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Atrial Fibrillation: a Marker or Risk Factor for Stroke

https://doi.org/10.20996/1819-6446-2023-01-06

Abstract

Atrial fibrillation (AF) is strongly associated with stroke risk, but an association by itself does not necessarily imply causation. The question remains whether AF is a risk factor for stroke and whether treatment that reduces the severity of AF will also reduce the burden of stroke. On the other hand, it is possible that AF is a risk marker associated with atrial insufficiency, in which structural and electrical atrial remodeling coexist, leading  to the clinical manifestations of AF and the risk of stroke simultaneously. Atrial fibrillation and stroke are inextricably linked to the classic Virchow pathophysiology, which explains thromboembolism as blood stasis in a fibrillating left atrium. This concept has been reinforced by the proven efficacy of oral anticoagulants for the prevention of stroke in AF. However, a number of observations showing that the presence of AF is neither necessary nor sufficient for stroke cast doubt on the causal role of AF in vascular brain injury. The growing recognition of the role of atrial cardiomyopathy and the atrial substrate in the development of stroke associated with AF, as well as stroke without AF, has led to a rethinking of the pathogenetic model of cardioembolic stroke. A number of recent studies have shown that AF is a direct cause of stroke. Studies in which cardiac implantable devices have been used to collect data on pre-stroke AF do not appear to show a direct time relationship. The presence of AF is neither necessary nor sufficient for stroke, which casts doubt on the causal role of AF in cerebrovascular injury. Known risk factors for stroke in the presence of AF are also recognized risk factors for ischemic stroke, regardless of the presence of AF. The risk of stroke in patients with AF in the absence of risk factors differs little from that in patients without AF. This work is devoted to an attempt to answer the question whether AF is a marker or a risk factor for ischemic stroke.

About the Authors

B. A. Tatarsky
Scientific Medical Research Center named after V.A. Almazova
Russian Federation

Boris A. Tatarsky.

St. Petersburg



D. A. Napalkov
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Dmitry A. Napalkov.

Moscow



References

1. Di Carlo Bellino L, Zaninell F, Baldereschi A, et al. Fibrillazione Atriale in Italia. Prevalence of atrial fibrillation in the Italian elderly population and projections from 2020 to 2060 for Italy and the European Union: the FAI Project. Europace. 2019;21(10):1468-75. DOI:10.1093/europace/euz141

2. Sumeet S, Havmoeller R, Narayanan K, et al. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation. 2014;129(8):837-47. DOI:10.1161/CIRCULATIONAHA.113.005119.

3. BalL J, Carrington MJ, McMurray JIW, et al. Atrial fibrillation: profile and burden of an evolving epidemic in the 21st century Int J Cardiol. Int J Cardiol. 2013;167(5):1807-24. DOI:10.1016/j.ijcard.2012.12.093.

4. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS) Eur Heart J. 2021;42(5):373-498. DOI:10.1093/eurheartj/ehaa612.

5. Cowan J, Wu J, Hall M, et al. A 10 year study of hospitalized atrial fibrillation-related stroke in England and its association with uptake of oral anticoagulation. Eur Heart J. 2018;39(32):2975-83. DOI: 10.1093/eurheartj/ehy411

6. Freedman B. Major progress in anticoagulant uptake for atrial fibrillation at last: does it translate into stroke prevention? Eur Heart J. 2018;39(32):2984-86. DOI: 10.1093/eurheartj/ehy487.

7. Chamberlain AM, Gersh BJ, Alonso A, et al. Decade-long trends in atrial fibrillation incidence and survival: a community study. Am J Med. 2015;128(3):260-7.e1. DOI:10.1016/j.amjmed.2014.10.030.

8. Marcucci M, Lip GYH, Nieuwlaat R, et al. Stroke and bleeding risk co-distribution in real-world patients with atrial fibrillation: the Euro Heart Survey. Am J Med. 2014;127(10):979-86.e2 42. DOI:10.1016/j.amjmed.2014.05.003.

9. Olesen JB, Lip GYH, Lindhardsen J, et al. Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: a net clinical benefit analysis using a ‘real world’ nationwide cohort study. Thromb Haemost. 2011;106(4):739-49. DOI:10.1160/TH11-05-0364

10. Chugh SS, Havmoeller R, Narayanan K, et al. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation 2014;129(8):837-47. DOI:10.1161/CIRCULATIONAHA.113.005119.

11. Singer DE, Chang Y, Borowsky LH, et al. A new risk scheme to predict ischemic stroke and other thromboembolism in atrial. J Am Heart Assoc. 2013.21;2(3):e000250. DOI:10.1161/JAHA.113.000250.

12. Brambatti M, Connolly SJ, Gold MR, et al., ASSERT Investigators. Temporal relationship between subclinical atrial fibrillation and embolic events. Circulation 2014;129(21):2094-9. DOI:10.1161/CIRCULATIONAHA.113.007825.

13. Martin DT, Bersohn MM, Waldo AL, et al. IMPACT Investigators. Randomized trial of atrial arrhythmia monitoring to guide anticoagulation in patients with implanted defibrillator and cardiac resynchronization devices. Eur Heart J. 2015;36(26):1660-8. DOI: 10.1093/eurheartj/ehv115.

14. Turakhia MP, Ziegler PD, Schmitt SK, et al. Atrial fibrillation burden and short-term risk of stroke: case-crossover analysis of continuously recorded heart rhythm from cardiac electronic implanted devices. Circ Arrhythm Electrophysiol. 2015;8(5):1040-7. DOI:10.1161/CIRCEP.114.003057.

15. Kottkamp H. Fibrotic atrial cardiomyopathy: a specific disease/syndrome supplying substrates for atrial fibrillation, atrial tachycardia, sinus node disease, AV node disease, and thromboembolic complications. J. Cardiovasc. Electrophysiol. 2012;23(7):797-9. DOI:10.1111/j.1540-8167.2012.02341.x.

16. Alkhouli M, Alqahtani F, Aljohani S, et al. Burden of atrial fibrillation-associated ischemic stroke in the United States. JACC Clin Electrophysiol. 2018;4:618–625. DOI:10.1016/j.jacep.2018.02.021.4.

17. Friberg L, Rosenqvist M, Lip GYH, Net clinical benefit of warfarin in patients with atrial fibrillation: a report from the Swedish atrial fibrillation cohort study. Circulation. 2012;125:2298–2307. DOI:10.1161/CIRCULATIONAHA.111.055079.

18. Glotzer TV, Daoud EG, Wyse GD, et al. The relationship between daily atrial tachyarrhythmia burden from implantable device diagnostics and stroke risk: the TRENDS study. Circ. Arrhythm. Electrophysiol. 2009;2:474–480. DOI:10.1161/CIRCEP.109.849638.

19. Suzuki T, Yamazaki T, Ogawa S, et al. Echocardiographic predictors of frequency of paroxysmal atrial fibrillation (AF) and its progression to persistent AF in hypertensive patients with paroxysmal AF: results from the Japanese Rhythm Management Trial II for Atrial Fibrillation (J‑RHYTHM II Study). HeartRhythm. 2011;8(12):1831-6. DOI:10.1016/j.hrthm.2011.07.035.

20. Ganesan AN, Chew DP, Hartshorne T,et al. The impact of atrial fibrillation type on the risk of thromboembolism, mortality, and bleeding: a systematic review and meta-analysis. Eur. Heart J 2016.37;20:1591–1602. DOI:10.1093/eurheartj/ehw007.

21. Darlington A, McCauley MD. Atrial Cardiomyopathy: An Unexplored Limb of Virchow's Triad for AF. Stroke Prophylaxis. 2020;7:Art11 DOI:org/10.3389/fcvm.2020.00011.

22. Teh AW, Kistler PM, Lee G, et al. Long-term effects of catheter ablation for lone atrial fibrillation: Progressive atrial electroanatomic substrate remodeling despite successful ablation. Heart Rhythm. 2012;9:473–80. DOI:10.1016/j.hrthm.2011.11.013.

23. Tandon K, Tirschwell D, Longstreth WT, et al. Embolic stroke of undetermined source correlates to atrial fibrosis without atrial fibrillation. Neurology. 2019;93:e381–e387. DOI:10.1212/WNL.000000000000782.

24. Chao TF, Liu CE, Chen SY, et al. Atrial fibrillation and the risk of ischemic stroke: does it still matter in patients with a CHA2DS2-VASc score of 0 or 1? Stroke. 2012;43:2551–2555 DOI:10.1161/STROKEAHA.112.667865.

25. Ganesan AN, Chew DP, Hartshorne T, et al. The impact of atrial fibrillation A type on the risk of thromboembolism, mortality and bleeding: a systematic review and meta-analysis. Eur. Heart J. 2016,37,20:1591–1602. DOI:10.1093/eurheartj/ehw007.

26. Goette A, Kalman JM, Aguinaga L, et al. EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication. Heart Rhythm. 2017;14(1):e3-e40. DOI:10.1016/j.hrthm.2016.05.028.

27. Goldberger J, Arora R, Green D, et al. Evaluating the atrial myopathy underlying atrial fibrillation: identifying the arrhythmogenic and thrombogenic substrate. Circulation. 2015;132:278–291. DOI:10.1161/CIRCULATIONAHA.115.016795.

28. Kottkamp H. Human atrial fibrillation substrate: towards a specific fibrotic atrial cardiomyopathy. Eur. Heart J. 2013;34:2731–2738 DOI:10.1093/eurheartj/eht194.

29. Nattel S, Harada M. Atrial remodeling and atrial fibrillation: recent advances and translational perspectives. J Am Coll Cardiol. 2014;63:2335–45. DOI:10.1016/j.jacc.2014.02.555.

30. Santulli G, Iaccarino C, De Luca N, et al. Atrial fibrillation and microRNAs. Front Physiol. 2014;5:15. DOI:10.3389/fphys.2014.00015.

31. Marrouche NF, Wilber D, Hindricks G, et al. Association of atrial tissue fibrosis identified by delayed enhancement MRI and atrial fibrillation catheter ablation: the DECAAF study. JAMA. 2014;311:498–506. DOI:10.1001/jama.2014.3.

32. Kloosterman M, Oldgren J, Conen D, et al. Characteristics and outcomes of atrial fibrillation in patients without traditional risk factors: a RE-LY AF registry analysis. Europace. 2020;22:870–877. DOI:10.1093/europace/euz360.

33. Wijesurendra RS, Liu A, Eichhorn C, et al. Lone atrial fibrillation is associated with impaired left ventricular energetics that persists despite successful catheter ablation. Circulation. 2016;134:1068–1081. DOI:10.1161/CIRCULATIONAHA.116.022931.

34. Ntaios G. Embolic stroke of undetermined source: JACC review topic of the week. J Am Coll Cardiol. 2020;75:333–340. DOI:10.1016/j.jacc.2019.11.024.

35. Hart RG, Sharma M, Mundl H, et al. NAVIGATE ESUS Investigators. Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med. 2018;378(23):2191-201. DOI:10.1056/NEJMoa1802686.

36. Diener HС, Sacco RL, Easton JD, et al. Committee R-SES and Investigators. Dabigatran for prevention of stroke after embolic stroke of undetermined source. N Engl J Med. 2019;380(20):1906-17. DOI:10.1056/NEJMoa1813959.

37. Healey JS, Gladstone DJ, Swaminathan B, et al. Recurrent stroke with rivaroxaban compared with aspirin according to predictors of atrial fibrillation: secondary analysis of the NAVIGATE ESUS randomized clinical trial. JAMA Neurol. 2019;76(7):764-73. DOI:10.1001/jamaneurol.2019.0617.

38. Longstreth WT, Kronmal RA, Thompson JLP, et al. Amino terminal pro-B-type natriuretic peptide, secondary stroke prevention, and choice of antithrombotic therapy. Stroke. 2013;44(3):714-9. DOI:10.1161/STROKEAHA.112.675942.

39. Kamel H, Longstreth W, Tirschwell D, et al. The AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke randomized trial: rationale and methods. Int J Stroke. 2019;14(2):207-14. DOI:10.1177/1747493018799981.


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For citations:


Tatarsky B.A., Napalkov D.A. Atrial Fibrillation: a Marker or Risk Factor for Stroke. Rational Pharmacotherapy in Cardiology. 2023;19(1):83-88. (In Russ.) https://doi.org/10.20996/1819-6446-2023-01-06

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ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)