Atrial Fibrillation Rate or Rhythm Control Saeed Oraii MD Tehran Arrhythmia Clinic April 2007...
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Transcript of Atrial Fibrillation Rate or Rhythm Control Saeed Oraii MD Tehran Arrhythmia Clinic April 2007...
Atrial Fibrillation
Rate or RhythmControl
Saeed Oraii MD
Tehran Arrhythmia Clinic
April 2007
Shiraz
Tehran Arrhythmia Clinic
• First described by Sir William Harvey in 17th century:
observed chaotic motion of atria in open chest animal
• Heart rhythm irregularity first described in 1903 by Hering
• ECG findings described in 1909 by Sir Thomas Lewis:
“irregular or fibrillatory waves and irregular ventricular response” or “absent atrial activity with grossly irregular ventricular response”
“Delirium Cordis”
Tehran Arrhythmia Clinic
Atrial fibrillation accounts for 1/3 of
all patient discharges
with arrhythmia as
principal diagnosis
2% VFBaily D. J Am Coll Cardiol. 1992;19(3):41A.
34% Atrial
Fibrillation
18% Unspecified
6% PSVT
6% PVCs
4% Atrial Flutter
9% SSS
8% Conduction
Disease
3% SCD
10% VT
Tehran Arrhythmia Clinic
Incidence and Prevalence
• Prevalence increases with age– 4.8 % in the 70-79 age group
• Increases to– 8.8% in the 80-89 age group
• During the next 7-8 years, the number of people over the age of 80 is expected to quadruple
Tehran Arrhythmia Clinic
Atrial Fibrillation Demographics by Age
Adapted from Feinberg WM. Arch Intern Med. 1995;155:469-473.
U.S. population
Population withatrial fibrillation
Age, yr
<5 5-9
10-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
80-84
85-89
90-94
>95
U.S. populationx 1000
Population with AFx 1000
30,000
20,000
10,000
0
500
400
300
200
100
0
Tehran Arrhythmia Clinic
Projected AF Prevalence: OLMSTED COUNTY DATA
12% observed increase in AF incidencebetween 1980 and 2000
Miyasaka et al, Circulation 2005; 114:119
Tehran Arrhythmia ClinicAdapted from Go. JAMA. 2001;285:2370.
0
1
2
3
4
5
6
7
2.3 2.4 2.72.9 3.3
3.84.3
4.85.2 5.4
5.6
Projections of AF Prevalence in the United
States
Ad
ult
s W
ith
AF
(m
illio
ns
)
Tehran Arrhythmia Clinic
Complications and Prognosis
• 5-fold increase in risk of stroke and thromboembolism
• Strokes associated with AF are more severe
• Death: OR 1.5 –1.9• AF worsens diagnosis in CHD and HF• Impairment in cognitive function• Reduced exercise tolerance
Tehran Arrhythmia Clinic
The 10,000 Foot View …• The prevalence of AF is rapidly increasing
– Aging population– True increase in incidence– Lifetime risk of AF at age 40 is 25%
• AF is a progressive disorder – Cardiac remodeling due to genetic factors, acquired
disease, atrial fibrillation itself– Up to 25% of initially self-terminating AF will become
chronic in 5 years, > 50% at 10 years
• Associated with substantial risk of adverse outcomes beyond immediate symptoms– Stroke– Congestive heart failure– Death
• Associated with substantial increase in health care costs and resource utilization
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Therapeutic Approaches to Atrial Fibrillation
• Anticoagulation
• Rate Control (ventricular response)
– Pharmacologic
– Catheter modification/ablation of AV node
• Rhythm Control
– Antiarrhythmic suppression
– Curative procedures
• Catheter ablation
• Surgery (maze)
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Thromboembolic prophylaxis
• Thromboembolic events do not just occur in permanent AF
• Consider treatment for all patients with AF• Clustering of events at the time of onset• 62% RR reduction with adjusted dose
Warfarin• 22% RR reduction with Aspirin• 0.9% absolute risk increase of major
haemorrhage with Warfarin
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Risk Assessment Tools
• Do not apply to valvular heart disease
• Risk of thromboembolism depends on other risk factors in patients with AF
• Various risk assessment tools available
• There are differences between CHAD2 and the tool favoured in the NICE guidelines
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CHAD 2 Score
Adjusted Annual Stroke Rate (%)
NNT Risk of major bleed (per 100 patient years)
0 1
1.9 2.8
80 55
Aspirin 1.5
2 3 4 5 6
4.0 5.9 8.5 12.5 18.2
38 26 18 12 8
Warfarin 2.2
CHAD2 risk assessment tool
Congestive heart failure 1 History of hypertension 1 Age > 75years 1 Diabetes 1 Prior stroke or TIA 2
PLEASE NOTE
The benefit of Warfarin outweighs risk when
CHAD2 Score > 2
C H A D 2
CHAD2 Score
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Therapeutic Approaches to Atrial Fibrillation
• Anticoagulation
• Rate Control
– Pharmacologic
– Catheter modification/ablation of AV node
• Rhythm Control
– Antiarrhythmic suppression
– Curative procedures
• Catheter ablation
• Surgery (maze)
Tehran Arrhythmia Clinic
AF: Pharmacologic Rate Control
• Digitalis
• Beta Blockers
• Calcium Channel Blockers (verapamil, diltiazem)
• Amiodarone (in special settings)
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Atrial Fibrillation: Rate Control
• Essential in all patients
• Persistent tachycardia rates can induce cardiomyopathy and heart failure
• Occasional follow-up holter monitor to ascertain rate control
• Target: 60-80 bpm rest
90-115 bpm with exercise
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Adequate Rate Control• AFFIRM
– Average HR of ≤80 beats/min at rest and either a maximum of ≤110 bpm during a 6-minute walk or an average of <100 bpm on 24-hour Holter monitoring, with the rate not exceeding 110% of maximum predicted age-adjusted exercise rate.
• RACE– Resting heart rate on a 12-lead ECG of ≤100
beats/min
• HOT CAFÉ– A heart rate of 70–90 beats/min on a resting 12-lead
ECG and ≤140 beats/min during moderate exercise
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Digoxin: some words of caution
• Oldest and most commonly prescribed drug for control of ventricular rate
• Predominant acute effect is mediated by the autonomic nervous system
• An important slowing effect of the AV node is mediated by enhanced vagal tone
• Not effective during periods of increased sympathetic tone
• Not effective in paroxysmal atrial fibrillation
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AVN Ablation and PPM• Paroxysmal AF –
DDDR pacing with mode switch
• Permanent AF – VVIR pacemaker
• Biventricular devices may be better in preserving LV function
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AVN Ablation and PPM• Pros:
– Controls and regularizes ventricular rate– Effective at improving symptoms, QOL and ? LV
function
• Cons:– Permanent– Detrimental effects of RV pacing, especially if
reduced LV function already– Still have thromboembolic risk– Continue to have loss of atrial contractile function
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Ablate and pace• Suitable for
– AF with symptomatic rapid ventricular rate unresponsive to drug Rx, or when drug Rx not tolerated
– Curative AF ablation not suitable or not possible
– Patients with a bradycardia indication for pacing
– More suited to elderly (less requirement for generator changes and lead revision)
Tehran Arrhythmia Clinic
Therapeutic Approaches to Atrial Fibrillation
• Anticoagulation
• Rate Control (ventricular response)
– Pharmacologic
– Catheter modification/ablation of AV node
• Rhythm Control
– Antiarrhythmic suppression
– Curative procedures
• Catheter ablation
• Surgery (maze)
Tehran Arrhythmia Clinic
AF: Rhythm Control Options
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• Disadvantages
• High recurrence rate
• High long-term cost
• Non-curative
• Adverse effects
• Potential proarrhythmia
Antiarrhythmic Therapy for Atrial Fibrillation
• Advantages
• High efficacy for somepatients, at leastinitially (< 50% of all patients)
• Low initial cost
• Noninvasive
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Proarrhythmia Drug-induced Torsade
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Rhythm vs Rate control Trials
• PIAF– Lancet 2000
• AFFIRM – NEJM 2002
• RACE– NEJM 2002
• STAF– JACC 2003
• Hot CAFÉ– Chest 2004
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Rate vs. Rhythm control• None of the RCTs found rate control inferior
in terms of mortality or quality of life.• One study showed rate control reduced the
mortality in patients without Heart Failure, in over 65s and in patients with CHD.
• Reduced rates of hospitalization and adverse events with rate control
• No difference in the rate of thromboembolic or hemorrhagic events
• Rate control is more cost effective.
Tehran Arrhythmia Clinic
AFFIRM: Atrial Fibrillation Follow-up Investigation of Rhythm Management
DesignMulticenter, randomized, open, parallel group
Patients4060 patients who had atrial fibrillation that was likely to be recurrent, with other risk factors for stroke or death. Patients with contraindications for anticoagulant therapy were excluded
Follow up and primary endpointPrimary endpoint: all-cause mortality. Mean 3.5 years follow up.
Treatment• Rate control: >1 rate-controlling drugs, plus anticoagulant, or• Rhythm control: >1 antiarrhythmics, plus cardioversion as
necessary; anticoagulant encouraged but could be discontinuedNonpharmacological therapies and changes in pharmacological therapy, including crossover between groups, were permitted.
The AFFIRM Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002;347:1825–33.
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AFFIRM
Age (years)a
Female (%)
Predominant cardiac diagnosis (%)Coronary artery diseaseCardiomyopathyHypertensionValvular diseaseOtherNo apparent heart disease
History of congestiveheart failure (%)
Baseline characteristics
70
39
265515112
23
Overall(n=4060)
70
41
255525113
23
Rate control(n=2027)
70
38
285505112
23
Rhythm control(n=2033)
AFFIRM Investigators. N Engl J Med 2002;347:1825–33.a Mean
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AFFIRM
Rate control: data availableDigoxinBeta-blockerDiltiazemVerapamil
Rhythm control: data availableAmiodaroneSotalol
Drugs used in rate and rhythm control groupsa
1957949915583187
126521
No.
(48.5)(46.8)(29.8)(9.6)
(0.2)b
(0.1)b
(%)
Used drug forinitial therapy
AFFIRM Investigators. N Engl J Med 2002;347:1825–33.
Rate control
202714321380935340
202720784
No.
(70.6)(68.1)(46.1)(16.8)
(10.2)(4.1)
(%)
Used drugat any time
126641727619856
1960735612
No.
(32.9)(21.8)(15.6)(4.4)
(37.2)(31.2)
(%)
Used drug forinitial therapy
Rhythm control
203311061008610204
20331277841
No.
(54.4)(49.6)(30.0)(10.0)
(62.8)(41.4)
(%)
Used drugat any time
a A few patients in the rate and a significant number in the rhythm control groups received other antiarrhythmicsb These patients immediately crossed over to the rhythm control group, a protocol violation
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AFFIRM
Goals of AFFIRM– Resting HR <80– 24 hr Holter average <100 bpm. No HR above 110%
of age predicted maximum– HR <110 on a six min walk
Anticoagulate:-If over 48hrs of AF, must anticoag before cardioversion.-Warfarin (6-12wks), heparin, LMWH-Aspirin-If Lone AF aspirin or nothing
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AFFIRM - RESULTS -
• No significant difference between rate control and rhythm control groups in:
—all-cause mortality (25.9 vs. 26.7%, P=0.08)
—composite secondary endpoint (death, disabling stroke or anoxic encephalopathy, major bleeding, and cardiac arrest)
—total number of central nervous system events (stroke or hemorrhage)
• Nonsignificant trends were towards reduction of all-cause mortality and CNS events with rate control, compared with rhythm control
• Significantly reduced hospitalization in rate control group compared with rhythm control
• Fewer patients initially assigned to rate control crossed over to rhythm control than crossed from rhythm to rate control (15 vs. 38% at 5 years; P<0.001)
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AFFIRM - RESULTS -
Years after randomization
Cumulativemortality
(%)
00
1 2 3 4 5
5
10
15
20
25
30
All-cause mortality
AFFIRM Investigators. N Engl J Med 2002;347:1825–33.
Rhythm control
Rate control
P=0.08
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AFFIRM - RESULTS -
P
Primary endpoint:all-cause mortality
Secondary endpoint:death, disabling stroke, disabling encephalopathy, majorbleeding, and cardiac arrest
CNS eventa
Hospitalization
0.08
0.33
0.93
<0.001
Primary and selected secondary endpoints
310
416
105
1220
No.
(25.9)
(32.7)
(7.4)
(73.0)
(%)
Rate control(n=2027)
356
445
106
1374
No.
(26.7)
(32.0)
(8.9)
(80.1)
(%)
666
861
211
2594
No.
(26.3)
(32.3)
(8.2)
(76.6)
(%)
Overall(n=4060)
Rhythm control(n=2033)
AFFIRM Investigators. N Engl J Med 2002;347:1825–33.a Ischemic stroke, or primary intracerebralor subdural/subarachonoid hemorrhage
Tehran Arrhythmia Clinic
AFFIRM - SUMMARY-
In patients who had atrial fibrillation and were at high risk for stroke or death, comparison of rate and rhythm control showed:
• No significant difference in all-cause mortality, composite secondary endpoint (death, disabling stroke, disabling anoxic encephalopathy, major bleeding, cardiac arrest) or ischemic stroke
• A nonsignificant trend to reduction of all-cause mortality and stroke with rate control
• Reduced hospitalization with rate control
Crossover to the other control method was lower in the rate control group
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RACE Trial Rate Control vs. Electrical Cardioversion
• 522 patients with persistent atrial fibrillation or atrial flutter (24 hours-1 year)
• 2 cardioversions within 1 year • Rate control to HR < 100 bpm and no symptoms • Rhythm control: Sotalol followed by Flecainide or
Propafenone followed by Amiodarone • Primary endpoint: cardiovascular death, admission
or CHF, Thromboembolic events, severe bleeding, pacemaker implantation or severe anti-arrhythmic side effects
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RACE Study
522 Patients
256 patients – rate control
266 patients – cardioversion
Outcome RateRhythm
Death/Stroke 17.2% 22.6%
Mortality 7% 6.7%
CHF 3.5% 3.4%
Hypertension Subgroup: Combined Endpoints:
Mortality/thromboembolism/severe complication
RateRhythm
19% 31%
Tehran Arrhythmia Clinic
Rate vs. Pharmacologic Rhythm control
Favor of rate control
• Persistent AF• History of AF more than 1
year• Less symptomatic• > than 65 years of age• History of HTN• Previous AAD failure• LA > 60 mm • No history of CHF• Patient preference
Favor of rhythm control
• Paroxysmal AF• First episode of AF• More Symptomatic• < than 65 years of age• No history HTN• No Previous AAD failure• LA < 60 mm • History CHF• Patient preference
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Who is under-represented in AFFIRM?
• Young patients • Paroxysmal atrial fibrillation• CHF
• Reduced systolic function• Isolated diastolic dysfunction
• Disabling symptoms of AF
What therapies are under-represented ?
Other (newer?) drugsNon-pharmacologic therapies
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What AFFIRM Does Not Tell Us?
• Optimal management for patients with moderate or severe disabling symptoms related to atrial fibrillation
• Outcome if better tools to maintain sinus rhythm were available
• Long-term implications of rate vs. rhythm control (mean duration of follow-up only 3.5 years)
Nonpharmacological Approaches to
Atrial Fibrillation
1. Pacemaker therapy
2. Ablation
3. Surgery
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Pulmonary Vein Triggers
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Segmental Ablation
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Segmental Ablation
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Circumferential Ablation
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Circumferential Ablation
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Circumferential Ablation
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Randomized Trials of Ablation for PAF
PAPPONE (N=198)
JAIS (N=112)
WANZI (N=70)
STABILE (N=137)
0 10 20 30 40 50 60 70 80 90 100
ONE YEAR AF-FREE
AAD ABL
• STABILE: EHJ 2006 27:216-221; prior AAD failure; 1 episode/mo 6 mo duration; included 32% persistent AF; AAD given to ablation group; PVI+MI+CTI; blanking 1 mo; HM + 3 mo daily event montioring; endpoint 30 sec AF
• WANZI: JAMA 2005: 293:2634-2640); No prior AAD; 1 episode/mo 3 mo duration; PVAI; blanking 2 mo; HM + 1,3 mo event monitoring; endpoint 15 sec AF. Pilot study for RAAFT (400 pt trial)
• JAIS: HRS Scientific Sessions 2006; Prior AAD failure, 2 episodes/mo 6 mo duration; PVI+CTI+lines; blanking 3 mo; HM + symptom diaries; endpoint 3 min AF or palpitations
• PAPPONE: JACC 2006 in press, doi 10:1016. Limited prior AAD; 2 episodes /mo 6 mo duration;CPVI+CTI+lines; blanking 6 wks, daily event monitoring; endpoint 30 sec AF Major complications in 1-4% of ablation groups
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Can Ablation Improve Survival?
Pappone et al JACC 2003; 42:186-197
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Catheter ABlation Versus ANtiarhythmic Drug Therapy for
Atrial Fibrillation (CABANA)• Randomized trial comparing ablation to best drug therapy (rate
or rhythm control)
• Primary endpoint: mortality (powered for 30% mortality reduction assuming 12% 3 yr mortality in drug group)
• Secondary endpoints:– Composite (death, disabling stroke, serious bleeding, cardiac arrest)
– Freedom from AF recurrence (irrespective of symptoms)
– Health care costs and resource utilization
– Quality of life
• Planned 3000 pts, 120 enrolling centers
• Pilot phase approved starting late 2006, full study pending approval
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Catheter ABlation Versus ANtiarhythmic Drug Therapy for Atrial
Fibrillation (CABANA)• Enrollment criteria
> age 65, or < 65 with > 1 risk factor for stroke
Eligible for both AF, and at least 2 membrane active drugs or 3 rate control drugs
Paroxysmal (at least 2 episodes in prior 3 mo), persistent or chronic AF
• Ablation technique to include PVI + additional procedures (lines, CFAE, ganglionated plexi)
• 3 month blanking period in both groups (repeat ablation, or change in AAD permitted). Crossover to ablation in drug group strongly discouraged
• Follow-up with holter monitor, daily TTM (2 wks every 6 mo), and ILR (proposed 750 pt substudy)
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Potential benefits Symptomatic
benefit No need for
AADs ? Thromboembolic
benefit ? Mortality benefit?
Potential harm Death Stroke Exacerbation of
arrhythmia (flutters)
Tamponade / PV stenosis
Failure and redo rate
Curative AF ablation
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Patients with symptomatic, drug refractory atrial fibrillation, should be judged on an individual basis according to the Ablation Centre’s experience
Ideally, the patient should satisfy the following criteria:
A rhythm control strategy is preferred and other therapeutic options are not as appropriate
Attempts with at least 1 AAD have failedPreferably <70 (certainly <80!)Preferably normal heart or mild-moderate structural
heart disease (LVEF>45%?)Preferably not a very dilated left atriumPrepared to accept risk of stroke (based on patient
factors and institution’s results)Prepared to accept failure (based on institution’s
results)Prepared to accept need for a re-do procedure (based
on institution’s results)
Who Should be Offered AblationHere and Now?
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Will need Warfarin 1 month before and minimum 3 months after procedure
May require ongoing AA drug Rx AFib and LA flutter often occur in first few
months after procedure. True success should be assessed after 3-6 months
Permanent AFib may be considered, but ~50% success rate
Points to remember:
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Summing up the evidence
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P O?
Who could we offer rhythm control to?
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Key Messages• All patients with AF need thromboembolic risk assessment.
• Rate control will benefit most of our patients but adequate rate control is necessary.
• Digoxin is not first line drug for rate control
• The plethora of antiarrhythmic drugs currently available for the treatment of AF is a reflection that none is wholly satisfactory, each having limited efficacy combined with poor safety and tolerability.
• Catheter ablation considered a Class 2a indication for patients with symptomatic persistent or paroxysmal AF after failure of an initial trial of AAD therapy (AHA/ACC/ESC 2006 Guidelines)
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