Abstract DP154: The Association Between Comprehensive Evaluation in ESUS and Stroke Recurrence: A secondary analysis of the Cardiac Abnormalities in Stroke Prevention and risk of Recurrence Study

Background: Although the embolic stroke of undetermined source (ESUS) construct was proposed as a unifying concept for embolic-appearing strokes without an identified cause, it includes patients with diverse and often unrecognized underlying mechanisms. This study investigates the differential rate of recurrent stroke according to the completeness of neurodiagnostic testing in a diverse multicenter cohort. Methods: This was a retrospective analysis of a multicenter observational cohort study (n=27 sites). Patients with ESUS were categorized into three groups: (1) established mechanism after further work up (ESUS-E), (2) patients who underwent a comprehensive diagnostic workup without an identified etiology (ESUS 2.0), and (3) no advanced workup (ESUS-NAW). The primary outcome of recurrent ischemic stroke was assessed by comparing ESUS 2.0 to both ESUS-E and ESUS-NAW groups using adjusted Cox proportional hazards models. Results: Of the 2,281 patients included, 694 (30%) were classified as ESUS-E, 344 (15%) as ESUS 2.0, and 1,443 (55%) as ESUS-NAW. The ESUS 2.0 group had a significantly lower annualized recurrence rate (1.98 per 100 person-years) compared to both the ESUS-NAW group (7.7 per 100 person-years; aHR 0.27, 95% CI: 0.11–0.62; p=0.002) and the ESUS-E group (6.10 per 100 person-years; aHR = 0.35; 95% CI 0.15–0.85, p=0.020). Within the ESUS-E group, cancer (aHR 5.33; 95% CI: 2.09–13.63; p < 0.001) and non-stenosing atherosclerotic disease or arch atheroma (aHR 3.40; 95% CI: 1.18–9.83; p = 0.023) were associated with significantly increased risk of recurrence when compared to ESUS 2.0. Conclusion: These findings demonstrate a lower risk of recurrent stroke in patients classified as ESUS 2.0, diverging from the 5–6% annual recurrence rates observed in prior ESUS trials. These findings suggest that patients who receive comprehensive diagnostic evaluation without identification of a specific etiology have a lower risk of recurrent stroke, an important consideration for the design of future ESUS studies.

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Journal
Stroke
Published
2026-01-29
DOI
https://doi.org/10.1161/str.57.suppl_1.dp154
Primary Topic
Cardiovascular and Diving-Related Complications
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article
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article

Abstract DP154: The Association Between Comprehensive Evaluation in ESUS and Stroke Recurrence: A secondary analysis of the Cardiac Abnormalities in Stroke Prevention and risk of Recurrence Study

Wayneho Kam, Hamid Ali, Dalia Chahien, Brian J. Stamm et al.
Stroke
Cardiovascular and Diving-Related Complications
article

Abstract DP154: The Association Between Comprehensive Evaluation in ESUS and Stroke Recurrence: A secondary analysis of the Cardiac Abnormalities in Stroke Prevention and risk of Recurrence Study

Wayneho Kam, Hamid Ali, Dalia Chahien, Brian J. Stamm, Setareh Salehi Omran, Franziska Herpich, Simona Nedelcu, Adeel Zubair, Diana Rojas-Soto, Mahan Shahrivari, Sean L. Thompson, Siddharth Sehgal, Dinesh V. Jillella, James Ernest Siegler, Collin J. Culbertson, Guillermo Linares, Kelsey Eklund, Eesha Singh, Jieun Kang, James R. Brorson, Kelly L. Sloane, Fahad Khan, D Liebeskind, Ahmad Abu Qdais, Skylar Lewis, Farid Khasiyev, Deborah Kerrigan, Mudassir Farooqui, Alicia Zha, Wenzheng Yu, Lucia Chen, Richa Sharma, Christina Lineback, Fawad Talat, Anna Bowman, Sami Al Kasab, Hassan Osama Mostafa Aboul Nour, Thanh N. Nguyen, Jesse Thon, Shadi Yaghi, Mary Penckofer, Shani Mannion, Christoph Stretz, Jennifer Ro, Yasmin Aziz, Fadi Nahab, Adam de Havenon, Oana Dumitrascu, Marissa D'Souza
article en

Abstract

Background: Although the embolic stroke of undetermined source (ESUS) construct was proposed as a unifying concept for embolic-appearing strokes without an identified cause, it includes patients with diverse and often unrecognized underlying mechanisms. This study investigates the differential rate of recurrent stroke according to the completeness of neurodiagnostic testing in a diverse multicenter cohort. Methods: This was a retrospective analysis of a multicenter observational cohort study (n=27 sites). Patients with ESUS were categorized into three groups: (1) established mechanism after further work up (ESUS-E), (2) patients who underwent a comprehensive diagnostic workup without an identified etiology (ESUS 2.0), and (3) no advanced workup (ESUS-NAW). The primary outcome of recurrent ischemic stroke was assessed by comparing ESUS 2.0 to both ESUS-E and ESUS-NAW groups using adjusted Cox proportional hazards models. Results: Of the 2,281 patients included, 694 (30%) were classified as ESUS-E, 344 (15%) as ESUS 2.0, and 1,443 (55%) as ESUS-NAW. The ESUS 2.0 group had a significantly lower annualized recurrence rate (1.98 per 100 person-years) compared to both the ESUS-NAW group (7.7 per 100 person-years; aHR 0.27, 95% CI: 0.11–0.62; p=0.002) and the ESUS-E group (6.10 per 100 person-years; aHR = 0.35; 95% CI 0.15–0.85, p=0.020). Within the ESUS-E group, cancer (aHR 5.33; 95% CI: 2.09–13.63; p < 0.001) and non-stenosing atherosclerotic disease or arch atheroma (aHR 3.40; 95% CI: 1.18–9.83; p = 0.023) were associated with significantly increased risk of recurrence when compared to ESUS 2.0. Conclusion: These findings demonstrate a lower risk of recurrent stroke in patients classified as ESUS 2.0, diverging from the 5–6% annual recurrence rates observed in prior ESUS trials. These findings suggest that patients who receive comprehensive diagnostic evaluation without identification of a specific etiology have a lower risk of recurrent stroke, an important consideration for the design of future ESUS studies.

StrokeVol. 57(Suppl_1)
Boston University (US), University of North Carolina at Chapel Hill (US), University of Iowa (US), Christiana Care Health System (US), Dartmouth–Hitchcock Medical Center (US), University of Minnesota (US), Royal College of Surgeons in Ireland (IE), Medical University of South Carolina (US), Brown University (US), University of Michigan (US), UCLA Health (US), University of Minnesota System (US), Yale University (US), University of Chicago (US), Northwestern Memorial Hospital (US), Lahey Medical Center (US), Michigan United (US), Mayo Clinic in Arizona (US), Hackensack Meridian Health (US), Saint Louis University (US), University of Colorado Anschutz Medical Campus (US), The Ohio State University (US), University of Cincinnati (US), University of Pennsylvania (US), University of Colorado Denver (US), Brookhaven College (US)
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Openalex Percentile: Top 74%
Cardiovascular and Diving-Related Complications
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