腦鈉肽(bnp)與心力衰竭的研究進展-教學課件幻燈

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2009年8月20日OutcomesinPatients

HospitalizedWithHFJongPetal.ArchInternMed.2002;162:1689025507510020%50%30days6moHospitalReadmissions025507510012%50%30days12moMortality33%5yrMedianhospitalLOS:6daysAnnualmortalityrate-NYHAclassIIIHF-12%[COPERNICUSDATA]NYHAclassIIHF-7%[SCD-HeFTDATA]在美國，因心衰入院人數(shù)=每年一百萬?？傎M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IncreasedmorbidityandmortalityDiuretictherapyImpairedrenalfunctionDecreasedrenalperfusionDiureticresistanceDiminishedbloodflowNeurohormonalactivationPotentialDeleteriousEffectsofDiuretics

andCardiorenalSyndromeofHFNeurohormonalactivationVasoconstrictionCongestionPathologicremodelingHemodynamic(balancedvasodilation)veinsarteriescoronaryarteriesB-TypeNatriureticPeptide(BNP)NeurohumoralaldosteroneendothelinnorepinephrineRenaldiuresisnatriuresisGFRDRIMKRGSSSSGLGFCCSSGSGQVMKVLRRHKPSCardiaclusitropicantifibroticanti-remodelingJamiesonandPalade.JCellBiol.1964;23:151.NatriureticPeptides:

TheHeartasaSecretoryOrganAtrialstretchreceptorslinkbloodvolumetorenalfunctionDistensionofaballooncatheterinatriaofdogsresultedindiuresisHenryetal(1956)SecretorygranulesdiscoveredintheatriaKisch(1956)JamiesonandPalade(1964)BNPwascharacterizedbyaminoacidsequenceandDNAclonesSudohetal(1988)Seilhameretal(1989)NatriureticPeptidesAdaptedfromBurnettJC.JHypertens.2000;17(Suppl1):S37-S43.ANP=AtrialNatriureticPeptideBNP=B-typeNatriureticPeptideCNP=C-typeNatriureticPeptidePeptide PrimaryOrigin StimulusofReleaseANP Cardiacatria AtrialdistensionBNP VentricularmyocardiumVentricularoverloadCNP Endothelium Endothelialstress

NatriureticPeptides:

OriginandStimulusofReleaseH2N—H2N——COOH—COOH—COOHpro-BNP(aa1-aa108)CleavageBNP(aa77-aa108)NT-proBNP(aa1-aa76)HPLGSPGSASYTLRAPRSPKMVQGSGCFCRKMDRISSSSGLCCKVLRRHHPLGSPGSASYTLRAPRSPKMVQGSGCFCRKMDRISSSSGLCCKVLRRHH2N—110707680901001081107076MyocardBloodpre-proBNP1-134

(134Aa)Signalpeptide

(26Aa)28171463kDa

Rec.ABCDEblankRec.ClinicalBNPResultspg/mL:ABCDEMaisel3920372040102090127in-houseTriage1140144012601570584在心衰患者中BNP主要的形式是proBNPproBNP

BNP5CHFpatients:Liang,Maiseletal.,JACC2007All55-6465-7475+AgeAllnon-CHFNon-CHFMaleNon-CHFFemaleBNPLevelsinNon-CHFPatientsBNP(pg/mL)050100(n=478)ADHF中的BNP水平和院內(nèi)死亡率

BNP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項目中僅3.3%的患者初始BNP水平<100pg/mLFonarowetal,JACC2007inpressBaselineBNPandMortalityinHF:

Val-HeFTStudy1.00.80.60.50024123648SurvivalMonthQ1<41AnandISetal.Circulation.2003;107:1276-1281.Q241-970.90.7Q397-238Q4>238P<0.0001RR95%CI1.01.47(1.15-1.89)2.27(1.80-2.86)3.953.18-4.92)BNPLevelsIndependentlyPredictMortalityinPatientswithESRDonHemodialysis246patientsonhemodialysiswithoutclinicalCHFdiagnosisJAmSocNephr.2001;12:1508-1515.7ortalityORBNPtertile1BNPtertile2BNPtertile3MortalityOR7.14(95%CI2.83-18.0)P<0.000013.201.00BNPPredictsSuddenDeathin

PatientswithChronicHeartFailure452ptswithHF,LVEF<35%,BNP>130pg/mLonlymultivariatepredictorofSD(P=0.0006)

Berger.Circulation.2002;105:2392-2397.連續(xù)BNP測定能指導住院治療嗎?CourtesyofDamienLogeart.住院期間BNP值LogeartD,etal,JACC,18February2004,Volume43,Issue4Pages635-641BNP在急性充血性心力衰竭

住院治療和結(jié)果評價05001000150020002500admissionfollow-up(pg/mL)n=22 Endpoints:13deaths 9re-admissions(30d)n=50 NoEndpointsBNP+233pg/mL

BNP-215pg/mL Cheng,…,Maisel.JACC2001;37:386-91入院和出院前BNP值(pg/mL)

和住院時間(天)121086420BNPonadmissionBNPondischargeLengthofstay39812348112710377292.26.86.9020040060080010001200BNP1BNP2LOSpg/mlBNP<250pg/mlonclinicalstabilityBNP<250pg/mlafteraggressivetherapyBNP>250pg/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<250pg/mlafter“normal”treatmentBNP>250pg/mlBNP<250pg/mlafter“intensive”treatmentTarone-Ware’stest<0.001.210246810BNP≤80pg/mL(n=1251)BNP>80pg/mL(n=1274)PercentofPatients(%)

Death

30daysP<0.005foreachcomparisonBraunwald.NEnglJMed.2001.

Vol345,No.14.BNPtoRiskStratifyPatientswith

AcuteCoronarySyndromes10monthsCHFMI

DeathCHFMI0481216Q1Q2Q3Q4

STElevationNon-STElevationUnstableAnginaMyocardialInfarctionMyocardialInfarctionn=825 565113310-monthMortality(%)

P<0.0012525patientswithACSinTIMI-16(orofibanvsplacebo)BNPlevelataverage40hours.Braunwald.NEnglJMed.2001;345(14).BNPLevel(pg/mL)5-4444-8182-138139-1456BNPtoRiskStratifyPatientswith

AcuteCoronarySyndromesMaiselA.RevCardiovascMed.2002;3(suppl4):S13.PatientpresentingwithdyspneaPhysicalexamination,chestx-ray,ECG,BNPlevelBNP<100pg/mLBNP100-400pg/mLBNP>400pg/mLCHFveryunlikely(2%)BaselineLVdysfunction,underlyingcorpulmonaleoracutepulmonaryembolism?YesNoPossibleexacerbationofCHF(25%)CHFlikely(75%)CHFverylikely(95%)HeartFailureDiagnosticAlgorithmBNPlevelsandNYHAclassofHFNYHAClass BNPlevel(pg/ml)I 244+286II 389+374III 640+447IV 817+435NesiritideIdenticaltohumanBNPCausingvasodilationanddecreaseLVfillingpressureDecreasepulmonarycapillarywedgepressureImprovespatients’symptomsnesiritideresultedinimprovementinhemodynamicsandsomeself-reportedsymptomsmoreeffectivelyandwithfeweradverseeffectsthanintravenousnitroglycerin(VMACtrial)HemodynamicEffectsofNesiritide

vsPlacebovsIVNTG*?*?*?????*PublicationCommitteefortheVMACInvestigators.JAMA.2002;287:1531During3-hrplaceboperiodPlacebo n=62IVNTG n=60Nesiritide n=124After3-hrperiodIVNTG n=92Nesiritide n=154*P

0.05vsplacebo?P

0.05vsIVNTG

PCWP–PlaceboPCWP–IVNTG

PCWP–NesiritideEndofPlacebo-ControlledPeriodTimeonStudyDrug(hr)00.250.51236912243648–9–8–7–6–5–4–3–2–10?

**ChangeFromBaselinein

PCWP(mmHg)24小時治療期間BNP和PAW*水平的變化Msaisel,A.etal.JCardiacFailure,Vol.7,No.1,2001N=15(responders)PAW(mmHg)HoursBNP(pg/ml)15171921232527293133baseline48121620246007008009001000110012001300PAWBNP*Pulmonaryarterywedge.VMAC:DyspneaImprovement

*AddedtostandardcarePublicationCommitteefortheVMACInvestigators.JAMA.2002;287:1531Dyspneaat3hrProportionofSubjects(%)Nitroglycerin*

(n=143)Nesiritide*

(n=204)Placebo*

(n=142)

40

30

20

100102030405060708090100P=0.191P=0.034MarkedlybetterModeratelybetterMinimallybetterNochangeMinimally

markedlyworseTHENAPATRIAL:

NesiritideAdministeredPeri-Anesthesia

inPatientsUndergoingCardiacSurgery

MarkJ.Russo,MD,MS

DivisionofCardiothoracicSurgery&InternationalCenterforHealthOutcomesandInnovationResearchCollegeofPhysiciansandSurgeons,ColumbiaUniversity,NewYork,NYNAPATRIALDESIGNMulti-center(54centers)RandomizedDouble-blindPlacebo-controlledIntroductionMethodsResultsSumma