Transcript AFib Management and the Role of Catheter Ablation
Contents - Slide Kit Section I
Section I. AFib Overview 1.
2.
3.
4.
5.
6.
7.
Definition and classification Epidemiology Aetiology of AFib Pathophysiology of AFib Symptoms Prognostic factors Economic burden of AFib
Contents – Slide Kit Section II
Section II. Clinical Management of AFib 1.
2.
• •
Clinical Evaluation 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 2.
3.
4.
5.
6.
7.
8.
1.
Left atrial (LA) and pulmonary vein (PV) anatomy Catheter ablation techniques Technological issues Success rates Complication rates Cost-effectiveness Indications for catheter ablation 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 Persistent Permanent Spontaneous termination usually < 7 days and most often < 48 hours Does not interrupt spontaneously and needs therapeutic intervention for termination (either pharmacological or electrical cardioversion) 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
(self-terminating)
Persistent
(non-self-terminating)
Permanent
ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation
J Am Coll Cardiol
(2006) 48: 854
60 Aetiopathology of Paroxysmal AFib
n = 161
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
35 Aetiopathology of Chronic AFib
n = 264
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 40 30 20 10 0 36 28 36 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
74 80 60 40 20 0 26 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
100 75 50 25 0 At diagnosis At follow-up 70 58 21 20 Lone AFib Recurrent AFib
Patients > 60 years
22 9 Chronic AFib 100 75 50 25 0 13 13 Lone AFib 29 20 58 67 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 ATRIA study Olmsted County HMO in California Different study settings 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
• 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 12 10 8 6 4 2 0
0.5
50-59
1.8
60-69
4.8
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%
Women Men 12 10 8 6 4 2 0
0.1
0.2
<55
0.4
0.9
55-59
1.0
1.7
60-64
1.7
3.0
3.4
5.0
65-69 70-74 Age (years) 75-79
7.2
10.3
9.1
11.1
80-84 ≥85
No.
Women Men
530 1259 310 634 566 934 896 1426 1498 1907 1572 1886 1291 1374 1132 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 Mayo Clinic Study Western Australia Study Cardiovascular Health Study
Feinberg WM, et al.
Arch Intern Med
(1995) 155: 469
Age Distribution of AFib versus US Population Figures
30000 Median age: 75 y Population with atrial fibrillation US population 20000 500 400 300 200 10000 100 0 <5 5-9 10-14 20-24 15-19 30-34 25-29 40-44 35-39 50-54 45-49 Age (years) 60-64 55-59 70-74 65-69 80-84 75-79 90-94 85-89 >95 AF: 2.3% >40y; 5.9% >65y 70%: >65y <85y 0 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
– Variation not explained by differences in traditional risk factors for AFib
60 50 40 30 20 10 0 38.3
p<0.001
19.7
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: 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
Progression from Paroxysmal to Persistent AFib Transformation of paroxysmal AFib to persistent AFib: 5.5% patients per year
1.0
0.8
Without structural heart disease 0.6
0.4
0.2
With structural heart disease 0 0 5
Paroxysmal AF onset
10 15 20 Follow-up (years) 25 30 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
60 40 Framingham (men) Framingham (women) CHS (men) CHS (women) Olmsted (men) Olmsted (women) 20 0 30 40 50 60 70 Age (years) 80 90 100 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: 0.2% per year • Population of ………: 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% – The prevalence of AFib is estimated to increase over 2-fold over the next decades 7.0
6.0
5.0
4.0
3.0
2.0
1.0
2.08 2.26
2.44
2.66
2.94
3.33
3.80
4.34
4.78
5.16
5.42
5.61
0 1990 1995 2000 2005 2010 2015 2020
Year
2025 2030 2035 2040 2045 2050 Go AS, et al.
JAMA
(2001) 285: 2370
Prevalence of AFib
Olmsted County study
15.9
16
15.2
14.3
14 12 10 8 6
5.1
4
5.1
2
5.9
5.6
6.7
6.1
7.7
6.8
8.9
7.5
10.2
8.4
11.7
9.4
13.1
10.3
11.1
11.7
12.1
0 2000 2005 2010 2015 2020 2025
Year
2030 2035 2040 2045 2050 Miyasaka Y, et al.
Circulation
(2006) 114: 119
Increasing Incidence of AFib Olmsted County study
6 5 4 3 2 1 0 1980 1985 1990
Year
Men Overall Women 1995 2000 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
Focal activation Multiple Wavelets 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 Permanent Trigger/initiation Substrate/maintenance
AFib duration
SYMPATHETIC TONE PARASYMPATHETIC TONE SYMPATHETIC TONE PARASYMPATHETIC TONE
Modulating factors
“Catheter ablation of arrhythmias” (2 nd 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
Anatomic factors
Ion channel expression Altered gap junction distribution Altered sympathetic innervation Atria dilatation Pulmonary vein dilatation Atrial myocyte apoptosis Interstitial fibrosis
Electrophysiological factors
Shortened atrial refractive period Atrial myocyte calcium overload Atrial myocyte triggered activity or automaticity Decreased atrial conduction velocity Non-homogeneity of atrial refractoriness Dispersion of conduction 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
Diagnosed heart failure
Hypertension
Diabetes mellitus Previous coronary heart disease
Baseline characteristics of 17,974 adults with diagnosed atrial fibrillation, July 1, 1996-December 31, 1997 (n=17,974)
29.2%
49.3%
17.1% 34.6%
Go AS, et al.
JAMA
(2001) 285: 2370
Risk Factors for AFib ALFA study
Characteristic
Hypertensive heart disease Valvular disease Coronary artery disease Dilated cardiomyopathy Hypertrophic cardiomyopathy Other
(n=534)
30.3% 26.2% 23.6% 13.1% 6.9% 8.6%
Levy S, et al.
Circulation
(1999) 99: 3028
30 20 10 0 Hypertension in Patients with AFib Patients with hypertension (%) 70 Recurrent persistent Recurrent persistent Paroxysmal persistent 60 Paroxysmal persistent Recurrent persistent Paroxysmal persistent 50 40 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 4 10 - 26 20 - 29 50
Study, y
SOLVD-prevention 1992 SOLVD-treatment 1991 CHF-STAT 1995 MERIT-HF 1999 Diamond 1999 Middlekauf 1991 Stevenson 1996 GESICA 1994 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
3.3%
(33 per • Development of AF at CHF onset: person-years)
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
200 150 100 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
AFCl F APD
Electrical remodeling
WL Cytosolic Ca ++ Ca ++ channels
AF Stretch
Circuit size
Contractile remodeling
Zig-zag conduction
Structural remodeling
Contractility Anisotropy Dilatation Connexins Compliance Fibrosis Allessie MA
J Cardiovasc Electrophysiol
(1998) 12: 1378
AFib Begets AFib Transformation of paroxysmal AFib to persistent AFib: 5.5% patients per year
1.0
0.8
Without structural heart disease 0.6
0.4
0.2
With structural heart disease 0 0 5
Paroxysmal AFib onset
10 15 20 Follow-up (years) 25 30 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 control CHF week 5 of AFib * p<0.01 vs CTL 18 16 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 ALFA study: total population, n=756 80 60 54.1
44.4
40 20 0.9
0 Other 10.1
10.4
Chest pain Syncope, dizzy spells 11.4
None 14.3
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 None 0 25 50 75 Paroxysmal Permament 100 Levy S, et al.
Circulation
(1999) 99: 3028
Symptoms of AFib According to Classification ALFA study Symptoms 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
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 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
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
General health Physical functioning Role physical Vitality Mental health Role emotional Social functioning Bodily pain
AFib patients (n=152)
54
±
21 68
±
27 47
±
42 47
±
21 68
±
18 65
±
41 71
±
28 69
±
19
Healthy controls (n=47)
78
±
17* 88
±
19* 89
±
28* 71
±
14* 81
±
11* 92
±
25* 92
±
14* 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 60 50 40 90 80 70 Healthy controls Recent MI PTCA AFib CHF 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 Severity of last episode (0-10) Severity of average episode (0-10) Total symptoms (0-6) Paroxysmal Persistent Permanent 5.0 4.5 2.8 5.5* 4.5 3.2
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 RISK FACTORS (control groups) Previous stroke or TIA History of hypertension Congestive heart failure Advanced age (continuous per decade) Diabetes mellitus Coronary artery disease Relative Risk 2.5
1.6
1.4
1.4
1.7
1.5
Atrial Fibrillation Investigators
Arch Intern Med
(1994) 154: 1449
Clinical Risk Factors for Thromboembolic Events
– Congestive heart failure – History of hypertension – Previous arterial thromboembolism 20
17.6
10 0
7.2
2.5
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
– AFib is responsible for a 5-fold increase in the risk of ischaemic stroke 12 8 4 Women AFib+ Women AFib Men AFib+ Men AFib 0 1 2 3 4 5
Years of follow-up
1 2 3 4 5 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 – AFib diagnosed in 304 (31%)
50 40 30 20 10 0 0 Men Women <65 65-74 75-84
Age groups (year)
>84 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 30 20 10 0 0 p<0.0004
No AFib AFib 50 40 30 20 10 0 0 p<0.0004
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 0.05
0.04
0.03
AF Present 0.02
0.01
AF Absent 0 0 10 20 30 40 50 60
Months of follow-up
70 80 90 100 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 3.3% in sustained AFib Intermittent Sustained 14 12 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 Tachycardia induced 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 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
28.9
20
4.2
0 SOLVD prevention
10.1
SOLVD treatment
14.4
V-HeFT
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
±
years 5.2
30 25 20 15 10 5 0 0 1 2 3
Years after diagnosis
4 5 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 CHF related Death and Hospitalization
60 50 40 30 20 10 0 0 AF present AF absent 1
1920 426
2 Relative risk 1.35 (95% Cl 1.20-1.51); p<0.001
3 Time (years) 4 5
1666 358 1458 299 1207 245 426 97
Swedberg K, et al.
Eur Heart J
(2005) 26: 1303
Time to CV Death or Hospitalization for Heart Failure in Patients with AFib
0.50
0.45
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0 AF at baseline (Low EF) No AF at baseline (Low EF) AF at baseline (Preserved) No AF at baseline (Preserved) 0 1 2
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 No AF & PEF AF & Low EF AF & PEF
3906 2545 670 478 3207 2294 509 399 2755 2096 417 353
3
1963 1276 289 203
3.5
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
CHECK PERMISSIONS FOR PHOTO 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
80 60 Men AFib+ Women AFib+ 40 20 Men AFib Women AFib 0 0 1 2 3 4 5 6 Follow-up (y) 7 8 9 10 Benjamin EJ, et al.
Circulation
(1998) 98: 946
Increased Risk of Cardiovascular Events Death or hospitalization in individuals with CV event(s) after 20 years
100 Men
89
Women 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
2 0 8 6 4 Manitoba Framingham (overall) Framingham (no HD) Whitehall
Total and Cardiovascular Mortality Risk PARIS Prospective study I Variable
Idiopathic AFib
Age at inclusion Systolic blood pressure Cholesterol Body mass index Tobacco consumption Total mortality RR (IC 95%) p Cardiovascular mortality RR (IC 95%) p
1.95
[1.13-3.37] 1.03 [1.01-1.11] 1.44 [1.38-1.51] 1.00 [0.96-1.04] 0.89 [0.85-0.94] 1.40 [1.34-1.45]
0.02
0.04
0.0001
ns 0.0001
0.0001
4.31 [2.14-8.68] 1.08 [0.98-1.19] 1.51 [1.39-1.63] 1.24 [1.14-1.35] 1.00 [0.92-1.10] 1.31 [1.22-1.41]
0.0001
ns 0.0001
0.0001
ns 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 Cost of stroke admission warfarin use 10% admission 10% community based care
Base cost of AF in 2000
0 +5.1% +7.4% +5.6% +50% +48% Base cost of AFib 100 200 300 400 500 600 Total health care expenditure (£ million) 700 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% 12%
Hospitalizations Drugs 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 9% 8% 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
Principal diagnosis Any diagnosis 140 1400 120 100 1200 1000 85+ 75-84 65-74 55-64 35-54 80 60 800 600 40 20 400 200 0 1985 1987 1989 1993 1991
Years
1995 1997 1999 0 1985 1987 1989 1993 1991
Years
1995 1997 1999 Wattigney WA, et al.
Circulation
(2003) 108: 711
Increase in Admissions for AFib 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% of all ER admissions
) • 61.9% of AFib/flutter patients were hospitalized (
3.3% of all hospitalizations
) • 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) Inpatient admissions ER visits Outpatient procedures Office visits Medication prescriptions Lab measurements Bordeaux Ghent Milwaukee TOTAL, mean 1.2+0.8
0.7+0.4
7.4+4.1
9.5+3.5
2.0+0.9
9.2+4.9
1.9+0.8
0.5+0.4
7.1+2.8
4.5+1.4
2.3+0.5
8.0+6.1
0.9+0.5
0.5+1.0
5.8+2.0
7.0+3.2
2.2+0.5
8.4+6.5
1.3+0.7
0.6+0.6
6.9+3.0
7.0+2.7
2.1+0.6
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 years
7.0
6.0
5.0
4.0
3.0
2.0
1.0
2.08 2.26
2.44
2.66
2.94
3.33
3.80
4.34
4.78
5.16
5.42
5.61
0 1990 1995 2000 2005 2010 2015 2020
Year
2025 2030 2035 2040 2045 2050 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