Management of Arrhythmias in Heart Failure

20 Pages·2017·0.58 MB·English

Journal of
Cardiovascular
Development and Disease
Review
Management of Arrhythmias in Heart Failure
DanieleMasarone*,GiuseppeLimongelli,MartaRubino,FabioValente,RossellaVastarella,
ErnestoAmmendola,RitaGravino,MarinaVerrengia,GemmaSalernoandGiuseppePacileo
CardiologiaSUN—HeartFailureUnit,DepartmentofCardiothoracicSciences,SecondUniversityofNaples,
viaL.Bianchi,Naples80100,Italy;[email protected](G.L.);[email protected](M.R.);
[email protected](F.V.);[email protected](R.V.);[email protected](E.A.);
[email protected](R.G.);[email protected](M.V.);[email protected](G.S.);[email protected](G.P.)
* Correspondence:[email protected];Tel./Fax:[phone]
AcademicEditor:JoelD.Schilling
Received:31August2016;Accepted:22February2017;Published:28February2017
Abstract:Heartfailurepatientsarepredisposedtodeveloparrhythmias.Supraventriculararrhythmias
can exacerbate the heart failure symptoms by decreasing the effective cardiac output and their
controlrequirepharmacological, electrical, orcatheter-basedintervention. Inthesettingofatrial
flutter or atrial fibrillation, anticoagulation becomes paramount to prevent systemic or cerebral
embolism. Patientswithheartfailurearealsopronetodevelopventriculararrhythmiasthatcan
presentachallengetothemanagingclinician. Themanagementstrategydependsonthetypeof
arrhythmia,theunderlyingstructuralheartdisease,theseverityofheartfailure,andtherangefrom
optimizationofheartfailuretherapytocatheterablation. Patientswithheartfailure,irrespective
ofejectionfractionareathighriskfordevelopingsuddencardiacdeath,howeverriskstratification
isaclinicalchallengeandrequiresamultiparametricevaluationforidentificationofpatientswho
shouldundergoimplantationofacardioverterdefibrillator. Finally,patientswithheartfailurecan
alsodevelopsymptomaticbradycardia,causedbysinusnodedysfunctionoratrio-ventricularblock.
Thetreatmentofbradycardiainthesepatientswithpacingisusuallystraightforwardbutneedssome
specificissue.
Keywords: heartfailure;tachyarrhythmias;bradyarrhythmias;suddencardiacdeath
1. Introduction
Arrhythmiasconfersasubstantialriskofmortalityandmorbidityinpatientswithheartfailure
(HF), and this represents a major health care burden worldwide. There are at least 15 million
patientswithHFinEurope[1]and6millionpatientsinUSA[2],withanoverallprevalenceranging
between 2% and 3% that increases sharply after 75 years of age, reaching 10%–20% among those
intheeighthdecadeoflife. HFhospitalizationsareincreasing, andmanyofthesemayberelated
tosupraventricular arrhythmias (SVAs)[3]such asatrial fibrillation(AF). Atrial fibrillationper se
contributestoanincreasedriskofmortalityandmorbidityofstrokeandthromboembolism,andsilent
AFiscommonamongpatientswithHF[4],notinfrequentlyleadingtoafirstpresentationofAFwith
an ischemic stroke [5]. Sudden cardiac death (SCD) is also a major cause of mortality among HF
patientsandiscommonlyrelatedtocardiacarrhythmias[6],particularlyventriculararrhythmias(VAs).
Finally,bradyarrhytmiasarecommoninHFandmayincludesinusnodedysfunction,tachy-brady
syndrome, and conduction disease [7]. This review focuses on the management of arrhythmias,
bothtachyarrhythmiasandbradyarrhytmias,inpatientswithHF.
J.Cardiovasc.Dev.Dis.2017,4,3;doi:10.3390/jcdd4010003 www.mdpi.com/journal/jcdd
J.Cardiovasc.Dev.Dis.2017,4,3 2of20
2. PathophysiologyofTachyarrhytmiasinHF
Highly complex, interactive, and dynamic changes in mechanical, structural, neurohumoral,
metabolic,andelectrophysiologicalpropertiescollectivelypredisposethefailinghearttotachyarrhytmias
(Table1),whichincreaseincomplexitywiththeseverityofleftventriculardysfunction[8].
Table1.Factorsinvolvedinpathogenesisoftachyarrhythmiasinpatientwithheartfailure.
Myocardialscar
StructuralandHemodynamicAbnormalities Leftventricularhypertrophy
Leftventricularstretch
Neurohormonalactivation
MetabolicAbnormalities
Electrolyteabnormalities
Prolongationofactionpotential
ElectrophysiologicChanges Changesofcalciumhomeostasis
Changesofpotassiumcurrent
Pharmacologicagents
Others
Myocardialischemia
2.1. StructuralandHemodynamicAbnormalities
2.1.1. Myocardial
Possibly the best understood relationship between arrhythmias and structural changes is
representedbypost-myocardialinfarctioncardiomyopathyandreentry.
In these patients there are focal areas of post-infarct scar with creating a heterogeneous
environmentthatpromotethedevelopmentofventriculararrhythmiasduetoanisotropy[9,10]and
reentry[11].
2.1.2. ChamberHypertrophyandStretch
InpatientswithHF,numerouscompensatorymechanismsareactivetoimprovecardiacoutput,
butthesemechanismscancontributetoarrhythmogenicmilieu. Leftventricularhypertrophyisknown
duetoproarrhythmicelectrophysiologicalchanges(reducedcell-cellcoupling,reductionofmembrane
potentials,sub-endocardialischemia)[12].Otherfactorsfavoringarrhythmiasincludeincreasespreload
andafterload,whichreducetherepolarizationphaseofactionpotential[13].Increasesinpreloadand
afterload,aswellashighleftventricularfillingpressurecanalsocontributetothearrhythmogenic
substratedeterminingtheonsetofsubendocardialischemia[14].
2.2. MetabolicAbnormalities
2.2.1. NeurohormonalActivation
The activation of the neurohormonal systems is responsible for a variety of proarrhythmic
changes. The increased plasma levels of adrenaline and noradrenaline plays an important role in
the pathophysiology of HF and are believed to be partly responsible for the beneficial effects of
beta-blockersandangiotensinconvertingenzyme(ACE)onthedeathsudden[15,16]. Meredithand
colleagues[17]haveshownasignificantincreaseofnorepinephrinerelapseinpatientswithHFthat
maycontributetoarrhythmias. Moreover,Caoandcolleaguesdescribeanassociationbetweenthe
densityofnervesympatheticfibers(whichareincreasedinpatientswithHF)andtheriskofVas[18].
2.2.2. ElectrolyteAbnormalities
HyperkalemiaiscommoninpatientswithHFandisoftenlinkedtotheuseofACEinhibitors,
angiotensinreceptorblockersandaldosteroneantagonists. Hyperkalemialeadingtoslowtheascent
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phaseofactionpotentialthatcancauseatrioventricularblock[19]. Althoughhypokalemiaisvery
commoninHFpatientsandmaybesecondarytoincreasedactivityoftherenin-angiotensinsystemor
theuseofloopdiuretics[20]. TheresultisamoreautomaticityinPurkinjefibersandarapidincrease
repolarization,withconsequentonsetofVT/VF[21]. Hypomagnesemiaitisalsocommoninpatients
withHF,however,theassociationbetweenhypomagnesemiaandVAsisnotasstrongasforpotassium
abnormalities[22].
2.3. PharmacologicAgents
Thedrugsthatinterferewithneuro-hormonalsystemcanoftencontributetothepro-arrhythmic
milieu. As mentioned diuretic therapy, ACE inhibitors and aldosterone antagonists often cause
electrolyte imbalances that contribute significantly to arrhythmogenesis and can increase the
proarrhythmiceffectofotherdrugs[23].
InotropicagentsthatmayberequiredinpatientswithacuteHFandhypoperfusionespeciallyin
thepresenceofelectrolyteabnormalitiesmayfurtherincreasetheriskofarrhythmias.
2.4. ElectrophysiologicChangesinHeartFailure
2.4.1. ActionPotentialProlongation
Anelectrophysiologicalhallmarkofcellsandtissuesisolatedfromhypertrophiedandfailing
hearts is a prolonged action potential duration, reflecting delayed terminal repolarization of the
cardiac myocyte [24]. These cellular electrophysiological changes were mechanistically linked to
downregulationofrepolarizingpotassiumcurrents,anincreaseinlatesodiumcurrentdensity,aswell
asmajorchangesinintracellularcalcium.
StudiesinhumansandanimalmodelsofHFshoweddelayedglobalrepolarizationandenhanced
temporalrepolarizationdynamicsusingclinicalnoninvasivemetrics,suchastheQT-intervalvariability
indexandT-wavealternansonthesurfaceelectrocardiogram[25]. However,despitethesestudies,
adirectmechanisticlinkbetweenrepolarizationchangesobservedinisolatedmyocytesoronthebody
surfaceandarrhythmiagenesisremainslacking.
2.4.2. CalciumHandling
AmongthenumerouselectrophysiologicalchangesthatarepresentintheclinicalsyndromeofHF,
noneissocloselyinvolvedinarrhythmogenesisascalciumhomeostasis. ThecalciumchannelL-type
voltage-dependentarethemainsourceofcalciuminfluxintomyocardialcellsandareresponsible
foritsreleasefromthesarcoplasmicreticulum. Thesechannelshaveadecreasedfunctioninpatients
withHF,resultinginaprolongationoftheactionpotential[26,27]. Recentstudieshavedemonstrated
a downregulation of SERCA2a calcium reuptake proteins, as well as an increase in the ryanodine
receptorduringdiastole,resultingincalcium“leak”[28].
Slowcalciumleakduringdiastoleincreasedcalciumreleaseduringthesarcoplasmicreticulum
stimulation,anddecreaseduptakebySERCA2afinallyestablishesanintracellularcalciumoverload
thatfavorsthearrhythmogenesis[29].
In addition blocking transient inward current (Iti) with tetracaine, Verker et al. showed
a complete suppression of delayed after depolarization confirming the role of these currents in
thearrhythmogenicprocess[30].Finally,theincreasedactivityofthebeta-adrenergicreceptormay
contributetospontaneousreleaseofcalciumfromthesarcoplasmicreticulum[31].
2.4.3. RoleoftheSodium–CalciumExchanger
The sarcolemmal sodium and calcium exchanger normally regulates the flow of calcium in
cardiomyocytefacilitatingtherelaxation[32].
InexperimentalmodelsofHFitwasreportedanincreaseofthesodiumandcalciumexchanger
withapossibleroleinthegenesisofarrhythmias[33].
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2.4.4. Voltage-DependentPotassiumChannels
InpatientswithadvancedHFthereisareducedfunctionofboththeexternalpotassiumcurrent
(Ito) and inward rectifier potassium current (IK1), these channels play a key role in the genesis of
the action potential [34]. Beuckelmann and colleagues [35] were the first to identify a decrease in
potassiumcurrentsinHFpatientsalthoughtheirroleinarrhythmogenesisremainedcontroversial.
3. PathophysiologyofBradyarrhytmiasinHF
Bradyarrhythmias may be due either to a reduction in heart rate or a block in the impulse
conductionafteritsformation.
3.1. SinusNodeDysfunction
Symptomatic sinus bradycardia is due to a reduction in impulse formation in the sinus node
or lack of impulse conduction from the sinus node to the atrial tissue. In most cases, the nodal
dysfunctioniscausedbyprogressivefibrosisofnodalcellsduetoaging;however,anyprocessthat
causesdamagetothesinoatrialnode(e.g.,nodalarteryatherosclerosis,infiltrativediseasesorcollagen
diseases), may be contribute to nodal dysfunction [36]. The sinoatrial dysfunction can occur with
episodes of sinoatrial block in a significant fraction of patients, in addition approximately 50% of
patientswithsicksinussyndromedevelopalternatingbradycardiaandtachycardia,alsoknownas
tachy-bradysyndrome[37]. Themostcommontachyarrhythmiasareatrialfibrillationorflutterwith
rapidventricularresponse. Thesetachyarrhythmiasaremorecommoninolderpatientswithadvanced
sinoatrialnodaldiseaseinwhomsinoatrialnodefibrosismayfavorreentrantbeatsortachycardia.
3.2. Atrio-VentricularNodeDysfunction
First-degree atrio-ventricular block is not associated with bradycardia except in the setting
of sinus bradycardia. First-degree atrio-ventricular block is commonly associated with damage
and/or fibrosis of the atrio-ventricular node, but it can also be due to beta-blockers therapy [38].
Like 1st degree atrio-ventricular block, Type I second-degree atrio-ventricular block can occur in
normal individuals and is common during sleep in 4%–6% of cases [39]. It may be particularly
prevalent among patients with HF and obstructive sleep apnea, in which therapy with positive
airwaypressureoftenalleviatesthefinding. TypeIsecond-degreeatrio-ventricularblockcanlead
tolossofatrio-ventricularsynchrony,althoughthisistypicallynotproblematicunlessasubstantial
firstdegreeatrio-ventricularisalsopresent. TypeIIsecond-degreeatrio-ventricularblockisassociated
with disease of the conduction system below the atrio-ventricular node, and as such has a higher
likelihoodofprogressiontocompleteatrio-ventricularblock[40].InpatientswithseconddegreetypeII
atrioventricularblockiscommonaslowingofimpulseconductiononHis-Purkinjesystem,thisis
demonstratedduringelectrophysiologicalstudybyanabnormallylongH-Vinterval[41]. High-grade
atrio-ventricularblockandcompleteheartblockrepresentthemostsevereformsofatrio-ventricular
nodaldiseaseandareusuallyassociatedwithunderlyingheartdisease[42].
4. ClinicalImpactofTachyarrhythmiasinHF
AlthoughanySVAsmayoccurinpatientswithHF,themostcommonisAF—indeed,AFand
congestiveHFcommonlyoccurtogetherandeachmayexacerbatetheother[43]. TheFramingham
HeartStudydemonstratedthateachconditionincreasestheriskfordevelopingtheother. Thereis
a15%5-yearincidenceofnew-onsetHFamongpatientswithAF;theconverseisalsotrue,witha25%
5-yearincidenceofnewAFinpatientswithHF[44]. TheprevalenceofAFprogresseswithworsening
HFwithaprevalenceof10%inHFpatientsintheNewYorkHeartAssociation(NYHA)ClassesIand
II,andupto50%inNYHAClassIV.HFandAFsharethepresenceofcommonriskfactors,suchasage,
highbloodpressure,diabetesmellitus,obesityandvalvulardysfunction[45]. However,experimental
and clinical data document a substrate of the atrial myocardium for the AF in patients with HF
J. Cardiovasc. Dev. Dis. 2017, 4, 3 5 of 19
worsening HF with a prevalence of 10% in HF patients in the New York Heart Association (NYHA)
Classes I and II, and up to 50% in NYHA Class IV. HF and AF share the presence of common risk
factors, such as age, high blood pressure, diabetes mellitus, obesity and valvular dysfunction [45].
However, experimental and clinical data document a substrate of the atrial myocardium for the AF
J.Cardiovasc.Dev.Dis.2017,4,3 5of20
in patients with HF regardless of the shared risk factors. HF patients may also experience other type
of SVAs (e.g., focal atrial tachycardias and atrial macroreentrant arrhythmias), sometimes
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o(itnh ewrhhiacnhd t,hme onsotrlympaal taietrniatsl wcointhtrHacFti-opnre isse rrvepedlaecejedc tbioyn infreafcfteicotniv(eH qFupiEvFer)ianrge odfe tpheen adterniat)o cnanad ceaquusaet ea
vraepnitdri counlsaert fiolfl iHngF. sFyomrpthtoismrse a[s4o7n]., onsetofAF(inwhichthenormalatrialcontractionisreplacedby
ineffeIcnt iavdedqiutiiovne,r aintrgiaolf ttahcehyatarrirah)yctahnmciaauss meaayr aipnifdluoennsceet coafrdHiFacs yremsypntocmhrso[n4i7z]a.tion therapy response
(i.e., Irnedaudcdtiitoionn o,fa ptraiaclintagc rhaytaersr) hayntdh msoiamsemtimayeisn iflnudeunccee icnaarpdpiarocprerisaytnec thhreornaipzya tfiroonmth tehrea pimyprelaspntoanbslee
(cia.er.d,iroevdeurctetiro dneofifbpriallcaitnogr r(aICteDs)).a ndsometimesinduceinappropriatetherapyfromtheimplantable
cardiFovinearltleyr, dpeafitbierniltlsa towrit(hIC ADF). and AFL bears a increased risk of ischemic stroke and systemic
emboFliinsamll yc,opmatpieanretsdw toit shinAuFs arnhdytAhFmL, baenadr sthaisin rcirseka isse dfurritshkeor finisccrheeamseidc sitnr opkaetiaenndtss wysittehm HicFe ,m[4b8]o.l ism
compMaroerde ttohsainn u8s0%rh yotfh mpa,taienndtst hwisitrhis kHiFsrfEuFr thhearvein fcrreeqauseednti nanpdat iceonmtspwleixth VHAFs,[ 4a8s] .documented on
HolteMr omreotnhitaonri8n0g%, aonfdp aatlmienotsst w50it%h HdeFmrEoFnshtraavtee frrueqnus eonft nanond-scuosmtapinleexdV vAesn,traiscudloacr utmacehnytceadrdoina
H(noolnte-srumstoainnietodr VinTg),. and almost 50% demonstrate runs of non-sustained ventricular tachycardia
(non-Tsuhset apirneesdenVcTe) .and severity of VAs increase along with the severity of HF, but their value to
predTicht eSpCrDes iesn ucnecalnedars [e4v9e]r. ityofVAsincreasealongwiththeseverityofHF,buttheirvaluetopredict
SCDisunclear[49].

Figure 1. Hemodynamic effects of supraventricular tachycardia.
Figure1.Hemodynamiceffectsofsupraventriculartachycardia.
Isolated premature ventricular complexes (PVCs) may be asymptomatic, whereas more
Isolatedprematureventricularcomplexes(PVCs)maybeasymptomatic,whereasmorecomplex
complex VAs may be accompanied by symptoms as palpitations, lightheadedness, presyncope or
VAs may be accompanied by symptoms as palpitations, lightheadedness, presyncope or syncope,
syncope, and a worsening of HF [50].
andaworseningofHF[50].
Of concern is the association of NSVT with sustained ventricular tachycardia (sustained VT)
OfconcernistheassociationofNSVTwithsustainedventriculartachycardia(sustainedVT)and
and ventricular fibrillation (VF), the usual mechanisms for SCD [51].
ventricularfibrillation(VF),theusualmechanismsforSCD[51].
However,theroleofVAstopredictsuddendeathisunclear;forthisreason,SCDriskstratification
inHFpatientsrequiresamultiparametricevaluation(seebelow).
J.Cardiovasc.Dev.Dis.2017,4,3 6of20
5. ClinicalImpactofBradyarrhythmiasinHF
ArrhythmiasintheHFpopulationarenotconfinedtotachyarrhythmias.Whiletheever-increasing
percentage of HF patients implanted with devices capable of pacing precludes quantification
of bradycardic risk at the current time, earlier registries illustrated that bradyarrhythmias with
electromechanicaldissociationwerethemechanismofSCDinasignificantnumberofselectedHF
patients[52]. Additionally,reversiblesinusnodedysfunctionandatrio-ventricularblockmayresult
fromdrugtoxicity[53](e.g.,digoxin,beta-blockers)orelectrolytedisordersandcaninduceworsening
ofHFsymptoms.
6. ManagementofSupraventricularTachyarrhythmiasinHF
6.1. ManagementofAtrialFibrillation
AccordingtoguidelinesofEuropeanSocietyofCardiology(ESC)[54],AFisclassifiedclinically
asparoxysmal(self-terminatingepisodeslasting<7days),persistent(non-self-terminatingepisodes
lasting 7 days to 6 months), long-standing persistent (lasting longer than 1 year), and permanent
(AFforwhichattemptsatterminationhavefailedorwhichisanacceptedrhythm).
ParoxysmsofAForrunsofrapidventricularresponsemayinstigateHFexacerbationorbecaused
byHFexacerbation; forthisreason, treatmentgoalsofHFmustaddressAF.Fortunately, manyof
thesamemedicationsusedtotreatHFalsotreatAF:β-blockersanddigoxinwillhelpcontrolheart
rate [55], while ACE inhibitors may lead to reverse remodeling and reductions in AF burden [56].
Antiarrhythmicdrugs,ontheotherhand,donothaveaprimaryroleinthetreatmentofHF;hence,
therhythmcontrolstrategy,althougheffectiveintreatingAF,hasshownnosurvivalbenefitinHF
patients. AFtreatmentstrategiescanbedividedintoratecontrolandrhythmcontrol; inaddition,
riskstratificationforstrokeiscentralinthemanagementofHFpatientswithAF[57].
6.1.1. RateControl
Rate control in the acute HF can be achieved with intravenous calcium channel blockers
(e.g.,verapamil0.075/0.15mg/kgivin2min,then0.005mg/kg/minorswitchto280–480mg/dayorally)
orβ-blockers(e.g.,metoprolol2.5–5mgivin2minevery5min,maximum15mg,then50–200mg/day
orally).Thesemedicationsshouldbeusedwithcautioninthehypotensiveorlownormotensivepatient,
sincehypotensionmaybeexacerbatedbynegativeinotropicmedications[58].Infusionsofshort-acting
medicationssuchasesmolol(500mcg/kgivin1min,then50–300mcg/kg/min)maybeusefulto
allow for a quickly reversible therapeutic trial, although such an approach is not evidence-based.
Thestrategyforlong-termratecontrolhasmoreevidencebasisthanacutetreatment. β-Blockersserve
adualroleintreatingHFandcontrollingrate,whereasdigoxinisbeneficialasanadjunctandreduces
HFexacerbations[59].
ThetargetforheartrateintheAFFollow-upInvestigationofRhythmManagement(AFFIRM)
trialwasdefinedaslessthan80beatsperminuteatrest,and110beatsperminuteduringa6min
walktest;however,theRateControlEfficacy(RACE-2)trialrandomizedpatientstoconventionalstrict
control(<80beatsperminuteatrest)ortoa“lenient”approach(<110beatsperminuteatrest)and
foundtheretobenosignificantdifferenceinmortality,NYHAclass,andHFhospitalizations[60].
6.1.2. RhythmControl
Maintenance of sinus rhythm with a strategy that may include a combination of rate control
therapy, antiarrhythmic medication, cardioversion, and radiofrequency ablation can be especially
challengingintheHFpatient. Severalfactorsmakerhythmcontrolmoredifficulttoachieveinthis
patientpopulation,includingleftatriumenlargement,comorbidities(e.g.,hypertension,obstructive
sleepapnea),andincreasedsympathetictone[61]. Nevertheless,despitelackofadvantagesoverrate
controlinmortality,strokereduction,orhospitalization,rhythmcontrolhasavitalroleintreating
symptomaticpatients.
J.Cardiovasc.Dev.Dis.2017,4,3 7of20
Acuterhythmcontrolisindicatedinhemodynamicallyunstablepatientsandcanbeachieved
witheitherpharmacotherapyordirectcurrentcardioversion. Electricalcardioversionwith200joules
biphasic energy is over 94% effective, and there is little benefit and potential harm (from repeat
cardioversion) in using lower energy levels [62]. In HF patients, care must be taken to assess for
hypokalemiaand/ordigoxintoxicitypriortocardioversion,inpatientswithhypokalemiapotassium
repletionisindicatedtoreducetheriskofVAs.
Pharmacologicalcardioversionwhendonesafelyprovidesalessinvasiveoption,butalower
successratewithhigherriskofadversedrugeffects.
Ibutilide (0.01 mg/kg iv with a second dose 10 min later if necessary) is approximately 50%
effectiveatcardioversion;however,theriskoftorsadesdepointesincreasesto11.4%comparedto
3.6%innon-HFpatients[63]. ClassIcagentsflecainideandpropafenonearecontraindicatedinthe
structuralheartdiseasebecauseofpro-arrhythmiaandshouldnotbeusedforchemicalcardioversion.
Amiodarone(150mgin10min,then1mg/minfor6h,then0.5mg/minfor18h)remainsanoption
formedicalcardioversionwithrestorationofsinusrhythmin80%ofpatients[64]. Theonlyother
antiarrhythmicmedicationthathasdemonstratedsafetyinHFinlargerandomizedtrialsisdofetilide
(125–500mcgonceevery12h);however,becauseofa3%riskoftorsades,inpatienthospitalizationto
monitorforQTprolongationduringinitiationismandatory[65].
6.1.3. RateControlversusRhythmControl
The landmark study comparing rate control to rhythm control is the AFFIRM trial, reported
in2002. Inthisstudy, therewasnodifferenceinmortalityorthromboemboliceventsbetweenthe
twogroupswith5yearsoffollow-up[66]. Morerecently,theAtrialFibrillationandCongestiveHeart
FailureTrial(AF-CHF)comparedrhythmcontrolversusratecontrolin1376patientswithEFlessthan
35%andclinicalsymptomofHF.Therewasnodifferenceindeath,stroke,orworseningheartfailure
betweenthetwogroupsat5yearsoffollow-up. FreedomfromAFwasachievedinjust20%intherate
controlarmand70%intherhythmcontrolarm[67].
WhilerhythmcontroldoesnotleadtodecreasedmortalityorHF,itremainsapreferredoption
insymptomaticpatients. Inconclusion,thechoicebetweenastrategyofrhythmversusratecontrol
shouldbeguidedbymanagementofsymptomsandpatientpreference,withnosignificantdifference
inmortalityorstrokedemonstratedinclinicaltrials.
6.1.4. Anticoagulation
ReductioninriskforstrokeinHFpatientswithAFrequiressystemicanticoagulationinmost
patientswithstructuralheartdisease. HFitselfcarriesa2.8%annualriskofstrokeintheCHADS-2
validationstudy,andcommoncomorbiditiessuchashypertensionanddiabetescanincreasetherisk
to5.8%peryear[68].
ThemorerecentCHA2DS2-VAScscore,developedinaDanishregistry[69],offersamorerefined
riskstratification,byaddinganextrapointforfemalegenderandvasculardisease,andatwo-tier
pointsystemforage: 1pointforage65–75yearsand2forageover75years.
Thisresultsinreclassificationofthelower-riskpatientsintheCHADS-2system, with39%of
thosedeemedlowriskbytheCHADS-2databasereclassifiedasintermediateriskbyCHA2DS2-VASc,
and21%reclassifiedashighrisk,withallthesepatientswarrantinganticoagulation.
The American College of Cardiology/American Heart Association/Heart Rhythm Society
guidelines recommend the CHA2DS2-VASc score as first line in risk stratification for stroke and
indicatetostartanticoagulationinpatientswithintermediateorhighriskforstroke[70].
The drugs of choice are novel oral anticoagulant while the use of vitamin K antagonists is
indicatedinpatientswithmechanicalvalve,leftventricularthrombus,andcontraindicationtonovel
oralanticoagulant[71].
J.Cardiovasc.Dev.Dis.2017,4,3 8of20
6.1.5. CatheterAblation
AFablationwithpulmonaryveinisolationremainsaviabletreatmentoptionforsymptomaticAF
thatcannotbetreatedadequatelywithantiarrhythmictherapy.
HF patients often have multiple comorbidities and left atrial enlargement, making them
unfavorableablationcandidates;however,single-centerstudieshavedemonstratedsimilarefficacyin
catheterablationforAFinHFpatientsascomparedwithnormalcontrols,withfreedomofAFat1year
around70%. Hsuetal. foundthatinthe86%ofpatientswithinadequateratecontrol,a20%increase
in EF was achieved with AF ablation [72], which raises the possibility that tachycardia-related
cardiomyopathyplaysalargerroleinHFwithAFthangenerallyappreciated.
Anintriguingstudy,thePulmonaryVeinAntrumIsolationversusAtrioVentricularNodeAblation
withBiventricularPacingforTreatmentofAtrialFibrillationinPatientswithCongestiveHeartFailure
(PABA-CHF),demonstratedthatpulmonaryveinisolationresultedinanimproved6minwalking
distance, increasedejectionfraction, andimprovedsymptomscomparedtoatrio-ventricularnode
ablationandpacing[73]. Whilepulmonaryveinisolationcanbevaluableinreducingthefrequencyof
AFinparoxysmalAF,theefficacyismuchlowerinpatientswithlong-termpersistentorpermanent
AF.Ifratecontrolcannotbeachievedmedically,thenatrio-ventricularnodeablationwithbiventricular
pacingremainsaviableoption[74].
InouropinioninpatientswithHFrEF,duethelowefficacyrateofAFablation,thebetteroption
wasatrio-ventricularnodeablationwithbiventricularpacing;viceversa,inpatientswithHFpEFor
HFmildreductionejectionfraction(HFmEF),particularlyifleftatrialvolumeindexislowerthan
40mL/mq,AFablationrepresentsthebeststrategy.
6.2. ManagementofAtrialFlutter
In1999,Albonietal. tookhemodynamicmeasurementsof23consecutivepatientsinAFLand
sinusrhythmanddemonstratedincreasedatrialpressureswithasubsequentfallinsystemicsystolic
pressureandriseindiastolicpressures[75]. Consequently,likeAF,AFLmayleadtoHFexacerbation.
TreatmentstrategiesforratecontrolandanticoagulationforAFLareoftengroupedunderthesame
approachesasforAFandaresimilartothosediscussedintheprevioussection. Themostfundamental
differenceinAFLascomparedtoAFisthatitisamoreorganizedrhythmandmoredifficulttorate
controladequately[76],andbecauseofthis,rhythmcontrolisoftenthepreferredstrategy. Fortunately,
incontrasttoAF,catheter-basedtreatmentfortypicalAFLflutterishighlyeffective[77],andoften
curative,andtheguidelinesreflectthisbymakinginitialcatheterablationforrecurrentsymptomatic
typicalatrialflutterarecommendedtreatmentstrategy.
6.3. ManagementofOtherTypeofSupraventricularArrhytmias
Patients with HF can develop paroxysmal SVAs that are otherwise observed in the healthy
population [78]. They may present with atrio-ventricular nodal reentrant tachycardia (AVNRT),
atrio-ventriculartachycardia(AVRT)mediatedbybypasstractsoratrialtachycardias(AT).
SucharrhythmiasaregenerallytreatedinasimilarfashionasinpatientswithoutHF;however,
generally, thethresholdforperformingcurativeradiofrequencyablationinHFpatientsshouldbe
lowerforthosearrhythmiasthatareeasilyamenabletosuchtherapy(i.e.,AVNRT,AVRT).
7. ManagementofVentricularTachyarrhythmiasinHF
7.1. PharmacologicManagement
In most patients with HF PVCs are asymptomatic, in those patients, correction of electrolyte
abnormalities(particularlylowserumpotassiumandmagnesium),withdrawalofagentsthatmight
provoke arrhythmias and optimization of HF pharmacological therapy is indicated; vice versa,
treatmentofarrhythmiasperseisgenerallynotindicated[79].
J.Cardiovasc.Dev.Dis.2017,4,3 9of20
Non-sustained VT will be commonly detected during 24–48 h Holter monitoring in HF
patientswithbothischemicandnon-ischemiccardiomyopathies. Inasmallproportionofpatients,
non-sustainedVTcanproducesymptoms,and,insuchcases,treatmentwithantiarrhythmicdrug
therapy is appropriate. First-line antiarrhythmic therapy for symptomatic patients consists of
optimization of β-blockers; if this approach fails to control symptoms, amiodarone or sotalol are
indicated [80]. The goal of acute therapy of sustained VT (defined by a duration of ≥30 s) is to
rapidlyrestoreastablerhythmwithaphysiologicallyappropriateventricularrateandtherebyprevent
organdamageorfurtherhemodynamicdeterioration. Patientswithseverehypotension,chestpain,
orevidenceforhypoperfusionshouldbeconsideredhemodynamicallyunstable,anddirectcurrent
cardioversionisusuallythemostexpeditiousmethodforterminatingthearrhythmia[81].
Inmanypatients,however,thetachycardiaisnotimmediatelylife-threateningandthepatientis
consciousandnotinseveredistress,insuchpatientspharmacologiccardioversionistheprocedureof
choice. PharmacologicconversionofasustainedVTepisodehasnotbeenstudiedinlargecontrolled
randomizedtrials;observationalandlimitedcontrolledtrialdata,however,indicatethatintravenous
lidocaine(100–150mgivthenslowivinfusionofadoseof2–4mg/min)hasoftenbeenregarded
as a first-line antiarrhythmic agent and can be useful in sustained VT associated with ischemia or
myocardialinfarction[82].
Intravenousprocainamide(10mg/kgiv)isanappropriatetherapyinthesepatients,asitrapidly
slowsandterminatessustainedVT;however,althoughprocainamideissuccessfulforacutearrhythmia
termination in around 75% of patients with monomorphic sustained VT, its use can be limited by
hypotension,whichoccursinapproximately20%oftheseindividuals[83].
Amiodarone(150–300mgin5miniv,followedbyaninfusionof1050mg/day)isalsouseful,
butitsonsetofactionisslowerthanlidocaineorprocainamide,andtheresultsofacutetermination
studieshavebeenvariable[84].
Medical therapy is also indicated for secondary prevention of sustained VT/VF. Together
with optimization of HF medical therapy amiodarone or sotalol must be used for reduce
recurrence [85]. We recommend amiodarone (200 mg/day) as first line therapy and reserve the
use of sotalol (240–480 mg/day in three times), together with beta-blockers, only in patients with
contraindication/adverse effects to amiodarone or in patients with persistence of SVT despite
amiodarone therapy. In case of recurrent sustained VT refractory to others antiarrhythmic drugs,
mexiletine(600mg/dayinthreetimes)canbeused(notcommerciallyavailableinsomeEuropean
countriessuchasGreeceorItaly).
7.2. CatheterAblation
Consensus document of European Heart Rhythm Association and Heart Rhythm Society’s
on catheter ablation of VAs [86] lists the current indications for this procedure as symptomatic
monomorphic sustained VT that recurs despite therapy with antiarrhythmic drugs or in patients
whodonotdesireorareintolerantofantiarrhythmicmedications. Catheterablationisalsoindicated
for patients with frequent PVCs, non-sustained VT or VT that results in myocardial dysfunction
(duetotachycardia-relatedcardiomyopathy),andforpatientswithVTfrombundlebranchreentry
or intrafascicular VTs and with recurrent sustained polymorphic VT or VF that is refractory to
antiarrhythmic medications when there is a suspected trigger (single PVC morphology) that can
betargetedforablation.
7.2.1. AblationofPrematureVentricularComplexandNon-SustainedVentricularTachycardia
PVCsarecommoninpatientswithHFandstructuralheartdisease.PVCsmayalsobeaccompanied
byshortrunsofnon-sustainedVT.ItiswelldocumentedthatfrequentPVCsmaybethecauseof
areversiblecardiomyopathy. ItisusuallydifficulttodistinguishwhetherthePVCsaretheprimary
problem or secondary to the cardiomyopathy. Cases in which PVCs represent more than 10% of
heartbeatsona24helectrocardiogram,withmostPVCsofthesameQRSmorphology,aremorelikely
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toinducetachycardiomyopathy[87]. PVCablationinthesepatientsmayresultinsignificantrecovery
oftheirleftventricularfunction.
7.2.2. AblationofIschemicCardiomyopathy
ThemechanismofVTinpatientswithpriormyocardialinfarctionisusuallyreentryaroundthe
myocardialscar,butfocalmechanismscanoccurin5%–10%ofpatients. Earlyreperfusionstrategies
haveresultedinsmallerinfarctsandlessaneurysmformationbutinpatientswithchronicischemic
cardiomyopathy,theriskofarrhythmiaremainssignificant. Althoughprogrammedstimulationcan
induceVTinalmost90%ofpatientswithischemiccardiomyopathyandclinicalsustainedVT,therate
and morphology often differ from that of spontaneous occurring VT [88]. These factors have led
toincreasingutilizationofsubstrate-basedablation,whichusesvoltageandpacemappingduring
sinusrhythmtoidentifytargetsforablation. ThisminimizestheepisodesofunstableVTduringthe
procedureandisbettertoleratedbypatientswithreducedleftventricularsystolicfunction. MostVT
canbeablatedfromtheendocardialapproach,butsomeVT,morecommonlypriortoinferiorinfarction,
mayrequireanepicardialapproach[89]. Outcomesofablationvaryconsiderablydependingonthe
studypopulation. Successfulablationisachievedin38%–72%,withaproceduralmortalityof0.5%–8%
over12months;afollow-upof50%–88%ofpatientswillremainfreeofVT[90].
7.2.3. AblationofNonIschemicCardiomyopathy
SustainedmonomorphicVTislesscommoninnon-ischemiccardiomyopathy,butthemechanism
isusuallyalsoreentry.Areasofscarinnon-ischemiccardiomyopathytendtobesmallerandmoreoften
locatedinthemid-myocardiumorepicardiallayers. Itiscommontoinducemultiplemorphologiesof
VTinthispatientgroupandendocardialablationaloneislesssuccessful[91]. Mappingandablating
epicardialsitsincreasethesuccessinthispatientgroup,buttheoptimaltimingofepicardialablation
isyettobedetermined[92].
8. SuddenCardiacDeath
8.1. SuddenCardiacDeathinPatientswithHFrEF
Sudden,presumablyarrhythmicdeathaccountsforasignificantproportionoftotalmortality
inHFpatientswithII–IIINYHAclass,whereasprogressivehemodynamicdeteriorationandpump
failurearethemajorcausesofdeathinpatientswithIVNYHAclass. Manyriskfactorsforarrhythmia
recurrence and SCD have been identified in patients who have structural heart disease; however,
developingacomprehensiveriskstratificationstrategyremainsachallenge. Here,webrieflyillustrate
theparameterusedinclinicalpracticeforstratificationofSCDriskinHFpatients.
8.1.1. LeftVentricularSystolicDysfunction
A reduced ejection fraction remains, according to international guidelines (Table 2), the most
consistent predictor of SCD in patients who have structural heart disease, irrespective of etiology.
Patients in the follow-up Multicenter Automatic Defibrillator Implantation Trial (MADIT-II) who
had an ejection fraction less than 30% had a rate of SCD of approximately 9.4% at 20 months [93].
Inasimilar population of patients, however, an ejection fraction greater than 35% and history of
myocardialinfarctionconferredonlya1.8%riskofSCD[94].