1

Atrial FibrillationAtrial Fibrillation

Troy E. Rhodes, MD, PhDDivision of Cardiovascular Medicine, ,

ElectrophysiologyOhio State University Medical Center

Learning ObjectivesLearning Objectives• Review the growing incidence andReview the growing incidence and

importance of AF in the population• Discuss the use of anticoagulation in

AF for stroke prevention• Summarize pharmacologic and non• Summarize pharmacologic and non-

pharmacologic options for AF management

2

Atrial FibrillationAtrial Fibrillation

5 165.425.61

5

6

s

Projected Number of Adults With AF in the US

Projected Number of Adults With AF in the US

2.082.262.442.662.94

3.333.80

4.344.78

5.16

1

2

3

4

5

s w

ith

AF, M

illio

ns

0

1

Ad

ult

Year

Go et al. JAMA. 2001;285:2370-2375.

3

Costs to the Health Care SystemEstimated US cost burden 15.7 billion

annually

Costs to the Health Care SystemEstimated US cost burden 15.7 billion

annually• 35% of arrhythmia hospitalizations

• Average hospital stay = 5 days

• Mean cost of hospitalization = $18,800

• Does not include:

Costs of outpatient cardioversions

Costs of drugs/side effects/monitoring

Costs of AF-induced strokes

Quality of Life with AFQuality of Life with AF

1 Jung et al, JACC. 1999 2 Ware et al, New England Medical Center Health Survey, 1993.

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Diagnostic EvaluationDiagnostic EvaluationMinimum Evaluation• History and physical – Sx with AF, CV

disease• Electrocardiogram – LVH, MI, BBB, WPW• Echocardiogram – LVH, LAE, LVEF, Valvesg , , ,• Labs – TSH, Renal fxn• Sleep history

AHA / ACC / ECS Guidelines 2006

Diagnostic EvaluationDiagnostic EvaluationAdditional Testing• ETT – CAD, Exercise induced SVT / AF• Holter / Event Monitor – Confirm AF and

Sxs• TEE – LA clot• EPS – SVT triggered AF • Sleep Study

AHA / ACC / ECS Guidelines 2006

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Incidence of AF Based on Presence or Absence of OSA

Incidence of AF Based on Presence or Absence of OSA

20 –

15 –

10 –

5 –

CumulativeFrequencyof AF (%)

OSA

No OSA

Gami et al. JACC 2007;49:565-71

0 –

Years0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Number at RiskOSANo OSA

8442,209

7091,902

5691,616

4781,317

3971,037

333848

273641

214502

173393

134296

110217

94195

70130

4694

2969

828

Heart Rhythm 2011; 8: 157-176.

6

Fi t

Classification of Atrial FibrillationACC/AHA/ESC Guidelines

Classification of Atrial FibrillationACC/AHA/ESC Guidelines

Paroxysmal(Self-

First Detected

Persistent(Not self-

terminating)

Permanent

terminating)

Maintenance of SR Stroke preventionRate control

Treatment OptionsTreatment Options

Pharmacologic Nonpharmacologic

Class IA Class ICClass III

Catheter ablationSurgery (MAZE)Pacing

Pharmacologic• Warfarin• Thrombin inhibitor• Aspirin

Nonpharmacologic• Removal / isolation

LA d

Pharmacologic• Ca2+ blockers• β-blockers• Digitalis• Amiodarone

Nonpharmacologicβ-blocker

gLA appendage

p g• Ablate and pace

Prevent remodeling ACE-IARB

Adapted from Prystowsky, Am J Cardiol. 2000;85:3D-11D.

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Atrial Fibrillation and StrokeAtrial Fibrillation and Stroke• 5 fold increased risk of CVA• AF accounts for 1 out of every 6 CVAsy• Paroxysmal same risk as persistent• Thromboemboli originating from LAA

Stroke Risk Assessment in AF: CHADS2 Score

Stroke Risk Assessment in AF: CHADS2 Score

CHADS Annual Stroke NNTClinical Parameter PointsCHF 1Hypertension 1Age > 75yo 1Diabetes 1Stroke 2

CHADS2Score

Annual Stroke Risk %

NNT

0 1.9 4171 2.8 1252 4.0 813 5.9 334 8.5 27

Gage et al, JAMA 2001; 285:2864.

5 or 6 12-18 44

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Stroke Risk Assessment in AF: CHADS2 Score

Stroke Risk Assessment in AF: CHADS2 Score

Clinical Parameter PointsCHF 1Hypertension 1Age > 75yo 1Diabetes 1Stroke 2

CHADS2 Score Treatment0 ASA1 ASA or Warfarin (INR 2-3)2+ Warfarin (INR 2-3)

Gage et al, JAMA 2001; 285:2864.

AnticoagulationAnticoagulation• Overall CHADS2

SEvents per 100 person- NNT

62% reduction with warfarin19% with ASA

• AFFIRM80% of CVAs

Score yearsWarfarin No Warfarin

0 0.25 0.49 417

1 0.72 1.52 125

2 1.27 2.50 81

3 2 20 5 27 33occurred after coumadin was stopped or was subtherapeutic

3 2.20 5.27 33

4 2.35 6.02 27

5 or 6 4.60 6.88 44

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Atrial Fibrillation-Anticoagulation

Atrial Fibrillation-Anticoagulation

Hylek EM and Singer DE. Ann Intern Med. 1994;120(11):897-902.

• Slow onset/offset

Warfarin LimitationsWarfarin Limitations

• Unpredictable dosing• Drug/diet interactions• Warfarin resistance (genetic)• Narrow therapeutic index• Routine monitoringg• Patient dissatisfaction (“rat

poison”)• Prescriber dissatisfaction

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DabigatranDabigatran• Direct thrombin inhibitor

R ibl bi diReversible bindingFree & clot-bound thrombin

• Inhibits platelet aggregation• Inhibits tissue factor-induced

thrombin generation• Renally cleared• No antidote

FDA-Approved LabelingFDA-Approved Labeling• Who it’s for:

Non-valvular AF patients for strokeNon-valvular AF patients for stroke prevention

• Who it’s NOT for:Mechanical heart valvesPEPEDVTProphylaxis for knee/hip replacementsHIT

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Management of AFManagement of AF

ANTITHROMBOTIC RX

RHYTHM RATE

AND

RHYTHMCONTROL

RATECONTROL

OR ?

Rate ControlRate Control

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Atrial FibrillationAtrial FibrillationRate control – Drug TherapyRate control – Drug Therapy

Digoxin – controls resting rate, OK in CHF patients.

Beta, Calcium channel blockers – controls resting and exercise rates.

Best therapy – combination of beta blockerand digoxin.

Primary Goal – Avoid Tachycardia InducedCardiomyopathy

What is optimum rate control?What is optimum rate control?• AFFIRM trial

Resting heart rate less than 80 bpmPeak heart rate less than 110 bpm

• RACE II

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RACE IIRACE II• 614 patients

L i t C t l (<110 b )• Lenient Control (<110 bpm) versus strict control (<80 at rest, <110 at peak).

• Mean follow up 2 years.• Primary Outcomes of death, CHF,

stroke embolism, life threatening arrhythmias

The RACE II Investigators. N Engl J Med. 2010;362: 1363-1373.

Rate ControlRate Control• No significant difference in two groups

The RACE II Investigators. N Engl J Med. 2010;362:.

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Rhythm ControlRhythm Control

Conversion of AFConversion of AF

< 3 Months3 - 12 Months

100

Length of timein AF prior tocardioversion

Duration of AF is the best predictor of recurrent AF after cardioversion

3 12 Months> 12 Months

80

60

40

nts

in s

inus

rhyt

hm (%

)

*cardioversion

Dittrich HC. Am J Cardiol. 1989;63:193-197.

20

0Initial One month

post-CVSix months

post-CV*P = <0.02

Patie

n

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Anticoagulation - CardioversionAnticoagulation - Cardioversion• Atrial stunning

Stunning can occur even with one hour ofeven with one hour of atrial fibrillationIf duration < 2 weeks, function may return within 24 hours to one weekweekIf duration > 2 weeks, stunning may persist for one month

Mattioli, AV. et al. Am J Cardiol 1998; 82:1368.

CardioversionCardioversion• Less than 48 hours durationLess than 48 hours duration

Cardioversion without TEEHeparin at time of cardioversionWarfarin for a month and re-evaluation as outpatient

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CardioversionCardioversion• If greater than 48 hours

Option 1: Anticoagulate for 4 weeks andOption 1: Anticoagulate for 4 weeks and then cardiovertOption 2: TEE and if no thrombus, cardiovert

If thrombus, 4 weeks warfarin and h krecheck

Anticoagulate for minimum of one month and re-evaluate

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30RateRhythm

AFFIRM: Rate vs. Rhythm Control AFFIRM: Rate vs. Rhythm Control All-Cause MortalityAll-Cause Mortality

5

10

15

20

Mor

talit

y, %

Rhythm

p=0.078 unadjusted p=0.068 adjusted

4060 ti t

Rate N:

Rhythm N:

2027

2033

1925

1932

1825

1807

1328

1316

774

780

236

255

0

5

0 1 2 3 4 5Time (years)

The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833.

4060 patients

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Rate vs. Rhythm Control Trials: Implications

Rate vs. Rhythm Control Trials: Implications

• AFFIRM demonstrated that a rate control “strategy” is an acceptable primary“strategy” is an acceptable primary therapy in a selected high-risk subgroup of AF patients

• Continuous anticoagulation seems warranted in all patients with risk factors f t kfor stroke

Asymptomatic recurrences

• AFFIRM did not define whether it is better to be in NSR.

Rhythm ControlRhythm ControlADVANTAGES DISADVANTAGESADVANTAGES• Avoids electrical and

anatomical remodeling• Improves hemodynamics• Enhanced exercise capacity • Symptom relief

I QOL

DISADVANTAGES• Ventricular proarrhythmia• Increased mortality?• Drug-induced

bradyarrhythmias• End-organ toxicity

Ad ff• Improves QOL• Restores atrial transport• Reduces thromboembolic

events?

• Adverse effects• Recurrences are likely• Asymptomatic (silent) AF

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Heart Rhythm 2011; 8: 157-176.

CTAF Trial*: Maintenance of SRCTAF Trial*: Maintenance of SR

nce,

% 100Amiodarone 10 mg/kg/2 wk, 300 mg/4 wk, 200 mg/d (n=201)

ents

with

out r

ecur

ren 80

60

40

20

Propafenone 300-450 mg/d (n=101)

Sotalol 160 mg BID or 80 mg TID (n=101)

Roy D, et al. N Engl J Med. 2000;342:913-920.

Patie

0 1000

200 300 400 500 600

Days of follow-up

* Excluded recurrence in first 21 days.

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AF AntiarrhythmicTherapy

AF AntiarrhythmicTherapy

• Treatment goalsTreatment goals ↓ frequency of recurrences↓ duration of recurrences↓ severity of recurrencesNot to abolish every episode

• Safety is primary concern• Minimize risk of proarrhythmia

Drug-Induced Proarrhythmia -Torsades

Drug-Induced Proarrhythmia -Torsades

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Factors Which InfluenceVentricular Proarrhythmia Risk

Factors Which InfluenceVentricular Proarrhythmia Risk

• Hypokalemia, hypomagnesemia• Long QT at baseline• CHF / Decreased EF• Ventricular hypertrophy • Bradycardia

F l d• Female gender• Reduced drug metabolism or

clearance • Amiodarone has lowest risk

Alternatives to Drug Therapy“Non-Pharmacologic Therapy”Alternatives to Drug Therapy

“Non-Pharmacologic Therapy”

C di LAA l (W t h )Coumadin – LAA closure (Watchman)

Rate Control – AVN RFA + PCMK

AAR Adj ti AFL RFAAARx – Adjunctive AFL RFA

AARX – Curative Afib RFA

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The Rational for the Watchman Device

The Rational for the Watchman Device

Clean Left Atrial Appendage Left Atrial Appendage ClotClean Left Atrial Appendage Left Atrial Appendage Clot

Manning WJ. N Engl J Med. 1993;328:750-755.

Watchman®Watchman®

•Efficacy of Watchman was non-inferior to warfarin for stroke prophylaxis in p p ypatients with non-valvular atrial fibrillation

•Higher rate of adverse events in the intervention group was mainly result of

NEJM

g p yperiprocedural complications

•Awaiting FDA approvalHolmes et al. Lancet 2009; 374: 534-42.

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Pacemaker + AV Node Ablation Pacemaker + AV Node Ablation

http://www.heartrhythmcenter.com/myweb2/av_nodal_ablation2.htmhttp://www.nlm.nih.gov/medlineplus/ency/images/ency/fullsize/19566.jpg

AVN RF AblationAVN RF Ablation

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70

mean

55

50 mean

Objective Benefits of AV Nodal AblationObjective Benefits of AV Nodal Ablation

60

50

40

30

LVEF

(%)

mean54 + 7

p < 0.001

mean43 + 8

45

35

30

LVES

D (m

m)

mean34 + 5

p < 0.003

mean40 + 5

40

25

Rodriguez LM. Am J Cardiol. 1993;72:1137-1141.

A Left ventricular ejection fraction (%)

B Left ventricular end systolic diameter (mm)

20Before After

20Before After

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AVN Ablation AVN Ablation Advantages:

100% efficacy85% symptomatic improvement85% symptomatic improvementImproved EF (LV remodeling)Eliminates need for rate control drugs

Disadvantages:Pacemaker dependant

Good Candidates:Good Candidates:Tachy / Brady SyndromePPM present – CHF with BiV deviceMedication refractory / intolerantElderly

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IC Antiarrhythmic Induced Atrial Flutter1:1 Conduction

IC Antiarrhythmic Induced Atrial Flutter1:1 Conduction

Atrial Flutter CircuitAtrial Flutter Circuit

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Approximately 15% of AF patients treated with an AARx will develop AFL

Atrial Flutter AblationAtrial Flutter Ablation

Advantages:95% efficacy≈ 80% arrhythmia control if AARx continuedAs primary Tx RFA more effective than AARx

Disadvantages: Invasivesad a tages as e

Good Candidates:Typical AFL (IVC / TV isthmus)Primary or AARx related Atrial Flutter

• 94% of AF RA LA

Focal Origin of Atrial FibrillationHassaiguerre M, NEJM, 1998

Focal Origin of Atrial FibrillationHassaiguerre M, NEJM, 1998

triggers from Pulmonary Veins

• “90-95% of all AF FO

SVC

Pulmonary Veins

is initiated by PV ectopy”

CS

IVC 6 11

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Atrial Fibrillation AblationAtrial Fibrillation AblationAtrial ShellAtrial Shell Cardiac MRICardiac MRI

Comparison of Antiarrhythmic Drug Therapy and Radiofrequency Catheter Ablation in Patients with Paroxysmal Atrial Fibrillation: A Randomized Controlled Trial

Comparison of Antiarrhythmic Drug Therapy and Radiofrequency Catheter Ablation in Patients with Paroxysmal Atrial Fibrillation: A Randomized Controlled Trial

66%vs.

16%

JAMA 2010

Major Adverse Events: Ablation 4.9% vs. AARx 8.8%Repeat Ablation in 12.6% of patients

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Current State of CurativeCatheter-Based RFA

Who is a good candidate?

Current State of CurativeCatheter-Based RFA

Who is a good candidate?Symptomatic / Frequent AFLimited Heart Dz

EF > 35%LA < 5.5cmNo MS / Rheumatic Dz

Younger PatientsNo LA thrombus or Hx of CVAMedically Refractory / Intolerant

(Ablation now second line therapy)

New TechnologyMultielectrode

Ablation Catheters

New TechnologyMultielectrode

Ablation Catheters

LSPV

LIPV

Catheter Positioning in Antrum of Left PVs

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Balloon TechnologyBalloon TechnologyRSPVRSPV LSPVLSPV

StereotaxisRemote Magnetic Control

StereotaxisRemote Magnetic Control

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Atrial FibrillationNew Technology / Studies at

Ohio State University

Atrial FibrillationNew Technology / Studies at

Ohio State UniversityStereotaxis – Magnetic Catheter Navigation

New Catheter Design / Energy Sources High Intensity Focused Ultrasound (HIFU)Ablation Frontiers – Circular CathetersCryoablationLaser Ablation

Cabana trial – Drug vs Ablation (including primary therapy)

Watchman – Left Atrial Appendage ClosureSurgical vs Catheter Ablation