Transcript No Slide Title

Challenges and Controversies
in Atrial Fibrillation
Marc J. Girsky, M.D
Director Electrophysiology Services
Harbor-UCLA Medical Center
Presenter Disclosure Information
Marc Girsky MD
 St. Jude Medical Corporation – Research projects
Atrial Fibrillation
One Patient’s Odyssey
76 y/o male with Htn, Paroxysmal Afib
 2/2006 – 1st visit
 2005 - 2 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

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

Underlying Pathogenesis of Atrial
Fibrillation
Paroxysmal
Persistent
Permanent
Relative
importance
100
80
60
Substrate
Initiation
substrate
40
20
Trigger
0
AF/disease progression
CP1206742-3
ACC/AHA/ESC
Guidelines for the
Management of
Patients With Atrial
Fibrillation

ACC/AHA/ESC guidelines prepared over two years:
12 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
Atrial Fibrillation Management
Updates 2006 - Present
2011 ACCF/AHA/HRS Focused Update
 2010 ESC Atrial Fibrillation Guidelines
 2010 CCS Atrial Fibrillation Guidelines

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

Anticoagulation Recommendations
AF May Affect Stroke Severity

1061 patients admitted with acute
ischemic stroke


Bedridden state



20.2% had AF
With AF
Without AF
41.2%
23.7%
P<.0005
Odds ratio for bedridden state following stroke
due to AF 2.23 (95% CI, 1.87-2.59; P<.0005)
Dulli et al. Neuroepidemiology. 2003;22:118-123.
Major Anticoagulation Trials in Atrial
Fibrillation

SPAF1

BAATAF2 Boston Area Anticoagulation Trial for
Atrial Fibrillation

CAFA3

AFASAK4 Copenhagen Investigators

SPINAF5
1 Circulation.
Stroke Prevention in Atrial Fibrillation
Canadian Atrial Fibrillation Anticoagulation
Stroke Prevention in Nonrheumatic
Atrial Fibrillation
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.
CHADS2 Score
Risk Factor
Score
CHF
1
Hypertension
1
Age > 75 years
1
Diabetes
1
Stroke/TIA
2
CHADS2 Score and CVA Risk
Gage, B. F. et al. JAMA 2001;285:2864-2870
Anticoagulation Recommendations for
Atrial Fibrillation - 2006
Risk Category
Recommended Therapy
No risk factors
CHADS2 = 0
One Moderate Risk Factor
CHADS2 = 1
CHADS2 > 2 or mitral
stenosis
Prosthetic valve
Aspirin, 81-325 mg/d
Aspirin, 81 mg-325 mg/d or
Warfarin – target INR 2.5
Warfarin – target INR 2.5
Warfarin – target INR 3.0
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
CHADS2 VASc Score
Risk Factor
CHF
Hypertension
Age > 75
Diabetes
Stroke/TIA
Vascular disease (MI,PVD)
Age 65-74
Sex Category Female
Score
1
1
1
1
2
1
1
1
CHADS2 VASc Stroke Rate
ESC Guidelines 2010
ESC Guidelines – Anticoagulant Tx
Lip G Y H et al. Chest 2011;139:738-741
Predicting Bleeding Risk
HAS-BLED Score
Hypertension (>160 mmHg systolic
Abnormal Renal/Hepatic function
Stroke
Bleeding history or anemia
Labile INR (TTR < 60%)
Elderly (age > 75 years)
Drugs/ETOH (antiplatelet/NSAIDs)
High Risk (>4%/year)
Moderate Risk (2-4%/year)
Low Risk (<2%/year)
1
1-2
1
1
1
1
1-2
>4
2-3
0-1
Pisters, R et al. Chest 2010
New Oral Anticoagulants
Agent
Dabigatran Rivaroxaban Apixaban Edoxaban
Route
Oral
Oral
Oral
Oral
Target
Thrombin
FXa
FXa
FXa
Dosing
BID
QD
BID
QD
Labs
No
No
No
No
T1/2
12-17
9-12
8-15
8-11
Renal/Hep
Ren/Hep
Renal
Eliminate Renal 80%
Cumulative Mortality From Any Cause in the
Rhythm-Control Group and the Rate-Control Group
No. of Deaths
Rhythm control
Rate control
0
0
80 (4)
78 (4)
AFFIRM Investigators NEJM 2002: 347;23
number (%)
175 (9)
148 (7)
257 (13)
210(11)
314 (18)
275 (16)
352 (24)
306 (21)
•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
Afib and CHF Investigators
Primary Endpoint Results
NEJM June 2008
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

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
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
Symptomatic Atrial Fibrillation!!
Focused Guidelines
Maintaining Sinus Rhythm
Wann, L. S. et al. J Am Coll Cardiol 2011;57:223-242
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
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)
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
EBCT – Pulmonary Vein/
LA Reconstruction
LSPV
LIPV
RIPV
Courtesy: Harbor - UCLA EBCT Center
Pulmonary Vein Circumferential
Ablation
RSPV
Spiral
cath
True Pulmonary Vein Isolation
•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;359:1778-85
PABA-CHF Investigators
Composite Results
NEJM 2008;359:1778-85
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
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