Supracardiac Atherosclerosis in Embolic Stroke of Undetermined Source

The Underestimated Source

George Ntaios; Max Wintermark; Patrik Michel

Disclosures

Eur Heart J. 2021;42(18):1789-1796. 

In This Article

Abstract and Introduction

Abstract

The term 'embolic stroke of undetermined source' (ESUS) is used to describe patients with a non-lacunar ischaemic stroke without any identified embolic source from the heart or the arteries supplying the ischaemic territory, or any other apparent cause. When the ESUS concept was introduced, covert atrial fibrillation was conceived to be the main underlying cause in the majority of ESUS patients. Another important embolic source in ESUS is the atherosclerotic plaque in the carotid, vertebrobasilar, and intracranial arteries, or the aortic arch—collectively described as supracardiac atherosclerosis. There is emerging evidence showing that the role of supracardiac atherosclerosis is larger than it was initially perceived. Advanced imaging methods are available to identify plaques which high embolic risk. The role of novel antithrombotic strategies in these patients needs to be assessed in randomized controlled trials. This review presents the evidence which points towards a major aetiological association between atherosclerotic plaques and ESUS, summarizes the imaging features which may aid to identify plaques more likely to be associated with ESUS, discusses strategies to reduce the associated stroke risk, and highlights the rationale for future research in this field.

Introduction

The term 'cryptogenic stroke' was used for several decades to describe patients with ischaemic stroke for whom the aetiology of stroke was undetermined.[1] This is a heterogeneous group consisting of three subgroups of patients: (i) those for whom the aetiology of stroke was unknown because of incomplete diagnostic work-up (a typical example being moribund patients), (ii) patients for whom the aetiology of stroke was undetermined because multiple potential causes were identified during the diagnostic work-up (a typical example being patients with atrial fibrillation (AF) and high-degree carotid stenosis ipsilateral to the infarct), and (iii) patients for whom the aetiology of stroke was undetermined despite proper diagnostic work-up.[1]

During recent years, the term 'embolic stroke of undetermined source' (ESUS) is used to describe the latter group of patients.[2] Embolic stroke of undetermined source is defined as a non-lacunar stroke (i.e. a cortical, cerebellar, brainstem, or subcortical infarct >1.5 cm in diameter[1]) without any certain identified embolic source from the heart or the arteries supplying the ischaemic territory, or any other apparent cause.[2] The two terms, cryptogenic and ESUS, are not synonyms and should not be mixed. Embolic stroke of undetermined source, rather than cryptogenic stroke, should be the preferred term when patients with ischaemic stroke of undetermined cause fulfilling ESUS criteria are described.[3]

Numerous potential embolic sources are associated with ESUS, and could broadly be grouped into the following potential embolic sources: covert AF, atrial cardiopathy, atherosclerotic plaques, left ventricular disease, cardiac valvular disease, patent foramen ovale (PFO), cancer-related emboli, and rare embolic mechanisms.[2,4,5] There is considerable degree of overlap of potential embolic sources in ESUS, as nearly half of ESUS patients have ≥2 diseases which could be considered as the cause of stroke.[4] Therefore, it is frequently challenging in ESUS patients to presume that a candidate embolic source is indeed the aetiology of stroke.[6]

When the ESUS concept was introduced, covert AF was conceived to be the main underlying cause in the majority of ESUS patients.[5] Another important embolic source in ESUS is the atherosclerotic plaque in the carotid, vertebrobasilar, and intracranial arteries, or the aortic arch—collectively described as supracardiac atherosclerosis (Figures 1–3). There is emerging evidence showing that the role of supracardiac atherosclerosis is larger than it was initially perceived. This review presents the evidence which point towards a significant aetiological association between atherosclerotic plaques and ESUS, summarizes the diagnostic approach which may aid to identify those plaques which are more likely to be associated with ESUS, discusses strategies to reduce the associated stroke risk and highlights the rationale for future research in this field.

Figure 1.

Schematic representation of the heart, aortic arch, carotid, and vertebral arteries, including their cervical and intracranial segments, all the way up to the Circle of Willis. Atherosclerotic deposits typically form in the aortic arch, at the origin of the carotid and vertebral arteries, at the carotid bifurcations, in the carotid siphons and intracranial vertebral arteries, and in the basilar artery.

Figure 2.

Endovascular and stretched out computed tomography angiogram views of a normal carotid artery bifurcation and a carotid bifurcation with calcified atherosclerotic plaque. The superior row shows a normal carotid artery bifurcation. The inferior row shows a carotid bifurcation with a calcified atherosclerotic plaque. The left column consists of endovascular volume renderings. The second column is stretched out views of the common and internal carotid artery, created by a software after semi-automated identification of the centreline. The third column consists of regular axial computed tomography angiogram images. The yellow arrows point at the calcified atherosclerotic plaque.

Figure 3.

A thrombus is identified in the lumen of the ascending aorta (arrows), likely resulting from the rupture of a calcified atherosclerotic plaque identified immediately underlying the thrombus. A fragment of this thrombus caused a right middle cerebral artery stroke visible on the perfusion computed tomography of the brain, with a tiny infarct (red) and a large penumbra (green).

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