The benefit of favorable venous outflow profile is mediated through reduced microvascular dysfunction in acute ischemic stroke

Introductions: Venous outflow (VO) is emerging as a marker of microvascular integrity in acute ischemic stroke. Using hemorrhagic transformation (HT) and infarct growth as mediators, we tested whether a favorable VO profile benefited functional outcome by reducing consequences of microvascular dysfunction. Patients and methods: Patients receiving thrombectomy in three comprehensive stroke centers due to acute anterior circulation occlusion were included. VO was assessed semi-quantitatively by the opacification of ipsilateral vein of Labbe, Trolard and superficial middle cerebral vein. HT was graded on follow-up CT. Infarct growth volume (IGV) was the difference of final infarct volume and baseline core volume. The association of VO and functional independence (90-day modified Rankin Scale <= 2) was examined by logistic regression. Mediation analysis was performed among VO, HT or IGV, and functional outcome in patients with or without recanalization, respectively. Results: In 242 patients analyzed, VO was strongly correlated with functional independence and VO >= 4 was defined favorable. In 175 patients recanalized, favorable VO was associated with a reduced risk of HT (OR = 0.82, 95% CI 0.71-0.95, p = 0.008), which accounted for 13.1% of the association between VO and favorable outcome. In 67 patients without recanalization, favorable VO was associated with decreased IGV (beta = -0.07, 95% CI -0.11 to -0.02, p = 0.007). The association of favorable VO and functional independence was no longer significant (aOR = 4.84, 95% CI 0.87-38.87, p = 0.089) after including IGV in the model, suggesting a complete mediation. Discussion and Conclusion: In patients with acute anterior large vessel occlusion, the clinical benefit of VO may be mediated through reduced microvascular dysfunction.