Криптогенный инсульт: кардиологические ключи к неврологической загадке

В настоящей статье подробно анализируются кардиологические аспекты этиологии криптогенного инсульта, в том числе ESUS (от англ. embolic stroke of undetermined source — эмболический инсульт из неустановленного источника эмболии). Особое внимание уделяется патофизиологическим механизмам и факторам риска развития кардиоэмболии при отсутствии инструментально подтвержденной фибрилляции предсердий. Детально рассматриваются несколько ключевых направлений: предсердная кардиопатия как комплекс структурных и функциональных изменений левого предсердия, субклиническая форма фибрилляции предсердий и аорто-артериальная эмболия, осуществляемая посредством нестенозирующих атеросклеротических бляшек, интракраниального атеросклероза и атероматоза дуги аорты. Представлен комплексный анализ современных диагностических биомаркеров, включая инструментальные (величина конечной части зубца P в отведении V1 на электрокардиограмме — PTFV1, наджелудочковые нарушения ритма, показатели структурных изменений левого предсердия) и лабораторные (N-концевой фрагмент мозгового натрийуретического пропептида, тропонин, D-димер), позволяющие идентифицировать скрытый эмбологенный субстрат. Освещены новые подходы в диагностике, в том числе расширенные протоколы электрокардиографического мониторинга, эхокардиографические методики и передовые методы визуализации сосудов. Подчеркивается необходимость комплексного раннего диагностического протокола, реализуемого в рамках персонализированного подхода.

1. Hart RG, Diener HC, Coutts SB, Easton JD, Granger CB, O'Donnell MJ, et al. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol. 2014;13(4):429– 438. https://doi.org/10.1016/S1474-4422(13)70310-7

2. Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J, Lombardi-Hill D, et al. 2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association / American Stroke Association. Stroke. 2021;52(7):e364–e467. https://doi.org/10.1161/STR.0000000000000375

3. Hart RG, Catanese L, Perera KS, Ntaios G, Connolly SJ. Embolic stroke of undetermined source: a systematic review and clinical update. Stroke. 2017;48(4):867–872. https://doi.org/10.1161/STROKEAHA.116.016414

4. Ntaios G. Embolic stroke of undetermined source: JACC review topic of the week. J Am Coll Cardiol. 2020;75(3):333–340. https://doi.org/10.1016/j.jacc.2019.11.024

5. Kamtchum-Tatuene J, Wilman A, Saqqur M, Shuaib A, Jickling G. Prevalence of high-risk plaques and risk of stroke in patients with asymptomatic carotid stenosis: a meta-analysis. JAMA Neurol. 2020;77(12):1524–1535. https://doi.org/10.1001/jamaneurol.2020.2658

6. Kato Y, Takahashi S. Atrial cardiopathy and cryptogenic stroke. Front Neurol. 2022;13:839398. https://doi.org/10.3389/fneur.2022.839398

7. Yaghi S. Diagnosis and management of cardioembolic stroke. Continuum (Minneap Minn). 2023;29(2):462–485. https://doi.org/10.1212/CON.0000000000001217

8. Демин Д.А., Кулеш А.А., Янишевский С.Н., Климчук Д.О., Мехряков С.А., Сыромятникова Л.И. и др. Криптогенный инсульт. Часть 3: предсердная кардиопатия и скрытая фибрилляция предсердий. Медицинский совет. 2022;16(21):8– 18. https://doi.org/10.21518/2079-701X-2022-16-21-8-18 [Demin DA, Kulesh AA, Yanishevskiy SN, Klimchuk DO, Mekhryakov SA, Syromyatnikova LI, et al. Cryptogenic stroke. Part 3: atrial cardiopathy and silent atrial fibrillation. Meditsinskiy Sovet = Medical Council. 2022;16(21):8–18. (In Russ.) https://doi.org/10.21518/2079-701X-2022-16-21-8-18]

9. Hamer M, Kienzle M, Olshan A, Capasso R, Garan H, Ruskin J. Incidence of symptomatic atrial fibrillation in patients with paroxysmal supraventricular tachycardia. J Am Coll Cardiol. 1995;25(5):984–988. https://doi.org/10.1016/0735-1097(94)00521-2

10. Gladstone D, Dorian P, Spring M, Panzov V, Mamdani M, Healey J, et al. Atrial premature beats predict atrial fibrillation in cryptogenic stroke: results from the EMBRACE trial. Stroke. 2015;46(4):936–941. https://doi.org/10.1161/STROKEAHA.115.008714

11. Yaghi S, Moon YP, Mora-McLaughlin C, Willey JZ, Cheung K, Di Tullio MR, et al. Left atrial enlargement and stroke recurrence: the Northern Manhattan Stroke Study. Stroke. 2015;46(6):1488–1493. https://doi.org/10.1161/STROKEAHA.115.008711

12. Fonseca A, Alves P, Inácio N, Marto J, Viana-Baptista M, Pinho-E-Melo T, et al. Patients with undetermined stroke have increased atrial fibrosis: a cardiac magnetic resonance imaging study. Stroke. 2018;49(3):734–737. https://doi.org/10.1161/STROKEAHA.117.019641

13. Kühnlein P, Mahnkopf C, Majersik J, Wilson B, Mitlacher M, Tirschwell D, et al. Atrial fibrosis in embolic stroke of undetermined source: a multicenter study. Eur J Neurol. 2021;28(11):3634–3639. https://doi.org/10.1111/ene.15022

14. Bifulco S, Scott G, Sarairah S, Birjandian Z, Roney C, Niederer S, et al. Computational modeling identifies embolic stroke of undetermined source patients with potential arrhythmic substrate. Elife. 2021;10:e64213. https://doi.org/10.7554/eLife.64213

15. Stroke Prevention in Atrial Fibrillation Investigators. The stroke prevention in atrial fibrillation III study: rationale, design, and patient features. J Stroke Cerebrovasc Dis. 1997;6(5):341–353. https://doi.org/10.1016/S1052-3057(97)80217-0

16. Gwak D, Kim Y, Park H, Kim M, Lee J, Kim S, et al. Impact of left atrial appendage morphology on recurrence in embolic stroke of undetermined source and atrial cardiopathy. Front Neurol. 2021;12:679320. https://doi.org/10.3389/fneur.2021.679320

17. Nadarajah R, Wu J, Fröhlich H, Gale C. Future Innovations in Novel Detection for Atrial Fibrillation (FIND-AF): pilot study of an electronic health record machine learning algorithm-guided intervention to identify undiagnosed atrial fibrillation. Open Heart. 2023;10(2):e002331. https://doi.org/10.1136/openhrt-2023-002447

18. Cushman M, Judd S, Howard V, Kissela B, Gutiérrez O, Jenny N, et al. N-terminal pro-B-type natriuretic peptide and stroke risk: the reasons for geographic and racial differences in stroke cohort. Stroke. 2014;45(6):1646–1650. https://doi.org/10.1161/STROKEAHA.114.004712

19. Merkler A, Gialdini G, Yaghi S, Okin P, Iadecola C, Navi B, et al. Association between troponin levels and embolic stroke of undetermined source. J Am Heart Assoc. 2017;6(9):e005905. https://doi.org/10.1161/JAHA.117.005905

20. Adams H, Bendixen B, Kappelle L, Biller J, Love B, Gordon D, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24(1):35–41. https://doi.org/10.1161/01.STR.24.1.35

21. Elsheikh S, Hill A, Irving G, Lip G, Abdul-Rahim A. Atrial fibrillation and stroke: state-of-the-art and future directions. Curr Probl Cardiol. 2024;49:102181. https://doi.org/10.1016/j.cpcardiol.2023.102181

22. Vinding N, Kristensen S, Rørth R, Butt J, Kruuse C, Østergaard L, et al. Ischemic stroke severity and mortality in patients with and without atrial fibrillation. J Am Heart Assoc. 2022;11(19):e026723. https://doi.org/10.1161/JAHA.121.022638

23. Freedman B, Camm J, Calkins H, Healey J, Rosenqvist M, Wang J, et al. Screening for atrial fibrillation: a report of the AF-SCREEN international collaboration. Circulation. 2017;135(19):1851–1867. https://doi.org/10.1161/CIRCULATIONAHA.116.026693

24. Freedman B, Potpara T, Lip G. Stroke prevention in atrial fibrillation. Lancet. 2016;388(10046):806–817. https://doi.org/10.1016/S0140-6736(16)31257-0

25. Wachter R, Gröschel K, Gelbrich G, Hamann G, Kermer P, Liman J, et al. Holter-electrocardiogram-monitoring in patients with acute ischaemic stroke (Find-AFRANDOMISED): an open-label randomised controlled trial. Lancet Neurol. 2017;16(4):282–290. https://doi.org/10.1016/S1474-4422(17)30002-9

26. Jauch E, Saver J, Adams H, Bruno A, Connors J, Demaerschalk B, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association / American Stroke Association. Stroke. 2013;44(3):870–947. https://doi.org/10.1161/STR.0b013e318284056a

27. Nadarajah R, Wahab A, Reynolds C, Raveendra K, Askham D, Dawson R, et al. Future Innovations in Novel Detection for Atrial Fibrillation (FIND-AF): pilot study of an electronic health record machine learning algorithm-guided intervention to identify undiagnosed atrial fibrillation. Open Heart. 2023;10(2):e002447. https://doi.org/10.1136/openhrt-2023-002447

28. Rubio Campal J, García Torres M, Fernández de la Vara Prieto R, García Arribas D, Marín R, Almendro Delia M, et al. Detecting atrial fibrillation in patients with an embolic stroke of undetermined source (from the DAF-ESUS registry). Am J Cardiol. 2020;125(3):409–414. https://doi.org/10.1016/j.amjcard.2019.10.047

29. Ntaios G, Perlepe K, Lambrou D, Sirimarco G, Strambo D, Eskandari A, et al. Identification of patients with embolic stroke of undetermined source and low risk of new incident atrial fibrillation: the AF-ESUS score. Int J Stroke. 2021;16(1):29–38. https://doi.org/10.1177/1747493020925281

30. Li Y, Bisson A, Bodin A, Herbert J, Grammatico-Guillon L, Joung B, et al. C2 HEST score and prediction of incident atrial fibrillation in poststroke patients: a french nationwide study. J Am Heart Assoc. 2019;8(13):e012546. https://doi.org/10.1161/JAHA.119.012546

31. Pajareya P, Phutinart S, Siranart N, Paksin S, Jansem P, Anukoolwittaya P, et al. Natural courses of atrial fibrillation following cryptogenic stroke: a systematic review and meta-analysis. Indian Pacing Electrophysiol J. 2025;25(4):207–217. https://doi.org/10.1016/j.ipej.2025.06.006

32. Ashburner J, Wang X, Li X, Khurshid S, Ko D, Trisini Lipsanopoulos A, et al. Re-CHARGE-AF: recalibration of the CHARGE-AF model for atrial fibrillation risk prediction in patients with acute stroke. J Am Heart Assoc. 2021;10(21):e022363. https://doi.org/10.1161/JAHA.121.022363

33. Hsieh C, Lee C, Sung S. Development of a novel score to predict newly diagnosed atrial fibrillation after ischemic stroke: the CHASE-LESS score. Atherosclerosis. 2020;295:1–7. https://doi.org/10.1016/j.atherosclerosis.2020.01.003

34. Ekizoglu E, Gezegen H, Ulusoy E, Tütüncü M, Demir T, Baykan B. CHADS 2 and CHA 2 DS 2 -VASc scores can guide the evaluation of cryptogenic ischemic stroke. Neurol India. 2021;69(6):1716–1721. https://doi.org/10.4103/0028-3886.333504

35. Кулеш А. А., Демин Д. А., Виноградов О. И. Криптогенный инсульт. Часть 1: аорто-артериальная эмболия. Медицинский совет. 2021;(4):78–87. https://doi.org/10.21518/2079-701X-2021-4-78-87

36. Cui X, Li Y, Liu J, He S, Liu M. Aortic arch atheroma and the risk of stroke: a meta-analysis. J Evid Based Med. 2014;7(3):185–191. https://doi.org/10.1111/jebm.12113

37. Amarenco P, Duyckaerts C, Tzourio C, Hénin D, Bousser M, Hauw J. The prevalence of ulcerated plaques in the aortic arch in patients with stroke. N Engl J Med. 1992;326(4):221–225. https://doi.org/10.1056/NEJM199201233260402

38. Ntaios G, Swaminathan B, Berkowitz S, Afzal M, Sirimarco G, Perlepe K, et al. Aortic arch atherosclerosis in patients with embolic stroke of undetermined source: an exploratory analysis of the NAVIGATE ESUS trial. Stroke. 2019;50(11):3184–3190. https://doi.org/10.1161/STROKEAHA.119.025813

39. Harloff A, Dudler P, Frydrychowicz A, Strecker C, Stroh A, Geibel A, et al. Reliability of aortic MRI at 3 Tesla in patients with acute cryptogenic stroke. J Neurol Neurosurg Psychiatry. 2008;79(5):540–546. https://doi.org/10.1136/jnnp.2007.125211

40. Zhao X, Hippe DS, Li R, Canton GM, Sui B, Song Y, CARE II Study Collaborators, et al. Prevalence and characteristics of carotid artery high-risk atherosclerotic plaques in Chinese patients with cerebrovascular symptoms: a Chinese atherosclerosis risk evaluation II study. J Am Heart Assoc. 2017;6(8):e005831. https://doi.org/10.1161/JAHA.117.005831

41. Sannananja B, Zhu C, Mossa-Basha M. Vessel wall imaging in cryptogenic stroke. Radiol Clin North Am. 2023;61(3):491–500. https://doi.org/10.1016/j.rcl.2023.01.006

42. Kamtchum-Tatuene J, Jickling G. Non-stenotic carotid plaques in embolic stroke of unknown source. Front Neurol. 2021;12:655674. https://doi.org/10.3389/fneur.2021.655674

43. Qureshi AI, Caplan LR. Intracranial atherosclerosis. Lancet. 2014;383(9921):984–998. https://doi.org/10.1016/S0140-6736(13)61088-0

44. Amarenco P. Underlying pathology of stroke of unknown cause (Cryptogenic Stroke). Cerebrovasc Dis. 2009;27(Suppl 1):97– 103. https://doi.org/10.1159/000200446

45. Schaafsma J, Rawal S, Coutinho J, Rasheed A, Kooi M, Sacchetti D, et al. Diagnostic impact of intracranial vessel wall MRI in 205 patients with ischemic stroke or TIA. AJNR Am J Neuroradiol. 2019;40(10):1701–1706. https://doi.org/10.3174/ajnr.A6202

46. Wang Y, Liu X, Wu X, Degnan A, Malhotra A, Zhu C. Culprit intracranial plaque without substantial stenosis in acute ischemic stroke on vessel wall MRI: a systematic review. Atherosclerosis. 2019;287:112–121. https://doi.org/10.1016/j.atherosclerosis.2019.06.907