Prediction of Atrial Fibrillation in Patients With Embolic Stroke of Undetermined Source (AF-ESUS)

A new clinical entity termed Embolic Stroke of Undetermined Source (ESUS) was recently introduced by the Cryptogenic Stroke/ESUS International Working Group, which describes stroke patients for whom the source of embolism remains undetected despite thorough investigation; potential embolic sources include diseases of the mitral and aortic valves, the left cardiac chambers, the proximal cerebral arteries of the aortic arch and the venous system via paradoxical embolism. ESUS has been proposed as a potential therapeutic entity with a possible indication for anticoagulation, a hypothesis which is currently tested in two randomized controlled trials.

ESUS is defined as a visualized non-lacunar brain infarct in the absence of a) extracranial or intracranial atherosclerosis causing ≥50% luminal stenosis in arteries supplying the area of ischaemia, b) major-risk cardioembolic source, and c) any other specific cause of stroke (e.g. arteritis, dissection, migraine/vasospasm, drug misuse). Major risk sources of cardioembolism include permanent or paroxysmal atrial fibrillation, sustained atrial flutter, intracardiac thrombus, prosthetic cardiac valve, atrial myxoma or other cardiac tumours, mitral stenosis, recent (<4 weeks) myocardial infarction, left ventricular ejection fraction less than 30%, valvular vegetations, or infective endocarditis.

Recently, our group presented a descriptive analysis of an ESUS population derived from the Athens Stroke Registry. Among the overall ischemic stroke population, 10% of patients were classified as ESUS. These strokes were of mild-moderate severity and covert AF was identified as the underlying etiopathogenetic mechanism in approximately 40% of ESUS patients. The mortality risk in ESUS patients is lower compared to patients with cardioembolic stroke despite similar rates of stroke recurrence.

Also, the risk of stroke recurrence is higher in ESUS patients than in patients with non-cardioembolic strokes which could be a sign that the current antithrombotic strategy of treating ESUS patients with antiplatelets is suboptimal. Indeed, currently, it is not clear whether antiplatelets or anticoagulants are the ideal antithrombotic strategy in ESUS. Recently, two international, phase III, double-blind, randomized, controlled clinical trial were launched aiming to investigate whether anticoagulant treatment is superior to antiplatelet treatment for the secondary prevention in ESUS patient : the Randomized Evaluation in Secondary stroke Prevention Comparing the Thrombin inhibitor dabigatran etexilate versus aspirin in Embolic Stroke of Undetermined Source (RE-SPECT ESUS) trial and the NAVIGATE trial will compare dabigatran etexilate and rivaroxaban respectively to aspirin in ESUS patients.

It would be clinically useful to identify the predictors of covert AF in the ESUS population as this could possibly influence the choice of antithrombotic treatment, e.g. anticoagulants in ESUS patients at high risk of covert AF, and antiplatelets for ESUS patients with low risk of covert AF.