2. Epidemiology
2.1 Incidence and prevalence
AF is the most common sustained arrhythmia encountered in clinical practice.[29] Current evidence suggests that the prevalence of AF is 1%-2% in the general population, and increases significantly with age (< 1.0% up to 50 years of age, to 4% at 65 years, and 12% of those 80 years of age or older).[29],[30] Although the incidence has been relatively stable over time (approximately 28 per 1000 person-years), the overall prevalence of AF is increasing because of changing population demographics (eg, from 41 cases per 1000 in 1993 to 85 cases per 1000 in 2007).[29],[31] However, the true prevalence of AF is likely to be substantially higher than 1-2%, as these historical estimates were derived from populations with AF diagnosed using ECG, and did not routinely account for patients with paroxysmal AF (which is estimated to be approximately two-thirds of the AF population) or patients with silent AF.[32]–[35] When factoring in patients with paroxysmal and silent AF, the prevalence of AF increases from 500,000 to nearly 1 million Canadians.[36],[37]
2.2 Morbidity and mortality
Although rarely acutely life-threatening, AF is associated with significant impairments in functional capacity and health-related quality of life (HRQOL), as well as with an increased morbidity and mortality. These impairments have been noted across multiple HRQOL domains, with a magnitude comparable or worse than that observed in patients with HF or who are on long-term hemodialysis.[38]–[42] Even in the absence of perceived symptoms, AF patients objectively experience reduced global life satisfaction.[38] AF is independently associated with a 1.5- to 4-fold increased risk of mortality, which is predominantly due to increased risk of thromboembolic events and ventricular dysfunction.[31],[40],[43]–[46] Nonanticoagulated patients with AF have a 3- to 5-fold increased risk of stroke, which are generally more severe (greater resource utilization, long-term disability, and mortality) and more recurrent than strokes unrelated to AF.[43],[47]–[50] To date, the only therapeutic intervention that has been consistently and definitively shown to improve survival in the AF population is the use of oral anticoagulation (OAC; see section 8).[51],[52] Strategies targeting modifiable cardiovascular risk factors and relevant comorbid conditions offer potential opportunities to further improve survival (see sections 3 and 6).
2.3 Health care resource utilization
The economic burden of AF care is substantial. A significant proportion of AF health care expenses are attributed to the direct costs associated with hospitalization and the provision of acute care.[29],[53]–[59] In Canada, AF resulted in 8815 same-day procedures, 76,964 ED visits, and 64,214 acute care admissions (25,892 with AF as the principal diagnosis and 38,222 with AF as a comorbid diagnosis) in the 2007-2008 fiscal year. The annual direct cost of AF care adjusted to 2020 Canadian dollars (CAD$) was $956 million: $66 million for ED visits with AF as the principal diagnosis and $20 million with comorbid AF; $204 million for hospitalization with AF as the principal diagnosis and $634 million with comorbid AF; and $32 million for AF-related day procedures.[58] On a per-patient basis, the excess annual direct cost of AF has been estimated to be $16,944-$19,529 (adjusted 2020 US dollars).[55],[56] In addition to these direct costs, the annual indirect costs (eg, days of work missed because of illness) have been estimated to be $3082 higher for AF patients compared with those without AF.[57] It is important to recognize that the cost of care is not uniform across the spectrum of AF. Specifically, the annual inpatient and outpatient direct costs are more than twice as high for patients with “primary AF” compared with patients with “secondary AF” (see section 1.2).[57]
References
29. Andrade J, Khairy P, Dobrev D, Nattel S. The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms. Circ Res 2014;114:1453-68.
30. Kannel WB, Wolf PA, Benjamin EJ, Levy D. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population based estimates. Am J Cardiol 1998;82:2N-9N.
31. Piccini JP, Hammill BG, Sinner MF, et al. Incidence and prevalence of atrial fibrillation and associated mortality among Medicare beneficiaries, 1993-2007. Circ Cardiovasc Qual Outcomes 2012;5:85-93.
32. Kannel WB, Abbott RD, Savage DD, McNamara PM. Epidemiologic features of chronic atrial fibrillation: the Framingham study. N Engl J Med 1982;306:1018-22.
33. Furberg CD, Psaty BM, Manolio TA, et al. Prevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study). Am J Cardiol 1994;74:236-41.
34. Rietbrock S, Heeley E, Plumb J, van Staa T. Chronic atrial fibrillation: incidence, prevalence, and prediction of stroke using the Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack (CHADS2) risk stratification scheme. Am Heart J 2008;156:57-64.
35. Chiang CE, Naditch-Brule L, Murin J, et al. Distribution and risk profile of paroxysmal, persistent, and permanent atrial fibrillation in routine clinical practice: insight from the real-life global survey evaluating patients with atrial fibrillation international registry. Circ Arrhythm Electrophysiol 2012;5:632-9.
36. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001;285:2370-5.
37. Miyasaka Y, Barnes ME, Gersh BJ, et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 2006;114:119-25.
38. Dorian P, Jung W, Newman D, et al. The impairment of health-related quality of life in patients with intermittent atrial fibrillation: implications for the assessment of investigational therapy. J Am Coll Cardiol 2000;36:1303-9.
39. Savelieva I, Paquette M, Dorian P, Luderitz B, Camm AJ. Quality of life in patients with silent atrial fibrillation. Heart 2001;85:216-7.
40. Singh SN, Tang XC, Singh BN, et al. Quality of life and exercise performance in patients in sinus rhythm versus persistent atrial fibrillation: a Veterans Affairs Cooperative Studies Program substudy. J Am Coll Cardiol 2006;48:721-30.
41. Thrall G, Lane D, Carroll D, Lip GY. Quality of life in patients with atrial fibrillation: a systematic review. Am J Med 2006;119. 448.e1-19.
42. Kang Y. Relation of atrial arrhythmia-related symptoms to health-related quality of life in patients with newly diagnosed atrial fibrillation: a community hospital-based cohort. Heart Lung 2006;35:170-7.
43. Wolf PA, Mitchell JB, Baker CS, Kannel WB, D’Agostino RB. Impact of atrial fibrillation on mortality, stroke, and medical costs. Arch Intern Med 1998;158:229-34.
44. Andersson T, Magnuson A, Bryngelsson IL, et al. All-cause mortality in 272,186 patients hospitalized with incident atrial fibrillation 1995-2008: a Swedish nationwide long-term case-control study. Eur Heart J 2013;34:1061-7.
45. Benjamin EJ, Virani SS, Callaway CW, et al. Heart disease and stroke statistics-2018 update: a report from the American Heart Association. Circulation 2018;137:e67-492.
46. Lee E, Choi EK, Han KD, et al. Mortality and causes of death in patients with atrial fibrillation: a nationwide population-based study. PLoS One 2018;13:e0209687.
47. Petty GW, Brown RD Jr, Whisnant JP, et al. Ischemic stroke subtypes: a population-based study of functional outcome, survival, and recurrence. Stroke 2000;31:1062-8.
48. Bruggenjurgen B, Rossnagel K, Roll S, et al. The impact of atrial fibrillation on the cost of stroke: the Berlin Acute Stroke study. Value Health 2007;10:137-43.
49. Gladstone DJ, Bui E, Fang J, et al. Potentially preventable strokes in high-risk patients with atrial fibrillation who are not adequately anticoagulated. Stroke 2009;40:235-40.
50. Healey JS, Connolly SJ, Gold MR, et al. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med 2012;366:120-9.
51. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007;146:857-67.
52. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014;383:955-62.
53. Stewart S, Murphy NF, Walker A, McGuire A, McMurray JJ. Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK. Heart 2004;90:286-92.
54. Humphries KH, Jackevicius C, Gong Y, et al. Population rates of hospitalization for atrial fibrillation/flutter in Canada. Can J Cardiol 2004;20:869-76.
55. Wu EQ, Birnbaum HG, Mareva M, et al. Economic burden and comorbidities of atrial fibrillation in a privately insured population. Curr Med Res Opin 2005;21:1693-9.
56. Lee WC, Lamas GA, Balu S, et al. Direct treatment cost of atrial fibrillation in the elderly American population: a Medicare perspective. J Med Econ 2008;11:281-98.
57. Kim MH, Lin J, Hussein M, Kreilick C, Battleman D. Cost of atrial fibrillation in United States managed care organizations. Adv Ther 2009;26:847-57.
58. O’Reilly DJ, Hopkins RB, Healey JS, et al. The burden of atrial fibrillation on the hospital sector in Canada. Can J Cardiol 2013;29:229-35.
59. Meyre P, Blum S, Berger S, et al. Risk of hospital admissions in patients with atrial fibrillation: a systematic review and meta-analysis. Can J Cardiol 2019;35:1332-43.
60. Nattel S. New ideas about atrial fibrillation 50 years on. Nature 2002;415:219-26.
61. Voigt N, Heijman J, Wang Q, et al. Cellular and molecular mechanisms of atrial arrhythmogenesis in patients with paroxysmal atrial fibrillation. Circulation 2014;129:145-56.
62. Voigt N, Li N, Wang Q, et al. Enhanced sarcoplasmic reticulum Ca2þ leak and increased Naþ-Ca2þ exchanger function underlie delayed afterdepolarizations in patients with chronic atrial fibrillation. Circulation 2012;125:2059-70.
63. Yao C, Veleva T, Scott L Jr, et al. Enhanced cardiomyocyte NLRP3 inflammasome signaling promotes atrial fibrillation. Circulation 2018;138:2227-42.
64. Nishida K, Datino T, Macle L, Nattel S. Atrial fibrillation ablation: translating basic mechanistic insights to the patient. J Am Coll Cardiol 2014;64:823-31.
65. Pathak RK, Middeldorp ME, Lau DH, et al. Aggressive risk factor reduction study for atrial fibrillation and implications for the outcome of ablation: the ARREST-AF cohort study. J Am Coll Cardiol 2014;64:2222-31.
66. Lau DH, Nattel S, Kalman JM, Sanders P. Modifiable risk factors and atrial fibrillation. Circulation 2017;136:583-96.