Sex Differences in Embolic Stroke of Undetermined Source: Echocardiographic Features and Clinical Outcomes

Background: Sex differences in stroke are well-documented, but in embolic stroke of undetermined source (ESUS) remains underexplored. This study aims to investigate sex-related differences in clinical and cardiac features and stroke outcomes in ESUS. Methods: Retrospective observational single-center study including consecutive ESUS patients. Multivariate regression analyses evaluated the association between sex, echocardiographic features, and 90-day outcomes. Cox regression assessed the independent effect of sex on ischemic stroke recurrence, all-cause death, and atrial fibrillation detection after stroke (AFDAS). Results: Among 556 patients, 248 (44.6%) were women, who were older and had more severe strokes. Women exhibited larger left atria (LA) as evidenced by a higher LA volume index (adjusted beta-coefficient = 2.59, 95% CI 0.53-4.65, p = 0.014) and more valve abnormalities, such as mitral annulus calcification (aOR 2.72; 95% CI 1.43-5.20, p = 0.002). Men showed more markers of left ventricular (LV) disease, including reduced ejection fraction < 50% (aOR 0.44; 95% CI 0.20-0.93, p = 0.033) and LV wall motion abnormalities (aOR 0.37; 95% CI 0.19-0.74, p = 0.005). In multivariate analyses, the female sex was independently associated with reduced all-cause death (aHR 0.59; 95% CI 0.38-0.91, p = 0.019) and showed a trend toward higher AFDAS risk (aHR 1.57; 95% CI 0.99-2.49, p = 0.053). No association was found with 90-day outcomes or stroke recurrence. Conclusion: ESUS patients exhibit significant sex-based differences in echocardiographic features, with women showing larger LA and more valve abnormalities, while men present greater LV dysfunction. Female sex is independently associated with a lower risk of long-term mortality and a potentially higher risk of AFDAS. These findings underscore the need for individualized, sex-specific ESUS management strategies.