This patient presented with recurrent embolic strokes of unknown source (ESUS). ESUS represents a subset of cryptogenic strokes in which the characteristics of the stroke suggest it occurred because of embolism. ESUS is responsible for approximately 50% of cryptogenic strokes or approximately 20% of all ischemic strokes.

Atrial fibrillation (AF) is a common cause of cardioembolism and typically results in severe, disabling strokes.¹ Although antiplatelet therapy is the cornerstone of secondary stroke prevention, these agents are insufficient in patients with AF-associated stroke who require oral anticoagulation (OAC) therapy.² Because AF is responsible for approximately one-third of ESUS cases, it has been proposed that patients with ESUS receive empiric OAC therapy. However, multiple randomized trials—NAVIGATE ESUS (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), RE-SPECT ESUS (Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source), ARCARDIA (Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke), and ATTICUS (Apixaban for the Treatment of Embolic Stroke of Undetermined Source)—have failed to demonstrate beneficial reduction in the risk of recurrent stroke with OAC compared with antiplatelet therapy.

As a result, the focus has shifted to identification of AF because AF detection in patients with previous stroke is likely to result is significant change in management. AF is underdetected due to a poor correlation between symptoms and AF episodes and due to the transient nature of paroxysmal forms of the disease.

In populations with unexplained stroke (cryptogenic stroke or ESUS), prolonged cardiac rhythm monitoring has detected AF in 17-34% of patients.^3-8 Similarly, prolonged rhythm monitoring has identified AF in a substantial proportion of patients with stroke risk factors,⁹ and in those with an index stroke attributed to large- or small-vessel disease (e.g., non-ESUS).^10,11

When prolonged cardiac monitoring is being pursued, a minimum of 2-4 weeks of prolonged noninvasive monitoring is recommended.¹² However, most cases of AF are identified outside this monitoring window. Specifically, the mean time to AF detection has ranged from 48 to 161 days across several series, with >60% of AF cases documented after 1 month of monitoring.^3-8 Given that noninvasive monitoring may miss most AF cases, it is thought that an implantable cardiac monitor is the most effective means to detect occult AF.

References

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2. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146(12):857-867. doi:10.7326/0003-4819-146-12-200706190-00007
3. Ritter MA, Kochhäuser S, Duning T, et al. Occult atrial fibrillation in cryptogenic stroke: detection by 7-day electrocardiogram versus implantable cardiac monitors. Stroke. 2013;44(5):1449-1452. doi:10.1161/STROKEAHA.111.676189
4. Christensen LM, Krieger DW, Højberg S, et al. Paroxysmal atrial fibrillation occurs often in cryptogenic ischaemic stroke. Final results from the SURPRISE study. Eur J Neurol. 2014;21(6):884-889. doi:10.1111/ene.12400
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6. Etgen T, Hochreiter M, Mundel M, Freudenberger T. Insertable cardiac event recorder in detection of atrial fibrillation after cryptogenic stroke: an audit report. Stroke. 2013;44(7):2007-2009. doi:10.1161/STROKEAHA.113.001340
7. Rojo-Martinez E, Sandín-Fuentes M, Calleja-Sanz AI, et al. Altorendimiento del holter implantable en la detecciónde fibrilación auricular paroxística oculta en pacientes con ictus criptogénico y sospecha de mecanismo embólico [High performance of an implantable Holter monitor in the detection of concealed paroxysmal atrial fibrillation in patients with cryptogenic stroke and a suspected embolic mechanism]. Rev Neurol. 2013;57(6):251-257.
8. Sanna T, Diener HC, Passman RS, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med. 2014;370(26):2478-2486. doi:10.1056/NEJMoa1313600
9. Ziegler PD, Glotzer TV, Daoud EG, et al. Detection of previously undiagnosed atrial fibrillation in patients with stroke risk factors and usefulness of continuous monitoring in primary stroke prevention. Am J Cardiol. 2012;110(9):1309-1314. doi:10.1016/j.amjcard.2012.06.034
10. Bernstein RA, Kamel H, Granger CB, et al. Effect of long-term continuous cardiac monitoring vs usual care on detection of atrial fibrillation in patients with stroke attributed to large- or small-vessel disease: the STROKE-AF randomized clinical trial. JAMA. 2021;325(21):2169-2177. doi:10.1001/jama.2021.6470
11. Wachter R, Gröschel K, Gelbrich G, 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. doi:10.1016/S1474-4422(17)30002-9
12. Writing Committee, Spooner MT, Messé SR, et al. 2024 ACC expert consensus decision pathway on practical approaches for arrhythmia monitoring after stroke: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2025;85(6):657-681. doi:10.1016/j.jacc.2024.10.100