AFib Management and the Role of Catheter Ablation

AFib Management and the Role of Catheter Ablation

Slide Kit Structure

Section I. AFib Overview

Section II. Clinical Management of AFib

Section III. Catheter Ablation for the Treatment of AFib

Section I:AFib Overview

Atrial fibrillation

•Atrial fibrillation (AFib) is a common disease that causes the upper chambers of the heart (atria) to beat rapidly and in an uncontrolled manner (fibrillation).

•Uncoordinated, rapid beating of the atria affects the flow of blood through the heart, causing an irregular pulse and sometimes a sensation of fluttering in the chest.

Classification of AFib Subtypes

Paroxysmal Spontaneous termination usually < 7 days and most often < 48 hours

Persistent Does not interrupt spontaneously and needs therapeutic intervention for termination(either pharmacological or electrical cardioversion)

Permanent AFib in which cardioversion is attempted but unsuccessful, or successful but immediately relapses, or a form of AFib for which a decision was taken not to attempt cardioversion

Levy S, et al. Europace (2003) 5: 119

Prevalence of AFib

General population-based prevalence

0.95%

Go AS, et al. JAMA (2001) 285: 2370

ATRIA study

2.5% Olmsted County study

Miyasaka Y, et al. Circulation (2006) 114: 119

Prevalence of AFib in the General Population in USA and EU

USA 2.8 million 7.4 million

EU 4.3 million 11.4 million

ATRIA Olmsted

( 300 million inhabitants)

( 456 million inhabitants of 25 member states)

Prevalence of AFibOlmsted County study

Pro

jecte

d n

um

ber

of

pers

on

s w

ith

AF

(mill

ions)

2000

Year

2005 2010 2015 2020 20302025 2035 2040 2045 20500

16

14

10

6

2

12

8

5.1

15.915.2

14.3

13.1

11.7

10.2

8.9

7.7

5.96.7

4 5.1

12.111.711.1

10.39.4

8.47.5

6.8

5.66.1


Men 0.49 %

Women 0.28 %

Ratio men to women = 1.86

Incidence of AFib in the General Population – Gender Differences

Observational period: 20 years

Olmsted County study


Principal Reasons for Increasing Incidence and Prevalence of AFib

1. The population is aging rapidly, increasing the pool of people most at risk of developing AFib

2. Survival from underlying conditions closely associated with AFib, such as hypertension, coronary heart disease and heart failure, is also increasing

3. According to the Olmsted County study, the increase is also related to the increasing population

4. These figures may also be significantly under-estimated because they do not take into account asymptomatic AFib (25% of cases in Olmsted survey)

Miyasaka Y, et al. Circulation (2006) 114: 119Steinberg JS, et al. Heart (2004) 90: 239

General health 54 ± 21 78 ± 17*

Physical functioning 68 ± 27 88 ± 19*

Role physical 47 ± 42 89 ± 28*

Vitality 47 ± 21 71 ± 14*

Mental health 68 ± 18 81 ± 11*

Role emotional 65 ± 41 92 ± 25*

Social functioning 71 ± 28 92 ± 14*

Bodily pain 69 ± 19 77 ± 15*

AFib patients(n=152)

Healthy controls(n=47)SF-36 scale

* p<0.001

AFib has an Impact on All Aspects of QoLSF-36 quality of life scores in AFib patients and healthy subjects

Dorian P, et al. J Am Coll Cardiol (2000) 36: 1303

Risk Factors for AFib

Diagnosed heart failure 29.2%

Hypertension 49.3%

Diabetes mellitus 17.1%

Previous coronary heart disease 34.6%

Characteristic (n=17,974)

Baseline characteristics of 17,974 adults with diagnosed AFib,July 1, 1996-December 31, 1997

Go AS, et al. JAMA (2001) 285: 2370

ATRIA study

AFib is Responsible for 15-20% of all Strokes

– AFib is responsible for a 5-fold increase in the risk of ischaemic stroke

Wolf PA, et al. Stroke (1991) 22: 983Go AS, et al. JAMA (2001) 285: 2370

Friberg J, et al. Am J Cardiol (2004) 94: 889

12

02

8

4

41 53 2 41 53

Cu

mu

lati

ve s

troke in

cid

en

ce (

%)

Women AFib+

Women AFib-

Men AFib+

Men AFib-

Years of follow-up

Increased Risk of Cardiovascular Events

Stewart S, et al. Am J Med (2002) 113: 359

At

least

on

e C

V e

ven

t (%

)

AFib No AFib0

20

40

80

100

45

60

66

AFib No AFib

27

89

Men Women

Death or hospitalization in individuals with CV event(s) after 20 years

80

60

40

20

0

Mortality Associated with AFib

20 10987641 53

Framingham Heart Study, n=5209

Benjamin EJ, et al. Circulation (1998) 98: 946

Follow-up (y)

Mort

ality

du

rin

g f

ollow

-up

(%

)

Men AFib+Women AFib+

Men AFib-Women AFib-

Total health care expenditure (£ million)

Incremental AFib Healthcare CostsUK costs for AFib in 1995 vs. 2000

Stewart S, et al. Heart (2004) 90: 286

7006005004003002001000

Cost of strokeadmission

warfarin use

10% admission

10% community-based care

Base cost of AFin 2000

Cost of heart failureadmission +50%

+5.1%

+7.4%

+5.6%

+48%

Base cost of associated conditions and procedures

Incremental cost of AFib

Other costsBase cost of AFib

• 1995: Direct cost of AFib in the UK between £244 and £531 million (0.6–1.2% of overall health care expenditure)

• 2000: £459 million direct cost – double that in 1995 (0.9–2.4% of NHS expenditure)

23%

9%

8%2% 6%

52%

Hospitalizations

Drugs

Consultations

Further investigations

Paramedical procedures

Loss of work

Major Costs in Treatment of AFib

Le Heuzey JY, et al. Am Heart J (2004) 147:121

COCAF Study

Cost of AFib (Europe)

• 4507 consecutive patients with AFib/flutter admitted to ER

enrolled in FIRE study (1.5% of all ER admissions)

• 61.9% of AFib/flutter patients were hospitalized (3.3% of all hospitalizations)

• Mean hospital stay 7+6 days

FIRE study

Santini M, et al. Ital Heart J (2004) 5: 205

The Burden of AFib

• AFib is responsible for significant economic and healthcare costs

– Hospitalization costs

– Drug treatment

– Treatment of AFib-associated co-morbidities and complications

• The health and economic impact will increase with the increasing prevalence and incidence of AFib

• AFib, owing to its epidemiology, morbidity, and mortality, represents a significant health problem with important social and economic implications that needs greater attention and allocation of more resources

Section II:Clinical Management of AFib

• Restore and maintain sinus rhythm whenever possible

• Prevent thromboembolic events

In order to:

– Reduce symptoms and improve QoL

– Minimize impact of AFib on cardiac performance

– Reduce risk of stroke

– Minimize cardiac remodelling

Primary Therapeutic Aims in AFib

ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial FibrillationJ Am Coll Cardiol (2006) 48: 854

Treatment Options for AFib

Cardioversion

• Pharmacological

• Electrical

Drugs to prevent AFib

• Antiarrhythmic drugs

• Non-antiarrhythmic drugs

Drugs to control ventricular rate

Drugs to reduce thromboembolic risk

Non-pharmacological options

• Electrical devices (implantable pacemaker and defibrillator)

• AV node ablation and pacemaker implantation (ablate & pace)

• Catheter ablation

• Surgery (Maze, mini-Maze)

Recurrence Following Cardioversion: AFFIRM Study

Raitt MN, et al. Am Heart J (2006) 151: 390

AFFIRM: most recurrences occur within 2 monthsof cardioversion

Time (years)

Pati

en

ts w

ith

AF R

ecu

rren

ce (

%)

0

20

40

60

80

100

0 1 2 3 4 5 6

Log rank statistic = 58.62p<0.0001

Rate control: 563, 3 (0) 167, 383 (69) 96, 440 (80) 42, 472 (87) 10, 481 (92) 2, 484 (95)

Rhythm control: 729, 2 (0) 344, 356 (50) 250, 422 (60) 143, 470 (69) 73, 494 (75) 18, 503 (79)

N, Events (%)

Rate control

Rhythm control

Treatment Arm

Pati

en

ts w

ith

ou

t A

Fib

(%

)

Roy D, et al. N Engl J Med (2000) 342: 913

Amiodarone to Prevent Recurrence of AFib

Follow-up (days)

0 100 200 300 400 500 600

p<0.001

Sotalol

Propafenone

Amiodarone

0

20

40

60

80

100

CTAF Study: mean follow-up 16 months

•Even with the most effective AAD, such as amiodarone, long-term efficacy is low

~50% or less at 1 year

Effectiveness of Current AADs

SurgeryElectrophysiologicalDevices

Pacemaker(single or dual chamber)

Internal atrialdefibrillators

Catheter ablation

AV node ablation

Non-Pharmacological Treatment Options for AFib

Maze procedure

Modified Maze

(mini-Maze)


• Pacemakers not curative and must be worn for life

• Surgical procedures may be effective but are not a practical solution for the millions of sufferers of AFib

• Catheter ablation is potentially curative

Management of AFib - Summary

• Current antiarrhythmic drug therapies are not highly effective in maintaining sinus rhythm and generally have poor outcomes– high recurrence rates– adverse effects and high discontinuation rate

• A potentially curative therapy for AFib is desirable

Section III:Catheter Ablation for the Treatment of AFib

Catheter Ablation

•Uses a series of long, thin wires (catheters) that are inserted through an artery or a vein and then guided through to the heart.

•One of the catheters is then used to localise the source of the abnormal electrical signals and another then delivers high energy waves that neutralise (ablate) abnormal areas.

•Using catheters to reach the heart is a common approach to treat a range of heart conditions and is much less invasive than surgical treatments.

Maze reproduction Schwarz 1994

Right atrial linear lesions Haïssaguerre 1994

Right and left atrial linear lesions Haïssaguerre 1996

PV foci ablation Jaïs / Haïssaguerre 1997/8

Ostial PV isolation Haïssaguerre 2000

Circumferential PV ablation Pappone 2000

Ablation of non-PV foci Lin 2003

Antral PV ablation Maroucche / Natale 2004

Double Lasso technique Ouyang / Kuck 2004

CFAE sites ablation Nademanee 2004

Ostial or circumferential or antral PV ablation plus extra lines (mitral isthmus, posterior wall, roof)

Jaïs / Hocini 2004/5

Circumferential PV ablation with vagal denervation

Pappone 2004

Technique Publication date

Landmarks in Catheter Ablation Techniques

1998: Ablation of PV Foci

• Pivotal study identifying the pulmonary veins as a major source of ectopic electrical activity

• Radiofrequency ablation of ectopic foci was associated with a 62% success rate (absence of recurrence at 8 6m follow-up)

Spontaneous Initiation of Atrial Fibrillation by Ectopic Beats Originating in the Pulmonary Veins

Haïssaguerre, M, Jaïs, P, Shah, DC, et al.N Engl J Med (1998) 339: 659

Trigger -Ectopic Foci

PV & non-PV Foci Ablation,

PV Isolation

Autonomic Nervous System

AFib

CFAEs AblationLinear Lesions

(e.g. mitral isthmus, roof)

Substrate -Atrial tissue

A Combination of Techniques may now be used Depending on the Type of AFib

Vagal Denervation

(parasympathetic ganglia ablation)

Cardiac Imaging Techniques

• Electroanatomical mapping– CARTO™ / CARTOMERGE™

• Fluoroscopy

• Angiography

• Intracardiac echography

• Cardiac spiral CT

• Cardiac MRI

CARTO™ System

• 3D-electroanatomic maps (CARTO™) showing ablation points encircling PVs

– Localization of catheter to within 1 mm

– Increase safety margin during ablation

LLPV

LUPV

RUPV

RLPV

RMPV

AC

LA

PV Antrum Isolation Guided by CARTOMERGE™ Image Integration Software Module

Courtesy of Professor Antonio Raviele, Mestre, Italy

Catheter Visualization under Fluoroscopic Guidance

LASSO®Ablation catheter

LAO RAO

Efficacy and Safety of Catheter Ablation

Linear 443 75% 26% 33% 55%

Focal 508 81% 35% 54% 71%

Isolation 2,187 83% 36% 62% 75%

Circumferential (all) 15,455 68% 37% 64% 74%

Circumferential (LACA, WACA) 2,449 65% 37% 59% 72%

Circumferential (PVAI) 11,132 68% 42% 67% 76%

Substrate ablation (CFAE) 559 51% 49% 75% 87%

TOTAL 23,626 61% 55% 63% 75%

PatientsParoxysmal

AF 6-month cure 6-months OKAblation method SHD

Fisher JD, et al. PACE (2006) 29: 523

Meta-analysis of Catheter Ablation

Cure (by each author’s criteria) means no further AFib 6 months after the procedure in the absence of AAD.OK means improvement (fewer episodes, no episodes with previously ineffective AAD).SHD indicates structural heart disease.

Worldwide Survey on Efficacy and Safety of Catheter Ablation for AFib

•Total success rate: 76%

•Of 8745 patients:

– 27.3% required 1 procedure

– 52.0% asymptomatic without drugs

– 23.9% asymptomatic with an AAD within <1 yr

•Outcome may vary between centres

Cappato R, et al. Circulation (2005) 111: 1100

Improved Survival with Ablation vs Drug Treatment

Pappone C, et al. J Am Coll Cardiol (2003) 42: 185

Days of follow-up Days of follow-up

100

0

80

60

1080

Ablation Group Medical Group

90

70

0 180 360 540 900720

One-sample log-rank testObs=36, Exp=31, Z=0.597, p=0.55

10800 180 360 540 900720

One-sample log-rank testObs=79, Exp=341, Z=7.07, p<0.001

Su

rviv

al p

rob

ab

ilit

y (

%)

ExpectedObserved

•589 ablated patients compared with 582 on AADs

More AFib-free Patients with Catheter Ablation vs Drug Treatment

Pappone C, et al. J Am Coll Cardiol (2003) 42: 185

AFib

-fre

esu

rviv

al p

rob

ab

ilit

y (

%)

Ablation

Medical

No. at risk

0

100

80

60

40

20

Follow-up (days)

282 135217

207 97141

0 300200100

589 479507

582 354456

379

277

Ablation GroupMedical Group

Randomised Clinical Trials of Catheter Ablation

RF ablation vs AAD as first-line treatment for AFib

• Wazni OM et al. JAMA (2005) 293: 2634-2640

Catheter ablation in drug-refractory AFib

• Stabile G et al. Eur Heart J (2006) 27: 216-221

Circumferential PV ablation for chronic AFib

• Oral H et al. N Engl J Med (2006) 354: 934-941

Wazni OM, et al. JAMA (2005) 293: 2634

AFib

.fre

e s

urv

ival

0

1.0

0.8

0.6

0.4

0.2

Follow-up (days)

0 300200100

PVI GroupAntiarrhythmic DrugGroup

•Patients randomised to receive ablation (n=33) or AADs (n=37): AFib-free Survival

RF Ablation vs Antiarrhythmic Drugs as First-line Therapy

Catheter Ablation vs. AADs Alone in Drug-refractory AFib

Stabile G, et al. Eur Heart J (2006) 27: 216

AFib

-fre

e s

urv

ival

(%)

0

100

80

60

40

20

Months

0 1295 11108764321

Ablation GroupMedical Group

AADs plus ablation (n=68) or AADs alone (n=69): 1 year follow-up

Randomized Controlled Trial of Amiodarone + Cardioversion + Catheter Ablation

Oral H, et al. N Engl J Med (2006) 354: 9

Sin

us r

hyth

m (

%)

120

20

60

100

80

40

Months

1110987654321

Circumferentialpulmonary-vein ablationControl

Amiodarone & cardioversion (n=69) vs. amiodarone & cardioversion plus PV ablation (n=77)

Catheter Ablation is Successful in the Long Term

Oral H, et al. J Am Coll Cardiol (2002) 40: 100

1.0

0.8

0.4

00 12108642

Months after PV isolation

Fre

ed

om

fro

m R

ecu

rren

t A

Fib

0.6

0.2

No ERAFERAF

Transient ischaemic attack 4 0.4 0 - 3

Permanent stroke 1 0.1 0 - 1

Severe PV stenosis(>70%, symptomatic) 3 0.3 0 - 3

Moderate PV stenosis(40-70%, asymptomatic) 13 1.3 0 - 5

Tamponade / perforation 5 0.5 0 - 3

Severe vascular access complication 3 0.3 0 - 4

Events(n)

Range in studies(%)

Rate(%)Complication

Complications Reported by Leading CentresMajor complications with pulmonary vein ablationin 1039 patients (6 series)

Verma A & Natale A Circulation (2005) 112: 1214

Cost EffectivenessAnalyses of Catheter Ablation

118 patients with symptomatic,drug-refractory AFib

32 weeks

1.52 ± 0.71 ablation procedures

Catheter ablationPharmacological treatment

Catheter Ablation May Be More Cost-effective than Pharmacological Therapy

Weerasooriya R, et al. Pacing Clin Electrophysiol (2003) 26: 292

€4715 followed by €445/year€1590/year

After 5 years, the cost of RF ablation was below that of medical management and further diverged thereafter

Clinical visits per year 7.4 (2.5) 1.1 (0.6)

Emergency room visits per year 1.7 (0.9) 0.03 (0.17)

Hospitalization days per year 1.6 (0.8) 0 (0)

Healthcare costs per year $1920 (889) $87 (68)

No ablation Catheter ablation

Differences in Hospital Visits and Costs with and without Catheter Ablation

Goldberg A, et al. J Interv Card Electrophysiol (2003) 8: 59

Although the initial cost of ablation is high, after ablation, utilization of healthcare resources is significantly reduced

Catheter Ablation Cost-Effective in Patients at High Risk of Stroke

Chan DP, et al. J Am Coll Cardiol (2006) 47: 2513

Model to compare the cost-effectiveness of left atrial catheter ablation (LACA), amiodarone, and rate control therapy in the management of AFib

The use of LACA may be cost-effective in patients with AFib at moderate risk for stroke

This model did not find it to be cost-effective in low-risk patients.

ConclusionsCost-effective in patients at moderate or high risk of stroke

Current Guidelines and Summary

Current ACC/AHA/ESC Guidelines

RecurrentParoxysmal AF

Minimal orno symptoms

Disabling symptomsin AF

Anticoagulation and rate control as needed

Anticoagulation and rate control as needed

No drug for preventionof AF AAD therapy

AF ablation if AADtreatment fails


Recent Commentary

Verma A & Natale A Circulation (2005) 112: 1214

“Current therapies, especially AAM, not onlyare ineffective but also pose a threat to patientQoL and even longevity.

In the hands of experienced operators, AF ablation is an effective, safe, and established treatment for AF that offers an excellent chance for a lasting cure … unlike other therapies, ablation tackles AF at its electrophysiological origin.”

Why Ablation for AFib might be Considered First-Line Therapy for Some Patients

Summary of catheter ablation (I)

•Catheter ablation for AFib has undergone significant methodological and technical revolution since its initial appearance two decades ago

•Discovery that PVs are a major source of ectopic triggers was pivotal in determining efficacy of procedure

•Significant technological advances in catheters and imaging are further improving the efficiency of catheter ablation

•3D reconstructions of actual left atrial PV anatomy using CT, MRI, or intracardiac echography enables ever more accurate placement of lesions

Summary of catheter ablation

• High success rate

• Improves survival, cardiac function and freedom from recurrence

• New data from RCTs confirm benefits

• Safe, with a risk comparable to other low-risk, routine interventions

• Cost effective compared to standard pharmacological therapy, at least in patients at moderate thromboembolic risk

Documents

AFib Management and the Role of Catheter Ablation