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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 FibrillationJ Am Coll Cardiol (2006) 48: 854
AFib
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
ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial FibrillationJ Am Coll Cardiol (2006) 48: 854
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
General population-based prevalence
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
General population-based prevalence
2.5%
Olmsted County study
Miyasaka Y, et al. Circulation (2006) 114: 119
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
Miyasaka Y, et al. Circulation (2006) 114: 119
• 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
USA ( 298 million inhabitants)
11.4 million people
European Union ( 456 million inhabitants of 25 member states)
Based on population prevalence of 2.5% (Olmsted Study)
3.2 million people
Japan ( 128 million inhabitants)
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%)
European Union ( 456 million inhabitants of 25 member states)
•Based on ~65% of all cases of AFib (EuroHeart Survey)
Nieuwlaat R, et al. Eur Heart J (2005) 26: 2422
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%)
European Union ( 456 million inhabitants of 25 member states)
•Based on ~35% of all cases of AFib (EuroHeart Survey)
Nieuwlaat R, et al. Eur Heart J (2005) 26: 2422
Epidemiology of AFib
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
Stewart S, et al. Heart (2001) 86: 516
Renfrew-Paisley study
Incidence of AFib in the General Population
Incidence
= 0.34% per year
Observational period: 20 yearsFirst documented AFib episode
Olmsted County study
Miyasaka Y, et al. Circulation (2006) 114: 119
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
Observational period: 38 years
Framingham study
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
Miyasaka Y, et al. Circulation (2006) 114: 119
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)
Miyasaka Y, et al. Circulation (2006) 114: 119
Age (years)
Incidence of AFib in the General Population in Selected Countries
600,000 new cases every year
USA ( 298 million inhabitants)
900,000 new cases every year
European Union ( 456 million inhabitants of 25 member states)
Based on population incidence of 0.2% per year
250,000 new cases every year
Japan ( 128 million inhabitants)
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
Epidemiology of AFib
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
Miyasaka Y, et al. Circulation (2006) 114: 119
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
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: 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
3. Aetiology of AFib
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
Paroxysmalpersistent
Paroxysmalpersistent
*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)
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
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
Levy S, et al. Circulation (1999) 99: 3028
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
Levy S, et al. Circulation (1999) 99: 3028
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
Levy S, et al. Circulation (1999) 99: 3028
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
Olmsted County 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
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
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
ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial FibrillationJ Am Coll Cardiol (2006) 48: 854
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
Tachycardia-induced Cardiomyopathy
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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
Tachycardia-induced Cardiomyopathy
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
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
Stewart S, et al. Heart (2004) 90: 286
• 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
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 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
Stewart S, et al. Heart (2004) 90: 286
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
Steger S, et al. Eur Heart J (2004) 25: 1734
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
Miyasaka Y, et al. Circulation (2006) 114: 119
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