Skip to main content

Advertisement

Log in

Age-related burden and characteristics of embolic stroke of undetermined source in the real world clinical practice

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

Few data are available on age-related burden and characteristics of embolic stroke of undetermined source (ESUS) in the real world clinical practice. The aim of our study was to provide information about it. We retrospectively analyzed data of patients consecutively admitted to our Stroke Unit along 1 year (2017, November 1st–2018, October 31st). The etiology of ischemic stroke was defined at hospital discharge; ESUS was considered as a subset of cryptogenic stroke, and defined according to the 2014 international criteria. In the analyzed period, 306 patients, 52.3% females, mean age ± SD 77.9 ± 11.9 years, were discharged with diagnosis of ischemic stroke. Ischemic strokes of cardioembolic and lacunar origin were the most frequent subtypes: 30.1% and 29.4%, respectively. Cardioembolic strokes were particularly frequent in patients ≥ 75 years, and almost always associated with atrial fibrillation. Overall, in 80 patients (26.1%) the etiology of stroke was undetermined; in 25 (8.2%) it remained undefined because of death or severe comorbidity, making further diagnostic work-up not worthy. Cryptogenic stroke occurred in 55 patients (18%), and ESUS criteria were satisfied in 39 of them (12.7%). According to age, cryptogenic stroke was diagnosed in 21.1% (21.1% ESUS) of patients < 65 years, 24.2% (19.4% ESUS) of patients aged 65–74 years, 15.5% (9.2% ESUS) of patients ≥ 75 years. After diagnostic work-up, patent foramen ovale was most commonly associated with ESUS (17.9%), especially in patients < 65 years (62.5%); covert paroxysmal atrial fibrillation was detected in 10.5% of ESUS patients ≥ 75 years. In the real world clinical practice, the frequency of ischemic strokes of undetermined etiology, and of those satisfying ESUS criteria, is not negligible, especially in younger patients. A thorough diagnostic work-up, with an age-specific approach, is therefore necessary and of the utmost importance for the identification of stroke etiology, in order to optimize secondary stroke prevention strategies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Chen PH, Gao S, Wang YJ et al (2012) Classyfing ischemic stroke, from TOAST to CISS. CNS Neurosci Ther 00:1–5. https://doi.org/10.1111/j.1755-5949.2011.00292.x

    Article  Google Scholar 

  2. Adams HP Jr, Bendixen BH, Kappelle LJ et al (1993) 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 24:35–41

    Article  PubMed  Google Scholar 

  3. Hart RG, Diener HC, Coutts SB, for the Cryptogenic Stroke/ESUS International Working Group et al (2014) Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol 13:429–438. https://doi.org/10.1016/S1474-4422(13)70310-7

    Article  PubMed  Google Scholar 

  4. Hart RG, Catanese L, Perera KS et al (2017) Embolic stroke of undetermined source. A systematic review and clinical update. Stroke 48:867–872. https://doi.org/10.1161/STROKEAHA.116.016414

    Article  PubMed  Google Scholar 

  5. Schulman S, Kearon C, Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis (2005) Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 3:692–694. https://doi.org/10.1111/j.1538-7836.2005.01204.x

    Article  PubMed  CAS  Google Scholar 

  6. Tatu L, Moulin T, Bogousslavsky J et al (1996) Arterial territories of the human brain: brainstem and cerebellum. Neurology 47:1125–1135

    Article  CAS  PubMed  Google Scholar 

  7. Tatu L, Moulin T, Bogousslavsky J et al (1998) Arterial territories of the human brain: cerebral hemispheres. Neurology 50:1699–1708

    Article  CAS  PubMed  Google Scholar 

  8. Perera KS, Vanassche T, Bosch J, Global Registry Investigators ESUS et al (2016) Global survey of the frequency of atrial fibrillation associated stroke: embolic stroke of undetermined source global registry. Stroke 47:2197–2202. https://doi.org/10.1161/STROKEAHA.116.013378

    Article  PubMed  CAS  Google Scholar 

  9. Perera KS, Vanassche T, Bosch J et al (2016) Embolic strokes of undetermined source: prevalence and patient features in the ESUS Global Registry. Int J Stroke 11:526–533. https://doi.org/10.1177/1747493016641967

    Article  PubMed  Google Scholar 

  10. Ntaios G, Papavasileiou V, Milionis H et al (2015) Embolic strokes of undetermined source in the Athens stroke registry: an outcome analysis. Stroke 46:2087–2093. https://doi.org/10.1161/STROKEAHA.115.009334

    Article  PubMed  Google Scholar 

  11. Van Gelder IC, Healey JS, Crijns HJGM et al (2017) Duration of device-detected subclinical atrial fibrillation and occurrence of stroke in ASSERT. Eur Heart J 38:1339–1344. https://doi.org/10.1093/eurheartj/ehx042

    Article  PubMed  Google Scholar 

  12. Glotzer TV, Daoud EG, Wyse DG et al (2009) The relationship between daily atrial tachyarrhythmia burden from implantable device diagnostics and stroke risk: the TRENDS study. Circ Arrhythm Electrophysiol 2:474–480. https://doi.org/10.1161/CIRCEP.109.849638

    Article  PubMed  Google Scholar 

  13. Martin DT, Bersohn MM, Waldo AL et al (2015) Randomized trial of atrial arrhythmia monitoring to guide anticoagulation in patients with implanted defibrillator and cardiac resynchronization devices. Eur Heart J 36:1660–1668. https://doi.org/10.1093/eurheartj/ehv115

    Article  PubMed  Google Scholar 

  14. Goette A, Kalman JM, Aguinaga L et al (2016) EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication. Europace 18:1455–1490. https://doi.org/10.1093/europace/euw161

    Article  PubMed  PubMed Central  Google Scholar 

  15. Guichard J-B, Nattel S (2017) Atrial cardiomyopathy: a useful notion in cardiac disease management or a passing fad? J Am Coll Cardiol 70:756–765. https://doi.org/10.1016/j.jacc.2017.06.033

    Article  PubMed  Google Scholar 

  16. Ricci B, Chang AD, Hemendinger M et al (2018) A simple score that predicts paroxysmal atrial fibrillation on outpatient cardiac monitoring after embolic stroke of unknown source. J Stroke Cerebrovasc Dis 27:1692–1696. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.01.028

    Article  PubMed  Google Scholar 

  17. Masotti L, Grifoni E, Dei A et al (2019) Direct oral anticoagulants in the early phase of non valvular atrial fibrillation-related acute ischemic stroke: focus on real life studies. J Thromb Thrombolysis 47:292–300. https://doi.org/10.1007/s11239-018-1775-2

    Article  PubMed  Google Scholar 

  18. Hankey GJ (2002) Warfarin-Aspirin Recurrent Stroke Study (WARSS) trial: is warfarin really a reasonable therapeutic alternative to aspirin for preventing recurrent noncardioembolic ischemic stroke? Stroke 33:1723–1726

    Article  PubMed  Google Scholar 

  19. Sacco RL, Prabhakaran S, Thompson JLP et al (2006) Comparison of warfarin versus aspirin for the prevention of recurrent stroke or death: subgroup analyses from the Warfarin-Aspirin Recurrent Stroke Study. Cerebrovasc Dis 22:4–12. https://doi.org/10.1159/000092331

    Article  PubMed  CAS  Google Scholar 

  20. Hart RG, Sharma M, Mundl H et al (2018) Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med 378:2191–2201. https://doi.org/10.1056/NEJMoa1802686

    Article  PubMed  CAS  Google Scholar 

  21. Diener HC, Sacco RL, Easton JD, RE-SPECT ESUS Steering Committee and Investigators et al (2019) Dabigatran for prevention of stroke after embolic stroke of undetermined source. N Engl J Med 380:1906–1917. https://doi.org/10.1056/NEJMoa1813959

    Article  PubMed  CAS  Google Scholar 

  22. Geisler T, Poli S, Meisner C et al (2017) Apixaban for treatment of embolic stroke of undetermined source (ATTICUS randomized trial): rationale and study design. Int J Stroke 12:985–990. https://doi.org/10.1177/1747493016681019

    Article  PubMed  Google Scholar 

  23. Kamel H, Longstreth WT, Tirschwell DL et al (2019) The atrial cardiopathy and antithrombotic drugs in prevention after cryptogenic stroke randomized trial: rationale and methods. Int J Stroke 14:207–214. https://doi.org/10.1177/1747493018799981

    Article  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Healey JS, Gladstone DJ, Swaminathan B et al (2019) Recurrent stroke with rivaroxaban compared with aspirin according to predictors of atrial fibrillation: secondary analysis of the NAVIGATE ESUS Randomized clinical trial. JAMA Neurol. https://doi.org/10.1001/jamaneurol.2019.0617

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Luca Masotti.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Grifoni, E., Giglio, D., Guazzini, G. et al. Age-related burden and characteristics of embolic stroke of undetermined source in the real world clinical practice. J Thromb Thrombolysis 49, 75–85 (2020). https://doi.org/10.1007/s11239-019-01951-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-019-01951-5

Keywords

Navigation