Supracardiac Atherosclerosis in Embolic Stroke of Undetermined Source

The Underestimated Source

George Ntaios; Max Wintermark; Patrik Michel


Eur Heart J. 2021;42(18):1789-1796. 

In This Article

Evidence Supporting a Significant Aetiological Association Between Supracardiac Atherosclerosis and Embolic Stroke of Undetermined Source

Carotid Plaques are More Prevalent Ipsilateral to the Infarct Than Contralateral

A growing body of evidence shows that carotid plaques are more prevalent ipsilateral to the infarct than contralateral, supporting an important aetiological role of non-stenotic carotid disease in ESUS. In a recent exploratory analysis of the NAVIGATE-ESUS trial, carotid plaques were much more frequently present ipsilateral to the qualifying ischaemic stroke than contralateral (65% vs. 8%).[25] In the same analysis, carotid stenosis was also more prevalent ipsilateral than contralateral to the qualifying ischaemic stroke (51% vs. 17%).[25] Similar results were reported also from smaller studies from Asia,[8,9] Europe,[28–31] and America[10,11,32–34] using various imaging modalities like ultrasound-, CT-, MRI- and positron emission tomography (PET)/MR-based studies. These results were confirmed by a recent meta-analysis of related studies which showed that the odds ratio of finding a plaque with high-risk features in the ipsilateral vs. the contralateral carotid was 5.5 (95% confidence interval 2.5–12.0).[35]

Carotid Plaques as a Competing Stroke Aetiology

If carotid plaque is indeed an important aetiology in ESUS, it would be rational to expect that the prevalence of other established potential embolic sources in such patients is lower. There is emerging evidence supporting this hypothesis. Recently, the AF-ESUS study showed that new incident AF was less frequently detected in ESUS patients with carotid plaques compared to those without.[7] Similarly, carotid plaques were strongly associated with the absence of PFO in young adults with cryptogenic stroke.[36] Both studies show that carotid plaques act as a competing stroke aetiology to other established stroke aetiologies, and hence, support their role as an underlying cause of ESUS. Similarly, aortic arch atherosclerosis is a frequent finding in ESUS patients.[27]

Clot Composition in Embolic Stroke of Undetermined Source

Embolic stroke of undetermined source is a heterogeneous group which may be caused by several thrombogenic diseases, some of which may lead to formation of red thrombi due to stagnating blood flow like AF and atrial cardiopathy, whereas other may be associated with white thrombi due to plaque ulceration with focal platelet aggregation like in carotid or aortic arch atherosclerotic plaques.[2,4,5] The composition of the clot could provide useful insight about the likely origin of the embolus. Recently, an analysis of consecutive emboli retrieved during mechanical thrombectomy showed that large artery atherosclerosis and cryptogenic patients had a similar proportion of platelet-rich clots, which was significantly higher compared with cardioembolic cases, supporting the argument that supracardiac atherosclerosis is the cause of stroke in a significant proportion of ESUS.[37]