Atrial Fibrillation:

An Escalating Cardiovascular Disease With

Significant Clinical and Economic Consequences
 Projection for Prevalence of
Atrial Fibrillation: 5.6 Million by 2050
Projected number of adults with atrial fibrillation in the United States between 1995 and 2050
7.0
Adults with atrial fibrillation

6.0
5.42 5.61
5.0 5.16
4.78
in millions

4.34
4.0 3.80
3.33
3.0 2.94
2.66
2.44
2.26
2.0 2.08

1.0
Upper and lower curves represent the upper and lower scenarios based on sensitivity analyses.
0
1990 1995 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050
Years

Go AS et al. JAMA. 2001;285:2370-2375. 2

 Atrial Fibrillation Is Associated
With Increased Mortality
Cumulative mortality over 3 years (%)

80 With atrial fibrillation Without atrial fibrillation

71.3
70 65.1*
62.4
60 54.5
51.0*
50 47.4* 47.5
38.6
40 34.0 36.1*
30.2*
30 25.4*

20
10
0
Men Women Men Women Men Women
65 to 74 years of age 75 to 84 years of age 85 to 89 years of age

* Significantly different from patients with atrial fibrillation (P<.05).

Wolf PA et al. Arch Intern Med. 1998;158:229-234. 3

Atrial Fibrillation:
Major Cause of Stroke in the United States
 15% of all strokes attributable to atrial fibrillation
 75,000 strokes per year attributable to
atrial fibrillation
 3- to 5-fold increase in risk of stroke in patients with
atrial fibrillation
 Stroke risk persists even in asymptomatic
atrial fibrillation

Go AS et al. JAMA. 2001;285:2370-2375; Go AS. Am J Geriatr Cardiol. 2005;14:56-61; Wolf PA et al. Stroke.
1991;22:983-988; Benjamin EJ et al. Circulation. 1998;98:946-952; Page RL et al. Circulation. 2003;107:1141-1145.
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 Increasing Hospitalizations in the United States

When Atrial Fibrillation Is Principal Diagnosis

(National Hospital Discharge Survey)
140
Prevalence per 10,000 persons

120

100

80

60

40

20

0
1985 1987 1989 1991 1993 1995 1997 1999
Year
Age (years) 85+ 75 to 84 65 to 74 55 to 64 35 to 54

Wattigney WA et al. Circulation. 2003;108:711-716. 5

 Atrial Fibrillation Adversely Affects
Quality of Life (QoL)
120
Lower scores = poorer QoL

100
92 Atrial fibrillation
80 88 85
78 81
76 Post myocardial
SF-36 score

68 70 71 68 infarction
60
59 Controls
54
40

20

0
General health Physical Social function Mental health
function

Dorian P et al. J Am Coll Cardiol. 2000;36:1303-1309. 6

Atrial Fibrillation Causes Several Types of Remodeling
Over Time That Have Adverse Physiologic Consequences
 Electrophysiologic changes
– Shortening of atrial refractory periods
– Loss of normal adaptation of atrial refractoriness
to heart rate

 Contractile changes
– Reduced atrial contractility

 Structural changes
– Left atrium and left atrial appendage enlargement
– Decrease in cardiac output
– Histologic changes

 Prothrombotic changes (increased propensity for clot formation)

– Atrial stasis
– Increases prothrombotic factors

Hobbs WJC et al. Circulation. 2000;101:1145-1151; Sanfilippo AJ et al. Circulation. 1990;82:792-797; Thijssen VLJL et al. Cardiovasc Pathol. 2000;9:17-28;
Van Gelder IC et al. Europace. 2006;8:943-949; Peters NS et al. Lancet. 2002;359:593-603.
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Atrial Fibrillation Causes Histologic
Remodeling of Atria as Early as 4 Months
Myolysis
Sinus rhythm Atrial fibrillation

 Enlarged atrial cells

 Severe myolysis
 Glycogen accumulation

Connexin 40

 Reduction in connexin
40 expression

Ausma J et al. Circulation. 1997;96:3157-3163; Van der Velden HMW et al. J Cardiovasc Electrophysiol. 1998;9:596-607.
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 Patients Converted to Sinus Rhythm Within 3 Months of Onset
Are More Likely to Remain in Sinus Rhythm

90 <3-month duration of atrial fibrillation prior to cardioversion

82%
>12-month duration of atrial fibrillation prior to cardioversion
Patients in sinus rhythm (%)

80

70 67%
60

50

40 36%
30 27%
20

10

0
1 month 6 months
P<.02 P<.07

The longer one waits to initiate a rhythm-control strategy,

the harder it is to regain sinus rhythm
Dittrich HC et al. Am J Cardiol. 1989;63:193-197. 9
Long-term Maintenance of Sinus Rhythm Improves
Functional Capacity: AFFIRM
 Mean New York Heart Association functional
class (NYHA-FC) score significantly better at each
visit in patients in sinus rhythm
0.50

0.45
Mean NYHA-FC score

0.40

0.35

0.30

0.25

0.20 (Lower NYHA-FC score = less

0.15 Adjusted P<.0001 symptomatic)
0.10 Current atrial fibrillation
No current atrial fibrillation
0.05

0
Initial 2 4 8 1 1⅓ 1⅔ 2 2⅓ 2⅔ 3 3⅓ 3⅔ 4 4⅓ 4⅔ 5
Months Years

Chung MK et al. J Am Coll Cardiol. 2005;46:1891-1899. 11

Decreasing Atrial Fibrillation Burden
Is an Important Goal
 As with heart failure or angina, success in managing
atrial fibrillation is defined as a decrease in:
Frequency
Frequency Duration
Duration Symptoms
Symptoms
of
of of
of during
during
episodes
episodes episodes
episodes episodes
episodes

 Decreasing atrial fibrillation burden offers potential

to successfully treat atrial fibrillation by:
– Decreasing mortality
– Decreasing hospitalizations
– Increasing QoL

Prystowsky EN. J Cardiovasc Electrophysiol. 2006;17(suppl 2):S7-S10; Wolf PA et al. Arch Intern Med. 1998;158:229-234.
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Summary
 Atrial fibrillation is a chronic, cardiovascular disease with increasing
socioeconomic impact
– Prevalence of atrial fibrillation is projected to be 5.6 million by 2050
– Atrial fibrillation is associated with increased risk of mortality, risk of stroke, and
compromised QoL
– Hospitalizations for atrial fibrillation have increased 2- to 3-fold and are projected to
continue rising

 Early restoration and maintenance of sinus rhythm has an integral role in

overall atrial fibrillation treatment strategy
– Atrial fibrillation causes several types of remodeling over time that have adverse
physiologic consequences
• Atrial fibrillation causes histologic remodeling of the atria as early as 4 months
– Sustaining sinus rhythm may be associated with decreased mortality

 Decreasing atrial fibrillation burden offers potential to successfully treat atrial

fibrillation
– As with other chronic cardiovascular diseases, successful management of atrial
fibrillation includes an overall reduction in frequency and duration of episodes, while
reducing symptoms during episodes
– A measure of success can be defined by decreased mortality, decreased
hospitalizations, and increased QoL

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