Atrial Fibrillation Learning Objectives

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Atrial Fibrillation
Troy E. Rhodes, MD, PhD
Division of Cardiovascular Medicine,,
Electrophysiology
Ohio State University Medical Center
Learning Objectives
• Review the growing incidence and
importance of AF in the population
• Discuss the use of anticoagulation in
AF for stroke prevention
• Summarize pharmacologic and non
nonpharmacologic options for AF
management
1
Atrial Fibrillation
Projected Number of Adults
With AF in the US
Adults with AF, Millions
s
6
5
4
3
2
2.26
2.08
5.425.61
5.16
5
16
4.78
4.34
3.80
3.33
2.94
2.442.66
1
0
Year
Go et al. JAMA. 2001;285:2370-2375.
2
Costs to the Health Care System
Estimated US cost burden 15.7 billion
annually
• 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
Quality of Life with AF
1 Jung
et al, JACC. 1999 2 Ware et al, New England Medical Center Health Survey, 1993.
3
Diagnostic Evaluation
Minimum Evaluation
• History and physical – Sx with AF, CV
disease
• Electrocardiogram – LVH, MI, BBB, WPW
• Echocardiogram
g
– LVH,, LAE,, LVEF,, Valves
• Labs – TSH, Renal fxn
• Sleep history
AHA / ACC / ECS Guidelines 2006
Diagnostic Evaluation
Additional Testing
• ETT – CAD, Exercise induced SVT / AF
• Holter / Event Monitor – Confirm AF and
Sxs
• TEE – LA clot
• EPS – SVT triggered AF
• Sleep Study
AHA / ACC / ECS Guidelines 2006
4
Incidence of AF Based on
Presence or Absence of OSA
20 –
15 –
OSA
Cumulative
10 –
Frequency
of AF (%)
5–
No OSA
0–
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Years
Number at Risk
OSA
No OSA
844
709
569
478
397
333
273
214
173
134
110
94
70
46
29
8
2,209
1,902
1,616
1,317
1,037
848
641
502
393
296
217
195
130
94
69
28
Gami et al. JACC 2007;49:565-71
Heart Rhythm 2011; 8: 157-176.
5
Classification of Atrial Fibrillation
ACC/AHA/ESC Guidelines
Firstt
Fi
Detected
Paroxysmal
(Selfterminating)
Persistent
(Not selfterminating)
Permanent
Treatment Options
Rate control
Pharmacologic
• Ca2+ blockers
• β-blockers
• Digitalis
• Amiodarone
Nonpharmacologic
p
g
• Ablate and pace
Maintenance of SR
Pharmacologic
Class IA
Class IC
Class III
β-blocker
Prevent remodeling
Nonpharmacologic
Catheter ablation
Surgery (MAZE)
Pacing
g
Stroke prevention
Pharmacologic
• Warfarin
• Thrombin inhibitor
• Aspirin
Nonpharmacologic
• Removal / isolation
LA appendage
d
ACE-I
ARB
Adapted from Prystowsky, Am J Cardiol. 2000;85:3D-11D.
6
Atrial Fibrillation and Stroke
•
•
•
•
5 fold increased risk of CVA
y 6 CVAs
AF accounts for 1 out of every
Paroxysmal same risk as persistent
Thromboemboli originating from LAA
Stroke Risk Assessment in AF:
CHADS2 Score
CHADS2
Score
Annual Stroke
Risk %
NNT
Points
CHF
1
0
1.9
417
Hypertension
1
1
2.8
125
Age > 75yo
1
2
4.0
81
Diabetes
1
3
5.9
33
Stroke
2
4
8.5
27
5 or 6
12-18
44
Clinical Parameter
Gage et al, JAMA 2001; 285:2864.
7
Stroke Risk Assessment in AF:
CHADS2 Score
Clinical Parameter
Points
CHF
1
Hypertension
1
Age > 75yo
1
Diabetes
1
Stroke
2
CHADS2 Score
Treatment
0
ASA
1
ASA or Warfarin (INR 2-3)
2+
Warfarin (INR 2-3)
Gage et al, JAMA 2001; 285:2864.
Anticoagulation
• Overall
9 62% reduction with
warfarin
9 19% with ASA
• AFFIRM
9 80% of CVAs
occurred after
coumadin was
stopped or was
subtherapeutic
CHADS2
S
Score
Events per 100 personyears
NNT
Warfarin
No Warfarin
0
0.25
0.49
417
1
0.72
1.52
125
2
1.27
2.50
81
3
2 20
2.20
5 27
5.27
33
4
2.35
6.02
27
5 or 6
4.60
6.88
44
8
Atrial FibrillationAnticoagulation
Hylek EM and Singer DE. Ann Intern Med. 1994;120(11):897-902.
Warfarin Limitations
•
•
•
•
•
•
•
Slow onset/offset
Unpredictable dosing
Drug/diet interactions
Warfarin resistance (genetic)
Narrow therapeutic index
g
Routine monitoring
Patient dissatisfaction (“rat
poison”)
• Prescriber dissatisfaction
9
Dabigatran
• Direct thrombin inhibitor
ƒ Reversible
R
ibl binding
bi di
ƒ Free & clot-bound thrombin
• Inhibits platelet aggregation
• Inhibits tissue factor-induced
thrombin generation
• Renally cleared
• No antidote
FDA-Approved Labeling
• Who it’s for:
ƒ Non-valvular AF patients for stroke
prevention
• Who it’s NOT for:
ƒ Mechanical heart valves
ƒ PE
ƒ DVT
ƒ Prophylaxis for knee/hip replacements
ƒ HIT
10
Management of AF
ANTITHROMBOTIC RX
AND
RHYTHM
CONTROL
OR ?
RATE
CONTROL
Rate Control
11
Atrial Fibrillation
Rate control – Drug Therapy
Digoxin – controls resting rate, OK in CHF
patients.
Beta, Calcium channel blockers – controls resting
and exercise rates.
Best therapy – combination of beta blocker
and digoxin.
Primary Goal – Avoid Tachycardia Induced
Cardiomyopathy
What is optimum rate control?
• AFFIRM trial
ƒ Resting heart rate less than 80 bpm
ƒ Peak heart rate less than 110 bpm
• RACE II
12
RACE II
• 614 patients
• Lenient
L i t Control
C t l (<110 b
bpm)) versus
strict control (<80 at rest, <110 at
peak).
• Mean follow up 2 years.
• Primary Outcomes of death, CHF,
stroke embolism, life threatening
arrhythmias
The RACE II Investigators. N Engl J Med. 2010;362: 1363-1373.
Rate Control
• No significant difference in two groups
The RACE II Investigators. N Engl J Med. 2010;362:.
13
Rhythm Control
Conversion of AF
Length of time
in AF prior to
cardioversion
Duration of
AF is the best
predictor of
recurrent AF
after
cardioversion
Patien
nts in sinus rhythm (%)
100
< 3 Months
3 - 12 Months
> 12 Months
80
60
40
*
20
0
*P = <0.02
Initial
One month
post-CV
Six months
post-CV
Dittrich HC. Am J Cardiol. 1989;63:193-197.
14
Anticoagulation - Cardioversion
• Atrial stunning
ƒ Stunning can occur
even with one hour of
atrial fibrillation
ƒ If duration < 2 weeks,
function may return
within 24 hours to one
week
ƒ If duration > 2 weeks,
stunning may persist
for one month
Mattioli, AV. et al. Am J Cardiol 1998; 82:1368.
Cardioversion
• Less than 48 hours duration
ƒ Cardioversion without TEE
ƒ Heparin at time of cardioversion
ƒ Warfarin for a month and reevaluation as outpatient
15
Cardioversion
• If greater than 48 hours
ƒ Option 1: Anticoagulate for 4 weeks and
then cardiovert
ƒ Option 2: TEE and if no thrombus,
cardiovert
ƒ If thrombus, 4 weeks warfarin and
recheck
h k
ƒ Anticoagulate for minimum of one month
and re-evaluate
AFFIRM: Rate vs. Rhythm Control
All-Cause Mortality
Mortality, %
30
Rate
Rhythm
25
20
p=0.078 unadjusted
15
p=0.068 adjusted
10
5
4060 patients
ti t
0
4
5
1932
3
Time (years)
1807
1316
780
255
1925
1825
774
236
0
1
Rhythm N:
2033
Rate N:
2027
2
1328
The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833.
16
Rate vs. Rhythm Control Trials:
Implications
• AFFIRM demonstrated that a rate control
“strategy” is an acceptable primary
therapy in a selected high-risk subgroup of
AF patients
• Continuous anticoagulation seems
warranted in all patients with risk factors
f stroke
for
t k
Asymptomatic recurrences
• AFFIRM did not define whether it is better
to be in NSR.
Rhythm Control
ADVANTAGES
DISADVANTAGES
•
•
•
•
•
•
•
•
•
•
Avoids electrical and
anatomical remodeling
Improves hemodynamics
Enhanced exercise capacity
Symptom relief
I
Improves
QOL
Restores atrial transport
Reduces thromboembolic
events?
•
•
•
•
Ventricular proarrhythmia
Increased mortality?
Drug-induced
bradyarrhythmias
End-organ toxicity
Ad
Adverse
effects
ff
Recurrences are likely
Asymptomatic (silent) AF
17
Heart Rhythm 2011; 8: 157-176.
Patie
ents without recurren
nce, %
CTAF Trial*: Maintenance of SR
100
Amiodarone 10 mg/kg/2 wk, 300 mg/4 wk, 200 mg/d (n=201)
80
60
Propafenone 300-450 mg/d (n=101)
40
Sotalol 160 mg BID or 80 mg TID (n=101)
20
0
0
100
200
300
400
500
600
Days of follow-up
* Excluded recurrence in first 21 days.
Roy D, et al. N Engl J Med. 2000;342:913-920.
18
AF Antiarrhythmic
Therapy
• Treatment goals
ƒ ↓ frequency of recurrences
ƒ ↓ duration of recurrences
ƒ ↓ severity of recurrences
ƒ Not to abolish every episode
• Safety is primary concern
• Minimize risk of proarrhythmia
Drug-Induced Proarrhythmia Torsades
19
Factors Which Influence
Ventricular Proarrhythmia Risk
•
•
•
•
•
•
•
Hypokalemia, hypomagnesemia
Long QT at baseline
CHF / Decreased EF
Ventricular hypertrophy
Bradycardia
F
Female
l gender
d
Reduced drug metabolism or
clearance
• Amiodarone has lowest risk
Alternatives to Drug Therapy
“Non-Pharmacologic Therapy”
‰C
‰Coumadin
di – LAA closure
l
(W
(Watchman)
t h
)
‰Rate Control – AVN RFA + PCMK
‰AAR – Adjunctive
‰AARx
Adj
ti AFL RFA
‰AARX – Curative Afib RFA
20
The Rational for the
Watchman Device
Clean Left Atrial Appendage
Left Atrial Appendage Clot
Manning WJ. N Engl J Med. 1993;328:750-755.
Watchman®
•Efficacy of Watchman was
non-inferior to warfarin for
stroke p
prophylaxis
p y
in
patients with non-valvular
atrial fibrillation
•Higher rate of adverse
events in the intervention
group
g
p was mainly
y result of
periprocedural
complications
NEJM
•Awaiting FDA approval
Holmes et al. Lancet 2009; 374: 534-42.
21
Pacemaker + AV Node Ablation
http://www.nlm.nih.gov/medlineplus/ency/images/ency/fullsize/19566.jpg
http://www.heartrhythmcenter.com/myweb2/av_nodal_ablation2.htm
AVN RF Ablation
22
Objective Benefits of AV Nodal Ablation
70
55
mean
34 + 5
45
50
LVESD (mm)
LVEF (%)
50
mean
54 + 7
60
mean
43 + 8
40
p < 0.001
30
20
40
35
mean
40 + 5
30
p < 0.003
25
20
Before
Before
After
A Left ventricular ejection
fraction (%)
After
B Left ventricular end systolic
diameter (mm)
Rodriguez LM. Am J Cardiol. 1993;72:1137-1141.
AVN Ablation
Advantages:
100% efficacy
85% symptomatic improvement
Improved EF (LV remodeling)
Eliminates need for rate control drugs
Disadvantages:
Pacemaker dependant
Good Candidates:
Tachy / Brady Syndrome
PPM present – CHF with BiV device
Medication refractory / intolerant
Elderly
23
IC Antiarrhythmic Induced Atrial Flutter
1:1 Conduction
Atrial Flutter Circuit
24
Atrial Flutter Ablation
Approximately 15% of AF patients treated with an
AARx will develop AFL
Advantages:
95% efficacy
≈ 80% arrhythmia control if AARx continued
As primary Tx RFA more effective than AARx
sad a tages Invasive
as e
Disadvantages:
Good Candidates:
Typical AFL (IVC / TV isthmus)
Primary or AARx related Atrial Flutter
Focal Origin of Atrial Fibrillation
Hassaiguerre M, NEJM, 1998
• 94% of AF
triggers from
Pulmonary Veins
RA
LA
SVC
FO
• “90-95% of all AF
is initiated by PV
ectopy”
Pulmonary
Veins
6
IVC
11
CS
25
Atrial Fibrillation Ablation
Atrial Shell
Cardiac MRI
Comparison of Antiarrhythmic Drug Therapy and
Radiofrequency Catheter Ablation in Patients with
Paroxysmal Atrial Fibrillation: A Randomized Controlled
Trial
66%
vs.
16%
Major Adverse Events: Ablation 4.9% vs. AARx 8.8%
Repeat Ablation in 12.6% of patients
JAMA 2010
26
Current State of Curative
Catheter-Based RFA
Who is a good candidate?
Symptomatic / Frequent AF
Limited Heart Dz
EF > 35%
LA < 5.5cm
No MS / Rheumatic Dz
Younger Patients
No LA thrombus or Hx of CVA
Medically Refractory / Intolerant
(Ablation now second line therapy)
New Technology
Multielectrode
Ablation Catheters
LSPV
LIPV
Catheter Positioning in
Antrum of Left PVs
27
Balloon Technology
RSPV
LSPV
Stereotaxis
Remote Magnetic Control
28
Atrial Fibrillation
New Technology / Studies at
Ohio State University
Stereotaxis – Magnetic Catheter Navigation
New Catheter Design / Energy Sources
High Intensity Focused Ultrasound (HIFU)
Ablation Frontiers – Circular Catheters
Cryoablation
Laser Ablation
Cabana trial – Drug vs Ablation (including primary
therapy)
Watchman – Left Atrial Appendage Closure
Surgical vs Catheter Ablation
29

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