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Secondary stroke prevention following embolic stroke of unknown source in the absence of documented atrial fibrillation: A clinical review

Research output: Contribution to journalReview articlepeer-review

Original languageEnglish
Article numbere021045
JournalJournal of the American Heart Association
Issue number13
Accepted/In press10 May 2021
Published6 Jul 2021

Bibliographical note

Funding Information: Dr Williams acknowledges support from the British Heart Foundation (FS/20/26/34952). This work was supported by the Wellcome/EPSRC Centre for Medical Engineering (WT203148/Z/16/Z) at King’s College London and the British Heart Foundation (PG/19/44/34368). This work is supported by the British Heart Foundation Centre for Research Excellence at The University of Edinburgh (RE/18/5/34216). Publisher Copyright: © 2021 The Authors. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors


Approximately one-ŧhird of ischemic strokes are classified as cryptogenic strokes. The risk of stroke recurrence in these patients is significantly elevated with up to one-ŧhird of patients with cryptogenic stroke experiencing a further stroke within 10 years. While anticoagulation is the mainstay of treatment for secondary stroke prevention in the context of documented atrial fibrillation (AF), it is estimated that up to 25% of patients with cryptogenic stroke have undiagnosed AF. Furthermore, the historical acceptance of a causal relationship between AF and stroke has recently come under scrutiny, with evidence to suggest that embolic stroke risk may be elevated even in the absence of documented atrial fibrillation at- tributable to the presence of electrical and structural changes constituting an atrial cardiomyopathy. More recently, the term embolic stroke of unknown source has garnered increasing interest as a subset of patients with cryptogenic stroke in whom a minimum set of diagnostic investigations has been performed, and a nonlacunar infarct highly suspicious of embolic etiol- ogy is suspected but in the absence of an identifiable secondary cause of stroke. The ongoing ARCADIA (Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke) randomized trial and ATTICUS (Apixiban for Treatment of Embolic Stroke of Undetermined Source) study seek to further define this novel term. This review summarizes the relationship between AF, embolic stroke, and atrial cardiomyopathy and provides an overview of the clinical relevance of cardiac imaging, electrocardiographic, and serum biomarkers in the assessment of AF and secondary stroke risk. The implications of these findings on therapeutic considerations is considered and gaps in the literature identified as areas for future study in risk strati- fying this cohort of patients.

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