Contents - Slide Kit Section I Section I. AFib Overview 1. Definition and classification 2....

Contents - Slide Kit Section I

Section I. AFib Overview

1. Definition and classification

2. Epidemiology

3. Aetiology of AFib

4. Pathophysiology of AFib

5. Symptoms

6. Prognostic factors

7. Economic burden of AFib

Contents – Slide Kit Section II

Section II. Clinical Management of AFib

1. Clinical Evaluation

2. Treatment Options for AFib

• Cardioversion

• Drugs to prevent AFib

• Drugs to control ventricular rate

• Drugs to reduce thromboembolic risk

• Non-pharmacological options

Contents – Slide Kit Section III

Section III: Catheter Ablation for the Treatment of AFib

1. Left atrial (LA) and pulmonary vein (PV) anatomy

2. Catheter ablation techniques

3. Technological issues

4. Success rates

5. Complication rates

6. Cost-effectiveness

7. Indications for catheter ablation

8. Centre experience

Section I:AFib Overview

Section I. AFib Overview

1. Definition and Classification

2. Epidemiology



5. Symptoms

6. Prognostic Factors

7. Economic Burden of AFib

1. Definition and Classification of AFib

Definition of AFib

AFib is a supraventricular tachyarrhythmia characterized by uncoordinated atrial activation with consequent

deterioration of atrial mechanical function

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

Atrial Flutter

To be clinically useful, a classification of AFib must be based on a sufficient

number of features and carry a specific therapeutic implication

Classification of AFib

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

Paroxysmal(self-terminating)

Persistent(non-self-terminating)

Permanent

First Detected and Recurrent AFib

First detected


Aetiopathology of Paroxysmal AFib

Camm AJ & Obel OA Am J Cardiol (1996) 78: 3

60

50

40

30

20

10

0Cardiomyopathy Ischaemic

cardiopathyValvulardisease

Miscellaneous Hypertension Idiopathic AFib

n = 161

Aetiopathology of Chronic AFib

35

25

20

15

10

5

0

30

n = 264

Cardiomyopathy Ischaemiccardiopathy

Valvulardisease

Miscellaneous Hypertension Idiopathic AFib

Camm AJ & Obel OA Am J Cardiol (1996) 78: 3

Presentation of AFib in EuroHeart Survey

4040

3030

1010

00Paroxysmal AFib

% p

ati

en

ts

Persistent AFib Permanent AFib

2020

5050

6060

3628

36

EuroHeart Survey 2005

– 5,333 patients enrolled with AFib on ECG or Holter recording during the qualifying admission/consultation, or in the preceding 12 months

Nieuwlaat R, et al. Eur Heart J (2005) 26: 2422

8080

6060

4040

2020

00

Presentation of AFib in Olmsted County Study

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

Olmsted County– 4,618 residents who had ECG-confirmed first AFib in the

period 1980-2000

% p

ati

en

ts

Paroxysmal AFib Other forms of AFib

74

26

Type of AFib at Diagnosisand Last Follow-up

100

75

25

0Lone AFib

Pati

en

ts (

%)

Recurrent AFib Chronic AFib

50

100

75

25

0Lone AFib

Pati

en

ts (

%)

Recurrent AFib Chronic AFib

50

21 20

58

9

22

13 13

2920

5867

At follow-upAt diagnosis

Patients < 60 years

Patients > 60 years

70

Chugh SS, et al. J Am Coll Cardiol (2001) 37: 371

2. Epidemiology of AFib

Epidemiology of AFib

Prevalence

Prevalence of AFib

General population-based prevalence

0.95%

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

ATRIA study

Prevalence in Europe

• UK epidemiological study used to calculate health care resource utilization in 1995 and 2000

• In 1995, approximately 534,000 people (281,000 men and 253,000 women) were treated for AFib

– 5% in patients aged >65

UK cost analysis study 1995-2000

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


0.90%

Prevalence in Europe

Heeringa J, et al. Eur Heart J (2006) 27: 949

• European population-based prospective cohort study among subjects aged 55 years and above (n=6808)

• Mean follow-up: 6.9y

– Overall prevalence (55y and above): 5.5%

– 0.7% in patients aged 55-59

– 17.8% in patients aged 85 and above

Rotterdam study

Prevalence of AFib


2.5%

Olmsted County study


Different study settings

HMO in California Entire population in a Midwest US county

Difference in ethnicity of studied populations

More mixed ethnic groups Higher proportion of Caucasians

Differences in case definitions

Active AFib during a specific time period

Clinical history of AFib with ECG confirmation

ATRIA study Olmsted County

Reasons Why the Prevalence of AFib may have Previously been Underestimated


• Both may, however, be significant underestimates based on the high prevalence of silent, asymptomatic AFib (25% in Olmsted County study)

Prevalence of AFib in the General Population by Age

10

8

6

4

2

0

Pre

vale

nce (

%)

50-59 60-69 70-79 80-89

12

8.8

4.8

1.80.5

Wolf PA, et al. Stroke (1991) 22: 983

– Prevalence of AFib roughly doubles with each advancing decade of age, from 0.5% at age 50–59 years to almost 9% at age 80–90 years

Framingham study

Prevalence of AFib Stratified by Age and Sex

10

8

6

4

2

0

Pre

vale

nce (

%)

Age (years)

<55 55-59 60-64 65-69 70-74 75-79 80-84 ≥85

12 11.1

9.1

10.3

7.27.3

5.05.0

3.43.0

1.71.71.00.90.40.20.1

Women

Men

1498566 1132530 896310 1572

1907934 7591259 1426634 1886

No.

1291

1374

WomenMen

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

ATRIA studyMen 1.1% Women 0.8%

Mean 0.95%

0

2

4

6

8

10

12

14

35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 >80

Framingham Study Western Australia StudyMayo Clinic StudyCardiovascular Health Study

Feinberg WM, et al. Arch Intern Med (1995) 155: 469

Similar Prevalence in the General Population across Epidemiological Studies

Feinberg WM, et al. Arch Intern Med (1995) 155: 469

Age Distribution of AFib versus US Population Figures

US

pop

ula

tion

x 1

00

0

0

30000

20000

10000

<5

5-9

10-14

15-19

20-24

25-29

30-34

35-39

40-44 50-54

45-49 55-59

60-64

65-69

70-74

75-79

80-84

85-89

90-94

>95

500

400

300

200

100

0

Population with atrial fibrillationUS population

Median age: 75 y

Age (years)

AF: 2.3% >40y; 5.9% >65y 70%: >65y <85y

Pop

ula

tion

with

AFib

x 1

00

0

4040

3030

1010

00Caucasian(n=1150)

Pre

va

len

t A

Fib

in

1,3

73

pa

tie

nts

wit

h H

F

African American(n=223)

2020

5050

6060

38.3

19.7

Ruo B, et al. J Am Coll Cardiol (2004) 43: 429Conway DSG & Lip GYH Am J Cardiol (2003) 92: 1476

Variation in Prevalence According to Ethnicity

•Significantly lower prevalence of AFib in Indo-Asians and African Americans

– Variation not explained by differences in traditional risk factors for AFib

p<0.001

Prevalence of AFib in the General Population in Selected Countries

2.8 million people

USA ( 298 million inhabitants)

4.3 million people

European Union ( 456 million inhabitants of 25 member states)

Based on population prevalence of 0.95% (ATRIA Study)

1.2 million people

Japan ( 128 million inhabitants)

Prevalence of AFib in the General Population in Selected Countries

7.45 million people


11.4 million people


Based on population prevalence of 2.5% (Olmsted Study)

3.2 million people


Prevalence of AFib in …

• General population prevalence: 0.90-0.95% to 2.5%

• Population of ………: X million

Prevalence:

•0.90-0.95 x X million to 2.5 x X million

Country specific numbers

Progression from Paroxysmal to Persistent AFib

Kato T, et al. Circ J (2004) 68: 568

Transformation of paroxysmal AFib to persistent AFib:5.5% patients per year

Rati

o in

sin

us r

hyth

m

0

1.0

0.8

0.6

0.4

0.2

Follow-up (years)

0 30

Without structural heart disease

With structural heart disease

252015105

Paroxysmal AF onset

Prevalence of Recurrent AFib in Europe

From 2.8 million people up to 7.4 million(based on prevalence range of 0.95% to 2.5%)


•Based on ~65% of all cases of AFib (EuroHeart Survey)


Prevalence of Chronic AFib in Europe

From 1.5 million people up to 4 million(based on prevalence range of 0.95% to 2.5%)


•Based on ~35% of all cases of AFib (EuroHeart Survey)



Incidence

Incidence of AFib in the General Population

2% for paroxysmal AFib2% for chronic AFib

= 0.2% per year

Observational period: 20 years

Kannel WB, et al. Am Heart J (1983) 106: 389

Framingham study

Incidence of AFib in the General Population (European Data)

Incident hospitalization

Men = 0.18% per year Women = 0.17% per year

Observational period: 20 yearspatients aged 45-65


Renfrew-Paisley study

Incidence of AFib in the General Population

Incidence

= 0.34% per year

Observational period: 20 yearsFirst documented AFib episode



Men 0.3 %

Women 0.2 %

Ratio men to women = 1.5

Kannel WB, et al. (1992) Atrial fibrillation: mechanisms and management. Falk RH & Podrid PJ eds., Raven Press, New York, NY

Incidence of AFib in the General Population – Gender Differences


Framingham study

Men 0.49 %

Women 0.28 %

Ratio men to women = 1.86

Incidence of AFib in the General Population – Gender Differences




Age-Specific Incidence of AFSummary of available data

Incid

en

ce/1

,00

0 p

ers

on

-years

0

60

30

40

20

Framingham (men)

40 50 60 70 80 90 100

Framingham (women)

CHS (men)CHS (women)

Olmsted (men)Olmsted (women)


Age (years)

Incidence of AFib in the General Population in Selected Countries

600,000 new cases every year




Based on population incidence of 0.2% per year



Incidence of AFib – Lifetime Risk

• 8725 patients free of AFib at 40 years of age followed from 1968-1999

•Lifetime risk to develop AFib at the age of 40 years:

– 26.0% in men

– 23.0% in women

• Lifetime risk high even in absence of CHF or MI (1 in 6)

Framingham study – 1 in 4 lifetime risk of developing AFib

Lloyd-Jones DM, et al. Circulation (2004) 110: 1042

Incidence of AFib – Lifetime Risk

• European population-based prospective cohort study among subjects aged 55 years and above (n=6808)

•Lifetime risk to develop AFib at the age of 55 years:

– 23.8% in men

– 22.2% in women

Rotterdam study

Heeringa J, et al. Eur Heart J (2006) 27: 949

Incidence of AFib in …

• General population incidence: 0.2% per year

• Population of ………: X million

Incidence:

•0.2 x X million per year

Country specific numbers


Secular Trends in Prevalence and Incidence

Prevalence of AFib and Flutter

– Prevalence increasing annually by 3-4%

– The prevalence of AFib is estimated to increase over 2-fold over the next decades

Ad

ult

s w

ith

AFib

(m

illio

ns)

7.0

6.0

4.0

2.0

1.0

01990

Year

5.0

3.0

1995 2000 2005 2010 2015 2020 20302025 2035 2040 2045 2050

2.082.26

5.615.42

5.164.78

4.34

3.803.33

2.94

2.442.66

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

ATRIA study

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


Increasing Incidence of AFibOlmsted County study

Incid

en

ce/1

,00

0 p

ers

on

-years

0

6

1980

4

2

1985 1990 1995 2000

Year

5

3

1MenOverallWomen


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 AF, such as hypertension, coronary heart disease and heart failure, is also increasing

3. According to the Olmsted County study, the increase is also associated with increasing population numbers

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

Epidemiology of AFib - Summary

• AFib is the most commonly experienced sustained arrhythmia, accounting for more than 30% of patients hospitalised with arrhythmia

• AFib affects 1 in 25 people over the age of 60 and almost 1 in 10 over the age of 80

• Estimated population-based prevalence (0.95-2.5%)

– USA: ≈ 3-7 million patients

– West Europe: 4-11 million patients

– Japan: 1-3 million patients

Go AS, et al. JAMA (2001) 285: 2370Miyasaka Y, et al. Circulation (2006) 114: 119

AFib May Be Focal or Caused by Reentrant Wavelets

Focal activationMultiple Wavelets

PVs

LA

IVC IVC

RA

SVC SVC

PVs

LA

RA

– May be initiated by focal triggers and maintained by substrate mediated factors that become more prevalent as AFib progresses

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

Electrophysiological Mechanisms of AFib

•Triggers

•Maintaining factors

•Modulating factors

Inter-relationships Between Triggers, Maintenance Factors and Modulating Factors

AFib duration

Paroxysmal

Permanent

PersistentR

ela

tive im

port

an

ce

Modulating factors

SYMPATHETIC TONEPARASYMPATHETIC TONE

SYMPATHETIC TONE

PARASYMPATHETIC TONE

Trigger/initiation Substrate/maintenance

Adapted from Zipes D, et al. (2002) “Catheter ablation of arrhythmias” (2nd Edition), Futura Publishing Company

Triggers and Maintaining Factors

TRIGGER

ROTORS

Modulating Factors

PARASYMPATHETIC GANGLIA

Courtesy of Professor Antonio Raviele, Mestre, Italy

Anatomic and Electrophysiological Factors Promoting the Initiation or Maintenance of AFib

Ion channel expression Shortened atrial refractive period

Altered gap junction distribution Atrial myocyte calcium overload

Altered sympathetic innervation Atrial myocyte triggered activity or automaticity

Atria dilatation Decreased atrial conduction velocity

Pulmonary vein dilatation Non-homogeneity of atrial refractoriness

Atrial myocyte apoptosis Dispersion of conduction

Interstitial fibrosis Supersensitivity to catecholamines and acetylcholine

Anatomic factorsElectrophysiological factors

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

Lone or Idiopathic AFib

Brand FN, et al. JAMA (1985) 254: 3449Kopecky SL, et al. N Engl J Med (1987) 317: 669

Scardi S, et al. Am Heart J (1999) 137: 686ACC/AHA/ESC 2006 Guidelines J Am Coll Cardiol (2006) 48: 854

2% - 31%

AFib that occurs in young individuals (under 60 years of age) in absence of a

cardiopulmonary disease (“lone” AFib) or of any disease (“idiopathic” AFib)

Prevalence

Secondary AFib

90 %

AFib that occurs in association with a detectable heart disease or other

pathological conditions that may promote it

Prevalence

Furberg CD, et al. Am J Cardiol (1994) 74: 236

Genetic Basis in Idiopathic AFib

Somatic mutations in the connexin 40 gene (GJA5) in AFib

• 15 patients with idiopathic AFib had DNA isolated from resected cardiac tissue and peripheral lymphocytes and GJA5 gene (coding for connexin 40) sequenced• Four patients had missense mutations• In three patients, mutations were just in the cardiac-tissue, indicating a somatic source of the genetic defects• In one patient, the mutation was in both cardiac tissue and lymphocytes, suggesting a germ-line origin• Analysis of the expression of mutant proteins revealed impaired intracellular transport or reduced intercellular electrical coupling

Gollob MH, et al. N Engl J Med (2006) 354: 2677

Risk Factors for AFib:Other Co-existing Conditions

Cardiac causes of AFib:

• Ischaemic heart disease• Rheumatic heart disease• Hypertension• Sick sinus syndrome• Pre-excitation syndromes (e.g. Wolff-Parkinson-White)

Less common cardiac causes:

• Cardiomyopathy or heart muscle disease• Pericardial disease (including effusion and constrictive pericarditis)• Atrial septal defect• Atrial myxoma

Risk Factors for AFib:Other Co-existing Conditions

Non-cardiac causes of AFib:

• Acute infections, especially pneumonia• Electrolyte depletion• Lung carcinoma• Other intrathoracic pathology (e.g. pleural effusion)• Pulmonary embolism• Thyrotoxicosis

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 atrial fibrillation,July 1, 1996-December 31, 1997

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

ATRIA study

Risk Factors for AFib

Hypertensive heart disease 30.3%

Valvular disease 26.2%

Coronary artery disease 23.6%

Dilated cardiomyopathy 13.1%

Hypertrophic cardiomyopathy 6.9%

Other 8.6%

Characteristic (n=534)

ALFA study

Levy S, et al. Circulation (1999) 99: 3028

70

50

40

30

20

10

0

60

PIAF STAF AFFIRM*RACE HOT CAFE AFFIRM**

Hypertension in Patients with AFib

Camm AJ & Savelieva I Dialogues in Cardiovasc Med (2003) 8: 183

Paroxysmalpersistent

Recurrentpersistent

Recurrentpersistent

Recurrentpersistent



*HT as predominant cardiac diagnosis; **Overall prevalence of hypertension

Patients with hypertension (%)

I 4 SOLVD-prevention 1992

II-III 10 - 26

SOLVD-treatment 1991CHF-STAT 1995MERIT-HF 1999Diamond 1999

III-IV 20 - 29Middlekauf 1991Stevenson 1996

GESICA 1994

IV 50 CONSENSUS 1987

Prevalence of AFib Study, y

Predominant NYHA type

Prevalence of AFib in Patients with Heart Failure

ACC/AHA/ESC Guidelines for the Management of Patients With Atrial FibrillationJ Am Coll Cardiol (2001) 38: 1266i

Incidence of AFib in Patients with HF

• Development of CHF at AFib onset: 3.3% (33 per 1000 person-years

• Development of AF at CHF onset: 5.4% (54 per 1000 person-years)

Framingham study

Wang TJ, et al. Circulation (2003) 107: 2920Miyasaka Y, et al. Eur Heart J (2006) 27: 936

Minnesota study

• 24% developed a first CHF during 6.1y follow-up

• Development of CHF at AFib onset: 4.4% (44 per 1000 person-years)

Physiological Consequences of AFib

•Reduced diastolic peak flow

•Reduced systolic ejection

•Dysfunction in atrio-ventricular valve closure

• Increased atrial size

•Ventricular dilatation

Physiological Consequences of AFib

Ch

an

ge (

%)

0

50

200

100

150

Pulmonarycapillarywedge

pressure

Cardiacoutput

Systemicvascular

resistance

Pulmonaryartery

pressure

Pulmonaryartery

diastolicpressure

Clark DM, et al. J Am Coll Cardiol (1997) 30: 1039

The AFib Vicious Cycle

AFCl

AFStretch

APD Electrical

remodeling

Structuralremodeling

Contractileremodeling

WL

Zig-zagconduction

CytosolicCa++

Ca++

channelsCircuit

size

FibrosisCompliance

AnisotropyContractility

ConnexinsDilatation

Allessie MA J Cardiovasc Electrophysiol (1998) 12: 1378

AFib Begets AFib

Kato T, et al. Circ J (2004) 68: 568

Transformation of paroxysmal AFib to persistent AFib:5.5% patients per year

Rati

o in

sin

us r

hyth

m

0

1.0

0.8

0.6

0.4

0.2

Follow-up (years)

0 30

Without structural heart disease

With structural heart disease

252015105

Paroxysmal AFib onset

Sustained AFib Induces Structural Changes

Shinagawa K, et al. Circulation (2002) 105: 2672

Fib

rosis

(%

)

0

4

18

10

14

Crista

e

term

inali

s

16

12

8

6

2

RA

free

wall

Bachm

ann’s

Bundle LA

appen

dage

LA

infe

rior w

allLA

poste

rior w

all

Avera

ge

*

* **

**

* **

*

**

**

controlCHFweek 5 of AFib

* p<0.01 vs CTL

– While acute physiological changes may be reversible, AFib can initiate irreversible fibrosis at many cardiac sites

AFib Pathophysiology - Summary

• AFib initiation and maintenance involves focal triggers and multiple reentrant wavelets

• Electrical remodeling occurs early in AFib and is closely inter-related with contractile and structural remodelling

• Patients with recurrent AFib will often progress to a chronic form with increasing age and duration of disease

• Physiological changes contribute to heart failure and risk of stroke

• The longer AFib progresses, the more resistant it becomes to treatment

5. Symptoms of AFib

8080

6060

4040

2020

00Syncope,

dizzy spellsFatigue

Pat

ien

ts e

xper

ien

cin

g s

ymp

tom

(%

)

Chest painOther Dyspnoea

10.410.410.110.10.90.9

14.314.3

44.444.4

11.411.4

54.154.1

None Palpitations

Symptomatology of AFib


ALFA study: total population, n=756

0

Palpitations

Dyspnea

Syncope, dizziness

Chest pain

Fatigue

None

25 50 10075

Symptoms of AFib

ParoxysmalPermament

ALFA study: paroxysmal n=167; permanent/chronic n=389


Palpitations

Chest pain

Dyspnoea

Syncope

Fatigue

Other

None

Paroxysmal% (n=167)

79.0

13.2

22.8

17.4

12.6

0

5.4

Chronic% (n=389)

44.7

8.2

46.8

8.0

13.1

1.8

16.2

Recent onset% (n=200)

51.5

11.0

58.0

9.5

18.0

0

7.0

Symptoms

Symptoms of AFib According to ClassificationALFA study


Asymptomatic AFib

•The Canadian Registry of Atrial Fibrillation (CARAF) enrolled subjects at the time of first ECG-confirmed diagnosis of AF

•21% of patients diagnosed with AFib on ECG were asymptomatic

•25% of patients diagnosed with AFib on ECG were asymptomatic

CARAF study


Kerr C, et al. Eur Heart J (1996) 17 Suppl C: 348Miyasaka Y, et al. Circulation (2006) 114: 119

In patients with an implanted device (AT500 pacemaker) and known symptomatic AFib

>50% of AFib episodes asymptomatic

Israel CW, et al. J Am Coll Cardiol (2004) 43: 47

Asymptomatic AFib

303 patients in sinus rhythm followed-up for 6 months post-cardioversion using trans-

telephonic monitoring every 2 weeks of a 30 second ECG

17% of cases experienced asymptomatic episodes before developing symptomatic

episodes

Page RL, et al. Circulation (2003) 107: 1141

Asymptomatic AFib

Asymptomatic vs symptomatic episodes

12 to 1

In patients diagnosed with symptomatic paroxysmal AFib monitored for 29 days using

trans-telephonic ECG monitoring

Page RL, et al. Circulation (2003) 107: 1141

Asymptomatic AFib

• Asymptomatic episodes may occur more frequently than symptomatic ones

• In symptomatic patients undergoing ambulatory monitoring, asymptomatic episodes outnumbered symptomatic episodes by a 12:1 ratio

• Holter monitoring or trans-telephonic ambulatory ECG monitoring should be considered in patients with suspected paroxysmal AFib undetected by standard ECG recording

AFib Symptoms - Summary

Page RL, et al. Circulation (1994) 89: 224ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation

J Am Coll Cardiol (2006) 48: 854

6. Prognostic Issues

Prognostic Issues Associated with AFib

•Impact of AFib on quality of life

•Thromboembolic complications

•Relationship to heart failure

•Tachycardia-induced cardiomyopathy

•Mortality

Prognostic Issues

Impact of AFib on Quality of Life

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

Poorer QoL vs Healthy Controls and Patients with Coronary Artery Disease

7070

6060

4040

3030Physical

SF

-36

sc

ale

5050

8080

9090

QoL Survey 2000

– 152 patients with paroxysmal or persistent AFib

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

100100

Vitality General Mental Emotional Social

Healthy controls

AFib

Recent MI

CHF

PTCA

Luderitz B & Jung W Arch Intern Med (2000) 160: 1749

Poorer QoL in Patients with Paroxysmal AFib

• Patients with paroxysmal AFib who have frequent, highly symptomatic recurrences have a higher incidence of more severe symptoms and a significantly lower QoL than those with persistent or permanent AFib

Severity of last episode (0-10) 5.0 4.5 2.8

Severity of average episode (0-10) 5.5* 4.5 3.2

Total symptoms (0-6) 3.7 ** 2.7 2.9

*p=0.001 vs other types of AFib**p<0.001 vs other types of AFib

ParoxysmalSymptom score Persistent Permanent

Prognostic Issues

Thromboembolic Complications

AFib 4.5%

(2.5% disabling strokes)

Controls 0.2% - 1.4%

Annual incidence in patients with AFib

Thromboembolic Events

The Stroke Prevention in Atrial Fibrillation Investigators Arch Int Med (1992) 116: 1

The Stroke Prevention in Atrial Fibrillation Investigators Arch Int Med (1992) 116: 1 Atrial Fibrillation Investigators Arch Intern Med (1994) 154: 1449

Hart RG, et al. Ann Intern Med (1999) 131: 492

including TIA/silent strokes incidence of thromboembolic events increases to 7%

Note: adjusted-dose warfarin reduces risk of stroke by approx 62%, and aspirin by 22%

Thromboembolic Events

Annual incidence in patients with AFib

Previous stroke or TIA 2.5

History of hypertension 1.6

Congestive heart failure 1.4

Advanced age (continuous per decade) 1.4

Diabetes mellitus 1.7

Coronary artery disease 1.5

Relative RiskRISK FACTORS (control groups)

Risk Factors for Ischaemic Stroke and Systemic Embolism in AFib

Atrial Fibrillation Investigators Arch Intern Med (1994) 154: 1449

Clinical Risk Factors for Thromboembolic Events

– Congestive heart failure

– History of hypertension

– Previous arterial thromboembolism

The Stroke Prevention in Atrial Fibrillation Investigators. Ann Intern Med (1992) 116: 1

Ris

k o

f S

troke p

er

year

(%)

1 risk factor 2 risk factors 3 risk factors0

10

20

17.6

7.2

2.5

AFib is Responsible for 15-20% of all Strokes

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

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

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

Stroke in Patients with AFib

• 992 consecutive patients recruited with stroke – AFib diagnosed in 304 (31%)

% o

f p

ati

en

ts (

n=

30

4)

0

10

20

40

Age groups (year)0 <65 65-74 75-84 >84

50

30

The Austrian Stroke Registry

Men

Women

Steger S, et al. Eur Heart J (2004) 25: 1734

Higher Mortality and More Severe Stroke in Patients with AFib

The Austrian Stroke Registry

Mort

ality

(%

)

0

10

20

40

0

50

30

No AFib AFib

10

20

40

0

50

30

0S

troke s

everi

ty

(Bart

hel In

dex o

n

ad

mis

sio

n)

No AFib AFib

p<0.0004

p<0.0004


Higher Mortality and More Severe Stroke in Patients with AFib

The European Community Stroke Project

Lamassa M, et al. Stroke (2001) 32: 392

• Multi-centre, multi-national hospital-based registry involving 4462 patients hospitalized for first stroke

• AFib diagnosed in 803 stroke patients (18%)

• At 3 months, 32.8% of stroke patients with AFib were dead vs 19.9% of stroke patients without AFib

• AFib increased by approximately 50% the probability of remaining disabled

AFib is Associated with Progressive Risk of Stroke

• Independent predictor of stroke recurrence and severity

Simons LA, et al. Stroke (1998) 29: 1341

Cu

mu

lati

ve h

aza

rd o

f fa

tal str

oke

1000

0.01

0.02

0.04

0.05

0.03

9080706050403020100

Months of follow-up

AF Present

AF Absent

An

nu

alize

d s

troke

rate

(%

/ y

r)

0

4

8

12

Low-risk High-riskModerate-risk

• Rate of ischaemic stroke 3.2% in intermittent AFib and 3.3% in sustained AFib

Stroke Risk Equivalent in Recurrent and Permanent (Chronic) AFib

2

14

6

10

Hart RG, et al. J Am Coll Cardiol (2000) 35: 183

Intermittent

Sustained

Prognostic Issues

Heart Failure and Tachycardia-induced Cardiomyopathy

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

AFib and Congestive Heart FailureATRIA study

Characteristic

Age, mean (SD), years

≥80years

Women

Known valvular heart disease

Previous ischaemic stroke

Diagnosed heart failure

Hypertension

Diabetes mellitus

Previous coronary heart disease

Angina

Myocardial infarction

(n= 17974)

71.2 (12.2)

25.4

43.4

4.9

8.9

29.2

49.3

17.1

34.6

21.8

9.4

Pre

vale

nce o

f A

Fib

(%

)

0

20

40

60

SOLVD prevention

Prevalence of AFib in Major Heart Failure Trials2-fold excess risk of mortality compared with healthy control

4.2

SOLVD treatment

10.1

V-HeFT

14.4

CHF-STAT

15.4

DIAMONDCHF

25.8

GESICA

28.9

CONSENSUS

49.8

NYHA Functional Class

I II-III III-IV IV

Maisal WH & Stevenson LW Am J Cardiol (2003) 91: 2D

Risk of CHF After Diagnosis of AFib

After diagnosis, 24% of patients develop CHF within 6.1 ± 5.2 years

Miyasaka Y, et al. Eur Heart J (2006) 27: 936

Cu

mu

lati

ve in

cid

en

ce

of

CH

F (

%)

0

5

10

30

20

5

Years after diagnosis0 1 2 3 4

25

15

Prognosis of Patients with AFib and Heart Failure is Worse

•There is a mutual relationship between AFib and CHF (HF begets AFib and AFib begets CHF)

•Survival is significantly worse for heart failure patients with AFib than for patients with sinus rhythm

•AFib in associated with an increased risk of morbidity and mortality in patients with heart failure regardless of baseline ejection fraction (EF), but is even higher in patients with preserved EF


AFib Significantly Increases CHF-related Death and Hospitalization

60

40

20

10

020 541 3

Even

t ra

te (

%)

Swedberg K, et al. Eur Heart J (2005) 26: 1303

50

30

120716661920 1458

245358426 299

426

97

AF presentAF absent

Relative risk 1.35 (95% Cl 1.20-1.51); p<0.001

Time (years)

Time to CV Death or Hospitalization for Heart Failure in Patients with AFib

0.30

0.20

0.15

0.10

0.05

0

Cu

mu

lati

ve

dis

trib

uti

on

fu

ncti

on

Year

0 1 2 3

0.40

No AF & Low EF

No AF & PEF

196332073906 2755

127622942545 2096

Number at risk

289509670 417

203399478 353

AF & Low EF

AF & PEF

3.5

0.50

0.25

0.35

0.45

AF at baseline (Low EF)No AF at baseline (Low EF)AF at baseline (Preserved)No AF at baseline (Preserved)

Low EF: Hazard ratio 1.29 (95% Cl 1.14-1.46); p<0.001Preserved EF (PEF): Hazard ratio 1.72 (95% Cl 1.45-2.06); p<0.001

Olsson LG, et al. J Am Coll Cardiol (2006) 47: 1997

Martha Grogan, Hugh C. Smith, Bernard J. Gersh and Douglas L. Wood

Left Ventricular Dysfunction Due to Atrial Fibrillation in Patients Initially Believed to Have Idiopathic Dilated Cardiomyopathy

Tachycardia-induced Cardiomyopathy

Grogan M, et al. Am J Cardiol (1992) 69: 1570


CHECK PERMISSIONS FOR PHOTO

Grogan M, et al. Am J Cardiol (1992) 69: 1570

Nerheim P, Birger-Botkin S, Piracha L, Olshansky B

Circulation (2004) 110: 247-252

Heart Failure and Sudden Death in Patients with Tachycardia-Induced Cardiomyopathy and Recurrent Tachycardia


Nerheim P, et al. Circulation (2004) 110: 247


• Tachycardia-induced cardiomyopathy develops slowly and appears reversible by left ventricular ejection fraction improvement

• However, recurrent tachycardia causes rapid decline in left ventricular function and development of heart failure

Nerheim P, et al. Circulation (2004) 110: 247

Prognostic Issues

Mortality

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-

Increased Risk of Cardiovascular Events

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

At

least

on

e c

ard

iovascu

lar

even

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

Rela

tive r

isk o

f m

ort

ality

0

2

8

4

6

Framingham(overall)

Manitoba WhitehallFramingham(no HD)

Relative Risk of Mortality in Patients with AFib2-fold excess risk of mortality compared with healthy controls

Jouven X, et al. Eur Heart J (1999) 20: 896

Idiopathic AFib 1.95 [1.13-3.37] 0.02 4.31 [2.14-8.68] 0.0001

Age at inclusion 1.03 [1.01-1.11] 0.04 1.08 [0.98-1.19] ns

Systolic blood pressure 1.44 [1.38-1.51] 0.0001 1.51 [1.39-1.63] 0.0001

Cholesterol 1.00 [0.96-1.04] ns 1.24 [1.14-1.35] 0.0001

Body mass index 0.89 [0.85-0.94] 0.0001 1.00 [0.92-1.10] ns

Tobacco consumption 1.40 [1.34-1.45] 0.0001 1.31 [1.22-1.41] 0.0001

Total mortality RR Cardiovascular mortality RR

Variable (IC 95%) p (IC 95%) p

PARIS Prospective study I

Total and Cardiovascular Mortality Risk

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

Prognostic Issues Associated with AFib - Summary

7. Economic Burden of AFib

AFib Healthcare Cost Analysis – UK DataUK costs for AFib in 1995 vs 2000


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

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

Total health care expenditure (£ million)

Incremental AFib Healthcare CostsUK costs for AFib in 1995 vs 2000


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 costs

• 0.9-2.4% of total healthcare budget in 2000

Base cost of AFib

20%

12%

13%

6%

50%

Hospitalizations

Drugs

GP outpatient referral

GP visits

Post discharge outpatient visits

Major Costs in Treatment of AFibStewart UK Study


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 (US)

•1% of all hospital admissions– 34% of all admissions for arrhythmia

•Mean hospital stay: 3.7 days

•2-3 fold increase in hospitalisations between 1985-1994

Wattigney WA, et al. Circulation (2003) 108: 711

US National Discharge Survey

Cost of AFib (US)US National Discharge Survey – Age-specific prevalence(per 10,000 population) for hospitalizations with AFib

0

40

20

80

60

Principal diagnosis

19850

400

200

800

600

1000

Any diagnosis

Per

10

,00

0 p

ers

on

s

Years Years

120

140 1400

100

1200

19991997

19951993

19911989

19871985

19991997

19951993

19911989

1987

85+75-8465-7455-6435-54

Wattigney WA, et al. Circulation (2003) 108: 711

Increase in Admissions for AFibN

um

ber

of

AFib

ad

mis

sio

ns

1996 1997280,000

300,000

320,000

360,000

380,000

340,000

1998 1999

Number of admissions with a primary diagnosis of AFib to hospitals in the US 1996-2001

Khairallah F, et al. Am J Cardiol (2004) 94: 500

2000 2001

Extra Costs Associated with AFib

•Cost of hospital assistance higher in patients between ages of 65-74y with AFib than in patients with similar conditions without AFib

– Men 8.6% - 22.6% higher

– Women 9.8% - 11.2% higher

Wolf PA, et al. Arch Intern Med (1998) 158: 229

Impact of Stroke in Patients with AFib Higher

•Stroke patients with AFib compared with stroke patients without AFib:

– More cerebrovascular risk factors

– Poorer neurological outcome

– More medical complications (e.g. pneumonia, heart failure)

– Higher in-hospital mortality

Austria Stroke Registry


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

Inpatient admissions 1.2+0.8 1.9+0.8 0.9+0.5 1.3+0.7

ER visits 0.7+0.4 0.5+0.4 0.5+1.0 0.6+0.6

Outpatient procedures 7.4+4.1 7.1+2.8 5.8+2.0 6.9+3.0

Office visits 9.5+3.5 4.5+1.4 7.0+3.2 7.0+2.7

Medication prescriptions 2.0+0.9 2.3+0.5 2.2+0.5 2.1+0.6

Lab measurements 9.2+4.9 8.0+6.1 8.4+6.5 8.5+5.8

Bordeaux Ghent Milwaukee TOTAL, mean

AFib Patient Healthcare Utilisation (per patient/year)

Impact on the Healthcare System

Garrigue S, et al. Arch Mal Coeur Vaiss (1998) 91(Special III): 69

Costs of AFib Likely to Increase Significantly in the Future

• Projected 3-fold increase in prevalence over next 50 years


Ad

ult

s w

ith

AFib

(m

illio

ns)

7.0

6.0

4.0

2.0

1.0

01990

Year

5.0

3.0

1995 2000 2005 2010 2015 2020 20302025 2035 2040 2045 2050

2.082.26

5.615.42

5.164.78

4.34

3.803.33

2.94

2.442.66

The Burden of AFib: Summary

• 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

Contents - Slide Kit Section I Section I. AFib Overview 1. Definition and classification 2....

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Transcript of Contents - Slide Kit Section I Section I. AFib Overview 1. Definition and classification 2....