Atrial cardiomyopathy in patients with cryptogenic embolic stroke: incidence, instrumental diagnostic features, impact on prognosis

Latent atrial fibrillation (AF), whose substrate is atrial cardiomyopathy (AC), is considered the main potential pathogenetic mechanism of cryptogenic embolic stroke (CES). Early detection of AC allows to intensify the search for AF in such patients.

Objective: to compare the characteristics of patients with CES in terms of clinical and anamnestic data, echocardiographic parameters, MRI patterns of infarction foci and disease outcomes depending on the presence of the major markers for AC.

Material and methods. We studied 103 patients in the acute phase of CES with a lesion confirmed by MRI data, who were divided into two groups according to the presence (n=17) or absence (n=86) of AC. A comprehensive clinical, laboratory, and instrumental examination was performed and long-term outcomes were assessed. The median follow-up period was 32 months.

Results. The incidence of AC in the CES population was 17%; the most common markers were an increase in left atrial volume index and paroxysms of supraventricular tachycardia. Patients with AC-CES were characterised by older age and a two-fold increase in the prevalence of coronary heart disease. Patients with AC-CES were nine times more likely to have a "black artery" symptom on MRI than patients without AC. The predictive accuracy of this clinical pattern was 84%, the sensitivity was 60% and the specificity was 86%. Patients with AC-CES had a significantly higher risk (odds ratio 3.4; 95% confidence interval 1.1–9.9; p=0.023) for a composite outcome that included the development of recurrent ischemic stroke, transient ischemic attack, myocardial infarction or death.

Conclusion. AC diagnosed by a combination of echocardiographic and electrocardiographic signs is present in 17% of patients with CES. Patients with AC-CES are characterised by elderly age, the presence of atherosclerosis-associated disease, a specific MRI pattern (the “black artery” symptom) and an unfavourable prognosis during the 2.5-year follow-up period.

1. Perera KS, Vanassche T, Bosch J, et al; ESUS Global Registry Investigators. Embolic strokes of undetermined source: Prevalence and patient features in the ESUS Global Registry. Int J Stroke. 2016 Jul;11(5):526-33. doi: 10.1177/1747493016641967. Epub 2016 Apr 11.

2. Hart RG, Diener HC, Coutts SB, et al; Cryptogenic Stroke/ESUS International Working Group. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol. 2014 Apr;13(4):42938. doi: 10.1016/S1474-4422(13)70310-7

3. Kulesh AA, Demin DA, Vinogradov OI. Cryptogenic stroke. Part 1: Aorto-arterial embolism. Meditsinskiy sovet = Medical Council. 2021;(4):78-87. doi: 10.21518/2079-701X-2021-4-78-87 (In Russ.).

4. Kulesh AA, Demin DA, Belopasova AV, et al. Cryptogenic stroke. Part 2: paradoxical embolism. Meditsinskiy sovet = Medical Council. 2021;(19):16-33. doi: 10.21518/2079-701X-2021-19-16-33 (In Russ.).

5. Demin DA, Kulesh AA, Yanishevskiy SN, et al. Cryptogenic stroke. Part 3: atrial cardiopathy and silent atrial fibrillation. Meditsinskiy sovet = Medical Council. 2022;(21):8-18. doi: 10.21518/2079-701X-2022-16-21-8-18 (In Russ.).

6. Ay H, Benner T, Arsava EM, et al. A computerized algorithm for etiologic classification of ischemic stroke: the Causative Classification of Stroke System. Stroke. 2007 Nov;38(11):2979-84. doi: 10.1161/STROKEAHA.107.490896. Epub 2007 Sep 27.

7. Li TYW, Yeo LLL, Ho JSY, et al. Association of Electrocardiographic P-Wave Markers and Atrial Fibrillation in Embolic Stroke of Undetermined Source. Cerebrovasc Dis. 2021;50(1):46-53. doi: 10.1159/000512179. Epub 2020 Dec 11.

8. Kamel H, Okin PM, Longstreth WT Jr, et al. Atrial cardiopathy: a broadened concept of left atrial thromboembolism beyond atrial fibrillation. Future Cardiol. 2015 May;11(3):323-31. doi: 10.2217/fca.15.22

9. Jalini S, Rajalingam R, Nisenbaum R, et al. Atrial cardiopathy in patients with embolic strokes of unknown source and other stroke etiologies. Neurology. 2019 Jan 22;92(4):e288e294. doi: 10.1212/WNL.0000000000006748. Epub 2018 Dec 5.

10. Silva AR, Pires C, Meira-Carvalho F, et al. Atrial cardiopathy predicts detection of atrial fibrillation in embolic stroke of undetermined source: real-life data. Neurol Sci. 2022 Apr;43(4):2383-6. doi: 10.1007/s10072-02105692-3. Epub 2021 Oct 27.

11. Ntaios G, Perlepe K, Lambrou D, et al. Prevalence and Overlap of Potential Embolic Sources in Patients With Embolic Stroke of Undetermined Source. J Am Heart Assoc. 2019 Aug 6;8(15):e012858. doi: 10.1161/JAHA.119.012858. Epub 2019 Jul 31.

12. Yaghi S, Boehme AK, Hazan R, et al. Atrial Cardiopathy and Cryptogenic Stroke: A Crosssectional Pilot Study. J Stroke Cerebrovasc Dis. 2016 Jan;25(1):110-4. doi: 10.1016/j.jstrokecerebrovasdis.2015.09.001. Epub 2015 Oct 21.

13. Tan BYQ, Ho JSY, Sia CH, et al. Left Atrial Volume Index Predicts New-Onset Atrial Fibrillation and Stroke Recurrence in Patients with Embolic Stroke of Undetermined Source. Cerebrovasc Dis. 2020;49(3):285-91. doi: 10.1159/000508211. Epub 2020 Jun 17.

14. Jordan K, Yaghi S, Poppas A, et al. Left Atrial Volume Index Is Associated With Cardioembolic Stroke and Atrial Fibrillation Detection After Embolic Stroke of Undetermined Source. Stroke. 2019 Aug;50(8):1997-2001. doi: 10.1161/STROKEAHA.119.025384. Epub 2019 Jun 13.

15. 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 Jun 7;378(23):2191-201. doi: 10.1056/NEJMoa1802686. Epub 2018 May 16.

16. Kirchhof P, Toennis T, Goette A, et al. Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes. N Engl J Med. 2023;10.1056/NEJMoa2303062. doi: 10.1056/NEJMoa2303062. Epub 2023 Aug 25.

17. Perlepe K, Sirimarco G, Strambo D, et al. Left atrial diameter thresholds and new incident atrial fibrillation in embolic stroke of undetermined source. Eur J Intern Med. 2020 May;75:30-4. doi: 10.1016/j.ejim.2020.01.002. Epub 2020 Jan 15.

18. Tajmirriahi M, Salari P, Saadatnia M. Left atrial function index in embolic stroke of undetermined source: A case-control study. Neurol Asia. 2022;27(2):275-9. doi: 10.54029/2022cnz

19. Poli S, Diedler J, Härtig F, et al. Insertable cardiac monitors after cryptogenic stroke – a risk factor based approach to enhance the detection rate for paroxysmal atrial fibrillation. Eur J Neurol. 2016 Feb;23(2):375-81. doi: 10.1111/ene.12843. Epub 2015 Oct 16.

20. Kneihsl M, Bisping E, Scherr D, et al. Predicting atrial fibrillation after cryptogenic stroke via a clinical risk score-a prospective observational study. Eur J Neurol. 2022 Jan;29(1):149-57. doi: 10.1111/ene.15102. Epub 2021 Sep 23.

21. Ntaios G, Perlepe K, Lambrou D, et al. Supraventricular Extrasystoles on Standard 12lead Electrocardiogram Predict New Incident Atrial Fibrillation after Embolic Stroke of Undetermined Source: The AF-ESUS Study. J Stroke Cerebrovasc Dis. 2020 Apr;29(4):104626. doi: 10.1016/j.jstrokecerebrovasdis.2019.104626. Epub 2020 Jan 15.

22. Vollmuth C, Stoesser S, Neugebauer H, et al. MR-imaging pattern is not a predictor of occult atrial fibrillation in patients with cryptogenic stroke. J Neurol. 2019 Dec;266(12):3058-64. doi: 10.1007/s00415-019-09524-5. Epub 2019 Sep 11. Erratum in: J Neurol. 2020 Oct;267(10):3117.

23. Di Meglio L, Derraz I, Solonomenjanahary M, et al; compoCLOT Research Investigators group. Two-layered susceptibility vessel sign is associated with biochemically quantified thrombus red blood cell content. Eur J Neurol. 2020 Jul;27(7):1264-71. doi: 10.1111/ene.14241. Epub 2020 May 3.

24. Kang DW, Jeong HG, Kim DY, et al. Prediction of Stroke Subtype and Recanalization Using Susceptibility Vessel Sign on Susceptibility-Weighted Magnetic Resonance Imaging. Stroke. 2017 Jun;48(6):1554-9. doi: 10.1161/STROKEAHA.116.016217. Epub 2017 Apr 21.

25. Bourcier R, Derraz I, Delasalle B, et al; THRACE investigators. Susceptibility Vessel Sign and Cardioembolic Etiology in the THRACE Trial. Clin Neuroradiol. 2019 Dec;29(4):685-92. doi: 10.1007/s00062-0180699-8. Epub 2018 Jun 12.

26. Alhazmi H, Bani-Sadr A, Bochaton T, et al. Large vessel cardioembolic stroke and embolic stroke of undetermined source share a common profile of matrix metalloproteinase-9 level and susceptibility vessel sign length. Eur J Neurol. 2021 Jun;28(6):1977-83. doi: 10.1111/ene.14806. Epub 2021 Apr 17.

27. Del Brutto VJ, Diener HC, Easton JD, et al. Predictors of Recurrent Stroke After Embolic Stroke of Undetermined Source in the RE-SPECT ESUS Trial. J Am Heart Assoc. 2022 Jun 7;11(11):e023545. doi: 10.1161/JAHA.121.023545. Epub 2022 Jun 3.

28. Hou Y, Elmashad A, Staff I, et al. Potential Embolic Sources Differ in Patients With Embolic Stroke of Undetermined Source According to Age: A 15-Year Study. Front Neurol. 2022 May 17;13:860827. doi: 10.3389/fneur.2022.860827

29. Jagadeesan V, Culver A, Raiker N, et al. Left Atrial Dilation and Risk of One-Year Readmission after Embolic Stroke of Undetermined Source. J Stroke Cerebrovasc Dis. 2020 Aug;29(8):104975. doi: 10.1016/j.jstrokecerebrovasdis.2020.104975. Epub 2020 Jun 9.