Introduction: Hemorrhagic transformation, especially symptomatic intracranial hemorrhage (sICH), is a common complication after mechanical embolectomy. This study explored a grading scale based on clinical and radiological parameters to predict sICH after mechanical embolectomy. Methods: Demographic and clinical data were retrospectively collected from patients with acute ischemic stroke treated with mechanical embolectomy at West China Hospital. Clinical and radiological factors associated with sICH were identified and used to develop the “STBA” grading scale. This score was then validated using data from an independent sample at the First Affiliated Hospital of Kunming Medical University. Results: We analyzed 268 patients with acute ischemic stroke who were treated with mechanical embolectomy at West China Hospital, of whom 30 (11.2%) had sICH. Patients were rated on an “STBA” score ranging from 0 to 6 based on whether systolic blood pressure was ≥145 mm Hg at admission (yes = 2 points; no = 0 points), time from acute ischemic stroke until groin puncture was ≥300 min (yes = 1; no = 0), blood glucose was ≥8.8 mmol/L (yes = 1; no = 0), and the Alberta Stroke Program Early Computed Tomography score at admission was 0–5 (2 points), 6–7 (1 point), or 8–10 (0 points). The STBA score showed good discrimination in the derivation sample (area under the receiver operating characteristic curve = 0.858) and in the validation sample (area = 0.814). Conclusions: The STBA score may be a reliable clinical scoring system to predict sICH in acute ischemic stroke patients treated with mechanical embolectomy.

© 2022 The Author(s). Published by S. Karger AG, Basel

Introduction

Mechanical embolectomy, with or without prior intravenous thrombolysis, is now accepted as a standard treatment for selected patients with acute ischemic stroke (AIS) due to intracranial large vessel occlusion [1-4]. A common complication after mechanical embolectomy is hemorrhagic transformation, especially symptomatic intracranial hemorrhage (sICH) [5, 6]. Despite advances in our understanding of sICH, treatments remain relatively ineffective. This highlights the importance of further research into factors affecting sICH. Studies have identified several risk factors for hemorrhagic transformation after mechanical embolectomy. These include high serum glucose at admission, high systolic blood pressure (BP), low score on the Alberta Stroke Program Early Computed Tomography (ASPECT) scale, sex, high score on the National Institutes of Health Stroke Scale (NIHSS) at admission, and long time from puncture to recanalization [5-8].

Improving the efficacy of mechanical embolectomy will depend on scoring systems that have been validated and optimized based on real-world practice. These scores can help physicians, patients, and families develop realistic prognostic expectations. Previous studies proposed several scoring systems to predict sICH, including the TICI-ASPECTS-glucose (TAG) score [9], which was developed using data mostly from Caucasian patients in the USA. However, sICH after mechanical embolectomy occurs more often in Asian populations than in American populations, and clinical characteristics of the disease may also differ between the two regions.

Thus, the present study aimed to develop an accurate scoring system, based on clinical and radiological parameters and validated for Asian populations, that could predict sICH after mechanical embolectomy. To do that, we retrospectively analyzed data from AIS patients treated with mechanical embolectomy and tried to identify factors associated with sICH. Then, we defined a new score, evaluated its prognostic ability in our cohort, and validated it in a different cohort of AIS patients treated with mechanical embolectomy.

Materials and MethodsStudy Population

We retrospectively reviewed data from AIS patients who underwent mechanical embolectomy and not acute stenting at the Department of Neurology of West China Hospital (Chengdu, China) from January 2017 to August 2020. The study protocol was designed in accordance with international ethics criteria for human research and was approved by the Scientific Research Department of First Affiliated Hospital of Kunming Medical University. This study protocol was reviewed and approved by the Scientific Research Department of First Affiliated Hospital of Kunming Medical University, and approval number was 2018B125.

Patients were eligible for the study if they (a) presented angiographically confirmed intracranial large vessels at admission; (b) received a groin puncture within 8 h after onset of anterior circulation stroke or 24 h after onset of posterior circulation stroke; and (c) had a pretreatment National Institutes of Health Stroke Scale (NIHSS) score >5. Patients were excluded if (a) intracranial hemorrhage was detected in a pretreatment imaging study; (b) acute anterior circulation infarction was larger than one-third of the middle cerebral artery territory on computerized tomography (CT) or magnetic resonance imaging; (c) patients had serious sensitivity to radiographic contrast agents or uncontrolled hypertension; and/or (d) patients had a premorbid modified Rankin Scale (mRS) score >2. For selected patients who did not meet these criteria, mechanical embolectomy was still performed if the benefit-risk ratio was considered favorable.

As the validation cohort, we enrolled AIS patients who underwent mechanical embolectomy at the First Affiliated Hospital of Kunming Medical University (Kunming, China) from June 2017 to September 2021. The same inclusion and exclusion criteria were applied as for the West China sample.

Pre-Procedure Imaging

Each patient was examined using non-contrast cranial CT to exclude intracranial hemorrhage, followed by CT angiography of the head and neck to detect large vessel occlusion. CT angiograms were reviewed by two neurologists for the presence of large vessel occlusion, which was defined as occlusion of the internal carotid artery, middle cerebral artery, and basilar artery. The ASPECT score was used to assess early ischemic changes [1, 10].

Patient Evaluation

At admission, all patients underwent laboratory examinations, which included determinations of blood glucose, platelet count, and international normalized ratio, as well as intravenous thrombolytic therapy. The following time intervals were recorded: time from stroke onset to arrival at hospital, time from arrival at hospital to groin puncture, time from onset to groin puncture, and time from groin puncture to recanalization. The following baseline clinical and demographic data were collected from all patients on admission: sex, age, NIHSS score, risk factors (hypertension, diabetes mellitus, coronary heart disease, hypercholesterolemia, valvular heart disease, history of stroke, current smoking status, and current drinking status), antiplatelet treatment, anticoagulation treatment, and BP.

Post-Thrombectomy Imaging

Radiological findings were evaluated by two neurologists blinded to the clinical outcome. Post-treatment recanalization was assessed using the modified Thrombolysis in Cerebral Infarction (mTICI) grading system [11]. Non-recanalized reperfusion was defined as mTICI grade 0 or 1. Inadequate reperfusion was defined as grade 2a (revascularization <50%). Successful recanalization was defined as mTICI grade 2b (revascularization >50%) or 3 (complete distal branch filling).

Outcome Variables

sICH was defined as hemorrhagic transformation associated with neurological worsening (increase of ≥4 points in NIHSS score) [12] when the deterioration could not be explained by causes other than sICH.

Statistical Analysis

All statistical analyses were performed using SPSS version 21.0 (IBM, Armonk, NY, USA). Continuous data were described as mean ± standard deviation and/or median (interquartile range). Differences in categorical variables were assessed for significance using χ2 or Fisher’s exact tests. Differences in variables showing a normal distribution and homogeneous variance were assessed using Student’s t test, while differences in variables showing skew or heterogeneous variance were assessed using the Mann-Whitney U test. Where appropriate, inter-group differences in continuous variables were presented as odds ratios (ORs) with 95% confidence intervals (CIs).

Univariate analyses were performed to identify risk factors associated with sICH after mechanical embolectomy. Multivariate regression was used to identify risk factors independently associated with sICH from among variables that were associated with p < 0.1 in univariate models. For continuous variables, an additional multivariable logistic regression model was created using standard or previously defined threshold values to yield a more practical scoring system. Receiver operating characteristic curves were constructed by plotting test sensitivity against 1 − specificity, and the area under the curve (AUC) was determined. A two-sided p < 0.05 was considered statistically significant.

ResultsPatient Characteristics

A total of 268 AIS patients from West China Hospital were included as the derivation cohort, and 79 patients from the First Affiliated Hospital of Kunming Medical University were included as the validation cohort. The two samples showed similar baseline demographic and clinical characteristics (Table 1). Across both samples, the characteristics at admission were the following: age, 68 (57–76) years; NIHSS score, 16 (12–20); ASPECT score, 7 (5–9); and serum glucose level, 7.13 (6.27–9.10) mmol/L. In total, 113 cases (32.6%) received intravenous thrombolysis before mechanical embolectomy.

Table 1.

Baseline characteristics between the derivation cohort and validation cohort

The average time from onset of AIS to hospital arrival was 196.2 ± 81.1 min; time from arrival at hospital to groin puncture, 120.3 ± 52.2 min; and time from groin puncture to recanalization, 96.1 ± 40.1 min. A total of 276 patients (79.5%) had successful recanalization (mTICI grades 2b–3) (Table 1).

Factors Associated with sICH in Univariate and Multivariate Analyses

Table 2 shows the baseline demographic and clinical characteristics of patients stratified by the presence or not of sICH. Patients in the sICH group were more likely than those without sICH to wait ≥300 min from onset to groin puncture (66.7% vs. 45.8%; p = 0.042). The sICH group also showed significantly higher baseline blood glucose (7.85 [6.82–9.91] vs. 7.01 [6.25–8.54]; p = 0.029), systolic BP (165.18 ± 20.99 vs. 142.64 ± 25.75; p < 0.001), and diastolic BP (92.05 ± 16.34 vs. 82.65 ± 15.28; p < 0.001). Conversely, the sICH group had significantly lower baseline ASPECT score (5.00 [3.00–9.00] vs. 8.00 [6.00–9.00]; p < 0.001). Univariate analysis identified the following factors associated with sICH: systolic BP at admission (OR per 1 mm Hg increase: 1.04, 95% CI: 1.02–1.05, p < 0.001), diastolic BP (OR per 1 mm Hg increase: 1.03, 95% CI: 1.02–1.05, p = 0.028), blood glucose (OR per 1 mmol/L increase: 1.18, 95% CI: 1.08–1.29, p < 0.001), ASPECT score (OR: 0.75 per 1-point decrease, 95% CI: 0.61–0.87, p < 0.001), and time from onset to groin puncture ≥300 min (OR: 2.45, 95% CI: 0.91–6.85, p = 0.047).

Table 2.

Baseline characteristics between the sICH group and no sICH group

Multivariate analysis identified the following independent predictors of sICH: systolic BP (OR per 1 mmg Hg increase: 1.03, 95% CI: 1.02–1.05, p < 0.001), blood glucose (OR per 1 mmol/L increase: 1.17, 95% CI: 1.07–1.29, p = 0.001), ASPECT score (OR: 0.79 per 1-point decrease, 95% CI: 0.70–0.93, p = 0.005), and time from onset to groin puncture ≥300 min (OR: 2.07, 95% CI: 1.12-0.5.09, p = 0.044). These factors remained significantly associated with sICH presence after applying cut-offs for systolic BP (≥145 mm Hg), glucose (≥8.8 mmol/L) [13], and ASPECT score (0–5, 6–8, and 9–10) [9] (Table 3).

Table 3.

Multivariate analysis of characteristics of AIS patients treated with MT to identify independent predictors of sICH

Development of the STBA Score

Based on the multivariate analysis, we constructed the STBA score based on systolic BP at admission, time from AIS until groin puncture, blood glucose, and the Alberta Stroke Program Early Computed Tomography score at admission. To facilitate the use of the scoring system, we categorized ASPECT scores as low (0–5), medium (6–8), or high (9–10). The range of possible STBA values was 0–6 (Table 4). Higher STBA scores independently predicted a higher risk of sICH: logistic regression showed that a 1-point increase in the STBA score was associated with an OR of 3.03 for sICH (95% CI: 2.09–4.39, p < 0.001).

Table 4.

As an additional assessment of the ability of the STBA score to predict sICH, we determined AUCs. The AUC of the STBA score for the prediction of sICH was 0.858 (0.805–0.911) (Fig. 1).

Fig. 1.

a, b Analysis of receiver operating characteristic curves to assess the ability of STBA score and TAG score to predict sICH in AIS patients treated with mechanical embolectomy in the derivation and validation cohorts.

Validation of the STBA Score

To confirm the reliability of the STBA score, we applied it to an independent validation cohort. The AUC of the STBA score in the validation cohort was 0.814 (0.637–0.992) for the prediction of sICH (Fig. 1). Higher STBA score was associated with higher risk of sICH (OR per unit increase: 1.91, 95% CI: 1.20–3.04, p = 0.006).

Validation of the TAG Score

To benchmark the performance of our STBA score, we also assessed the performance of the previously described TAG score against both of our patient samples. AUCs for the TAG score to predict sICH were 0.728 (95% CI: 0.643–0.814) in the derivation cohort (Fig. 1a) and 0.749 (95% CI: 0.589–0.909) in the validation cohort (Fig. 1b). Logistic regression showed that a 1-point increase in the TAG score was associated with increased risk of sICH, with an OR of 1.50 (95% CI: 1.49–1.81, p < 0.001) in the derivation cohort and 1.81 (95% CI: 1.15–2.84, p = 0.01) in the validation cohort.

Discussion

Here, we present the development of a scoring system with good specificity and sensitivity for the prediction of sICH after AIS treatment with mechanical embolectomy in Asian patients. Predicting the risk of sICH at admission may help clinicians optimize treatment. The proposed STBA score includes four parameters that are easy to assess without specific training: systolic BP, time from onset to groin puncture, blood glucose, and ASPECT score. The new score showed good discriminatory power for predicting sICH, with AUCs exceeding 0.81. The previously proposed TAG score, validated in Caucasians, did not predict sICH as well as the STBA score in Asian AIS patients treated with mechanical embolectomy.

Among Asian patients, the prevalence of intracranial atherosclerosis appears to be higher than that of extracranial arterial stenosis. In China, intracranial atherosclerosis occurs in 33–50% of ischemic strokes [14]. Our study found a prevalence of 37% for large artery atherosclerosis. Atherosclerotic occlusion may be more difficult to recanalize than a cardioembolic one because atherosclerotic occlusion is usually accompanied by severe stenosis. One multicenter study in China found that sICH occurred in 16.0% patients, which may be attributed to the higher proportion of intracranial atherosclerotic stenosis among Asian patients [14]. The clinical features of sICH may differ among Asian, white, black, and Hispanic populations due to genetic differences. Thus, the STBA score may help improve the treatment and management of Asian patients with AIS.

The four components of the STBA score have previously been linked to outcomes after acute ischemic injury. The ASPECT score is an imaging measure of ischemic injury in the brain, and it can reliably predict clinical outcomes [11]. In fact, consistent with the present study, previous work has shown ASPECT score at admission to be independently associated with sICH [9]. Time from stroke onset to groin puncture has been shown to predict sICH [5, 14], reflecting the generally worse prognosis with longer delays in treatment [15]. Blood glucose and history of diabetes mellitus at admission have been associated with poor clinical outcomes and increased risk of sICH in patients treated by intra-arterial therapy [16-19]. Several mechanisms have been proposed to explain how higher glucose might increase risk of sICH. Hyperglycemia is associated with larger infarct volume. Hyperglycemia after mechanical embolectomy may compromise the blood-brain barrier and cerebrovascular reactivity in the microvasculature, or it may increase cortical acidosis [20-23]. Hypertension is independently associated with higher risk of sICH [24, 25]. Following ischemia, cerebral autoregulation is frequently impaired, and cerebral blood flow is sensitive to changes in systemic BP [25]. Persistent hypertension during reperfusion may also aggravate blood-brain barrier damage [25].

In both of our Chinese patient cohorts, the TAG score, which is based on TICI, ASPECT score, and glucose level, performed worse than the STBA score at predicting sICH. Another disadvantage of the TAG score is that it cannot be assessed at admission because TICI is an index of post-treatment recanalization. Moreover, successful recanalization can depend strongly on surgical technique and experience, which can make the scoring less reliable. Thus, the STBA score may have several advantages over the TAG score for predicting risk of sICH in Asian AIS patients treated with mechanical embolectomy.

Our study presents some limitations. We did not consider some factors with potential prognostic value, such as treatment or follow-up neuroimaging because they cannot be assessed at admission, or they may require complicated assessment procedures. Second, our cohorts included relatively small numbers of only Chinese patients from two hospitals. Therefore, the STBA score needs to be validated in larger and non-Asian cohorts.

Despite these limitations, our study provides evidence that the STBA score can reliably predict sICH in Chinese patients after mechanical embolectomy. If the score can be validated in larger cohorts from various ethnic groups, it may prove effective for personalizing the treatment and management of AIS patients and perhaps even for preventing sICH.

Statement of Ethics

This study protocol was reviewed and approved by the Scientific Research Department of First Affiliated Hospital of Kunming Medical University, and approval number was 2018B125. The requirement for patient consent was waived because of the retrospective nature of this study as well as the minimal risk that it posed to participants.

Conflict of Interest Statement

None of the authors had any conflict of interest with any pharmaceutical companies or organizations in carrying out this study.

Funding Sources

This study was supported by National Natural Science Foundation of China (82060230), Yunnan Training Project for High-Level Talents (RLQB20200003), and middle-aged academic and technical Training Project for High-Level Talents (202105AC160065).

Author Contributions

Chunyan Lei designed the subject. Yongyu Li, Xianlian Zhou, Shihan Lin, and Xiaoyan Zhu collected and extracted data for the article. Xinglong Yang and Chun Chen revised the important intellectual content. Chunyan Lei approved the final version of the manuscript.

Data Availability Statement

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

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