Stroke Recurrence in Embolic Stroke of Undetermined Source Without Atrial Fibrillation on Invasive Cardiac

Background More than half of patients with embolic stroke of undetermined source (ESUS) suffer from recurrent ischaemic stroke, despite the absence of atrial fibrillation (AF) on invasive cardiac monitoring (ICM). This study investigated the predictors and prognosis of recurrent stroke in ESUS without AF on ICM. Method This prospective study included patients with ESUS at two tertiary hospitals from 2015 to 2021 who underwent comprehensive neurological imaging, transthoracic echocardiography, and inpatient continuous electrographic monitoring for >= 48 hours prior to ICM for definitive exclusion of AF. Recurrent ischaemic stroke, all-cause mortality, and functional outcome by the modified Rankin scale (mRS) at 3 months were evaluated in patients without AF. Results Of 185 consecutive patients with ESUS, AF was not detected in 163 (88%) patients (age 62 +/- 12 years, 76% men, 25% prior stroke, median time to ICM insertion 26 [7, 123] days), and stroke recurred in 24 (15%) patients. Stroke recurrences were predominantly ESUS (88%), within the first 2 years (75%), and involved a different vascular territory from qualifying ESUS (58%). Pre-existing cancer was the only independent predictor of recurrent stroke ( adjusted hazard ratio [AHR] 5.43, 95% CI 1.43-20.64), recurrent ESUS (AHR 5.67, 95% CI 1.15-21.21), and higher mRS score at 3 months (beta 1.27, 95% CI 0.23-2.42). All-cause mortality occurred in 17 (10%) patients. Adjusting for age, cancer, and mRS category (>= 3 vs,3), recurrent ESUS was independently associated with more than four times greater hazard of death (AHR 4.66, 95% CI 1.76-12.34). Conclusions Patients with recurrent ESUS are a high-risk subgroup. Studies elucidating optimal diagnostic and treatment strategies in non-AF-related ESUS are urgently required.