1. Challenges and Controversies in Atrial Fibrillation
Marc J. Girsky, M.D
Director Electrophysiology Services
Harbor-UCLA Medical Center

2. Presenter Disclosure Information
Marc Girsky MD
St. Jude Medical Corporation – Research projects

3. Atrial Fibrillation One Patient’s Odyssey
76 y/o male with Htn, Paroxysmal Afib
2/2006 – 1st visit
Cardioversions, Amiodarone – Recurrent Afib, Increased LFT’s
3/2006 – 1st Cath ablation – Flecainide 50 BID, increased to 100 mg BID
1/2007 – Syncope, Amaurosis fugax, start Dofetilide, resume warfarin

4. One Patient’s Odyssey 3/2007 – 2nd RFA, continue Dofetilide
12/2007 – Recurrent Afib Q8 days
7/2008 – 3rd RFA, continue Dofetilide
9/2008 – Hematuria, INR – 6
10/2009 – D/C Dofetilide, start Dronedarone
11/2009 – Cerebellar infarct, resume warfarin
12/2010 – D/C Warfarin, initiate Pradaxa
3/2011 – Recurrent AFib

5. Underlying Pathogenesis of Atrial Fibrillation AF/disease progression
Paroxysmal
Persistent
Permanent
Substrate
Initiation
substrate
Relative importance
Trigger
AF/disease progression CP

6. ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation
ACC/AHA/ESC guidelines prepared over two years: committee members, 4 European, 4 North American electrophysiologists. Updated 2006
Exhaustive review process based on published literature: evidence-based recommendations and derived from published data.
Strong emphasis on randomized trials: little tolerance for “experience” or anecdotal data

7. Atrial Fibrillation Management Updates 2006 - Present
2011 ACCF/AHA/HRS Focused Update
2010 ESC Atrial Fibrillation Guidelines
2010 CCS Atrial Fibrillation Guidelines

8. AFib Management Guidelines New Concepts – 2006 - Present
Implications of Rate vs Rhythm control studies for clinical practice
Optimal anticoagulant therapy
Recommendations for catheter based therapies
Introduce the role of angiotensin inhibition in reducing the occurrence and complications of afib
Primary prevention of atrial fibrillation

9. Anticoagulation Recommendations

10. AF May Affect Stroke Severity
1061 patients admitted with acute ischemic stroke
20.2% had AF
Bedridden state
With AF 41.2%
Without AF 23.7%
Odds ratio for bedridden state following stroke due to AF 2.23 (95% CI, ; P<.0005)
In order to assess if the severity of AF-associated acute ischemic stroke is worse than ischemic stroke associated with other etiologies, Dulli et al examined an acute ischemic stroke patient population for the clinical characteristics of acute ischemic stroke in patients with and without underlying AF in a retrospective study.
AF was present in 20.2% of the patient population (acute ischemic stroke patients admitted between 1990 and 2001). Many of the factors associated with ischemic stroke varied between patients with AF and without AF. Hypertension, ischemic heart disease (IHD), and other cardioembolic risks were significantly higher in patients with AF. The study also showed that the frequency of the bedridden state was markedly higher in patients with AF (41.2%) versus patients without AF (23.7%); P< The odds ratio for the bedridden state following stroke with AF was 2.23 (95% confidence interval [CI], ; P<.0005). The significance of AF in the severity of stroke compared with other variables demonstrated that AF was a strong independent predictor of severe ischemic stroke. The study also showed that the disability caused by acute ischemic stroke increases with age, and is significantly worse when associated with AF in groups aged 65 to 74 (P<.05) and 75 to 84 years (P<.0005).
The study investigators concluded that acute ischemic stroke in the presence of underlying AF is often more severe than ischemic stroke due to other etiologies.
P<.0005
Dulli DA, Stanko H, Levine RL. AF is associated with severe acute ischemic stroke. Neuroepidemiology. 2003;22:
Dulli et al. Neuroepidemiology. 2003;22:

11. Major Anticoagulation 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
4 The Lancet. 1989;1:
5 N Eng J Med. 1992;327:
1 Circulation. 1991;84:
2 N Engl J Med. 1990;323:
3 J Am Coll Cardiol. 1991;18:

12. CHADS2 Score Risk Factor Score CHF 1 Hypertension Age > 75 years
Diabetes
Stroke/TIA 2

13. CHADS2 Score and CVA Risk
Table 2. Risk of Stroke in National Registry of Atrial Fibrillation (NRAF) Participants, Stratified by CHADS2 Score*
Gage, B. F. et al. JAMA 2001;285:

14. Anticoagulation Recommendations for Atrial Fibrillation - 2006
Risk Category
Recommended Therapy
No risk factors
CHADS2 = 0
Aspirin, mg/d
One Moderate Risk Factor
CHADS2 = 1
Aspirin, 81 mg-325 mg/d or Warfarin – target INR 2.5
CHADS2 > 2 or mitral stenosis
Warfarin – target INR 2.5
Prosthetic valve
Warfarin – target INR 3.0

15. Afib Guidelines OAC Contraindicated Pt
In patients in whom OAC therapy is contraindicated, combination of Plavix and Aspirin is recommended to reduce risk of thromboembolic complications
IIb indication
ACC/AHA/HRS Guidelines 2011

16. Vascular disease (MI,PVD)
CHADS2 VASc Score
Risk Factor
Score
CHF 1
Hypertension
Age > 75
Diabetes
Stroke/TIA 2
Vascular disease (MI,PVD)
Age 65-74
Sex Category Female

17. CHADS2 VASc Stroke Rate
ESC Guidelines 2010

18. ESC Guidelines – Anticoagulant Tx
Algorithm summarizing the approach to thromboprophylaxis in the 2010 European Society of Cardiology guidelines for management of patients with AF. CHADS2 = congestive heart failure, hypertension, age, diabetes, prior stroke or transient ischemic attack; OAC = oral anticoagulation; TIA = transient ischemic attack. (Republished with permission from the European Heart Journal1).
Lip G Y H et al. Chest 2011;139:

19. Predicting Bleeding Risk HAS-BLED Score
Hypertension (>160 mmHg systolic 1
Abnormal Renal/Hepatic function
1-2
Stroke
Bleeding history or anemia
Labile INR (TTR < 60%)
Elderly (age > 75 years)
Drugs/ETOH (antiplatelet/NSAIDs)
High Risk (>4%/year)
>4
Moderate Risk (2-4%/year)
2-3
Low Risk (<2%/year)
0-1
Pisters, R et al. Chest 2010

20. New Oral Anticoagulants
Agent
Dabigatran
Rivaroxaban
Apixaban
Edoxaban
Route
Oral
Target
Thrombin
FXa
Dosing
BID QD
Labs No
T1/2
12-17
9-12
8-15
8-11
Eliminate
Renal 80%
Renal/Hep
Ren/Hep
Renal

21. AFFIRM Investigators NEJM 2002: 347;23
Cumulative Mortality From Any Cause in the Rhythm-Control Group and the Rate-Control Group
No. of Deaths number (%)
Rhythm control 0 80 (4) 175 (9) 257 (13) 314 (18) 352 (24)
Rate control 0 78 (4) 148 (7) 210(11) 275 (16) 306 (21)
AFFIRM Investigators NEJM 2002: 347;23

22. Study design: Randomized trial comparing rate vs rhythm control
in patients with Afib and EF<35%
1376 patients from 123 centers
Primary endpoint – Death from cardiovascular causes

23. Afib and CHF Investigators Primary Endpoint Results
NEJM June 2008

24. Optimal Rate Control Therapy Afib Guidelines Focused Update
Treatment to achieve strict heart rate control (<80 bpm resting, <110 bpm during exercise) is not beneficial compared to achieving a resting heart rate < 110 bpm.
New recommendation

25. Rhythm Control vs Heart Rate Control
“Reasons for restoration and maintenance of sinus rhythm in patients with AF include relief of symptoms, prevention of embolism, and avoidance of cardiomyopathy.”
ACC/AHA/ESC AF Guidelines, 2001

26. Rhythm Control vs Heart Rate Control
“An effective method for maintaining sinus rhythm with fewer side effects would address a presently unmet need”
ACC/AHA/ESC AF Guidelines, 2006

27. Symptomatic Atrial Fibrillation!!

28. Focused Guidelines Maintaining Sinus Rhythm
Wann, L. S. et al. J Am Coll Cardiol 2011;57:

29. Expectations of Antiarrhythmic Drug Therapy in Treatment of AF
Complete suppression
Best, but AF recurrence likely (>50% of patients)
Recurrence, per se, is not failure of therapy
Frequency of recurrence
More realistic measure of efficacy
May vary from patient to patient

30. ACE/ARB Antiarrhythmic Properties
Healey, et al JACC 2005
Meta-analysis of randomized trials involving ACE/ARB
therapy
Included trials if atrial fibrillation events were followed as
endpoints
11 Trials/56,308 patients – 4 CHF, 3 Htn, 2 post CV, 2 post MI
Overall risk reduction of AF occurrence 28% (greatest benefit
seen in CHF patients, limited benefit in hypertensive patients)

31. Curative Ablation for Atrial Fibrillation
Appropriate for Patients
With symptomatic paroxysmal or persistent atrial fibrillation
Who are intolerant of drug therapy
Who have frequent ambient atrial ectopic activity
Who have tachycardia mediated tachycardia

32. Courtesy: Harbor - UCLA EBCT Center
EBCT – Pulmonary Vein/
LA Reconstruction
LSPV
RIPV
LIPV
Courtesy: Harbor - UCLA EBCT Center

33. Pulmonary Vein Circumferential
Ablation
RSPV
Spiral
cath

34. True Pulmonary Vein Isolation

36. Randomized trial comparing pulmonary vein isolation (41 patients)
to AV node ablation and biventricular pacing (40 patients)
Drug refractory atrial fibrillation and EF <40%
Composite endpoint included QOL questionnaire, 2D-echo follow
up and 6 minute walk distance
NEJM 2008;359:

37. PABA-CHF Investigators Composite Results
NEJM 2008;359:

38. PABA-CHF Investigators Conclusions
In patients with EF<40% and symptomatic atrial
fibrillation, pulmonary vein isolation was superior
to AV node ablation
In such a population, pulmonary vein isolation should
be considered at experienced centers

39. A Rational Approach to the Afib Patient
What is the pathophysiology of the patient’s Afib?
What are the patients symptoms?
Will the patient benefit from cardioversion? SR
maintenance?
Has anticoagulation been considered and implemented?
Has the patient failed drug therapy?
Invasive strategy considered for pharmacologic failures