Clinical markers of atrial abnormality as predictors of cardioembolic events in patients with embolic stroke of undetermined source
Authors: Guichard J B , Vial M , Hean V , Da Costa A , Camdessanche J P , Garnier P 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: Private company. Main funding source(s): Unrestrictive grant for fellowship support - Abbot Medical

Background
Embolic stroke of undetermined source (ESUS) represents 17% of ischemic strokes. The lack of etiology leads to unsuitable treatment, higher stroke recurrence, and death. Several features presume atrial cardiomyopathy (ACM) as a potential etiology of embolism among ESUS population, but its causative role is not steadily grounded.

Purpose
To assess predictors, focusing on markers of ACM, of diagnosis of a cardioembolic source in ESUS patients during a long-term follow-up.

Methods
(Figure 1) - This study was an observational, retrospective, monocentric, cohort trial designed to assess predictors of cardioembolic events occurrence in an ESUS population along a 9-year follow-up. 128 ESUS patients who faced an ischemic stroke with a negative extensive etiological assessment from 2009 to 2012 were consecutively included. Upon ESUS diagnosis, clinical, echocardiographic (including transthoracic and transoesophageal echocardiogram), electrocardiographic (ECG), and Holter-ECG features were recorded. The occurrence of atrial fibrillation (AF) and the recurrence of ischemic stroke were registered during follow-up. Diagnosis of a cardioembolic source, a composite outcome, was defined as AF occurrence and/or recurrence of ischemic stroke, for which a cardioembolic cause was diagnosed secondary to the etiologic evaluation.

Results
(Figure 2) - AF and a cardioembolic source were diagnosed in 13 patients (10.2%) and 17 patients (13.3%) respectively, during the 9-year follow-up. Overall ischemic stroke recurrence was diagnosed in 13 patients (10.2%). Through univariate analyses, age higher than 65 (HR=4.9, p&lt;0.01, 95%CI:1.5-16.1), abnormal P-wave axis (HR=4.3, p=0.01, 95%CI:1.4-13.2), increased PAC burden (HR=6.0, p&lt;0.01, 95%CI:2.0-18.5), left atrial (LA) dilation (HR=6.1, p&lt;0.01, 95%CI:2.0-18.7), and abnormal LA appendage outflow velocity (HR=8.6, p&lt;0.01, 95%CI:1.8-41.7) were associated with AF occurrence. The AF occurrence was independently predicted by LA dilation (HR=6.69, 95%CI:1.17-37.47, p=0.02) and abnormal P-wave axis (HR=5.91, 95%CI:1.37-25.56,p=0.02). High blood pressure(HR=4.7, p=0.04, 95%CI:1.1-20.6), CHA2DS2-VASc score higher than 2 (HR=3.3, p=0.03, 95%CI:1.1-9.3), age higher than 65 (HR=3.5, p=0.02, 95%CI:1.5-16.1), increased of PAC burden (HR=6.2, p&lt;0.01, 95%CI:2.2-17.1), and LA dilation (HR=4.2, p&lt;0.01, 95%CI=1.6-10.9) were found as predictors of the diagnosis of a cardioembolic source during follow-up. The abnormal P-wave axis was an independent predictor of the diagnosis of a cardioembolic source (HR=3.82, 95%CI:1.03-14.09, p=0.04) in ESUS population. No risk marker assessed at baseline was associated to the recurrence of overall ischemic stroke recurrence.

Conclusion
LA dilation and abnormal P-wave axis are significant and independent predictors of the diagnosis of cardioembolic source and AF occurrence in ESUS population. ACM seems to be involved in the cardioembolic process in a significant portion of ESUS population.