1. Current Approaches to Management DRTEIMOURI H
Atrial Fibrillation
Current Approaches to Management DRTEIMOURI H

2. 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

3. Atrial fibrillation accounts for 1/3 of all patient discharges with arrhythmia as principal diagnosis.
6% PSVT
6% PVCs
18% Unspecified
4% Atrial Flutter
9% SSS
34% Atrial Fibrillation
8% Conduction Disease
10% VT
3% SCD
2% VF
Data source: Baily D. J Am Coll Cardiol. 1992;19(3):41A.

4. Atrial Fibrillation Demographics by Age
U.S. population x 1000
Population with AF x 1000
30,000
20,000
10,000
Population with atrial fibrillation
500
400
300
200
100
U.S. population
<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
Age, yr
Adapted from Feinberg WM. Arch Intern Med. 1995;155:

5. Atrial Fibrillation: Nomenclature
Paroxysmal: Terminates spontaneously.
Persistent: Does not terminate spontaneously. Will cardiovert.
Permanent: Will not cardiovert.

6. A Fib: Pathophysiologic Basis
Wandering wavelet
Rapid firing focus

7. Atrial Fibrillation: Causes
Cardiac
Non-cardiac
“Lone” atrial fibrillation

8. 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

9. Atrial Fibrillation: Non-Cardiac Causes
Pulmonary
COPD
Pneumonia
Pulmonary embolism
Metabolic
Thyroid disease: hyperthyroidism
Electrolyte disorder
Toxic: alcohol (‘holiday heart’ syndrome)

10. “Lone” Atrial Fibrillation
Absence of identifiable cardiovascular, pulmonary, or associated systemic disease
Approximately % 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): Van Gelder IC. Am J Cardiol. 1991;68:41-46.

11. Atrial Fibrillation: Clinical Symptoms
Often asymptomatic
Symptoms can include:
Palpitations
Weakness
Dyspnea
Rapid fatigability
Nervousness
TIA/CVA

12. 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

13. Role of Echo in Atrial Fibrillation
Identify structural heart disease
Identify LVH
Identify LA size
Detect “smoke”
Detect clot in LA

14. 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

15. 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

16. Atrial Fibrillation: Clinical Issues
Rate control
Anticoagulation
Conversion to and mantenance of sinus rhythm

17. Atrial Fibrillation
Rate control

18. 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

19. A Fib: Control Ventricular Response
Digitalis
Beta Blockers
Calcium Channel Blockers (verapamil, diltiazem)
IV Amiodarone (in the ICU setting)
Electrical ablation

20. 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

21. 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

22. 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%

23. Atrial Fibrillation: Beta Blockers
Controls the resting ventricular rate and blunts the exercise response
May help prevent paroxysmal atrial fibrillation

24. Atrial Fibrillation
Anticoagulation

25. Atrial Fib: Management Stragegies Question Remains?
Anticoagulation and rate control vs. conversion to and maintenance of normal sinus rhythm
AFFIRM trial is currently looking at this

26. Incidence of Stroke by Left Atrial Size (Framingham Study)9% 9%
MEN
WOMEN 8% 8% 7%
Tertile of LA size 7% 6% 6% 5% 3 5% 2 4% 1 4% 3% 3% 2% 2% 1% 1% 0% 0% 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8
Years of follow-up
Years of follow-up
Benjamin EJ. Circulation, 1995;92:

27. 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.

28. 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 Nonrheumatic Atrial Fibrillation
1 Circulation. 1991;84:
2 N Engl J Med. 1990;323:
3 J Am Coll Cardiol. 1991;18:
4 The Lancet. 1989;1:
5 N Eng J Med. 1992;327:

29. Stroke Prevention in Atrial Fibrillation: Warfarin Data
No. of Events
Patient- Years
Stroke Prevention in Atrial Fibrillation: Warfarin Data
AFASAK 27
811
BAATAF 15
922
CAFA 14
478
SPAF 23
508
SPINAF 29
972
Combined
108
3691
100 50
-50
-100
Warfarin Better
Warfarin Worse
Atrial Fibrillation Investigators. Arch Intern Med. 1994;154:
Risk Reduction, %

30. Stroke Prevention in Atrial Fibrillation: ASA Data
No. of Events
Patient- Years
AFASAK 35
807
SPAF 65
1457
Combined
100
2264
100 50
-50
-100
Atrial Fibrillation Investigators. Arch Intern Med. 1994;154:
Aspirin Better
Aspirin Worse
Risk Reduction, %

31. SPAF III
SPAF III study evaluated the benefit of adjusted-dose warfarin vs. low-intensity, fixed-dose warfarin (INR ) plus ASA in high-risk patients with atrial fibrillation.
SPAF Investigators. Lancet ;348:

32. Stroke Rate in Adjusted-Dose Warfarin vs. Combination Therapy
Cumulative event rate (% per year) 20 18 16 14 12 10 8 6 4 2
365
730
Days from randomisation
Number at Risk
Combination therapy
Warfarin therapy
521
523
378
397
265
273
166
173 61 65
Cumulative Rate of Ischemic Stroke or Systemic Embolism
SPAF Investigators. Lancet ;348:

33. Relative Risk of Adjusted-Dose Warfarin and Combination Therapy
Primary event
Disabling ischemic stroke
All disabling stroke
Primary event or vascular death
Stroke, myocardial infarction or vascular death
Major hemorrhage
0.5 1
1.5 2
Adjusted-dose warfarin better
Combination therapy better
Relative risk and 95% CI (horizontal bar)
SPAF Investigators. Lancet ;348:

34. 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:

35. Echocardiographic Risk Factors for Stroke Factors in Patients with Atrial Fibrillation
LV systolic dysfunction
Increased LA size
SPAF Investigators. Ann Intern Med. 1992;116:6-12.

36. Current Recommendations: Management of Patients with Atrial Fibrillation
Therapy recommendations for AF are currently in flux.1,2
1 Prystowski EN. Circulation. 1996;93: Blackshear JL. Mayo Clin Proc. 1996;71:

37. Atrial Fibrillation: Anticoagulation
Chest 1998;114(suppl):439S-769S

38. Guidelines Regarding Anticoagulation for Atrial Fibrillation
Clinical Background
Elective cardioversion
Elective surgery for anticoagulated patient:
Minor surgery
Major surgery
Treatment
Warfarin (INR ) 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 before surgery

39. Atrial Fibrillation
Conversion to and maintenance of sinus rhythm

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

41. A Fib: Restoration/Maintenance of NSR
DC Cardioversion
Antiarrhythmic therapy
Non-pharmacologic approaches

42. A Fib: Cardioversion Poor Candidates
Untreated mitral valve disease
Untreated thyrotoxicosis
Large left atrium ( > 5 cm )
Duration > 1 year
Slow ventricular response without drugs
Digitalis toxicity

43. Length of time in AF prior to cardioversion
Atrial Fibrillation
100
< 3 Months
Months
> 12 Months
Duration of atrial fibrillation may predict likelihood of remaining in normal sinus rhythm after cardioversion 80 60
Patients in sinus rhythm (%) 40 * 20
Initial
One month post-CV
Six months post-CV
*P = <0.02
Dittrich HC. Am J Cardiol ;63:

44. Previous duration (months)
Dependence of Cardioversion Rate on Patient Age and Arrhythmia Duration
120
Cardioversion Rates:
Atrial Flutter
Atrial Fibrillation
100 80
Previous duration (months) 60 40
90% 20
90%
80%
70% 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90
Age (years)
Van Gelder IC. Am J Cardiol ;68:41-46.

45. Timing of Cardioversion for Atrial Fibrillation
Chronic 1 month coumadin ® cardioversion (CV)
Uncertain duration Stable ® 1 month coumadin ® CV Unstable ® TEE ® CV
Acute
no clot
CV ® coumadin
Heparin ® TEE
coumadin ® repeat TEE ® CV
clot

46. 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 ;328:

47. B Left Atrial Appendage Clot
A Left Atrium
B Left Atrial Appendage Clot
Manning WJ. N Engl J Med ;328:

48. 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.

49. Left atrial appendage (LAA) before (A) and after (B) cardioversion
Increase in Spontaneous Echo Contrast (“Smoke”) Following Electrical Cardioversion
Left atrial appendage (LAA) before (A) and after (B) cardioversion
Grimm RA. J Am Coll Cardiol ;22(5):

50. A Fib: The Tough Questions
Which drug?
Does the patient need to be hospitalized?

51. Antiarrhythmic Drugs to Suppress Atrial Fibrillation
Class I agents
IA: quinidine, procainamide, disopyramide
IC: flecainide, propafenone
Class III agents
amiodarone, sotalol, dofetilide

52. Atrial Fibrillation: Prevention of Recurrence
Percent of patients in NSR (%)
Quinidine-treated group remained in NSR better than control group (p < 0.001).
Time (months)
Coplen SE. Circulation. 1990;82:

53. Odds Ratio for Total Mortality for Patients Treated with Quinidine Compared to Control
RCT n
Boissel
212
Byrne-Quinn 92
Hartel
175
Hillestad
100
Lloyd 53
Sodermark
176
ALL STUDIES N = 808 1 2 3 4 5 6 7 8 9 10 11 12
Quinidine Better
Quinidine Worse
Odds Ratio (Quinidine: Control)
Coplen SE. Circulation. 1990;82:

54. Proarrhythmia from Antiarrhythmics Used in SPAF Study
Number of Arrhythmic Adjusted Risk Patients Deaths Hazard
All patients 1,
Patients with definite CHF
Patients without 1, definite CHF
Adapted from Flaker GC. J Am Coll Cardiol. 1992;20:

55. 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

56. Amiodarone In clinical trials 41% stopped taking Amiodarone
Toxic effects
Liver
Thyroid
Lungs

57. Medication for Rate Control in Atrial Fibrillation
Drug
Oral Dose
Useful in
Avoid in
Class IA Quinidine gluconate mg Q 8-12 hr Chronic renal failure CHF, liver failure
Procainamide g Q 12 hr* Men, short-term therapy Renal failure, CHF, joint disease
Disopyramide mg Q 12 hr Women Older men at risk for urinary retention, CHF, glaucoma, renal failure
Class IC Flecainide mg Q 12 hr Failure of Class IA drugs CHF, CAD
Propafenone mg Q 8 hr Failure of Class IA drugs CHF
Class III Sotalol mg Q 12 hr Failure of IA or IC drug Where beta blockade is May be used with mild- contraindicated moderate 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 disease 1 month, then mg QD CHF, renal failure Many alternative dosing regimens
* For newer preparation. Adapted from Gilligan DM. Am J Med. 1996;101:

58. 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.

59. Antiarrhythmic Therapy for Atrial Fibrillation
Advantages
High efficacy for some patients, at least initially (< 50% of all patients)
Low initial cost
Noninvasive
Disadvantages
High recurrence rate
High long-term cost
Noncurative
Adverse effects
Potential proarrhythmia

60. 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

61. Atrial Fibrillation: Maintenance of Sinus Rhythm

62. 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:

63. Atrial Fibrillation: Hospitalization with Initiation of Rx
Inpatient therapy
Patients with structural heart disease
Outpatient therapy
Patients without structural heart disease
Caution with sotalol

64. Recommendations for Management of Atrial Fibrillation < 48 Hours
Control ventricular rate
Consider antithrombotic therapy
Observe for spontaneous
conversion
Prompt electrical or pharmacologic conversion
Antiarrhythmic therapy if
No antiarrhythmic therapy if
Unstable hemodynamics or frequent recurrences
Stable hemodynamics, infrequent recurrences, or first episode
Adapted from Golzari H. Ann Intern Med ;125:

65. Recommendations for Management of Atrial Fibrillation > 48 Hours
Control ventricular rate
Start antithrombotic therapy (heparin and/or warfarin or aspirin)
Duration < 1 year
Duration > 1 year or
Warfarin therapy 3-4 weeks
Cardioversion or pharmacologic conversion
Antiarrhythmic therapy if
No antiarrhythmic therapy if
Stable hemodynamics, infrequent recurrences, or first episode
Unstable hemodynamics or frequent recurrences
Continue warfarin 1-2 months Monitor for recurrences
Chronic antithrombotic therapy
Assure control of ventricular rate
Adapted from Golzari H. Ann Intern Med ;125:

66. 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.

67. AV Nodal Modification by Intracardiac Ablation
RAO
LAO

68. Catheter Ablation of AV Nodal Conduction and Permanent Pacemaker Implantation
Treatment for patients with atrial fibrillation with a rapid ventricular response

69. 16 15 14
Subjective Benefits of Catheter Ablation of AV Nodal Conduction and Permanent Pacemaker Implantation 13 12 11 10 9
Minutes 8 7
Treadmill exercise performance before and after procedure.
All patients were in rate-adaptive pacing mode for follow-up. 6 5 4 3 2 1
Pre
Post
Kay GN. Am J Cardiol ;62:

70. Efficacy of Surgical Maze Procedure for Atrial Fibrillation
100
Maze 90 80 70 60
Freedom from atrial fibrillation (%) 50 40 30 20
Control 10 1 2 3
Post-op years
Kawaguchi AT. J Am Coll Cardiol. 1996;28:

71. Catheter Maze Procedure for Atrial Fibrillation
Haïssaguerre M. J Cardiovasc Electrophysiol.
1994;5:

72. 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

73. Transvenous Atrial Defibrillation
Prospective multicenter trial to define efficacy and safety of low-energy shocks for atrial defibrillation
Delivery of shocks between right atrial and coronary sinus electrode catheters
141 patients enrolled
Levy S. J Am Coll Cardiol. 1997;29:

74. Catheter Position for Intracardiac Atrial Defibrillation
Levy S. J Am Coll Cardiol. 1997;29:

75. 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.

76. Atrial Fibrillation Issues to Address
Rate Control
Anticoagulation
Conversion to sinus