Abstract
Introduction
This study aimed to determine whether venous sinus opacification time on final digital subtraction angiography (DSA), a proposed marker of microcirculatory perfusion, predicts futile recanalization after successful endovascular thrombectomy (EVT) in patients who experienced anterior circulation large vessel occlusion (LVO) stroke.
Methods
We retrospectively enrolled consecutive patients with anterior circulation LVO who underwent EVT and achieved successful recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] 2c–3). Venous sinus opacification time was defined as the interval from first contrast opacification of the internal carotid artery to first venous sinus opacification on the final angiographic run. Futile recanalization was defined as poor functional outcome at 3 months (modified Rankin Scale [mRS] > 3). Multivariable logistic regression, restricted cubic spline, receiver operating characteristic (ROC), and subgroup interaction analyses were performed. Incremental prognostic value was assessed by comparing models with and without venous sinus opacification time.
Result
A total of 205 patients were included, and 102 (49.8%) had futile recanalization. Venous sinus opacification time was independently associated with futile recanalization (odds ratio per 1-s increase 2.148; 95% confidence interval 1.543–2.991; p < 0.001). Adding venous sinus opacification time improved discrimination (AUC 0.700 vs. 0.782; DeLong p = 0.003) and reduced the Brier score (0.22 to 0.19). The association was approximately linear (p for nonlinearity = 0.143). A cutoff of 5.7 s showed high specificity (0.893) and modest sensitivity (0.392). No significant interactions were observed across prespecified subgroups.
Conclusion
Venous sinus opacification time on final DSA independently predicts futile recanalization after EVT and provides incremental prognostic value beyond established clinical predictors.
Supplementary Information
The online version contains supplementary material available at https://doi.org/10.1007/s40120-026-01001-2.
Keywords: Endovascular thrombectomy, Large vessel occlusion, Futile recanalization, Microcirculation, Venous sinus opacification time
Key Summary Points
| Why carry out this study? |
| Microcirculatory dysfunction is a key determinant of futile recanalization after EVT. |
| Currently, there is lack of standardized and practical imaging markers in clinical practice for assessing microcirculatory perfusion. |
| What was learned from this study? |
| Venous sinus opacification time, a proposed angiographic surrogate of microcirculatory perfusion status, independently predicts futile recanalization. |
| Venous sinus opacification time is a readily available angiographic metric derived from routine final post-recanalization DSA, requiring no additional imaging or specialized equipment, and may improve risk stratification and facilitate individualized management in patients with EVT-treated LVO stroke. |
Introduction
Endovascular thrombectomy (EVT) has become an established and highly effective treatment for acute ischemic stroke caused by large vessel occlusion (LVO) [1–4]. However, despite successful angiographic recanalization, nearly half of patients failed to achieve favorable functional outcomes [2–4]. This phenomenon has been termed futile recanalization and represented a major unmet clinical challenge [5]. Previous clinical studies had identified several factors associated with futile recanalization, including baseline NIHSS, large ischemic core volume, advanced imaging parameters, plasma biomarkers, and procedural factors related to endovascular treatment [6–9]. Nevertheless, the underlying pathophysiological mechanisms remained incompletely understood.
Increasing evidence suggested that futile recanalization might be driven by the no-reflow phenomenon and ischemia–reperfusion injury [10,11]. Accordingly, macrovascular recanalization does not necessarily translate into effective reperfusion at the tissue level. Microcirculatory dysfunction had therefore been proposed as a key contributor to poor clinical outcomes after EVT [12]. Such dysfunction might reflect multiple pathological processes, including microvascular thrombosis, endothelial dysfunction, and impaired capillary perfusion [13]. However, to date, there was no consensus regarding standardized definitions or reliable imaging-based approaches to assess microcirculatory perfusion status following EVT in patients with LVO stroke.
Final digital subtraction angiography (DSA) after successful recanalization provides a unique opportunity to capture the integrated arterial, capillary, and venous phases of cerebral perfusion in real time. This dynamic angiographic sequence may offer an accessible surrogate of microcirculatory perfusion status within ischemic brain regions after large vessel recanalization. In this context, venous sinus opacification time, measured as the arterial-to-venous transit interval on the final angiographic run, might reflect microcirculatory perfusion status. The present study quantified venous sinus opacification time on final DSA as a proposed marker of microcirculatory perfusion and evaluated its association with futile recanalization in patients with anterior circulation LVO stroke after successful EVT.
Methods
Ethics Statement
Ethical approval for the research protocol was obtained from the ethics committee (approval number 2023-067). The study was conducted according to the principles expressed in the Declaration of Helsinki. Written informed consent for EVT was obtained from all patients or their legally authorized representatives. Because patient information was deidentified and anonymized before being released to the researchers, the informed consent requirement for this study was waived by the institutional review board.
Study Design and Population
This retrospective study consecutively included patients with anterior circulation LVO ischemic stroke who underwent endovascular thrombectomy (EVT) at Shaoxing People’s Hospital between January 2023 and June 2025. Patients were enrolled according to the following including criteria: (1) age ≥ 18 years; (2) diagnosis of acute ischemic stroke with a baseline National Institutes of Health Stroke Scale (NIHSS) score ≥ 6; (3) occlusion of the intracranial internal carotid artery (ICA) or M1 segment of the middle cerebral artery (MCA) confirmed by DSA; (4) successful recanalization after EVT, defined as complete or near-complete reperfusion (modified Thrombolysis in Cerebral Infarction [TICI] grade 2c–3); (5) time from symptom onset to groin puncture within 24 h. Exclusion criteria were (1) pre-existing disability with a modified Rankin Scale (mRS) score ≥ 2; (2) baseline Alberta Stroke Program Early CT Score (ASPECTS) < 6, to minimize the influence of large infarct core, as thrombectomy was not routinely performed in large-core stroke during the early study period; (3) poor-quality cerebral angiography due to insufficient imaging duration or incomplete anatomical coverage; (4) re-occlusion of the target vessel on follow-up computed tomography angiography (CTA); (5) missing follow-up outcome data (Fig. 1).
Fig. 1.
Flowchart of enrollment and imaging profile. EVT endovascular thrombectomy, MCA middle cerebral artery, TICI thrombolysis in cerebral infarction, ASPECTS Alberta Stroke Program Early CT Score
Data Collection
Clinical data were collected by neurologists blinded to patient outcomes. Variables included demographic characteristics; baseline NIHSS score; baseline systolic and diastolic blood pressure; history of smoking, hypertension, atrial fibrillation, coronary heart disease, diabetes mellitus, hyperlipidemia, prior stroke or transient ischemic attack (TIA); prior use of antiplatelet or anticoagulant therapy; stroke etiology according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification [14], time from symptom onset to successful recanalization; laboratory findings; and in-hospital clinical complications. Functional outcome at 3 months was assessed using the mRS during structured telephone follow-up by a neurologist blinded to baseline clinical and imaging data.
Radiologic and Clinical Assessment
DSA was routinely performed throughout the EVT procedure. Multiple angiographic runs were acquired to identify the occlusion site, guide device manipulation, assess reperfusion status, and confirm the final angiographic result after recanalization. Microcirculatory dysfunction was assessed using venous sinus opacification time on the final angiographic series after successful recanalization. It was quantified as the time interval from the first appearance of contrast opacification in the internal carotid artery to the first appearance of contrast in the venous sinuses, reflecting the integrated arterial, capillary, and venous phases of cerebral perfusion (Fig. 2). A longer interval was interpreted as microcirculatory dysfunction. Measurements were independently performed by two experienced thrombectomy physicians who were blinded to clinical outcomes. The intraclass correlation coefficient for venous sinus opacification time was 0.902 (95% CI 0.872–0.925). Any disagreements were resolved by consensus with a third reviewer.
Fig. 2.
Measurement of venous sinus opacification time on final angiography. In a patient with left middle cerebral artery M1 occlusion, successful recanalization was achieved after EVT (mTICI grade 3). a Initial contrast opacification of the left internal carotid artery (white arrows, reference time point, 1.3 s). b Initial opacification of the venous sinus during the same angiographic run (black arrows, time point, 6.0 s). The venous sinus opacification time, defined as the interval between arterial and venous sinus opacification, was 4.7 s. c Follow-up diffusion-weighted MRI showing the final infarct extent in the corresponding vascular territory. Venous sinus opacification time was used as an angiographic surrogate marker of microcirculatory perfusion status. The patient achieved a favorable functional outcome (mRS score of 2 at 3 months)
Futile recanalization was defined as successful angiographic recanalization after EVT with a poor functional outcome (modified Rankin Scale [mRS] score > 3) at 3 months. Conversely, a good outcome was defined as an mRS score of 0–3 at 3 months. Hemorrhagic transformation was classified as hemorrhagic infarction (HI) or parenchymal hemorrhage (PH) according to the European Cooperative Acute Stroke Study (ECASS) [15] criteria and was assessed on follow-up non-contrast CT within 24 h after EVT. Symptomatic intracranial hemorrhage (sICH) was defined as an increase in NIHSS score of ≥ 4 points attributable to hemorrhagic transformation, in accordance with the ECASS II definition [16].
Statistical Analysis
Statistical analyses were performed using R software (version 4.5.2). Continuous variables were assessed for normality and are presented as mean ± standard deviation (SD) or median (interquartile range [IQR]) as appropriate. Between-group comparisons were performed using the Student’s t test or Mann–Whitney U test for continuous variables and Fisher’s exact test for categorical variables.
Univariate logistic regression analyses were first conducted to screen variables associated with futile recanalization. Variables with a two-tailed p value < 0.10 in univariate analyses were entered into multivariable binary logistic regression models to identify independent predictors. Two prediction models were constructed: model A included established clinical predictors, whereas model B additionally incorporated venous sinus opacification time. Model discrimination was evaluated using the area under the receiver operating characteristic curve (AUC), and differences between AUCs were compared using the DeLong test. To further address concerns regarding optimism and potential overfitting, we performed internal validation using two complementary approaches: (1) bootstrap resampling with 1000 replicates to estimate optimism-corrected model performance, and (2) tenfold cross-validation using out-of-fold predicted probabilities. Overall predictive performance was additionally assessed using the Brier score.
To explore potential nonlinear associations between venous sinus opacification time and futile recanalization, restricted cubic spline (RCS) regression was performed, with p values reported for overall and nonlinear components. For risk stratification, venous sinus opacification time was further categorized into tertiles, and a linear trend across tertiles was assessed by modeling tertile categories as an ordinal variable in logistic regression. The optimal cutoff value of venous sinus opacification time was determined using the Youden index, and sensitivity and specificity were calculated.
Prespecified subgroup analyses were conducted to assess effect consistency. Interaction terms between venous sinus opacification time and each subgroup variable were entered into multivariable logistic regression models, and p values for interaction were reported. A two-tailed p value < 0.05 was considered statistically significant.
Results
Patient Characteristics
A total of 205 patients with anterior circulation LVO stroke who achieved successful recanalization after EVT were included. The median age was 71 years (range 33–91 years), and 80 patients (39.0%) were female. The median baseline NIHSS score was 15, and the mean onset-to-recanalization time was 351 ± 217 min. Overall, 103 patients (50.2%) achieved a good functional outcome, whereas 102 patients (49.8%) experienced futile recanalization at 3 months.
Clinical and Imaging Factors Associated with Futile Recanalization
Baseline characteristics stratified by outcome are summarized in Table 1. Univariate analyses showed that patients with futile recanalization were older (median [IQR], 73 [65–79] vs. 68 [61–74] years; p = 0.004) and had higher baseline NIHSS scores (median [IQR], 17 [12–20] vs. 13 [10–18]; p < 0.001). They also exhibited a prolonged venous sinus opacification time (5.56 ± 1.03 vs. 4.77 ± 1.04; p < 0.001), higher neutrophil-to-lymphocyte ratio (5.33 ± 4.78 vs. 4.32 ± 5.60; p = 0.096), and higher D-dimer levels (1.51 ± 2.67 vs. 1.12 ± 2.82; p = 0.002). Regarding clinical complications, the futile recanalization group had significantly higher incidences of hemorrhagic transformation (40.2% vs. 25.2%; p = 0.026), parenchymal hemorrhage (11.8% vs. 1.9%; p = 0.006), symptomatic intracranial hemorrhage (6.9% vs. 1.0%; p = 0.035), and aspiration pneumonia (72.5% vs. 57.8%; p = 0.039).
Table 1.
Baseline characteristics stratified by 3-month functional outcome after EVT
| Total (n = 205) | Good outcome (n = 103) | Futile recanalization (n = 102) | p value | |
|---|---|---|---|---|
| Demographics | ||||
| Age, years, median (IQR) | 71 (61,76) | 68 (61, 74) | 73 (65, 79) | 0.004 |
| Female gender, n (%) | 80 (39.0) | 41 (39.8) | 39 (38.2) | 0.886 |
| Male gender, n (%) | 125 (61.0) | 62 (60.2) | 63 (61.8) | 0.886 |
| Smoking, n (%) | 55 (26.8) | 26 (25.2) | 29 (28.4) | 0.639 |
| Hypertension, n (%) | 141 (68.8) | 69 (67.0) | 72 (70.6) | 0.652 |
| Atrial fibrillation, n (%) | 90 (43.9) | 43 (41.7) | 47 (46.1) | 0.575 |
| Diabetes mellitus, n (%) | 55 (26.8) | 25 (24.3) | 30 (29.4) | 0.434 |
| Dyslipidemia, n (%) | 23 (11.2) | 12 (11.7) | 11 (10.8) | 1.000 |
| Coronary artery disease, n (%) | 6 (2.9) | 3 (2.9) | 3 (2.9) | 1.000 |
| Stroke history, n (%) | 37 (18.0) | 21 (20.4) | 16 (15.8) | 0.469 |
| Hyperhomocysteinemia, n (%) | 18 (8.8) | 12 (11.7) | 6 (5.9) | 0.217 |
| Antiplatelet use, n (%) | 19 (9.3) | 13 (12.6) | 6 (5.9) | 0.147 |
| Anticoagulation use, n (%) | 23 (11.2) | 15 (14.6) | 8 (7.8) | 0.183 |
| Clinical variables | ||||
| Baseline NIHSS, median (IQR) | 15 (11, 20) | 13 (10, 18) | 17 (12, 20) | < 0.001 |
| ASPECTS, median (IQR) | 9 (8, 10) | 9 (8, 10) | 9 (8, 9) | 0.280 |
| Baseline SBP, mmHg | 149.37 ± 20.0 | 150.07 ± 17.25 | 148.66 ± 22.43 | 0.929 |
| Baseline DBP, mmHg | 84.4 ± 12.24 | 84.81 ± 13.12 | 83.99 ± 11.34 | 0.399 |
| Baseline glucose, mmol/l | 7.67 ± 2.71 | 7.52 ± 2.61 | 7.81 ± 2.81 | 0.477 |
| Onset to recanalization, min | 351 ± 217 | 329 ± 186 | 374 ± 243 | 0.150 |
| Venous sinus opacification time, min | 5.16 ± 1.11 | 4.77 ± 1.04 | 5.56 ± 1.03 | < 0.001 |
| TOAST, n (%) | 0.866 | |||
| LAA, n (%) | 106 (51.7) | 52 (50.5) | 54 (52.9) | |
| Cardioembolic, n (%) | 82 (40.0) | 43 (41.7) | 39 (38.2) | |
| Others, n (%) | 17 (8.3) | 8 (7.8) | 9 (8.8) | |
| Laboratory test | ||||
| Leukocyte, 109/L | 7.77 ± 2.87 | 7.55 ± 2.79 | 8.00 ± 2.95 | 0.281 |
| Neutrophil, 109/L | 5.63 ± 3.04 | 5.30 ± 2.83 | 5.95 ± 3.23 | 0.190 |
| Lymphocyte, 109/L | 1.64 ± 0.81 | 1.72 ± 0.84 | 1.57 ± 0.78 | 0.122 |
| NLR, mean±SD | 4.83 ± 5.22 | 4.32 ± 5.60 | 5.33 ± 4.78 | 0.096 |
| Platelet, 109/L | 200.33 ± 63.34 | 194.72 ± 56.52 | 206.00 ± 69.38 | 0.296 |
| LDL-C, mmol/L | 2.32 ± 0.72 | 2.35 ± 0.79 | 2.29 ± 0.65 | 0.587 |
| Albumin, g/L | 36.94 ± 4.33 | 36.64 ± 3.81 | 37.24 ± 4.79 | 0.146 |
| Fibrinogen, g/L | 2.93 ± 0.95 | 2.90 ± 0.98 | 2.97 ± 0.92 | 0.430 |
| D-dimer, mg/L | 1.31 ± 2.75 | 1.12 ± 2.82 | 1.51 ± 2.67 | 0.002 |
| Procedure | ||||
| Bailout stenting, n (%) | 46 (22.4) | 28 (27.5) | 18 (18.0) | 0.132 |
| Number of passes, median (IQR) | 2 (1, 3) | 2 (1, 3) | 2 (1, 3) | 0.153 |
| mTICI, n (%) | 0.241 | |||
| mTICI 2c, n (%) | 45 (22.0) | 19 (18.4) | 26 (25.5) | |
| mTICI 3, n (%) | 160 (78.0) | 84 (81.6) | 76 (74.5) | |
| Initiation of tirofiban within 24 h, n (%) | 57 (27.8) | 32 (31.1) | 25 (24.5) | 0.350 |
| Clinical complications | ||||
| Hemorrhagic transformation, n (%) | 67 (32.7) | 26 (25.2) | 41 (40.2) | 0.026 |
| HI, n (%) | 54 (26.3) | 25 (24.3) | 29 (28.4) | 0.529 |
| PH, n (%) | 14 (6.8) | 2 (1.9) | 12 (11.8) | 0.006 |
| sICH, n (%) | 8 (3.9) | 1 (1.0) | 7 (6.9) | 0.035 |
| Aspiration pneumonia, n (%) | 133 (64.9) | 59 (57.8) | 74 (72.5) | 0.039 |
| Deep vein thrombosis, n (%) | 42 (20.5) | 20 (19.4) | 22 (21.6) | 0.732 |
IQR interquartile range, NIHSS National Institutes of Health Stroke Scale, ASPECTS Alberta Stroke Program Early CT Score, SBP systolic blood pressure, DBP diastolic blood pressure, TOAST Trial of ORG 10172 in Acute Stroke Treatment, LAA large artery atherosclerosis, NLR neutrophil-to-lymphocyte ratio, LDL-C low-density lipoprotein cholesterol, mTICI modified Thrombolysis in Cerebral Infarction, HI hemorrhagic infarction, PH parenchymal hemorrhage, sICH symptomatic intracranial hemorrhage
Multivariable Analysis and Incremental Prognostic Value
To evaluate the incremental prognostic value of venous sinus opacification time, two multivariable models were constructed (Table 2). Model A included established clinical predictors, whereas model B additionally incorporated venous sinus opacification time. The addition of venous sinus opacification time significantly improved model discrimination with the area under the receiver operating characteristic curve increasing from 0.700 to 0.782 (DeLong test, p = 0.003; Fig. 3). The Brier score also decreased from 0.22 to 0.19, indicating improved overall predictive accuracy.
Table 2.
Multivariable logistic regression models for futile recanalization after EVT
| Variable | Model A | Model B | ||||
|---|---|---|---|---|---|---|
| OR | 95% CI | p value | OR | 95% CI | p value | |
| Age | 1.038 | 1.009, 1.068 | 0.009 | 1.037 | 1.007, 1.068 | 0.016 |
| Baseline NIHSS | 1.108 | 1.046, 1.174 | < 0.001 | 1.099 | 1.035, 1.167 | 0.002 |
| D-dimer | 1.013 | 0.918, 1.118 | 0.797 | 1.013 | 0.912, 1.125 | 0.813 |
| NLR | 1.059 | 0.992, 1.131 | 0.085 | 1.074 | 0.999, 1.156 | 0.054 |
| Venous sinus opacification time | 2.148 | 1.543, 2.991 | < 0.001 | |||
Model A included established clinical predictors. Model B additionally incorporated venous sinus opacification time. Variables with p value < 0.10 in univariate analyses were entered into the multivariable logistic model
NIHSS National Institutes of Health Stroke Scale, NLR neutrophil-to-lymphocyte ratio
Fig. 3.
Receiver operating characteristic (ROC) curves of model A and model B regression models for predicting futile recanalization after EVT in patients with anterior circulation LVO stroke. The AUC increased from 0.700 to 0.782 after adding venous sinus opacification time (DeLong test, p = 0.003)
To address the issue of overfitting, we performed internal validation using two complementary methods, namely bootstrap and tenfold cross-validation. The results were highly consistent across both validation methods. The estimated optimism was low (< 0.03 for both models), suggesting minimal overfitting. For model A, the apparent AUC was 0.700, with a bootstrap optimism-corrected AUC of 0.679 and a tenfold cross-validated AUC of 0.671 (95% CI 0.598–0.745). For model B, the apparent AUC was 0.782, with a bootstrap optimism-corrected AUC of 0.761 and a tenfold cross-validated AUC of 0.752 (95% CI 0.685–0.820). Importantly, model B consistently outperformed model A after internal validation, indicating that the incremental prognostic value of venous sinus opacification time was preserved.
Dose–Response Relationship and Risk Gradient
Restricted cubic spline analysis demonstrated a significant overall association between venous sinus opacification time and the risk of futile recanalization (p for overall < 0.001). After adjustment for age, baseline NIHSS, neutrophil-to-lymphocyte ratio, and D-dimer, no statistically significant nonlinear relationship was observed (p for nonlinearity = 0.083), supporting an approximately linear increase in risk across the observed range (Fig. 4). Consistently, when patients were categorized into tertiles according to venous sinus opacification time, the rate of futile recanalization increased progressively across tertiles (T1, 35.1%, T2, 46.4%, T3, 72.9%; p for trend < 0.001; Fig. 5), indicating a clear exposure–response relationship.
Fig. 4.
Restricted cubic spline analysis illustrating the association between venous sinus opacification time and futile recanalization. The solid line represents the adjusted odds ratio, and the shaded area indicates the 95% confidence interval. The dashed horizontal line denotes an odds ratio of 1. The histogram shows the distribution of venous sinus opacification time in the study population
Fig. 5.
Futile recanalization rates across tertiles of venous sinus opacification time. Patients were categorized into tertiles according to venous sinus opacification time (T1, 2.4–4.7 s; T2, 4.7–5.5 s; T3, 5.5–8.9 s). The proportion of futile recanalization increased progressively across tertiles (35.1%, 46.4%, and 72.9%, respectively; p for trend < 0.001)
Threshold Analysis
Receiver operating characteristic analysis identified an optimal venous sinus opacification time threshold of 5.7 s for predicting futile recanalization. This cutoff yielded a sensitivity of 0.392 and specificity of 0.893. Patients with venous sinus opacification time above this threshold had a significantly higher incidence of futile recanalization compared with those below the threshold (72.9% vs. 40.4%, p < 0.001).
Subgroup Analyses
Subgroup analyses demonstrated a consistent association between prolonged venous sinus opacification time and futile recanalization across predefined subgroups stratified by age, baseline NIHSS score, ASPECTS, reperfusion grade, intravenous thrombolysis status, and stroke etiology. No significant interaction was observed between venous sinus opacification time and subgroup variables (all p for interaction > 0.05), (Fig. 6).
Fig. 6.
Forest plot showing the association between venous sinus opacification time and futile recanalization across predefined subgroups. P for interaction values were derived from interaction terms between venous sinus opacification time and each subgroup variable in multivariable logistic regression models. ASPECTS Alberta Stroke Program Early CT Score, IVT intravenous thrombolysis, mTICI modified Thrombolysis in Cerebral Infarction
Discussion
In this retrospective cohort of patients with anterior circulation LVO stroke who achieved successful recanalization after EVT, venous sinus opacification time on the final DSA run was independently associated with futile recanalization and provided incremental prognostic value beyond established clinical predictors.
Although restoration of macrovascular patency was a prerequisite for tissue reperfusion, our findings supported the concept that angiographic recanalization did not necessarily translate into effective microvascular flow. Prolonged venous sinus opacification time on final angiography, reflecting delayed contrast transit through the capillary and venous phases, was strongly associated with futile recanalization. This suggested that microcirculatory impairment might play a pivotal role in determining tissue-level reperfusion and subsequent functional recovery.
Several mechanisms might explain impaired microcirculatory perfusion despite successful recanalization. Prolonged ischemia could lead to endothelial swelling, capillary collapse, leukocyte adhesion, and microthrombus formation, which might persist after reopening the large vessel and contribute to the no-reflow phenomenon [13]. Ischemia–reperfusion injury may further disrupt the blood–brain barrier, amplify inflammation, and aggravate secondary microvascular obstruction [17]. Microvascular occlusion might also result from distal embolization of thrombus fragments during thrombectomy or in situ thrombosis driven by platelet activation in the injured microcirculation [18,19]. Experimental studies had shown that neutrophil-mediated capillary plugging could obstruct a substantial proportion of capillaries within the ischemic territory [13, 20]. Clinically, randomized trials had suggested that adjunctive intra-arterial thrombolysis after EVT may improve functional outcomes in selected patients, indirectly supporting the clinical relevance of residual microvascular obstruction [18, 21–23].
In this context, the addition of venous sinus opacification time improved the AUC from 0.700 to 0.782, reflecting moderate discriminative ability. As an adjunctive predictor, venous sinus opacification time provided incremental prognostic value beyond established clinical predictors. Furthermore, a venous sinus opacification time cutoff of 5.7 s showed high specificity but modest sensitivity, indicating that markedly prolonged opacification time may help identify patients at particularly high risk of futile recanalization, whereas shorter time does not exclude poor outcome. Other established determinants such as advanced age, higher baseline NIHSS score, and hemorrhagic transformation remain important contributors to poor outcome [6–9]. Accordingly, venous sinus opacification time may provide additional value when integrated into a comprehensive risk stratification strategy, helping to identify patients who may benefit from closer monitoring or adjunctive interventions. Such strategies may include optimization of periprocedural hemodynamics, intensified neurocritical care surveillance, and, in carefully selected patients, evaluation of adjunctive antithrombotic or thrombolytic approaches aimed at mitigating residual microvascular obstruction. Nevertheless, these implications remain hypothesis-generating and require confirmation in prospective studies.
Although the risk appeared to rise more steeply at higher values, the confidence intervals widened substantially, likely reflecting limited sample size. Future studies with larger cohorts are needed to refine decision thresholds and integrate additional predictors to enhance clinical utility.
Prior angiographic studies had reported associations between early venous filling and hemorrhagic transformation or malignant edema, but not necessarily functional outcome [24,25]. Early venous filling was initially described as the appearance of venous drainage during the arterial phase on super-selective microcatheter angiography, which may indicate arteriovenous shunting or abnormal hemodynamics within severely injured tissue [24]. In contrast, venous sinus opacification time in our study quantified the interval from internal carotid artery opacification to the initial opacification of the venous sinuses, capturing the integrated arterial-to-venous transit across the ischemic microvascular bed. This metric may provide a practical angiographic surrogate for microcirculatory perfusion within the ischemic territory, as it can be readily derived from routine final angiographic runs without additional imaging.
This study has several limitations. First, the retrospective single-center design may limit generalizability and is inherently susceptible to selection bias. Second, although venous sinus opacification time can be derived from routine angiography, it may be influenced by multiple physiological and technical factors, including cardiac output, blood pressure, collateral circulation, catheter position, injection rate, contrast volume, and angiographic acquisition parameters. Future prospective studies with standardized imaging protocols and detailed hemodynamic assessment are warranted to further clarify the independent contribution of these factors. Third, the optimal cutoff value for venous sinus opacification time was determined on the basis of the patient cohort from our single institution. As such, its external generalizability is inherently restricted. Large-scale, multicenter prospective trials with standardized DSA acquisition and measurement protocols are therefore warranted to validate the reliability and clinical applicability of this cutoff.
Conclusion
Venous sinus opacification time on final angiography provides an easily accessible surrogate of tissue-level perfusion after EVT. A prolonged venous sinus opacification time was independently associated with futile recanalization and improved prognostic discrimination beyond established clinical predictors. Further prospective validation is required before routine clinical implementation.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgements
We thank the participants of the study. We also thank the patients and their families for their valuable contribution and support.
Author Contribution
Huan Tang, Hui Cheng, and Zhicai Chen contributed to the conception and design of the study and drafted and critically revised the manuscript. Fang Wang, Yanxing Zhang, Jianli Wang, Wuqiao Bao, Yiping Lou, Min Zheng, Xuan Fang, and Zihao Li contributed to clinical data collection and imaging data curation. Guo Jing provided statistical expertise and supervised the statistical analyses. All authors reviewed the manuscript, approved the final version, and agree to be accountable for all aspects of the work.
Funding
Sponsorship for this study and the journal’s Rapid Service Fee were funded by Medical and Health Science Program of Zhejiang Province (2024KY1731, 2025KY835).
Data Availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Declarations
Conflict of Interest
Huan Tang, Fang Wang, Yanxing Zhang, Jianli Wang, Wuqiao Bao, Yiping Lou, Min Zheng, Xuan Fang, Zihao Li, Jing Guo, Hui Cheng, and Zhicai Chen have nothing to disclose.
Ethical Approval
Ethical approval for the research protocol was obtained from the ethics committee (approval number 2023-067). The study was conducted according to the principles expressed in the Declaration of Helsinki. Written informed consent for EVT was obtained from all patients or their legally authorized representatives. Because patient information was deidentified and anonymized before being released to the researchers, the informed consent requirement for this study was waived by the institutional review board.
Contributor Information
Hui Cheng, Email: chenghui@zju.edu.cn.
Zhicai Chen, Email: chenzhicai@zju.edu.cn.
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.