心力衰竭管理发展历程课件

ManagementofHeartFailure:Past,PresentandFutureLexinWang,M.D.,Ph.D.,FCSANZProfessorofClinicalPharmacologyHead,CardiovascularResearch.ManagementofHeartFailure:P1Objectives

HistoryandpathogenesisEpidemiologyandriskfactorsCurrentmanagementFuturedirections.Objectives

Historyandpathoge2Katz,A.M.CircHeartFail2008;1:63-71WilliamHarvey,1628.Katz,A.M.CircHeartFail203

Changingviewsofheartfailure1.Aclinicalsyndrome2.Acirculatorydisorder3.Alteredarchitectureoftheheart4.Abnormalhemodynamics5.Disorderedfluidbalance6.Biochemicalabnormalities7.Maladaptivehypertrophy8.Genomics9.Epigenetics(实验胚胎学).

Changingviewsofheartfailu4Katz,A.M.CircHeartFail2008;1:63-71Changingmanagementofheartfailureoverthepast40years.Katz,A.M.CircHeartFail205CHF-PrevalenceApproximately5.5millionAmericanshaveCHF(2.2%ofthepopulation)550,000newcasesannuallyAccountsfor12millionclinicvisitsperyearEstimatedhealthcarecostsin2004isUS$28.8billion.CHF-PrevalenceApproximately5.6CHFprevalence-Australia2%ofadultpopulationApproximately241,000patients30,000newcaseseachyear42,000hospitalisationsin2004-2005Accountsfor0.8%ofallhospitalisationsinthecountry.CHFprevalence-Australia2%of7Age-relatedprevalenceofCHF

.Age-relatedprevalenceofCHF8..9AmericanNationalHFproject34,587hospitalizedpatientsAge(median,yrs) 73Gender(female,%) 59%History(%) hypertension 61% coronaryarterydisease 56% diabetes 38% COPD 33% atrialfibrillation 30%

HavranekEPetal.AmHeartJ2002;143:412-417.AmericanNationalHFproject310ClassificationofCHFSystolicCHFWeakenedabilityoftheventriclestocontractHeartfailurewithpreservedsystolicfunctionImpaireddiastolicfillingoftheleftventricle,resultinginhighfillingpressure,withorwithoutsystolicdysfunctionAccounts40%ofallCHF.ClassificationofCHFSystolic11ManagementofCHF

LifestylechangesPharmacologicalSurgicalDevicesCABG,PCICardiactransplantation.ManagementofCHF

Lifestylec12DrugtherapySTEP1Confirmleftventricularsystolicdysfunction(LVSD)byEchocardiographyRadionuclideventriculography,orRadiologicalleftventricularangiography.DrugtherapySTEP1.13DrugtherapySTEP2Initiatefirst-linetherapyinallpatientswithheartfailureduetoLVSDwithadiureticandanACEinhibitorforNYHAclassI-IV,andabeta-blockerforNYHAclassII-III,unlessthesearecontra-indicated.DrugtherapySTEP2.14DrugtherapySTEP3Initiatesecond-linetherapyinpatientswithpersistentsignsandsymptomsofheartfailure(NYHAclassIII/IV)withspironolactoneanddigoxinInitiatespironolactonefirstfollowedbydigoxin,bothatalowdoseandthenup-titrate,checktolerabilityandbloodchemistry..DrugtherapySTEP3.15Co-operativeNorthScandinavianEnalaprilSurvivalStudyI–CONSENSUSINEnglJMed1987;316:1429–1435

.Co-operativeNorthScandinavia16StudiesofLeftVentricularDysfunction–SOLVD(TreatmentStudy)SOLVDInvestigatorsNEnglJMed1991;325:293–302

.StudiesofLeftVentricularDy17NEnglJMed2003;349:1893–1906VALIANT:Results.NEnglJMed2003;349:1893–118NEnglJMed2003;349:1893–1906VALIANT:Adverseevents.NEnglJMed2003;349:1893–119UnitedStatesCarvedilolProgram(USCP)

PackerMetal.NEnglJMed1996;334:1349–1355

.UnitedStatesCarvedilolProgr20CardiacInsufficiencyBisoprololStudyII(CIBISII)CIBISIIInvestigators,Lancet1999;359:9–13

.CardiacInsufficiencyBisoprol21

MetoprololCR/XLRandomizedInterventionTrialinCongestiveHeartFailure(MERIT-HF)HjalmarsonAetal.Lancet1999;353:2001–2007.

MetoprololCR/XLRandomized22Remme,W.J.etal.JAmCollCardiol2007;49:963-971CombinedEndPointofanyMI,UnstableAngina,andStroke.Remme,W.J.etal.JAmColl23Remme,W.J.etal.JAmCollCardiol2007;49:963-971DeathAfteraNonfatalMyocardialInfarctionorNonfatalStroke.Remme,W.J.etal.JAmColl24CCBs:NHFrecommendationsAmlodipineandfelodipinecanbeusedtotreatcomorbiditiessuchashypertensionandCHDinpatientswithsystolicCHFTheyhavebeenshowntoneitherincreasenordecreasemortality.Non-dihydropyridinecalcium-channelblockerssuchasverapamilanddiltiazemarecontraindicatedinpatientswithsystolicheartfailure.CCBs:NHFrecommendationsAmlod25ElectromechanicaldysfunctionDefinedasanyabnormalityinthegenerationortransmissionofelectricalimpulsesthatresultsinclinicallysignificantalterationinthemechanicalfunctionoftheheart65-year-oldmale,LBBB,LVEF<20%.ElectromechanicaldysfunctionD26Cardiacresynchronizationtherapy

(biventricularpacing)in

appropriatelyselectedpatients:improvessymptomsimprovesexerciseperformanceimprovesQOLimproveslong-termmorbidity&mortalityWangLX.ExpClinCardiol2003;7:212..Cardiacresynchronizationther27VariableSuddenCardiacDeath(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

RiskofSuddenCardiacDeathSaxonLAetal.Circulation.2006;114:2766-72..VariableSuddenCardiacDeath28IndicationsforCRTNYHAIII-IV,despiteoptimalmedicaltherapyDilatedheartfailurewithEF<35%QRSduration>120msSinusrhythm.IndicationsforCRT.29FuturedirectionsCell-BasedTherapiesEmbryonicstemcellsBonemarrowcells(containsstemcellsandprogenitorcells)Circulatingblood-derivedprogenitorcells(EPCs).Futuredirections.30Cell-BasedTherapiesSeveralsmalltrialsdemonstratedimprovementofLVfunctionChallengesCurrentstudiesaretoosmalltoassessclinicaloutcomesMethodofpreparationanddeliveryuncertainThebesttypeofcellstouseisstillunclear.Cell-BasedTherapies.31GeneTherapyMajorchallengesDevelopmentofanidealvector(e.g.adenovirus)AmethodofdeliveryofthesevectorsIdentificationofappropriategenetargets,e.g.cardiacS100A1,acalciumbindinggene,andsarcoplasmicreticularCa2+gene.GeneTherapy.32MechanicalassistanceCardiactransplantationwillalwaysbelimitedtheavailabilityofdonorheartsVentricularassistdevices(VADs)MainlyusedasbridgestotransplantationAsdestinationtherapy?REMATCHtrial:encouragingbutthedevicewastoolargewithmanycomplications.Mechanicalassistance.33Ventricularassistdevices(VADs)CurrenteffortReducetheincidenceofcomplicationsandsizeofthedeviceIndicationsforVADsareexpectedtoexpandquicklyinthenextfiveyearstoprovidedestinationtherapy.Ventricularassistdevices(VA34ConclusionsThefieldofHFstudyisnowatahistoricjunctureThepandemicofHFisincreasingrapidlybecauseoftheagingpopulationandincreasednumberofsurvivalpatientsfollowingMIStudiesonpreventionandmanagementofHFisaccelerating.Conclusions.35Conclusions(continued)Advancesingenetics,cellbiologyandmolecularpharmacologywillenhanceunderstandingofthecausesofHFCurrentlyusedACEI,beta-blockersandCRThaveclearbenefitstoclinicaloutcomesofHFDevelopmentinbioengineeringcouldhaveanenormousbeneficialimpactonbothincidenceandmanagement.Conclusions(continued).36..37Chronicheartfailure(CHF)Definitionacomplexclinicalsyndromewithtypicalclinicalsymptomsthatcanoccuratrestoroneffort,andischaracterisedbyobjectiveevidenceofanunderlyingstructuralabnormalityorcardiacdysfunctionthatimpairstheventricletofillwithorejectbloodThetermcongestiveheartfailureisnolongerused..Chronicheartfailure(CHF)Def38MADIT-IIMossAJ.NEnglJMed.2002;346:877-83.DefibrillatorConventionalP=0.0071.00.90.80.70.60.0ProbabilityofSurvival01234YearNo.AtRiskDefibrillator 742 502(0.91) 274(0.94) 110(0.78) 9Conventional 490 329(0.90) 170(0.78) 65(0.69) 3.MADIT-IIMossAJ.NEnglJMed.39Non-pharmacologicalPhysicalactivitytailoredtoindividualsWalkSlowwalkingathome10-30minaday,7daysaweekClassIVpatientsrequiregentlemobilisationassymptomsallowBedrestforthosewithacutedeteriorationofsymptoms.Non-pharmacological.40Non-pharmacologicalSodiumrestriction <3gsodium/dayNomorethan2LfluidintakeperdayDailyweighingWeightvariationshouldbe<2kgintwoconsecutivedays.Non-pharmacological.41Katz,A.M.CircHeartFail2008;1:63-71Twoviewsofthecirculation.Katz,A.M.CircHeartFail2042Starlingcurve.Starlingcurve.43Katz,A.M.CircHeartFail2008;1:63-71Proliferativesignalingpathwaysthatmediatecardiachypertrophy.Katz,A.M.CircHeartFail2044..45..46ManagementofHeartFailure:Past,PresentandFutureLexinWang,M.D.,Ph.D.,FCSANZProfessorofClinicalPharmacologyHead,CardiovascularResearch.ManagementofHeartFailure:P47Objectives

HistoryandpathogenesisEpidemiologyandriskfactorsCurrentmanagementFuturedirections.Objectives

Historyandpathoge48Katz,A.M.CircHeartFail2008;1:63-71WilliamHarvey,1628.Katz,A.M.CircHeartFail2049

Changingviewsofheartfailure1.Aclinicalsyndrome2.Acirculatorydisorder3.Alteredarchitectureoftheheart4.Abnormalhemodynamics5.Disorderedfluidbalance6.Biochemicalabnormalities7.Maladaptivehypertrophy8.Genomics9.Epigenetics(实验胚胎学).

Changingviewsofheartfailu50Katz,A.M.CircHeartFail2008;1:63-71Changingmanagementofheartfailureoverthepast40years.Katz,A.M.CircHeartFail2051CHF-PrevalenceApproximately5.5millionAmericanshaveCHF(2.2%ofthepopulation)550,000newcasesannuallyAccountsfor12millionclinicvisitsperyearEstimatedhealthcarecostsin2004isUS$28.8billion.CHF-PrevalenceApproximately5.52CHFprevalence-Australia2%ofadultpopulationApproximately241,000patients30,000newcaseseachyear42,000hospitalisationsin2004-2005Accountsfor0.8%ofallhospitalisationsinthecountry.CHFprevalence-Australia2%of53Age-relatedprevalenceofCHF

.Age-relatedprevalenceofCHF54..55AmericanNationalHFproject34,587hospitalizedpatientsAge(median,yrs) 73Gender(female,%) 59%History(%) hypertension 61% coronaryarterydisease 56% diabetes 38% COPD 33% atrialfibrillation 30%

HavranekEPetal.AmHeartJ2002;143:412-417.AmericanNationalHFproject356ClassificationofCHFSystolicCHFWeakenedabilityoftheventriclestocontractHeartfailurewithpreservedsystolicfunctionImpaireddiastolicfillingoftheleftventricle,resultinginhighfillingpressure,withorwithoutsystolicdysfunctionAccounts40%ofallCHF.ClassificationofCHFSystolic57ManagementofCHF

LifestylechangesPharmacologicalSurgicalDevicesCABG,PCICardiactransplantation.ManagementofCHF

Lifestylec58DrugtherapySTEP1Confirmleftventricularsystolicdysfunction(LVSD)byEchocardiographyRadionuclideventriculography,orRadiologicalleftventricularangiography.DrugtherapySTEP1.59DrugtherapySTEP2Initiatefirst-linetherapyinallpatientswithheartfailureduetoLVSDwithadiureticandanACEinhibitorforNYHAclassI-IV,andabeta-blockerforNYHAclassII-III,unlessthesearecontra-indicated.DrugtherapySTEP2.60DrugtherapySTEP3Initiatesecond-linetherapyinpatientswithpersistentsignsandsymptomsofheartfailure(NYHAclassIII/IV)withspironolactoneanddigoxinInitiatespironolactonefirstfollowedbydigoxin,bothatalowdoseandthenup-titrate,checktolerabilityandbloodchemistry..DrugtherapySTEP3.61Co-operativeNorthScandinavianEnalaprilSurvivalStudyI–CONSENSUSINEnglJMed1987;316:1429–1435

.Co-operativeNorthScandinavia62StudiesofLeftVentricularDysfunction–SOLVD(TreatmentStudy)SOLVDInvestigatorsNEnglJMed1991;325:293–302

.StudiesofLeftVentricularDy63NEnglJMed2003;349:1893–1906VALIANT:Results.NEnglJMed2003;349:1893–164NEnglJMed2003;349:1893–1906VALIANT:Adverseevents.NEnglJMed2003;349:1893–165UnitedStatesCarvedilolProgram(USCP)

PackerMetal.NEnglJMed1996;334:1349–1355

.UnitedStatesCarvedilolProgr66CardiacInsufficiencyBisoprololStudyII(CIBISII)CIBISIIInvestigators,Lancet1999;359:9–13

.CardiacInsufficiencyBisoprol67

MetoprololCR/XLRandomizedInterventionTrialinCongestiveHeartFailure(MERIT-HF)HjalmarsonAetal.Lancet1999;353:2001–2007.

MetoprololCR/XLRandomized68Remme,W.J.etal.JAmCollCardiol2007;49:963-971CombinedEndPointofanyMI,UnstableAngina,andStroke.Remme,W.J.etal.JAmColl69Remme,W.J.etal.JAmCollCardiol2007;49:963-971DeathAfteraNonfatalMyocardialInfarctionorNonfatalStroke.Remme,W.J.etal.JAmColl70CCBs:NHFrecommendationsAmlodipineandfelodipinecanbeusedtotreatcomorbiditiessuchashypertensionandCHDinpatientswithsystolicCHFTheyhavebeenshowntoneitherincreasenordecreasemortality.Non-dihydropyridinecalcium-channelblockerssuchasverapamilanddiltiazemarecontraindicatedinpatientswithsystolicheartfailure.CCBs:NHFrecommendationsAmlod71ElectromechanicaldysfunctionDefinedasanyabnormalityinthegenerationortransmissionofelectricalimpulsesthatresultsinclinicallysignificantalterationinthemechanicalfunctionoftheheart65-year-oldmale,LBBB,LVEF<20%.ElectromechanicaldysfunctionD72Cardiacresynchronizationtherapy

(biventricularpacing)in

appropriatelyselectedpatients:improvessymptomsimprovesexerciseperformanceimprovesQOLimproveslong-termmorbidity&mortalityWangLX.ExpClinCardiol2003;7:212..Cardiacresynchronizationther73VariableSuddenCardiacDeath(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

RiskofSuddenCardiacDeathSaxonLAetal.Circulation.2006;114:2766-72..VariableSuddenCardiacDeath74IndicationsforCRTNYHAIII-IV,despiteoptimalmedicaltherapyDilatedheartfailurewithEF<35%QRSduration>120msSinusrhythm.IndicationsforCRT.75FuturedirectionsCell-BasedTherapiesEmbryonicstemcellsBonemarrowcells(containsstemcellsandprogenitorcells)Circulatingblood-derivedprogenitorcells(EPCs).Futuredirections.76Cell-BasedTherapiesSeveralsmalltrialsdemonstratedimprovementofLVfunctionChallengesCurrentstudiesaretoosmalltoassessclinicaloutcomesMethodofpreparationanddeliveryuncertainThebesttypeofcellstouseisstillunclear.Cell-BasedTherapies.77GeneTherapyMajorchallengesDevelopmentofanidealvector(e.g.adenovirus)AmethodofdeliveryofthesevectorsIdentificationofappropriategenetargets,e.g.cardiacS100A1,acalciumbindinggene,andsarcoplasmicreticularCa2+gene.GeneTherapy.78MechanicalassistanceCardiactransplantationwillalwaysbelimitedtheavailabilityofdonorheartsVentricularassistdevices(VADs)MainlyusedasbridgestotransplantationAsdestinationtherapy?REMATCHtrial:encouragingbutthedevicewastoolargewithmanycomplications.Mechanicalassistance.79Ventricularassistdevices(VADs)CurrenteffortReducetheincidenceofcomplicationsandsizeofthedeviceIndicationsforVADsareexpectedtoexpandquicklyinthenextfiveyearstoprovidedestinationtherapy.Ventricularassistdevices(VA80ConclusionsThefieldofHFstudyisnowatahistoricjunctureThepandemicofHFisincreasingrapidlybecauseoftheagingpopulationandincreasednumberofsurvivalpatientsfollowingMIStudiesonpreventionandmanagementofHFisacc