Multimodal Assessment of Atrial Cardiomyopathy Identifies a High-Risk Subgroup of Embolic Stroke of Undetermined Source

Abstract Background Embolic stroke of undetermined source (ESUS) is associated with a high risk of recurrence. However, randomized trials have not shown superiority of anticoagulation over aspirin in unselected patients. Atrial cardiomyopathy (AtCM) may identify a high-risk ESUS phenotype. We investigated whether multimodal AtCM markers distinguish ESUS from controls and predict adverse clinical outcomes. Methods In this prospective single-center study, consecutive ESUS patients and age– and sex-matched controls without known cardiac disease were enrolled and followed for ≥12 months. All participants underwent clinical assessment, measurement of NT-proBNP, 12-lead ECG, and transthoracic echocardiography. The primary endpoint was a composite of all-cause death, recurrent stroke, transient ischemic attack, myocardial infarction, or newly detected atrial fibrillation. Cox regression analyses identified independent predictors and optimal cutoff values. Results The study included 103 ESUS patients (mean age 70.6±13.3 years) and 123 controls. Compared with controls, ESUS patients had higher NT-proBNP levels, more frequent advanced interatrial block (IAB), and impaired left atrial function. Over a mean follow-up of 470±205 days, 29 ESUS patients experienced the primary endpoint. Independent predictors were NT-proBNP >420 pg/mL, advanced IAB, E′ ≤9 cm/s, left atrial volume index ≥29 mL/m², and left atrial ejection fraction 50% experienced a cardiovascular event within 1 year. Conclusions AtCM features are common in ESUS and strongly associated with adverse outcomes. A multimodal assessment incorporating NT-proBNP, ECG, and echocardiography identifies a high-risk ESUS subgroup that merits targeted evaluation in future anticoagulation trials.