Атерома дуги аорты как источник артерио-артериальной эмболии и ишемического инсульта

Введение. В настоящее время, несмотря на внедрение современных диагностических алгоритмов, у 20–40 % пациентов с ишемическим инсультом не удаётся установить его причину. Потенциальными причинами острой церебральной ишемии у пациентов с криптогенным ишемическим инсультом могут быть пароксизмальная фибрилляция предсердий, открытое овальное окно, предсердная кардиомиопатия, каротидная сеть, атерома дуги аорты, а также канцер-ассоциированная тромбофилия.

Цель: систематизация данных о методах диагностики и профилактики атеромы дуги аорты.

Материал и методы. Поиск литературы проводили в электронных поисковых системах Scopus, eLibrary, PubMed по ключевым словам: ишемический инсульт, криптогенный инсульт, атерома дуги аорты, патогенез ишемического инсульта.

Результаты. В настоящее время, несмотря на столь детальную проработку терапевтических стратегий профилактики повторных тромботических событий у пациентов с атеромой дуги аорты, ни один из препаратов не доказал своего преимущества. Несмотря на то, что исследования NAVIGATE ESUS и RESPECT ESUS не показали превосходства пероральных антикоагулянтов над антиагрегантами в отношении предотвращения повторных ишемических инсультов у пациентов с криптогенным инсультом, было установлено, что криптогенный ишемический инсульт неоднороден, что требует дифференцированного подхода ко вторичной профилактике.

Выводы. Атерома аорты может быть причиной эмболического синдрома и криптогенного инсульта. Основные методы диагностики атеромы аорты – чрезпищеводная эхокардиография и компьютерно-томографическая ангиография. Терапевтическая стратегия лечения атеромы аорты – гиполипидемическая, антитромботическая терапия в комбинации с блокаторами ренин-ангиотензин-альдостероновой системы. 

1. Timsit S. From cryptogenic to ESUS: Toward precision medicine? Rev Neurol (Paris). 2022;178(9):939-952. PMID: 35597610 https://doi.org/10.1016/j.neurol.2022.01.016

2. Рамазанов Г.Р., Ковалева Э.А., Ахматханова Л.Х.-Б., Петриков С.С. Открытое овальное окно как причина криптогенного ишемического инсульта. Российский неврологический журнал. 2022;27(2):53-59. https://doi.org/10.30629/2658-7947-2022-27-2-53-59.

3. Рамазанов Г.Р., Ковалева Э.А., Новиков Р.А., Петриков С.С. Предсердная кардиомиопатия и криптогенный инсульт. Журнал им. Н.В. Склифосовского Неотложная медицинская помощь. 2022;11(3):493-500. https://doi.org/10.23934/2223-9022-2022-11-3-493-500

4. Рамазанов Г.Р., Ковалева Э.А., Шамалов Н.А. Онкологические заболевания как фактор риска криптогенного инсульта. Журнал им. Н.В. Склифосовского Неотложная медицинская помощь. 2021;10(4):778-786. https://doi.org/10.23934/2223-9022-2021-10-4-778-786

5. Fisher C.M. Occlusion of the internal carotid artery. AMA Arch Neurol Psychiatry. 1951;65(3):346-377. PMID: 14810286 https://doi.org/10.1001/archneurpsyc.1951.02320030083009

6. Winter WJ.Jr. Atheromatous emboli; a cause of cerebral infarction; report of two cases. AMA Arch Pathol. 1957;64(2):137-142. PMID: 13443604

7. Khatibzadeh M, Mitusch R, Stierle U, Gromoll B, Sheikhzadeh A. Aortic atherosclerotic plaques as a source of systemic embolism. J Am Coll Cardiol. 1996;27(3):664-669. PMID: 8606279 https://doi.org/10.1016/07-35-1097(95)00526-9

8. Di Tullio MR, Sacco RL, Gersony D, Nayak H, Weslow RG, Kargman DE, et al. Aortic atheromas and acute ischemic stroke: A transesophageal echocardiographic study in an ethnically mixed population. Neurology. 1996;46(6):1560-1566. PMID: 8649549 https://doi.org/10.1212/wnl.46.6.1560

9. Alvarez C, Aslam HM, Wallach S, Mustafa Muhammad U. A Large Grade 5 Mobile Aortic Arch Atheromatous Plaque: Cause of Cerebrovascular Accident. Case Rep Med. 2018;5134309. PMID: 29808095 https://doi.org/10.1155/2018/5134309

10. Kondakov A, Lelyuk V. Clinical Molecular Imaging for Atherosclerotic Plaque. J Imaging. 2021;7(10):211. PMID: 34677297 https://doi.org/10.3390/jimaging7100211

11. Sinzinger H, Silberbauer K, Auerswald W. Quantitative Investigation of Sudanophilic Lesions around the Aortic Ostia of Human Fetuses, Newborn and Children. Blood Vessels. 1980;17(1):44-52. PMID: 7357095 https://doi.org/10.1159/000158233

12. Zieske AW, Malcom GT, Strong JP. Natural History And Risk FactorsOf Atherosclerosis In Children And Youth: The PDAY study. Pediatr Pathol Mol Med. 2002;21(2):213-237. PMID: 11942537 https://doi.org/10.1080/15227950252852104

13. Enos WF, Holmes RH, Beyer J. Coronary Disease Among United States Soldiers Killed In Action in Korea; preliminary report. J Am Med Assoc. 1953;152(12):1090-1093. PMID: 13052433 https://doi.org/10.1001/jama.1953.03690120006002

14. Ali L, Safan A, Kamran S, Akhtar N, Elalamy O. Acute Thromboembolic Ischemic Stroke From Complex Aortic Arch Plaque. Cureus. 2021;13(8):e16977. PMID: 34540387 https://doi.org/10.7759/cureus.16977

15. Viedma-Guiard E, Guidoux C, Amarenco P, Meseguer E. Aortic Sources of Embolism. Front Neurol. 2021;11:606663. PMID: 33519684 https://doi.org/10.3389/fneur.2020.606663

16. Andersen ND, Hart SA, Devendra GP, Kim ESH, Johnston DR, Schroder JN, et al. Atheromatous disease of the aorta and perioperative stroke. J Thorac Cardiovasc Surg. 2018;155(2):508-516. PMID: 28987736 https://doi.org/10.1016/j.jtcvs.2017.08.132

17. Kim HG, Lee SH, Nam TM, Jang JH, Kim YZ, Kim KH, et al. Association of Aortic Arch Calcification on Chest X-ray with Procedural Thromboembolism after Mechanical Thrombectomy for Acute Ischemic Stroke. Medicina (Kaunas). 2021;57(9):859. PMID: 34577782 https://doi.org/10.3390/medicina57090859

18. Tunick PA, Nayar AC, Goodkin GM, Mirchandani S, Francescone S, Rosenzweig BP, et al. Effect of treatment on the incidence of stroke and other emboli in 519 patients with severe thoracic aortic plaque. Am J Cardiol. 2002;90(12):1320-1325. PMID: 12480041 https://doi.org/10.1016/s0002-9149(02)02870-9

19. Meissner I, Whisnant JP, Khandheria BK, Spittell PC, O'Fallon WM, Pascoe RD, et al. Prevalence of potential risk factors for stroke assessed by transesophageal echocardiography and carotid ultrasonography: the SPARC study. Stroke Prevention: Assessment of Risk in a Community. Mayo Clin Proc. 1999;74(9):862-869. PMID: 10488786 https://doi.org/10.4065/74.9.862

20. Strong JP, Restrepo C, Guzman M. Coronary and Aortic atherosclerosis in New Orleans. II. Comparison of lesions by age, sex, and race. Lab Invest. 1978;39(4):364-369. PMID: 703259

21. Amarenco P, Duysckaerts C, Tzourio C, Henin D, Bousser MG, Hauw JJ. The prevalence of ulcerated plaques in the aortic arch in patients with stroke. N Engl J Med. 1992;326(4):221-225. PMID: 1727976 https://doi.org/10.1056/NEJM199201233260402

22. Arun K, Nambiar Poornima N, Kannath Santhosh Kumar, Sreedharan Sapna E, Sukumaran Sajith, Sarma Sankara, et al. Prevalence of Aortic Plaques in Cryptogenic Ischemic Stroke: Correlation to Vascular Risk Factors and Future Events. Neurol India. 2022;70(1):182-187. PMID: 35263881 https://doi.org/10.4103/0028-3886.336332

23. Amarenco P, Cohen A, Tzourio C, Bertrand B, Hommel M, Besson G, et al. Atherosclerotic disease of the aortic arch and the risk of ischemic stroke. N Eng J Med. 1994;331(22):1474-1479. PMID: 7969297 https://doi.org/10.1056/NEJM199412013312202

24. French Study of Aortic Plaques in Stroke Group; Amarenco P, Cohen A, Hommel M, Moulin T, Leys D, Bousser M-G. Atherosclerotic disease of the aortic arch as a risk factor for recurrent ischemic stroke. N Engl J Med. 1996;334(19):1216-1221. PMID: 8606716 https://doi.org/10.1056/NEJM199605093341902

25. Rundek T, Di Tullio MR, Sciacca RR, Titova IV, Mohr JP, Homma S, et al. Association between large aortic arch atheromas and high-intensity transient signals in elderly stroke patients. Stroke. 1999;30(12):2683-2686. PMID: 10582997 https://doi.org/10.1161/01.str.30.12.2683

26. Kronzon I, Tunick PA. Aortic atherosclerotic disease and stroke. Circulation. 2006;114(1):63-75. PMID: 16818829 https://doi.org/10.1161/CIRCULATIONAHA.105.593418

27. Kasner SE, Swaminathan B, Lavados P, Sharma M, Muir K, Veltkamp R, et al. Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial. Lancet Neurol. 2018;17(12):1053-1060. PMID: 30274772 https://doi.org/10.1016/S1474-4422(18)30319-3

28. Agmon Y, Khandheria BK, Meissner I, Schwartz GL, Petterson TM, O'Fallon WM, et al. Independent association of high blood pressure and aortic atherosclerosis: a population-based study. Circulation. 2000;102(17):2087-2093. PMID: 11044425 https://doi.org/10.1161/01.cir.102.17.2087

29. Tunick PA, Perez JL, Kronzon I. Protrunding atheromas in the thoracic aorta and systemic embolization. Ann Intern Med. 1991;115(6):423- 427. PMID: 1872490 https://doi.org/10.7326/0003-4819-115-6-423

30. Jones EF, Kalman JM, Calafiore P, Tonkin AM, Donnan GA. Proximal aortic atheroma. An independent risk factor for cerebral ischemia. Stroke. 1995;26(2):218-224. PMID: 7831691

31. Tunick PA, Rosenzweig BP, Katz ES, Freedberg RS, Perez JL, Kronzon I. High risk for vascular events in patients with protruding aortic atheromas: a prospective study. J Am Coll Cardiol. 1994;23(5):1085-1090. PMID: 8144773 https://doi.org/10.1016/0735-1097(94)90595-9

32. Transesophageal echocardiographic correlates of thromboembolism in high-risk patients with nonvalvular atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography. Ann Intern Med. 1998;128(8):639-647. PMID: 9537937 https://doi.org/10.7326/0003-4819-128-8-199804150-00005

33. Zabalgoitia M, Halperin JL, Pearce LA, Blackshear JL, Asinger RW, Hart RG. Transesophageal echocardiographic correlates of clinical risk of thromboembolism in nonvalvular atrial fibrillation. Stroke Prevention in Atrial Fibrillation III Investigators. J Am Coll Cardiol. 1998;31(7):1622- 1626. PMID: 9626843 https://doi.org/10.1016/s0735-1097(98)00146-6

34. Ueno Y, Tateishi Y, Doijiri R, Kuriki A, Shimizu T, Kikuno M, et al. Large aortic arch plaques correlate with CHADS2 and CHA2DS2-VASc scores in cryptogenic stroke. Atherosclerosis. 2019;284:181-186. PMID: 30921601 https://doi.org/10.1016/j.atherosclerosis.2019.03.009

35. Suzuki M, Furuya K, Ozawa M, Miura K, Ozawa T, Matsuzono K, et al. Complex Aortic Arch Atherosclerosis in Acute Ischemic Stroke Patients with Non-Valvular Atrial Fibrillation. J Atheroscler Thromb. 2021;28(7):776-785. PMID: 32908035 https://doi.org/10.5551/jat.58339

36. Anan Y, Mashiko T, Matsuzono K, Miura K, Ozawa T, Suzuki M, et al. Coexisting of aortic arch atheroma and atrial fibrillation for short-term recurrence and poor functional outcome in acute stroke. Neurol Sci. 2022;43(4):2387-2396. PMID: 34748067 https://doi.org/10.1007/s10072-021-05722-0

37. Ntaios G, Pearce LA, Meseguer E, Endres M, Amarenco P, Ozturk S, 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. PMID: 31526123 https://doi.org/10.1161/STROKEAHA.119.025813

38. Kim SW, Kim YD, Chang HJ, Hong GR, Shim CY, Chung SJ, et al. Different infarction patterns in patients with aortic atheroma compared to those with cardioembolism or large artery atherosclerosis. J Neurol. 2018;265(1):151-158. PMID: 29177549 https://doi.org/10.1007/s00415-017-8685-7

39. Tunick PA, Culliford AT, Lamparello PJ, Kronzon I. Atheromatosis of the Aortic Arch as an Occult Source of Multiple Systemic Emboli. Ann Intern Med. 1991;114(5):391-392. PMID: 1992882 https://doi.org/10.7326/0003-4819-114-5-391

40. Stern A, Tunick PA, Culliford AT, Lachmann J, Baumann FG, Kanchuger MS, et al. Protruding aortic arch atheromas: risk of stroke during heart surgery with and without aortic arch endarterectomy. Am Heart J. 1999;138(4Pt1):746-752. PMID: 10502222 https://doi.org/10.1016/s0002-8703(99)70191-2

41. Song JY, Choi JB, Kim JH, Kim KH, Kim TY. Aortic Arch Endarterectomy Associated with On-Pump Cardiac Surgery in Patients with a Mobile Arch Atheroma. Korean J Thorac Cardiovasc Surg. 2019;52(2):112-115. PMID: 31089450 https://doi.org/10.5090/kjtcs.2019.52.2.112

42. Ferrari E, Vidal R, Chevallier T, Baudouy M. Atherosclerosis of the thoracic aorta and aortic debris as a marker of poor prognosis: benefit of oral anticoagulants. J Am Coll Cardiol. 1999;33(5):1317-1322. PMID: 10193733 https://doi.org/10.1016/s0735-1097(99)00003-0

43. Dressler FA, Craig WR, Castello R, Labovitz AJ. Mobile aortic atheroma and systemic emboli: efficacy of anticoagulation and influence of plaque morphology on recurrent stroke. J Am Coll Cardiol. 1998;31(1):134-138. PMID: 9426031 https://doi.org/10.1016/s0735-1097(97)00449-x

44. Amarenco P, Davis S, Jones EF, Cohen AA, Heiss WD, Kaste M, et al. Clopidogrel plus aspirin versus warfarin in patients with stroke and aortic arch plaques. Stroke. 2014;45(5):1248-1257. PMID: 24699050 https://doi.org/10.1161/STROKEAHA.113.004251

45. Mohr JP, Thompson JL, Lazar RM, Levin B, Sacco RL, Furie KL, et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med. 2001; 345(20):1444-1451. PMID: 11794192 https://doi.org/10.1056/NEJMoa011258

46. Palaparti R, Palaparthi S, Chowdary PS, Koduru GK, Maganti P, Kondru PR, et al. Transesophageal echocardiography for aortic arch atheromas in patients with cryptogenic stroke/transient ischemic attack - An underutilized entity. Heart India. 2020;8(2):56-62. https://doi.org/10.4103/heartindia.heartindia_49_19

47. Kim Dae-Young, Kim In-Soo, Jung Yo Han, Lee Kyung Yul, Kim Jong-Youn, Min Pil-Ki, et al. Impact of aortic atheroma and distensibility on diastolic function and prognosis in patients with ischemic stroke. Rev Cardiovasc Med. 2022;23(1):10. PMID: 35092202 https://doi.org/10.31083/j.rcm2301010

48. Amarenco P, Kim JS, Labreuche J, Charles H, Abtan J, Béjot Y, et al. A comparison of two LDL cholesterol targets after ischemic stroke. N Engl J Med. 2020;382(1):9. PMID: 31738483 https://doi.org/10.1056/NEJMoa1910355

49. Amarenco P, Kim JS, Labreuche J, Charles H, Giroud M, Lee BC, et al. Benefit of Targeting a LDL (Low-Density Lipoprotein) Cholesterol ˂ 70 mg/dL During 5 Years After Ischemic Stroke. Stroke. 2020;51(4):1231-1239. PMID: 32078484 https://doi.org/10.1161/STROKEAHA.119.028718

50. Ueno Y, Yamashiro K, Tanaka Y, Watanabe M, Miyamoto N, Shimada Y, et al. Rosuvastatin may stabilize atherosclerotic aortic plaque: transesophageal echocardiographic study in the EPISTEME trial. Atherosclerosis. 2015;239(2):476-842. PMID: 25702618 https://doi.org/10.1016/j.atherosclerosis.2015.02.021

51. Corti R, Fuster V, Fayad ZA, Worthley SG, Helft G, Smith D, et al. Lipid lowering by simvastatin induces regression of human atherosclerotic lesions: two years' follow-up by high-resolution noninvasive magnetic resonance imaging. Circulation. 2002;106(23):2884-2887. PMID: 12460866 https://doi.org/10.1161/01.cir.0000041255.88750.f0

52. Kawahara T, Nishikawa M, Kawahara C, Inazu T, Sakai K, Suzuki G. Atorvastatin, etidronate, or both in patients at high risk for atherosclerotic aortic plaques: a randomized, controlled trial. Circulation. 2013;127(23):2327-2335. PMID: 23658438 https://doi.org/10.1161/CIRCULATIONAHA.113.001534

53. Yogo M, Sasaki M, Ayaori M, Kihara T, Sato H, Takiguchi S, et al. Intensive lipid lowering therapy with titrated rosuvastatin yields greater atherosclerotic aortic plaque regression: serial magnetic resonance imaging observations from RAPID study. Atherosclerosis. 2014;232(1):31- 39. PMID: 24401214 https://doi.org/10.1016/j.atherosclerosis.2013.10.007

54. Tahara N, Kai H, Ishibashi M, Nakaura H, Kaida H, Baba K, et al. Simvastatin attenuates plaque inflammation: evaluation by fluorodeoxyglucose positron emission tomography. J Am Coll Cardiol. 2006;48(9):1825-1831. PMID: 17084257 https://doi.org/10.1016/j.jacc.2006.03.069

55. Watanabe T, Kawasaki M, Tanaka R, Ono K, Kako N, Saeki M, et al. Anti-inflammatory and morphologic effects of pitavastatin on carotid arteries and thoracic aorta evaluated by integrated backscatter trans-esophageal ultrasound and PET/CT: a prospective randomized comparative study with pravastatin (EPICENTRE study). Cardiovasc Ultrasound. 2015;3:17. PMID: 25889304 https://doi.org/10.1186/s12947-015-0012-9

56. Nishimura Y, Honda K, Yuzaki M, Tajima K, Nakamura R, Nakanishi Y, et al. Serum Cystatin C Level as a Biomarker of Aortic Plaque in Patients with an Aortic Arch Aneurysm. J Atheroscler Thromb. 2021;28(5):506-513. PMID: 32848109 https://doi.org/10.5551/jat.57091

57. Jansen Klomp WW, Brandon Bravo Bruinsma GJ, van 't Hof AW, Grandjean JG, Nierich AP. Imaging techniques for diagnosis of thoracic aortic atherosclerosis. Int J Vasc Med. 2016; 2016:4726094. PMID: 26966580 https://doi.org/1155/2016/4726094

58. Krinsky GA, Freedberg R, Lee VS, Rockman C, Tunick PA. Innominate artery atheroma: a lesion seen with gadolinium-enhanced MR angiography and often missed by transesophageal echocardiography. Clin Imaging. 2001;25(4):251-257. PMID: 11566085 https://doi.org/10.1016/S0899-7071(01)00292-3

59. Barazangi N, Wintermark M, Lease K, Rao R, Smith W, Josephson SA. Comparison of computed tomography angiography and transesophageal echocardiography for evaluating aortic arch disease. J Stroke Cerebrovasc Dis. 2011;20(5):436-442. PMID: 20813553 https://doi.org/10.1016/j.jstrokecerebrovasdis.2010.02.016

60. Wehrum T, Dragonu I, Strecker C, Hennig J, Harloff A. Multi-contrast and three-dimensional assessment of the aortic wall using 3T MRI. Eur J Radiol. 2017;91:148-154. PMID: 28629561 https://doi.org/10.1016/j.ejrad.2017.04.011

61. Wehrum T, Dragonu I, Strecker C, Schuchardt F, Hennemuth A, Drexl J, et al. Aortic atheroma as a source of stroke - assessment of embolization risk using 3D CMR in stroke patients and controls. J Cardiovasc Magn Reson. 2017;19(1):67. PMID: 28877718 https://doi.org/10.1186/s12968-017-0379-x

62. Sakai Y, Lehman VT, Eisenmenger LB, Obusez EC, Kharal GA, Xiao J, et al. Vessel wall MR imaging of aortic arch, cervical carotid and intracranial arteries in patients with embolic stroke of undetermined source: A narrative review. Front Neurol. 2022;13:968390. PMID: 35968273 https://doi.org/10.3389/fneur.2022.968390

63. Harloff A, Dudler P, Frydrychowicz A, Strecker C, Stroh AL, 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. PMID: 17965147 https://doi.org/10.1136/jnnp.2007.125211

64. Harloff A, Brendecke SM, Simon J, Assefa D, Wallis W, Helbing T, et al. 3D MRI provides improved visualization and detection of aortic arch plaques compared to transesophageal echocardiography. J Magn Reson Imaging. 2012;36(3):604-611. PMID: 22552960 https://doi.org/10.1002/jmri.23679

65. Yamaguchi Y, Tanaka T, Morita Y, Yoshimura S, Koga M, Ihara M, et al. Associations of high intensities on magnetization-prepared rapid acquisition with gradient echo with aortic complicated lesions in ischemic stroke patients. Cerebrovasc Dis. 2019;47(1-2):15-23. PMID: 30763926 https://doi.org/10.1159/000497068

66. Morihara K, Nakano T, Mori K, Fukui I, Nomura M, Suzuki K, et al. Usefulness of rapid MR angiography using two-point Dixon for evaluating carotid and aortic plaques. Neuroradiology. 2022;64(4):693-702. PMID: 34559244 https://doi.org/10.1007/s00234-021-02812-w

67. Jarvis K, Soulat G, Scott M, Vali A, Pathrose A, Syed AA, et al. Investigation of aortic wall thickness, stiffness and flow reversal in patients with cryptogenic stroke: a 4D flow MRI study. J Magn Reson Imaging. 2021;53(3):942-952. PMID: 32864836 https://doi.org/10.1002/jmri.27345

68. Kim J, Song HC. Role of PET/CT in the Evaluation of Aortic Disease. Chonnam Med J. 2018;54(3):143-152. PMID: 30288369 https://doi.org/10.4068/cmj.2018.54.3.143

69. Espitia O, Schanus J, Agard C, Kraeber-Bodéré F, Hersant J, et al. Specific features to differentiate Giant cell arteritis aortitis from aortic atheroma using FDG-PET/CT. Sci Rep. 2021;11(1):17389. PMID: 34462502 https://doi.org/10.1038/s41598-021-96923-2