,K,V,L,R,R,H,H2N,1,10,70,76,80,90,100,108,1,10,70,76,Myocard,Blood,pre-proBNP 1-134(134 Aa),Signal peptide(26 Aa),28,17,14,6,3,kDa,Rec.A B C D E blank Rec.,Clinical BNP Results pg/,mL,:,A,B,C,D,E,Maisel,3920 3720 4010 2090 127,in,-,house Triage 1140 1440 1260,1570 584,在心衰患者中BNP主要的形式是proBNP,proBNP,BNP,5 CHF patients:,Liang,Maisel et al.,JACC 2007,All,55-64,65-74,75+,Age,All non-CHF,Non-CHF Male,Non-CHF Female,BNP Levels in Non-CHF Patients,BNP(pg/mL),0,50,100,(n=478),ADHF中的BNP水平和院内死亡率 BNP水平的分布,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/mL,Fonarow et al,JACC 2007 in press,Baseline BNP and Mortality in HF:Val-HeFT Study,1.0,0.8,0.6,0.5,0,0,24,12,36,48,Survival,Month,Q1 41,Anand IS et al.Circulation.2003;107:1276-1281.,Q2 41-97,0.9,0.7,Q3 97-238,Q4 238,P0.0001,RR 95%CI,1.0,1.47(1.15-1.89),2.27(1.80-2.86),3.95 3.18-4.92),BNP Levels Independently Predict Mortality in Patients with ESRD on Hemodialysis,246 patients on hemodialysis without clinical CHF diagnosisJ Am Soc Nephr.2001;12:1508-1515.,7.14,0,1,2,3,4,5,6,7,8,Mortality OR,BNP tertile 1,BNP tertile 2,BNP tertile 3,Mortality OR 7.14(95%CI 2.83-18.0)P0.00001,3.20,1.00,BNP Predicts Sudden Death in Patients with Chronic Heart Failure,452 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 635-641,BNP在急性充血性心力衰竭 住院治疗和结果评价,0,500,1000,1500,2000,2500,admission follow-up,(pg/mL),n=22Endpoints:13 deaths 9 re-admissions(30d),n=50No Endpoints,BNP+233 pg/mL,BNP-215 pg/mL,Cheng,Maisel.JACC 2001;37:386-91,入院和出院前BNP值(pg/mL)和住院时间(天),12,10,8,6,4,2,0,BNP onadmission,BNP ondischarge,Length of stay,398,123,481,127,1037,729,2.2,6.8,6.9,0,200,400,600,800,1000,1200,BNP1,BNP2,LOS,pg/ml,BNP 250 pg/ml on clinical stability,BNP 250 pg/ml after aggressive therapy,BNP 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/ml after“normal”treatment,BNP 250 pg/ml,BNP 250 pg/ml after“intensive”treatment,Tarone-Wares test 0.001.,21,0,2,4,6,8,10,BNP 80 pg/mL(n=1251),BNP 80 pg/mL(n=1274),Percent of Patients(%),Death,30 days,P0.005 for each comparison,Braunwald.N Engl J Med.2001.Vol 345,No.14.,BNP to Risk Stratify Patients withAcute Coronary Syndromes,10 months,CHF,MI,Death,CHF,MI,0,4,8,12,16,Q1,Q2,Q3,Q4,ST Elevation Non-ST Elevation Unstable AnginaMyocardial Infarction Myocardial Infarction,n=825 565 1133,10-month Mortality(%),P0.001,2525 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,Maisel A.Rev Cardiovasc Med.2002;3(suppl 4):S13.,Patient presenting with dyspnea,Physical examination,chest x-ray,ECG,BNP level,BNP 100 pg/mL,BNP 100-400 pg/mL,BNP 400 pg/mL,CHF very unlikely(2%),Baseline LV dysfunction,underlying cor pulmonale oracute pulmonary embolism?,Yes,No,Possibleexacerbation of CHF(25%),CHF likely(75%),CHF very likely(95%),Heart Failure Diagnostic Algorithm,BNP levels and NYHA class of HF,NYHA ClassBNP level(pg/ml)I244+286 II389+374 III640+447 IV817+435,Nesiritide,Identical 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 intravenous nitroglycerin(VMAC trial),Hemodynamic Effects of Nesiritide vs Placebo vs IV NTG,*,*,*,*,Publication Committee for the VMAC Investigators.JAMA.2002;287:1531,During 3-hr placebo periodPlacebon=62 IV NTGn=60Nesiritiden=124After 3-hr periodIV NTGn=92Nesiritiden=154,*P0.05 vs placeboP0.05 vs IV NTG,PCWP Placebo,PCWP IV NTG,PCWP Nesiritide,End of Placebo-Controlled Period,Time on Study Drug(hr),0,0.25,0.5,1,2,3,6,9,12,24,36,48,9,8,7,6,5,4,3,2,1,0,*,*,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.1,2001,*Pulmonary artery wedge.,VMAC:Dyspnea Improvement,*Added to standard carePublication Committee for the VMAC Investigators.JAMA.2002;287:1531,Dyspnea at 3 hr,Proportion of Subjects(%),Nitroglycerin*(n=143),Nesiritide*(n=204),Placebo*(n=142),40,30,20,10,0,10,20,30,40,50,60,70,80,90,100,P=0.191,P=0.034,Markedly better,Moderately better,Minimally better,No change,Minimallymarkedly worse,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,New York,NY,NAPA TRIAL DESIGN,Multi-center(54 centers)RandomizedDouble-blindPlacebo-controlled,IntroductionMethodsResultsSummary,NAPA TRIAL DESIGN,LV dysfunction(EF40%)NYHA Class II-IVundergoing CABG MVS using cardiopulmonary bypass,IntroductionMethodsResultsSummary,EXCLUSION CRITERIA,Planned AVR/rOff-pumpOngoing or chronic dialysis Hemodynamic criteriaMean PAP 15 mm HgCVP 6 mm HgSBP 90 mm Hg,IntroductionMethodsResultsSummary,STUDY PROTOCOL,IntroductionMethodsResultsSummary,NAPA FINDINGS,IntroductionMethodsResultsSummary,Improved Survival at 180 daysImproved Postop Renal FunctionGreater improvement in patients with renal dysfunction at baselineDecreased LOS,新活素TM的处方资料,通用名 基因重组人脑钠肽(rhBNP)商品名 新活素TM结构及分子式,脑钠肽是人体分泌的一种内源性利钠肽，它是在各种病理因素诱导下发 生心功能受损时，人体产生的一种代偿性心脏保护因子。新活素TM与内源性人脑利钠肽具有相同的氨基酸排序和立体结构。,药代动力学,起效时间 2-15min最大药效时间 30minT1/2 18min代谢/排泄途径C型受体分解失活(血管内皮细胞)中性肽链内切酶肾脏过滤清除(2%),适应症,急、慢性失代偿性心力衰竭急性冠脉综合征（ACS）心脏导管手术心胸外科手术血浆脑利钠肽浓度升高的其他疾病,谢谢,