Introduction Atrial septal defect (ASD) is the most common congenital cardiac anomaly diagnosed in adults. It often remains asymptomatic until the fourth or fifth decade of life. Significant left-to-right interatrial shunting is associated with the risk of heart failure, pulmonary hypertension...

Background/Objectives: Embolic Stroke of Undetermined Source (ESUS) refers to non-lacunar ischemic stroke without an identified cause and is presumed to be related to a cardioembolic mechanism. A potential etiological factor is atrial fibrosis leading to left atrial (LA) dysfunction, also known as atrial cardiomyopathy. This study aimed to compare advanced transthoracic echocardiographic parameters of LA function in patients with ESUS and age- and sex-matched controls. Methods: In this prospective matched observational case–control study, fifty patients with ESUS and 50 age- and sex-matched controls were analyzed. All participants underwent comprehensive transthoracic echocardiography (TTE). LA parameters included four-dimensional volumetry, LA strain (LAS), and LA stiffness index calculated as the ratio of E/eʹ to reservoir strain. All ESUS patients additionally underwent transesophageal echocardiography (TEE) to assess the presence of patent foramen ovale (PFO). Results: Compared with controls, ESUS patients had significantly reduced LAS in the reservoir phase (LAS-r 37.3% vs. 42.3%; p < 0.01) and conduit phase (LAS-cd 22.9% vs. 28.4%; p < 0.01), as well as a higher LA stiffness index (0.171 vs. 0.149; p < 0.01). No significant differences were found in LA size or volume. In subgroup analysis, ESUS patients with and without PFO did not differ, while both subgroups showed significant impairment compared with controls. Conclusions: ESUS is associated with impaired LA functional properties despite preserved LA size. LAS may provide complementary information on subclinical LA functional abnormalities in patients with ESUS; however, its clinical and prognostic significance requires validation in prospective studies.