Neurology, Neuropsychiatry, Psychosomatics

Advanced search

Biomarkers of atrial cardiopathy in patients with different pathogenetic subtypes of ischemic stroke

Full Text:


Studies of the biomarkers of atrial cardiopathy seem to be promising for identifying patients with cryptogenic stroke (CS), in which an intensive search for atrial fibrillation is indicated. Nevertheless, the diagnostic value of these markers and their threshold values require clarification.

Objective: to present the characteristics of echocardiographic markers for atrial cardiopathy and the serum concentration of N-terminal pro-Btype natriuretic peptide (NT-proBNP) in embolic CS versus cardioembolic stroke (CES) and non-cardioembolic stroke (non-CES) to determine the threshold values of parameters with the highest sensitivity and specificity in differentiating CES and non-CES.

Patients and methods. A total of 259 patients with ischemic stroke were examined. The standard examination additionally involved calculation of the parameters that reflected left atrial LA) function (LAF): LA emptying fraction (LAEF), and LA functional index (LAFI). The serum NT-proBNP concentration was also determined in 75 patients.

Results and discussion. The patients with CES versus those with CS and non-CES were characterized by a considerable increase in LA diameter (4.3 [3.5; 4.5] cm vs 3.7 [3.4; 4.0] cm vs 3.7 [3.4; 3.9] cm; p=0.005 and p=0.009, respectively), LAVI (35.7 [30.5; 39.9] ml/m2 vs 28.5 [25.6; 34.6] ml/m2 vs 27.1 [24.5; 31.2] ml/m2 ; p< 0.001) and NT-proBNP level (559 [409; 1144] pg/ml vs 164 [65; 308] pg/ml vs 191 [63; 446] pg/ml; p=0.002 and p=0.019, respectively), as well as by a lower LAEF value [50.3 [48.5; 51.1]% vs 54.7 [51.6; 56.6]% vs 54.9 [52.5; 56.8]%; p< 0.001). The only parameter that showed significant differences between all the three groups (CES, CS, and nonCES) was LAFI (0.24 [0.2; 0.32] units vs 0.37 [0.3; 0.47] units vs 0.40 [0.34; 0.47] units; p<0.00 1), while maintaining the differences in the values for the two groups (CS and non-CES) (p=0.004). The following threshold values of biomarkers were obtained for CES and nonCES; these were a LA diameter of 41.5 mm (p< 0.001), a LAVI of 36.3 ml/m2 (p< 0.001), a LAEF of 51.8% (p< 0.001), a LAFI of 0.28 units (p< 0.001), and an NT-proBNP of 316 pg/ml (p< 0.001). Analysis of the ROC curves and the area under the curve (AUC) revealed that the most informative criteria for sensitivity and specificity were LAEF (79 and 88%, AUC 0.89), NT-proBNP (67 and 91%, AUC 0.89) and LAFI (93 and 72%, AUC 0.81).

Conclusion. The CS group and non-CES one are comparable in the echocardiographic manifestations of atrial cardiopathy and in serum NTproBNP values. LAEF and NT-proBNP concentrations are promising biomarkers to classify CS patients into potential arterio- and cardioembolic types.

About the Authors

S. A. Mekhryakov
City Clinical Hospital Four
Russian Federation

2, KIM St., Perm 614107

A. A. Kulesh
City Clinical Hospital Four; Acad. E.A. Vagner Perm State Medical University, Ministry of Health of Russia
Russian Federation

Aleksey Aleksandrovich Kulesh

2, KIM St., Perm 614107,

26, Petropavlovskaya St., Perm 614990

L. I. Syromyatnikova
City Clinical Hospital Four; Acad. E.A. Vagner Perm State Medical University, Ministry of Health of Russia
Russian Federation

2, KIM St., Perm 614107,

26, Petropavlovskaya St., Perm 614990

К. V. Sobyanin
National Research University «Higher School of Economics»
Russian Federation

38, Studencheskaya St., Perm 614070


1. Nouh A, Hussain M, Mehta T, Yaghi S. Embolic Strokes of Unknown Source and Cryptogenic Stroke: Implications in Clinical Practice. Front Neurol. 2016 Mar 21;7:37. doi: 10.3389/fneur.2016.00037. eCollection 2016.

2. Hart RG, Diener HC, Coutts SB, et al. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol. 2014 Apr;13(4):429-38. doi: 10.1016/S1474-4422(13)70310-7

3. Kalashnikova LA, Dobrynina LA. Ischemic stroke in young adults. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2017;117(8):3-12. doi: 10.17116/jnevro2017117823-12 (In Russ.).

4. Kulesh AA, Ognerubov DV, Mekhryakov SA, et al. Patent foramen ovale-related stroke: diagnostic approaches and the possibility of endovascular prophylaxis (clinical cases and literature review). Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2020;12(2):72-8. doi: 10.14412/2074-2711-2020-2-72-78 (In Russ.).

5. Mekhryakov SA, Kulesh AA, Pokalenko EA, et al. The paradoxical embolism phenomenon in patients with embolic cryptogenic stroke. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2020;12(1):13-21. doi: 10.14412/2074-2711-2020-1-13-21 (In Russ.).

6. Kulesh AA, Shestakov VV. Patent foramen ovale and embolic cryptogenic stroke. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2019;11(2):4-11. doi: 10.14412/2074-2711-2019-2-4-11 (In Russ.).

7. Kulesh AA, Drobakha VE, Shestakov VV. Cryptogenic stroke. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2019;11(4): 14-21. doi: 10.14412/2074-2711-2019-4-14-21 (In Russ.).

8. Kulesh AA, Syromyatnikova LI, Drobakha VE, et al. Kriptogennyy insul't: Rukovodstvo [Cryptogenic stroke: A guide]. Moscow: GEOTAR-Media; 2020. 128 p. doi: 10.33029/9704-5597-5-CS-2020-1-128 (In Russ.).

9. Brambatti M, Connolly SJ, Gold MR, et al. Temporal relationship between subclinical atrial fibrillation and embolic events. Circulation. 2014 May 27;129(21):2094-9. doi: 10.1161/CIRCULATIONAHA.113.007825. Epub 2014 Mar 14.

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

11. Tandon K, Tirschwell D, Longstreth WT, et al. Embolic stroke of undetermined source correlates to atrial fibrosis without atrial fibrillation. Neurology. 2019 Jul 23;93(4):e381-7. doi: 10.1212/WNL.0000000000007827. Epub 2019 Jun 25.

12. Kamel H, Bartz TM, Elkind MSV, et al. Atrial Cardiopathy and the Risk of Ischemic Stroke in the CHS (Cardiovascular Health Study). Stroke. 2018 Apr;49(4):980-6. doi: 10.1161/STROKEAHA.117.020059. Epub 2018 Mar 13.

13. Meisel K, Yuan K, Fang Q, et al. Embolic Stroke of Undetermined Source: A Population with Left Atrial Dysfunction. J Stroke Cerebrovasc Dis. 2019 Jul;28(7):1891-6. doi: 10.1016/j.jstrokecerebrovasdis.2019.04.004. Epub 2019 Apr 26.

14. 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;75:30-4. doi: 10.1016/j.ejim.2020.01.002

15. 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;50(8):1997-2001. doi:10.1161/STROKEAHA.119.025384

16. Kamel H, Okin PM, Merkler AE, et al. Relationship between left atrial volume and ischemic stroke subtype. Ann Clin Transl Neurol. 2019;6(8):1480-6. doi: 10.1002/acn3.50841

17. Zhao J, Zhang Y, Yuan F, et al. Diagnostic value of N-terminal pro B-type natriuretic peptide for nonvalvular atrial fibrillation in acute ischemic stroke patients: A retrospective multicenter case-control study [published online ahead of print, 2020 Apr 6]. J Neurol Sci. 2020;414:116822. doi: 10.1016/j.jns.2020.116822

18. Fonseca AC, Brito D, Pinho e Melo T, et al. N-terminal pro-brain natriuretic peptide shows diagnostic accuracy for detecting atrial fibrillation in cryptogenic stroke patients. Int J Stroke. 2014;9(4):419-25. doi: 10.1111/ijs.12126

19. Kneihsl M, Gattringer T, Bisping E, et al. Blood Biomarkers of Heart Failure and Hypercoagulation to Identify Atrial Fibrillation-Related Stroke. Stroke. 2019;50(8):2223-6. doi: 10.1161/STROKEAHA.119.025339

20. Sargento L, Vicente Simоes A, Longo S, et al. Left atrial function index predicts longterm survival in stable outpatients with systolic heart failure. Eur Heart J Cardiovasc Imaging. 2017 Feb;18(2):119-27. doi: 10.1093/ehjci/jew196. Epub 2016 Sep 27.

21. Guichard JB, Nattel S. Atrial cardiomyopathy: a useful notion in cardiac disease management or a passing fad? J Am Coll Cardiol. 2017 Aug 8;70(6):756-65. doi: 10.1016/j.jacc.2017.06.033

22. Schnabel RB, Haeusler KG, Healey JS, et al. Searching for Atrial Fibrillation Poststroke: A White Paper of the AF-SCREEN International Collaboration [published correction appears in Circulation. 2020 Feb 25;141(8):e99]. Circulation. 2019;140(22):1834-50. doi: 10.1161/CIRCULATIONAHA.119.040267

23. Vasilets LM, Grigoriadi NE, Karpunina NS, et al. Immune status in patients with ischemic heart disease with persistent atrial fibrillation. Klinicheskaya meditsina. 2013;(5):32-4 (In Russ.).

24. Grigoriadi NE, Vasilets LM, Ratanova EA, et al. The role of inflammation and cardiac fibrosis in the onset and development of atrial fibrillation of various etiologies. Klinicheskaya meditsina. 2013;(10):34-7 (In Russ.).

25. Elkind MSV. Atrial cardiopathy and stroke prevention. Review. Curr Cardiol Rep. 2018 Sep 12;20(11):103. doi: 10.1007/s11886-018-1053-0

26. Yaghi S, Bernstein RA, Passman R, Okin PM. Furie Cryptogenic Stroke: Research and Practice. Circ Res. 2017 Feb 3;120(3):527- 40. doi: 10.1161/CIRCRESAHA.116.308447

27. Kamel H, Longstreth WT Jr, Tirschwell DL, et al. The AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke randomized trial: Rationale and methods. Int J Stroke. 2019 Feb;14(2):207-14. doi: 10.1177/1747493018799981

28. Ferkh A, Brown P, O’Keefe E, et al. Clinical and echocardiographic characteristics of cardioembolic stroke. Eur J Neurol. 2019 Oct;26(10):1310-7. doi: 10.1111/ene.13981. Epub 2019 May 31.

29. Wasser K, Weber-Krüger M, Gröschel S, et al. Brain Natriuretic Peptide and Discovery of Atrial Fibrillation After Stroke: A Subanalysis of the Find-AFRANDOMISED Trial. Stroke. 2020 Feb;51(2):395-401. doi: 10.1161/STROKEAHA.119.026496. Epub 2019 Dec 9.

30. Mehrzad R, Rajab M, Spodick DH. The three integrated phases of left atrial macrophysiology and their interactions. Int J Mol Sci. 2014 Aug 27;15(9):15146-60. doi: 10.3390/ijms150915146

31. Chung-Chuan Chou, Hui-Ling Lee, Po-Cheng Chang, et al. Left atrial emptying fraction predicts recurrence of atrial fibrillation after radiofrequency catheter ablation. PLoS One. 2018;13(1):e0191196. doi: 10.1371/journal.pone.0191196

32. Russo C, Jin Z, Liu R, et al. Left Atrial Volumes and Reservoir Function Are Associated With Subclinical Cerebrovascular Disease: The Cardiovascular Abnormalities and Brain Lesions (CABL) Study. JACC Cardiovasc Imaging. 2013 Mar;6(3):313-23. doi: 10.1016/j.jcmg.2012.10.019


For citations:

Mekhryakov S.A., Kulesh A.A., Syromyatnikova L.I., Sobyanin К.V. Biomarkers of atrial cardiopathy in patients with different pathogenetic subtypes of ischemic stroke. Neurology, Neuropsychiatry, Psychosomatics. 2020;12(6):33-41.

Views: 484

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 2074-2711 (Print)
ISSN 2310-1342 (Online)