Post on 26-Dec-2015
Rhythm Management
www.HRSonline.org
2
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.
www.HRSonline.org
3
Management of Patient With AF
Initial Presentation With AF
Initial Presentation With AF
Hemodynamically Stable
Hemodynamically Stable
Hemodynamically Unstable
Hemodynamically Unstable
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
www.HRSonline.org
4
Classification of AFACC/AHA/ESC Guidelines
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
Persistent(Not self-terminating)
Persistent(Not self-terminating)
Paroxysmal(Self-terminating)
Paroxysmal(Self-terminating)
First Detected
First Detected
PermanentPermanent
www.HRSonline.org
5
Pharmacologic Management of Patients With Newly Discovered AFACC/AHA/ESC Guidelines
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
Newly Discovered AFNewly Discovered AFNewly Discovered AFNewly Discovered AF
ParoxysmalParoxysmalParoxysmalParoxysmal
No therapy needed, No therapy needed, unless severe unless severe
symptoms symptoms (eg, hypotension, HF,(eg, hypotension, HF,
angina pectoris)angina pectoris)
No therapy needed, No therapy needed, unless severe unless severe
symptoms symptoms (eg, hypotension, HF,(eg, hypotension, HF,
angina pectoris)angina pectoris)
PersistentPersistentPersistentPersistent
Accept permanent AFAccept permanent AFAccept permanent AFAccept permanent AF
AnticoagulationAnticoagulationand rate control,and rate control,
as neededas needed
AnticoagulationAnticoagulationand rate control,and rate control,
as neededas needed
Rate control andRate control andanticoagulation,anticoagulation,
as neededas needed
Rate control andRate control andanticoagulation,anticoagulation,
as neededas needed
Consider antiarrhythmicConsider antiarrhythmicdrug therapydrug therapy
Consider antiarrhythmicConsider antiarrhythmicdrug therapydrug therapy
Long-term drugLong-term drugprevention unnecessaryprevention unnecessary
Long-term drugLong-term drugprevention unnecessaryprevention unnecessary
Anticoagulation,Anticoagulation,
as neededas needed
Anticoagulation,Anticoagulation,
as neededas neededCardioversionCardioversionCardioversionCardioversion
www.HRSonline.org
6
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
www.HRSonline.org
7
Pharmacologic Management of Patients With Newly Discovered AFRecurrent Paroxysmal AF
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
Newly Discovered AFNewly Discovered AFNewly Discovered AFNewly Discovered AF
ParoxysmalParoxysmalParoxysmalParoxysmal
No therapy needed, No therapy needed, unless severe unless severe
symptoms symptoms (eg, hypotension, HF,(eg, hypotension, HF,
angina pectoris)angina pectoris)
No therapy needed, No therapy needed, unless severe unless severe
symptoms symptoms (eg, hypotension, HF,(eg, hypotension, HF,
angina pectoris)angina pectoris)
PersistentPersistentPersistentPersistent
Accept permanent AFAccept permanent AFAccept permanent AFAccept permanent AF
AnticoagulationAnticoagulationand rate control,and rate control,
as neededas needed
AnticoagulationAnticoagulationand rate control,and rate control,
as neededas needed
Rate control andRate control andanticoagulation,anticoagulation,
as neededas needed
Rate control andRate control andanticoagulation,anticoagulation,
as neededas needed
Consider antiarrhythmicConsider antiarrhythmicdrug therapydrug therapy
Consider antiarrhythmicConsider antiarrhythmicdrug therapydrug therapy
Long-term drugLong-term drugprevention unnecessaryprevention unnecessary
Long-term drugLong-term drugprevention unnecessaryprevention unnecessary
Anticoagulation,Anticoagulation,
as neededas needed
Anticoagulation,Anticoagulation,
as neededas neededCardioversionCardioversionCardioversionCardioversion
www.HRSonline.org
8
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.
www.HRSonline.org
9
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
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
www.HRSonline.org
10
Etiologies and Factors Predisposing Patients to AF
Endocrine disorders
Hyperthyroidism
Pheochromocytoma
Changes in autonomic tone
Increased parasympathetic activity
Increased sympathetic activity
Primary or metastatic disease
Postoperative
Cardiac, pulmonary, or esophageal
Congenital heart disease
Neurogenic
Subarachnoid hemorrhage
Nonhemorrhagic, major stroke
Idiopathic (lone AF)
Familial AF
Electrophysiologic abnormalities Enhanced automaticity (focal AF)
Conduction abnormality (reentry)
Atrial pressure elevation Mitral or tricuspid valve disease
Myocardial disease (1o or 2o, with systolic or diastolic dysfunction)
Aortic valve disease with LVH
Systemic or pulmonary hypertension
Intracardiac tumors or thrombi
Atrial ischemia (CAD)
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.
www.HRSonline.org
11
Mechanisms of AF
Focal ActivationFocal Activation Multiple WaveletsMultiple Wavelets
RARALALA
PVsPVs
IVCIVC
SVCSVCRARALALA
PVsPVs
IVCIVC
SVCSVC
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
www.HRSonline.org
12
Anatomy of Pulmonary Veins
Extension of muscular fibers into pulmonary vein (PV)
Ganglia noted in yellow
Large and small reentrant wavelets that play a role in initiating andsustaining AF
Common locations of PV (purple) and common sites of origin of non-PVtriggers (black)
Composite of anatomic and arrhythmic mechanisms of AF
Calkins et al. Heart Rhythm. 2007;4:1-46.
LSPV
LIPV
RSPV
IVC
RIPV
SVC
LSPV
LIPV
RSPV
IVC
SVC
LSPV
LIPV
RSPV
IVC
RIPV
SVC
LSPV
LIPV
RSPV
IVC
RIPV
SVC
RIPV
www.HRSonline.org
13
Mechanisms of AF: Triggers for Induction of AF
Triggers that induce AF includeSympathetic 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.
www.HRSonline.org
14
Allessie et al. Circulation. 2001;103:769-777.
Mechanisms of AF: Perpetuation
Substrate that sustains AFPersistence 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
www.HRSonline.org
15
Perpetuation of AF: Electrophysiologic Mechanisms
Wijffels et al. Circulation. 1995;92:1954-1968.
ControlControl
After After 24 hours24 hours
After After 2 weeks2 weeks
BurstBurstpacingpacing AFAF Sinus rhythmSinus rhythm Duration ofDuration of
fibrillationfibrillation
5 seconds5 seconds
20 seconds20 seconds
>24 hours>24 hours
AFAF
Sustained AFSustained AF
www.HRSonline.org
16
Pharmacologic Management of Patients With Newly Discovered AFRate Control vs Rhythm control
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
Newly Discovered AFNewly Discovered AFNewly Discovered AFNewly Discovered AF
ParoxysmalParoxysmalParoxysmalParoxysmal
No therapy needed, No therapy needed, unless severe unless severe
symptoms symptoms (eg, hypotension, HF,(eg, hypotension, HF,
angina pectoris)angina pectoris)
No therapy needed, No therapy needed, unless severe unless severe
symptoms symptoms (eg, hypotension, HF,(eg, hypotension, HF,
angina pectoris)angina pectoris)
PersistentPersistentPersistentPersistent
Accept permanent AFAccept permanent AFAccept permanent AFAccept permanent AF
AnticoagulationAnticoagulationand rate control,and rate control,
as neededas needed
AnticoagulationAnticoagulationand rate control,and rate control,
as neededas needed
Rate control andRate control andanticoagulation,anticoagulation,
as neededas needed
Rate control andRate control andanticoagulation,anticoagulation,
as neededas needed
Consider antiarrhythmicConsider antiarrhythmicdrug therapydrug therapy
Consider antiarrhythmicConsider antiarrhythmicdrug therapydrug therapy
Long-term drugLong-term drugprevention unnecessaryprevention unnecessary
Long-term drugLong-term drugprevention unnecessaryprevention unnecessary
Anticoagulation,Anticoagulation,
as neededas needed
Anticoagulation,Anticoagulation,
as neededas neededCardioversionCardioversionCardioversionCardioversion
www.HRSonline.org
17
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.
www.HRSonline.org
18
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.
www.HRSonline.org
19
Achieving Rate Control Class/Recommendations
AcutelyIV 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-termMeasurement 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.
www.HRSonline.org
20
Agents for Heart Rate Control Acute Setting
Drug Loading Dose Onset Maintenance Dose Major Side Effects
Heart rate control in patients without accessory pathway
Esmolol 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 IVover 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
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
www.HRSonline.org
21
Agents for Heart Rate Control: Acute Setting
Drug Loading Dose OnsetMaintenance
Dose Major Side Effects
Heart rate control in patients with accessory pathway
Amiodarone 150 mg over 10 min
Days 0.5 to1 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.
www.HRSonline.org
22
Agents for Heart Rate Control: Nonacute and Chronic Maintenance
Drug OnsetLoading 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 individed 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.
www.HRSonline.org
23
Agents for Heart Rate Control: Nonacute and Chronic Maintenance
Drug Loading Dose OnsetMaintenance
Dose Major Side Effects
Heart rate control in patients with HF and without accessory pathway
Digoxin 0.5 mgPO daily
2days
0.125 to 0.375 mg qd, PO
Digitalis toxicity, HB, ↓ HR
Amiodarone 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
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
www.HRSonline.org
24
Pharmacologic Management of Patients With Newly Discovered AFACC/AHA/ESC Guidelines
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
Newly Discovered AFNewly Discovered AFNewly Discovered AFNewly Discovered AF
ParoxysmalParoxysmalParoxysmalParoxysmal
No therapy needed, No therapy needed, unless severe unless severe
symptoms symptoms (eg, hypotension, HF,(eg, hypotension, HF,
angina pectoris)angina pectoris)
No therapy needed, No therapy needed, unless severe unless severe
symptoms symptoms (eg, hypotension, HF,(eg, hypotension, HF,
angina pectoris)angina pectoris)
PersistentPersistentPersistentPersistent
Accept permanent AFAccept permanent AFAccept permanent AFAccept permanent AF
AnticoagulationAnticoagulationand rate control,and rate control,
as neededas needed
AnticoagulationAnticoagulationand rate control,and rate control,
as neededas needed
Rate control andRate control andanticoagulation,anticoagulation,
as neededas needed
Rate control andRate control andanticoagulation,anticoagulation,
as neededas needed
Consider antiarrhythmicConsider antiarrhythmicdrug therapydrug therapy
Consider antiarrhythmicConsider antiarrhythmicdrug therapydrug therapy
Long-term drugLong-term drugprevention unnecessaryprevention unnecessary
Long-term drugLong-term drugprevention unnecessaryprevention unnecessary
Anticoagulation,Anticoagulation,
as neededas needed
Anticoagulation,Anticoagulation,
as neededas neededCardioversionCardioversionCardioversionCardioversion
www.HRSonline.org
25
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.
www.HRSonline.org
26
Rhythm vs Rate Control in AF Evidence Base
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
5 prospective, controlled, randomized trials comparing 2 different treatment strategies
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
www.HRSonline.org
27
Rhythm vs Rate Control in AF Evidence Base
Trial Follow-up (y)Age, y
(mean SD) Patients in SRa
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%
aComparison between rate and rhythm control group.Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
www.HRSonline.org
28
02468
101214161820 Rate Rhythm
Rhythm vs Rate Control in AF Evidence Base (cont'd)
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
Per
cen
t
Stroke Death
www.HRSonline.org
29
The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833; Waldo. Am J Cardiol. 1999;84:698-700.
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 months1 episode documented by ECG in past 12 weeks1 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
www.HRSonline.org
30
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.
www.HRSonline.org
31
Primary End Point All-Cause Mortality in AFFIRM
Cu
mu
lati
ve M
ort
alit
y (%
)C
um
ula
tive
Mo
rtal
ity
(%)
Time (years)
3030
2525
2020
1515
1010
55
00
00 11 22 33 44 55
Rhythm ControlRhythm Control
Rate ControlRate Control
PP=.058=.058
Wyse. Presented at: American College of Cardiology 51st Annual Meeting; March 17-20, 2002; Atlanta, GA.
Rhythm N:Rhythm N: 20332033 19321932 18071807 13161316 780780 255255Rate N:Rate N: 20272027 19251925 18251825 13281328 774774 236236
www.HRSonline.org
32
00 11 22 33 44 55
Cumulative Cardiac Mortality in AFFIRM
N, Events (%)Rate 2027, 0 (100) 1926, 42 (2) 1827, 69 (3) 1329, 92 (5) 774, 115 (7) 236, 130 (10) 1, 130 (10)Rhythm 2033, 0 (100) 1932, 37 (2) 1807, 70 (4) 1316, 94 (5) 780, 116 (7) 255, 129 (9) 1, 129 (9)
Steinberg et al. Circulation. 2004;109:1973-1980.
Log-rank statistic=0Log-rank statistic=0PP=.9517=.9517
3030
2525
2020
1515
1010
55
00
Dea
th (
%)
Dea
th (
%)
Rhythm ControlRhythm Control
Rate ControlRate Control
Time (years)
www.HRSonline.org
33
Cumulative Noncardiovascular Mortality in AFFIRM
Steinberg et al. Circulation. 2004;109:1973-1980.
11 22 33 44 55
Time (years)
00
3030
2525
2020
1515
1010
55
00
Dea
th (
%)
Dea
th (
%)
Rhythm ControlRhythm Control
Rate ControlRate Control
Log-rank statistic=11.2Log-rank statistic=11.2PP=.0008=.0008
www.HRSonline.org
34
AFFIRM Results Post-hoc Analysis
The benefits of sinus rhythm areoffset by the toxicity of AADs used in AFFIRM
The benefits of sinus rhythm areoffset by the toxicity of AADs used in AFFIRM
Corley et al. Circulation. 2004;109:1509-1513.
AAD use
Digoxin use
Warfarin use
Sinus rhythm
Time dependent
Covariate
.0005.0005
.0007.0007
<.0001<.0001
<.0001<.0001
PP Value Value
0 0.5 1 1.5 2 2.5
HR 99% CIHR 99% CI
www.HRSonline.org
35
Quality of Life in AF RACE Study
5463
47
8174 77
71
5962 64 6773
7781 84
65
0
20
40
60
80
100Control subjects (n=172) RACE subjects (n=352)
Hagens et al. J Am Coll Cardiol. 2004;43:241-247.
Sco
re (
mea
n)
on
SF
-36
Sca
les
General Health
Physical Functioning
Role Physical
Bodily Pain
Mental Health
Social Functioning
Role EmotionalVitality
www.HRSonline.org
36
A4 Study Results: Quality of Life
0 20 40 60 80 100
AAD Group(n=59)
Ablation Group(n=53)
Physical function
Social function
Mental health
Physical component
Mental componentP=.0106
P=.0174
P=.0018
P=.0024
P=.0012
Jaïs et al. Presented at: Heart Rhythm Society 2006 Annual Scientific Sessions; May 17-20, 2006; Boston, MA.
www.HRSonline.org
37
0
5
10
15
20
25
Frequency Severity
AF (n=152) PTCA (n=69) Healthy (n=47)
a
b
aP<.001 compared with AF patients; bP<.01 compared with AF patients.Dorian et al. J Am Coll Cardiol. 2000;36:1303-1309.
Symptoms in AF
a
b
Qu
alit
y o
f L
ife
Sco
re
www.HRSonline.org
38
Incr
ease
in
Du
rati
on
(se
con
ds)
Sinus Rhythm Atrial Fibrillation
Exercise Duration: AF vs SRSAFE-T Trial
Singh et al. J Am Coll Cardiol. 2006;48:721-730.
P=.01P=.02
0
20
40
60
80
100
8 Weeks 1 Year
www.HRSonline.org
39
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.
www.HRSonline.org
40
AF in Patients With HF
HF may develop or deteriorate with AFProgression of underlying cardiac disease
Uncontrolled heart rate
Antiarrhythmic drug toxicity
AF may exacerbate HF symptoms due toLoss 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.
www.HRSonline.org
41
Impact of Rhythm Control on HF
Study Key Findings
PIAF 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.
www.HRSonline.org
42
Hospitalization for Worsening HFDIAMOND CHF
Dofetilide Events=229Dofetilide Events=229n=762n=762
Placebo Events=290Placebo Events=290n=756n=756
HR=0.75HR=0.7595% CI, 0.63-0.8995% CI, 0.63-0.89PP<.001<.001
Pro
bab
ilit
y o
f S
urv
ival
Pro
bab
ilit
y o
f S
urv
ival
Time (months)Time (months)
0.80.8
0.60.6
0.20.2
0.00.0
1.01.0
0.40.4
00 1212 2424
Torp-Pedersen et al. N Engl J Med. 1999;341:857-865.
www.HRSonline.org
43
0 1 3 6 12
P.001
P.001P.001 P.001
45
0
25
30
35
40
50
55
60
65
70
LV Function Postablation in HF
Hsu et al. N Engl J Med. 2004;351:2373-2383. Month
LV
Eje
ctio
n F
ract
ion
(%
)
www.HRSonline.org
44
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.
www.HRSonline.org
45
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.
www.HRSonline.org
46
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.
www.HRSonline.org
47
AF-CHF Trial of Rate vs Rhythm
0
10
20
30
40
50
CV Death Hospitalization Rate Bradyarrhythmias
Rate
Rhythm
Roy. Presented at: American Heart Association 2007 Scientific Sessions; November 2007; Orlando, Florida.
Per
cen
tP
erce
nt
Also, no differences noted in secondary end points of total mortality, worsening CHF, and stroke
Also, no differences noted in secondary end points of total mortality, worsening CHF, and stroke
www.HRSonline.org
48
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 besymptom-driven
Roy. Presented at: American Heart Association 2007 Scientific Sessions; November 2007; Orlando, FL.
www.HRSonline.org
49
Symptom-driven decisions are recommendedSymptom-driven decisions are recommendedCaveat: symptoms may be subtle or difficult to elicit,Caveat: symptoms may be subtle or difficult to elicit,
so question patients carefullyso question patients carefully
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
Benefits of SR may be offset by AAD
toxicity
QoL studies have indicated better results with SR
www.HRSonline.org
50
Pharmacologic Management of Patients With Newly Discovered AFCardioversion
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
Newly Discovered AFNewly Discovered AFNewly Discovered AFNewly Discovered AF
ParoxysmalParoxysmalParoxysmalParoxysmal
No therapy needed, No therapy needed, unless severe unless severe
symptoms symptoms (eg, hypotension, HF,(eg, hypotension, HF,
angina pectoris)angina pectoris)
No therapy needed, No therapy needed, unless severe unless severe
symptoms symptoms (eg, hypotension, HF,(eg, hypotension, HF,
angina pectoris)angina pectoris)
PersistentPersistentPersistentPersistent
Accept permanent AFAccept permanent AFAccept permanent AFAccept permanent AF
AnticoagulationAnticoagulationand rate control,and rate control,
as neededas needed
AnticoagulationAnticoagulationand rate control,and rate control,
as neededas needed
Rate control andRate control andanticoagulation,anticoagulation,
as neededas needed
Rate control andRate control andanticoagulation,anticoagulation,
as neededas needed
Consider antiarrhythmicConsider antiarrhythmicdrug therapydrug therapy
Consider antiarrhythmicConsider antiarrhythmicdrug therapydrug therapy
Long-term drugLong-term drugprevention unnecessaryprevention unnecessary
Long-term drugLong-term drugprevention unnecessaryprevention unnecessary
Anticoagulation,Anticoagulation,
as neededas needed
Anticoagulation,Anticoagulation,
as neededas neededCardioversionCardioversionCardioversionCardioversion
www.HRSonline.org
51
Druga
Route of Administration Dosageb Potential Adverse Effects
Amiodarone Oral Inpatient: 1.2 to 1.8 g qd in divided doseuntil 10 g total, then 200 to 400 mg qd
maintenance or 30 mg/kg as single doseOutpatient: 600 to 800 mg qd in divided dose
to 10 g total, then 200 to 400 mg qd
Hypotension, bradycardia, QT, TdP (rare), GI upset, constipation,
phlebitis (IV)
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)
>6040 to 6020 to 40
<20
500250125
Contraindicated
QT, TdP; adjust dose for renal function, body size, and age
Recommended Doses of Drugs Effective for Pharmacologic Cardioversion of AF
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.
www.HRSonline.org
52
Druga
Route of Administration Dosageb Potential Adverse Effects
Flecainide Oral 200 to 300 mgc Hypotension, atrial flutter with high ventricular rate
Intravenous 1.5 to 3.0 mg/kg over10 to 20 minc
Ibutilide Intravenous 1 mg over 10 min;repeat 1 mg prn
QT, TdP;
Propafenone Oral 600 mg Hypotension, atrial flutter with high ventricular rate
Intravenous 1.5 to 2.0 mg/kg over10 to 20 minc
Quinidined Oral 0.75 to 1.5 g in divided doses over 6 to 12 h, usually with a rate-
slowing drug
QT, TdP, GI upset, hypotension
Recommended Doses of Drugs Effective for Pharmacologic Cardioversion of AF (cont’d)
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.
www.HRSonline.org
53
Pooled Results for the Efficacy and Adverse Effects of Drugs Used in Acute Conversion of AF
aControl indicates placebo, calcium channel blockers, -blockers, or digoxin.McNamara et al. Ann Intern Med. 2003;139:1018-1033.
Sotalol (3) >.2 0-2
Disopyramide (1) .10 Not reported
Quinidine (3) .02 0-12
Amiodarone (15) <.01 0
Propafenone (14) <.01 0-2
Dofetilide (6) <.01 1-12
Flecainide (5) <.01 0-2
Ibutilide (4) <.01 0-9Strong (# trials)
Moderate (# trials)
Inconclusive (# trials)
Level of EvidenceDrug
Odds Ratio of Conversion Compared With Control
(95% CI)a
Range of Sustained Ventricular Arrhythmia
in All Trials ReportingSide Effects P Value
903025201510501
%
www.HRSonline.org
54
Pharmacologic Management of Patients With Recurrent Paroxysmal Atrial Fibrillation : Sinus Rhythm Maintenance
Recurrent Paroxysmal AFRecurrent Paroxysmal AFRecurrent Paroxysmal AFRecurrent Paroxysmal AF
Minimal orMinimal orno symptomsno symptoms
Minimal orMinimal orno symptomsno symptoms
AnticoagulationAnticoagulationand rate controland rate control
as neededas needed
AnticoagulationAnticoagulationand rate controland rate control
as neededas needed
DisablingDisablingsymptoms in AFsymptoms in AF
DisablingDisablingsymptoms in AFsymptoms in AF
AnticoagulationAnticoagulationand rate controland rate control
as neededas needed
AnticoagulationAnticoagulationand rate controland rate control
as neededas needed
AAD therapyAAD therapyAAD therapyAAD therapyNo drug forNo drug for
prevention of AFprevention of AFNo drug forNo drug for
prevention of AFprevention of AF
AF ablation if AAD AF ablation if AAD treatment failstreatment fails
AF ablation if AAD AF ablation if AAD treatment failstreatment fails
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
www.HRSonline.org
55
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.
www.HRSonline.org
56
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 et al. Fuster et al. J Am Coll CardiolJ Am Coll Cardiol. 2006;48:854-906.. 2006;48:854-906.
www.HRSonline.org
57
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.
www.HRSonline.org
58Fuster et al. Fuster et al. J Am Coll CardiolJ Am Coll Cardiol. 2006;48:854-906.. 2006;48:854-906.
Maintenance of Sinus RhythmMaintenance of Sinus RhythmMaintenance of Sinus RhythmMaintenance of Sinus Rhythm
No (or minimal)heart disease
No (or minimal)heart disease
FlecainidePropafenone
Sotalol
FlecainidePropafenone
Sotalol
AmiodaroneDofetilide
AmiodaroneDofetilide
CatheterablationCatheterablation
HypertensionHypertension
SubstantialLVH
SubstantialLVH
NoNo YesYes
FlecainidePropafenone
Sotalol
FlecainidePropafenone
SotalolAmiodaroneAmiodarone
AmiodaroneDofetilide
AmiodaroneDofetilide
CatheterablationCatheterablation
CatheterablationCatheterablation
CatheterablationCatheterablation
CatheterablationCatheterablation
AmiodaroneDofetilide
AmiodaroneDofetilide
DofetilideSotalol
DofetilideSotalol
Coronary artery disease
Coronary artery disease
HeartfailureHeartfailure
AmiodaroneAmiodarone
www.HRSonline.org
59
Maintenance of Sinus RhythmMaintenance of Sinus RhythmMaintenance of Sinus RhythmMaintenance of Sinus Rhythm
No (or minimal)heart disease
No (or minimal)heart disease
FlecainidePropafenone
Sotalol
FlecainidePropafenone
Sotalol
AmiodaroneDofetilide
AmiodaroneDofetilide
CatheterablationCatheterablation
HypertensionHypertension
SubstantialLVH
SubstantialLVH
NoNo YesYes
FlecainidePropafenone
Sotalol
FlecainidePropafenone
SotalolAmiodaroneAmiodarone
AmiodaroneDofetilide
AmiodaroneDofetilide
CatheterablationCatheterablation
CatheterablationCatheterablation
CatheterablationCatheterablation
CatheterablationCatheterablation
AmiodaroneDofetilide
AmiodaroneDofetilide
DofetilideSotalol
DofetilideSotalol
Coronary artery disease
Coronary artery disease
HeartfailureHeartfailure
AmiodaroneAmiodarone
Fuster et al. Fuster et al. J Am Coll CardiolJ Am Coll Cardiol. 2006;48:854-906.. 2006;48:854-906.
www.HRSonline.org
60
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 amiodaroneand dofetilide
• Utilize -blocker and ACE inhibitor (or ARB) therapyas indicated for HF or LV dysfunction
• Flecainide and propafenone should be avoided
Fuster et al. J Am Coll Cardiol. 2006;48:854-906.
www.HRSonline.org
61
Maintenance of Sinus RhythmMaintenance of Sinus RhythmMaintenance of Sinus RhythmMaintenance of Sinus Rhythm
No (or minimal)heart disease
No (or minimal)heart disease
FlecainidePropafenone
Sotalol
FlecainidePropafenone
Sotalol
AmiodaroneDofetilide
AmiodaroneDofetilide
CatheterablationCatheterablation
HypertensionHypertension
SubstantialLVH
SubstantialLVH
NoNo YesYes
FlecainidePropafenone
Sotalol
FlecainidePropafenone
SotalolAmiodaroneAmiodarone
AmiodaroneDofetilide
AmiodaroneDofetilide
CatheterablationCatheterablation
CatheterablationCatheterablation
CatheterablationCatheterablation
CatheterablationCatheterablation
AmiodaroneDofetilide
AmiodaroneDofetilide
DofetilideSotalol
DofetilideSotalol
Coronary artery disease
Coronary artery disease
HeartfailureHeartfailure
AmiodaroneAmiodarone
Fuster et al. Fuster et al. J Am Coll CardiolJ Am Coll Cardiol. 2006;48:854-906.. 2006;48:854-906.
www.HRSonline.org
62
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 neutraleffects 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.
www.HRSonline.org
63
Maintenance of Sinus RhythmMaintenance of Sinus RhythmMaintenance of Sinus RhythmMaintenance of Sinus Rhythm
No (or minimal)heart disease
No (or minimal)heart disease
FlecainidePropafenone
Sotalol
FlecainidePropafenone
Sotalol
AmiodaroneDofetilide
AmiodaroneDofetilide
CatheterablationCatheterablation
HypertensionHypertension
SubstantialLVH
SubstantialLVH
NoNo YesYes
FlecainidePropafenone
Sotalol
FlecainidePropafenone
SotalolAmiodaroneAmiodarone
AmiodaroneDofetilide
AmiodaroneDofetilide
CatheterablationCatheterablation
CatheterablationCatheterablation
CatheterablationCatheterablation
CatheterablationCatheterablation
AmiodaroneDofetilide
AmiodaroneDofetilide
DofetilideSotalol
DofetilideSotalol
Coronary artery disease
Coronary artery disease
HeartfailureHeartfailure
AmiodaroneAmiodarone
Fuster et al. Fuster et al. J Am Coll CardiolJ Am Coll Cardiol. 2006;48:854-906.. 2006;48:854-906.
www.HRSonline.org
64
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.
www.HRSonline.org
65
Maintenance of Sinus RhythmMaintenance of Sinus RhythmMaintenance of Sinus RhythmMaintenance of Sinus Rhythm
No (or minimal)heart disease
No (or minimal)heart disease
FlecainidePropafenone
Sotalol
FlecainidePropafenone
Sotalol
AmiodaroneDofetilide
AmiodaroneDofetilide
CatheterablationCatheterablation
HypertensionHypertension
SubstantialLVH
SubstantialLVH
NoNo YesYes
FlecainidePropafenone
Sotalol
FlecainidePropafenone
SotalolAmiodaroneAmiodarone
AmiodaroneDofetilide
AmiodaroneDofetilide
CatheterablationCatheterablation
CatheterablationCatheterablation
CatheterablationCatheterablation
CatheterablationCatheterablation
AmiodaroneDofetilide
AmiodaroneDofetilide
DofetilideSotalol
DofetilideSotalol
Coronary artery disease
Coronary artery disease
HeartfailureHeartfailure
AmiodaroneAmiodarone
Fuster et al. Fuster et al. J Am Coll CardiolJ Am Coll Cardiol. 2006;48:854-906.. 2006;48:854-906.
www.HRSonline.org
66
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.
www.HRSonline.org
67
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.
www.HRSonline.org
68
Lafuente-Lafuente et al. Arch Intern Med. 2006;166:719-728.
AF Recurrence
Odds Ratio (95% CI)
Class IA
11,322 patients; 44 trials
Summary of Antiarrhythmic Trials for SR Maintenance
Class IC
(Class II) Metoprolol
Class III:
Amiodarone
Sotalol
0.10 1 10Odds Ratio (95% CI)
Disopyramide vs other Class I drugs
Flecainide vs propafenone
Class I drugs
Sotalol
Sotalol vs class I except quinidine
0.10 1 10
www.HRSonline.org
69
Pritchett et al. Am J Cardiol. 2002;92:941-946; Meinerz et al. Am J Cardiol. 2002;90:1300-1306.
RAFT (n=523)RAFT (n=523)
AF recurrence at 1 year (%)
ERAFT 325 mg BIDERAFT 425 mg BID
RAFT 225 mg BIDRAFT 325 mg BIDRAFT 425 mg BID
0 0.25 0.5 0.75 1
Propafenone better
New Formulations of AADsPropafenone RAFT and ERAFT Studies
ERAFT (n=293)ERAFT (n=293)
Pro
po
rtio
n F
ree
of
Eve
nts
0 50 100 150 200 250 3000
0.2
0.4
0.6
0.8
1
Days
PlaceboPropafenone 225 BIDPropafenone 325 BIDPropafenone 425 BID
P 425 BID vs placebo: OR, 0.604 (95% CI, 0.433-0.843) P=.002
www.HRSonline.org
70
Sotalol vs Amiodarone SAFE-T
Singh et al. N Engl J Med. 2005;352:1861-1872.
1.01.0
0.90.9
0.80.8
0.70.7
0.60.6
0.50.5
0.40.4
0.30.3
0.20.2
0.10.1
SotalolSotalol
PlaceboPlacebo
Amiodarone809/487
DaysDays
Fre
e F
rom
AF
Rec
urr
ence
(O
T/I
TT
)F
ree
Fro
m A
F R
ecu
rren
ce (
OT
/IT
T)
Sotalol 209/74
Placebo 13/6
300300 1000100090090080080070070060060050050040040020020010010000
www.HRSonline.org
71
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.
www.HRSonline.org
72
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
www.HRSonline.org
73
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.
www.HRSonline.org
74
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.
www.HRSonline.org
75
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 et al. Fuster et al. J Am Coll CardiolJ Am Coll Cardiol. 2006;48:854-906.. 2006;48:854-906.
www.HRSonline.org
76
Valsartan and AF in VALIANT
Maggioni et al. Am Heart J. 2005;149:548-557.
Est
imat
ed P
rob
abil
ity
of
AF
Est
imat
ed P
rob
abil
ity
of
AF
Months Since RandomizationMonths Since Randomization
0.000.00
0.050.05
0.100.10
0.150.15
00 33 66 99 1212 1515 1818 2121 2424 2727
Log-rank test, Log-rank test, PP=.0001=.0001
ValsartanPlacebo
www.HRSonline.org
77
Candesartan and AF in CHARM
Ducharme et al. Am Heart J. 2006;152:86-92.
0.686 (0.470-1.002)
0.856 (0.617-1.187)
0.894 (0.618-1.295)
0.779 (0.608-0.997), .0472
0.812 (0.662-0.998), .0476
Alternative
Added
Preserved
2 Low EF trials
Overall
P heterogeneity=0.57 Odds Ratio (95% CI), P Value
0.2 0.4 0.6 0.8 1.0 1.2 1.4
Odds Ratio (95% CI)
www.HRSonline.org
78
Kaplan-Meier Plot of Occurrence of Postop AF
Calo et al. J Am Coll Cardiol. 2005;45:1723-1728.
Pat
ien
ts F
ree
of
AF
(%
)P
atie
nts
Fre
e o
f A
F (
%)
Days After SurgeryDays After Surgery
00 11 22 33 44 55 66 77 88 99 1010 1111 1212 1313 1414 1515 1616 1717 18185050
6060
7070
8080
9090
100100
Control GroupControl Group
Log-rank, Log-rank, PP=.009=.009
PUFAs GroupPUFAs Group
www.HRSonline.org
79
Ablation
Catheter-basedSecond-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
SurgicalGenerally MAZE procedure, utilized in patients already undergoing cardiac procedure
Fuster et al. Fuster et al. J Am Coll CardiolJ Am Coll Cardiol. 2006;48:854-906.. 2006;48:854-906.
www.HRSonline.org
80
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
Calkins et al. Heart Rhythm. 2007;4:1-46.
www.HRSonline.org
81
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
www.HRSonline.org
82
Patient Selection for Ablation
More Optimal Patient Less Optimal Patient
Variable
Symptoms Highly symptomatic Minimally symptomatic
Class I and III drugs failed 1 0
AF type Paroxysmal Long-standing persistant
Age Younger (<70 years) Older (70 years)
LA size Smaller (<5.0 cm) Larger (5.0 cm)
Ejection fraction 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
Courtesy of Hugh Calkins, MD.
www.HRSonline.org
83
Controlled Trials of AF Ablation Patients Free of AF (% at 1 Year)
87
56
75
8679
86
0
10
20
30
40
50
60
70
80
90
100
RAAFT CACAF A4 APAF Milan/NR PABA CHF
Ablation Control
Courtesy of Jeremy N. Ruskin, MD, Massachusetts General Hospital.
Per
cen
t
www.HRSonline.org
84
Pooled Studies: Observational and RCTs Patients Free of AF at 1-2 Years (%)
23%
77%
0
20
40
60
80
100
Free of AF Recurrent AF
10%
76%
0
20
40
60
80
100
Ablation Control
RCT: N=517; 4 StudiesOBS: N=1965; 8 Studies
Courtesy of Jeremy N. Ruskin, MD, Massachusetts General Hospital.
Per
cen
t
Per
cen
t
www.HRSonline.org
85
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.
www.HRSonline.org
86
Success Rates With Ablation Worldwide Survey
0
10
20
30
40
50
60
70
80
90
100
0-3 4-6 7-9 10-12 13-18 19-24 >24
Success Without AADs Success With AADs Overall Success
Cappato et al. Circulation. 2005;111:1100-1105.
Rat
es (
%)
Rat
es (
%)
Range of Follow-up (months)Range of Follow-up (months)
www.HRSonline.org
87
Worldwide Survey on Ablation for AF Major Complications
Cappato et al. Circulation. 2005;111:1100-1105.
0
0.5
1
1.5
2
Death Tamponade Stroke TIA PVstenosis
Infection,pneumo/Hemo-thorax,
diaphragmparalysis
Femoralpseudo-
aneurysm,AV
fistula
Valvedamage,
Aodissection
Per
cen
t
www.HRSonline.org
88
AF-Free Survival Ablation vs Pharmacologic Therapy
Pappone et al. J Am Coll Cardiol. 2003;42:185-197.
No. at riskNo. at riskAblationAblation 589589 507507 479479 379379 282282 217217 135135MedicalMedical 582582 456456 354354 277277 207207 141141 9797
AF
-Fre
e A
F-F
ree
Su
rviv
al P
rob
abil
ity
(%)
Su
rviv
al P
rob
abil
ity
(%)
100100
8080
6060
4040
2020
0000 180180 360360 540540 720720 900900 10801080
Days of Follow-upDays of Follow-up
Ablation GroupAblation Group
Medical GroupMedical Group
www.HRSonline.org
89
Freedom From AF Following Pulmonary Vein Isolation Normal vs Impaired LV Function
Chen et al. J Am Coll Cardiol. 2004;43:1004-1009.
3030 6060 9090 120 150150 180180 210210 240240 270 300300 330 360360 390390 4204204040
5050
6060
7070
8080
9090
100100
Cu
mu
lati
ve A
F-F
ree
Su
rviv
alC
um
ula
tive
AF
-Fre
e S
urv
ival
Follow-up Time (days)Follow-up Time (days)
Impaired LV Function (n=94)Impaired LV Function (n=94)
Normal LV Function (n=283)Normal LV Function (n=283)
P=.03
www.HRSonline.org
90
RAAFT Outcomes at 1 Year
No significant difference in Severe, moderate, or mild pulmonary vein stenosisa
Bradycardia
Bleeding
Thromboembolic eventsb
Significant difference Hospitalization
• AAD (54%) vs PVI (9%)
• P<.001
Symptomatic AF recurrence
• AAD (63%) vs PVI (13%)
• P<.001 Su
rviv
al F
ree
From
Atr
ial F
ibril
latio
nSu
rviv
al F
ree
From
Atr
ial F
ibril
latio
n
1.01.0
0.90.9
0.80.8
0.70.7
0.60.6
0.50.5
0.40.4
0.30.3
0.20.2
0.10.1
0.00.00.00.0 100100 200200 300300
Follow-up (days)Follow-up (days)
Antiarrhythmic Antiarrhythmic Drug GroupDrug Group
PVI GroupPVI Group
www.HRSonline.org
91
CACAF Study of Ablation in Drug-Refractory AF
Stabile et al. Eur Heart J. 2006;27:216-221.
Atrial Arrhythmia–Free Survival Curves After the Blanking Period
MonthsMonths
Per
cen
t S
urv
ival
Per
cen
t S
urv
ival
100100
8080
6060
4040
2020
00
00 11 22 33 44 55 66 77 88 99 1010 1111 1212
PP<.001<.001
Ablation Group (n=68)Ablation Group (n=68)
Control Group (n=69)Control Group (n=69)
www.HRSonline.org
92
A4 Study Results
Jaïs et al. Presented at: Heart Rhythm Society 2006 Annual Scientific Sessions;May 17-20, 2006; Boston, MA.
0
10
20
30
40
50
60
70
80 Ablation Group (n=53) AAD Group (n=59)
Per
cen
t
Free of Arrhythmia Recurrenceat 1 Year (%)
Discontinued OralAnticoagulation (%)
www.HRSonline.org
93
A4 Study Results
Kaplan-Meier Plots for Time to AF Recurrence
75%
1.0
7%
Pro
bab
ilit
y o
f N
o
AF
Rec
urr
ence
0.9
0.80.7
0.6
0.50.4
0.30.2
0.10.0
0 100 500
Follow-up Days
200 300 400
P<.0001 (log-rank test)
Ablation
Antiarrhythmic Drug
Jaïs et al. Presented at: Heart Rhythm Society 2006 Annual Scientific Sessions; May 17-20, 2006; Boston, MA.
www.HRSonline.org
94
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
www.HRSonline.org
95
CABANA Trial
Packer. Presented at 2005 Scientific Sessions of the American Heart Association. November 13-16; Dallas, TX.
Recent-onset AFEligible 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)
Primary Ablation(technique at
operator discretion)
Drug Therapy(rate or rhythm control[at operator discretion]with anticoagulation)
Drug Therapy(rate or rhythm control[at operator discretion]with anticoagulation)
ContinuedAnticoagulation
ContinuedAnticoagulation
DiscontinuedAnticoagulation
DiscontinuedAnticoagulation
www.HRSonline.org
96
Improvement in LV Function and Dimensions After Ablation in Patients With CHF
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.
70
60
50
40
30
025
35
45
55
65
LV E
ject
ion
Frac
tion
(%)
0 1 3 6 12Month
7570
6055
04550
65
LV E
nd-D
iast
olic
D
iam
eter
(mm
)
0 1 3 6 12Month
P<.001P<.001P<.001P<.001
P<.001P<.001P<.001P<.001
P=.001P=.001P<.001P<.001P=.001P=.02P=.03P=.001
LV E
nd-S
ysto
lic
Dia
met
er (m
m) 55
03035404550
0 1 3 6 12Month
40
25
20
0
35
LV F
ract
iona
l Sh
orte
ning
(%)
0 1 3 6 12Month
30
15
www.HRSonline.org
97
Estimated Outcomes and Risks of AF Ablation
Courtesy of Hugh Calkins, MD.
Success Single Procedure Multiple Procedure
Optimal patient 60%-80% 80%-90%
Less optimal patient 50%-70% 70%-80%
Poor candidate <40% 40%-60%
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%
www.HRSonline.org
98
Common Lesions Performed in AF Ablation
Calkins et al. Heart Rhythm. 2007;4:1-46.
LSPV
LIPV
RSPV
IVC
RIPV
SVC
LSPV
LIPV
RSPV
IVC
RIPV
SVC
LSPV
LIPV
RSPV
IVC
RIPV
SVC
LSPV
LIPV
RSPV
IVC
RIPV
SVC
www.HRSonline.org
99
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.
www.HRSonline.org
100
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.
www.HRSonline.org
101
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.
www.HRSonline.org
102
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.
www.HRSonline.org
103
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.
www.HRSonline.org
104
Take-Home Points
• Heart rate control at rest and with exertion is critical foreither 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