Transcript AFib Management and the Role of Catheter Ablation

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
3. Aetiology of AFib
4. Pathophysiology of AFib
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 Fibrillation
J Am Coll Cardiol (2006) 48: 854
AFib
Atrial Flutter
Classification of AFib
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 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
First Detected and Recurrent AFib
First detected
Paroxysmal
Persistent
(self-terminating)
(non-self-terminating)
Permanent
ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation
J Am Coll Cardiol (2006) 48: 854
Aetiopathology of Paroxysmal AFib
n = 161
60
50
40
30
20
10
0
Cardiomyopathy Miscellaneous
Ischaemic
cardiopathy
Hypertension
Valvular
disease
Idiopathic AFib
Camm AJ & Obel OA Am J Cardiol (1996) 78: 3
Aetiopathology of Chronic AFib
n = 264
35
30
25
20
15
10
5
0
Cardiomyopathy Miscellaneous
Ischaemic
cardiopathy
Hypertension
Valvular
disease
Idiopathic AFib
Camm AJ & Obel OA Am J Cardiol (1996) 78: 3
Presentation of AFib in EuroHeart
Survey
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
60
50
% patients
40
36
36
28
30
20
10
0
Paroxysmal AFib
Persistent AFib
Permanent AFib
Nieuwlaat R, et al. Eur Heart J (2005) 26: 2422
Presentation of AFib in Olmsted
County Study
Olmsted County
– 4,618 residents who had ECG-confirmed first AFib in the
period 1980-2000
% patients
80
74
60
40
26
20
0
Paroxysmal AFib
Other forms of AFib
Miyasaka Y, et al. Circulation (2006) 114: 119
Type of AFib at Diagnosis
and Last Follow-up
Patients < 60 years
Patients (%)
100
75
At diagnosis
At follow-up
70
58
50
25
0
21
22
20
9
Lone AFib
Recurrent AFib
Chronic AFib
Patients > 60 years
Patients (%)
100
75
58
67
50
29
25
0
13
13
Lone AFib
20
Recurrent AFib
Chronic AFib
Chugh SS, et al. J Am Coll Cardiol (2001) 37: 371
2. Epidemiology of AFib
Epidemiology of AFib
Prevalence
Prevalence of AFib
ATRIA study
General population-based
prevalence
0.95%
Go AS, et al. JAMA (2001) 285: 2370
Prevalence in Europe
UK cost analysis study 1995-2000
• 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
General population-based
prevalence
0.90%
– 5% in patients aged >65
Stewart S, et al. Heart (2004) 90: 286
Prevalence in Europe
Rotterdam study
• 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
Heeringa J, et al. Eur Heart J (2006) 27: 949
Prevalence of AFib
Olmsted County study
General population-based
prevalence
2.5%
Miyasaka Y, et al. Circulation (2006) 114: 119
Reasons Why the Prevalence of AFib may
have Previously been Underestimated
Olmsted County
ATRIA study
Different study settings
Entire population in a Midwest US
county
HMO in California
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
• Both may, however, be significant underestimates based on
the high prevalence of silent, asymptomatic AFib (25% in
Olmsted County study)
Miyasaka Y, et al. Circulation (2006) 114: 119
Prevalence of AFib in the General
Population by Age
Framingham study
– 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
Prevalence (%)
12
10
8.8
8
4.8
6
4
2
0
0.5
50-59
1.8
60-69
70-79
80-89
Wolf PA, et al. Stroke (1991) 22: 983
Prevalence of AFib Stratified by
Age and Sex
ATRIA study
Men 1.1% Women 0.8%
Mean 0.95%
12
Prevalence (%)
Women
Men
10
9.1
7.3
8
5.0
6
3.0
4
2
0
11.1
10.3
0.1 0.2
0.4 0.9
<55
55-59
1.0
1.7
60-64
7.2
5.0
3.4
1.7
65-69
70-74
75-79
80-84
≥85
Age (years)
No.
Women
Men
530
310
566
896
1498
1572
1291
1132
1259
634
934
1426
1907
1886
1374
759
Go AS, et al. JAMA (2001) 285: 2370
Similar Prevalence in the General
Population across Epidemiological Studies
14
12
10
8
6
4
2
0
35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79
>80
Framingham Study
Western Australia Study
Mayo Clinic Study Cardiovascular Health Study
Feinberg WM, et al. Arch Intern Med (1995) 155: 469
Age Distribution of AFib versus US
Population Figures
Median age: 75 y
Population with atrial fibrillation
US population
500
400
20000
300
200
10000
100
0
Population with AFib x 1000
US population x 1000
30000
0
<5
10-14
5-9
20-24
15-19
30-34
25-29
40-44
35-39
50-54
45-49
60-64
55-59
70-74
65-69
80-84
75-79
90-94
85-89
>95
Age (years)
AF: 2.3% >40y; 5.9% >65y
70%: >65y <85y
Feinberg WM, et al. Arch Intern Med (1995) 155: 469
Variation in Prevalence According to
Ethnicity
• Significantly lower prevalence of AFib in Indo-
Asians and African Americans
Prevalent AFib in 1,373 patients with HF
– Variation not explained by differences in traditional risk
factors for AFib
60
p<0.001
50
40
38.3
30
19.7
20
10
0
Caucasian
(n=1150)
African American
(n=223)
Ruo B, et al. J Am Coll Cardiol (2004) 43: 429
Conway DSG & Lip GYH Am J Cardiol (2003) 92: 1476
Prevalence of AFib in the General
Population in Selected Countries
Based on population prevalence of 0.95% (ATRIA Study)
USA ( 298 million inhabitants)
 2.8 million people
European Union ( 456 million
inhabitants of 25 member states)
 4.3 million people
Japan ( 128 million inhabitants)
 1.2 million people
Prevalence of AFib in the General
Population in Selected Countries
Based on population prevalence of 2.5% (Olmsted Study)
USA ( 298 million inhabitants)
 7.45 million people
European Union ( 456 million
inhabitants of 25 member states)
 11.4 million people
Japan ( 128 million inhabitants)
 3.2 million people
Prevalence of AFib in …
Country specific numbers
• General population prevalence:
• Population of ………:
0.90-0.95% to 2.5%
X million
Prevalence:
• 0.90-0.95 x X million to 2.5 x X million
Progression from Paroxysmal to
Persistent AFib
Transformation of paroxysmal AFib to persistent AFib:
5.5% patients per year
Ratio in sinus rhythm
1.0
0.8
Without structural heart disease
0.6
0.4
With structural heart disease
0.2
0
0
5
Paroxysmal AF onset
10
15
20
25
30
Follow-up (years)
Kato T, et al. Circ J (2004) 68: 568
Prevalence of Recurrent AFib in
Europe
• Based on ~65% of all cases of AFib (EuroHeart
Survey)
European Union ( 456 million
inhabitants of 25 member states)
 From 2.8 million people up to
7.4 million
(based on prevalence range of 0.95% to 2.5%)
Nieuwlaat R, et al. Eur Heart J (2005) 26: 2422
Prevalence of Chronic AFib in
Europe
• Based on ~35% of all cases of AFib (EuroHeart
Survey)
European Union ( 456 million
inhabitants of 25 member states)
 From 1.5 million people up to 4
million
(based on prevalence range of 0.95% to 2.5%)
Nieuwlaat R, et al. Eur Heart J (2005) 26: 2422
Epidemiology of AFib
Incidence
Incidence of AFib in the General
Population
Framingham study
Observational period: 20 years
2% for paroxysmal AFib
2% for chronic AFib
= 0.2% per year
Kannel WB, et al. Am Heart J (1983) 106: 389
Incidence of AFib in the General
Population (European Data)
Renfrew-Paisley study
Observational period: 20 years
patients aged 45-65
Incident hospitalization
Men = 0.18% per year
Women = 0.17% per year
Stewart S, et al. Heart (2001) 86: 516
Incidence of AFib in the General
Population
Olmsted County study
Observational period: 20 years
First documented AFib episode
Incidence
= 0.34% per year
Miyasaka Y, et al. Circulation (2006) 114: 119
Incidence of AFib in the General
Population – Gender Differences
Framingham study
Observational period: 38 years
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
Olmsted County study
Observational period: 20 years
Men
0.49 %
Women
0.28 %
Ratio men to women = 1.86
Miyasaka Y, et al. Circulation (2006) 114: 119
Age-Specific Incidence of AF
Summary of available data
Framingham (men)
Framingham (women)
Incidence/1,000 person-years
60
CHS (men)
CHS (women)
Olmsted (men)
Olmsted (women)
40
20
0
30
40
50
60
70
80
90
100
Age (years)
Miyasaka Y, et al. Circulation (2006) 114: 119
Incidence of AFib in the General
Population in Selected Countries
Based on population incidence of 0.2% per year
USA ( 298 million inhabitants)
 600,000 new cases every year
European Union ( 456 million
inhabitants of 25 member states)
 900,000 new cases every year
Japan ( 128 million inhabitants)
 250,000 new cases every year
Incidence of AFib – Lifetime Risk
Framingham study – 1 in 4 lifetime risk of developing AFib
• 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)
Lloyd-Jones DM, et al. Circulation (2004) 110: 1042
Incidence of AFib – Lifetime Risk
Rotterdam study
• 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
Heeringa J, et al. Eur Heart J (2006) 27: 949
Incidence of AFib in …
Country specific numbers
• General population incidence:
• Population of ………:
0.2% per year
X million
Incidence:
• 0.2 x X million per year
Epidemiology of AFib
Secular Trends in Prevalence
and Incidence
Prevalence of AFib and Flutter
ATRIA study
– Prevalence increasing annually by 3-4%
Adults with AFib (millions)
– The prevalence of AFib is estimated to increase over 2-fold over the
next decades
7.0
4.78
6.0
5.16
5.42
5.61
4.34
5.0
3.80
3.33
4.0
3.0
2.08
2.26
2.44
2.66
2.94
2.0
1.0
0
1990 1995 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050
Year
Go AS, et al. JAMA (2001) 285: 2370
Prevalence of AFib
Olmsted County study
15.2
Projected number of persons with AF
(millions)
16
15.9
14.3
14
13.1
11.7
12
10.2
10
8.9
8
6
4
11.1
7.7
5.1
5.1
5.9
5.6
6.1
6.8
7.5
12.1
10.3
9.4
6.7
11.7
8.4
2
0
2000
2005
2010
2015
2020
2025
2030
2035
2040
2045
2050
Year
Miyasaka Y, et al. Circulation (2006) 114: 119
Increasing Incidence of AFib
Olmsted County study
Incidence/1,000 person-years
6
5
4
3
2
Men
Overall
Women
1
0
1980
1985
1990
1995
2000
Year
Miyasaka Y, et al. Circulation (2006) 114: 119
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: 119
Steinberg 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: 2370
Miyasaka Y, et al. Circulation (2006) 114: 119
3. Aetiology of AFib
AFib May Be Focal or Caused by
Reentrant Wavelets
– May be initiated by focal triggers and maintained by substrate
mediated factors that become more prevalent as AFib progresses
Multiple Wavelets
Focal activation
SVC
SVC
LA
LA
RA
RA
PVs
PVs
IVC
IVC
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
Paroxysmal
Persistent
Relative importance
Permanent
Trigger/initiation
Substrate/maintenance
AFib duration
SYMPATHETIC TONE
PARASYMPATHETIC TONE
SYMPATHETIC TONE
PARASYMPATHETIC TONE
Modulating factors
“Catheter ablation of arrhythmias”
(2nd
Adapted from Zipes D, et al. (2002)
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
Electrophysiological
factors
Anatomic factors
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
ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation
J Am Coll Cardiol (2006) 48: 854
Lone or Idiopathic AFib
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
2% - 31%
Brand FN, et al. JAMA (1985) 254: 3449
Kopecky SL, et al. N Engl J Med (1987) 317: 669
Scardi S, et al. Am Heart J (1999) 137: 686
ACC/AHA/ESC 2006 Guidelines J Am Coll Cardiol (2006) 48: 854
Secondary AFib
AFib that occurs in association with a
detectable heart disease or other
pathological conditions that may promote it
Prevalence
 90 %
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
ATRIA study
Characteristic
(n=17,974)
Diagnosed heart failure
29.2%
Hypertension
49.3%
Diabetes mellitus
17.1%
Previous coronary heart disease
34.6%
Baseline characteristics of 17,974 adults with diagnosed atrial fibrillation,
July 1, 1996-December 31, 1997
Go AS, et al. JAMA (2001) 285: 2370
Risk Factors for AFib
ALFA study
Characteristic
(n=534)
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%
Levy S, et al. Circulation (1999) 99: 3028
Hypertension in Patients with AFib
Paroxysmal
persistent
Patients with hypertension (%)
70
60
Recurrent
persistent
Paroxysmal
persistent
Recurrent
persistent
Recurrent
persistent
Paroxysmal
persistent
50
40
30
20
10
0
PIAF
RACE
STAF
HOT CAFE
AFFIRM*
AFFIRM**
*HT as predominant cardiac diagnosis; **Overall prevalence of hypertension
Camm AJ & Savelieva I Dialogues in Cardiovasc Med (2003) 8: 183
Prevalence of AFib in Patients with
Heart Failure
Predominant
NYHA type
I
II-III
III-IV
IV
Prevalence of
AFib
Study, y
4
SOLVD-prevention 1992
10 - 26
SOLVD-treatment 1991
CHF-STAT 1995
MERIT-HF 1999
Diamond 1999
20 - 29
Middlekauf 1991
Stevenson 1996
GESICA 1994
50
CONSENSUS 1987
ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation
J Am Coll Cardiol (2001) 38: 1266i
Incidence of AFib in Patients with
HF
Framingham study
• Development of CHF at AFib onset:
1000 person-years
• Development of AF at CHF onset:
person-years)
3.3% (33 per
5.4% (54 per 1000
Minnesota study
• 24% developed a first CHF during 6.1y follow-up
• Development of CHF at AFib onset:
1000 person-years)
4.4% (44 per
Wang TJ, et al. Circulation (2003) 107: 2920
Miyasaka Y, et al. Eur Heart J (2006) 27: 936
4. Pathophysiology of AFib
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
200
Change (%)
150
100
50
0
Cardiac
output
Pulmonary
capillary
wedge
pressure
Pulmonary
artery
diastolic
pressure
Pulmonary
artery
pressure
Systemic
vascular
resistance
Clark DM, et al. J Am Coll Cardiol (1997) 30: 1039
The AFib Vicious Cycle
F
AFCl 
APD 
Cytosolic
Ca++
Contractility 
Electrical
remodeling
Ca++
channels
AF
Circuit
size
Stretch
Contractile
remodeling
Dilatation
Compliance 
WL 
Zig-zag
conduction
Structural
remodeling
Anisotropy
Connexins
Fibrosis
Allessie MA J Cardiovasc Electrophysiol (1998) 12: 1378
AFib Begets AFib
Transformation of paroxysmal AFib to persistent AFib:
5.5% patients per year
Ratio in sinus rhythm
1.0
0.8
Without structural heart disease
0.6
0.4
With structural heart disease
0.2
0
0
5
Paroxysmal AFib onset
10
15
20
25
30
Follow-up (years)
Kato T, et al. Circ J (2004) 68: 568
Sustained AFib Induces Structural
Changes
– While acute physiological changes may be reversible, AFib can
initiate irreversible fibrosis at many cardiac sites
18
16
control
CHF
week 5 of AFib
* p<0.01 vs CTL
*
Fibrosis (%)
14
12
10
*
*
*
*
*
*
*
*
*
*
*
*
*
8
6
4
2
0
Shinagawa K, et al. Circulation (2002) 105: 2672
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
Symptomatology of AFib
Patients experiencing symptom (%)
ALFA study: total population, n=756
80
60
54.1
44.4
40
20
10.1
10.4
11.4
Chest pain
Syncope,
dizzy spells
None
14.3
0.9
0
Other
Fatigue
Dyspnoea
Palpitations
Levy S, et al. Circulation (1999) 99: 3028
Symptoms of AFib
ALFA study: paroxysmal n=167; permanent/chronic n=389
Palpitations
Dyspnea
Syncope, dizziness
Chest pain
Fatigue
Paroxysmal
Permament
None
0
25
50
75
100
Levy S, et al. Circulation (1999) 99: 3028
Symptoms of AFib According to
Classification
ALFA study
Symptoms
Paroxysmal
% (n=167)
Chronic
% (n=389)
Recent onset
% (n=200)
Palpitations
79.0
44.7
51.5
Chest pain
13.2
8.2
11.0
Dyspnoea
22.8
46.8
58.0
Syncope
17.4
8.0
9.5
Fatigue
12.6
13.1
18.0
Other
0
1.8
0
None
5.4
16.2
7.0
Levy S, et al. Circulation (1999) 99: 3028
Asymptomatic AFib
CARAF study
• 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
Olmsted County study
• 25% of patients diagnosed with AFib on ECG were
asymptomatic
Kerr C, et al. Eur Heart J (1996) 17 Suppl C: 348
Miyasaka Y, et al. Circulation (2006) 114: 119
Asymptomatic AFib
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 transtelephonic 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
AFib Symptoms - Summary
• 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
Page RL, et al. Circulation (1994) 89: 224
ACC/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
AFib has an Impact on All Aspects
of QoL
SF-36 quality of life scores in AFib patients and healthy subjects
SF-36 scale
AFib patients
(n=152)
Healthy controls
(n=47)
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*
* p<0.001
Dorian P, et al. J Am Coll Cardiol (2000) 36: 1303
Poorer QoL vs Healthy Controls and
Patients with Coronary Artery Disease
QoL Survey 2000
– 152 patients with paroxysmal or persistent AFib
100
Healthy controls
SF-36 scale
90
Recent MI
80
PTCA
AFib
70
CHF
60
50
40
30
Physical
Vitality
General
Mental
Emotional
Social
Dorian P, et al. J Am Coll Cardiol (2000) 36: 1303
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
Symptom score
Paroxysmal
Persistent
Permanent
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
Luderitz B & Jung W Arch Intern Med (2000) 160: 1749
Prognostic Issues
Thromboembolic Complications
Thromboembolic Events
Annual incidence in patients with AFib
AFib
4.5%
(2.5% disabling strokes)
Controls
0.2% - 1.4%
The Stroke Prevention in Atrial Fibrillation Investigators Arch Int Med (1992) 116: 1
Thromboembolic Events
Annual incidence in patients with AFib
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%
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
Risk Factors for Ischaemic Stroke
and Systemic Embolism in AFib
Relative Risk
RISK FACTORS (control groups)
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
Atrial Fibrillation Investigators Arch Intern Med (1994) 154: 1449
Clinical Risk Factors for
Thromboembolic Events
– Congestive heart failure
– History of hypertension
Risk of Stroke per year (%)
– Previous arterial thromboembolism
20
17.6
10
7.2
2.5
0
1 risk factor
2 risk factors
3 risk factors
The Stroke Prevention in Atrial Fibrillation Investigators. Ann Intern Med (1992) 116: 1
AFib is Responsible for 15-20% of
all Strokes
Cumulative stroke incidence (%)
– AFib is responsible for a 5-fold increase in the risk of
ischaemic stroke
12
8
Women AFib+
Men AFib+
Women AFib-
Men AFib-
4
0
1
2
3
4
5
1
2
3
4
5
Years of follow-up
Wolf PA, et al. Stroke (1991) 22: 983
Go AS, et al. JAMA (2001) 285: 2370
Friberg J, et al. Am J Cardiol (2004) 94: 889
Stroke in Patients with AFib
The Austrian Stroke Registry
• 992 consecutive patients recruited with stroke –
% of patients (n=304)
AFib diagnosed in 304 (31%)
50
Men
40
Women
30
20
10
0
0
<65
65-74
75-84
>84
Age groups (year)
Steger S, et al. Eur Heart J (2004) 25: 1734
Higher Mortality and More Severe Stroke in
Patients with AFib
The Austrian Stroke Registry
50
40
p<0.0004
30
20
10
0
0
Stroke severity
(Barthel Index on
admission)
Mortality (%)
50
p<0.0004
40
30
20
10
0
No AFib
AFib
0
No AFib
AFib
Steger S, et al. Eur Heart J (2004) 25: 1734
Higher Mortality and More Severe Stroke in
Patients with AFib
The European Community Stroke Project
• 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
Lamassa M, et al. Stroke (2001) 32: 392
AFib is Associated with
Progressive Risk of Stroke
• Independent predictor of stroke recurrence and severity
Cumulative hazard of fatal stroke
0.05
0.04
AF Present
0.03
0.02
AF Absent
0.01
0
0
10
20
30
40
50
60
70
80
90
100
Months of follow-up
Simons LA, et al. Stroke (1998) 29: 1341
Stroke Risk Equivalent in Recurrent
and Permanent (Chronic) AFib
• Rate of ischaemic stroke 3.2% in intermittent AFib and
Annualized stroke
rate (% / yr)
3.3% in sustained AFib
14
12
Intermittent
Sustained
10
8
6
4
2
0
Low-risk
Moderate-risk
High-risk
Hart RG, et al. J Am Coll Cardiol (2000) 35: 183
Prognostic Issues
Heart Failure and Tachycardiainduced Cardiomyopathy
AFib and Congestive Heart Failure
ATRIA study
Characteristic
(n= 17974)
Age, mean (SD), years
≥80years
Women
71.2 (12.2)
25.4
43.4
Known valvular heart disease
Previous ischaemic stroke
Diagnosed heart failure
Hypertension
Diabetes mellitus
Previous coronary heart disease
Angina
Myocardial infarction
4.9
8.9
29.2
49.3
17.1
34.6
21.8
9.4
Go AS, et al. JAMA (2001) 285: 2370
Prevalence of AFib in Major Heart
Failure Trials
Prevalence of AFib
(%)
2-fold excess risk of mortality compared with healthy control
NYHA Functional Class
I
II-III
III-IV
IV
60
49.8
40
25.8
20
4.2
0
10.1
SOLVD
SOLVD
prevention treatment
14.4
V-HeFT
28.9
15.4
CHF-STAT DIAMOND
CHF
GESICA CONSENSUS
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
Cumulative incidence
of CHF (%)
30
25
20
15
10
5
0
0
1
2
3
4
5
Years after diagnosis
Miyasaka Y, et al. Eur Heart J (2006) 27: 936
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
ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation
J Am Coll Cardiol (2006) 48: 854
AFib Significantly Increases CHFrelated Death and Hospitalization
AF present
AF absent
60
Event rate (%)
50
40
30
20
10
0
Relative risk 1.35 (95% Cl 1.20-1.51); p<0.001
0
1
2
3
4
5
Time (years)
1920
1666
1458
1207
426
426
358
299
245
97
Swedberg K, et al. Eur Heart J (2005) 26: 1303
Time to CV Death or Hospitalization for
Heart Failure in Patients with AFib
Cumulative
distribution function
0.50
0.45
0.40
AF at baseline (Low EF)
No AF at baseline (Low EF)
AF at baseline (Preserved)
No AF at baseline (Preserved)
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0
0
1
2
3
3.5
Year
Low EF: Hazard ratio 1.29 (95% Cl 1.14-1.46); p<0.001
Preserved EF (PEF): Hazard ratio 1.72 (95% Cl 1.45-2.06); p<0.001
Number at risk
No AF & Low EF
3906
3207
2755
1963
No AF & PEF
2545
2294
2096
1276
AF & Low EF
670
509
417
289
AF & PEF
478
399
353
203
Olsson LG, et al. J Am Coll Cardiol (2006) 47: 1997
Tachycardia-induced
Cardiomyopathy
Left Ventricular Dysfunction Due to
Atrial Fibrillation in Patients Initially Believed
to Have Idiopathic Dilated Cardiomyopathy
Martha Grogan, Hugh C. Smith, Bernard J. Gersh and
Douglas L. Wood
Grogan M, et al. Am J Cardiol (1992) 69: 1570
Tachycardia-induced
Cardiomyopathy
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Grogan M, et al. Am J Cardiol (1992) 69: 1570
Tachycardia-induced
Cardiomyopathy
Heart Failure and Sudden Death in Patients
with Tachycardia-Induced Cardiomyopathy
and Recurrent Tachycardia
Nerheim P, Birger-Botkin S, Piracha L, Olshansky B
Circulation (2004) 110: 247-252
Nerheim P, et al. Circulation (2004) 110: 247
Tachycardia-induced
Cardiomyopathy
• 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
Mortality Associated with AFib
Framingham Heart Study, n=5209
Mortality during follow-up (%)
80
60
Men AFib+
Women AFib+
40
Men AFibWomen AFib20
0
0
1
2
3
4
5
6
7
8
9
10
Follow-up (y)
Benjamin EJ, et al. Circulation (1998) 98: 946
Increased Risk of Cardiovascular
Events
At least one cardiovascular event (%)
Death or hospitalization in individuals with CV event(s) after 20
years
Men
100
Women
89
80
66
60
45
40
27
20
0
AFib
No AFib
AFib
No AFib
Stewart S, et al. Am J Med (2002) 113: 359
Relative Risk of Mortality in
Patients with AFib
2-fold excess risk of mortality compared with healthy controls
Relative risk of
mortality
8
6
4
2
0
Manitoba
Framingham Framingham
(overall)
(no HD)
Whitehall
Total and Cardiovascular Mortality
Risk
PARIS Prospective study I
Total mortality RR
Variable
(IC 95%)
Cardiovascular mortality RR
p
(IC 95%)
p
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
Jouven X, et al. Eur Heart J (1999) 20: 896
Prognostic Issues Associated with
AFib - Summary
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
7. Economic Burden of AFib
AFib Healthcare Cost Analysis – UK
Data
UK 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)
Stewart S, et al. Heart (2004) 90: 286
Incremental AFib Healthcare Costs
UK costs for AFib in 1995 vs 2000
• 0.9-2.4% of total healthcare budget in 2000
Cost of heart failure
admission
+50%
Cost of stroke
admission
+48%
+5.1%
warfarin use
10% admission
+7.4%
10% communitybased care
+5.6%
Base cost of AF
in 2000
0
100
200
300
400
500
600
700
Total health care expenditure (£ million)
Base cost
of AFib
Base cost of associated
conditions and
procedures
Incremental cost
of AFib
Other costs
Stewart S, et al. Heart (2004) 90: 286
Major Costs in Treatment of AFib
Stewart UK Study
6%
13%
50%
Hospitalizations
Drugs
12%
GP outpatient referral
GP visits
Post discharge outpatient
visits
20%
Stewart S, et al. Heart (2004) 90: 286
Major Costs in Treatment of AFib
COCAF Study
8%
9%
2%
6%
52%
Hospitalizations
Drugs
Consultations
Further investigations
Paramedical procedures
Loss of work
23%
Le Heuzey JY, et al. Am Heart J (2004) 147:121
Cost of AFib (US)
US National Discharge Survey
• 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
Cost of AFib (US)
US National Discharge Survey – Age-specific prevalence
(per 10,000 population) for hospitalizations with AFib
Per 10,000 persons
Principal diagnosis
Any diagnosis
140
1400
120
1200
100
1000
80
800
60
600
40
400
20
200
0
1985
1987
1989
1991
1993
Years
1995
1997
1999
0
1985
85+
75-84
65-74
55-64
35-54
1987
1989
1991
1993
1995
1997
1999
Years
Wattigney WA, et al. Circulation (2003) 108: 711
Increase in Admissions for AFib
Number of AFib admissions
Number of admissions with a primary diagnosis of AFib to
hospitals in the US 1996-2001
380,000
360,000
340,000
320,000
300,000
280,000
1996
1997
1998
1999
2000
2001
Khairallah F, et al. Am J Cardiol (2004) 94: 500
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
Austria Stroke Registry
• 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
Steger S, et al. Eur Heart J (2004) 25: 1734
Cost of AFib (Europe)
FIRE study
• 4507 consecutive patients with AFib/flutter admitted to ER
enrolled in FIRE study (1.5%
admissions)
of all ER
• 61.9% of AFib/flutter patients were hospitalized (3.3%
all hospitalizations)
of
• Mean hospital stay 7+6 days
Santini M, et al. Ital Heart J (2004) 5: 205
Impact on the Healthcare System
AFib Patient Healthcare Utilisation (per patient/year)
Bordeaux
Ghent
Milwaukee
TOTAL, mean
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
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
Adults with AFib (millions)
years
7.0
4.78
6.0
5.16
5.42
5.61
4.34
5.0
3.80
3.33
4.0
3.0
2.08
2.26
2.44
2.66
2.94
2.0
1.0
0
1990 1995 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050
Year
Miyasaka Y, et al. Circulation (2006) 114: 119
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