Supracardiac Atherosclerotic Lesions in Embolic Stroke of Undetermined Source: Predicting Stroke Recurrence and Enhancing Secondary Prevention Strategies

Background Identifying the potential cause of embolic stroke of undetermined source is essential for secondary prevention. We analyzed retrospectively collected real‐world data from the South Korean cohort with embolic stroke of undetermined source to examine trends in baseline characteristics, diagnostic practices, and secondary prevention strategies and to identify cardioembolic factors and supracardiac atherosclerotic lesions associated with stroke recurrence. Methods We analyzed 5787 patients from the Real‐World Study of Embolic Stroke of Undetermined Source cohort from 19 South Korean stroke centers (2014–2019). Baseline characteristics, diagnostic and secondary prevention trends were evaluated. Factors associated with 1‐year stroke recurrence were identified using multivariable Cox regression analysis in 4036 patients with follow‐up data. Results Over 6 years, vascular risk factors and cardioembolic evaluations significantly increased. Stroke recurrence was strongly associated with intracranial nonrelevant stenosis involving ≥2 vessels (hazard ratio [HR], 2.756, P <0.001), paroxysmal atrial fibrillation (HR, 5.590, P =0.033), atrial septal aneurysm (HR, 4.741, P =0.005), and serum creatinine levels (HR, 1.166, P =0.008). In patients without moderate‐risk cardioembolic sources, a single intracranial nonrelevant stenosis and complex aortic atheroma were also linked to stroke recurrence. Conclusions Intracranial nonrelevant stenosis and complex aortic atheroma, along with cardioembolic factors like paroxysmal atrial fibrillation and atrial septal aneurysm, are key predictors of stroke recurrence in embolic stroke of undetermined source, especially those without moderate‐risk cardioembolic sources. These findings emphasize the need to consider both supracardiac atherosclerotic and cardioembolic mechanisms in embolic stroke of undetermined source and to develop tailored secondary prevention strategies for atherosclerotic stroke, particularly in cases with supracardiac atherosclerotic lesions to reduce stroke recurrence.