Potential Embolic Sources in Embolic Stroke of Undetermined Source in Patients with Patent Foramen Ovale: Look Harder

Between 20 and 30% of ischaemic strokes are cryptogenic [1]. This refers to non-lacunar brain infarct not attributable to large-vessel atherosclerosis, small-artery disease, or embolism after thorough vascular, serological, and cardiac evaluation [2]. In 2014, the term “embolic stroke of undetermined source” (ESUS) was proposed to describe cryptogenic strokes likely caused by an embolic mechanism and for which anticoagulation may be warranted [1, 3]. ESUS constitutes 17% of all ischaemic strokes and is associated with high annual stroke recurrence rate of 4-5% [4]. Besides covert atrial fibrillation [4, 5], other purported embolic sources in ESUS include atrial cardiopathy [4, 6], left ventricular disease, paradoxical emboli (e.g., patent foramen ovale [PFO]), cardiac valvular disease, arteriogenic emboli, and cancer [4]. In this issue, Toh and colleagues [7] explored this field and looked into the prevalence and association of concomitant potential embolic sources (PESs) in patients with ESUS and PFO.

PFO is common and found on autopsy in 1 in 4 of the general population [8], but only small number of people with PFO will develop an ischaemic stroke over time [9]. Among those who developed ischaemic stroke, PFO has progressively described as being causally involved in approximately 10% of all strokes in young and middle-aged adults (≤55 years old) and approximately 42% of cryptogenic strokes in this age group [9]. The proposed pathophysiology involved paradoxical thromboembolism through the PFO and/or thrombus formation in the PFO which subsequently embolized as the main cause of ESUS in patients with PFO [9].

Nevertheless, the stroke recurrence on medical treatment after a cryptogenic stroke with PFO is as low as 1.27 events per 100 person-years [10], representing an incidence of 4.6% after 3.8 years of follow-up in the available randomized trials [11]. Meanwhile, a systematic review and meta-analysis of randomized controlled trials of PFO closure versus medical treatment showed that stroke recurrence is less frequent in patients who had their PFO closed compared with patients receiving medical treatment. However, new-onset atrial fibrillation was more frequent in the PFO closure group [12]. The major challenge is to identify which patients with cryptogenic stroke have causally implicated PFO, especially in the presence of other competing PESs.

In this retrospective study by Toh and colleagues [7], 309 out of 1,487 patients with ESUS were identified to have PFO. Clinical and imaging data were collected. Data on the patients’ Risk of Paradoxical Embolus (RoPE) score were also available. This score was developed in 2013 to assess the probability of PFO being the cause of stroke rather than an incidental finding [13].

Among patients with identified PFO, the proportions of patients with one, two, and three or more PES were 34.0%, 11.0%, and 5.2%, respectively. The remaining (49.8%) had no PES findings apart from the demonstrated PFO. Among the PES findings, atrial cardiopathy and left ventricular dysfunction were the most prevalent in this study cohort. Older patients were more likely to have more comorbidities, more PES, and lower RoPE score. On the other hand, patients with PFO only were found to have a higher RoPE score of >6, suggesting possible causation relationship between PFO and stroke in this group. No significant association was noted in this study between the size of the right to left shunt in PFO and the likelihood of having more PES [7].

The overall message of the study by Toh and colleagues is not new but deserves to be reinforced. It highlights the complexity of determining the potential causality of stroke in patients with PFO and concomitant PES. Two risk scores, one including mainly clinical features, the RoPE score, and one clinical plus anatomical PFO features (the PFO-Associated Stroke Causal Likelihood [PASCAL] Classification System) [14], may help clinicians in the assessment of the probability of a causal role of PFO in any cryptogenic stroke, in conjunction with a comprehensive evaluation to identify PES. Understanding the potential causality of stroke will guide individualized decision-making, hence the move towards a more integrated or holistic approach to care [15, 16]. Further studies are required to establish PFO characteristics that convey higher risk of stroke recurrence and the efficacy of PFO closure in patients with concomitant PES.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

We have not received any funds in relation to this work.

Author Contributions

Dr Sandra Elsheikh wrote and drafted the initial version of the manuscript. Professor Gregory Y.H. Lip and Dr Azmil H. Abdul-Rahim provided critical revision of the work for important intellectual content and approved the final version.

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

留言 (0)

沒有登入
gif