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Ростовский Государственный Медицинский Университет

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Медицина общая

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Medications

Medical managementbeginswith considerationofappropriateantithrombotic therapy.Coumadinhas shown to be superior to aspirin (ASA) or ASA in combination with clopidogrel for prevention of thromboemboliceventsinpatientswithnonvalvular-associatedAF. Directoralanticoagulants(DOAC)suchasdabigatran,rivaroxaban,apixaban,andedoxabanhavebeen directlycompared withwarfarininrandomizedprospective trials and havebeen showntobe either noninferiororsuperiortocoumadininpreventingstrokeinAFpatients. RatecontrolofAFisachievedwithmedicationsthatlimitconductionthroughtheAVnodesuchasnon-

dihydropyridine calcium channel blockers (verapamil, diltiazem, etc.), β-adrenergic antagonists, anddigoxin.

Rhythm control can be attempted with selected antiarrhythmic drugs. Pharmacologic control with antiarrhythmic drugs is more effective at preventing recurrence of AF than chemical cardioversion (Table7-3).

TABLE7-3

PHARMACOLOGICAGENTSUSEDFORHEARTRATECONTROLINATRIAL FIBRILLATION

Drug Loading

Dose

Onsetof Action

Maintenance Dose

MajorSide Effects

Recommendation

WithoutEvidenceofAccessoryPathway

Esmolol

IV: 500μg/kg over1min, followedby 50μg/kgfor 4min

IV:2–10min IV:Upto

200μg/kg/min continuous infusion

↓BP,↓HR,HB, HF, bronchospasm

MetoprololaIV:2.5–5mg

over2min, repeat dosesevery 5minas neededupto 15mg

IV:20min – ↓BP,↓HR,HB,

HF, bronchospasm

PO:50–100 mg(insingle ordivided doses depending upon formulation)

PO:Within1hPO:Upto

400mgdaily

– –

PropranololaIV:1mg

over1min,

– – ↓BP,↓HR,HB,

HF,

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repeatevery 2minas neededupto 3doses

bronchospasm

PO:10–30 mgevery6– 8h

PO:1–2h PO:10–40

mgtidorqid

– –

Diltiazem IV:0.25

mg/kgover2 min,followed by0.35 mg/kgover2 minif needed

IV:3min IV:5–10

mg/h,upto 15mg/h

↓BP,HB,HF I

PO:120mg daily(in singleor divided doses depending upon formulation)

PO:30–60 min(for immediate release formulation)

PO:120–360 mgdaily

– –

Verapamil IV:0.075–

0.15mg/kg over2min, followedby 10mgbolus after15–30 minif needed

IV:3–5min IV:5mg/h ↓BP,HB,HF I

PO:180– 480mgdaily (insingleor divided doses depending upon formulation)

PO:1–2h (for immediate release formulation)

PO:Upto 480mgdaily

– –

Amiodarone IV:150mg

over10min, followedby 1mg/minfor 6h,followed by0.5

2d–3wkfor antiarrhythmic effectsofIV andPO

PO:200mg oncedaily, canbe decreasedto 100mgin elderlyand

↓BP,HB,↓HR, warfarin interaction; seetextfor descriptionof dermatologic,

Acutesetting:IIa (IV) Nonacute/chronic: IIb(PO)

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mg/minfor 18h PO:600– 800mgdaily individed dosesfor totalloadof 10gover2– 4wk

patientswith lowBMI

thyroid, pulmonary, corneal,and liverside effects

WithEvidenceofAccessoryPathway

Amiodarone IV:150mg

over10min, followedby 1mg/minfor 6h,followed by0.5 mg/minfor 18h

2d–3wk PO:200mg

oncedaily

Seeabove IIa

WithHeartFailureandWithoutAccessoryPathway

Digoxin IV:0.25–0.5

mgover severalmin, repeat0.25 mgdoses every6hto maximum doseof1.5 mgin24h; dosemay needtobe reducedby 50%in patientswith CKD/ESRD

IV:5–60min PO:1–2h

PO:0.125–

0.25mgonce daily;0.0625 mgoncedaily forGFRof 10–50 mL/min;

0.0625mg onceevery48 hforGFR <10mL/min

Digoxin toxicity,HB, ↓HR

BMI,bodymassindex;↓BP,hypotension;CKD,chronickidneydisease;ESRD,end-stagerenaldisease;GFR,glomerular filtrationrate;HB,heartblock;HF,heartfailure;↓HR,bradycardia;NA,notapplicable.

Onlyrepresentativeβ-blockersareincludedinthetable,butothersimilaragentscouldbeusedforthisindicationinappropriate

doses.

Onsetisvariable,andsomeeffectsoccurearlier.

Conversiontosinusrhythmandcatheterablationoftheaccessorypathwayaregenerallyrecommended;pharmacologictherapy forratecontrolmaybeappropriatetherapyincertainpatients.Seetextfordiscussionofatrialfibrillationinsettingof preexcitation/Wolff–Parkinson–Whitesyndrome.

Amiodaronecanbeusefultocontroltheheartrateinpatientswithatrialfibrillationwhenothermeasuresareunsuccessfulor contraindicated.

FIRSTLINE

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Preventionofstrokeandsystemicemboli—centraltenetofAFmanagementisguidedbyindividual risk assessment. Systemic anticoagulation with coumadin or DOAC attenuates risk of stroke or systemicemboliassociatedwithAF. Use of oral anticoagulants requires careful risk–benefit analysis to identify patients who are at sufficientriskforthromboemboliceventswithoutsignificantriskofhemorrhagiccomplications.

CHA2DS2-VAScscore—validatedriskstratificationtoolusedinnonvalvularAFtopredictstroke orsystemicembolusriskbased onthepresenceoffollowing riskfactors:CHF, HTN,age>65or

>75 years, diabetes mellitus, female gender, prior stroke or transient ischemic attack (TIA), and historyofvasculardisease(Table7-4).

TABLE7-4

ANNUAL STROKE RISK IN PATIENTS WITH NONVALVULAR ATRIAL FIBRILLATION NOT TREATED WITH ANTICOAGULATION ACCORDING TO THE CHA2DS2-VASC

SCORE

CHA2DS2-VAScScore StrokeRisk(%)

0 0

1 1.3

2 2.2

3 3.2

4 4.0

5 6.7

6 9.8

7 9.6

8 12.5

9 15.2

CHA2DS2-VASc, cardiac failure, hypertension, age65–74 years or age >74 years (doubled), diabetes, female sex, stroke (doubled),andahistoryofvasculardisease.

Theadjustedstrokeratewasderivedfrommultivariateanalysisassumingnoaspirinusage.

AntithrombotictherapycanbeomittedinpatientswithaCHA2DS2-VAScscore=0. In patientswithaCHA2DS2-VAScscore of 1, noantithrombotictherapy ortreatment with an

oralanticoagulantorASAmaybeconsidered.

Systemic anticoagulation with coumadin or DOAC is recommended for male patients with a CHA2DS2-VASc riskof ≥2 andfemale patientswith a CHA2DS2-VASc riskof≥3 inwomen who

havenocontraindicationsforanticoagulation. DOACsarerecommendedovercoumadinforDOAC-eligiblepatients. Measurementofrenalfunctioniscriticaltoassesssafety anddosingofcertainDOACsinpatients withCHA2DS2-VAScscoreof≥2andchronickidneydisease.

For AF patients at risk for thromboembolism but unable to tolerate long-term anticoagulation,

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considerationcan be given to percutaneous occlusionor surgical ligation of left atrial appendage (LAA). RoleofantithrombotictherapyleadinguptoandafterrestorationofSRdiscussedinthecontextof

cardioversion. Pharmacologic rate control of AF is achieved with drugs that prolong conduction through the AV node. Principally, these include the non-dihydropyridine calcium channel blockers (diltiazem, verapamil), β-adrenergic blockers, and digoxin. Refer to Table 7-3 for loading and dosing recommendations.

DigoxincanbeusefulincontrollingtherestingventricularrateinAFinthesettingofLVdysfunction

andCHFwhenotheragents fail. Utility inother clinical settings islimitedbyreducedefficacyof

ratecontrolduringexertionandsignificantconcernsoftoxicity.

Digitalistoxicity is characterized bynausea, abdominalpain, vision changes, confusion,and delirium.Patientswithrenaldysfunctionareatriskfordigitalistoxicityasarepatientsonagents

knowntoincreasedigoxinlevels(e.g.,verapamil,diltiazem,erythromycin,cyclosporine). ParoxysmalATwithvaryingdegreesofAVblockandbidirectionalVT—mostcommonlyseen arrhythmiasinassociationwithdigitalistoxicity.Treatmentissupportive(i.e.,withholdingdrug, inserting temporary pacemaker for prolonged AV block, administering IV phenytoin for

bidirectionalVT).

Nonpharmacologic rate control—accomplished by AV nodal ablation in association with PPM

implantation. Strategy reserved for patients deemed to be in permanent AF, who have failed pharmacologicratecontrol,andinwhomrhythmcontroliseitherineffectiveorcontraindicated.

SECONDLINE

PharmacologicrhythmcontrolofAFaccomplishedwithantiarrhythmicdrugsthatmodifyimpulse formationorpropagationtopreventinitiationofAF.Riskofthromboembolismassociatedwith

pharmacologiccardioversionshouldbeconsideredbeforebeginningantiarrhythmicdrugtherapy.

PharmacologiccardioversionshouldbeperformedinhospitalsettingwithcontinuousECGmonitoring

duetosmallriskoflife-threateningtachy-orbradyarrhythmias.

Ibutilide—only drug approved by US Food and Drug Administration for pharmacologic

cardioversion.Clinicaltrialshaveshowna45%conversionrateforAFanda60%conversionrate

forAFL.

Ibutilideisassociatedwith4%–8%riskfortorsadesdepointes(TdP),especiallyinfirst2–4hours

afteradministration.Becauseofthis risk,patientsmustbe monitoredontelemetrywithanexternal

defibrillator immediatelyavailableduringibutilideinfusionandfor atleast4hoursafterinfusion.

TheriskforTdPishigherinpatientswithcardiomyopathyandCHF.

Ibutilideisadministeredintravenously,atdosageof1mg(0.01mg/kgifpatientis<60kg),infused

slowlyover10minutes.FasteradministrationcanpromoteTdP.

EfficacyofantiarrhythmicstoachievepharmacologicconversiondropssharplywhenAFis>7days

in duration. For shorter duration episodes, dofetilide, sotalol, flecainide, and propafenone have

someefficacy;amiodaronehaslimitedefficacytoachievepharmacologiccardioversion. Maintenance of NSR with antiarrhythmic agents is associated with small risk for life-threatening proarrhythmia. As a result, antiarrhythmic therapy should be reserved for patients who have symptomatic AF with or without adequaterate control. Commonly used antiarrhythmic agents, their major route of elimination, and dosing regimens are listed in Table 7-5. Most effective agents for maintenanceofSRareflecainide,propafenone,sotalol,dofetilide,amiodarone,anddronedarone.

Flecainideandpropafenone

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FormaintenanceofNSRinpatientswithstructurallynormalhearts.

TABLE7-5

COMMONLYUSEDANTIARRHYTHMICDRUGS

Class Drug Routeof

Administration (Elimination)

Initial/Loading Dose

Maintenance Dose

MajorAdverse Effectsa/Comments

Ia Procainamide IV(R,H)

PO(R,H)

15–18mg/kg at20mg/min 50mg/kg/24h, max:5g/24h

1–4mg/min IR:250–500 mgq3–6h SR:500mg q6h Procanbid: 1000–2500mg q12h

GI,CNS, +ANA/SLE-like syndrome,fever, hematologic, anticholinergic. FollowQTc,serum

procainamide(4– 8mg/L)andNAPA levels(<20mg/mL)

Quinidine PO(H) Sulfate,200–

400mgq6h; gluconate, 324–972mg q8–12h

NA ↑QT,TdP,↓BP,

thrombocytopenia, cinchonism,GI upset

Disopyramide PO(H,R) 300–400mg IR:100–

200mgq6h SR:200–400 mgq12h

Anticholinergic,HF

Ib Lidocaine IV(H) 1mg/kgover

2min(may repeat×2up to3mg/kg total)

1–4mg/min ↓HR,CNS,GI;

adjustdosein patientswithhepatic failure,AMI,HF,or shock

Mexiletine PO(H) 400mgone-

timedose

200–300mg q8h

GI,CNS

Ic Flecainide PO(H,R) 50mgq12h Increaseby

50–100mg/d every4dto max400mg/d

HF,GI,CNS, blurredvision

Propafenone PO(H) IR:150mgq8h

ER:225mg q12h

IR:Increaseat 3-to4-day intervalsupto 300mgq8h ER:May

GI,dizziness

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increaseat5dayintervals, upto425mg q12h

III Sotalol PO(R) 80mgq12h Mayincrease

every3dupto 240–320mg/d intwotothree divideddoses

↓HR,↓BP,CHF, CNS LimitQT

prolongationto <550ms

Dofetilide PO(R,H) CrCl(mL/min):

Dose(μgbid): >60:500 40–60:250 20–39:125 <20: Contraindicated

Doseadjusted basedonQT

2–3hafter inpatientdoses 1through5 Chronic therapy requires calculationof QTcandCrCl

every3mo withadjustment asnecessary

↑QT,VT/TdP,HA, dizziness;seetext forfurtherdetailson initiatingand monitoringtreatment

Ibutilide IV(H) 1mg

(0.01mg/kgif patient<60kg) over10min; canrepeatifno response 10minafter initialinfusion

NA ↑QT,TdP,AVblock,

GI,HA

Amiodarone IV(H)

PO(H)

IV:150mg over10min PO:800mg/d for1wk,then 600mg/dfor1 wk,then 400mg/dfor1 wk

1mg/min×6h, then

0.5mg/min 100–400mg POdaily

↓BP,HB,↓HR, warfarininteraction; seetextfor descriptionof dermatologic, thyroid,pulmonary, corneal,andliver effects

AMI, acute myocardial infarction; ANA, antinuclear antibodies; ↓BP, hypotension; CNS, central nervous system; CHF,

congestiveheartfailure;CrCl,creatinineclearance;ER,extendedrelease;GI,gastrointestinal;H,hepatic;HA,headache;

HB, heart block; HF, heart failure; ↓HR, bradycardia; IR, immediate release; NA, not applicable; NAPA, N-

acetylprocainamide;R,renal;SLE,systemiclupuserythematosus;SR,sustainedrelease;TdP,torsadesdepointes;VT,

ventriculartachycardia.

Eithercommonorlife-threateningadverseeffectsofthesemedicationsarelisted.Thisisnotacomprehensivelistofall

possibleadverseeffects.

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Associatedwithincreasedmortalityrateinpatientswithstructuralheartdisease.

Potentnegativeinotropesthatcanprovokeorexacerbateheartfailure. ProlongQRSdurationasearlymanifestationoftoxicity. □ Toxicityincreaseswithheartratebecauseofpreferentialblockadeofactivesodiumchannels.

Propertyisdescribedaspositive-usedependence.

□ ExerciseECGusedtogiveadditionalinformationaboutdosesafetyathigherheartrates. □ Flecainide should be used cautiously without concomitant dosing with AV nodal blocker

becauseparadoxicalincrease intheventricular ratemayoccurfrom drug-inducedconversion ofAFtoAFL.Propafenoneislesspronetothisbecauseofintrinsicβ-adrenergicantagonism.

Sotalol—mixtureofstereoisomers(dl-)

d-sotalolisapotassiumchannelblocker,whereasl-sotalol isaβ-antagonist.Sideeffectsofthe drugreflectbothmechanismsofaction. dl-sotalolmayresultinQTintervalprolongationleadingtoTdPaswellassinusbradycardiaor AVconductionabnormalities. ShouldnotbeusedinpatientswithdecompensatedCHF(becauseofnegativeinotropiceffect)or withaprolongedQTinterval. Initiationshouldbeperformedinaninpatientmonitoredsetting. Renaladjustmentisnecessaryassotalolisexcretedbythekidneys.

Dofetilide—purepotassiumchannelblocker.

InitiationofdofetilideshouldbedoneinaninpatientmonitoredsettingduetoincreasedriskofQT intervalprolongationleadingtoTdP. QTprolongationwithsotalolordofetilideisintensifiedbybradycardia,knownas“reverse-use dependence.” ContraindicatedinpatientswithbaselinecorrectedQTinterval(QTc)>440ms(or>500mswith

baselinebundlebranchblock). Dosingis basedonthecreatinineclearance.A12-lead ECGshouldbe obtainedbeforethefirst dose and1–2 hours aftereachdose,thereafter.If QTcprolongs by15% of baselineor exceeds

500 ms,50% dosagereduction is indicated.If theQTc exceeds 500 ms after the seconddose, dofetilidemustbediscontinued.

Severalmedicationsblockrenalsecretionofdofetilide(verapamil,cimetidine,prochlorperazine, trimethoprim,megestrol,ketoconazole)andarecontraindicatedwiththeuseofdofetilide. Not associated with increased mortality in patients with LV dysfunction and does not cause conductiondisturbances.

Dronedarone—newestantiarrhythmicagentapprovedformanagementofAF.

SharespropertieswithVaughanWilliamsclassesI–IVantiarrhythmicdrugs. More effective than placebo but less effective than amiodarone at maintaining SR after cardioversion. Incidenceofproarrhythmiaandorgantoxicitylowwithdronedarone. Trend toward increased mortality has been shown in patients with advanced heart failure symptoms;assuch,itiscontraindicatedinthispatientgroup. Metabolizedbytheliverandshouldnotbeusedinpatientswithsignificanthepaticdysfunction. Canbeusedinpatientswithsignificantrenaldysfunction.

Amiodarone—mosteffectiveantiarrhythmicagentformaintenanceofSR.

Because of extensive toxicityprofile, should not be consideredfirst-line agent forrhythm controlofAFinpatientsinwhomalternativeantiarrhythmiccanbesafelyused.

LowefficacyforacuteconversionofAF,althoughconversionafterseveraldaysofIVhasbeen

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observed.Adverseeffectsoforalamiodaronearepartiallydosedependentandmayoccurinupto 75%ofpatientstreatedathighdosesfor5years.Atlowerdoses(200–300mg/d),adverseeffects thatrequirediscontinuationoccurinapproximately5%–10%ofpatientsperyear. Pulmonarytoxicityin1%–15%oftreatedpatientsbutappears lesslikely inthosewhoreceive <300mg/d.

□ Drycoughanddyspneaassociatedwithpulmonaryinfiltratesandrales. □ Processreversibleifdetectedearly,but undetectedcasesmayresultinmortalityrateofupto

10%.

□ CXRandpulmonaryfunctiontestsshouldbeobtainedatbaselineandevery12monthsorwhen

patients report symptoms of dyspnea. The presence of interstitial infiltrates on CXR and

decreaseddiffusioncapacityraiseconcernforamiodarone-inducedpulmonarytoxicity. Photosensitivity—common adverse reaction. Violaceous skin discoloration can develop in sunexposedareas;blue-graydiscolorationmaynotresolvecompletelywithdiscontinuationoftherapy. Thyroid dysfunction—common adverse effect. Both hypothyroidism and hyperthyroidism are reported,withanincidenceof2%–5%peryear.Thyroid-stimulatinghormoneshouldbeobtainedat baseline and monitored every 6 months. If hypothyroidism develops, concurrent treatment with levothyroxinemayallowcontinuedamiodaroneuse. Corneal microdeposits—detectable on slit-lamp examination, develop in virtually all patients. Depositsrarelyinterferewithvisionandnotanindicationfordiscontinuationofdrug.Opticneuritis, leadingtoblindness,israrebuthasbeenreportedinassociationwithamiodarone. MostcommonECGchangesarelengthenedPRintervalandbradycardia;however,high-gradeAV block may occur in patients who have preexisting conduction abnormalities. May prolong QT intervals,althoughusuallynot extensively, andTdPisrare.OtherQT-prolongingagentsshouldbe avoidedinpatientstakingamiodarone. Liverdysfunctionusuallymanifestsinasymptomaticandtransientriseinhepatictransaminases.If increase exceeds three times normal or doubles in patient with an elevated baseline level, amiodaroneshouldbediscontinuedordoseshouldbereduced.Aspartatetransaminaseandalanine transaminaseshouldbemonitoredevery6months. Druginteractions—amiodaronemayraisebloodlevelsofwarfarinanddigoxin;thesedrugsshould bereducedroutinelybyone-halfwhenamiodaroneisinitiated,andlevelsfollowedclosely.

NonpharmacologicTherapies

Nonpharmacologic methods of rhythm control include electrical cardioversion, catheter ablation,or surgicaltechniquesthatblockinitiationandmaintenanceofAF. Direct current cardioversion (DCCV)—safest and most effective method of acutely restoring SR. Priortocardioversion:

Consideration of anticoagulation is critical, to minimize thromboembolic events triggered by the cardioversionprocess. AFwith RVR insetting of ongoing myocardial ischemia, MI,hypotension,or respiratorydistress shouldreceivepromptcardioversionregardlessoftheanticoagulationstatus. If duration of AF is <48 hours, cardioversion may proceed without anticoagulation. If AF has persistedfor>48hours(orforunknownduration),patientsshouldbetherapeuticallyanticoagulated for at least 3 weeks before cardioversion (elective situation), and anticoagulation should be continuedfollowingsuccessfulcardioversionforaminimumof4weeks. Alternative to anticoagulation for 3 weeks prior to cardioversion is to perform transesophageal echocardiogram to rule out LAA thrombus before cardioversion. This method is safe and has

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advantage of shorter time to cardioversion. Therapeutic anticoagulation is indicated after cardioversionforminimumof4weeks.

Whenpractical, periprocedural sedationis accomplished withmidazolam(1–2 mgIV q2minto a maximumof5mg),methohexital(25–75mgIV),etomidate(0.2–0.6mg/kgIV),orpropofol(initial dose,5mg/kg/hIV). Proper synchronization of DC shock to the QRS is critical to avoid induction of VT by shock deliveredduringvulnerableperiodoftheventricle. Forcardioversionofatrial arrhythmias, anterior patchelectrode shouldbe positionedjustrightof the sternum at the level ofthird or fourthintercostal space, withsecondelectrode positionedjust belowleftscapulaposteriorly. Careshould betakentoposition patchelectrodesatleast6cm fromPPMorimplantablecardioverter–defibrillator(ICD)generators.If electrodepaddlesare used, firm pressure andconductive gel should be applied to minimize contact impedance. Direct contact with the patient or the bed should be avoided. Atropine (1 mg IV) should be readily available to treat prolonged pauses. Reports of serious arrhythmias, such as VT, ventricular fibrillation (VF), or asystole are rare and more likely in setting of improperly synchronized cardioversions,digitalistoxicity,orconcomitantantiarrhythmicdrugtherapy.

Catheter ablation of AF—highly effective in younger patients with structurally normal hearts and paroxysmalpatternofAF.

Successratesinthiscohortareintherangeof70%–80%over12–18monthsfollow-upperiod. Successratesarediminishedinpatientswithstructuralheartdisease,advancedage,andpersistent AF.Asignificantfractionofpatientsrequiremorethanoneablationproceduretoachievelong-term successfuleliminationofAF. Goal of catheter ablation in paroxysmal AF patients is to achieve electrical isolation of the pulmonary veins. In patients with persistent AF, this goal is frequently combined with substrate modificationstrategieswherebyregionsoftheatriaaretargetedforablationtoblockreentryorthe presenceoffocaldriversofAF.

SurgicalManagement

SurgicaltechniquesforcureofAFhavebeenevaluatedsincethe1980s.Amongthese,theCoxmaze procedurehashighestdemonstratedefficacyandmostrobustfollow-updatadocumentingsustained efficacy.IncludingpatientswithpersistentAFandstructuralheartdisease,successratesapproach90%. Becauseofitsinvasivenature,surgicaltreatmentisusuallyreservedforthosewhohavefailedcatheter ablationorwhohaveplannedconcomitantcardiacsurgery.

VentricularTachyarrhythmias

GENERALPRINCIPLES

Ventricular tachyarrhythmias should be initially approached with assumption that they will have malignantcourse,untilprovenotherwise. Characterizationofthearrhythmiainvolvesconsiderationofhemodynamicstability,durationandECG morphologyoftachycardia,andthepresenceorlackofunderlyingstructuralheartdisease. Characterizationwillaidindeterminingthepatient’sriskforsuddencardiacarrest(SCA)andneed fortherapeuticinterventionand/ordeviceimplantation.

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