Diagnostic criteria for determining the type of the right-to-left shunt using contrast-enhanced transcranial Doppler ultrasound in young patients with ischemic stroke/transient ischemic attack

Objective. To determine specific diagnostic criteria for detecting the type of the right-to-left shunt by contrast-enhanced transcranial Doppler ultrasound (cTCD) in young patients with paradoxical embolism and ischemic stroke/TIA.

Material and methods. The study included 64 ischemic stroke or transient ischemic attack patients (age 28–44 years) with patent foramen ovale (PFO), atrial septal defect (ASD) or pulmonary arteriovenous malformation (PAVM). cTCD was used to assess the degree of shunting, its change during the Valsalva maneuver (VM), time to the fi rst microembolic signal (MES) detection, and the duration of MES registration.

Results. According to cTCD data, 20% of patients with PFO had no shunt at rest, and 80% had a mild to moderate right-to-left shunt. After VM, a severe shunt was detected in 75% of patients in this group and a moderate shunt in 25%. All patients with ASD and PAVM had a marked shunt at rest. The difference in time to first MES detection from the start of contrast administration was not statistically significant for all groups. The duration of MES registration that indicated shunting was shorter in patients with PFO compared to those with ASD (p < 0.001) or with PAVM (p < 0.001) and it was significantly longer in patients with PAVM compared to those with ASD (p < 0.001).

Conclusion. The key diagnostic criteria to defi ne the right-to-left shunt type are the functional shunt degree at rest and the duration of MES registration. Severe shunting at rest can suggest the presence of ASD or PAVM, while the duration of MES registration > 2 min suggests a PAVM.

1. Dobrynina LA, Kalashnikova LA, Pavlova LN. Ischemic stroke in young age. S.S. Korsakov Journal of Neurology and Psychiatry. 2011;111(3):4–8. (In Rus.). https://doi.org/10.1007/978-3-540-46129-6

2. Stack СA, Cole JW. Ischemic stroke in young adults. Current Opinion in Cardiology. 2018;33(6):594–604. https://doi.org/10.1097/HCO.0000000000000564

3. Silvestry FE, Cohen MS, Armsby LB, Burkule NJ, Fleishman CE, Hijazi ZM et al. Guidelines for the Echocardiographic Assessment of Atrial Septal Defect and Patent Foramen Ovale: From the American Society of Echocardiography and Society for Cardiac Angiography and Interventions. Journal of the American Society of Echocardiography. 2015;28(8):910–958. https://doi.org/10.1016/j.echo.2015.05.015

4. Cartin-Ceba R, Swanson KL, Krowka MJ. Pulmonary arteriovenous malformations. Chest. 2013;144(3):1033–44. https://doi.org/10.1378/chest.12-0924

5. Miranda B, Fonseca AC, Ferro JM. Patent foramen ovale and stroke. J Neurol. 2018;265(8):1943–49. https://doi.org/10.1007/s00415-018-8865-0

6. Abdelghani M, El-Shedoudy S, Nassif M, Bouma BJ, Winter RJ. Management of Patients with Patent Foramen Ovale and Cryptogenic Stroke: An Update. Cardiology. 2019;143(1):62–72. https://doi.org/10.1159/000501028

7. Rigatelli G, Dell’Avvocata F, Tarantini G, Giordan M, Cardaioli P, Nguyen T. Clinical, hemodynamic, and intracardiac echocardiographic characteristics of secundum atrial septal defectsrelated paradoxical embolism in adulthood. J Interv Cardiol. 2014;27:542–47. https://doi.org/10.1111/joic.12159

8. Cappa R, Du J, Carrera J, Berthaud V, Southerland AM. Ischemic Stroke Secondary to paradoxical embolism through a pulmonary arteriovenous malformation: case report and review of the literature. J Stroke Cerebrovasc Dis. 2018;27(7):e125–e127. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.02.015

9. Mojadidi MK, Winoker JS, Roberts SC, Msaouel P Zaman MO, Gevorgyan R, Tobis JM. Accuracy of conventional transthoracic echocardiography for the diagnosis of intracardiac right-to-left shunt: a meta-analysis of prospective studies. Echocardiography. 2014;31(9):1036–48. https://doi.org/10.1111/echo.12583

10. Mojadidi MK, Bogush N, Caceres JD, Msaouel P, Tobis JM. Diagnostic accuracy of transesophageal echocardiogram for the detection of patent foramen ovale: a meta-analysis. Echocardiography. 2014;31(6):752–8. https://doi.org/10.1111/echo.12462

11. Zhan J, Dong C, Li M, Zhan L, Chen H, Lu L, Liu J. Cryptogenic Stroke Caused by Pulmonary Arterial Venous Malformation with Massive Right-to-Left Shunt: A Case Report. Neurol Ther. 2021;10(2):1135–42. https://doi.org/10.1007/s40120-021-00275-y

12. Pristipino C, Sievert H, D’Ascenzo F, Mas L, Meier B, Scacciatella P et al. European position paper on the management of patients with patent foramen ovale. General approach and left circulation thromboembolism. International Experts.Eur Heart J. 2019;7;40(38):3182–95. https://doi.org/10.1093/eurheartj/ehy649

13. Mojadidi MK, Roberts SC, Winoker JS, Romero J, GoodmanMeza D, Gevorgyan R, Tobis JM. Accuracy of transcranial Doppler for the diagnosis of intracardiac right-to-left shunt: a bivariate meta-analysis of prospective studies. JACC Cardiovasc Imaging. 2014;7(3):236–50. https://doi.org/10.1016/j.jcmg.2013.12.011

14. Chechetkin AO. Contrast Transcranial Doppler Ultrasound in the Diagnosis of the Patent Foramen Ovale — Methodical Aspects. Ultrasound and functional diagnostics. 2007;1:102–18. (In Russ.).

15. Kitamura T, Arakawa S, Murao K, Kitazono T, Ago T. Paradoxical Brain Embolism in Elderly Subjects with Small Atrial Septal Defects. Journal of Stroke and Cerebrovascular Diseases. 2018;27(17):1987–91. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.02.053

16. Belopasova AV, Dobrynina LA, Chechetkin AO, Karshieva AR, Ananieva LY, Pyshkina DS. Atrial septal defects: the role in the development of cerebral circulation disorders caused by paradoxical embolism. Neurology, Neuropsychiatry, Psychosomatics. 2021;13(6):142–6. (In Russ.). https://doi.org/10.14412/2074-2711-2021-6-142-146

17. Sen G, Lwin MT, Smith L, Weir N. Young stroke due to pulmonary arteriovenous malformation. BMJ Case Reports CP. 2021;14(6):e242581. https://doi.org/10.1136/bcr-2021-242581

18. Belopasova AV, Dobrynina LA, Kalashnikova LA, Chechetkin AO, Karshieva AR, Abugov SA et al. Pulmonary arteriovenous shunt — a rare cause of recurrent stroke due to paradoxical embolism. S.S. Korsakov Journal of Neurology and Psychiatry. 2020;120(9):107–13. (In Russ.). https://doi.org/10.17116/jnevro2020120091107

19. Zetola VF, Lange MC, Scavasine VC, Bazan R, Braga GP, Leite AC et al. Latin American Consensus Statement for the Use of Contrast-Enhanced Transcranial Ultrasound as a Diagnostic Test for Detection of Right-to-Left Shunt. Cerebrovascular Diseases. 2019;48(3):99–108. https://doi.org/10.1159/000503851

20. Jauss M, Zanette E. Detection of right-to-left shunt with ultrasound contrast agent and transcranial Doppler sonography. Cerebrovasc. Dis. 2000;10(6):490–6. https://doi.org/10.1159/000016119

21. Rushmer R. Dynamics of the cardiovascular system. Moscow: Medicine; 1981:488. (In Russ.).

22. Liu C, Lu T, Zhai NN, Bu N, Wang HQ, Chen MY, Wu HQ. Different Valsalva Manoeuvre Procedures for the Diagnosis of Right-to-Left Shunt by Contrast-Transcranial Doppler. Ultrasound in Medicine and Biology. 2017;43(8):1716–21. https://doi.org/10.1016/j.ultrasmedbio.2017.04.006

23. Sastry S, MacNab A, Daly K, Ray S, McCollum C. Doppler detection of venous-to-arterial circulation shunts: Criteria for patent foramen ovale. Journal of Clinical Ultrasound. 2009;37(5):276–80. https://doi.org/10.1002/jcu.20564

24. Levin AR, Spach MS, Boineau JP, Canent JRV, Capp MP, Jewett PH. Atrial Pressure-Flow Dynamics in Atrial Septal Defects (Secundum Type). Circulation. 1968;37:476–88. https://doi.org/10.1161/01.CIR.37.4.476

25. Montrief T, Alerhand S, Denault A, Scott J. Point-of-care echocardiography for the evaluation of right-to-left cardiopulmonary shunts: a narrative review. Can J Anesth. 2020;67:1824–38. https://doi.org/10.1007/s12630-020-01813-2

26. Saboo SS, Chamarthy M, Bhalla S, Park H, Sutphin P, Kay F et al. Pulmonary arteriovenous malformations: diagnosis. Cardiovasc Diagn Ther. 2018;8(3):325–37. https://doi.org/10.21037/cdt.2018.06.01

27. Mas JL, Derumeaux G, Guillon B, Massardier E, Hosseini H, Mechtouff L et al. CLOSE Investigators. Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke. N Engl J Med. 2017;377(11):1011–21. https://doi.org/10.1056/NEJMoa1705915

28. Droste DW, Silling K, Stypmann J, Grude M, Kemény V, Wichter T et al. Contrast transcranial doppler ultrasound in the detection of right-to-left shunts: time window and threshold in microbubble numbers. Stroke. 2000;31(7):1640–5. https://doi.org/10.1161/01.str.31.7.1640

29. Zanati Bazan SG, Braga GP, Luvizutto GJ, Trindade AP, Pontes-Neto OM, Bazan R. Bihemispheric Paradoxical Cerebral Embolism in a Patient with Pulmonary Thromboembolism and Presumptive Fistula Right-to-Left Shunt. Journal of Stroke and Cerebrovascular Diseases. 2016;25(6):95–7. https://doi.org/10.1016/j.jstrokecerebrovasdis.2016.03.038

30. Mahmoud AN, Elgendy IY, Agarwal N, Tobis JM, Majardidi MK. Identification and Quantification of Patent Foramen Ovale-Mediated Shunts: Echocardiography and Transcranial Doppler. Interventional cardiology clinics. 2017;6(4):495–504. https://doi.org/10.1016/j.iccl.2017.05.002

31. Woods TD, Patel A. A critical review of patent foramen ovale detection using saline contrast echocardiography: When bubbles lie. Journal of the American Society of Echocardiography. 2006;19(2):215–22. https://doi.org/10.1016/j.echo.2005.09.023