Atrial Fibrillation Rate or Rhythm Control Saeed Oraii MD Tehran Arrhythmia Clinic April 2007 Shiraz

Atrial Fibrillation

Rate or RhythmControl

Saeed Oraii MD

Tehran Arrhythmia Clinic

April 2007

Shiraz


• 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”


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


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


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


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

)


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


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


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)


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


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


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



• Anticoagulation

• Rate Control

– Pharmacologic


• Rhythm Control




• Surgery (maze)


AF: Pharmacologic Rate Control

• Digitalis

• Beta Blockers

• Calcium Channel Blockers (verapamil, diltiazem)

• Amiodarone (in special settings)


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


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


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


AVN Ablation and PPM• Paroxysmal AF –

DDDR pacing with mode switch

• Permanent AF – VVIR pacemaker

• Biventricular devices may be better in preserving LV function


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


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)



• Anticoagulation

• Rate Control (ventricular response)

– Pharmacologic


• Rhythm Control




• Surgery (maze)


AF: Rhythm Control Options


• 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


Proarrhythmia Drug-induced Torsade


Rhythm vs Rate control Trials

• PIAF– Lancet 2000

• AFFIRM – NEJM 2002

• RACE– NEJM 2002

• STAF– JACC 2003

• Hot CAFÉ– Chest 2004


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.


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.


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


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


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


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)


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


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


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


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


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%


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


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


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


Pulmonary Vein Triggers


Segmental Ablation


Segmental Ablation


Circumferential Ablation






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


Can Ablation Improve Survival?

Pappone et al JACC 2003; 42:186-197


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


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)


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


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?


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:


Summing up the evidence


P O?

Who could we offer rhythm control to?


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)

Tehran Arrhythmia ClinicTehran Arrhythmia Center

Tehran Arrhythmia Clinicwww.IranEP.org

Documents

Atrial Fibrillation Rate or Rhythm Control Saeed Oraii MD Tehran Arrhythmia Clinic April 2007 Shiraz