Although endovascular treatment (EVT) was the first-line therapeutic strategy for acute ischemic stroke (AIS), half of the patients could not achieve functional independence. Previous studies suggested arterial collateral was an important predictor of this phenomenon. However, cerebral collateral circulation was regulated by arteries, venous, and microcirculation, and its role remained unclear. Therefore, based on the integrated cerebral collateral cascade (CCC) system, this study aimed to explore the relationship and potential mechanisms between CCC and futile recanalization. This was a multicenter retrospective study for AIS patients receiving EVT. The CCC model was used to comprehensively assess the collateral circulation, which consisted of arterial collaterals, venous outflow, and tissue-level collaterals. Imaging outcomes included ischemic core, hypoperfusion volume, and penumbra volume. The clinical outcome was futile recanalization, defined as a 90-day modified Rankin Scale (mRS) 3-6 after successful recanalization. Multivariate regression and mediation analyses were used to assess the relationship between CCC, futile recanalization, and potential mediators. Among 513 patients with successful recanalization, 50.6% (260) experienced futile recanalization. In the multivariable regression analysis, favorable CCC (aOR 0.48, 95% CI 0.31-0.75
P = 0.001) was independently associated with unfavorable outcome despite successful recanalization. Furthermore, mediation analysis revealed that favorable CCC significantly reduced the ischemic core accounting for 27.62% (95% CI 9.69-66.00%) of its beneficial effect on futile recanalization. The benefit of favorable CCC on futile recanalization may be mediated by a reduction in ischemic core volume in AIS patients undergoing EVT. Our findings deepen the understanding of futile recanalization and microcirculation.