updates in atrial fibrillation - ucsf cme in atrial fibrillation ... holter monitor ... fuster et...

Updates in Updates in AtrialAtrialFibrillationFibrillationKatherine Julian, MDKatherine Julian, MD

July 3, 2008July 3, 2008

EpidemiologyEpidemiology

Most common arrhythmia in clinical practiceMost common arrhythmia in clinical practice2.3 million people in North America2.3 million people in North America

Average cost of $3600/patient/yearAverage cost of $3600/patient/year

Accounts for 1/3 of all hospitalizations for cardiac Accounts for 1/3 of all hospitalizations for cardiac rhythm disturbancesrhythm disturbancesPrevalence: 0.4Prevalence: 0.4--1% in the general population and 1% in the general population and 8% in those older than 80 years8% in those older than 80 years

Why Is This Important?Why Is This Important?

AF associated with an increased risk of strokeAF associated with an increased risk of strokeSixSix--fold increase in rate of ischemic strokefold increase in rate of ischemic strokeRate of ischemic stroke in nonRate of ischemic stroke in non--valvularvalvular AF approx AF approx 5%/year5%/yearAF accounts for 15% of all strokesAF accounts for 15% of all strokes

AFAF--associated strokes more severeassociated strokes more severe

Singer DE, et al. Chest, 2004;126.

AtrialAtrial FibrillationFibrillation

WorkWork--UpUpRate vs. Rhythm ControlRate vs. Rhythm ControlTreatment OptionsTreatment OptionsAntiAnti--coagulation coagulation Future Treatment OptionsFuture Treatment Options

Case ICase I

55 55 yoyo woman being seen for a new patient visit. woman being seen for a new patient visit. Asymptomatic.Asymptomatic.PMH: HTN (untreated)PMH: HTN (untreated)PE: 150/80, HR 125 Irregularly irregularPE: 150/80, HR 125 Irregularly irregular

The EKGThe EKG……

What WorkWhat Work--Up Does She Need?Up Does She Need?

1)1) TSHTSH2)2) ECHOECHO3)3) r/o MI with troponinsr/o MI with troponins4)4) 1 and 21 and 25)5) All of the aboveAll of the above


Complete history and Complete history and physicalphysicalPIRATESPIRATES


PIRATES PIRATES –– secondary causessecondary causesPericarditisPericarditisPulmonary/pulmonary embolismPulmonary/pulmonary embolismIschemiaIschemiaRheumatic heart diseaseRheumatic heart diseaseAtrial myxomaAtrial myxomaThyrotoxicosisThyrotoxicosisEthanolEthanolSepsisSepsis


Complete history and physical examComplete history and physical examPulmonary/pulmonary embolismPulmonary/pulmonary embolismIschemiaIschemiaEthanolEthanolSepsisSepsis

Fuster et al. AcC/AHA/ESC Practice Guidelines. JACC, 2006;48(4)


ECHOECHORheumatic heart diseaseRheumatic heart diseaseAtrial myxomaAtrial myxoma

The real reasonThe real reason……LVHLVHOccult valvular diseaseOccult valvular diseaseOccult pericardial diseaseOccult pericardial disease



Complete history and physical examComplete history and physical examTTETTEEKGEKGCXRCXRAssociated labsAssociated labs

TSH, (CBC, renal and hepatic function)TSH, (CBC, renal and hepatic function)

Other tests based on historyOther tests based on history……



1)1) TSHTSH2)2) ECHOECHO3)3) r/o MI with troponinsr/o MI with troponins4)4) 1 and 21 and 25)5) All of the aboveAll of the above

ClassificationClassification

Recurrent:Recurrent: 2 or more episodes2 or more episodesParoxysmal:Paroxysmal: arrhythmia terminates spontaneouslyarrhythmia terminates spontaneouslyPersistent: Persistent: sustained beyond 7 dayssustained beyond 7 days

Permanent:Permanent: cardioversion has failed (or been cardioversion has failed (or been foregone)foregone)Lone:Lone: patients <60 years without clinical/EKG patients <60 years without clinical/EKG evidence of cardiopulmonary disease (incl htn)evidence of cardiopulmonary disease (incl htn)

What is the Next Step for Our Case?What is the Next Step for Our Case?

What should be our goal in treatment?What should be our goal in treatment?1)1) Convert her to sinus rhythmConvert her to sinus rhythm2)2) RateRate--controlcontrol3)3) Stroke preventionStroke prevention4)4) #1 and #3#1 and #35)5) #2 and #3#2 and #3

Hemodynamic Consequences of Hemodynamic Consequences of AFAF

Loss of atrial mechanical functionLoss of atrial mechanical functionIrregular ventricular responseIrregular ventricular responseElevated HRElevated HRResults in:Results in:

Reduction in diastolic filling, stroke volume, COReduction in diastolic filling, stroke volume, CORisk of cardiomyopathy (chronic > 130 bpm)Risk of cardiomyopathy (chronic > 130 bpm)

Asymptomatic events 12X more commonAsymptomatic events 12X more common……

Rate or Rhythm?Rate or Rhythm?

AFFIRM StudyAFFIRM StudyRandomized 4070 patients with AF to rateRandomized 4070 patients with AF to rate--control vs. control vs. rhythmrhythm--controlcontrol

RateRate--control = coumadincontrol = coumadinRhythmRhythm--control = cardioversion/medscontrol = cardioversion/meds

No difference in survival, stroke or QOLNo difference in survival, stroke or QOLTrend towards increased survival in rateTrend towards increased survival in rate--control (P = .08)control (P = .08)Pts Pts >> 65 yrs and pts without h/o CHF had better outcomes 65 yrs and pts without h/o CHF had better outcomes with ratewith rate--control therapycontrol therapy

AFFIRM Investigators, NEJM, 2002;347

Rhythm Control in AFRhythm Control in AF……””One Setback After AnotherOne Setback After Another””

RCT comparing rhythm control vs. rate control RCT comparing rhythm control vs. rate control in patients with EF < 35%, sx of CHF, and AFin patients with EF < 35%, sx of CHF, and AF

Primary outcome = time to death from Primary outcome = time to death from cardiovascular causescardiovascular causes1376 patients enrolled1376 patients enrolledFollowed 37 monthsFollowed 37 months

Roy D, et al. NEJM, 2008;358(25)

Rhythm Control in AFRhythm Control in AF……””One Setback After AnotherOne Setback After Another””

ResultsResults……27% in rhythm27% in rhythm--control group died from control group died from cardiovascular causes vs. 25% in ratecardiovascular causes vs. 25% in rate--control groupcontrol groupSecondary outcomes similar (overall death, stroke, Secondary outcomes similar (overall death, stroke, worsened heart failure)worsened heart failure)

Result of SE from rhythm drugs (amiodarone, Result of SE from rhythm drugs (amiodarone, sotolol, dofetilide)?sotolol, dofetilide)?Result of crossResult of cross--over?over?

21% in rhythm21% in rhythm--control crossed over to rate; 10% in control crossed over to rate; 10% in raterate--control crossedcontrol crossed--over to rhythmover to rhythm

Studies Are ConvincingStudies Are Convincing……

Rate control is OKRate control is OK……

Rate ControlRate Control

Goal HR: 60Goal HR: 60--80 bpm at rest; 9080 bpm at rest; 90--115 bpm 115 bpm during exerciseduring exercise

SixSix--minute walk testminute walk testHolter monitorHolter monitor

Rate ControlRate Control

What do I use?What do I use?First choice: betaFirst choice: beta--blockers or calciumblockers or calcium--channel channel blockersblockers

DonDon’’t give if Wolft give if Wolf--ParkinsonParkinson--White or other accessory White or other accessory pathwayspathways

OK to combine nodalOK to combine nodal--blocking agentsblocking agentsDigoxin is secondDigoxin is second--line as it does not control HR line as it does not control HR during exerciseduring exercise


What About Paroxysmal AF?What About Paroxysmal AF?PillPill--inin--thethe--Pocket ApproachPocket Approach

268 patients presenting to ER with AF. Given 268 patients presenting to ER with AF. Given flecanide or propafenoneflecanide or propafenone

58 patients had treatment failure or SE 58 patients had treatment failure or SE -- excludedexcludedOutOut--ofof--hospital selfhospital self--administration of flecanide or administration of flecanide or propafenone studied in remaining 210propafenone studied in remaining 210

79% had episodes of arrhythmia (618 episodes)79% had episodes of arrhythmia (618 episodes)92% treated 36 92% treated 36 ++ 93 minutes after sx onset93 minutes after sx onsetTreatment successful in 94% of episodes Treatment successful in 94% of episodes

ER visits/hospitalizations lower than in previous yearER visits/hospitalizations lower than in previous year

Alboni P, et al. NEJM, 2004;351:23.

PillPill--InIn--TheThe--Pocket ApproachPocket Approach

Approach advised ONLY for those patients Approach advised ONLY for those patients with low risk of prowith low risk of pro--arrhythmia and other arrhythmia and other adverse side effectsadverse side effects

No structural heart diseaseNo structural heart diseaseNo CHF or LV dysfunctionNo CHF or LV dysfunctionSBP >100mmHg and HR >70 bpmSBP >100mmHg and HR >70 bpmPts who have shown to tolerate medicationPts who have shown to tolerate medicationBetaBeta--blocker or Ca+ blocker recommended 30 min blocker or Ca+ blocker recommended 30 min before 1C agent to prevent rapid conductionbefore 1C agent to prevent rapid conduction

PillPill--inin--thethe--Pocket CaveatPocket Caveat

Class IC agents can be proarrhythmicClass IC agents can be proarrhythmicOther risk factors for ventricular proarrhythmia:Other risk factors for ventricular proarrhythmia:

FEMALE GENDERFEMALE GENDERLong QT intervalLong QT intervalRenal insufficiencyRenal insufficiencyOther meds: diuretics, meds that increase QT Other meds: diuretics, meds that increase QT intervalinterval

Patients with Paroxysmal AFPatients with Paroxysmal AFAdminister appropriate

thromboprophylaxis

Is a pill-in-the-pocket treatment appropriate?Pill in the pocket

Standard beta-blocker

Treatment Failure?

CAD or LV dysfunctionSotolol

Class IC agent or sotolol

Amiodarone or referral

Treatment Failure?

YES NO

CAD LV Dys

NO

Heart, 2007;93

Rhythm vs. RateRhythm vs. Rate……Bottom LineBottom Line

Highly symptomatic or unstable: rhythm Highly symptomatic or unstable: rhythm controlcontrolIf minimal symptoms: rate control is safe and If minimal symptoms: rate control is safe and appropriate (maintain goal HR)appropriate (maintain goal HR)Anticoagulation therapy should be continued Anticoagulation therapy should be continued regardless of the strategy (rhythm vs. rate)regardless of the strategy (rhythm vs. rate)

What About What About Cardioversion?Cardioversion?

Electrical cardioversion preferredElectrical cardioversion preferredRequires conscious sedation or anesthesiaRequires conscious sedation or anesthesia

Most thrombi in atrial fibrillation arise from the Most thrombi in atrial fibrillation arise from the LA appendageLA appendageCardioversion can reduce LA appendage Cardioversion can reduce LA appendage functionfunctionPeriPeri--cardioversion period is particularly procardioversion period is particularly pro--thromboticthrombotic

Regardless of mode of cardioversionRegardless of mode of cardioversion

Electrial CardioversionElectrial Cardioversion

If AF < 48 hrs, can safely undergo cardioversion If AF < 48 hrs, can safely undergo cardioversion without anticoagulant therapywithout anticoagulant therapy

Must be documented!Must be documented!If AF > 48 hrs (or unknown duration), then 2 If AF > 48 hrs (or unknown duration), then 2 choices:choices:

AntiAnti--coagulate X 3 weeks (therapeutic INR) before coagulate X 3 weeks (therapeutic INR) before cardioversioncardioversionTEE to r/o clotTEE to r/o clot

AntiAnti--coagulate for at least 4 weeks afterwardcoagulate for at least 4 weeks afterwardAntiAnti--coagulate also for those who would not normally coagulate also for those who would not normally require coumadinrequire coumadin


Pharmacologic Cardioversion Pharmacologic Cardioversion ––Stable PatientsStable Patients

Pharmacologic cardioversion in AF < 7 daysPharmacologic cardioversion in AF < 7 daysType 1CType 1C

FlecainideFlecainidePropafenonePropafenone

Type IIIType IIIDofetilideDofetilideIbutilideIbutilide

Pharmacologic cardioversion in AF > 7 daysPharmacologic cardioversion in AF > 7 daysProven efficacy: dofetilide, ibutilide, amiodaroneProven efficacy: dofetilide, ibutilide, amiodarone

Fuster et al. ACC/AHA/ESC Practice Guidelines. JACC, 2006;48(4).

Unstable PatientsUnstable Patients

Electrical Cardioversion first choiceElectrical Cardioversion first choicePharmacologic cardioversion when electrical Pharmacologic cardioversion when electrical cardioversion not possible or has to be delayedcardioversion not possible or has to be delayed

IV betaIV beta--blockers or nondihydropyridine calcium blockers or nondihydropyridine calcium channel blockers (take care if CHF)channel blockers (take care if CHF)IV digoxin or amiodarone in patients with heart IV digoxin or amiodarone in patients with heart failurefailure

The Next StepThe Next Step……

55 yo woman being seen for a new patient visit. 55 yo woman being seen for a new patient visit. Asymptomatic.Asymptomatic.

PMH: HTN (untreated)PMH: HTN (untreated)PE: 150/80, HR 125 Irregularly irregularPE: 150/80, HR 125 Irregularly irregular

Does she need antiDoes she need anti--coagulation?coagulation?1)1) Yes, with coumadinYes, with coumadin2)2) Yes, with ASAYes, with ASA3)3) Yes, with coumadin and ASAYes, with coumadin and ASA4)4) NoNo

Key PointKey Point……

A rhythm control strategy does not negate the A rhythm control strategy does not negate the need for warfarin therapyneed for warfarin therapy

Assuming warfarin is indicatedAssuming warfarin is indicated

Risk/Benefits of CoumadinRisk/Benefits of Coumadin

Pooled analysis from five primary prevention Pooled analysis from five primary prevention trials in nontrials in non--valvular AFvalvular AF

Annual rate of stroke 4.3% in control groupAnnual rate of stroke 4.3% in control group1.4% risk of stroke in the warfarin group1.4% risk of stroke in the warfarin groupNeed to consider warfarin risksNeed to consider warfarin risks

Symptomatic intracranial hemorrhage 0.4% with warfarin; Symptomatic intracranial hemorrhage 0.4% with warfarin; 0.2% in control0.2% in controlMajor bleeding: 2.2% with warfarin; 0.9% in controlMajor bleeding: 2.2% with warfarin; 0.9% in control

Bath PMW, et al. European Heart Journal, 2005

What About Aspirin?What About Aspirin?

Two randomized trials evaluated the use of ASA Two randomized trials evaluated the use of ASA in primary stroke preventionin primary stroke prevention

Pooled data: Risk of stroke with ASA 4.2%; risk of Pooled data: Risk of stroke with ASA 4.2%; risk of stroke in controls 6.4%stroke in controls 6.4%

Bath PMW, et al. European Heart Journal, 2005

Secondary Prevention of StrokeSecondary Prevention of Stroke

Risk of stroke with warfarin 3.1%; placebo 10%Risk of stroke with warfarin 3.1%; placebo 10%Risk of stroke with ASA (300mg) 7.7%Risk of stroke with ASA (300mg) 7.7%

Bottom lineBottom line……anticoagulation with warfarin anticoagulation with warfarin superior to ASA. Effective in the prevention of superior to ASA. Effective in the prevention of primary and secondary stroke.primary and secondary stroke.

EAFT Study Group, Lancet, 1993

Who Needs AntiWho Needs Anti--Coagulation in AF?Coagulation in AF?

CHADSCHADS22 index the most accurate predictor of index the most accurate predictor of strokestroke

1 point each for:1 point each for:CHF (or reduced systolic function)CHF (or reduced systolic function)HtnHtnAge Age >> 75 years75 yearsDiabetesDiabetes

2 points for:2 points for:History of stroke or TIAHistory of stroke or TIA

Gage BF, et al. JAMA, 2001;285.

AnticoagulationAnticoagulation……Who Needs It?Who Needs It?

CHADSCHADS22

Stroke rate per 100 patientStroke rate per 100 patient--years without antiyears without anti--thrombotic therapythrombotic therapy

0 points: 1.90 points: 1.91 point: 2.81 point: 2.82 points: 42 points: 43 points: 5.93 points: 5.94 points: 8.54 points: 8.55 points: 12.55 points: 12.5


AnticoagulationAnticoagulation……Who Needs It?Who Needs It?

CHADSCHADS22

Stroke rate per 100 patientStroke rate per 100 patient--years without antiyears without anti--thrombotic therapythrombotic therapy

0 points: 1.90 points: 1.9→→Low risk, Offer ASALow risk, Offer ASA1 point: 2.81 point: 2.8→→Low risk, Offer ASALow risk, Offer ASA2 points: 42 points: 4→→Moderate risk, Offer warfarinModerate risk, Offer warfarin3 points: 5.93 points: 5.9→→Moderate risk, Offer warfarinModerate risk, Offer warfarin4 points: 8.54 points: 8.5→→High risk, warfarinHigh risk, warfarin5 points: 12.55 points: 12.5→→High risk, warfarinHigh risk, warfarin


Back to Our CaseBack to Our Case……

55 yo woman being seen for a new patient visit. 55 yo woman being seen for a new patient visit. Asymptomatic.Asymptomatic.PMH: HTN (untreated)PMH: HTN (untreated)PE: 150/80, HR 125 Irregularly irregularPE: 150/80, HR 125 Irregularly irregular

CHADSCHADS22 score = 1 pointscore = 1 pointOffer ASAOffer ASA

AntiAnti--Coagulation Special ConsiderationsCoagulation Special Considerations

What about my 85 yo patient who falls?What about my 85 yo patient who falls?Predisposition to falling not considered a Predisposition to falling not considered a contraindication for warfarincontraindication for warfarin

What about my patient with a remote h/o GIB?What about my patient with a remote h/o GIB?Resolved peptic ulcer disease bleeding (with H. Resolved peptic ulcer disease bleeding (with H. Pylori testing/treatment) not a contraindication for Pylori testing/treatment) not a contraindication for warfarinwarfarin

Man‐Son‐Hing M et al. Arch Intern Med, 2003;163.


What are absolute contraindications to warfarin?What are absolute contraindications to warfarin?Bleeding diathesisBleeding diathesisThrombocytopenia (<50K)Thrombocytopenia (<50K)Untreated or poorlyUntreated or poorly--controlled htn (> 160/90)controlled htn (> 160/90)NonNon--compliance with INR monitoringcompliance with INR monitoring

Relative contraindicationsRelative contraindicationsSignificant ETOH use, NSAID use without PPI, Significant ETOH use, NSAID use without PPI, activities predisposing to traumaactivities predisposing to trauma

Man‐Son‐Hing M et al. Arch Intern Med, 2003;163.


What about stopping antiWhat about stopping anti--coagulation for a coagulation for a procedure?procedure?

Mechanical heart valveMechanical heart valve→→heparin (UFH vs LMWH)heparin (UFH vs LMWH)NonNon--valvular AFvalvular AF

Can stop antiCan stop anti--coagulation for up to 1 week for procedures coagulation for up to 1 week for procedures without substituting heparinwithout substituting heparin

HighHigh--risk patients (prior CVA/TIA, embolism) OR risk patients (prior CVA/TIA, embolism) OR necessity off coumadin > 1 weeknecessity off coumadin > 1 week

Can use heparinCan use heparin

AntiAnti--Coag TidbitsCoag Tidbits

Goal INR 2Goal INR 2--33Patient selfPatient self--monitoring of oral antimonitoring of oral anti--coagulation coagulation more effective in terms of patient satisfaction more effective in terms of patient satisfaction (compared to supervised management) and (compared to supervised management) and accuracy of anticoagulation controlaccuracy of anticoagulation controlGuidelines in patient selfGuidelines in patient self--management have been management have been publishedpublishedPatients at high stroke risk should be antiPatients at high stroke risk should be anti--coagulated regardless of whether ratecoagulated regardless of whether rate-- or rhythmor rhythm--control strategy usedcontrol strategy used

Sawicki PT. JAMA, 1999;281Fitzmaurice DA et al. BMJ, 2001;323

Future DirectionsFuture Directions……AblationAblation

Paroxysmal AF primarily emanates from the Paroxysmal AF primarily emanates from the pulmonary veinspulmonary veinsHigh success (>90High success (>90--95%) and low95%) and low--risk (<1%):risk (<1%):

Ablation within the RAAblation within the RAAV nodal ablation with pacemakerAV nodal ablation with pacemakerAtrial flutter ablationAtrial flutter ablationSVT ablationSVT ablation

AblationAblation

Lower success (60Lower success (60--90%) and higher risk (490%) and higher risk (4--6%):6%):Ablation within the LAAblation within the LA

Atrial fibrillationAtrial fibrillation

Who should have ablation?Who should have ablation?Those who are symptomaticThose who are symptomatic

Failed 1Failed 1--2 anti2 anti--arrhythmic medicinesarrhythmic medicines

Better for paroxysmal aBetter for paroxysmal a--fibfib

The Future?The Future?

What about other anticoagulant agents?What about other anticoagulant agents?2 studies comparing ximelagatran (36mg BID) with 2 studies comparing ximelagatran (36mg BID) with warfarinwarfarin

SPORTIF IIISPORTIF IIISPORTIF VSPORTIF VCombined patient population of 7,329 patientsCombined patient population of 7,329 patientsOutcomes: all stroke and systemic embolismOutcomes: all stroke and systemic embolismDesigned as nonDesigned as non--inferiority trialinferiority trialNo difference in primary outcomesNo difference in primary outcomes

Major bleeding incidence: 2.01% ximelagatran; 2.68% warfarin Major bleeding incidence: 2.01% ximelagatran; 2.68% warfarin (RRR 25.1%)(RRR 25.1%)More information needed about liver injury with ximelagatranMore information needed about liver injury with ximelagatran

Douketis JD, et al. Arch Intern Med, 2006;166.

RecapRecap……Current GuidelinesCurrent Guidelines


Current GuidelinesCurrent Guidelines






Thank You!!Thank You!!

updates in atrial fibrillation - ucsf cme in atrial fibrillation ... holter monitor ... fuster et...

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