Our study of patients with LVO-related anterior circulation stroke transferred from a PSC to CSC for consideration of thrombectomy showed that: (1) 59.5% of PSC patients treated with IVT experience poor 90-day functional outcome despite documented recanalization; (2) baseline variables obtained at the PSC that are independently associated with risk of FR and 90-day death include age, PSC-NIHSS score and CS.

The rates of recanalization following IVT treatment show considerable variation across various studies. Flores et al. [14] showed that partial or complete recanalization occurred in 10.5% of patients with a confirmed LVO in the PSC transferred to a CSC for EVT evaluation while Ospel et al. documented 41% recanalization rate [15]. However, the rates and predictors of FR in these patients remain uncertain. Recanalization is the mainstay of ischemic stroke treatment and is generally considered a prognostic factor for good outcome [16, 17]. Recanalization is the prerequisite to establish reperfusion. Several processes including distal clot fragmentation, pericyte constriction or poor collaterals may hamper reperfusion of the ischemic brain [18]. Therefore, progressive infarct expansion in patients with poor clinical outcome despite recanalization is caused by reperfusion failure. In our study we showed that patients with FR compared to those with ER had a statistically significant difference in terms of the distribution of the CS. Indeed, FR patients more often presented lower collateral grades compared to their counterparts with ER. Of note, the two groups of patients did not have significant differences in terms of any median treatment time delays taken into consideration, ASPECTS on NCCT and site of the LVO occlusions. Our data are in line with the results of a recent landmark trials of endovascular stroke therapy [19] showing that at least 50% of patients with anterior circulation LVO may be ‘fast progressors’, whose infarct growth is most sensitive to duration of ischemia because of rapid failing collaterals and who would benefit from fastest possible access to EVT within the early time window [20].

In our analysis CS, obtained with the CTA at the PSCs, correlated with 90-day functional outcome and risk of death. Collateral circulation of the brain refers to alternative vessels, consisting of primary circle of Willis and secondary pial leptomeningeal anastomoses, that can compensate for reduced blood flow in the setting of LVO [21]. Indeed, after arterial occlusion, there can be temporal growth of the ischemic core into the penumbral area that is modulated by collateral blood flow, the key element setting the pace of the ischemic process [22, 23]. Collateral patterns assessed by presentation CTA vary dramatically among patients with stroke and are highly related to larger volumes of salvageable ischemic tissue, slow rate of ASPECTS decay between hospital transfer and improved clinical outcomes [24,25,26]. A strong body of evidence has demonstrated that collateral status plays a crucial role in the prognosis of patients with acute ischemic stroke. Leng et al. demonstrated the prognostic value of baseline collateral circulation for outcomes of acute ischemic stroke patients receiving IVT [27]. However, the authors did not specify the percentage of patients with acute ischemic stroke due to anterior circulation LVO. Conversely, a previous meta-analysis of twelve studies enrolling 2138 patients with acute ischemic stroke due to anterior circulation LVO, treated with or without IVT, failed a significant impact of collateral status on futile recanalization after MT treatment [28]. This was mainly due to the limited number of studies, variation in scales assessing collateral status, and presence of heterogeneity. Overall, the latest American Heart Association/American Stroke Association guidelines suggest that it may be reasonable to incorporate collateral flow status into clinical decision-making in some candidates to determine eligibility for MT with a IIb level of evidence although no specific criteria are suggested [1].

In our study we documented also that age and PSC-NIHSS score independently predicting functional outcome after IVT-induced recanalization. We also found that grade of CS in combination with age and severity of stroke syndrome represented a model with good predictive accuracy for poor outcome and death at 3 months after the index. Several models have been developed to predict poor functional outcome despite recanalization of the LVO in patients treated with EVT rather than for IVT-only patients [28,29,30,31,32,33,34,35]. The MR PREDICT tool combing multiple baseline clinical and radiological characteristics aided in distinguishing between patients who may experience benefit from intra-arterial treatment for acute ischemic stroke and those will not [36]. Meinel et al. developed and validated a multivariable prognostic model to prospectively predict futile recanalization therapies in patients with acute ischemic stroke [37]. The authors documented that several clinical variables (higher stroke severity, older age, active cancer, pre-stroke disability), laboratory values (higher glucose, higher C-reactive protein), imaging biomarkers (more white matter hyperintensities), and longer onset-to-admission time were associated with futile recanalization. However, only 42.6% of the patients included in their analysis had a detectable LVO and only 11% of the patients received IVT alone. Our model might be able to identify the most relevant features in the emergency setting that can predict outcomes in these patients with early recanalization of the LVO post-IVT.

Finally, our data showed that patients who experienced FR were more likely to develop haemorrhagic transformation on follow-up CT at 24 h. Haemorrhagic transformation is a known complication of IVT. In our study, the higher incidence of haemorrhagic transformation in the futile recanalization group suggests that these patients may be at greater risk of adverse outcomes not solely due to the recanalization status but also due to the underlying pathology and treatment complications. This highlights the need to consider both factors in evaluating patient outcomes. This observation warrants further investigation to differentiate the direct effects of recanalization efficacy from those of therapy-related complications.

Our study has the following strengths: (1) large cohort of patients; (2) recanalization was assessed with angiography image for intervention at the two thrombectomy capable centres. Nevertheless, our study has several limitations. First, the observational design of the study. We did not routinely repeat a NCCT in spoke patients with acute ischemic stroke on arrival at the CSC when patients presented an NIHSS > 6 and per our criteria were eligible for EVT. Moreover, our study provides insights into the predictors of futile recanalization, these predictors primarily aid in post-transfer processes, such as prognostication and care planning, rather than influencing the initial decision to transfer a patient for thrombectomy. The immediate clinical decision to transfer should continue to prioritize timely and effective treatment for AIS due to LVO.

In conclusion, our study showed the rates and predictors of FR in patients with acute ischemic stroke due to LVO transferred from a PSC to a CSC. Our findings also highlight the importance of assessing collateral circulation as part of the routine neuroimaging protocols for PSC-patients with acute ischemic stroke when considering a transfer to a CSC for intervention. In the emergency setting, identifying predictors of FR can guide clinicians in early decision-making, allowing for tailored interventions and informed discussions about expected outcomes, potentially leading to more optimized patient management.