Farhan Khan, Christoph Stretz, Skylar Lewis, Dalia Chahien, Eric Goldstein, James E Siegler, Christina M Lineback, Kelsey Eklund, Farid Khasiyev, Sami Al Kasab, Collin J Culbertson, Marissa D'Souza, Brian Stamm, Jennifer Ro, Deborah Kerrigan, Richa Sharma, Hassan Aboul-Nour, Fadi Nahab, Setareh Salehi Omran, Guillermo Linares, Siddharth Sehgal, Emiliya Melkumova, Eesha Singh, Alicia M Zha, Neeharika Thottempudi, Shani Mannion, Russel Van Coevering, Lucia Chen, Sean L Thompson, Jesse M Thon, Mary Penckofer, Wenzheng Yu, Ahmad Abu Qdais, Dinesh Jillella, Kelly L Sloane, Oana M Dumitrascu, Frank G Conyers, Fawad Talat, Patrick A Glover, Jieun Kang, Vivek Patel, Yasmin Aziz, Adeel Zubair, Adam de Havenon, Camelia Valhuerdi Porto, Anna Bowman, Mahan Shahrivari, James R Brorson, David S Liebeskind, Simona Nedelcu, Hamid Ali, Ahmed Abdalwahab, Wayneho Kam, Thanh N Nguyen, Franziska Herpich, Mudassir Farroqui, Diana Rojas-Soto, Shadi Yaghi
These findings demonstrate a lower risk of recurrent stroke in patients classified as ESUS 2.0 than reported in prior ESUS trials and highlight the importance of age-appropriate advanced diagnostic evaluation.
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). ESUS was categorized into 3 groups: (1) established mechanism after further workup (ESUS-E), (2) comprehensive diagnostic workup without an identified cause (ESUS 2.0), and (3) no advanced workup. The primary outcome of recurrent ischemic stroke was compared between ESUS with established mechanism and ESUS 2.0 versus ESUS with no advanced workup and was assessed using adjusted Cox proportional hazards models.
RESULTS: Among 2281 patients, the mean age was 65 years, and 50.1% were men. 694 (30.4%) classified as ESUS-E, 1,243 (54.5%) classified as ESUS-NAW, and 344 (15.1%) as ESUS 2.0. The ESUS 2.0 group had a significantly lower risk of recurrent stroke than both the group with ESUS with no advanced workup (adjusted hazard ratio [aHR], 0.31 [95% CI, 0.13-0.76]) and the group with ESUS with established mechanism (aHR, 0.35 [95% CI, 0.15-0.85]). Within the group with ESUS with established mechanism, cancer (aHR, 5.33 [95% CI, 2.09-13.63]) and nonstenosing atherosclerotic disease or arch atheroma (aHR, 3.40 [95% CI, 1.18-9.83]) were associated with significantly increased risk of recurrence when compared with the group with ESUS 2.0.
CONCLUSIONS: These findings demonstrate a lower risk of recurrent stroke in patients classified as ESUS 2.0 than reported in prior ESUS trials and highlight the importance of age-appropriate advanced diagnostic evaluation.
REGISTRATION: URL: https://www.clinicaltrials.gov. Identifier: NCT06398366.