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NCBIBookshelf.AserviceoftheNationalLibraryofMedicine,NationalInstitutesofHealth.

AshleyEA,NiebauerJ.CardiologyExplained.London:Remedica2004.

Chapter7 Heartfailure
Background
Thesurvivalrateformyocardialinfarction(MI)hasgreatlyincreasedinrecentyearsduetothe
successofthrombolysisandprimaryangioplasty.However,theensuingepidemicofheartfailure
hascreatedamajorpublichealthproblem.DatafromtheUKsuggestthatheartfailureaffects
approximately2%ofthepopulation.Furthermore,theprognosisforchronicheartfailure(CHF)is
poor:apatientadmittedtohospitalwithpulmonaryedemahasapoorerprognosis(the5year
mortalityrateisaround50%)thanapatientpresentingwithacarcinomainanyorganotherthan
thelung.
Themanycausesofheartfailure(seeTable1)operatethroughthecentralmechanismofreduced
ventricularfunction.Asaconsequence,theheartisunabletoperfusethetissuesadequately.The
resultingclinicalsyndrome(seeTable2)canbeexplainedbycompensatorymeasures,suchas
cardiachypertrophyandactivationofthesympatheticnervoussystemandthereninangiotensin
system.
Table1

Causesofheartfailure.
Table2

Themultiorgansymptomsofheartfailure.

Heartfailureiscategorizedaseithersystolicordiastolic.Systolicdysfunctionisduetopoorleft
ventricular(LV)contraction,usuallyexpressedasejectionfraction(EF).Heartfailurepatientswith
diastolicdysfunction(morecommonintheelderly)havenormalLVejectionfractionthedefect
seemstolieinrelaxationoftheleftventricleandisassociatedwithdelayedfilling.Forthe
generalist,onecluetodiastolicdysfunctionliesinthechestxray(CXR),whichcanshowsignsof
congestionwithoutsignificantLVdilatation.However,echocardiographyisrequiredforafirm
diagnosis(seeChapter4,Understandingtheechocardiogram).
Pathophysiology
Theapproachtoheartfailurehaschangedenormouslyoverthepastfewyears(seeFigure1).
Earlierthinkingfocusedoninadequatepumpfunctionandtheacceptedtherapeuticwisdomwasto
bolsteritwithagonistinotropes.Theideaoftreatingheartfailurebyblockingthesympathetic
nervoussystemwouldhavebeenregardedashereticalanddangerous.However,ithasnowbeen
realizedthatmostCHFpathologyisaresultofthebody'sowncompensatorymechanisms(see
Figure2)andthatinterruptingtheseneurohumoralpathwaysachievesmorethanattemptingto
"overdrive"thefailingheart.Theexceptionisacutedecompensation(acuteheartfailure,
pulmonaryedema,cardiogenicshock),wherethefocusisonshorttermsurvivalalthoughthe
primaryaimisstillthereductionofpreloadandafterloadusingdiureticsandvasodilators,inotropes
intheformofagonistsarealsoused.
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Figure1

Treatmentofheartfailureaccordingto(a)oldand(b)new
paradigms.ADH:antidiuretichormone(vasopressin).
Figure2

Chronicheartfailure.TNF:tumornecrosisfactor.

Clinicalhistoryandexamination
Thehallmarkofheartfailureisdyspnea.Theclassiccombinationofraisedjugularvenouspressure
(JVP),peripheraledema,palpableliver,basalcrepitations,tachycardia,andathirdheartsoundis
wellknown.Orthopnea(shortnessofbreathwhenlyingflat)andparoxysmalnocturnaldyspnea
(acutenocturnalshortnessofbreath)arebothmanifestationsofdecompensationofventricular
functionprecipitatedbydiurnalsusceptibilityandincreasedvenousreturnresultingfrom
adoptionofthesupineposition.
Inanelderlyperson,thecauseofacuteshortnessofbreathcanoftenbedifficulttodiagnose,and
thechestmayrevealnothingbutcoarsebreathsoundsthroughout.Inthissituation,twofactorsare
helpful:theJVPandovertsympatheticoveractivation(coldperipheriesandprofusesweating).
Investigations
Electrocardiography

TheelectrocardiogramofapatientwithheartfailureoftenshowsLVhypertrophy(LVH).This
mayshowa"strain"pattern(LVHplusSTdepression),mostcommonlyinthelateralchestleads.
Arrhythmiasarealsocommoninheartfailure.
Chestxray

ClassicsignsonCXRsarecommononlyforacuteheartfailure.Typically,someofthefollowing
signsareseen(seeFigure3):
Figure3

(a)Classicsignsofacuteheartfailurethatcanbeseenona
chestxrayofleftventricularfailure.(b)Pleuraleffusionona
chestxray.

cardiomegaly(seeFigure4)
upperlobeblooddiversion
"bat'swing"alveolaredema
pleuraleffusions
KerleyBlines(lymphatics)

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Figure4

Cardiomegalyandpleuraleffusion(ontherightside)inapatientwithheart
failure.
Echocardiography

ThisistheinvestigationofchoiceandcanidentifyandquantifyLVHanddysfunction(both
systolicanddiastolic)aswellasexaminecausesofheartfailure,suchasvalveabnormalities.
Bloodtests

Themeasurementofnatriureticpeptidesforthediagnosisofheartfailureisnotyetroutine.
However,otherbloodtestscancontributetotheclinicalpicture.Thesodiumconcentrationisoften
low(<130mmol/L,despitehightotalbodysodium)asaresultofdilutionandisastrong
prognosticindicator.Thepotassiumlevelisalteredbymanyofthetherapeuticagentsandshould
bekeptinthemidtohighnormalrange(4.255mmol/L)tominimizetheriskofarrhythmia.Ifthe
pulseisoffullvolume,investigativebloodtestsforanemiaandthyroidfunctionshouldbecarried
out.Ifechosuggestsrestrictivecardiomyopathy,furthertestscanbecarriedoutforironstorage
disease,amyloidosis,orsarcoidosis.
Management:acuteheartfailure
TheapproachtothemanagementofacutedecompensationisdifferentfromthattoCHF.Acute
pulmonaryedemashouldbemanagedby:
sittingthepatientup
givinghighflowoxygen
givingdiamorphine(2.55mgintravenous[IV])
givingnitrates(sublingualatfirst,thenisosorbidemononitrate210mg/hourIV)
givingloopdiuretics(eg,furosemide[frusemide]4080mgslowIV)
Bloodpressureisakeymeasurementandshouldbeconsideredwhendecidingtherateofanitrate
infusionorwhethertouseagonists.Ifthesystolicbloodpressuredropsbelow100mmHg,
considerationshouldbegiventoreplacingthenitrateinfusionwithonecontainingdobutamine(2
10g/kg/min).AlthoughtheeffectofanIVdiureticcanoftenbedramatic(probablyduetoan
earlyeffectonpulmonaryvenousdilatation),nitratesarepreferredbecause,inadditionto
decreasingpreload,theyalsodecreaseperipheralresistanceanddonotreducecardiacoutput.
Itisalsoimportanttotaketheprecipitatingfactorintoaccount.If,forexample,apatientisinatrial
fibrillation,slowingtheventricularratemaybemoreeffectivethanacombinationofmoregeneral
measures.Similarly,ifapatienthassufferedanMIthenthrombolysisorinterventionmaybethe
keytotheirrecovery.
Management:cardiogenicshock
Cardiogenicshock,whichhasa90%mortalityrate,isthemostsevereformofacuteheartfailure.It
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isdiagnosedwhenacuteheartfailureandhypotensionareresistanttothemeasuresdescribed
aboveandthereisevidenceoftissuehypoxia.Treatment,whichshouldbeinthecoronarycare
unitofaspecialistcenter,involvesinotropicsupport,invasivemonitoringequipment,intraaortic
balloonpumping,and,inthesettingofMI,cardiaccatheterization.
Intraaorticballoonpumpcounterpulsation

Intraaorticballoonpump(IABP)counterpulsationwasdevelopedintheearly1960s.Aballoonis
inserted,viathefemoralartery,intothedescendingaorta(seeFigure5).Usingelectrocardiography
forsynchronization,theballoonisalmostinstantaneously,automaticallyinflatedwithheliumatthe
onsetofdiastole,thendeflatedjustpriortosystole.Thisservesadualpurpose:
Figure5

(a)Insertionofanintraaorticballoonpumpand(b)the
correspondingarterialpressurewaveform.
itimprovescoronarybloodflowbyincreasingtheperfusionpressureintheascendingaorta
duringdiastole
itencouragessystemicperfusionbyreducingimpedancetoventricularejectionatthepoint
ofballoondeflation(itcreatesanegativepressurewhichhelpsto"suck"thebloodout)
ContraindicationstoIABPincludesevereaorticregurgitationandaorticdissection.
Management:chronicheartfailure
Thechronicformofheartfailureisaconditionthatmostgeneraliststreateveryday.When
referringthesepatients,itisusefultoclassifytheseverityofheartfailure.Thisisfacilitatedbya
verysimplescale:theNewYorkHeartAssociation(NYHA)functionalclassification(seeTable
3).Itisstraightforwardandprovidesacommonlanguagethatisunderstoodbycardiologists
worldwide.
Table3

TheNewYorkHeartAssociationfunctionalclassificationof
chronicheartfailure.
Diagnosisandassessment

TheinitialdiagnosisandassessmentoftheseverityandprogressionofCHFcanbemadeusing
echoandexercisetestingwithgasanalysis.ThemostcommonlyusedechomeasureistheEF.
Thisisratedas:
45%70%,normal
35%45%,mildlyimpaired
25%35%,moderatelyimpaired
<25%,severelyimpaired
<15%,endstage/transplantcandidates
5%iscompatiblewithlife,butnotlonglife
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Thesinglebestexercisetestingmeasurementisthemaximumrateofoxygenconsumption(VO2
max).Inasituationwherecardiacandrespiratorycausesofdyspneacoexist,exercisetestingwith
gasanalysiscanbeparticularlyusefulindiscerningwhichisthegreaterproblem.
Treatment

ThefirststepinthemanagementofCHFispatienteducation.Itiseasyforphysicianstoforget
(sincetheyusethetermeveryday)that,tomostpatients,heart"failure"soundssignificantlyworse
than"myocardialinfarction","heartattack",oreven"cardiacarrest".Educatingpatientsabouttheir
conditionbygivingtheminformationaboutavoidingexcessivesaltintakeandteachingthem
howtousetheirdailyweighttomonitorfluidbalancewillpaydividendsinlongterm
management.

HistoricalHearts

Hippocratesbelievedthattheleftsideoftheheartanditsassociatedarterieswereconduits
forairratherthanblood.Galen(AD138201)thoughtthatbloodpassedthroughinvisible
poresintheventricularseptum.SuchwashisinfluenceonRomanmedicalthinkingthatthis
idearemainedinplaceuntilthe15thcenturywhenanembargoonthedissectionofhuman
cadaverswasliftedbythePope.Notlongafterthis,LeonardodaVinciandothersbeganto
producedetailedanatomicaldrawings,andWilliamHarveyfinallydescribedthefunctionof
theheartasapumpthatpushedbloodthroughacirculatorysystem,beatbybeat.

Spironolactone,angiotensinconvertingenzymeinhibitors(ACEIs),andblockersaretheonly
agentsthathavebeenshowntoreduceheartfailuremortality,andallarenowwidelyusedinthe
community.However,theiruserequirescaution.Althoughnotstrictlynecessary,most
practitionersuseshortactingpreparations(eg,captopril,metoprolol)whenfirststartingthese
treatments.
Diuretics

AlthoughdiureticsarethemainstayofCHFmanagement,theirmainroleisinsymptomcontrol
theymayevenincreaseneurohumoralactivation.Anapproachthatallowspatientstotakecontrol
oftheirowndiureticdosageandalteritaccordingtotheirdailyweight(inmuchthesamewayas
diabeticsaltertheirinsulindosage)maybesuccessfulinmanypatients.Itisrecommendedthat
diureticsshouldalwaysbeusedwithanACEI.Inaddition,theskillfuluseofdiureticswith
complementaryactions(seeFigure6,Tables4and5)canaiddiuresisandevenavoidhospital
admissionifthebalanceisupset.Giventhechoicebetweenincreasingthedoseofaloopdiuretic
oraddinganotheragent,itisusuallybesttoaddanotheragent.
Figure6

Themechanismofactionofdiureticsinchronicheartfailure
management.

Table4

Diureticsusedinthetreatmentofheartfailure.
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Table5

Treatmentofheartfailurewithdiuretics(loopdiuretics,
thiazides,metolazone).
SpironolactonehasbeenshowntoimproveoutcomesinstageIIIIVheartfailurewithaneffect
equivalenttothatofACEinhibition(25mgspironolactonehasabeneficialeffectonremodeling,
butessentiallynoeffectonpotassiumlevelsanddiuresis).
Metolazoneisathiazidelikediureticthathasapowerfulsynergisticactionwithloopdiuretics,so
shouldbeusedinthecommunityonlyasalastresort,forshortperiods,andbeaccompaniedby
dailyelectrolytechecks.

DefiningHearts

PulmonaryedemawasfirstexplainedbyHenryWelch,whoshowedthatitcouldbe
reproducedbyobstructingtheoutflowoftheleftventricle.However,thefirstdefinitionof
heartfailurewasprovidedbyTheophileBonet(16201689),whopublishedclinico
pathologicalstudieslinkingtheeffectsofvalvulardiseaseandcardiacchambersizetothe
clinicalfeaturesofdyspneaandedema.

Angiotensinconvertingenzymeinhibitors

ACEIswerethefirstagentsshowntoreducemortalityinheartfailure.Angiotensinreceptor
blockers(ARBs)arecurrentlyreservedforthosepatientswithanACEcough.Guidelinesfor
startingACEIsareoutlinedinTable6.
Table6

Therecommendedprocedureforstartinganangiotensin
convertingenzymeinhibitor(ACEI).
Betablockers

Muchoftheearlyworkonblockersusedcarvedilolanonselectiveblocker,antagonist,and
antioxidant.However,althoughitssignificanteffectappearedtoresultfromblockaderesultingin
manydifferentblockingagentsbeingused,recenttrialshavesuggestedtheremaybeeffectsover
andabovethatofblockade.Beneficialeffectsofblockadeincludeareductioninheartrate
(whichincreasesmyocardialperfusion),regressionofLVH(probablyrelatedtoinhibitionofthe
deleteriouseffectsofexcesscatecholamines),andareductioninsuddendeath(probablyrelatedto
areductioninventricularfibrillation50%ofheartfailuredeathsareduetoarrhythmia).
Digoxin

Digoxinhasperhapsthelongesthistoryofanyofthetreatmentsforheartfailure.However,beinga
positiveinotrope,itoccupiesacontroversialplaceoverarchingtheoldandnewparadigmsforthe
treatmentofsinusrhythmheartfailure.Itworksbyincreasingcellularcalciumviainhibitionof
+

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2+

2+

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Na /K ATPaseandconsequentreductionofCa2+extrusionviaNa+/Ca2+exchange(seeFigure
7).AsK+"competes"withdigoxinattheATPasesite,digoxincanbecometoxicinhypokalemic
patients.Symptomsofdigoxintoxicityaregastrointestinalupsetand(morerarely)visual
disturbancesandheadache.However,despiteitswidespreaduse,therehavebeennolarge,
prospective,placebocontrolledtrialstodeterminetheefficacyofdigoxininreducingmortality
(althoughithasbeenshowntoreducehospitaladmissions).
Figure7

Mechanismofactionofdigoxin.DigoxininhibitsNa+/K+
ATPase.AsaconsequenceofanincreasedintercellularNa+
concentration,Ca2+extrusion(viaNa+/Ca2+exchange)is
reduced.TheresultisanincreaseincellularCa2+.
Hydralazineandnitrates

Thevasodilatorcombinationofhydralazine(upto300mg)andnitrates(160mgisosorbide
dinitrate)hasbeentestedwithdigoxinanddiureticsinseverallargetrialsandhasbeenassociated
withmortalityreductionsinheartfailure.However,theadventofARBsislikelytoofferabetter
alternativetoACEIsthanthisdrugcombination.
Futuredirections

AreasofcontroversystillexistinthemanagementofCHF.Forexample,aspirinisknowntobe
effectiveasanaidtosecondarypreventionofcoronaryarterydisease.However,itcanreducethe
efficacyofACEIs.Also,despitethehighrateofheartfailuredeathsduetoarrhythmia(50%),
amiodaroneistheonlyantiarrhythmic(sofar)thathasbeenshowntoreducemortality.
Newagentscurrentlybeinginvestigatedintrialsinclude:
calciumsensitizers(increasecontractileresponsetointracellularCa2+)
endothelinantagonists(thereareincreasedlevelsofendothelinapotentvasoconstrictor
inheartfailure)resultsofallrecenttrialshavebeennegativeorneutralatbest
TNFantibodiesrecenttrialsallproducednegativeresults
neutralendopeptidaseinhibitors(neutralendopeptidasebreaksdownatrialnatriureticpeptide
andbrainnatriureticpeptidepeptideswithdiuretic,natriuretic,andvasodilatorproperties)
Heartfailuretreatments,accordingtoNYHAclassification,areoutlinedinTable7.
Table7

TreatmentofheartfailureaccordingtotheNewYorkHeart
Association(NYHA)functionalclassificationofcongestive
heartfailure.
Nonpharmacotherapies
Recentevidencesuggeststhatindividualizedexercisetrainingprogramscanbebeneficialinstable,
mildtomoderateheartfailure.Likemostotheraspectsofthetreatmentofheartfailure,today's
advice(exercise)istheoppositeofthatfrom30yearsago(bedrest).
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EarlyTreatments

ThefirstbreakthroughinthetreatmentofheartfailurewasbyWilliamWithering(1741
1799),whopublishedobservationsofthetherapeuticuseofdigitalis(foxglove).Ironically,
hebelieveditsmainmechanismofactionwasdiuretic.Untilthediscoveryofdigitalis,
treatmentforheartfailurehadremainedunchangedsinceEgyptiantimes:bedrest,fluid
restriction,andweakherbaldiureticswerecombinedwithstarvation,laxatives,and
venesection.Patientscanperhapsderivesomesolacefromthefacttheyarelivingtoday,
ratherthan200yearsago.

Revascularizationofpatientswithheartfailureisbeingconsideredincreasinglyasitisrealizedthat
chronicLVdysfunctiondoesnotnecessarilymeanpermanentorirreversiblecelldamage.
Myocardiumthathassufferedlowlevelischemiaandnolongercontributessignificantlyto
ventricularfunction(hibernatingmyocardium)remainsviable,andthereforepotentiallyrescuable.
Itcanbedetectedbycardiovascularmagneticresonanceimaging,perfusionimaging,lowdose
dobutaminestressecho,orPETscanning(perfusionmetabolismmismatch).
Manypatientswithsystolicheartfailureexhibitsignificantintraorinterventricularconduction
delays(IVCDs)thatcauseventriculardysynchrony,recognizedbyawideQRScomplexonthe
ECG(typically,aleftbundlebranchblockmorphology).Ventriculardysynchronyhasseveral
importantconsequencesforcardiacperformance,whichincludeabnormalinterventricularseptal
wallmotion,reduceddiastolicfillingtime,andprolongedmitralregurgitationduration.Inaddition,
thereisaproportionalincreaseinmortalitywithincreasingQRSduration.Cardiac
resynchronizationtherapy(CRT)providesatrialsynchronized,biventricularpacingusingstandard
pacingtechnologycombinedwithaspecialthirdlead.Thisthirdleadisimplantedviathecoronary
sinusandpositionedinacardiacveintosenseandpacetheleftventricle.Followingasensedatrial
contraction,bothventriclesarestimulatedtocontractsimultaneously.Theresulting
resynchronizationofventricularcontractionreducesmitralregurgitationandoptimizesleft
ventricularfilling,therebyimprovingcardiacfunction.
Transplantationandventricularassistdevicesareoptionsforendstagedisease.Localavailability
andguidelinesvary.Indicationsare:
severeLVdysfunction(eg,EF<20%asdemonstratedbyradionuclideventriculography)
VO2max<14mL/kg/min(patientswithvaluesabovethistendtohaveabetterprognosis
withoutsurgery)
Contraindicationscenteroncomorbidities,eg,vasculopathy,diabetesmellituswithtargetorgan
damage,orpulmonaryhypertension.Inaddition,fewcenterswilltransplantpatientsovertheage
of60years.
Severalstudieshaveshownclearbenefitfromamultidisciplinaryapproachtoheartfailure
treatment.Specialistnurseswhovisitpatientsinthecommunitycansignificantlyreducetherateof
hospitalizationbyhelpingwithexercise,symptomcontrol,andfluidbalance,andbyalertingthe
medicalteamearlytoanypotentialdeterioration.
Palliativecare
Theverypoorprognosisassociatedwithheartfailurebegsthequestionoftheavailabilityof
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hospicecareandendoflifesupportforthispopulation.Theironyremainsthatwhilecancer
patientsreceiveendoflifesupportandoftenreportdyspneaasanequivalentproblemtopain,
manymoreheartfailurepatientswhosechiefsymptomisdyspneahaveapoorerprognosisandgo
unattended.Themanagementofthesepatientsisanareadeservingofmoreinvestigationand
analysis.Forexample,whatistheplaceofdrugsthatareknowntohelpsymptomsbutwhich
mightincreasetheriskofsuddendeath(eg,inotropes)?Does"dualintent"apply?Whatarethe
wishesofthepatient?Ascardiologybecomesmoretechnologicalthereislessfocusonpatients
andmoreontheirlesionsandthetoolsusedtotreatthem.Generalistsarealmostcertainlybetter
thancardiologistsatpractisingholisticcare.
Unfortunately,conventionaldrugsforthetreatmentofheartfailuredonotadequatelycontrolthe
mostcommonsymptomsoffatigueanddyspnea.Thelatteristhemostcommondistressing
symptominrefractoryheartfailure.Maintainingaveryclosecontrolofplasmavolumeisfacilitated
byregularweighingandadjustmentofdiuresis,butthisrarelyprovidesfullsymptomcontrol.
Fortunately,reliefispossiblethroughtheuseofopiates.Thesedrugsreducepreloadandafterload,
dampenthecentralrespiratorydrive,andrelievedistressthroughacentralnarcoticaction.Thus,
theyarewellsuitedforuseinthissituation.Drawbacks,suchastoleranceanddependence,should
notdetertheiruseasstudiessuggestthattheyareminimalinthissetting.Physicaldependenceis
inevitable,butonlyrelevantinthecaseofdiscontinuationoftherapy,inwhichcaseitcanbe
managedbygradualwithdrawal.Morphinecanbegivenatadoseof2.5mg4hourlyandas
required,withthe4hourlydosereadjustedafter48hourstotakeaccountofinterimdosing.
Controlofconstipationshouldalwaysaccompanychronicopioidtreatment.
Furtherreading
1.JongP,DemersC,McKelvieRS.etal.Angiotensinreceptorblockersinheartfailure:meta
analysisofrandomizedcontrolledtrials.JAmCollCardiol.200239:46370.[PubMed:
11823085]
2.KrumholzHM,BakerDW,AshtonCM.etal.Evaluatingqualityofcareforpatientswith
heartfailure.Circulation.2000101:E12240.[PubMed:10736303]
3.NiebauerJ,VolkHD,KempM.etal.Endotoxinandimmuneactivationinchronicheart
failure:aprospectivecohortstudy.Lancet.1999353:183842.[PubMed:10359409]
4.NolanJ.Ahistoricalreviewofheartfailure.ScottMedJ.199338:537.[PubMed:
8502981]
5.TaskForceoftheWorkingGrouponHeartFailureoftheEuropeanSocietyofCardiology.
Thetreatmentofheartfailure.EurHeartJ.199718:73653.[PubMed:9152644]

Copyright2004,Remedica.
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