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 6.0 5.42 5.61 5.0 5.16 4.78 4.34 4.0 Adults with atrial fibrillation in millions 3.80 3.33 3.0 2.94 2.66 2.44 2.0 2.08 2.26 1.0 Upper and lower curves represent the upper and lower scenarios based on sensitivity analyses. 1990 1995 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050 Years Go AS et al. JAMA. 2001;285:2370-2375.

Atrial Fibrillation Is Associated With Increased Mortality With atrial fibrillation Without atrial fibrillation 71.3 65.1* 62.4 54.5 51.0* 47.4* 47.5 38.6 Cumulative mortality over 3 years (%) 34.0 36.1* 30.2* 25.4* 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.

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.

Prevalence per 10,000 persons Increasing Hospitalizations in the United States When Atrial Fibrillation Is Principal Diagnosis (National Hospital Discharge Survey) 20 40 60 80 100 120 140 Prevalence per 10,000 persons 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.

Atrial Fibrillation Adversely Affects Quality of Life (QoL) Lower scores = poorer QoL SF-36 score Dorian P et al. J Am Coll Cardiol. 2000;36:1303-1309.

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. Hobbs WJC, Fynn S, Todd DM, Wolfson P, Galloway M, Garratt CJ. Reversal of atrial electrical remodeling after cardioversion of persistent atrial fibrillation in humans. Circulation. 2000;101:1145-1151. Sanfilippo AJ, Abascal VM, Sheehan M, et al. Atrial enlargement as a consequence of atrial fibrillation: a prospective echocardiographic study. Circulation. 1990;82:792-797. Thijssen VLJL, Ausma J, Liu GS, Allessie MA, van Eys GJJM, Borgers M. Structural changes of atrial myocardium during chronic atrial fibrillation. Cardiovasc Pathol. 2000;9:17-28.

Atrial Fibrillation Causes Histologic Remodeling of Atria as Early as 4 Months Myolysis Sinus rhythm Atrial fibrillation Enlarged atrial cells Severe myolysis Glycogen accumulation Reduction in connexin 40 expression Connexin 40 Ausma J et al. Circulation. 1997;96:3157-3163; Van der Velden HMW et al. J Cardiovasc Electrophysiol. 1998;9:596-607.

Patients in sinus rhythm (%) Patients Converted to Sinus Rhythm Within 3 Months of Onset Are More Likely to Remain in Sinus Rhythm 82% 67% Patients in sinus rhythm (%) 36% 27% 1 month P<.02 6 months 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.

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 0.40 0.35 0.30 0.25 0.20 0.15 0.10 0.05 Mean NYHA-FC score (Lower NYHA-FC score = less symptomatic) Adjusted P<.0001 Current atrial fibrillation No current atrial fibrillation Initial 2 4 8 1 1⅓ 1⅔ 2⅓ 2⅔ 3 3⅓ 3⅔ 4⅓ 4⅔ 5 Months Years Chung MK et al. J Am Coll Cardiol. 2005;46:1891-1899.

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: Decreasing atrial fibrillation burden offers potential to successfully treat atrial fibrillation by: Decreasing mortality Decreasing hospitalizations Increasing QoL Frequency of episodes Duration of episodes Symptoms during episodes Prystowsky EN. J Cardiovasc Electrophysiol. 2006;17(suppl 2):S7-S10; Wolf PA et al. Arch Intern Med. 1998;158:229-234.

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