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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
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