Abstract
Atrial fibrillation (AF) is an epidemic, affecting 1% to 1.5% of the population in the developed world. Projected data from the population‐based studies suggest that the prevalence of AF will grow at least 3‐fold by 2050. The health and economic burden imposed by AF and AF‐related morbidity is enormous.
Atrial fibrillation has a multiplicity of causes ranging from genetic to degenerative, but hypertension and heart failure are the commonest and epidemiologically most prevalent conditions associated with AF as both have been shown to create an arrhythmogenic substrate. Several theories emerged regarding the mechanism of AF, which can be combined into two groups: the single focus hypothesis and the multiple sources hypothesis. Several lines of evidence point to the relevance of both hypotheses to the mechanism of AF, probably with a different degree of involvement depending on the variety of AF (paroxysmal or persistent). Sustained AF alters electrophysiological and structural properties of the atrial myocardium such that the atria become more susceptible to the initiation and maintenance of the arrhythmia, a process known as atrial remodeling. Angiotensin II has been recognized as a key element in atrial remodeling in association with AF opening the possibility of exploitation of “upstream” therapies to prevent or delay atrial remodeling.
The clinical significance of AF lies predominantly in a 5‐fold increased risk of stroke. The limitations of warfarin prompted the development of new antithrombotic drugs, which include anticoagulants, such as direct oral thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban). Novel mechanical approaches for the prevention of cardioembolic stroke have recently been evaluated: percutaneous left atrial appendage occluders, minimally invasive surgical isolation of the left atrial appendage, and implantation of carotid filtering devices. Copyright © 2008 Wiley Periodicals, Inc.
Keywords: atrial fibrillation, mechanisms, remodeling, antithrombotic drugs, antiarrhythmic drugs, catheter ablation, prevention
Full Text
The Full Text of this article is available as a PDF (358.9 KB).
References
- 1. Savelieva I, Camm AJ: Clinical trends in atrial fibrillation at the turn of the millennium. J Intern Med 2001; 250: 369–372. [DOI] [PubMed] [Google Scholar]
- 2. Lloyd‐Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, et al.: Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation 2004; 110: 1042–1046. [DOI] [PubMed] [Google Scholar]
- 3. Heeringa J, van der Kuip DA, Hofman A, Hofman A, Breteler MM, et al.: Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J 2006; 27: 949–953. [DOI] [PubMed] [Google Scholar]
- 4. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, 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: 2370–2375. [DOI] [PubMed] [Google Scholar]
- 5. Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, 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: 119–125. [DOI] [PubMed] [Google Scholar]
- 6. Wolf PA, Abbot RD, Kannel WB: Atrial fibrillation as independent risk factor for stroke: the Framingham Study. Stroke 1991; 22: 983–938. [DOI] [PubMed] [Google Scholar]
- 7. Gottdiener JS, Arnold AM, Aurigemma GP, Polak JF, Tracy RP, et al.: Predictors of congestive heart failure in the elderly: the Cardiovascular Health Study. J Am Coll Cardiol 2000; 35: 1628–1637. [DOI] [PubMed] [Google Scholar]
- 8. Wattigney WA, Mensah GA, Croft JB: Increasing trends in hospitalization for atrial fibrillation in the United States, 1985 through 1999: implications for primary prevention. Circulation 2003; 108: 711–716. [DOI] [PubMed] [Google Scholar]
- 9. Tsang TS, Miyasaka Y, Barnes ME, Gersh BJ: Epidemiological profile of atrial fibrillation: a contemporary perspective. Prog Cardiovasc Dis 2005; 48: 1–8. [DOI] [PubMed] [Google Scholar]
- 10. Ellinor PT, Yoerger DM, Ruskin JN, MacRae CA: Familial aggregation in lone atrial fibrillation. Hum Genet 2005; 118: 179–184. [DOI] [PubMed] [Google Scholar]
- 11. Stewart S, Murphy N, Walker A, McGuire A, McMurray JJ: Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK. Heart 2004; 90: 286–292. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Coyne KS, Paramore C, Grandy S, Mercader M, Reynolds M, et al.: Assessing the direct costs of treating nonvalvular atrial fibrillation in the United States. Value Health 2006; 9: 348–356. [DOI] [PubMed] [Google Scholar]
- 13. Savelieva I, Camm AJ: Clinical relevance of silent atrial fibrillation: prevalence, prognosis, quality of life, and management. J Interv Card Electrophysiol 2000; 4: 369–382. [DOI] [PubMed] [Google Scholar]
- 14. Israel CW, Gronefeld G, Ehrlich JR, Li YG, Hohnloser SH: Long‐term risk of recurrent atrial fibrillation as documented by an implantable monitoring device: implications for optimal patient care. J Am Coll Cardiol 2004; 43: 47–52. [DOI] [PubMed] [Google Scholar]
- 15. Hindricks G, Piorkowski C, Tanner H, Kobza R, Gerds‐Li JH, et al.: Perception of atrial fibrillation before and after radiofrequency catheter ablation: relevance of asymptomatic arrhythmia recurrence. Circulation 2005; 112: 307–313. [DOI] [PubMed] [Google Scholar]
- 16. Camm AJ, Savelieva I, Bharati S, Lindsay BD, Nattel S: Atrial tachycardia, flutter and fibrillation In Electrophysiological Disorders of the Heart (Eds. Saksena S, Camm AJ.), pp 283–363. Philadelphia, PA: Elsevier Inc.: 2005. [Google Scholar]
- 17. Vaziri SM, Larson MG, Benjamin EJ, Levy D: Echocardiographic predictors of nonrheumatic atrial fibrillation. The Framingham Heart Study. Circulation 1994; 89: 724–730. [DOI] [PubMed] [Google Scholar]
- 18. Sanders P, Berenfeld O, Hocini M, Jais P, Vaidyanathan R, et al.: Spectral analysis identifies sites of high‐frequency activity maintaining atrial fibrillation in humans. Circulation 2005; 112: 789–797. [DOI] [PubMed] [Google Scholar]
- 19. Allessie MA, Boyden PA, Camm AJ, Kleber AG, Lab MJ, et al.: Pathophysiology and prevention of atrial fibrillation. Circulation 2001; 103: 769–777. [DOI] [PubMed] [Google Scholar]
- 20. Allessie M, Ausma J, Schotten U: Electrical, contractile and structural remodeling during atrial fibrillation. Cardiovasc Res 2002; 54: 230–246. [DOI] [PubMed] [Google Scholar]
- 21. Goette A, Lendeckel U, Klein HU: Signal transduction systems and atrial fibrillation. Cardiovasc Res 2002; 54: 247–258. [DOI] [PubMed] [Google Scholar]
- 22. Kumagai K, Nakashima H, Urata H, Gondo N, Arakawa K, et al.: Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation. J Am Coll Cardiol 2003; 41: 2197–2204. [DOI] [PubMed] [Google Scholar]
- 23. Li D, Shinagawa K, Pang L, Leung TK, Cardin S, et al.: Effects of angiotensin‐converting enzyme inhibition on the development of atrial fibrillation substrate in dogs with ventricular tachycardia‐induced congestive heart failure. Circulation 2001; 104: 2608–2614. [DOI] [PubMed] [Google Scholar]
- 24. Albers GW, Dalen JE, Laupacis A, Manning WJ, Petersen P, et al.: Antithrombotic therapy in atrial fibrillation. Chest 2001; 119: 194S–206S. [DOI] [PubMed] [Google Scholar]
- 25. Atrial Fibrillation Investigators : Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation: analysis of pooled data from five randomized controlled trials. Arch Intern Med 1994; 154: 1449–1457. [PubMed] [Google Scholar]
- 26. Hart RG, Pearce LA, McBride R, Rothbart RM, Asinger RW: Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I‐III clinical trials. The Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. Stroke 1999; 30: 1223–1229. [DOI] [PubMed] [Google Scholar]
- 27. Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, et al.: Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001; 285: 2864–2870. [DOI] [PubMed] [Google Scholar]
- 28. Fuster V, Ryden LE, Fuster V, Ryden LE, Cannom DS, et al.: ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation‐executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation). J Am Coll Cardiol 2006; 48: 854–906. [DOI] [PubMed] [Google Scholar]
- 29. Fagan SM, Chan KL: Transesophageal echocardiography risk factors for stroke in nonvalvular atrial fibrillation. Echocardiography 2000; 17: 365–372. [DOI] [PubMed] [Google Scholar]
- 30. Lip GY, Edwards SJ: Stroke prevention with aspirin, warfarin and ximelagatran in patients with non‐valvular atrial fibrillation: a systematic review and meta‐analysis. Thromb Res 2006; 118: 321–333. [DOI] [PubMed] [Google Scholar]
- 31. Hylek EM, Skates SJ, Sheehan MA, Singer DE: An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation. N Engl J Med 1996; 335: 540–546. [DOI] [PubMed] [Google Scholar]
- 32. Bates SM, Weitz JI: The status of new anticoagulants. Br J Haematol 2006; 134: 3–19. [DOI] [PubMed] [Google Scholar]
- 33. Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, et al, ACTIVE Writing Group on behalf of the ACTIVE Investigators : Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006; 367: 1903–1912. [DOI] [PubMed] [Google Scholar]
- 34. Ostermayer SH, Reisman M, Kramer PH, Matthews RV, Gray WA, et al.: Percutaneous left atrial appendage transcatheter occlusion (PLAATO system) to prevent stroke in high‐risk patients with non‐rheumatic atrial fibrillation: results from the international multi‐center feasibility trials. J Am Coll Cardiol 2005; 46: 9–14. [DOI] [PubMed] [Google Scholar]
- 35. Sick PB, Schuler G, Grobe E, Yakubov S, et al.: Initial worldwide experience with the WATCHMAN left atrial appendage system for stroke prevention in atrial fibrillation. J AM Coll Cardiol 2007; 49: 1490–1495. [DOI] [PubMed] [Google Scholar]
- 36. Fountain RB, Holmes DR, Chandrasekaran K, Packer D, Asirvatham S, et al.: The PROTECT AF (WATCHMAN Left Atrial Appendage System for Embolic PROTECTion in Patients with Atrial Fibrillation) trial. Am Heart J 2006; 151: 956–961. [DOI] [PubMed] [Google Scholar]
- 37. Healey JS, Crystal E, Lamy A, Teoh K, Semelhago L, et al.: Left Atrial Appendage Occlusion Study (LAAOS): results of a randomized controlled pilot study of left atrial appendage occlusion during coronary bypass surgery in patients at risk for stroke. Am Heart J 2005; 150: 288–293. [DOI] [PubMed] [Google Scholar]
