Atrial FibrillationCurrent Approaches

to Management DRTEIMOURI H

Atrial Fibrillation: General Comments

Affects approximately 1.5 million people in the US More common in men than in women Incidence increases with age May cause symptoms of palpitations, fatigue, chest pain, and

syncopy Embolic CVA’s are most dreaded complication

Atrial fibrillation accounts for 1/3 of all patient

discharges with arrhythmia as principal diagnosis.

2% VF

Data source: Baily D. J Am Coll Cardiol. 1992;19(3):41A.

34% Atrial

Fibrillation

18% Unspecified

6% PSVT

6% PVCs

4% Atrial Flutter

9% SSS

8% Conduction

Disease

3% SCD

10% VT

Atrial Fibrillation Demographics by Age

Adapted from Feinberg WM. Arch Intern Med. 1995;155:469-473.

U.S. population

Population withatrial fibrillation

Age, yr

<5 5-9

10-14

15-19

20-24

25-29

30-34

35-39

40-44

45-49

50-54

55-59

60-64

65-69

70-74

75-79

80-84

85-89

90-94

>95

U.S. populationx 1000

Population with AFx 1000

30,000

20,000

10,000

0

500

400

300

200

100

0

Atrial Fibrillation: Nomenclature

Paroxysmal: Terminates spontaneously. Persistent: Does not terminate spontaneously. Will

cardiovert. Permanent: Will not cardiovert.

A Fib: Pathophysiologic Basis

Wandering wavelet Rapid firing focus

Atrial Fibrillation: Causes

Cardiac

Non-cardiac

“Lone” atrial fibrillation

Atrial Fibrillation: Cardiac Causes Hypertensive heart disease Ischemic heart disease Valvular heart disease

– Rheumatic: mitral stenosis

– Non-rheumatic: aortic stenosis, mitral regurgitation

Pericarditis Cardiac tumors: atrial myxoma Sick sinus syndrome Cardiomyopathy

– Hypertrophic

– Idiopathic dilated (? cause vs. effect)

Post-coronary bypass surgery

Atrial Fibrillation: Non-Cardiac Causes

Pulmonary

– COPD

– Pneumonia

– Pulmonary embolism

Metabolic

– Thyroid disease: hyperthyroidism

– Electrolyte disorder

Toxic: alcohol (‘holiday heart’ syndrome)

“Lone” Atrial Fibrillation

Absence of identifiable cardiovascular, pulmonary, or associated systemicdisease

Approximately 0.8 - 2.0% of patients with atrial fibrillation (Framingham Study)1

In one series of patients undergoing electrical cardioversion, 10% had lone AF.2

1 Brand FN. JAMA. 1985;254(24):3449-3453.

2 Van Gelder IC. Am J Cardiol. 1991;68:41-46.

Atrial Fibrillation: Clinical Symptoms

Often asymptomatic Symptoms can include:

– Palpitations– Weakness– Dyspnea– Rapid fatigability– Nervousness– TIA/CVA

Atrial Fibrillation: Screening Procedures

All patients– History

– Physical examination

– ECG

– Echocardiogram

– CBC, Thyroid function

Many/most patients– Exercise stress test

– Holter monitor

Selected patients– Chest x-ray

– Invasive procedures

Role of Echo in Atrial Fibrillation

Identify structural heart disease

Identify LVH

Identify LA size

Detect “smoke”

Detect clot in LA

Atrial Fibrillation: Clinical Problems Embolism and stroke (presumably due to LA clot)

Acute hospitalization with onset of symptoms

Anticoagulation, especially in older patients (> 75 yr.)

Congestive heart failure

– Loss of AV synchrony

– Loss of atrial “kick”

– Rate-related cardiomyopathy due to rapid ventricular response

Rate-related atrial myopathy and dilatation

Chronic symptoms and reduced sense of well-being

A Fib: Consequences

Electrical remodeling of atrium Atrial ischemia Structural remodeling of atrium Dilated/hypocontractile atrium Atrial fibrillation can be considered a type of tachycardia

induced atrial cardiomyopathy

Atrial Fibrillation: Clinical Issues

Rate control Anticoagulation Conversion to and mantenance of sinus rhythm

Atrial Fibrillation

Rate control

Atrial Fibrillation: Rate Control

Essential in all patients Persistent tachycardic rates can induce cardiomyopathy and

heart failure Occasional follow-up holter monitor to ascertain rate control

A Fib: Control Ventricular Response

Digitalis Beta Blockers Calcium Channel Blockers (verapamil, diltiazem) IV Amiodarone (in the ICU setting) Electrical ablation

Atrial Fibrillation: Digoxin

Oldest and most commonly prescribed drug for control of ventricular rate

Predominant acute effect is mediated by the autonomic nervous system

An important slowing effect of the AV node is mediated by enhanced vagal tone

Not effective during periods of increased sympathetic tone Not effective in paroxysmal atrial fibrillation

Atrial Fibrillation: Role of Digoxin

Patients with chronic AF and sedentary life-style Symptom free patient with AF in whom digoxin provides

adequate control of the resting heart rate

Atrial Fibrillation: Verapamil/Diltiazem

Both are effective in controlling the ventricular rate Control the resting ventricular rate and blunt the exercise

response Verapamil may increase digoxin levels by up to 50%

Atrial Fibrillation: Beta Blockers

Controls the resting ventricular rate and blunts the exercise response

May help prevent paroxysmal atrial fibrillation

Atrial Fibrillation

Anticoagulation

Atrial Fib: Management StragegiesQuestion Remains?

Anticoagulation and rate control vs. conversion to and maintenance of normal sinus rhythm

AFFIRM trial is currently looking at this

Incidence of Stroke by Left Atrial Size(Framingham Study)

Benjamin EJ. Circulation, 1995;92:835-841.

9%

8%

7%

6%

5%

4%

3%

2%

1%

0 1 2 3 4 5 6 7 80%

WOMEN

Years of follow-up

9%

8%

7%

6%

5%

4%

3%

2%

1%

0%0 1 2 3 4 5 6 7 8

Tertile ofLA size

3

2

1

Years of follow-up

MEN

Atrial Fibrillation and Stroke

Risk: 5 - 8% per year in high-risk patients

Anticoagulant therapy is clearly indicated and beneficial in rheumatic atrial fibrillation.

In non-rheumatic atrial fibrillation, major randomized trials have provided useful guidelines for identifying and treating patients at risk.

Major Clinical Trials in Atrial Fibrillation

SPAF1 Stroke Prevention in Atrial Fibrillation

BAATAF2 Boston Area Anticoagulation Trial for Atrial Fibrillation

CAFA3 Canadian Atrial Fibrillation Anticoagulation

AFASAK4 Copenhagen Investigators

SPINAF5 Stroke Prevention in NonrheumaticAtrial Fibrillation

1 Circulation. 1991;84:527-539.2 N Engl J Med. 1990;323:1505-1511.3 J Am Coll Cardiol. 1991;18:349-355.

4 The Lancet. 1989;1:175-178.5 N Eng J Med. 1992;327:1406-1412.

Stroke Prevention in Atrial Fibrillation:

Warfarin Data

Warfarin Better Warfarin Worse

Risk Reduction, %

Combined 108 3691

SPINAF 29 972

SPAF 23 508

CAFA 14 478

BAATAF 15 922

AFASAK 27 811

No. ofEvents

Patient-Years

100 50 0 -50 -100

Atrial Fibrillation Investigators. Arch Intern Med. 1994;154:1449-1457.

Stroke Prevention in Atrial Fibrillation:

ASA Data

Atrial Fibrillation Investigators. Arch Intern Med. 1994;154:1449-1457.

Aspirin Better Aspirin Worse

Risk Reduction, %

Combined 100 2264

SPAF 65 1457

AFASAK 35 807

No. ofEvents

Patient-Years

100 50 0 -50 -100

SPAF III

SPAF III study evaluated the benefit of

adjusted-dose warfarin vs. low-intensity, fixed-dose

warfarin (INR 1.2 - 1.5) plus ASA

in high-risk patients with atrial fibrillation.

SPAF Investigators. Lancet. 1996;348:633-638.

Stroke Rate in Adjusted-Dose

Warfarin vs. Combination

Therapy

SPAF Investigators. Lancet. 1996;348:633-638.

Combination therapy

Adjusted-dose warfarin

Cu

mu

lati

ve e

ven

t ra

te (

% p

er y

ear)

20

18

16

14

12

10

8

6

4

2

0

0 365 730

Days from randomisation

521

523

378

397

265

273

166

173

61

65

Combination therapy

Warfarin therapy

Number at Risk

Cumulative Rate of Ischemic Stroke or Systemic Embolism

Relative Risk of Adjusted-Dose Warfarin and Combination Therapy

SPAF Investigators. Lancet. 1996;348:633-638.

Combination therapy better

Adjusted-dose warfarin better

Major hemorrhage

Stroke, myocardialinfarction or vascular

death

Primary event orvascular death

All disabling stroke

Disabling ischemicstroke

Primary event

0 0.5 1 1.5 2

Relative risk and 95% CI (horizontal bar)

Predictors of Thromboembolic Risk in Atrial Fibrillation

History of hypertension

Prior stroke or TIA

Diabetes

Recent heart failure

Age > 65 years

Atrial Fibrillation Investigators. Arch Intern Med. 1994;154:1449-1457.

Echocardiographic Risk Factorsfor Stroke Factors in Patients with

Atrial Fibrillation

LV systolic dysfunction

Increased LA size

SPAF Investigators. Ann Intern Med. 1992;116:6-12.

Current Recommendations: Management of Patients with Atrial Fibrillation

Therapy recommendations for AF are currently in flux.1,2

1 Prystowski EN. Circulation. 1996;93:1262-1277.2 Blackshear JL. Mayo Clin Proc. 1996;71:150-160.

Atrial Fibrillation: Anticoagulation

Chest 1998;114(suppl):439S-769S

Treatment

Warfarin (INR 2.0 - 3.0) 4 wks. before and 4 wks. after cardioversion

– Hold warfarin for 3 days

– Stop warfarin 7 days prior to surgery

Daily INR when < 1.5

Start SQ heparin 10,000u every 12 hours and follow PT/PTT

Stop heparin 12 hours beforesurgery

Guidelines Regarding Anticoagulation for Atrial Fibrillation

Clinical Background

Elective cardioversion

Elective surgery for anticoagulated patient:

– Minor surgery

– Major surgery

Atrial Fibrillation

Conversion to and maintenance of sinus rhythm

Atrial Fibrillation

We have no data to say that sinus rhythm, once achieved with antiarrhythmics, prolongs life.

A Fib: Restoration/Maintenance of NSR

DC Cardioversion Antiarrhythmic therapy Non-pharmacologic approaches

A Fib: CardioversionPoor Candidates

Untreated mitral valve disease Untreated thyrotoxicosis Large left atrium ( > 5 cm ) Duration > 1 year Slow ventricular response without drugs Digitalis toxicity

AtrialFibrillation

Duration of atrial fibrillation may predict likelihood of remaining in normal sinus rhythm 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

*

Dependence of Cardioversion Rate on Patient Age and Arrhythmia Duration

Van Gelder IC. Am J Cardiol. 1991;68:41-46.

Cardioversion Rates:Atrial FlutterAtrial Fibrillation

90%

70%80%90%

Age (years)20 25 30 35 40 45 50 55 60 65 70 75 80 85 90

0

20

40

60

80

100

120P

revi

ou

s d

ura

tio

n (

mo

nth

s)

Chronic1 month coumadin cardioversion (CV)

Uncertain durationStable 1 month coumadin CVUnstable TEE CV

Acute

Timing of Cardioversion for Atrial Fibrillation

coumadin repeat TEE CV

no clot

clot

Heparin TEE

CV coumadin

Role of TEE in Atrial Fibrillation

Transesophageal echo is more sensitive (92%) and specific (98%) for detecting left atrial clot.

Thromboembolic event is presumably due to left atrial clot.

Most clots are in left atrial appendage but poorly visualized by transthoracic surface echo.

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

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

A Left Atrium B Left Atrial Appendage Clot

Rationale for Precardioversion TEE

Absence of clot on TEE may obviate need for anticoagulation.

Avoiding delay necessary for prolonged anticoagulation prior to cardioversion increases likelihood of successful cardioversion and maintenance of normal sinus rhythm.

Increase in Spontaneous Echo Contrast (“Smoke”) Following Electrical Cardioversion

Grimm RA. J Am Coll Cardiol. 1993;22(5):1359-1366.

Left atrial appendage (LAA) before (A) and after (B) cardioversion

A Fib: The Tough Questions

Which drug? Does the patient need to be hospitalized?

Antiarrhythmic Drugs to SuppressAtrial Fibrillation

Class I agents

– IA: quinidine, procainamide, disopyramide

– IC: flecainide, propafenone

Class III agents

– amiodarone, sotalol, dofetilide

0

20

40

60

80

100

3 6 12

Quinidine

Control

Atrial Fibrillation:

Prevention of Recurrence

Coplen SE. Circulation. 1990;82:1106-1116.

Quinidine-treated group remained in NSR better than control group(p < 0.001).

Pe

rce

nt

of

pa

tien

ts in

NS

R (

%)

Time (months)

Odds Ratio for Total Mortality for Patients Treated with Quinidine Compared to Control

Coplen SE. Circulation. 1990;82:1106-1116.

RCT

Boissel

Byrne-Quinn

Hartel

Hillestad

Lloyd

Sodermark

ALL STUDIES N = 808

0 1 2 3 4 5 6 7 8 9 10 11 12

Odds Ratio (Quinidine: Control)

Quinidine Better Quinidine Worse

212

92

175

100

53

176

n

Proarrhythmia from Antiarrhythmics Used in SPAF Study

Number of Arrhythmic Adjusted RiskPatients Deaths Hazard

All patients 1,307 28 2.1

Patients with 239 12 5.8definite CHF

Patients without 1,068 16 0.83definite CHF

Adapted from Flaker GC. J Am Coll Cardiol. 1992;20:527-532.

A Fib: Amiodarone

Safe in CHF patients CHF-STAT Trial ( CIRC 1998;98:2574) 31% converted to sinus rhythm Patients who converted to sinus rhythm had increased

survival

Amiodarone

In clinical trials 41% stopped taking Amiodarone Toxic effects

– Liver– Thyroid– Lungs

Medication for Rate Control in Atrial Fibrillation

Class IAQuinidine gluconate 324-648 mg Q 8-12 hr Chronic renal failure CHF, liver failure

Procainamide 0.5-1.5 g Q 12 hr* Men, short-term therapy Renal failure, CHF,joint disease

Disopyramide 200-400 mg Q 12 hr Women Older men at risk forurinary retention, CHF,glaucoma, renal failure

Class ICFlecainide 75-150 mg Q 12 hr Failure of Class IA drugs CHF, CAD

Propafenone 150-300 mg Q 8 hr Failure of Class IA drugs CHF

Class IIISotalol 80-240 mg Q 12 hr Failure of IA or IC drug Where beta blockade is

May be used with mild- contraindicatedmoderate LV dysfunction

Amiodarone 1200 mg QD for 5 days Severe LV dysfunction, Young patients,followed by 400 mg QD for failure of other drugs, pulmonary disease1 month, then 200-400 mg QD CHF, renal failure Many alternative dosingregimens

* For newer preparation.Adapted from Gilligan DM. Am J Med. 1996;101:413-421.

Drug Oral Dose Useful in Avoid in

A Fib: Antiarrhythmic Therapy

Antiarrhythmic drug therapy is like baseball. Your best hitters hit the ball one third of the time. Only 30-50% of patients on antiarrhythmic therapy will be in sinus rhythm at one year.

Disadvantages

– High recurrence rate

– High long-term cost

– Noncurative

– Adverse effects

– Potential proarrhythmia

Antiarrhythmic Therapy for Atrial Fibrillation

Advantages

– High efficacy for somepatients, at leastinitially (< 50% of all patients)

– Low initial cost

– Noninvasive

A Fib: Selection of Antiarrhythmic Rx

No structural heart disease, Nml EF– All

CAD, EF>40– Sotalol, Amiodarone

Other HD (HTN), EF>40– IC, Sotalol, Amiodarone

CHF, EF<40– Amiodarone, Dofetilide

Atrial Fibrillation: Maintenance of Sinus Rhythm

Atrial Fibrillation: Hospitalization of Sotalol Therapy

Retrospective record review of 120 patients monitored during initiation of treatment with sotalol

80% of patients with underlying heart disease Arrhythmic complications observed in 21% of patients

JACC 1998;32:169-176

Atrial Fibrillation:Hospitalization with Initiation of Rx

Inpatient therapy– Patients with structural heart disease

Outpatient therapy– Patients without structural heart disease– Caution with sotalol

Recommendations for Management of Atrial Fibrillation < 48 Hours

Adapted from Golzari H. Ann Intern Med. 1996;125:311-323.

Atrial Fibrillation < 48 hours

Prompt electrical or pharmacologic

conversion

Control ventricular rateConsider antithrombotic therapy

Observe for spontaneous conversion

Antiarrhythmic therapyif

No antiarrhythmic therapyif

Unstable hemodynamics or frequent recurrences

Stable hemodynamics, infrequent

recurrences, or first episode

Adapted from Golzari H. Ann Intern Med. 1996;125:311-323.

Recommendations for Management of Atrial Fibrillation > 48 HoursAtrial Fibrillation > 48 Hours

Control ventricular rateStart antithrombotic therapy

(heparin and/or warfarin or aspirin)

Duration < 1 year Duration > 1 year

Warfarin therapy 3-4 weeks

Cardioversion or pharmacologic conversion

Antiarrhythmic therapyif

No antiarrhythmic therapyif

Unstable hemodynamics or frequent recurrences

Stable hemodynamics,infrequent recurrences, or

first episode

Continue warfarin 1-2 monthsMonitor for recurrences

Chronic antithrombotic therapy

Assure control of ventricular rate

or

Rate Control for Atrial Fibrillation

Some “idiopathic” cardiomyopathies are due to

atrial fibrillation with rapid ventricular response.

When rate control is achieved, LV function often

improves dramatically.

In some patients, pharmacologic therapy is ineffective for

rate control, and catheter ablation and permanent pacing

are indicated.

AV Nodal Modification by Intracardiac Ablation

RAO LAO

Catheter Ablation of AV Nodal Conduction and Permanent

Pacemaker Implantation

Treatment for patients with atrial fibrillation with a rapid ventricular response

Subjective Benefits of Catheter Ablation of AV Nodal

Conduction and Permanent Pacemaker Implantation

Kay GN. Am J Cardiol. 1988;62:741-744.

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

Pre Post

Min

ute

s

Treadmill exercise performance before and after procedure. All patients were in rate-adaptive pacing mode for follow-up.

Efficacy ofSurgical MazeProcedure for

Atrial Fibrillation

Kawaguchi AT. J Am Coll Cardiol. 1996;28:985-990.

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3

Fre

edo

m f

rom

atr

ial f

ibri

llati

on

(%

)

Post-op years

Control

Maze

Haïssaguerre M. J Cardiovasc Electrophysiol.

1994;5:1045-1052.

Catheter MazeProcedure for

Atrial Fibrillation

Atrial Fibrillation: Areas of Research AFFIRM study

– National Heart Institutes atrial fibrillation study– Heart rate control and anticoagulation vs. rhythm control with

antiarrhythmic drugs

Patient-activated or automatic atrial defibrillator

Dual-site and biatrial pacing

Atrial pacing therapies for AF prevention

Catheter ablation therapies for AF– Catheter “maze” procedure– Ablation for “focal” AF

Transvenous Atrial Defibrillation

Prospective multicenter trial to define efficacy and safety of low-energy shocksfor atrial defibrillation

Delivery of shocks between right atrial and coronary sinus electrode catheters

141 patients enrolled

Levy S. J Am Coll Cardiol. 1997;29:750-755.

Catheter Position for Intracardiac Atrial Defibrillation

Levy S. J Am Coll Cardiol. 1997;29:750-755.

Atrial Defibrillation: Conclusions

Atrial defibrillation using transvenous intracardiac leads can be highly efficacious and requires relatively low energies.

The optimal waveform characteristics of delivered energy to minimize patient discomfort during defibrillation continues to be evaluated.

Atrial FibrillationIssues to Address

Rate Control Anticoagulation Conversion to sinus