The dark side of the moon: the impact of venous hemodynamic in acute ischemic stroke

Introduction: despite successful endovascular treatment (EVT), about 50% of patients carry an important disability after acute ischemic stroke (AIS) due to large vessel occlusion (LVO). The exact mechanisms of stroke disability are not fully understood, preventing significant improvements in patients’ management. Recently, the venous system has been proposed to play a role as a predictive prognostic factor of AIS, but evidence is still very limited. Therefore, we conducted two studies on venous hemodynamics in LVO-AIS and successful EVT. Specifically, in a first study we aimed to explore the role of venous capacity, measured by cerebral blood volume (CBV) index, in predicting tissue fate and potential drug delivery after EVT, while in a second study we investigate whether a comprehensive venous drainage evaluation might be indicative of stroke evolution and functional outcome. Materials and methods: we analyzed acute stroke patients with a documented anterior LVO who underwent successful recanalization. Perfusion indices and volumes were calculated on pre-treatment perfusion imaging, while venous opacification and drainage time were evaluated on digital subtraction angiography sequences. Final infarct and hemorrhagic transformation (HT) were assessed on 24/48-hour MRI or CT scans. Clinical outcomes were measured with the 90-day modified Rankin Scale (mRS). For the first study we conducted a retrospective analysis of prospectively collected AIS patients from January 2021 to June 2024 where CBV index was compared to Hypoperfusion Intensity Ratio (HIR) and Alberta Stroke Program Early Computed Tomography Score (ASPECTS). In the second study, we prospectively enrolled acute stroke patients between February 2023 and February 2024 to evaluate the predictive role of venous outflow on ischemic lesion growth (ILG), HT and functional outcomes. Results: in the first study, we found that CBV index was a strong predictor of both ischemic lesion growth (B=-0.572, SE=7.899, p<0.001) and percentage of saved penumbra (B=0.522, SE= 0.376, p<0.001), whereas ASPECTS was only associated with baseline ischemic core volume (B=-0.269; SE=1.133; p=0.07). No association was found for HIR. In the second study, longer median washout times of superficial venous system, in particular cortical frontal veins, were found to be independently associated with poor functional outcomes (aOR=1.36; 95%CI 1.06-1.83; p=0.024), ILG (aB=3.8; SE 1.63; p=0.003) and HT (aOR=1.70; 95%CI 1.25-2.56; p=0.003). Moreover, opacification of Labbè and superficial middle cerebral veins predicted HT (aOR=0.303; 95%CI 0.085- 0.865; p=0.040) and ILG (aB=1.37; SE 0.85; p=0.037), respectively. Conclusions: venous hemodynamics significantly impact ischemic lesion evolution and can predict the functional outcome in LVO-AIS patients after successful EVT. Additionally, venous capacity may provide a standardized measure of potential neuroprotective drug delivery.