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Rhythm Management
Defining Atrial Fibrillation
• A supraventricular tachycardia characterized by uncoordinated atrial
activation with consequent deterioration of atrial mechanical function
• Characterized by replacement of consistent P waves with rapid
oscillation of fibrillatory waves, varying in amplitude, shape, and
timing
• Associated with an irregular and frequently rapid ventricular response
(with intact AV conduction)
• For management purposes, atrial flutter should be treated as AF
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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Management of Patient With AF
Initial Presentation
With AF
Hemodynamically
Stable
Hemodynamically
Unstable
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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Classification of AF
ACC/AHA/ESC Guidelines
First
Detected
Paroxysmal
(Self-terminating)
Persistent
(Not self-terminating)
Permanent
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Pharmacologic Management of Patients With Newly Discovered AF
ACC/AHA/ESC Guidelines
Newly Discovered AF
Paroxysmal
No therapy needed,
unless severe
symptoms
(eg, hypotension, HF,
angina pectoris)
Anticoagulation,
as needed
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
Persistent
Accept permanent AF
Rate control and
anticoagulation,
as needed
Anticoagulation
and rate control,
as needed
Consider antiarrhythmic
drug therapy
Cardioversion
Long-term drug
prevention unnecessary
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Management of Stable Patients With AF
• Control heart rate
• Determine duration of AF
• Anticoagulation as appropriate
• Assess for comorbidities and contributing/reversible factors
• Decide rate or rhythm strategy
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Pharmacologic Management of Patients With Newly Discovered AF
Recurrent Paroxysmal AF
Newly Discovered AF
Paroxysmal
No therapy needed,
unless severe
symptoms
(eg, hypotension, HF,
angina pectoris)
Anticoagulation,
as needed
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
Persistent
Accept permanent AF
Rate control and
anticoagulation,
as needed
Anticoagulation
and rate control,
as needed
Consider antiarrhythmic
drug therapy
Cardioversion
Long-term drug
prevention unnecessary
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Anatomic and Electrophysiologic Substrates Promoting AF Initiation
and Maintenance
Substrates
Diseases
Anatomic
Cellular
Electrophysiologic
Substrate pathways during sinus rhythm (remodeling related to stretch and
dilatation). Main pathways involve the RAAS, TGF-Beta, and CTGF
Htn
Atrial dilatation
Myolysis
Conduction
Abnormalities
HF
PV dilatation
Apoptosis,
necrosis
ERP dispersion
CAD
Fibrosis
Channel
expression
change
Ectopic activity
Valvular disease
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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Anatomic and Electrophysiologic Substrates Promoting AF Initiation
and Maintenance
Substrates
Diseases
Anatomic
Cellular
Electrophysiologic
Substrate develops due to tachycardia (tachycardia-related modeling, downregulation of
calcium channel, and calcium handling).
Focal AF
None or
None or
Ectopic activity
A Flutter
Atrial dilatation
Ca++ channel
downregulation
Microreentry
PV dilatation
Myolysis
Short ERP
Large PV sleeves
Connexin downregulation
ERP dispersion
Decrease Contractility
Adrenergic
supersensitivity
Slowed conduction
Fibrosis
Changed sympathetic
innervation
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Etiologies and Factors Predisposing Patients to AF
Endocrine disorders
Electrophysiologic abnormalities

Hyperthyroidism
 Enhanced automaticity (focal AF)

Pheochromocytoma
 Conduction abnormality (reentry)
Changes in autonomic tone
Atrial pressure elevation

Increased parasympathetic activity
 Mitral or tricuspid valve disease

Increased sympathetic activity
 Myocardial disease (1o or 2o, with
systolic or diastolic dysfunction)
Primary or metastatic disease
Postoperative

 Aortic valve disease with LVH
 Systemic or pulmonary hypertension
 Intracardiac tumors or thrombi
Cardiac, pulmonary, or esophageal
Atrial ischemia (CAD)
Congenital heart disease
Neurogenic

Subarachnoid hemorrhage

Nonhemorrhagic, major stroke
Idiopathic (lone AF)
Familial AF
Inflammatory/infiltrative atrial disease
 Pericarditis, amyloidosis, myocarditis
 Age-induced atrial fibrotic changes
Drugs
 Alcohol
 Caffeine
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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Mechanisms of AF
Focal Activation
Multiple Wavelets
SVC
SVC
LA
RA
LA
RA
PVs
PVs
IVC
IVC
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Anatomy of Pulmonary Veins
SVC
Extension of
muscular fibers
into pulmonary
vein (PV)
Ganglia noted
in yellow
LSPV
LIPV
Common
locations of PV
(purple) and
common sites
of origin of
non-PV
triggers (black)
LSPV
LIPV
RSPV
RIPV
SVC
LSPV
LIPV
RIPV
IVC
IVC
SVC
SVC
RSPV
RIPV
LSPV
LIPV
IVC
Calkins et al. Heart Rhythm. 2007;4:1-46.
www.HRSonline.org
RSPV
Large and small
reentrant
wavelets that
play a role in
initiating and
sustaining AF
RSPV
Composite of
anatomic and
arrhythmic
mechanisms
of AF
RIPV
IVC
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Mechanisms of AF: Triggers for Induction of AF
Triggers that induce AF include
Sympathetic or parasympathetic stimulation
Bradycardias or atrial tachycardias or atrial premature contractions
Acute atrial stretch
Ectopic foci
• Pulmonary vein, RA, SVC, coronary sinus, other areas
Reentrant wavelets if wavelengths are short
• Depressed conduction velocity
• Unstable reentrant circuit of short cycling
• Stable reentrant circuit of short cycling
Allessie et al. Circulation. 2001;103:769-777.
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Mechanisms of AF: Perpetuation
Substrate that sustains AF
Persistence of triggers
Persistence of atrial dilation
Persistence of shortened AERP
Increased dispersion in AERP
Inhomogeneous dispersion of conduction abnormalities
Disorganization and fragmentation of gap junctions
Allessie et al. Circulation. 2001;103:769-777.
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Perpetuation of AF: Electrophysiologic Mechanisms
Burst
pacing
AF
Sinus rhythm
Duration of
fibrillation
5 seconds
Control
AF
After
24 hours
20 seconds
Sustained AF
After
2 weeks
>24 hours
Wijffels et al. Circulation. 1995;92:1954-1968.
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Pharmacologic Management of Patients With Newly Discovered AF
Rate Control vs Rhythm control
Newly Discovered AF
Paroxysmal
No therapy needed,
unless severe
symptoms
(eg, hypotension, HF,
angina pectoris)
Anticoagulation,
as needed
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
Persistent
Accept permanent AF
Rate control and
anticoagulation,
as needed
Anticoagulation
and rate control,
as needed
Consider antiarrhythmic
drug therapy
Cardioversion
Long-term drug
prevention unnecessary
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Rate and Rhythm Control Definitions
•Rate control
• Ventricular rate is controlled both at rest and with exertion
• No commitment to maintaining SR
•Rhythm control
• Attempts restoration and maintenance of SR
• Rate control required as needed
•Can switch from rhythm control to rate control, but harder to
switch from rate control to rhythm control if AF has been
persistent for a long period of time
•DO NOT FORGET ANTICOAGULATION AS NEEDED for
either strategy
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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What Is Adequate Rate Control?
• Adequate rate control is critical to avoid tachycardia-mediated
cardiomyopathy
• 60-80 beats per minute at rest AND
• 90-115 beats per minute with exertion
• Criteria vary with age
• May be evaluated using 24-hour Holter recording
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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Achieving Rate Control Class/Recommendations
Acutely
IV administration of -blockers (esmolol, metropolol, or propranolol) or
nondihydropyridine calcium channel blocker (verapamil, diltiazem)
IV administration of digoxin or amiodarone in patients with HF (only in the
absence of an accessory pathway)
Long-term
Measurement of heart rate at rest and with exertion
Beta blockers or nondihydropyridine calcium channel blocker
Digoxin only in patients with HF, LV dysfunction, or sedentary individuals
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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Agents for Heart Rate Control Acute Setting
Drug
Loading Dose
Onset
Maintenance Dose
Major Side Effects
Heart rate control in patients without accessory pathway
500 mcg/kg IV
over 1 min
5 min
60 to 200 mcg/kg/m
IV
↓ BP, HB, ↓ HR,
asthma, HF
Metoprolol
2.5 to 5 mg IV bolus
over 2 min; up to 3
doses
5 min
NA
↓ BP, HB, ↓ HR,
asthma, HF
Propranolol
0.15 mg/kg IV
5 min
NA
↓ BP, HB, ↓ HR,
asthma, HF
Diltiazem
0.25 mg/kg IV
over 2 min
2 to
7 min
5 to 15 mg/h IV
↓ BP, HB, HF
Verapamil
0.75 to 0.15 mg/kg IV
over 2 min
3 to
5 min
NA
↓ BP, HB, HF
Esmolol
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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www.HRSonline.org
Agents for Heart Rate Control: Acute Setting
Drug
Loading Dose
Onset
Maintenance
Dose
Major Side Effects
Heart rate control in patients with accessory pathway
Amiodarone
150 mg over 10
min
Days
0.5 to
1 mg/min IV
↓ BP, HB, pulmonary toxicity, skin
discoloration, hypo- and
hyperthyroidism, corneal deposits,
optic neuropathy, warfarin
interaction, sinus bradycardia
Heart rate control in patients with HF and without accessory pathway
Digoxin
0.25 mg IV each
2 h, up to 1.5 mg
60 min
0.125 to
0.375 mg daily IV
or PO
Digitalis toxicity,
HB, ↓ HR
Amiodarone
150 mg over 10
min
Days
0.5 to
1 mg/min IV
As above
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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Agents for Heart Rate Control: Nonacute and Chronic
Maintenance
Drug
Onset
Loading and Maintenance
Dose
Major Side Effects
Heart rate control
Metoprolol
4 to 6 h
25 to 100 mg bid, PO
↓ BP, HB, ↓ HR,
asthma, HF
Propranolol
60 to 90 min
80 to 240 mg daily in
divided doses, PO
↓ BP, HB, ↓ HR,
asthma, HF
Diltiazem
2 to 4 h
120 to 360 mg daily in divided
doses; slow release available, orally
↓ BP, HB, HF,
digoxin interaction
Verapamil
1 to 2 h
120 to 360 mg daily in divided
doses; slow release available, PO
↓ BP, HB, HF,
digoxin interaction
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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www.HRSonline.org
Agents for Heart Rate Control: Nonacute and Chronic
Maintenance
Drug
Loading Dose
Onset
Maintenance
Dose
Major Side Effects
Heart rate control in patients with HF and without accessory pathway
0.5 mg
PO daily
2
days
0.125 to
0.375 mg qd, PO
Digitalis toxicity, HB, ↓ HR
800 mg qd for
1 wk, PO
600 mg qd for
1 wk, PO
400 mg qd for 4 to
6 wk, PO
1 to 3
wk
200 mg qd, PO
↓ BP, HB, pulmonary toxicity, skin
discoloration, hypo- and
hyperthyroidism, corneal deposits,
optic neuropathy, warfarin
interaction, sinus bradycardia
Digoxin
Amiodarone
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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www.HRSonline.org
Pharmacologic Management of Patients With Newly Discovered AF
ACC/AHA/ESC Guidelines
Newly Discovered AF
Paroxysmal
No therapy needed,
unless severe
symptoms
(eg, hypotension, HF,
angina pectoris)
Anticoagulation,
as needed
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
Persistent
Accept permanent AF
Rate control and
anticoagulation,
as needed
Anticoagulation
and rate control,
as needed
Consider antiarrhythmic
drug therapy
Cardioversion
Long-term drug
prevention unnecessary
24
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Clinical Considerations for Management Strategy
• Duration and patterns of AF
• Type and severity of symptoms
• Associated cardiovascular disease
• Potential for changes in cardiac function over time
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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Rhythm vs Rate Control in AF Evidence Base
5 prospective, controlled, randomized trials comparing 2
different treatment strategies
AFFIRM
Atrial Fibrillation Follow-up Investigation of Rhythm
Management
RACE
RAte Control versus Electrical Cardioversion for Persistent
Atrial Fibrillation
PIAF
Pharmacological Intervention in Atrial Fibrillation (pilot)
STAF
STrategies in Atrial Fibrillation (pilot)
HOT CAFÉ
HOw to Treat Chronic Atrial Fibrillation
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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Rhythm vs Rate Control in AF Evidence Base
Follow-up (y)
Age, y
(mean  SD)
AFFIRM (2002)
3.5
70  9
35% vs 63%
(at 5 y)
RACE (2002)
2.3
68  9
10% vs 39%
(at 2.3 y)
PIAF (2000)
1.0
61  10
10% vs 56%
(at 1 y)
STAF (2003)
1.6
66  8
11% vs 26%
(at 2 y)
HOT CAFÉ (2004)
1.7
61  11
NR vs 64%
Trial
aComparison
Patients in SRa
between rate and rhythm control group.
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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Rhythm vs Rate Control in AF Evidence Base (cont'd)
Rate
20
18
16
14
12
10
8
6
4
2
0
Rhythm
Death
AF
É
AF
H
O
T
C
ST
AF
PI
E
R
AC
FI
R
M
C
T
H
O
AF
AF
É
AF
ST
AF
PI
E
R
AC
AF
FI
R
M
Percent
Stroke
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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Patient Characteristics in AFFIRM
• Long-term treatment of chronic and paroxysmal AF
• Patients 65 years of age or other risk factor
for stroke with
•
•
•
•
•
•
AF 6 hours in past 6 months
Not continuous AF for 6 months
1 episode documented by ECG in past 12 weeks
1 risk factor for stroke (age 65 years)
AF likely to be recurrent
Able to participate in trials of ≥2 drugs in both strategies
• Randomized to rate vs rhythm control
• Patients required to be able to tolerate AF; therefore, patients were a
relatively asymptomatic group
• Both groups anticoagulated
The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833; Waldo. Am J Cardiol. 1999;84:698-700.
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Patient Characteristics in RACE
• Inclusion criteria
• Recurrent, persistent atrial fibrillation or flutter
• No contraindication to anticoagulation
• Undergone 1-2 cardioversions within 2 years prior to enrollment
• Exclusion criteria
• Duration of arrhythmia >1 year
• NYHA functional class IV CHF
• Current or previous treatment with amiodarone or pacemaker
Van Gelder et al. N Engl J Med. 2002;347:1834-1840.
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Primary End Point All-Cause Mortality in AFFIRM
Cumulative Mortality (%)
30
Rhythm N:
Rate N:
Rhythm Control
25
Rate Control
20
15
10
P=.058
5
0
0
1
2033
2027
1932
1925
2
3
Time (years)
1807
1316
1825
1328
4
5
780
774
255
236
Wyse. Presented at: American College of Cardiology 51st Annual Meeting; March 17-20, 2002; Atlanta, GA.
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Cumulative Cardiac Mortality in AFFIRM
30
Rhythm Control
25
Death (%)
Rate Control
20
15
Log-rank statistic=0
P=.9517
10
5
0
0
1
2
3
4
5
Time (years)
N, Events (%)
Rate
Rhythm
2027, 0 (100)
2033, 0 (100)
1926, 42 (2)
1932, 37 (2)
1827, 69 (3)
1807, 70 (4)
1329, 92 (5)
1316, 94 (5)
774, 115 (7)
780, 116 (7)
236, 130 (10) 1, 130 (10)
255, 129 (9)
1, 129 (9)
Steinberg et al. Circulation. 2004;109:1973-1980.
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Cumulative Noncardiovascular Mortality in AFFIRM
30
Rhythm Control
25
Death (%)
Rate Control
20
15
Log-rank statistic=11.2
P=.0008
10
5
0
0
1
2
3
4
5
Time (years)
Steinberg et al. Circulation. 2004;109:1973-1980.
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AFFIRM Results Post-hoc Analysis
Covariate
HR 99% CI
P Value
Time dependent
Sinus rhythm
<.0001
Warfarin use
<.0001
Digoxin use
.0007
.0005
AAD use
0
0.5
1
1.5
2
2.5
The benefits of sinus rhythm are
offset by the toxicity of AADs used in AFFIRM
Corley et al. Circulation. 2004;109:1509-1513.
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Score (mean) on SF-36 Scales
Quality of Life in AF RACE Study
Control subjects (n=172)
100
81
80
62
60
67
63 64
73
RACE subjects (n=352)
74 77
77
84
81
71
59
54
65
47
40
20
0
Hagens et al. J Am Coll Cardiol. 2004;43:241-247.
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A4 Study Results: Quality of Life
P=.0012
Physical function
AAD Group
(n=59)
Ablation Group
(n=53)
P=.0024
Social function
Mental health
P=.0018
Physical component
P=.0174
Mental component
P=.0106
0
20
40
60
80
100
Jaïs et al. Presented at: Heart Rhythm Society 2006 Annual Scientific Sessions; May 17-20, 2006; Boston, MA.
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Symptoms in AF
AF (n=152)
Healthy (n=47)
PTCA (n=69)
25
Quality of Life Score
b
b
20
a
15
a
10
5
0
Frequency
Severity
aP<.001
compared with AF patients; bP<.01 compared with AF patients.
Dorian et al. J Am Coll Cardiol. 2000;36:1303-1309.
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Increase in Duration (seconds)
Exercise Duration: AF vs SR
SAFE-T Trial
Sinus Rhythm
100
Atrial Fibrillation
80
P=.01
P=.02
60
40
20
0
8 Weeks
1 Year
Singh et al. J Am Coll Cardiol. 2006;48:721-730.
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Rate vs Rhythm Control
ACC/AHA/ESC
“Before choosing rate control as a long-term strategy, the clinician should
consider how permanent AF is likely to affect the patient in the future.
RACE…and AFFIRM…do not necessarily apply to younger patients
without heart disease or to patients whose dependency upon sinus
rhythm is likely to change appreciably over time. This makes it important
to ensure that a window of opportunity to maintain sinus rhythm is not
overlooked early in the course of management
of a patient with atrial fibrillation.”
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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www.HRSonline.org
AF in Patients With HF
HF may develop or deteriorate with AF
Progression of underlying cardiac disease
Uncontrolled heart rate
Antiarrhythmic drug toxicity
AF may exacerbate HF symptoms due to
Loss of atrial “kick”
Rapid heart rate
Patients in AFFIRM did not develop or deteriorate differently in rate vs
rhythm arms
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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Impact of Rhythm Control on HF
Study
PIAF
Key Findings
Rhythm control resulted in better exercise capacity when
compared with rate control
CHF-STAT
Patients with AF who converted to normal sinus rhythm on
amiodarone had a lower mortality compared with those who
did not
Catheter ablation for atrial
fibrillation in congestive
heart failure
Restoration and maintenance of sinus rhythm using catheter
ablation improved cardiac function, symptoms, exercise
capacity, and quality of life in patients with CHF and AF
PABA-CHF trial
AF ablation was superior to AV nodal ablation with
biventricular pacing in improving ejection fraction, 6-minute
walk distance and quality of life in a cohort of patients with
CHF
CHF=congestive heart failure.
Akoum and Hamdan. Current Heart Failure Reports. 2007;4:78-83.
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Hospitalization for Worsening HF
DIAMOND CHF
Probability of Survival
1.0
Placebo Events=290
n=756
Dofetilide Events=229
n=762
0.8
0.6
0.4
0.2
HR=0.75
95% CI, 0.63-0.89
P<.001
0.0
0
12
Time (months)
24
Torp-Pedersen et al. N Engl J Med. 1999;341:857-865.
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LV Function Postablation in HF
P.001
LV Ejection Fraction (%)
70
65
P.001
P.001
6
12
P.001
60
55
50
45
40
35
30
25
0
0
Hsu et al. N Engl J Med. 2004;351:2373-2383.
1
3
Month
43
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AF-CHF Trial
• Prospective, open-label, multicenter trial
• Inclusion criteria
–Symptomatic (NYHA class 2-4) with LVEF 35%
–Asymptomatic with prior hospitalization for CHF or LVEF 25%
–History of significant AF
–1 episode >6-hour duration within past 6 months or
–1 episode of shorter duration but with prior electrical cardioversion
• 1376 patients randomly allocated to rhythm or rate control
• 123 sites in North America, South America, and Europe
• Minimum follow-up 2 years
• Optimal heart failure management with ACE inhibitors,
-blockers, and anticoagulation therapy for both groups
Roy. Presented at: American Heart Association 2007 Scientific Sessions; November 2007; Orlando, FL.
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AF-CHF Trial: Methods and Patients
•
>66% had persistent AF
•
>50% previously hospitalized for AF or CHF
•
Cardioversion in rhythm-control group
• Initial attempt with antiarrhythmic therapy
• Electrical cardioversion within 6 weeks of randomization for those not converting on
antiarrhythmic drugs
» Amiodarone initial drug of choice
» Sotalol and dofetilide used in select cases
» Second cardioversion within 3 months if necessary
» Patients refractory to antiarrhythmic drug therapy may receive additional
nonpharmacologic therapies (eg, catheter ablation)
•
Rate control
• Titrated doses of -blockers, digitalis, or both
• Pacemaker and AV-node ablation as needed
Roy. Presented at: American Heart Association 2007 Scientific Sessions; November 2007; Orlando, FL.
45
www.HRSonline.org
AF-CHF Trial: Results
•
No difference in primary end point of CV death
• 182 (26.7%) rhythm control vs 175 (25.2%) rate control (HR 1.058, P=.59)
•
No difference in prespecified secondary end points
• Total mortality, worsening CHF, and stroke
• Composite of CV death, worsening CHF, and stroke
• CV mortality
•
21% crossover from rhythm to rate control
• Primarily due to inability to maintain SR
•
10% crossover from rate to rhythm control
• Primarily due to worsening HF
•
Higher hospitalization rate in rhythm control (46% vs 39% at 1 year; P=.0063)
• Mainly due to hospitalization for AF and bradyarrhythmias (8.5% vs 4.9%; P=.0074)
•
Higher rate of cardioversions in rhythm control (39% vs 8%)
Roy. Presented at: American Heart Association 2007 Scientific Sessions; November 2007; Orlando, FL.
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AF-CHF Trial of Rate vs Rhythm
50
Rate
Rhythm
Percent
40
30
20
10
0
CV Death
Hospitalization Rate
Bradyarrhythmias
Also, no differences noted in secondary end points
of total mortality, worsening CHF, and stroke
Roy. Presented at: American Heart Association 2007 Scientific Sessions; November 2007; Orlando, Florida.
47
www.HRSonline.org
AF-CHF Trial: Implications
• In stable patients, no advantage to rhythm control for mortality or
secondary end points
• QoL results pending
• Cannot be extrapolated to patients with clear-cut deterioration in
clinical status at onset of AF
• Decision for rate versus rhythm strategy must be
symptom-driven
Roy. Presented at: American Heart Association 2007 Scientific Sessions; November 2007; Orlando, FL.
48
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Rate vs Rhythm Control
Current randomized studies do not demonstrate mortality
differences in rate vs rhythm treatment approaches
Patients randomized
to these studies were
older, relatively
asymptomatic, and
considered appropriate
for either strategy
QoL studies have
indicated better
results with SR
Benefits of SR may
be offset by AAD
toxicity
Symptom-driven decisions are recommended
Caveat: symptoms may be subtle or difficult to elicit,
so question patients carefully
49
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Pharmacologic Management of Patients With Newly Discovered AF
Cardioversion
Newly Discovered AF
Paroxysmal
No therapy needed,
unless severe
symptoms
(eg, hypotension, HF,
angina pectoris)
Anticoagulation,
Persistent
Accept permanent AF
Rate control and
anticoagulation,
as needed
Anticoagulation
and rate control,
as needed
Consider antiarrhythmic
drug therapy
as needed
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
Cardioversion
Long-term drug
prevention unnecessary
50
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Recommended Doses of Drugs Effective for Pharmacologic
Cardioversion of AF
Druga
Amiodarone
Route of
Administration
Oral
Dosageb
Potential Adverse Effects
Inpatient: 1.2 to 1.8 g qd in divided dose
Hypotension, bradycardia, QT,
until 10 g total, then 200 to 400 mg qd
TdP (rare), GI upset, constipation,
maintenance or 30 mg/kg as single dose
phlebitis (IV)
Outpatient: 600 to 800 mg qd in divided dose
to 10 g total, then 200 to 400 mg qd
Intravenous/oral 5 to 7 mg/kg over 30 to 60 min, then 1.2 to 1.8
g qd continuous IV or in divided oral doses until
10 g total, then 200 to 400 mg qd maintenance
Dofetilide
Oral
Creatinine Clearance
Dose
(mL/min)
(mcg BID)
>60
500
40 to 60
250
20 to 40
125
<20
Contraindicated
QT, TdP; adjust dose for renal
function, body size, and age
aDrugs
are listed alphabetically. bDosages given in the table may differ from those recommended by the manufacturers.
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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Recommended Doses of Drugs Effective for Pharmacologic
Cardioversion of AF (cont’d)
Druga
Flecainide
Ibutilide
Route of
Administration
Oral
Dosageb
200 to 300 mgc
Potential Adverse Effects
Hypotension, atrial flutter with
high ventricular rate
Intravenous
1.5 to 3.0 mg/kg over
10 to 20 minc
Intravenous
1 mg over 10 min;
repeat 1 mg prn
QT, TdP;
Oral
600 mg
Hypotension, atrial flutter with
high ventricular rate
Intravenous
1.5 to 2.0 mg/kg over
10 to 20 minc
Propafenone
Quinidined
Oral
0.75 to 1.5 g in divided doses
QT, TdP, GI upset, hypotension
over 6 to 12 h, usually with a rateslowing drug
aDrugs
are listed alphabetically. bDosages given in the table may differ from those recommended by the manufacturers.
cInsufficient data are available on which to base specific recommendations for the use of one loading regimen over
another for patients with ischemic heart disease or impaired left ventricular function, and these drugs should be used
cautiously or not at all in such patients. dThe use of quinidine loading to achieve pharmacologic conversion of AF is
controversial, and safer methods are available with the alternative agents listed in the table. Quinidine should be used with
caution.
52
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Pooled Results for the Efficacy and Adverse Effects of Drugs Used
in Acute Conversion of AF
Level of Evidence
Drug
Strong (# trials)
Ibutilide (4)
Range of Sustained Ventricular
Arrhythmia
in All Trials Reporting
P Value
Side Effects
%
<.01
0-9
Flecainide (5)
<.01
0-2
Dofetilide (6)
<.01
1-12
Propafenone (14)
<.01
0-2
Amiodarone (15)
<.01
0
Moderate (# trials)
Quinidine (3)
.02
0-12
Inconclusive (# trials)
Disopyramide (1)
.10
Not reported
Sotalol (3)
>.2
0-2
indicates placebo, calcium channel blockers, -blockers, or digoxin.
McNamara et al. Ann Intern Med. 2003;139:1018-1033.
aControl
Odds Ratio of Conversion
Compared With Control
(95% CI)a
01
5
10
15
20
25
30
90
53
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Pharmacologic Management of Patients With Recurrent
Paroxysmal Atrial Fibrillation : Sinus Rhythm Maintenance
Recurrent Paroxysmal AF
Minimal or
no symptoms
Disabling
symptoms in AF
Anticoagulation
and rate control
as needed
Anticoagulation
and rate control
as needed
No drug for
prevention of AF
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
AAD therapy
AF ablation if AAD
treatment fails
54
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Indications for Use of Antiarrhythmic Therapy for SR
Maintenance
• First treat all precipitating or reversible causes
• However, many factors, such as age, hypertension, HF,
and enlarged LA, are not reversible
• Success of SR maintenance can include infrequent,
well-tolerated episodes of AF
• Risk factors for recurrence of AF
• Frequent AF (>1 episode per month)
• Female, underlying heart disease
• 4-year recurrence
• Hypertension, age >55 years, AF duration >3 months
• General risks
• LA enlargement, rheumatic heart disease, HF
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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Indications for Use of Antiarrhythmic Therapy for SR
Maintenance
• Short-term use
• In AF >3 months, short-term therapy after cardioversion may be useful
• Should be started before cardioversion (but after adequate length of
anticoagulation)
• Can be used for approximately 1 month
• Long-term use
• Best utilized in patients with recurrent paroxysmal AF in whom rhythm
control is preferred
• eg, patients with significant symptoms during AF
Fuster www.HRSonline.org
et al. J Am Coll Cardiol. 2006;48:854-906.
56
Determining Choice of Antiarrhythmic Agent for SR Maintenance
• Guidelines contain an algorithm for choosing therapy to
maintain SR
• Choices include antiarrhythmic agents and nonpharmacologic
therapy (ablation)
• Algorithm is safety-based with clinical trial evidence of
efficacy
• Choices are dependent on patient characteristics
• Classifying patients into appropriate categories is critical
for management approach
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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Maintenance of Sinus Rhythm
No (or minimal)
heart disease
Hypertension
Coronary artery
disease
Heart
failure
Flecainide
Propafenone
Sotalol
Substantial
LVH
Dofetilide
Sotalol
Amiodarone
Dofetilide
Amiodarone
Dofetilide
Catheter
ablation
No
Yes
Flecainide
Propafenone
Sotalol
Amiodarone
Amiodarone
Dofetilide
www.HRSonline.org
Catheter
ablation
Amiodarone
Catheter
ablation
Catheter
ablation
Catheter
ablation
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
58
Maintenance of Sinus Rhythm
No (or minimal)
heart disease
Hypertension
Coronary artery
disease
Heart
failure
Flecainide
Propafenone
Sotalol
Substantial
LVH
Dofetilide
Sotalol
Amiodarone
Dofetilide
Amiodarone
Dofetilide
Catheter
ablation
No
Yes
Flecainide
Propafenone
Sotalol
Amiodarone
Amiodarone
Dofetilide
www.HRSonline.org
Catheter
ablation
Amiodarone
Catheter
ablation
Catheter
ablation
Catheter
ablation
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
59
Special Considerations for Patients With HF
• Particularly prone to proarrhythmic effects of antiarrhythmic drugs
–Myocardial vulnerability
–Electrolyte imbalance
–Drug interactions
–Renal dysfunction
• Clinical trial evidence for safety with amiodarone
and dofetilide
• Utilize -blocker and ACE inhibitor (or ARB) therapy
as indicated for HF or LV dysfunction
• Flecainide and propafenone should be avoided
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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Maintenance of Sinus Rhythm
No (or minimal)
heart disease
Hypertension
Coronary artery
disease
Heart
failure
Flecainide
Propafenone
Sotalol
Substantial
LVH
Dofetilide
Sotalol
Amiodarone
Dofetilide
Amiodarone
Dofetilide
Catheter
ablation
No
Yes
Flecainide
Propafenone
Sotalol
Amiodarone
Amiodarone
Dofetilide
www.HRSonline.org
Catheter
ablation
Amiodarone
Catheter
ablation
Catheter
ablation
Catheter
ablation
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
61
Special Considerations for Patients With Coronary Disease
• Beta blockers can be used, but data are not convincing for
SR maintenance
• Sotalol, amiodarone, and dofetilide have neutral
effects on mortality
• Sotalol preferred as monotherapy because of
-blocking activity and fewer extracardiac side effects
• Flecainide and propafenone should not be used in these
patients because of increased mortalitya
aIncreased
mortality seen in CAST studies with flecainide and extrapolation to all class IC agents.
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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Maintenance of Sinus Rhythm
No (or minimal)
heart disease
Hypertension
Coronary artery
disease
Heart
failure
Flecainide
Propafenone
Sotalol
Substantial
LVH
Dofetilide
Sotalol
Amiodarone
Dofetilide
Amiodarone
Dofetilide
Catheter
ablation
No
Yes
Flecainide
Propafenone
Sotalol
Amiodarone
Amiodarone
Dofetilide
www.HRSonline.org
Catheter
ablation
Amiodarone
Catheter
ablation
Catheter
ablation
Catheter
ablation
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
63
Special Considerations for Patients With Hypertension
• Hypertension is the most prevalent and modifiable risk factor for AF
• Increased risk of torsades de pointes because of early ventricular
after-depolarizations in hypertensive heart disease
• In absence of ischemia or significant LVH, propafenone
or flecainide are reasonable choices
• Amiodarone first line in patients with LVH
• In patients with substantial hypertensive heart disease, flecainide and
propafenone should be avoided
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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Maintenance of Sinus Rhythm
No (or minimal)
heart disease
Hypertension
Coronary artery
disease
Heart
failure
Flecainide
Propafenone
Sotalol
Substantial
LVH
Dofetilide
Sotalol
Amiodarone
Dofetilide
Amiodarone
Dofetilide
Catheter
ablation
No
Yes
Flecainide
Propafenone
Sotalol
Amiodarone
Amiodarone
Dofetilide
www.HRSonline.org
Catheter
ablation
Amiodarone
Catheter
ablation
Catheter
ablation
Catheter
ablation
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
65
No or Minimal Heart Disease
• Patients with no obvious evidence of structural heart disease
• Normal ECG and ventricular structure and function by
echocardiogram; negative stress test (if indicated)
• Flecainide, propafenone, and sotalol have demonstrated efficacy with
fewer noncardiac side effects and minimal rates of proarrhythmia in
this patient category
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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Initiation of Antiarrhythmic Drug Therapy
• Ensure normal electrolyte status
• Initiate AV node blockade prior to use of antiarrhythmic agent without
substantial AV-node–blocking activity
• Initiate therapy with lower dose and appropriate up-titration as needed
and after evaluating drug effects on ECG parameters
• Ensure appropriate anticoagulation prior to starting antiarrhythmic
drug therapy
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
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Summary of Antiarrhythmic Trials for SR Maintenance
11,322 patients; 44 trials
AF Recurrence
Class IA
Disopyramide vs other
Class I drugs
Class IC
(Class II) Metoprolol
Flecainide vs propafenone
Class I drugs
Class III:
Sotalol
Amiodarone
Sotalol vs class I except
quinidine
Sotalol
0.10 1
10
Odds Ratio (95% CI)
0.10 1
10
Odds Ratio (95% CI)
Lafuente-Lafuente et al. Arch Intern Med. 2006;166:719-728.
68
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New Formulations of AADs
Propafenone RAFT and ERAFT Studies
Proportion Free of Events
RAFT (n=523)
ERAFT (n=293)
AF recurrence at 1 year (%)
P 425 BID vs placebo: OR, 0.604
(95% CI, 0.433-0.843) P=.002
1
ERAFT 325 mg BID
ERAFT 425 mg BID
0.8
0.6
0.4
RAFT 225 mg BID
RAFT 325 mg BID
RAFT 425 mg BID
Placebo
Propafenone 225 BID
Propafenone 325 BID
Propafenone 425 BID
0.2
0
0
50
100
150
Days
200
250
0
300
0.25
0.5
0.75
1
Propafenone better
Pritchett et al. Am J Cardiol. 2002;92:941-946; Meinerz et al. Am J Cardiol. 2002;90:1300-1306.
69
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Free From AF Recurrence (OT/ITT)
Sotalol vs Amiodarone SAFE-T
1.0
0.9
Amiodarone
809/487
0.8
0.7
Sotalol
209/74
0.6
Placebo
13/6
0.5
Sotalol
0.4
0.3
0.2
Placebo
0.1
0
100 200 300 400 500 600 700 800 900 1000
Days
Singh et al. N Engl J Med. 2005;352:1861-1872.
70
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Typical Doses of Drugs Used to Maintain Sinus Rhythm in
Patients With AF
Drug
Daily
Potential Adverse Effects
Amiodarone
100 to 400 mg
Photosensitivity, pulmonary toxicity, polyneuropathy, GI
upset, bradycardia, TdP (rare), hepatic toxicity, thyroid
dysfunction,
eye complications
Disopyramide
400 to 750 mg
TdP, HF, glaucoma, urinary retention, dry mouth
Dofetilide
500 to 1000 mcg
TdP
Flecainide
200 to 300 mg
VT, HF, conversion to atrial flutter with rapid conduction
through AV node
Propafenone
450 to 900 mg
VT, HF, conversion to atrial flutter with rapid conduction
through AV node
Sotalol
160 to 320 mg
TdP, HF, bradycardia, exacerbation of chronic obstructive or
bronchospastic lung disease
Fuster et al. Am Coll Cardiol. 2006;48:854-906.
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New AAD Development
• Beta blockers with Class I or III effects
• Amiodarone congeners
• Atrial-selective antiarrhythmic drugs
– IKur- , Ito and IKACh- blocker
– Atrial-selective Na channel blocker
– 5-HT4 receptor antagonist
• Stretch-activated channel blockers
• ACEI/ARB
• NCX (Na/Ca exchanger) inhibitor
• Anti-inflammatories (statins)
• Gap junction conduction facilitation
72
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Selective Atrial Ion Channel Blockade
Agent
Mechanism of Action
MPS
IKur
JTV 519
IKACh, IKr
S1185, S9947, S2091
IKur
AVE 0118
IKur, Ito, IKACh
RS100302 (piboserod)
5-HT4 receptor
Vernakalant
IKur, Ito, INa, IKACh
Wijffels et al. J Cardiovasc Electrophysiol. 2003;14(9 suppl):S40-S4;
Camm et al. Heart Rhythm. 2004;1:244-246.
73
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Drugs That Block Multiple Ion Channels
Agent
Mechanism of Action
Dronedarone
IKr IKur Ito IKa INa -blocker
Ambasilide
IKr IKur IKs
Azimilide
IKr IKs
Tedisamil
IKr Ito IKATP INa IKur
ATI-2042
IKr IKs B1 ICa Ito INa
AZD 7009
IKr IKur INa
Wijffels et al. J Cardiovasc Electrophysiol. 2003;14(9 suppl):S40-S4;
Camm et al. Heart Rhythm. 2004;1:244-246.
74
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Upstream Therapy for Possible Prevention of AF: ACEIs and
ARBs
• Empiric observation of benefit in clinical trials
• Decreased atrial pressure, frequency of APBs, fibrosis
• May reduce signal-averaged P-wave duration, number of defibrillation
attempts required, number of hospital readmissions for AF
• May have role for primary prevention in patients with hypertension,
MI, HF, or diabetes mellitus
• May also reduce the recurrence of AF
Fuster www.HRSonline.org
et al. J Am Coll Cardiol. 2006;48:854-906.
75
Valsartan and AF in VALIANT
Estimated Probability of AF
0.15
Placebo
Valsartan
0.10
Log-rank test, P=.0001
0.05
0.00
0
3
6
9
12
15
18
21
24
27
Months Since Randomization
Maggioni et al. Am Heart J. 2005;149:548-557.
76
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Candesartan and AF in CHARM
P heterogeneity=0.57
Odds Ratio (95% CI), P Value
Alternative
0.686 (0.470-1.002)
Added
0.856 (0.617-1.187)
Preserved
0.894 (0.618-1.295)
2 Low EF trials
0.779 (0.608-0.997), .0472
Overall
0.812 (0.662-0.998), .0476
0.2
0.4 0.6 0.8 1.0 1.2
Odds Ratio (95% CI)
1.4
Ducharme et al. Am Heart J. 2006;152:86-92.
77
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Kaplan-Meier Plot of Occurrence of Postop AF
Patients Free of AF (%)
100
90
PUFAs Group
80
Log-rank, P=.009
70
Control Group
60
50
0
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18
Days After Surgery
Calo et al. J Am Coll Cardiol. 2005;45:1723-1728.
78
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Ablation
Catheter-based
Second-line therapy in most patient categories
• Especially in patients who cannot tolerate antiarrhythmics
• In rare instances, may be first-line therapy
Success rates vary depending on underlying disease, experience of operators,
and definitions of success but
are ~75% in select groups of patients
Presence of LA thrombus is contraindication
Surgical
Generally MAZE procedure, utilized in patients already undergoing cardiac
procedure
Fuster www.HRSonline.org
et al. J Am Coll Cardiol. 2006;48:854-906.
79
Indications for Catheter AF Ablation
• Symptomatic AF refractory or intolerant to at least one Class I or III
antiarrhythmic medication
• In rare clinical situations, it may be appropriate as first-line therapy
• Selected symptomatic patients with heart failure and/or reduced
ejection fraction
• Presence of a left atrial thrombus is contraindication to catheter
ablation of AF
Calkinswww.HRSonline.org
et al. Heart Rhythm. 2007;4:1-46.
80
Who Should Be Referred for Ablation?
• Patients who have been adequately evaluated for AF etiology and
underlying diseases
• Highly symptomatic patients in whom one or more antiarrhythmic
agents have failed
• Patients with understanding of efficacy and risks of ablation
81
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Patient Selection for Ablation
More Optimal Patient
Less Optimal Patient
Highly symptomatic
Minimally symptomatic
1
0
Paroxysmal
Long-standing persistant
Younger (<70 years)
Older (70 years)
Smaller (<5.0 cm)
Larger (5.0 cm)
Normal
Reduced
Congestive heart failure
No
Yes
Other cardiac disease
No
Yes
Pulmonary disease
No
Yes
Sleep apnea
No
Yes
Obesity
No
Yes
Prior stroke/TIA
No
Yes
Variable
Symptoms
Class I and III drugs failed
AF type
Age
LA size
Ejection fraction
Courtesy of Hugh Calkins, MD.
82
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Controlled Trials of AF Ablation Patients Free of AF (% at 1 Year)
Ablation
100
90
Control
87
86
79
75
80
86
70
56
Percent
60
50
40
30
20
10
0
RAAFT
CACAF
A4
APAF
Milan/NR
PABA CHF
Courtesy of Jeremy N. Ruskin, MD, Massachusetts General Hospital.
83
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Pooled Studies: Observational and RCTs Patients Free of AF at 1-2
Years (%)
OBS: N=1965; 8 Studies
RCT: N=517; 4 Studies
100
77%
80
60
Percent
Percent
80
100
40
76%
60
40
23%
20
20
0
0
Free of AF
Recurrent AF
10%
Ablation
Control
Courtesy of Jeremy N. Ruskin, MD, Massachusetts General Hospital.
84
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Worldwide Survey on Ablation Procedures for AF (1995-2002)
• 8745 patients (age range 16-86 years); 90 ablation centers
• Overall success rate: 76%
–52% without AADs
–24% with AADs
• Major complication rate: 6%
• 27% required >1 procedure
• Follow-up: 11.6  7.7 months
Cappato et al. Circulation. 2005;111:1100-1105.
85
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Success Rates With Ablation Worldwide Survey
Success Without AADs
Success With AADs
Overall Success
100
90
80
Rates (%)
70
60
50
40
30
20
10
0
0-3
4-6
7-9
10-12
13-18
19-24
>24
Range of Follow-up (months)
Cappato et al. Circulation. 2005;111:1100-1105.
86
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Worldwide Survey on Ablation for AF Major Complications
2
Percent
1.5
1
0.5
0
Death Tamponade Stroke
TIA
PV
Infection, Femoral
Valve
stenosis pneumo/ pseudo- damage,
Hemo- aneurysm,
Ao
thorax,
AV
dissection
diaphragm fistula
paralysis
Cappato et al. Circulation. 2005;111:1100-1105.
www.HRSonline.org
87
AF-Free Survival
Ablation vs Pharmacologic Therapy
AF-Free
Survival Probability (%)
100
80
60
40
Ablation Group
Medical Group
20
0
0
No. at risk
Ablation
589
Medical
582
180
360
540
720
Days of Follow-up
900
1080
507
456
479
354
217
141
135
97
379
277
282
207
Pappone et al. J Am Coll Cardiol. 2003;42:185-197.
88
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Cumulative AF-Free Survival
Freedom From AF Following Pulmonary Vein Isolation
Normal vs Impaired LV Function
100
90
80
P=.03
70
60
Impaired LV Function (n=94)
Normal LV Function (n=283)
50
40
30
60
90 120 150 180 210 240 270 300 330 360 390 420
Follow-up Time (days)
Chen et al. J Am Coll Cardiol. 2004;43:1004-1009.
89
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RAAFT Outcomes at 1 Year
No significant difference in
Severe, moderate, or mild pulmonary vein stenosisa
Bleeding
Thromboembolic eventsb
Significant difference
Hospitalization
• AAD (54%) vs PVI (9%)
• P<.001
Symptomatic AF recurrence
• AAD (63%) vs PVI (13%)
• P<.001
Survival Free From Atrial Fibrillation
Bradycardia
1.0
0.9
PVI Group
0.8
0.7
0.6
Antiarrhythmic
Drug Group
0.5
0.4
0.3
0.2
0.1
0.0
0.0
100
200
Follow-up (days)
300
90
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CACAF Study of Ablation in Drug-Refractory AF
Atrial Arrhythmia–Free Survival Curves After the Blanking Period
100
Percent Survival
Ablation Group (n=68)
80
Control Group (n=69)
60
40
P<.001
20
0
0
1
2
3
4
Stabile et al. Eur Heart J. 2006;27:216-221.
5
6
7
8
9
10
11
12
Months
91
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A4 Study Results
Ablation Group (n=53)
80
AAD Group (n=59)
70
60
Percent
50
40
30
20
10
0
Free of Arrhythmia Recurrence
at 1 Year (%)
Discontinued Oral
Anticoagulation (%)
Jaïs et al. Presented at: Heart Rhythm Society 2006 Annual Scientific Sessions;
May 17-20, 2006; Boston, MA.
92
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A4 Study Results
Kaplan-Meier Plots for Time to AF Recurrence
Probability of No
AF Recurrence
Ablation
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
Antiarrhythmic Drug
75%
P<.0001 (log-rank test)
7%
0
100
200
300
400
500
Follow-up Days
Jaïs et al. Presented at: Heart Rhythm Society 2006 Annual Scientific Sessions; May 17-20, 2006; Boston, MA.
93
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Limitations of Current Ablation Data
• Few current trials are prospective
• Single-center results not necessarily reflective of general
results
• Ablation patients frequently also receive AADs
• Therapy crossovers
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CABANA Trial
Recent-onset AF
Eligible for ablation
or drug therapy
65 years old or
<65 years with 1
risk factor for CAD
or stroke
Primary Ablation
(technique at
operator discretion)
Discontinued
Anticoagulation
Continued
Anticoagulation
Drug Therapy
(rate or rhythm control
[at operator discretion]
with anticoagulation)
Packer. Presented at 2005 Scientific Sessions of the American Heart Association. November 13-16; Dallas, TX.
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P<.001
LV End-Diastolic
Diameter (mm)
0
75
70
65
60
55
50
45
0
1
3
Month
P=.001
0
1
P<.001 P<.001 P<.001
P=.03
3
Month
6
P=.02
6
LV Fractional
Shortening (%)
70
65
60
55
50
45
40
35
30
25
0
40
35
P=.001
12
P<.001
P<.001 P<.001 P<.001
30
25
20
15
0
12
0
LV End-Systolic
Diameter (mm)
LV Ejection
Fraction (%)
Improvement in LV Function and Dimensions After Ablation in
Patients With CHF
55
50
45
40
35
30
0
1
3
Month
6
12
P<.001 P<.001 P=.001 P=.001
0
1
3
Month
6
12
Plotted values are means SD. P values, which are for the comparison with baseline data, were determined with the use of Fisher’s
least-significant-difference test. The numbers of patients included at each time point were as follows: 0 month, 58; 1 month, 55;
3 months, 48; 6 months, 40; 12 months, 34.
Hsu et al. N Engl J Med. 2004;351:2373-2383.
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Estimated Outcomes and Risks of AF Ablation
Success
Single Procedure
Multiple Procedure
Optimal patient
60%-80%
80%-90%
Less optimal patient
50%-70%
70%-80%
<40%
40%-60%
Poor candidate
Major Complication Rates
2%-12%
Left atrial flutter
2%-5%
Vascular access related
1%-5%
Cardiac tamponade
0.5%-3%
Stroke
0.5%-2%
PV stenosis
<1%
Phrenic nerve injury
<0.5%
Esophageal perforations
<0.2%
Mitral valve entrapment
<0.1%
Acute coronary occlusion
<0.1%
Death
<0.1%
Courtesy of Hugh Calkins, MD.
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Common Lesions Performed in
AF Ablation
SVC
LSPV
LIPV
LSPV
LIPV
RSP
V
RIPV
SVC
LSPV
LIPV
RSPV
RIPV
IVC
IVC
SVC
SVC
RSP
V
RIPV
IVC
LSPV
LIPV
RSP
V
RIPV
IVC
Calkins et al. Heart Rhythm. 2007;4:1-46.
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Ablation Techniques
• Ablation strategies that target PVs and/or PV antrum are cornerstones
for most AF ablation procedures
• If PVs are targeted, complete electrical isolation should be goal
• For surgical PV isolation, entrance and/or exit block should be
demonstrated
• Careful identification of PV ostia is mandatory to avoid ablation within
PVs
• If focal trigger is identified outside PV at time of AF ablation
procedure, it should be targeted if possible
Calkins et al. Heart Rhythm. 2007;4:1-46.
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Postablation Management
• LMWH or IV heparin as bridge to systemic anticoagulation
• Warfarin for all patients for 2 months
• Use of warfarin >2 months following ablation based on patient’s risk
factors for stroke and not presence or type of AF
• Discontinuation of warfarin therapy postablation generally not
recommended for CHADS2 score 2
Calkins et al. Heart Rhythm. 2007;4:1-46.
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Postablation Management
Blanking period
• Blanking period 3 months after ablation when reporting outcomes
Definition of success
• Freedom from AF/flutter/tachycardia without antiarrhythmic therapy is
1o end point
• Freedom from AF at various points following ablation may be better
marker of true benefit; consider as 2o end point
• Atrial flutter and other atrial tachyarrhythmias=treatment failures
• An episode of AF/flutter/tachycardia with duration of 30 seconds
detected by monitoring considered recurrence
Calkins et al. Heart Rhythm. 2007;4:1-46.
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Postablation Management
Minimal monitoring
• Follow-up minimum of 3 months following ablation procedure; then
every 6 months for 2 years
• Obtain event monitor to screen for recurrrent AF/flutter/tachycardia in
patients with palpitations during follow-up
• AF/flutter/tachycardia episode present if documented by ECG lasting
30 seconds
• 24-hour Holter monitoring is acceptable minimal monitoring strategy
for patients in clinical trials and recommended at
3-6 month intervals for 1-2 years
Calkins et al. Heart Rhythm. 2007;4:1-46.
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Postablation Management
Repeat procedures
• Repeat procedures should be delayed for at least 3 months following
initial ablation if patient’s symptoms can be controlled with medical
therapy
Complication reporting
• Major complications are defined as those that result in permanent
injury or death, require intervention for treatment, or prolong or require
hospitalization
Calkins et al. Heart Rhythm. 2007;4:1-46.
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Take-Home Points
• Heart rate control at rest and with exertion is critical for
either AF strategy
• Rate vs rhythm approach should be guided by many factors, most
importantly, symptoms and appropriate application of clinical trials
• Guidelines contain algorithms on how to choose method
for SR maintenance
• Certain antiarrhythmics are appropriate for select groups
of patients
• Ablation is an important option in SR maintenance
• Appropriate patient categorization is critical for management
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