AccScience Publishing / AN / Volume 3 / Issue 1 / DOI: 10.36922/an.2287

Subclinical atrial fibrillation in embolic stroke of undetermined source: Management and stroke recurrence

Luca Masotti1* Elisa Grifoni1 Alessia Baglini1 Teresa Sansone1 Mariella Baldini2 Sara Giannoni2 Elisabetta Bertini2 Ilaria Di Donato2 Irene Sivieri1 Marianna Mannini1 Gina Iandoli1 Ira Signorini1 Eleonora Cosentino1 Irene Micheletti1 Elisa Cioni1 Giulia Pelagalli1 Elisa Giglio1 Eleonora Brai1 Alessandro Dei1 Antonio Giordano1 Francesca Dainelli1 Mario Romagnoli1 Chiara Mattaliano1 Elena Schipani1 Giuseppe Salvatore Murgida1 Stefania Di Martino1 Valentina Francolini1
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1 Internal Medicine II and Stroke Unit, San Giuseppe Hospital, Empoli, Italy
2 Neurology, San Giuseppe Hospital, Empoli, Italy
Advanced Neurology 2024, 3(1), 2287
Submitted: 21 November 2023 | Accepted: 19 January 2024 | Published: 20 March 2024
(This article belongs to the Special Issue Advances in stroke research and therapy)
© 2024 by the Author (s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( )

Subclinical atrial fibrillation (SAF) represents the most prevalent underlying etiology detected after an embolic stroke of undetermined source (ESUS). Investigating SAF is strongly recommended during the diagnostic work-up. The efficacy of oral anticoagulant (OAC) therapy in reducing the risk of stroke recurrence post-SAF detection remains a conundrum. Thus, our study aimed to analyze the management of secondary antithrombotic prophylaxis and the rate of 12-month stroke recurrence in real-life ESUS patients. We retrospectively analyzed clinical, radiographic, and echocardiographic findings of patients with ESUS who underwent non-implantable 2-week electrocardiogram (ECG) monitoring after discharge. Episodes of SAF of any duration were considered diagnostic. Antithrombotic treatment at hospital discharge and after ECG monitoring, as well as 12-month recurrence, were registered. We compared the rate of stroke recurrence between patients with and without detection of SAF. One hundred and fifty-nine patients (75 females) with a median age of 73.5 (interquartile range [IQR] = 66.75 – 79) years represented the study population. At hospital discharge, 96.9% of patients received antiplatelet therapy as secondary antithrombotic prophylaxis. SAF was detected in 82 patients (51.5%), and OAC was prescribed in 98.6% of them. The median time from stroke onset to OAC prescription was 143 (IQR = 94 – 178) days. Overall, 12-month stroke recurrence occurred in eight patients (5%). The stroke recurrence rate was lower in patients prescribed OAC compared with those not prescribed it, although the difference was not significant (3.7% vs. 6.25%; P = 0.7202). In our study, OACs prescribed post-SAF detection in patients with ESUS reduced, but not significantly, the risk of stroke recurrence. Future research and prospective multicenter studies are warranted.

Atrial fibrillation
Embolic stroke of undetermined source
Electrocardiogram monitoring
Oral anticoagulants
  1. 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. doi: 10.1161/STROKEAHA.116.016414


  1. Kleindorfer DO, Towfighi A, Chaturvedi S, 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. doi: 10.1161/STR.0000000000000375


  1. Diener HC, Easton JD, Hart RG, Kasner S, Kamel H, Ntaios G. Review and update of the concept of embolic stroke of undetermined source. Nat Rev Neurol. 2022;18(8):455-465. doi: 10.1038/s41582-022-00663-4


  1. Toi S, Shirai Y, Ishizuka K, et al. Recurrent stroke incidence and etiology in patients with embolic stroke of undetermined source and other stroke subtypes. J Atheroscler Thromb. 2022;29(3):393-402. doi: 10.5551/jat.61895


  1. Veltkamp R, Pearce LA, Korompoki E, et al. Characteristics of recurrent ischemic stroke after embolic stroke of undetermined source: Secondary analysis of a randomized clinical trial. JAMA Neurol. 2020;77(10):1233-1240. doi: 10.1001/jamaneurol.2020.1995


  1. Leventis I, Perlepe K, Sagris D, et al. Characteristics and outcomes of Embolic Stroke of Undetermined Source according to stroke severity. Int J Stroke. 2020;15(8):866-871. doi: 10.1177/1747493020909546


  1. Ntaios G, Perlepe K, Lambrou D, et al. Prevalence and overlap of potential embolic sources in patients with embolic stroke of undetermined source. J Am Heart Assoc. 2019;8(15):e012858. doi: 10.1161/JAHA.119.012858


  1. Ntaios G, Papavasileiou V, Milionis H, et al. Embolic strokes of undetermined source in the Athens stroke registry: An outcome analysis. Stroke. 2015;46(8):2087-2093. doi: 10.1161/STROKEAHA.115.009334


  1. Rubiera M, Aires A, Antonenko K, et al. European stroke organisation (ESO) guideline on screening for subclinical atrial fibrillation after stroke or transient ischaemic attack of undetermined origin. Eur Stroke J. 2022;7(3):6. doi: 10.1177/23969873221099478


  1. Schnabel RB, Haeusler KG, Healey JS, et al. Searching for atrial fibrillation poststroke: A white paper of the AF-SCREEN international collaboration. Circulation. 2019;140(22):1834-1850. doi: 10.1161/CIRCULATIONAHA.119.040267


  1. Dilaveris PE, Antoniou CK, Caiani EG, et al. ESC Working Group on e-Cardiology Position Paper: Accuracy and reliability of electrocardiogram monitoring in the detection of atrial fibrillation in cryptogenic stroke patients: In collaboration with the Council on Stroke, the European Heart Rhythm Association, and the Digital Health Committee. Eur Heart J Digit Health. 2022;3(3):341-358. doi: 10.1093/ehjdh/ztac026


  1. Masotti L, Grifoni E. Clinical predictive scores for detection of sub-clinical atrial fibrillation after cryptogenic or embolic stroke of undetermined source: A brief systematic review. Brain Heart. 2023;1(2):0955. doi: 10.36922/bh.095


  1. Diener HC, Hankey GJ, Easton JD, Lip GYH, Hart RG, Caso V. Non-vitamin K oral anticoagulants for secondary stroke prevention in patients with atrial fibrillation. Eur Heart J Suppl. 2020;22(Suppl 1):I13-I21. doi: 10.1093/eurheartj/suaa104


  1. Hart RG, Diener HC, Coutts SB, et al. Embolic strokes of undetermined source: The case for a new clinical construct. Lancet Neurol. 2014;13(4):429-438. doi: 10.1016/S1474-4422(13)70310-7


  1. Ratajczak-Tretel B, Lambert AT, Al-Ani R, et al. Underlying causes of cryptogenic stroke and TIA in the nordic atrial fibrillation and stroke (NOR-FIB) study-the importance of comprehensive clinical evaluation. BMC Neurol. 2023;23:115. doi: 10.1186/s12883-023-03155-0


  1. Noubiap JJ, Agbaedeng TA, Kamtchum-Tatuene J, et al. Rhythm monitoring strategies for atrial fibrillation detection in patients with cryptogenic stroke: A systematic review and meta-analysis. Int J Cardiol Heart Vasc. 2021;34:100780. doi: 10.1016/j.ijcha.2021.100780


  1. Kitsiou A, Sagris D, Schäbitz WR, Ntaios G. Validation of the AF-ESUS score to identify patients with embolic stroke of undetermined source and low risk of device-detected atrial fibrillation. Eur J Intern Med. 2021;89:135-136. doi: 10.1016/j.ejim.2021.04.003


  1. Ratajczak-Tretel B, Tancin Lambert A, Al-Ani R, et al. Atrial fibrillation in cryptogenic stroke and TIA patients in The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study: Main results. Eur Stroke J. 2023;8(1):148-156. doi: 10.1177/23969873221123122


  1. von Falkenhausen AS, Feil K, Sinner MF, et al. Atrial fibrillation risk assessment after embolic stroke of undetermined source. Ann Neurol. 2023;93:479-488. doi: 10.1002/ana.26545


  1. Ntaios G, Perlepe K, Lambrou D, et al. Prevalence and overlap of potential embolic sources in patients with embolic stroke of undetermined source. J Am Heart Assoc. 2019;8(15):e012858. doi: 10.1161/JAHA.119.012858


  1. He J, Jiang Y, Xiao Y, et al. Effect of implantable cardiac monitors on preventing stroke: A systematic review and meta-analysis of randomized clinical trials. PLoS One. 2023;18(7):e0287318. doi: 10.1371/journal.pone.0287318


  1. Kitsiou A, Rogalewski A, Kalyani M, et al. Atrial fibrillation in patients with embolic stroke of undetermined source during 3 years of prolonged monitoring with an implantable loop recorder. Thromb Haemost. 2021;121(6):826-833. doi: 10.1055/a-1346-2899


  1. Ntaios G, Pearce LA, Veltkamp R, et al. Potential embolic sources and outcomes in embolic stroke of undetermined source in the NAVIGATE-ESUS trial. Stroke. 2020;51:1797-1804. doi: 10.1161/STROKEAHA.119.028669


  1. Kirchhof P, Toennis T, Goette A, et al. Anticoagulation with edoxaban in patients with atrial high-rate episodes. N Engl J Med. 2023;389(13):1167-1179. doi: 10.1056/NEJMoa2303062


  1. Uhe T, Wasser K, Weber-Krüger M, et al. Intensive heart rhythm monitoring to decrease ischemic stroke and systemic embolism-the Find-AF 2 study-rationale and design. Am Heart J. 2023;265:66-76doi: 10.1016/j.ahj.2023.06.016


  1. 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. 2020;49(1):75-85. doi: 10.1007/s11239-019-01951-544


  1. Perera KS, de Sa Boasquevisque D, Rao-Melacini P, et al. Evaluating rates of recurrent ischemic stroke among young adults with embolic stroke of undetermined source: The young ESUS longitudinal cohort study. JAMA Neurol. 2022;79(5):450-458. doi: 10.1001/jamaneurol.2022.0048
Conflict of interest
The authors declare that they have no competing interests.
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Advanced Neurology, Electronic ISSN: 2810-9619 Published by AccScience Publishing