心力衰竭管理发展历程.ppt

ManagementofHeartFailure:Past,PresentandFuture,LexinWang,M.D.,Ph.D.,FCSANZProfessorofClinicalPharmacologyHead,CardiovascularResearch,Objectives,HistoryandpathogenesisEpidemiologyandriskfactorsCurrentmanagementFuturedirections,Katz,A.M.CircHeartFail2008;1:63-71,WilliamHarvey,1628,Changingviewsofheartfailure1.Aclinicalsyndrome2.Acirculatorydisorder3.Alteredarchitectureoftheheart4.Abnormalhemodynamics5.Disorderedfluidbalance6.Biochemicalabnormalities7.Maladaptivehypertrophy8.Genomics9.Epigenetics(实验胚胎学),Katz,A.M.CircHeartFail2008;1:63-71,Changingmanagementofheartfailureoverthepast40years,CHF-Prevalence,Approximately5.5millionAmericanshaveCHF(2.2%ofthepopulation)550,000newcasesannuallyAccountsfor12millionclinicvisitsperyearEstimatedhealthcarecostsin2004isUS$28.8billion,CHFprevalence-Australia,2%ofadultpopulationApproximately241,000patients30,000newcaseseachyear42,000hospitalisationsin2004-2005Accountsfor0.8%ofallhospitalisationsinthecountry,Age-relatedprevalenceofCHF,AmericanNationalHFproject34,587hospitalizedpatients,Age(median,yrs)73Gender(female,%)59%History(%)hypertension61%coronaryarterydisease56%diabetes38%COPD33%atrialfibrillation30%HavranekEPetal.AmHeartJ2002;143:412-417,ClassificationofCHF,SystolicCHFWeakenedabilityoftheventriclestocontractHeartfailurewithpreservedsystolicfunctionImpaireddiastolicfillingoftheleftventricle,resultinginhighfillingpressure,withorwithoutsystolicdysfunctionAccounts40%ofallCHF,ManagementofCHF,LifestylechangesPharmacologicalSurgicalDevicesCABG,PCICardiactransplantation,Drugtherapy,STEP1Confirmleftventricularsystolicdysfunction(LVSD)byEchocardiographyRadionuclideventriculography,orRadiologicalleftventricularangiography,Drugtherapy,STEP2Initiatefirst-linetherapyinallpatientswithheartfailureduetoLVSDwithadiureticandanACEinhibitorforNYHAclassI-IV,andabeta-blockerforNYHAclassII-III,unlessthesearecontra-indicated,Drugtherapy,STEP3Initiatesecond-linetherapyinpatientswithpersistentsignsandsymptomsofheartfailure(NYHAclassIII/IV)withspironolactoneanddigoxinInitiatespironolactonefirstfollowedbydigoxin,bothatalowdoseandthenup-titrate,checktolerabilityandbloodchemistry.,Co-operativeNorthScandinavianEnalaprilSurvivalStudyICONSENSUSINEnglJMed1987;316:14291435,StudiesofLeftVentricularDysfunctionSOLVD(TreatmentStudy)SOLVDInvestigatorsNEnglJMed1991;325:293302,NEnglJMed2003;349:18931906,VALIANT:Results,NEnglJMed2003;349:18931906,VALIANT:Adverseevents,UnitedStatesCarvedilolProgram(USCP)PackerMetal.NEnglJMed1996;334:13491355,CardiacInsufficiencyBisoprololStudyII(CIBISII)CIBISIIInvestigators,Lancet1999;359:913,MetoprololCR/XLRandomizedInterventionTrialinCongestiveHeartFailure(MERIT-HF)HjalmarsonAetal.Lancet1999;353:20012007,Remme,W.J.etal.JAmCollCardiol2007;49:963-971,CombinedEndPointofanyMI,UnstableAngina,andStroke,Remme,W.J.etal.JAmCollCardiol2007;49:963-971,DeathAfteraNonfatalMyocardialInfarctionorNonfatalStroke,CCBs:NHFrecommendations,AmlodipineandfelodipinecanbeusedtotreatcomorbiditiessuchashypertensionandCHDinpatientswithsystolicCHFTheyhavebeenshowntoneitherincreasenordecreasemortality.Non-dihydropyridinecalcium-channelblockerssuchasverapamilanddiltiazemarecontraindicatedinpatientswithsystolicheartfailure,Electromechanicaldysfunction,Definedasanyabnormalityinthegenerationortransmissionofelectricalimpulsesthatresultsinclinicallysignificantalterationinthemechanicalfunctionoftheheart,65-year-oldmale,LBBB,LVEF20%,Cardiacresynchronizationtherapy(biventricularpacing),inappropriatelyselectedpatients:improvessymptomsimprovesexerciseperformanceimprovesQOLimproveslong-termmorbidity7:212.,TABLE2.RiskofSuddenCardiacDeath,RiskofSuddenCardiacDeath,SaxonLAetal.Circulation.2006;114:2766-72.,IndicationsforCRTNYHAIII-IV,despiteoptimalmedicaltherapyDilatedheartfailurewithEF120msSinusrhythm,FuturedirectionsCell-BasedTherapiesEmbryonicstemcellsBonemarrowcells(containsstemcellsandprogenitorcells)Circulatingblood-derivedprogenitorcells(EPCs),Cell-BasedTherapiesSeveralsmalltrialsdemonstratedimprovementofLVfunctionChallengesCurrentstudiesaretoosmalltoassessclinicaloutcomesMethodofpreparationanddeliveryuncertainThebesttypeofcellstouseisstillunclear,GeneTherapyMajorchallengesDevelopmentofanidealvector(e.g.adenovirus)AmethodofdeliveryofthesevectorsIdentificationofappropriategenetargets,e.g.cardiacS100A1,acalciumbindinggene,andsarcoplasmicreticularCa2+gene,MechanicalassistanceCardiactransplantationwillalwaysbelimitedtheavailabilityofdonorheartsVentricularassistdevices(VADs)MainlyusedasbridgestotransplantationAsdestinationtherapy?REMATCHtrial:encouragingbutthedevicewastoolargewithmanycomplications,Ventricularassistdevices(VADs)CurrenteffortReducetheincidenceofcomplicationsandsizeofthedeviceIndicationsforVADsareexpectedtoexpandquicklyinthenextfiveyearstoprovidedestinationtherapy,ConclusionsThefieldofHFstudyisnowatahistoricjunctureThepandemicofHFisincreasingrapidlybecauseoftheagingpopulationandincreasednumberofsurvivalpatientsfollowingMIStudiesonpreventionandmanagementofHFisaccelerating,Conclusions(continued)Advancesingenetics,cellbiologyandmolecularpharmacologywillenhanceunderstandingofthecausesofHFCurrentlyusedACEI,beta-blockersandCRThaveclearbenefitstoclinicaloutcomesofHFDevelopmentinbioengineeringcouldhaveanenormousbeneficialimpactonbothincidenceandmanagement,Chronicheartfailure(CHF),Definitionacomplexclinicalsyndromewithtypicalclinicalsymptomsthatcanoccuratrestoroneffort,andischaracterisedbyobjectiveevidenceofanunderlyingstructuralabnormalityorcardiacdysfunctionthatimpairstheventricletofillwithorejectbloodThetermcongestiveheartfailureisnolongerused.,MADIT-II,MossAJ.NEnglJMed.2002;346:877-83.,Defibrillator,Conventional,P=0.007,1.0,0.9,0.8,0.7,0.6,0.0,ProbabilityofS