Application of the AHA-Proposed Cancer-Related Ischemic Stroke Classification: Reclassification and Prognostic Impact

BACKGROUND: Ischemic stroke in patients with active cancer is heterogeneous and frequently classified as cryptogenic under the TOAST classification (Trial of Org 10172 in Acute Stroke Treatment). The American Heart Association recently proposed an etiological classification for cancer-related ischemic stroke (CRIS). This study aimed to evaluate its clinical and prognostic implications. METHODS: We analyzed data from the prospective SCAN study (Ischemic Stroke in Patients With Cancer and Neoplasia), which enrolled patients with acute ischemic stroke and active cancer in Japan. Among the registered patients, those with available D-dimer data were included in the analysis. Stroke subtypes initially classified according to the TOAST criteria were reclassified using the CRIS framework. Kaplan-Meier survival curves were constructed, and differences were assessed using the log-rank test. RESULTS: Of 135 enrolled patients, 132 (median age, 75; 37.9% female) were included. Under the TOAST classification, 9 patients had small vessel occlusion, 20 large artery atherosclerosis, 28 cardioembolism, 10 other determined cause, and 65 cryptogenic strokes. After reclassification, 2 patients originally categorized as other determined etiology due to disseminated intravascular coagulation, and 46 patients previously classified as cryptogenic stroke were reclassified as CRIS. Patients classified as CRIS demonstrated significantly worse 1-year survival than those classified as conventional etiologies or cryptogenic stroke (global log-rank, P <0.001). The 3-month survival rate was 37.5% in the CRIS group and 89.2% in the reclassified cryptogenic stroke group. CONCLUSIONS: The newly proposed CRIS classification reduced the proportion of cryptogenic strokes under the TOAST system and enabled prognostic stratification by identifying a subgroup with markedly worse outcomes.