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CurrentManagementofCongestiveHeartFailure:2004UpdateHishamDokainish,MD,FACCAssistantProfessorofMedicineBaylorCollegeofMedicine,Director,N
on-InvasiveCardiology,BenTaubGeneralHospitalHouston,Texas,USATheProblem(USA)•5,000,000patients•6,500,000hospitaldays/yea
r•300,000deaths/year•6%-10%ofpeople>65years•5.4%ofhealthcarebudget(38billion)•Incidencex2inlasttenyearsGottdienerJetal.JACC2000;3
5:1628HaldemanGAetal.AmHeartJ1999;137:352KannelWBetal.AmHeartJ1991;121:951O’ConnellJBetal.JHeartLungTra
nsplant1993;13:S107DefinitionofheartfailureAHA/ACCHFguidelines2001Clinicalsyndromethatcanresultfromanystructuralorfunctionalcardiacd
isorderthatimpairstheabilityoftheventricletofillwithorejectbloodSuspectedHeartFailurebecauseofSYMPTOMSand/orSIGNSAssesspresenceof
CARDIACDISEASEbyECG,X-RayorBNPTestsabnormalVENTRICULARFUNCTIONImagingbyEcho-Doppler,NuclearangiographyorMRIifava
ilableTestsabnormalNORMALNoHeartFailureNORMALNoHeartFailureHeartFailure:Systolic/DiastolicIdentifyetiology,evaluatese
verity,choosetherapyESCHFguidelines2001HeartdiseaseNosymptomsHFRiskFactorsNoHeartdiseaseNosymptomsAsymptoma
ticLVdysfunctionRefractoryHFsymptomsPriororcurrentHFSymptomsStagesintheevolutionofHeartFailureABCDAHA/ACCHFguidelines2001ACE-iblockersTre
atriskfactorsDietandexerciseAvoidtoxicsACE-iinselectedp.InselectedpatientsPalliativetherapyMech.AssistdeviceHeartTransplantACE-ib
lockersDiuretics/DigitalisStagesintheEvolutionofHeartFailureTreatmentABCDAHA/ACCHFguidelines2001AggravatingFactors•Medications•Newheartdisea
se•Myocardialischemia•Endocarditis•Obesity•Hypertension•Physicalactivity•Dietaryexcess•Pregnancy•Arrhyth
mias(AF)•Infections•Thromboembolism•Hyper/hypothyroidismInitial/OngoingEvaluation•Identifyheartdisease•Assessfunction
alcapacity(NYHA,6minwalk,…)•Assessvolumestatus:(edema,rales,jugular,hepatomegaly,bodyweight)•Labassessment:routine:electrolytes,renalfunct.RepeatEc
ho,RXonlyifsignificantchangesinfunctionalstatus•Assessprognosis8070605040302054-60>6050403020100PostMIn=196<3031-3536-4546-53CardiacMortality%L
VEFBrodieB.etalAmJCardiol1992;69:1113PrognosisTreatmentObjectivesSurvivalMorbidityExercisecapacityQualityoflifeNeurohormonalchangesProgressio
nofCHFSymptoms(Cost)PharmacologicTherapy•Diuretics•ACEinhibitors•BetaBlockers•Digitalis•Spironolactone(Eplerenone)•An
giotensinIIBlockers(Candesartan)•HMG-CoAReductaseInhibitors(“Statins”)Diuretics•Essentialtocontrolsymptomssecondarytoflui
dretention•PreventprogressionfromHTNtoHFDiuretics.Indications1.SymptomaticHF,withfluidretention•Edema•Dyspnea•LungRales•Jugulardistension•
Hepatomegaly•Pulmonaryedema(Xray)AHA/ACCHFguidelines2001ESCHFguidelines2001VASOCONSTRICTIONVASODILATATIONKininogenKallikreinInactiveFragment
sAngiotensinogenAngiotensinIRENINKininaseIIInhibitorALDOSTERONESYMPATHETICVASOPRESSINPROSTAGLANDINStPAANGIOTENSINIIBRADYKININACE-i.MechanismofActionA
.C.E.ACE-I:ClinicalEffects•Improvesymptoms•Reduceremodelling/progression•Reducehospitalization•ImprovesurvivalMortalityReductionwithACE-iStudyA
CE-iClinicalSettingCONSENSUSEnalaprilCHFSOLVDtreatmentEnalaprilCHFAIRERamiprilCHFVHeft-IIEnalaprilCHFTRACETrandolaprilCHF/LVDSAVECaptopr
ilLVDSMILEZofenoprilHighriskHOPERamiprilHighriskACE-i.Dose(mg)InitialMaximumCaptopril6.25/8h50/8hEnalapril2.5/12
h10to20/12hFosinopril5to10/day40/dayLisinopril2.5to5.0/day20to40/dayQuinapril10/12h40/12hRamipril1.25to2.5/day10/dayAHA/ACCHFguidelines2001ACE
-I.Contraindications•Intolerance(angioedema,anuricrenalfail.)•Bilateralrenalarterystenosis•Pregnancy•Renalinsufficiency(cr
eatinine>3mg/dl)•Hyperkalemia(>5,5mmol/l)•Severehypotensionß-AdrenergicBlockersMechanismofaction•Densityofß1receptors•Inhibitcardiotoxicity
ofcatecholamines•Neurohormonalactivation•HR•Antiischemic•Antihypertensive•Antiarrhythmic•Antioxidant,
Antiproliferativeß-AdrenergicBlockersClinicalEffects•Improvesymptoms(onlylongterm)•Reduceremodelling/progression•Reducehospit
alization•Reducesuddendeath•ImprovesurvivalUSCarvedilolHFNEJM1996;334:1349-55Carvedilol(n=696)Placebo(n=398)Riskreduction=65%p<0.00105010015
02002503003504001.00.90.80.70.6ß-AdrenergicBlockers0.70.80.91.0Survival%DaysI-IIHF•Symptomaticheartfailure•Asymptomaticventric
ulardysfunction-LVEF<35-40%•AfterAMIAHA/ACCHFguidelines2001ESCHFguidelines2001ß-AdrenergicBlockers:I
ndications•Patientstable•Nophysicalevidenceoffluidretention•Noneedfori.v.inotropicdrugs•StartACE-I/diureticfirst•N
ocontraindications•Inhospitalornotß-AdrenergicBlockersWhentostartInitialTargetBisoprolol1.25/24h10/24hCarvedilol3.125/1
2h25/12hMetoprololtartrate6.25/12h75/12hMetoprololsuccinnate12,5-25/24h200/24h•StartLow,IncreaseSlowly•Increasethedoseevery2-4weeksß-Adren
ergicBlockersDose(mg)•Hypotension•Fluidretention/worseningheartfailure•Fatigue•Bradycardia/heartblockß-AdrenergicBlockersAdverseEffects•Reviewt
reatment(+/-diuretics,otherdrugs)•Reducedose•Considercardiacpacing•DiscontinuebetablockeronlyinseverecasesDigi
talis:MechanismofActionBlocksNa+/K+ATPase=>Ca++•Inotropiceffect•Natriuresis•Neurohormonalcontrol-PlasmaNoradrenaline-Peripheraln
ervoussystemactivity-RAASactivity-Vagaltone-NormalizesarterialbaroreceptorsNEJM1988;318:358Digitalis.Clinic
alEffects•Improvesymptoms•Modestreductioninhospitalization•Doesnotimprovesurvival•Digoxintoxicity•AdvancedA-Vblockwi
thoutpacemaker•BradycardiaorsicksinuswithoutPM•PVC’sandVT•Markedhypokalemia•W-P-WwithatrialfibrillationDigoxin.Contraindication
sRENINAngiotensinogenAngiotensinIANGIOTENSINIIACEOtherpathwaysVasoconstrictionProliferativeActionVasodilatationAntiproliferativeActionAT1AT2AT1R
eceptorBlockersRECEPTORSAngiotensinIIReceptorBlockers(ARB)•Candesartan,Eprosartan,IrbesartanLosartan,Telmisartan,Valsartan•Efficacynotsuperiorto
ACE-I•Likelynotindicatedwithbetablockers•IndicatedinpatientsintoleranttoACE-IAngiotensinIIReceptorBlockers(ARB)AHA/ACCHFguidelines20
01ESCHFguidelines2001Months1.00.90.80.7ValsartanPlaceboP=0.8Survival0369122118152427AngiotensinIIReceptorBlockers(
ARB)Val-HeFTAHA2000Nitrates:ClinicalUse•CHFwithmyocardialischemia•Orthopneaandparoxysmalnocturnaldyspnea•InacuteCHFandpulmonaryedema:NTGsl/iv•Nitrate
s+HydralazineinintolerancetoACE-I(hypotension,renalinsufficiency)0,540,480122448600.750.500.2500.470.360.250
.130.090.310.180.4236Monthsp=0.08V-HeFTIINEnglJMed1991;325:303EnalaprilHZ+ISDNn=804p=0.016ProbabilityofdeathNitra
te+Hydralazine•Inotropes,longterm/intermittent•Antiarrhythmics(exceptamiodarone)•Calciumantagonists(exceptamlodipine)•N
on-steroidalantiinflammatorydrugs(NSAIDS)•Tricyclicantidepressants•Corticosteroids•LithiumDrugstoAvoid(mayincreasesymptoms
,mortality)ESCHFguidelines2001RefractoryEnd-StageHF•Reviewetiology,treatment&aggrav.factors•Controlfluidretention•Resis
tancetodiuretics•Ultrafiltration?•ivinotropics/vasodilatorsduringdecompensation•Considerresynchronization•Considermechanicalassistdevices•Consider
hearttransplantationHeartTransplant.Indications•Refractorycardiogenicshock•DocumenteddependenceonIVinotropicsupporttomaintainadequateorganperfusion•P
eakVO2<10ml/kg/min•Severesymptomsofischemianotamenabletorevascularization•Recurrentsymptomaticventriculararrhythmiasrefractor
ytoalltherapeuticmodalitiesContraindications:age,severecomorbidityNewHeartFailureTrials1.Candesartan(ARB):CHARMProgramme2.Carvedilolvs.Metoprolol:
COMET3.BiventricularPacemaker+/-Internalcardiacdefibrillator(ICD):COMPANION4.ICDonlyinnonischemicHF:DEFINITECHARMStu
dy:DesignPurpose:Todeterminetheefficacyofcandasartan(ARB)invariousscenariosinHF:–AddedtoACEinhibitor–Inst
eadofACEinhibitor–InpatientswithHFbutpreservedEFPfeffer,etal:Lancet2003CHARMStudy:AllgroupsPfeffer,etal:Lancet2003Purpose:To
answerthequestion:•WhichBeta-BlockerisbetterinpatientswithdepressedEFandCHF:MetoprololorCarvedilol?COMET:Carvedilolvs.MetoprololPoole-Wilso
n,etal:Lancet2003Poole-Wilson,etal:Lancet2003COMET:Carvedilolvs.MetoprololCardiac-Resynchronization+/-ICDinHeartFailure:COMPANIONTrial•Patientswithh
eartfailureandwidenedQRScomplex>120mscanbenefitfromresynchronizationtherapy•Threeleads:oneinRVapex,oneinRAando
neincoronarysinus(LVpacing)•Purpose:tohelprestoreinterventricularsynchrony,andimprovehemodynamics•InternalCardia
cDebrillators(ICD)topreventarrhythmicsuddencardiacdeath•1520patients:meanage67years;meanEF22%;meanQRS160ms;ischemiccause~55%ofpatientsBri
stow,etal:NEnglJMed2004ICDTherapyinNonischemicCardiomyopathy:DEFINITETrial•MADITIItrialshowedthatpatien
tswithEF<35%afterMIhavelowermortalitywithprophylacticICDtherapy•458patientswithnonischemicDCMrandomizedandPVCsorNSVTtooptimum
medicaltherapy+/-internalcardiacdefibrillator•Meanage:58years;meanQRS115ms;meanEF21%Kadish,etal:NEnglJMed2004CHFTreatmentSummary1.Maketh
erightdiagnosis:Echoisessential2.Dietandexerciseareimportant3.Diureticforsymptoms4.ACEinhibitorforsymptomsandsurvival5.Beta-blockerfo
rsymptomsandsurvival(Carvedilollikelybetter)CHFTreatmentSummary6.Spironolactone(oreplerenone)forClassIIIorI
Vheartfailure7.Candesartanisagoodadjunctivemedication8.Devices:CardiacresynchronizationtherapyandICDhelpreducemorbidityandmortalit
yinqualifyingHFpatients