Early Onset of Cerebral Vasospasm and the Mediating Impact of Secondary Infarction on In-Hospital Mortality Following Aneurysmal Subarachnoid Hemorrhage

<b>Background:</b> Cerebral vasospasm (CV) as a complication after aneurysmal subarachnoid hemorrhage (aSAH) is a major determinant of secondary vasospasm-associated ischemic infarction (SVS-I) and poor outcome. Data on the interplay among the onset of CV, SVS-I, and in-hospital mortality remain limited. <b>Methods:</b> We conducted a retrospective, single-center study including patients admitted with aSAH between January 2016 and May 2024 who developed treatment-relevant CV. The primary outcome was the rate of in-hospital mortality. The relationship between the onset of CV, demographics, imaging, and treatment data and the primary outcome was analyzed using logistic regression. A confounder-adjusted mediation analysis was performed to quantify the extent to which the effect of time to CV onset on in-hospital mortality was mediated by SVS-I. <b>Results:</b> A total of 165 patients with aSAH and treatment-relevant CV were included. The median age was 55 (IQR, 48-64), and 67.2% (111) were female. Of the included patients, 13.3% (22) died during hospitalization. In multivariable logistic regression analysis, earlier onset of treatment-relevant CV (adjusted odds ratio [aOR] 0.79; 95% CI, 0.66-0.95) and the occurrence of SVS-I (aOR 13.47; 95% CI, 2.78-65.3) were associated with the primary outcome. Mediation analysis indicated that SVS-I accounted for 28% of the effect of earlier onset of CV on in-hospital mortality. <b>Conclusions:</b> Twenty-eight percent of the effect of earlier onset of cerebral vasospasm on in-hospital mortality was mediated by secondary ischemic infarction. Targeting patients with early-onset vasospasm and the associated risk of infarction may reduce in-hospital mortality following aneurysmal subarachnoid hemorrhage.