Electrical and Structural Atrial Remodeling Identifies a High-Risk Phenotype in Embolic Stroke of Undetermined Source
Background Embolic stroke of undetermined source (ESUS) carries a substantial recurrence risk, yet anticoagulation has not proven superior to antiplatelet therapy in unselected patients. Atrial cardiomyopathy, reflecting electrical and structural atrial remodeling, may identify a high-risk ESUS subgroup. Objectives The purpose of this study was to characterize the extent of electrical and structural atrial remodeling in patients with ESUS and to evaluate its association with adverse cardiovascular outcomes during follow-up. Methods In this prospective single-center study, 103 consecutive ESUS patients and 123 age- and sex-matched controls without known cardiac disease underwent clinical evaluation, NT-proBNP measurement, 12-lead electrocardiogram, and transthoracic echocardiography. Patients were followed for ≥12 months. The primary endpoint was a composite of all-cause death, recurrent stroke, transient ischemic attack, myocardial infarction, or newly diagnosed atrial fibrillation. Independent predictors were determined using multivariable Cox regression. Results ESUS patients exhibited higher NT-proBNP, more frequent advanced interatrial block, and impaired left atrial function compared with controls. Over a median follow-up of 382 days (IQR: 366-697 days), 29 ESUS patients (29/103, 28%) reached the primary endpoint. Independent predictors were NT-proBNP >420 pg/mL, advanced interatrial block, E′ ≤9 cm/s, left atrial volume index ≥29 mL/m2, and left atrial ejection fraction <50%. A risk score integrating ≥3 markers identified a subgroup with markedly increased risk, in whom Kaplan-Meier estimated event-free survival at 1 year was approximately 50% (95% CI: 31.6%-68.4%). Conclusions Multimodal assessment of electrical and structural atrial remodeling identifies a subgroup of ESUS patients with an increased risk of adverse events. These findings underscore the potential clinical relevance of atrial cardiomyopathy and may support further evaluation in future rhythm-guided or anticoagulation studies.