John D. Hummel, MDOhio State University Medical Center

Ross Heart Hospital Columbus, Ohio

Current Mangement of Atrial Fibrillation: An Evidence-Based Approach

Learning Objectives

• Understand the guidelines for anticoagulation and where there is latitude for physician decisionmaking.

• Be able to discriminate between patients requiring restoration of sinus rhythm vs. rate control alone.

• Be able to determine when patients should be evaluated for curative ablation.

5.615.425.16

4.784.34

3.803.33

2.942.66

2.442.26

2.08

0

1

2

3

4

5

6

1995

2000

2005

2010

2015

2020

2025

2030

2035

2040

2045

2050

2060

Year

Ad

ult

s w

ith

AF,

MM

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

Projected Number of Adults With AF in the US: 1995 to 2050.

Atrial Fibrillation: Costs to the Health Care System

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

Estimated US cost burden 15.7 billion

ALOT!!

Paroxysmal(Self-terminating)

First Detected

Permanent

Classification of Atrial FibrillationACC/AHA/ESC Guidelines

Persistent(Not self-terminating)

DIAGNOSTIC WORKUP• Minimum Evaluation• History and physical – Sx with AF, CV dz• Electrocardiogram – WPW, BBB, LVH, MI• Echocardiogram – LVH, LAE, EF, Valve Dz• Labs – TSH, Renal fxn, LFTs• Additional Testing• ETT – CAD, Exercise induced SVT / AF• Holter / Event Monitor – Confirm AF and Sxs• TEE – LA clot• EPS – SVT triggered AF

AHA / ACC / ECS Guidelines 2006

Maintenance of SR

Pharmacologic

Stroke prevention

Nonpharmacologic

Class IA Class ICClass III-blocker

Catheter ablationSurgery (MAZE)Pacing

Pharmacologic• Warfarin• Thrombin inhibitor• Aspirin

Nonpharmacologic• Removal / isolation

LA appendage

Rate control

Pharmacologic• Ca2+ blockers-blockers• Digitalis• Amiodarone

Nonpharmacologic• Ablate and pace

Prevent remodeling ACE-IARB

AF: TREATMENT OPTIONS

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

Risk Factors for Thromboembolism in AF

High-Risk Factors Recommended TherapyPrevious CVA / TIA / Embolism High-risk factor or > 2 Mitral Stenosis moderate-risk factorsProsthetic heart valve Coumadin INR 2-3

Moderate-Risk Factors (mechanical valve INR > 2.5)Age > 75 yrsHTN 1 moderate-risk factorCHF ASA or CoumadinDMEF < 35% No risk factors

Weaker-Risk Factors ASA 81-325mg dailyFemaleCADThyrotoxicosisAge 65 – 74 yrs

AHA / ACC / ECS Guidelines 2006

AF THERAPY

ANTITHROMBOTIC RX

RHYTHMCONTROL

RATECONTROL

OR ?

AND

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

AFFIRM Trial: Rate vs Rhythm ControlManagement Strategy Trial

• Design– 5-year, randomized, parallel-group study

comparing rate control vs. AARx attempt at NSR– Primary endpoint: overall mortality

• Patient population– 4060 patients with AF and risk factors for stroke– Mean Age = 69 yo– Hx of hypertension: 70.8%– CAD: 38.2%– Enlarged LA: 64.7%– Depressed EF: 26.0%

AFFIRM: All-Cause Mortality

Rate N:

Rhythm N:

2027

2033

1925

1932

1825

1807

1328

1316

774

780

236

255

0

5

10

15

20

25

30

0 1 2 3 4 5

Mo

rtal

ity,

%

Rate

Rhythm

p=0.078 unadjusted

Time (years)

p=0.068 adjusted

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

Rate Rhythm

Ischemic stroke 77 (5.5%)* 80 (7.1%)*

INR < 2.0 27 (35%) 17 (21%)

Not taking warfarin

25 (32%) 44 (55%)

* p=0.79

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

AFFIRM: Adverse Events

AF Rate vs. Rhythm Control Trials: Implications

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

• Continuous anticoagulation seems warranted in all patients with risk factors for stroke– Asymptomatic recurrences

Atrial fibrillation

Rate control – the problem:Increased rates – more symptomatic, greater

hemodynamic impact.

Persistent increased rates – tachycardia induced cardiomyopathy

Rate control – the goal:PAF – control symptomatic tachycardiaChronic afib – mean 24hr HR < 80-90 bpm

Atrial fibrillation

Rate control – Drug Therapy:

Digoxin – controls resting rate, OK in CHF patients .

Beta, Ca+2 blockers – controls resting and exercise rates.

Best therapy – combination of beta blocker and digoxin.

Even in the best of circumstances pacing support is sometimes required

Rate control plusanticoagulation preferred

Rhythm controlpreferred

• No or lesser AF symptoms• Longer AF Hx• More SHD• Toxicity Risk• Elderly• Greater risk of

proarrhythmia • Greater AF symptoms• Symptoms despite rate control• Younger age• No or lesser SHD• Rx option of class IC AAD

In anticoagulation candidates, continue anticoagulation indefinitely

APPROACHES TO AF THERAPY

Atrial Fibrillation

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

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

< 3 Months3 - 12 Months> 12 Months

100

80

60

40

20

0Initial One month

post-CVSix months

post-CV*P = <0.02

Pat

ien

ts in

sin

us

rhyt

hm

(%

)

Length of timein AF prior tocardioversion

*

AF TREATMENT GOALS• AF is rarely life-threatening and is

typically recurrent • Treatment goals in symptomatic pts

frequency of recurrences duration of recurrences severity of recurrences

• Minimize risk of tachycardia induced cardiomyopathy

• Safety is primary concern

Class IA

Quinidine

Procainamide

Disopyramide

Class IC

Propafenone

Propafenone SR

Flecainide

Class III

Sotalol

Amiodarone

Dofetilide

Miller and Zipes. In: Braunwald, et al (eds). Heart Disease. 6th ed. 2001.

Procainamide, disopyramide, and amiodarone are not FDA-approved for treatment of AF.

Rhythm Control for AF: Commonly Used Oral Antiarrhythmic Drugs

AF Efficacy: Maintaining NSR > 6 Months

0

10

20

30

40

50

60

70

NS

R,

%

Nodrug

Quin Diso Prop Flec Sot Dof Azim Amio

ORGAN TOXICITY

• Examples:– Lupus, agranulocytosis, thrombocytopenia, optic

neuritis, pulmonary fibrosis, hepatitis, etc.

• Negligible:– Dofetilide, flecanide, propafenone, sotalol

• Acceptible:– Azimilide, disopyramide

• High:– Amiodarone, procainamide, quinidine

Drug-Induced Proarrhythmia - Torsades

Factors Which InfluenceVentricular Proarrhythmia Risk

• Hypokalemia, hypomagnesemia• Long QT at baseline• CHF / Decreased EF / Ventricular hypertrophy • Bradycardia• Female gender• Reduced drug metabolism or clearance • Amiodarone has lowest risk

Atrial fibrillation

Heart disease Antiarrhythmic

None IC Vagal afib DisopyramideHTN IC (if no sig. LVH)CAD SotalolCHF/Substantial AmiodaroneLVH

Alternatives to Drug therapy“Non-Pharmacologic Therapy”

Coumadin – LAA closure (Watchman)

Rate Control – AVN RFA + PCMK

AARx – Adjunctive AFL RFA

AARX – Curative Afib RFA

WATCHMAN® LAA Filter System

Complete AVN ablation

Pacemaker PlacementPacemaker Placement

AVN RF ablation

Objective Benefits of AV nodal Ablation

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

A Left ventricular ejection fraction (%)

B Left ventricular end systolic diameter (mm)

70

60

50

40

30

20Before After

LV

EF

(%

)

mean54 + 7

p < 0.001

mean43 + 8

55

50

45

35

30

20Before After

LV

ES

D (

mm

)

mean34 + 5

p < 0.003

mean40 + 5

40

25

Complete AVN Ablation Advantages:

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

Disadvantages:Pacemaker dependant

Good Candidates:Tachy / Brady SyndromePCMK in Place – CHF with BiV deviceMedication refractory / intolerantElderly

60 F with PAF treated with RythmolPresented with recurrent tachycardia

Atrial Flutter Circuit

Atrial Flutter Circuit

Atrial Flutter AblationAtrial Flutter Ablation

Atrial Flutter RFA

Atrial Flutter Ablation Approximately 15% of AF patients treated with an AA will develop

AFL

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

Disadvantages: Invasive

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

Focal Origin of Atrial Fibrillation

Hassaiguerre M, NEJM, 1998

• 94% of AF triggers from Pulmonary Veins

• “90 – 95% of all AF is initiated by PV ectopy”

RA LA

CS

FO

SVC

IVC

Pulmonary Veins

17 31

6 11

74 yo medically refractory AF, Echo – Normal AA Rx - Verapamil, Rythmol, Betapace, Norpace

IIIIII

V1RSPV

distRSPV

prox

LIPV

RA

*

Lasso Catheter

Circular Mapping & Ablation Catheter inRight Superior Pulmonary Vein

Atrial Fibrillation AblationAtrial Shell and Cardiac MRI

45 yo F with medically refractory 45 yo F with medically refractory Highly Symptomatic PAF Highly Symptomatic PAF

45 yo F with Medically Refractory PAFCT Scan / Carto Images – PA View

45 yo with PAFConversion of AF to NSR, LSPV with AF

Lasso

LSPV

CS

Abl

Current State of CurativeCatheter-Based RFA

Procedural Success & Complications

• Total Patients > 800 (70% PAF)• Expected success @ 1yr

– ≈ 70% after first procedure– ≈ 80% after second procedure

• Complications ≈ 2 to 3%– Tamponade – 0.6%– Pulmonary vein stenosis – 0.6%– TIA / CVA – 0.5%– Esophageal-LA fistula - 0– Groin Bleeding / Hematoma

(Last 200 pts complications < 1%)

Atrial Fibrillation: Ablation vs Drug Rx.Ablation80% successPV stenosisAE fistula TIA/CVA

Drug Rx.50% successProarrhythmiaEnd Organ Toxicity

No Free Lunch

PV stenosis

AE fistula

Torsades

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)

Industry Estimates: AF Demographics

• Approximately 26,000 AF ablation procedures (surgery + EP) were performed in 2004.

• Currently, only about 1% of AF population being addressed with curative therapies.

• Estimates for EP Afib RFA:2005 = 19,000

2006 = 21,000

AF Patients 2,400,000

AF Patients Treated 26,000

AF Patients AF Patients Treated

Physicians estimate apporx. 30% of Afib pts are RFA candidates.

(1%)

The Trouble With a Moving Target

Atrial Fibrillation AblationAtrial Fibrillation AblationEvolution of the Moving TargetEvolution of the Moving Target

Early Rumors (20 hr cases)

20062006Mid 90’sMid 90’s

Right Sided Linear

Phrenic Nerve Injury

Left Sided Focal

Tamponade

TIA/CVA

PV Isolation

PV Stenosis

WACA + Linear

Esophageal FistulasLeft Atrial Flutters

Fractionated Egms

Back to the Right Side

Hybrid Approaches

Need for Stereotaxis,Cryoablation, HIFU?

IVUS / Transeptal Lasso 3D Mapping CT integration

Atrial FibrillationNew Technology Coming Your Patients Way at

Ohio State University

Stereotaxis – Magnetic Catheter Navigation

Energy SourcesHigh Intensity Focused Ultrasound (HIFU)Cryoablation Balloon

Watchman – Left Atrial Appendage Closure

A-Fib vs. EP Labs