AccScience Publishing / BH / Online First / DOI: 10.36922/BH026090012
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REVIEW ARTICLE

Expanding cardiac substrates in embolic stroke of undetermined source beyond atrial fibrillation

Osman Karaarslan1 ,  Macit Kalçık2* ,  Mehmet Mustafa Yılmaz2 ,  Oğuzhan Çelik3 ,  Abdullah Sarıhan4 ,  Mehmet Murat Şahin1 ,  Mucahit Yetim2 ,  Muhammet Cihat Çelik1 ,  Lütfü Bekar2 ,  Yusuf Karavelioğlu2
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1 Department of Cardiology, Hitit University Erol Olçok Education and Research Hospital, Corum, Türkiye
2 Department of Cardiology, Faculty of Medicine, Hitit University, Corum, Türkiye
3 Department of Cardiology, Faculty of Medicine, Muğla Sıtkı Koçman University, Muğla, Türkiye
4 Department of Cardiology, Gediz State Hospital, Kütahya, Türkiye
Brain & Heart, 026090012 https://doi.org/10.36922/BH026090012
Received: 28 February 2026 | Revised: 9 April 2026 | Accepted: 13 April 2026 | Published online: 8 May 2026
© 2026 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 ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Embolic stroke of undetermined source (ESUS) represents a significant proportion of ischemic strokes in which a definite etiology cannot be identified despite comprehensive diagnostic evaluation. Traditionally, occult atrial fibrillation has been considered the primary underlying mechanism; however, emerging evidence suggests that a broader spectrum of cardiac abnormalities may contribute to embolic risk. The concept of atrial cardiopathy has expanded the understanding of thromboembolic stroke beyond overt atrial fibrillation, highlighting the role of structural, functional, and electrophysiological alterations of the left atrium. In addition to atrial pathology, other potential cardiac sources—including left atrial appendage dysfunction, ventricular thrombus, valvular abnormalities, patent foramen ovale, and heart failure—have been implicated in ESUS. Advances in cardiac imaging, prolonged rhythm monitoring, and biomarker assessment have improved the detection of these covert substrates. Despite these developments, optimal strategies for risk stratification and secondary prevention remain uncertain, as recent trials of empiric anticoagulation in ESUS have yielded neutral results. This review summarizes current evidence on diverse cardiac mechanisms underlying ESUS, outlines diagnostic approaches for identifying occult embolic sources, and discusses implications for targeted management. A more individualized evaluation of cardiac substrates may refine therapeutic decisions and improve the prevention of recurrent stroke in this heterogeneous population.

Keywords
Embolic stroke of undetermined source
Atrial cardiopathy
Cardioembolic stroke
Left atrial appendage
Cryptogenic stroke
Funding
None.
Conflict of interest
The authors declare they have no competing interests.
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