心力衰竭管理发展历程

ManagementofHeartFailure:Past,PresentandFutureLexinWang,M.D.,Ph.D.,FCSANZProfessorofClinicalPharmacologyHead,CardiovascularResearchHistoryandpathogenesis01Futuredirections04Epidemiologyandriskfactors02Currentmanagement03ObjectivesWilliamHarvey,1628

Changingviewsofheartfailure1.Aclinicalsyndrome2.Acirculatorydisorder3.Alteredarchitectureoftheheart4.Abnormalhemodynamics5.Disorderedfluidbalance6.Biochemicalabnormalities7.Maladaptivehypertrophy8.Genomics9.Epigenetics(实验胚胎学)Katz,A.M.CircHeartFail2008;1:63-71Changingmanagementofheartfailureoverthepast40yearsApproximately5.5millionAmericanshaveCHF(2.2%ofthepopulation)550,000newcasesannuallyAccountsfor12millionclinicvisitsperyearEstimatedhealthcarecostsin2004isUS$28.8billionCHF-PrevalenceCHFprevalence-Australia2%ofadultpopulationApproximately241,000patients30,000newcaseseachyear42,000hospitalisationsin2004-2005Accountsfor0.8%ofallhospitalisationsinthecountryAge-relatedprevalenceofCHFAmericanNationalHFproject34,587hospitalizedpatientsAge(median,yrs) 73Gender(female,%) 59%History(%) hypertension 61% coronaryarterydisease 56% diabetes 38% COPD 33% atrialfibrillation 30%

HavranekEPetal.AmHeartJ2002;143:412-417ClassificationofCHFSystolicCHFWeakenedabilityoftheventriclestocontractHeartfailurewithpreservedsystolicfunctionImpaireddiastolicfillingoftheleftventricle,resultinginhighfillingpressure,withorwithoutsystolicdysfunctionAccounts40%ofallCHFLifestylechangesPharmacologicalSurgicalDevicesCABG,PCICardiactransplantationManagementofCHFDrugtherapySTEP1Confirmleftventricularsystolicdysfunction(LVSD)byEchocardiographyRadionuclideventriculography,orRadiologicalleftventricularangiographySTEP2Initiatefirst-linetherapyinallpatientswithheartfailureduetoLVSDwithadiureticandanACEinhibitorforNYHAclassI-IV,andabeta-blockerforNYHAclassII-III,unlessthesearecontra-indicatedDrugtherapySTEP3Initiatesecond-linetherapyinpatientswithpersistentsignsandsymptomsofheartfailure(NYHAclassIII/IV)withspironolactoneanddigoxinInitiatespironolactonefirstfollowedbydigoxin,bothatalowdoseandthenup-titrate,checktolerabilityandbloodchemistry.DrugtherapyCo-operativeNorthScandinavianEnalaprilSurvivalStudyI–CONSENSUSINEnglJMed1987;316:1429–1435StudiesofLeftVentricularDysfunction–SOLVD(TreatmentStudy)SOLVDInvestigatorsNEnglJMed1991;325:293–302VALIANT:ResultsNEnglJMed2003;349:1893–1906VALIANT:AdverseeventsUnitedStatesCarvedilolProgram(USCP)PackerMetal.NEnglJMed1996;334:1349–1355CardiacInsufficiencyBisoprololStudyII(CIBISII)CIBISIIInvestigators,Lancet1999;359:9–13MetoprololCR/XLRandomizedInterventionTrialinCongestiveHeartFailure(MERIT-HF)HjalmarsonAetal.Lancet1999;353:2001–2007CombinedEndPointofanyMI,UnstableAngina,andStrokeDeathAfteraNonfatalMyocardialInfarctionorNonfatalStrokeCCBs:NHFrecommendationsAmlodipineandfelodipinecanbeusedtotreatcomorbiditiessuchashypertensionandCHDinpatientswithsystolicCHFTheyhavebeenshowntoneitherincreasenordecreasemortality.Non-dihydropyridinecalcium-channelblockerssuchasverapamilanddiltiazemarecontraindicatedinpatientswithsystolicheartfailure0102ElectromechanicaldysfunctionDefinedasanyabnormalityinthegenerationortransmissionofelectricalimpulsesthatresultsinclinicallysignificantalterationinthemechanicalfunctionoftheheart65-year-oldmale,LBBB,LVEF<20%Cardiacresynchronizationtherapy

(biventricularpacing)in

appropriatelyselectedpatients:improvessymptomsimprovesexerciseperformanceimprovesQOLimproveslong-termmorbidity&mortalityWangLX.ExpClinCardiol2003;7:212.VariableSuddenCardiacDeath(n=83/1519)HazardRatioPValue95%CICRT-D0.470.02(0.24to0.91)CRT1.210.48(0.71to2.09)LVEF>20%0.550.01(0.35to0.87)QRS>160ms0.630.05(0.40to0.997)Femalegender0.47<0.01(0.27to0.82)NYHAclassIV2.62<0.01(1.61to4.26)Renaldysfunction1.690.03(1.06to2.69)TABLE2.RiskofSuddenCardiacDeath

RiskofSuddenCardiacDeathIndicationsforCRTNYHAIII-IV,despiteoptimalmedicaltherapyDilatedheartfailurewithEF<35%QRSduration>120msSinusrhythmFuturedirectionsCell-BasedTherapiesEmbryonicstemcellsBonemarrowcells(containsstemcellsandprogenitorcells)Circulatingblood-derivedprogenitorcells(EPCs)Cell-BasedTherapiesSeveralsmalltrialsdemonstratedimprovementofLVfunctionChallengesCurrentstudiesaretoosmalltoassessclinicaloutcomesMethodofpreparationanddeliveryuncertainThebesttypeofcellstouseisstillunclearGeneTherapyMajorchallengesDevelopmentofanidealvector(e.g.adenovirus)AmethodofdeliveryofthesevectorsIdentificationofappropriategenetargets,e.g.cardiacS100A1,acalciumbindinggene,andsarcoplasmicreticularCa2+geneMechanicalassistanceCardiactransplantationwillalwaysbelimitedtheavailabilityofdonorheartsVentricularassistdevices(VADs)MainlyusedasbridgestotransplantationAsdestinationtherapy?REMATCHtrial:encouragingbutthedevicewastoolargewithmanycomplicationsVentricularassistdevices(VADs)CurrenteffortReducetheincidenceofcomplicationsandsizeofthedeviceIndicationsforVADsareexpectedtoexpandquicklyinthenextfiveyearstoprovidedestinationtherapyThefieldofHFstudyisnowatahistoricjunctureThepandemicofHFisincreasingrapidlybecauseoftheagingpopulationandincreasednumberofsurvivalpatientsfollowingMIStudiesonpreventionandmanagementofHFisaccelerating010302ConclusionsConclusions(continued)Advancesingenetics,cellbiologyandmolecularpharmacologywillenhanceunderstandingofthecausesofHFCurrentlyusedACEI,beta-blockersandCRThaveclearbenefitstoclinicaloutcomesofHFDevelopmentinbioengineeringcouldhaveanenormousbeneficialimpactonbothincidenceandmanagementChronicheartfailure(CHF)acomplexclinicalsyndromewithtypicalclinicalsymptomsthatcanoccuratrestoroneffort,andischaracterisedbyobjectiveevidenceofanunderlyingstructuralabnormalityorcardiacdysfunctionthatimpairstheventricletofillwithorejectbloodThetermcongestiveheartfailureisnolongerused.DefinitionMADIT-IIMossAJ.NEnglJMed.2002;346