To determine whether advanced cardiac imaging improves diagnostic yield and impacts clinical management in patients with embolic stroke of undetermined source (ESUS), compared with transthoracic echocardiography.

The optimal role of advanced cardiac imaging in embolic stroke of undetermined source (ESUS) remains unclear. We hypothesized that advanced imaging would provide greater diagnostic utility than transthoracic echocardiography with bubble study (bTTE).

We retrospectively analyzed adults ≥18 years admitted with ESUS/cryptogenic stroke or recurrent embolic stroke with known atrial fibrillation (Aug 2024–Aug 2025). Patients with incomplete workup or known stroke mechanism prior to advanced imaging were excluded. Transesophageal echocardiography (TEE), cardiac MRI (CMRI), or CT heart morphology (CTH) were considered diagnostic if thrombus, patent foramen ovale (PFO), aortic plaque, or valvular pathology was detected. Outcomes included (1) etiology determination, (2) management change, and (3) diagnostic yield comparison between bTTE and advanced imaging.

Of 588 ischemic strokes, 178 met inclusion criteria; 48 were excluded for incomplete workup. Among 130 eligible patients, 65 (50%) underwent advanced imaging (40 TEE, 19 CTH, 6 CMRI). Etiology was identified in 41.5% (95% CI 30–54%), and management was changed in 40.0% (95% CI 29–52%). Compared with bTTE alone (14.6% yield), advanced imaging identified additional etiologies in 42.9% (McNemar p<0.001). Advanced imaging was more frequently performed in younger patients (mean 59.6 vs 69.2 years, p<0.001), while posterior circulation strokes were associated with higher odds of positive findings (OR 5.25, 95% CI 1.01–27.2).

Advanced cardiac imaging identified a potential etiology and changed management in ~40% of ESUS/cryptogenic strokes, significantly outperforming bTTE. Although younger patients more often underwent advanced imaging in this cohort, only posterior circulation strokes predicted clinically actionable findings. Routine incorporation of advanced cardiac imaging into ESUS evaluation may improve diagnostic accuracy and treatment decisions.