心衰處理入門

A,B,C,D,Esofthe

ManagementofHeartFailureNanetteKassWenger,MD

EmoryUniversitySchoolofMedicine

GradyMemorialHospital

Atlanta,Georgia9/981ObjectivesUnderstandthecornerstonesoftherapyangiotensin-convertingenzymeinhibitors,diuretics,anddigitalisreviewtheroleofothertherapies:pharmacotherapeuticaswellasnonpharmacotherapeuticapproaches9/982Epidemiology4.7millionpatientsintheUnitedStatesareestimatedtohaveheartfailure470,000newcasesrecognizedannuallyEachyear,875,000hospitalizedpatientshaveaprimarydiagnosisofheartfailure.ItisthemajorhospitaldischargediagnosisforpatientsintheMedicareagegroup.9/983Epidemiologyheartfailureincreaseswithagehalfofallheartfailurehospitalizationsoccurinindividuals>age65years.IntheUnitedStates,theestimatedcostsforthemanagementofpatientswithheartfailureexceed$10billionannually.9/984TreatmentobjectivesDecreasesymptomsImproveexercisecapacityEnhancequalityoflifeDecreasemorbidityRetardtheprogressionofheartfailureImprovesurvival9/985CornerstonesofTherapyAngiotensinconvertingenzyme(ACE)inhibitorsdiureticsdigitalisguidelinesfortheseverity-basedtherapyofheartfailure.9/986AsymptomaticPatients

Forasymptomaticpatientswithleftventriculardysfunction(NYHAclassI),typicallythosewithanejectionfractionbelow40%,

ACEinhibitorsarerecommended

9/987SymptomaticPatientsNYHAclassIIACEinhibitors,milddiuretics,anddigoxin,withorwithouttheuseofB-blockertherapyNYHAclassIIIaddloopdiureticsNYHAclassIVconsiderpositiveinotropicagentssurgicaltherapiesmayalsobeapplied9/988A,B,C,D,EsofHeartFailureTherapyA

angiotensinconvertingenzymeinhibitors

anticoagulants,amiodarone,AICD,assist

devicesB

betablockingdrugsC

calciumchannelblockingdrugs,coronary

revascularization,cardiactransplant,

cardiomyoplasty,cardiacreductionsurgeryD

diet,diuretics,digitalis,dobutamineE

exercise

9/989AngiotensinConvertingInhibitorsphysiologicbenefits

ArteriovenousVasodilatationpulmonaryarterialdiastolicpressurepulmonarycapillarywedgepressureleftventricularend-diastolicpressuresystemicvascularresistancesystemicbloodpressuremaximaloxygenuptake(MVO2)9/9810AngiotensinConvertingInhibitors

physiologicbenefits

LVfunctionandcardiacoutputrenal,coronary,cerebralbloodflowNochangeinheartrateormyocardialcontractilitynoneurohormonalactivationresultantdiuresisandnatriuresis9/9811AngiotensinConvertingInhibitors

clinicalbenefits

IncreasesexercisecapacityimprovesfunctionalclassattenuationofLVremodelingpostMIdecreaseintheprogressionofchronicHFdecreasedhospitalizationenhancedqualityoflifeimprovedsurvival9/9812AsymptomaticPatientsEnalopril

SOLVDPreventionTrial

EF<35%

HFprogression,hospitalizationCaptopril SAVE,GISSI-3,ISIS-4

PostMI,EF<40%

overallmortality,re-infarction

hospitalization,HFprogression9/9813SymptomaticPatientsHydralazine+Isosorbidedinitrate

VHeFT-I

mortality,improvedfunctionalclass

ascomparedwithuseofdigoxinanddiuretics

VHeFT-II

provedlesseffectivethanenalopril

9/9814SymptomaticPatientsEnalopril+digoxin+diuretics

SOLVDTreatmentTrial

EF<35%,FCIII-IV

mortality,hospitalization

CONSENSUS-II

FCIV

mortality(40%),symptoms,hospitalization

improvedfunctionalclass9/9815SymptomaticPatientsLosartan(AT-IIinhibitor)

ELITETrial

losartanimprovedthesurvivalofelderlyheartfailurepatientstreatedcomparedwithcaptopriltherapy9/9816GuidelinestoACEInhibitorTherapyContraindicationsRenalarterystenosisRenalinsufficiency(relative)HyperkalemiaArterialhypotensionCoughAngioedemaAlternativesHydralazine+ISDN,AT-IIinhibitor9/9817GuidelinestoACEInhibitorTherapyItisimportanttotitratetothedosageregimenusedintheclinicaltrials…intheabsenceofsymptomsoradverseeffectsonend-organperfusioninverysevereheartfailure,hydralazineandnitratesaddedtoACEinhibitortherapycanfurtherimprovecardiacoutput9/9818AnticoagulantTherapyRecommendedforpatientswithNYHAIII-IVandEF<30%orventricularaneurysmorverydilatedLVIndicatedforpatientswithheartfailurewhohaveatrialfibrillation,apriorembolicepisode,identifiedintracardiacthrombus,leftventricularaneurysm,thrombophlebitis,orprolongedbedresttitrateINRto2to39/9819Arrhythmias

Suddendeathoccursinabout50%ofpatientswithheartfailure9/9820AmiodaroneRandomizedclinicaltrialsCHF-STAT

NYHAII-IIIpatientswithischemiccardiomyopathy-amiodaronehadnoaffectonsurvivalGESICA

NYHAIII-IVpatientswithmorenon-ischemiccardiomyopathy-openlabeledamiodaronedecreasedmortality9/9821AICDRandomizedclinicaltrialsAVID

amiodaronevsimplantabledefibrillator

showedtheAICDgrouphadlowermortalityAICDshouldbeconsideredforpatientswithventricularfibrillationorpriorsuddendeathBeta-blockersoramiodaronemaybeappropriateforpatientswithsustainedVT,withorwithoutsymptoms9/9822AssistDevicesabridgetocardiactransplantationcandidatesmustmeettheinclusionandexclusioncriteriaforcardiactransplantation9/9823-blockingDrugsPhysiologicbenefitsincreasethedensityof-1receptorsinhibitcatecholaminetoxicitydecreaseneurohormonalactivationdecreaseheartrateprovideantihypertensive,antianginal,andantiarrhythmiceffectsantioxidantandantiproliferativeeffects9/9824-blockingDrugsClinicalbenefitsdecreasesymptomsofHFimproveleftventricularfunctionimproveexercisetolerance9/9825-blockingDrugs-ClinicalTrialsBHAT(-BlockerHeartAttackTrial)propranololdecreasedcardiovascularmortality,suddendeath,andreinfarctioninpost-MIpatientsbenefitisgreatestinpatientswhoalsohadleftventriculardysfunction9/9826-blockingDrugs-ClinicalTrialsSAVE(SurvivalandVentricularEnlargement)post-MIpatientswithanEF<40%-blockersreducedmortalitybothintheACEinhibitorandtheplacebogrouplowestmortalityoccurredinpatientsreceivingbothACEand-blockingtherapy9/9827-blockingDrugs-ClinicalTrialsMDC(MetoprololinDilatedCardiomyopathy)NYHAII-IIIwithdilatedcardiomyopathynodecreaseinmortalitysignificantdecreaseinsymptomssignificantincreaseinexercisetolerance,LVejectionfraction,qualityoflife9/9828-blockingDrugs-ClinicalTrialsMOCHA(MulticenterOralCarvedilolHeartFailureAssessmentTrial)NYHAII-IIIheartfailurequadrupletherapy(+ACE,diuretic,digoxin)49%decreaseinthecombinedendpointsofmortalityandhospitalizationnoimprovementsinexercisetolerance9/9829-blockingDrugs-ClinicalTrialsPRECISE

(ProspectiveRandomizedEvaluationofCarvedilolonSymptomsandExercise)decreaseinmortalityfrom8%to3%40%decreaseinhospitalizationdecreaseinsymptomsimprovementinLVejectionfractionnoaffectonexercisetolerance9/9830CalciumChannelBlockingDrugsPotentialbenefit:anti-ischemicandvasodilatoryeffectsAdverseeffect:

negativeinotropicpropertiesMDPIT/SPRINTtrialsdiltiazem,verapamil,andnifedipinearenotrecommendedforpatientswithHF9/9831CalciumChannelBlockingDrugsPRAISE-1

(ProspectiveRandomizedAmlodipineSurvivalEvaluation)NYHAIII-IVheartfailureACE,digoxin,diuretics±amlodipinenochangeintotalmortality

nosurvivalbenefitinischemics

improvedsurvivalinnon-ischemicsnochangeinexercisetolerance9/9832CoronaryRevascularization80%ofpatientswithheartfailurehavecoronarydiseasePatientsshouldbeevaluatedforthepresenceofmyocardialischemiaandthepotentialbenefitofrevacularizationSurvivalwasimprovedbyrevascularizationcomparedwithmedicaltherapy,evenintheabsenceofanginapectoris(Dukedatabase)9/9833CardiacTransplantationSurvivalof60%-90%at1-yr,70%at5-yrInclusionCriteria:mustfirstexcluderemediablemyocardialischemiaheartfailurerefractorytooptimalmedicalRxleftventricularejectionfraction<20%VO2max14mL/kg/minProblems:rejection,graftatherosclerosis,neoplasia,cost/availability9/9834Cardiomyoplasty

CardiacReductionSurgerycurrentlyconsideredexperimental9/9835DietTraditionalapproachnon-pharmacologicmanagementissodiumandwaterrestrictionSodiumexcessisthemainreasonforheartfailureexacerbationRestrictsodiumto2to3grams/day9/9836Diuretics

sodiumandwaterretention

symptomsofvolumeoverloadthiazidediureticsarenotactivewithGFR<30mL/mininresistantedema,loopdiuretics,K+-sparingdiuretics,andmetolazoneareindicated9/9837DigitalisBeneficialhemodynamiceffects

cardiacoutput

leftventricularejectionfraction

leftventriculardiastolicpressure

exercisetolerance

natriuresis

neurohormonalactivation9/9838Digitalis-ClinicalTrialsDIG(DigitalisInvestigationGroup)NYHAclassI-IVheartfailurenochangeinmortalitycomparedwithplacebotherapy

combinedendpointofhospitalizationsanddeath

seriousarrhythmiaandMI9/9839Digitalis-ClinicalTrialsRADIANCE(RandomizedAssessmentoftheeffectofDigoxinonInhibitorsofACE)ejectionfraction<35%ACE,diuretics,digoxinassociatedwith

exercisetoleranceinpatientswithnormalsinusrhythmwithdrawalofdigoxinresultedin

exercisetolerance,and

inhospitalization9/9840Digitalis-ClinicalTrialsPROVED

(ProspectiveRandomizedStudyofVentricularFunctionandEfficacyofDigoxin)mild-to-moderateHFwithEF<35%inNSRandnotonACEinhibitortherapywithdrawalofdigoxinresultedin

exercisetoleranceand

inhospitalization9/9841Dobutamine?-1receptoragonistlow-dosedobutamine(2-3ug/kg/min)

myocardialcontractilityandcardiacoutput,arteriovenousdilatationhigh-dosedobutamine(5-15ug/kg/min)tachycardia,arrhythmia,splanchnicandrenalvasoconstrictionassociatedwithsymptomaticbenefitcontinuoushomepumpinfusion9/9842ExerciseTraining

AHCPR

CardiacRehabilitationGuidelinesExercisetraininginpatientswithHFdecreasesymptomsimprovesexercisetolerancebenefitadditive