Embolic Stroke of Undetermined Source(ESUS)

A. Embolic Stroke of Undetermined Source(ESUS) – published in JACC January 2020

(i) Introduction

1. Patients with a nonlacunar ischemic stroke and no convincing etiology

2. The terms ESUS and cryptogenic stroke are not synonyms, as the latter also includes patients with multiple stroke etiologies or incomplete diagnostic work-up.

3. It involves approximately 17% of all ischemic stroke patients, who are typically younger patients with mild strokes.

4. Considerable rate of stroke recurrence of 4% to 5%/year

(ii) POTENTIAL EMBOLIC SOURCES

1. Atrial cardiopathy
2. Covert AF – most common
3. Left ventricular disease
4. Atherosclerotic plaques
5. Patent foramen ovale(PFO) :Patients <60 years old with patent foramen ovale (PFO) should not be included under the ESUS umbrella given evidence from two randomized controlled trials (REDUCE and CLOSE) that PFO closure is superior to antithrombotic therapy in this age group.
6. Cardiac valvular disease
7. Cancer

Three most prevalent potential embolic sources are left ventricular disease, arterial disease, and atrial cardiopathy, each being present in nearly one-half of all patients

Distribution of Potential Etiologies of ESUS in the Athens Stroke Registry

(iii) Management

1. Two large randomized controlled trials, NAVIGATE ESUS (Rivaroxaban Versus Aspirin in Secondary Prevention of Stroke and Prevention of Systemic Embolism in Patients With Recent Embolic Stroke of Undetermined Source) and RE-SPECT (Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source), tested whether empiric anticoagulation with rivaroxaban or dabigatran, respectively, would reduce the risk of recurrent stroke in ESUS patients when compared to aspirin.

2. These studies found that empiric anticoagulation was not associated with lower rates of stroke recurrence than aspirin.

3. One potential reason NAVIGATE ESUS and RE-SPECT ESUS were negative is heterogeneity of stroke etiology, including etiologies that may not respond well to anticoagulation such as atherosclerotic vessel disease (of the aortic arch, carotid and vertebral arteries, and/or intracranial vessels).

4. Thrombi may form in a diseased left atrium, even in the absence of atrial fibrillation, and lead to embolic stroke. The ongoing ARCADIA (AtRial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke) trial will test whether ESUS patients with atrial cardiopathy have less stroke recurrence with apixaban versus with aspirin.