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CurrentManagementofCongestiveHeartFailure:2004UpdateHishamDokainish,MD,FACCAssistantProfessorofMedicineBaylor

CollegeofMedicine,Director,Non-InvasiveCardiology,BenTaubGeneralHospitalHouston,Texas,USATheProblem(USA)•5,000,000patients•6,500,000h

ospitaldays/year•300,000deaths/year•6%-10%ofpeople>65years•5.4%ofhealthcarebudget(38billion)•Incidencex2inlasttenyearsGottdiene

rJetal.JACC2000;35:1628HaldemanGAetal.AmHeartJ1999;137:352KannelWBetal.AmHeartJ1991;121:951O’ConnellJBetal.JHeartLungTransplant1993;13:S107Defini

tionofheartfailureAHA/ACCHFguidelines2001Clinicalsyndromethatcanresultfromanystructuralorfunctionalcard

iacdisorderthatimpairstheabilityoftheventricletofillwithorejectbloodSuspectedHeartFailurebecauseofSYMPTOMSand/orSIGNSAsse

sspresenceofCARDIACDISEASEbyECG,X-RayorBNPTestsabnormalVENTRICULARFUNCTIONImagingbyEcho-Doppler,NuclearangiographyorMRIifavailableTestsabn

ormalNORMALNoHeartFailureNORMALNoHeartFailureHeartFailure:Systolic/DiastolicIdentifyetiology,evaluateseverity,choosetherapyESCHFguidelines2001He

artdiseaseNosymptomsHFRiskFactorsNoHeartdiseaseNosymptomsAsymptomaticLVdysfunctionRefractoryHFsymptomsPr

iororcurrentHFSymptomsStagesintheevolutionofHeartFailureABCDAHA/ACCHFguidelines2001ACE-iblockersTreatriskfactorsDietandexerciseAv

oidtoxicsACE-iinselectedp.InselectedpatientsPalliativetherapyMech.AssistdeviceHeartTransplantACE-iblockersDiuretics/Di

gitalisStagesintheEvolutionofHeartFailureTreatmentABCDAHA/ACCHFguidelines2001AggravatingFactors•Medications•Newheartdisease•Myocardialischemia•Endoc

arditis•Obesity•Hypertension•Physicalactivity•Dietaryexcess•Pregnancy•Arrhythmias(AF)•Infections•Thromboembolism•Hyper/hypothyro

idismInitial/OngoingEvaluation•Identifyheartdisease•Assessfunctionalcapacity(NYHA,6minwalk,…)•Assessvolumestatus:(edema,rales,jugular,hepatomegal

y,bodyweight)•Labassessment:routine:electrolytes,renalfunct.RepeatEcho,RXonlyifsignificantchangesinfunctionalstatus•Assessprognosis807060504030205

4-60>6050403020100PostMIn=196<3031-3536-4546-53CardiacMortality%LVEFBrodieB.etalAmJCardiol1992;69:1113PrognosisTreatmentObjectivesSur

vivalMorbidityExercisecapacityQualityoflifeNeurohormonalchangesProgressionofCHFSymptoms(Cost)PharmacologicTherapy•Diuretics•ACEinhibitors•BetaBlock

ers•Digitalis•Spironolactone(Eplerenone)•AngiotensinIIBlockers(Candesartan)•HMG-CoAReductaseInhibitors(“Statins

”)Diuretics•Essentialtocontrolsymptomssecondarytofluidretention•PreventprogressionfromHTNtoHFDiuretics.Indications1.SymptomaticHF

,withfluidretention•Edema•Dyspnea•LungRales•Jugulardistension•Hepatomegaly•Pulmonaryedema(Xray)AHA/ACCHFguidelines2001ESCHFguidelines2001VASOCONSTR

ICTIONVASODILATATIONKininogenKallikreinInactiveFragmentsAngiotensinogenAngiotensinIRENINKininaseIIInhibitorALDOST

ERONESYMPATHETICVASOPRESSINPROSTAGLANDINStPAANGIOTENSINIIBRADYKININACE-i.MechanismofActionA.C.E.ACE-I:Clinica

lEffects•Improvesymptoms•Reduceremodelling/progression•Reducehospitalization•ImprovesurvivalMortalityReductionwithACE-iStud

yACE-iClinicalSettingCONSENSUSEnalaprilCHFSOLVDtreatmentEnalaprilCHFAIRERamiprilCHFVHeft-IIEnalaprilCHFTRACETr

andolaprilCHF/LVDSAVECaptoprilLVDSMILEZofenoprilHighriskHOPERamiprilHighriskACE-i.Dose(mg)InitialMaximumCaptopril6.25/8h50/8hEna

lapril2.5/12h10to20/12hFosinopril5to10/day40/dayLisinopril2.5to5.0/day20to40/dayQuinapril10/12h40/12hRamipril1.25to2.5/day10/

dayAHA/ACCHFguidelines2001ACE-I.Contraindications•Intolerance(angioedema,anuricrenalfail.)•Bilateralrenalarterystenosis•Pregna

ncy•Renalinsufficiency(creatinine>3mg/dl)•Hyperkalemia(>5,5mmol/l)•Severehypotensionß-AdrenergicBlockersMechanismofaction•Densityofß1recepto

rs•Inhibitcardiotoxicityofcatecholamines•Neurohormonalactivation•HR•Antiischemic•Antihypertensive•Antiarrhythmic•Antioxida

nt,Antiproliferativeß-AdrenergicBlockersClinicalEffects•Improvesymptoms(onlylongterm)•Reduceremodelling/progression•Reduc

ehospitalization•Reducesuddendeath•ImprovesurvivalUSCarvedilolHFNEJM1996;334:1349-55Carvedilol(n=696)Placebo

(n=398)Riskreduction=65%p<0.0010501001502002503003504001.00.90.80.70.6ß-AdrenergicBlockers0.70.80.91.0Survival%DaysI-IIHF•Symptomaticheartfailur

e•Asymptomaticventriculardysfunction-LVEF<35-40%•AfterAMIAHA/ACCHFguidelines2001ESCHFguidelines2001ß-AdrenergicBlockers:Indications•Patientstab

le•Nophysicalevidenceoffluidretention•Noneedfori.v.inotropicdrugs•StartACE-I/diureticfirst•Nocontraindications•Inhospitalornotß-AdrenergicBlockersWhe

ntostartInitialTargetBisoprolol1.25/24h10/24hCarvedilol3.125/12h25/12hMetoprololtartrate6.25/12h75/12hMetoprololsuccinnate12,5-25/24h200

/24h•StartLow,IncreaseSlowly•Increasethedoseevery2-4weeksß-AdrenergicBlockersDose(mg)•Hypotension•Fluidretent

ion/worseningheartfailure•Fatigue•Bradycardia/heartblockß-AdrenergicBlockersAdverseEffects•Reviewtreatment(+/-diuretics,otherdrugs)•Reducedose•Con

sidercardiacpacing•DiscontinuebetablockeronlyinseverecasesDigitalis:MechanismofActionBlocksNa+/K+ATPase=>Ca++•Inotropiceffect•Natr

iuresis•Neurohormonalcontrol-PlasmaNoradrenaline-Peripheralnervoussystemactivity-RAASactivity-Vagaltone-Normalizesarterialbaroreceptors

NEJM1988;318:358Digitalis.ClinicalEffects•Improvesymptoms•Modestreductioninhospitalization•Doesnotimprovesurvival•Digoxintoxicity•Advanc

edA-Vblockwithoutpacemaker•BradycardiaorsicksinuswithoutPM•PVC’sandVT•Markedhypokalemia•W-P-Wwithatrialfibrillati

onDigoxin.ContraindicationsRENINAngiotensinogenAngiotensinIANGIOTENSINIIACEOtherpathwaysVasoconstrictionProliferativ

eActionVasodilatationAntiproliferativeActionAT1AT2AT1ReceptorBlockersRECEPTORSAngiotensinIIReceptorBlo

ckers(ARB)•Candesartan,Eprosartan,IrbesartanLosartan,Telmisartan,Valsartan•EfficacynotsuperiortoACE-I•L

ikelynotindicatedwithbetablockers•IndicatedinpatientsintoleranttoACE-IAngiotensinIIReceptorBlockers(ARB)AHA/ACCHFguidelines2001ESCHFguidelines2

001Months1.00.90.80.7ValsartanPlaceboP=0.8Survival0369122118152427AngiotensinIIReceptorBlockers(ARB)Val-HeFTAHA2000Nitrates:ClinicalUse•CHFwithm

yocardialischemia•Orthopneaandparoxysmalnocturnaldyspnea•InacuteCHFandpulmonaryedema:NTGsl/iv•Nitrates+HydralazineinintolerancetoACE-I(hypotens

ion,renalinsufficiency)0,540,480122448600.750.500.2500.470.360.250.130.090.310.180.4236Monthsp=0.08V-HeFTIINEnglJMed1991;

325:303EnalaprilHZ+ISDNn=804p=0.016ProbabilityofdeathNitrate+Hydralazine•Inotropes,longterm/intermittent•Antiarrhythmics(exceptamiodaro

ne)•Calciumantagonists(exceptamlodipine)•Non-steroidalantiinflammatorydrugs(NSAIDS)•Tricyclicantidepressants•Corticosteroids•LithiumDrugs

toAvoid(mayincreasesymptoms,mortality)ESCHFguidelines2001RefractoryEnd-StageHF•Reviewetiology,treatment&aggrav.factors

•Controlfluidretention•Resistancetodiuretics•Ultrafiltration?•ivinotropics/vasodilatorsduringdecompensation•Considerresyn

chronization•Considermechanicalassistdevices•ConsiderhearttransplantationHeartTransplant.Indications

•Refractorycardiogenicshock•DocumenteddependenceonIVinotropicsupporttomaintainadequateorganperfusion•PeakVO2<10ml

/kg/min•Severesymptomsofischemianotamenabletorevascularization•Recurrentsymptomaticventriculararrhythmiasrefractorytoallthe

rapeuticmodalitiesContraindications:age,severecomorbidityNewHeartFailureTrials1.Candesartan(ARB):CHARMProgramme2

.Carvedilolvs.Metoprolol:COMET3.BiventricularPacemaker+/-Internalcardiacdefibrillator(ICD):COMPANION4.IC

DonlyinnonischemicHF:DEFINITECHARMStudy:DesignPurpose:Todeterminetheefficacyofcandasartan(ARB)invariousscenar

iosinHF:–AddedtoACEinhibitor–InsteadofACEinhibitor–InpatientswithHFbutpreservedEFPfeffer,etal:Lancet2003CHARMStudy:

AllgroupsPfeffer,etal:Lancet2003Purpose:Toanswerthequestion:•WhichBeta-BlockerisbetterinpatientswithdepressedEFandCHF:Metopr

ololorCarvedilol?COMET:Carvedilolvs.MetoprololPoole-Wilson,etal:Lancet2003Poole-Wilson,etal:Lancet2003COMET:Carvedi

lolvs.MetoprololCardiac-Resynchronization+/-ICDinHeartFailure:COMPANIONTrial•Patientswithheartfailureandwiden

edQRScomplex>120mscanbenefitfromresynchronizationtherapy•Threeleads:oneinRVapex,oneinRAandoneincoronarysinus(LVpacing)•P

urpose:tohelprestoreinterventricularsynchrony,andimprovehemodynamics•InternalCardiacDebrillators(ICD)topreventarrhythmicsuddencardiacdeath•152

0patients:meanage67years;meanEF22%;meanQRS160ms;ischemiccause~55%ofpatientsBristow,etal:NEnglJMed2004ICDTherapyinNonischemicCar

diomyopathy:DEFINITETrial•MADITIItrialshowedthatpatientswithEF<35%afterMIhavelowermortalitywithprophylacticICDtherapy•45

8patientswithnonischemicDCMrandomizedandPVCsorNSVTtooptimummedicaltherapy+/-internalcardiacdefibrillator•

Meanage:58years;meanQRS115ms;meanEF21%Kadish,etal:NEnglJMed2004CHFTreatmentSummary1.Maketherightdiagnosis:Echoisessential2.Die

tandexerciseareimportant3.Diureticforsymptoms4.ACEinhibitorforsymptomsandsurvival5.Beta-blockerforsymptomsandsurvival(Carvedilollikelybetter)

CHFTreatmentSummary6.Spironolactone(oreplerenone)forClassIIIorIVheartfailure7.Candesartanisagoodadjunct

ivemedication8.Devices:CardiacresynchronizationtherapyandICDhelpreducemorbidityandmortalityinqualifyingHFpatients