3/23/2017 Atrialfibrillation:classification,pathophysiology,mechanismsanddrugtreatment

Heart.2003Aug89(8):939943. PMCID:PMC1767799

Atrialfibrillation:classification,pathophysiology,mechanismsanddrug
treatment
ViasMarkides1andRichardJSchilling2
1
StMarysHospital,London,UK
2
StBartholomewsHospital,London,UK
Correspondenceto:
DrViasMarkides,WallerCardiacDepartment,StMarysHospital,PraedStreet,LondonW21NY,UK
v.markides@imperial.ac.uk

Keywords:atrialfibrillation,pharmacologicaltreatment

CopyrightCopyright2003byHeart

ThisarticlehasbeencitedbyotherarticlesinPMC.

Theprevalenceofatrialfibrillation(AF),alreadythemostcommonsustainedcardiacarrhythmia,isconstantly
rising,evenafteradjustingforageandpresenceofstructuralheartdisease.AFincreasestheriskofstrokesixfold
andisassociatedwithatwofoldincreaseinmortality,whichremainsabove1.5foldafteradjustingforco
morbidity,predominantlycausedbycerebrovascularevents,progressiveventriculardysfunction,andincreased
coronarymortality.TheadversehaemodynamiceffectsofAFarewelldescribedandrelatenotonlytolossofatrial
contraction,butalsototheaccompanyingrapidityandirregularityofventricularcontraction.AlthoughAFmaybe
asymptomatic,uptotwothirdsofpatientsreportthatthearrhythmiaisdisruptivetotheirlives.Finally,thetreatment
ofAFanditsassociatedcomplicationscreatesasignificantandincreasingeconomicburden.Thisarticlefocuses
predominantlyonthepathophysiologyofthearrhythmiaanditspharmacologicaltreatment.Anticoagulationfor
preventionofthromboembolism,afundamentalprincipleinthemanagementofthisarrhythmia,electrical
cardioversion,percutaneousablationtechniques,andsurgeryforAFarenotdiscussedinanydetail.

CLASSIFICATION Goto:

AFmaybeclassifiedbasedonaetiology,dependingonwhetheritoccurswithoutidentifiableaetiologyinpatients
withastructurallynormalheart(loneAF),orwhetheritcomplicateshypertensive,valvar,orotherstructuralheart
disease.

Aclassificationsystembasedonthetemporalpatternofthearrhythmiahasbeenrecentlyrecommended.1Patients
presentingtomedicalattentionmayhaveafirstdetectedepisodeofAFor,ifpreviousepisodeshavebeen
documented,recurrentarrhythmia.Episodesthemselvesmaybeparoxysmal,iftheyterminatespontaneously,
usuallywithinsevendays,orpersistentifthearrhythmiacontinuesrequiringelectricalorpharmacological
cardioversionfortermination.AFthatcannotbesuccessfullyterminatedbycardioversion,andlongstanding(>1
year)AF,wherecardioversionisnotindicatedorhasnotbeenattempted,istermedpermanent(fig1).

Figure1
Temporalclassificationofatrialfibrillation(AF).AnincidentepisodeofAF
presentingtomedicalattentionmaybethefirsteverdetectedepisodeofthe
arrhythmia,orrepresentrecurrenceofpreviouslyrecognisedarrhythmia
(left).Theepisodemay...

PATHOPHYSIOLOGYANDMECHANISMS Goto:

Hypertensive,valvar,ischaemic,andothertypesofstructuralheartdiseaseunderliemostcasesofpersistentand
permanentAF,whereasloneAFaccountsforapproximately15%ofAFcases.FamilialAFiswelldescribed,
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althoughatpresentconsideredrare.Aregiononchromosome10(10q22q24)wasoriginallyidentifiedas
containingthegeneresponsibleforAFinfamiliesinwhichthearrhythmiasegregatedasanautosomaldominant
trait.However,familialAFappearstobeaheterogeneousdisease.Afamilywithamutationinthegeneencoding
theporeformingsubunitofthecardiacIKschannelonchromosome11thatresultsinincreasedfunctionofthis
channel,withaffectedmembersdevelopingpersistentAFprobablycausedbyareductioninrefractoriness,has
morerecentlybeendescribed.2

ThepathogenesisofAFisnowthoughttoinvolveaninteractionbetweeninitiatingtriggers,oftenintheformof
rapidlyfiringectopicfocilocatedinsideoneormorepulmonaryveins,andanabnormalatrialtissuesubstrate
capableofmaintainingthearrhythmia.AlthoughstructuralheartdiseaseunderliesmanycasesofAF,the
pathogenesisofAFinapparentlynormalheartsislesswellunderstood.Althoughthereisconsiderableoverlap,
pulmonaryveintriggersmayplayadominantroleinyoungerpatientswithrelativelynormalheartsandshort
paroxysmsofAF,whereasanabnormalatrialtissuesubstratemayplayamoreimportantroleinpatientswith
structuralheartdiseaseandpersistentorpermanentAF.

FocalinitiatorsofAF
Itisnowknownthatfociofrapidectopicactivity,oftenlocatedinmuscularsleevesthatextendfromtheleftatrium
intotheproximalpartsofpulmonaryveins,playapivotalroleintheinitiationofAFinhumans.3Lessfrequently,
focalinitiationofAFmayberesultfromectopicactivitythatarisesfrommuscularsleevesintheproximalsuperior
venacava,fromtheligamentofMarshall,orotherpartsoftherightandleftatria.InitiationofAFbyrapidfocal
activityhasbeendemonstratednotonlyinpatientswithstructurallynormalheartsandparoxysmalAF,butalso
duringtheprocessofreinitiationofpersistentAFafterelectricalcardioversion,bothinthepresenceandabsenceof
associatedstructuralheartdisease.4

Muscularsleevesthatextendintotheproximalpulmonaryveinsarepresentinthenormalheart.Themechanisms
involvedintheproductionofectopicactivitybythesesleevesinpatientswithAF,aswellastheexactmechanism
ofinitiationofAFbytherapidactivity,remaintobeelucidated.Proposedmechanismsforgenerationofabnormal
focusactivityincludeincreasedautomaticity,triggeredactivity,andmicroreentry.Changesinautonomictone
aroundthetimeofinitiationofAFparoxysms,withanincreaseinsympatheticactivityfollowedbyanabrupt
changetoparasympatheticpredominance,havealsorecentlybeendemonstrated.5

TissuesubstratecapableofmaintainingAF
BothexperimentalandhumanmappingstudieshavedemonstratedthatpersistentAFisgenerallycharacterisedby
thepresenceofmultiplewaveletsofexcitationthatpropagatearoundtheatrialmyocardium.However,thereis
considerablevariabilityintheobservedpatternsofactivation,bothbetweenpatientsandbetweenthetwoatriaof
individualpatients.PerpetuationofAFisfacilitatedbytheexistenceordevelopmentofanabnormalatrialtissue
substratecapableofmaintainingthearrhythmia,6withthenumberofmeanderingwaveletsthatcanbe
accommodatedbythesubstratedeterminingthestabilityofAF.7,8Reentrywithintheatrialmyocardiumis
facilitatedbyconductionslowingandshorteningoftherefractoryperiod.Bothhavebeendemonstratedinanimal
modelsandpatientswithAF,withincreaseddispersionofrefractorinessfurthercontributingtoarrhythmogenesis.
Shorteningoftheatrialactionpotential,reducedexpressionofLtypecalciumchannels,andmicrofibrosisofthe
atrialmyocardiumhavealsobeendemonstrated.

Electrophysiologicalremodelling
AFinitselfcancauseprogressivechangesinatrialelectrophysiologysuchassubstantialrefractoryperiod
shortening,whichfurtherfacilitateperpetuationofthearrhythmia.Inanimalstudies,changesinionchannel
functionandshorteningofrefractoryperiodsstartwithinminutesofAFonsetand,by24hours,sufficientatrial
remodellinghasoccurredtoincreasethelikelihoodofAFpersisting.However,restorationofsinusrhythminthis
animalmodel,evenaftertwoweeksofpersistentAF,resultsinarapidreversaloftheelectrophysiological
remodelling.9

Classification,pathophysiology,andmechanismsofAF:keypoints

Atrialfibrillation(AF)isthemostcommonsustainedcardiacarrhythmia
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AFisusuallyclassifiedaccordingtoitstemporalpatternasparoxysmal,persistent,orpermanent.
AFadverselyaffectscardiachaemodynamicsbecauseoflossofatrialcontractionandtherapidityand
irregularityoftheventricularrate
AFcausessignificantsymptomsinapproximatelytwothirdsofpatients
AFisassociatedwitha1.5to2foldincreaseinmortality
AFisassociatedwitha6foldincreaseinriskofstroke
thisriskcanbesubstantiallyreducedwithantithrombotictreatment
decisionsregardingantithrombotictreatmentshouldnotbebasedonthetemporalpatternofthe
arrhythmia,butonthepresenceorabsenceofriskfactorsforthromboembolisminpatientswith
AF
AFisinitiatedbyrapidelectricalactivity,oftenarisingfromarrhythmogenicfocilocatedinthemuscular
sleevesofpulmonaryveins.Thearrhythmiaismaintainedbymultiplereentrantwavelets.Reduced
refractorinessandconductionslowingfacilitatereentry
AfteraperiodofcontinuousAF,electricalremodellingoccurs,furtherfacilitatingAFmaintenance(AF
begetsAF).Thesechangesareinitiallyreversibleifsinusrhythmisrestored,butmaybecomepermanent
andbeassociatedwithstructuralchangesiffibrillationisallowedtocontinue

Electricalremodellinganditsreversalalsoappeartooccurinhumans.Clinicalobservations,aswellasanumberof
studies,havesuggestedthatpatientswithrecurrentAFmaydevelopincreasingproblemswithtimeanda
significantproportionmayprogresstopermanentAF.Inpatientsundergoingelectricalcardioversionofpersistent
AF,thedurationoftheantecedentepisodeisapotentpredictorofmaintenanceofsinusrhythm.Moreover,patients
withAFareatparticularlyhighriskofrecurrenceofthearrhythmiainthefirstfewdaysaftercardioversion.10
Indeed,ithasbeendemonstratedthatshortenedrightatrialrefractoryperiodsobservedimmediatelyafter
cardioversionofpersistentAFlengthenagainwithinfourweeks.11Althoughreverseremodellingafterrestoration
ofsinusrhythmdoesoccurinhumanswithestablishedAF,thismaynolongerbepossibleafterveryprolonged
periodsofAF12andthusrestorationandmaintenanceofsinusrhythminthesepatientsisoftendifficult.

PHARMACOLOGICALTREATMENT Goto:

InpatientswithshortparoxysmsofAF,therapeuticstrategiesshouldgenerallyconcentrateonprovidingcontrolof
thearrhythmiaitself.InpatientswithpersistentAF,however,theclinicianisoftenfacedwiththedilemmaasto
whethertotryandrestoreandthenmaintainsinusrhythm(rhythmcontrol),ortoacceptthearrhythmia(asinthe
caseofpermanentAF)andcontroltheventricularrate(ratecontrol).Regardlessofthearrhythmiapatternorthe
therapeuticstrategychosen,andintheabsenceofcontraindications,patientsshouldbeconsideredfor
anticoagulationiftheyhaveoneormoreriskfactorsforthromboembolism(fig2).Patientsatloworintermediate
risk,andhigherriskpatientsinwhomwarfariniscontraindicated,maybenefitfromantiplatelettreatment.13

Figure2
Therapeuticgoalsinpatientswithatrialfibrillation

Rateversusrhythmcontrol
ThereisstillnoconsensusregardingwhetherpatientswithpersistentAFarebestmanagedusingstrategiesthat
targetthearrhythmiaitself,orthosethatacceptthearrhythmiaandcontroltheventricularrate.Withratecontrol
strategies,thearrhythmiaisallowedtocontinue,andsymptomaticimprovementisachievedsolelybecauseofbetter
controloftheventricularrate.Astheatriacontinuetofibrillate,theriskofthromboembolismpersistsand
ventricularfillingoccursonlypassively,withouttheactivecontributionofatrialcontraction.Rhythmcontrol,onthe
otherhand,aimstorestoresinusrhythmandthussynchronisedatrioventricularcontraction.Intheory,thisstrategy
shouldalsohelpsloworpreventtheprogressiontopermanentAFandreducetheriskofthromboembolism,
althoughthereisasyetnoevidencetosupportthelatterassumption.Anotherimportantconsideration,however,is
thepropensityfordrugsusedforrhythmcontroltocauseseriousproarrhythmia.

Inarandomisedopenlabelpilottrialcomparingratecontrol,predominantlyusingdiltiazem,andrhythmcontrol,
predominantlyusingamiodaronewithorwithoutdirectcurrent(DC)cardioversioninpatientswithAF,thetwo

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strategiesproducedsimilarimprovementsinqualityoflife.Asignificantimprovementinexercisetoleranceas
assessedbyasixminutewalktestwasdemonstratedintherhythmcontrolgroup,eventhoughonly56%ofthe
patientsinthisgroupachievedsinusrhythm.However,hospitaladmissions,predominantlyforDCcardioversions,
werehigherintherhythmcontrolgroup.14

TheresultsofthemuchlargerAFFIRM(atrialfibrillationfollowupinvestigationofrhythmmanagement)trialhave
recentlybeenreported.15Thestudyenrolledmorethan4000patientswithpredominantlypersistentAF.Enrolled
patients(meanage70years)hadatleastoneriskfactorforstrokeordeathaccompanyingAFandcould
symptomaticallytoleratethearrhythmiaatbaseline.Approximately50%ofpatientsrandomisedhadahistoryof
hypertension,whereas25%hadcoronaryarterydiseaseorheartfailure.Patientsrandomisedtoratecontrol
receiveddigoxin,blockers,orcalciumantagonists,whereasthoserandomisedtorhythmcontrolreceived
amiodarone,sotalolorpropafenoneand,ifnecessary,DCcardioversion.Atfollowup,sinusrhythmwasachieved
inonly60%ofpatientsintherhythmarm,whereassatisfactoryratecontrolwasachievedin80%ofpatientsinthe
ratecontrolarm.Theprimaryendpointofthestudy,allcausemortality,wasnotsignificantlydifferentbetweenthe
twogroups,althoughtherewasatrendfavouringratecontrol.Therewerealsonodifferencesinsecondaryend
pointcomponents,includingstrokerate,qualityoflife,orfunctionalstatusand,althoughatrendfavouringrate
controlwasonceagainnoted,anticoagulationwasdiscontinuedinmorepatientsintherhythmthanintherate
controlgroup.Themajorityofstrokesinbothgroupsoccurredinpatientswithsubtherapeuticlevelsof
anticoagulation,orafterwarfarinhadbeenstopped.Inthepredefinedgroupofpatientswhowereundertheageof
65,whichaccountedforapproximatelyaquarterofpatientsincludedinthestudy,atrendfavouringrhythmcontrol
wasnoted.

Theseresultssuggestthat,atleastinthiselderlypopulationofpatientswithAFandriskfactorsforstrokeordeath,
ratecontrolisatleastasgoodasrhythmcontrol.Itshould,however,beemphasisedthattheseconclusionsarenot
necessarilyapplicabletodifferentpatientpopulations,includingyoungerpatientswithstructurallynormalhearts,or
patientswhoareunabletotoleratethearrhythmiadespitereasonableratecontrol.TheresultsofAFFIRMalso
appeartobeatoddswiththeresultsofaDIAMOND(Danishinvestigationsofarrhythmiaandmortalityon
dofetilide)substudy,inwhichpatients(meanage72years)withheartfailureorrecentmyocardialinfarctionand
AFhadbeenrandomisedtotreatmentwithdofetilideorplacebo.Inthisstudy,dofetilidewasshowntobe
moderatelyeffectiveatrestoringsinusrhythm,buthadnodemonstrableeffectonmortality.However,ina
multivariatemodel,restorationofsinusrhythm,regardlessofwhetherthiswasachievedpharmacologically,
spontaneously,orelectrically,wasassociatedwithanotablereductioninmortality.16

Restorationofsinusrhythm
RestorationofsinusrhythminpatientswithAFmayimprovesymptomsandcardiachaemodynamics,reversethe
atrialremodellingassociatedwithcontinuingarrhythmia,and,atleastintheory,reducetheriskof
thromboembolism.Ithasbeendemonstratedthatrestorationofsinusrhythmisassociatedwithimprovementsin
exercisecapacityandpeakoxygenconsumption,bothinpatientswithstructuralheartdiseaseandinthosewith
normalhearts.17

SincethereisanimportantinverseassociationbetweendurationofAFandlikelihoodofsuccessfulcardioversion
orrecurrenceofarrhythmia,itisimportantthatattemptstorestoresinusrhythmaremadeassoonasthisispossible
andsafe.However,althoughmostguidelinessuggestthatcardioversion,beitpharmacologicalorelectrical,within
48hoursofarrhythmiaonsethasalowriskofthromboembolismevenwithoutanticoagulation,theauthorspolicy
isnottoelectivelycardiovertpatientswhohavebeeninAFwithoutanticoagulationforlongerthan1224hours.

ForpatientswhohavebeeninAFforlonger,orinwhomthedurationofthearrhythmiaisnotclear,aminimum
periodofanticoagulationofthreeweeksisrecommendedbeforecardioversion.1Analternativeapproach,
particularlyusefulifthereisclinicalurgencytorestoresinusrhythm,istoperformtransoesophageal
echocardiographyinanattempttoexcludethepresenceofatrialthrombusbeforecardioversion.However,evenif
transoesophagealechocardiographyhasdemonstratednothrombusbeforecardioversion,patientsmustbe
anticoagulatedforatleastonemonthaftercardioversion,sincemechanicalatrialfunctionmayreturnslowlyafter
cardioversion.

PharmacologicalcardioversionisoftenpossibleforthetreatmentofAFofrecentonset,butefficacyisdramatically
reducedinpatientswithAFthatpersistsformorethan48hours.Flecainide,administeredintravenouslyinpatients
withAFofrecentonset,hasbeenshowntorestoresinusrhythmin7295%ofpatients,withthegreatestsuccess
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ratesinpatientswhoreceivetreatmentwithin24hoursofAFonset.Flecainidealsoappearstobesuperiortoboth
propafenoneandamiodaroneinthissetting.

PharmacologicalcardioversionismuchlesslikelytobeeffectivewhenAFhaspersistedformorethan48hours.
AdministrationofdofetilidetopatientswithpersistentAFofmorethantwoweeksdurationhasbeenshownto
restoresinusrhythmin2242%withinthreedays.However,becauseofasignificantriskofproarrhythmia,
treatmentmustbeinitiatedduringcontinuousmonitoringinhospital.Amiodaroneappearstobethemosteffective
agentforrestoringsinusrhythminpatientswithpersistentAF,withonesmallstudydemonstratingsinusrhythm
restorationin44%and68%ofpatientsattwodaysandninemonths,respectively.18Electricalcardioversion,which
hassuccessratesbetween6590%,isnotdiscussedhere.

Sinusrhythmmaintenance
Flecainideandpropafenonehavebeenshowntobesimilarlyeffectiveatsuppressingsymptomaticparoxysmsof
AFand,intheabsenceofstructuralheartdisease,neitherdrugappearstocausesignificantproarrhythmia.In
general,theseclassIcagentstendtobebettertoleratedandmoreeffectivethanclassIaagents,suchasquinidine
anddisopyramide.

Digoxinadministrationdoesnotaltertheprobabilityofrestorationormaintenanceofsinusrhythminpatientswith
AFofrecentonset.Pureadrenoceptorantagonistshaveasmallbeneficialeffectinmaintainingsinusrhythmin
patientswhohavebeencardiovertedfromAF.Thereappearstobenodifferencebetweenpure1antagonistsand
sotalol,eitherinreductionofAFburdeninpatientswithparoxysmalAF,orinthelikelihoodofAFrelapseafter
cardioversion,butanexcessofproarrhythmiceventshasbeennotedinpatientsreceivingsotalol.Sotalolmaybe
betterthanpropafenoneatpreventingAFparoxysms.

TheefficacyofamiodaronehasbeendemonstratedbothinpatientswithparoxysmalAFandthosewithpersistent
AFrefractorytootherdrugs,withaprobabilityofarrhythmiasuppressionof5080%at13years.Inadirect
comparison,amiodaronehasmorerecentlybeenshowntobesuperiortobothpropafenoneandsotalolat
maintainingsinusrhythm.19Animportantconsiderationwhenprescribingamiodaroneforlongtermtreatmentis
that,inadditiontoitsrareserioussideeffects,patientsonamiodaroneforlongperiods(>5years)frequently
developthyroiddysfunction.

Ultimately,thechoiceofpharmacologicalagentforsinusrhythmmaintenanceneedstobeindividualised,and
basednotonlyontherelativeefficacyofthedifferentagents,butalsoontheirsideeffectprofiles,contraindications,
andthepatientsventricularfunction.Adrenoceptorantagonistsmaybepreferredinpatientswithrelatively
normalhearts,withclassIcagentsasanalternative,andamiodaronereservedforpatientsunresponsivetoother
drugsorthosewithpoorventricularfunction.

PrinciplesofAFmanagement:keypoints

Assessmentofthromboembolicriskandantithrombotictreatmentforpatientsatrisk
Achoiceof:
Restorationandmaintenanceofsinusrhythm(rhythmcontrol)
usingelectricalcardioversion,drugs,ablation,orsurgerymaybeparticularlyusefulin
youngerpatientswithstructurallynormalheartsandparoxysmalAF,orpersistentAFof
recentonset
surgerysuitableeveninlongstandingAF,butassociatedwithsubstantialmorbidityand
mortality
Acceptanceofthearrhythmiaandcontroloftheventricularrate(ratecontrol)
usingdrugs(usuallyorcalciumchannelblockerswithorwithoutdigoxin),or
occasionallyatrioventricularnodeablationandimplantationofapermanentpacemaker
maybemoreappropriateinelderlypatientswithhypertensionorstructuralheartdisease
andpersistentorpermanentarrhythmia,especiallyifthiscanbetoleratedsymptomatically

Ventricularratecontrol

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DigoxiniswidelyusedforventricularratecontrolduringAF.Althoughgenerallysafetouseeveninpatientswith
poorventricularfunction,itappearstobelesseffectivethanotheragentsatcontrollingventricularrate,particularly
duringacuteorparoxysmalAF,exercise,orcriticalillnesses.Theefficacyofdigoxinatcontrollingtheventricular
rateinAFisalsolimitedduringacuteparoxysmsofAF,anduseofthedrugmayprolongthedurationof
paroxysms.20DiltiazemiseffectiveatcontrollingventricularrateinpatientswithAFandfastventricularrates.
Bothdiltiazemandverapamilaresuperiortodigoxinatcontrollingventricularratesduringexerciseandallow
modestimprovementsinexercisecapacity,withoutcausingrestingbradycardiaorpauses.Thebenefitsofcalcium
channelblockersaswellasofblockersoverdigoxinappeartobeparticularlypronouncedinpatientswith
impaireddiastolicfilling,suchasthosewithmitralstenosis.Combinationsofdigoxinwithcalciumchannel
blockersorblockersmaynotonlyimproveventricularratecontrol,bothatrestandduringexercise,butmayalso
improveexercisecapacity,eveninpatientswithunderlyingventriculardysfunction.

Inpatientswithimpairedventricularfunction,chronicadministrationofamiodarone,inadditiontoreducingAF
burden,significantlyreducestheventricularrate.Intravenousamiodaronemayalsobemoderatelyeffectiveat
controllingtheventricularrateincriticallyillpatientswithAF.

Commonmistakes
Anticoagulation Inclinicalpractice,physiciansareoftenlesskeentoprescribeanticoagulationforpatientswith
paroxysmalAFthanforthosewithpersistentAF.Althoughtheriskofthromboembolismmayindeedbehigherin
patientswithpersistentAF,thromboembolicriskmaybesubstantialeveninpatientswithparoxysmalAF.
Thereforedecisionsregardinganticoagulationshouldbepredominantlybasedonthepresenceorabsenceofwell
establishedriskfactorsforthromboembolism,includingpreviousstrokeortransientischaemicattack,valvaror
otherstructuralheartdisease,hypertension,diabetes,agemorethan65years,andechocardiographicparameters
suchasleftventricularfunctionandleftatrialsize,ratherthanonthetemporalpatternofthedisease.

Ratecontrol Itiscommonforphysicianstoprescribedigoxinaloneinattemptstocontroltheventricularresponse
toAF.Blockersorcalciumantagonistsaremoreeffective.

Rhythmcontrol Itisalsocommonforphysicianstoprescribedigoxintocardiovertpatients.Digoxinhasnoeffect
onthelikelihoodofcardioversion,whereasclassIantiarrhythmicdrugsoramiodaroneareofteneffective.

CONCLUSIONS Goto:

AFisacommonandincreasinglyprevalentarrhythmiathatisassociatedwithsubstantialmorbidityandmortality.
Becauseofthelimitedefficacyofcatheterbasedtreatments,especiallyforpatientswithpersistentAF,andthe
substantialmorbidityandmortalityassociatedwithsurgeryforthearrhythmia,pharmacologicaltherapyremainsthe
mainstayoftreatmentforthemajorityofpatients.TheoptimumtreatmentstrategyforpatientswithpersistentAF
remainscontroversial,withsomecliniciansfavouringrhythmcontrolandothersratecontrol.Ultimately,treatment
needstobeindividualised,basedonsymptomatologyandthelikelihoodofmaintenanceofsinusrhythm.
Regardlessofthesecontroversiesinarrhythmiamanagement,anticoagulationorantiplatelettherapyforstroke
preventionformanintegralpartoftreatmentofpatientswithAFandriskfactorsforthromboembolism.

ThepredominantfocusofrecentdevelopmentsinpharmacologicaltherapyforAFhasbeenthedevelopmentof
novelclassIIIantiarrhythmicagents,eachwithcharacteristiceffectsonpotassiumchannels.Ingeneral,theseagents
haveprovenmoderatelyefficaciousbutcarryasignificantriskofproarrhythmia.Whileresearchinthisfield
continues,otherdrugssuchasspecificserotoninreceptorantagonistscontinuetobedeveloped.Further
developmentsincatheterablationtechnologiesmaygreatlyfacilitatesafeisolationofmultiplepulmonaryveinsfor
patientswithpredominantlyparoxysmalAF,whereasimprovementsinlinearcatheterablationtechnologies,
accompaniedbythreedimensionalatrialmappingandcatheternavigation,mayfacilitatecreationoflinearleftatrial
lesions,whichappeartobecriticalforthesuccessfultreatmentofpatientswithpersistentarrhythmia.

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majorityofstrokesinbothgroupsoccurredinpatientswithsubtherapeuticanticoagulationorafter
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