Acute ischemic stroke is the most common form, accounting for 80-85% of all strokes [1]. There have been many remarkable advances in imaging techniques as well as the endovascular intervention window being extended to 24 hours through the Dawn Trial [2]. However, acute ischemic stroke is still a very complex clinical emergency, with many difficulties in early diagnosis and timely intervention. Thrombolysis as well as endovascular intervention significantly increases the recanalization rate, but from there, the HT rate increases, negatively affecting stroke outcomes [3,4]. Therefore, finding valuable prognostic factors for HT is of more interest to researchers than ever, with the aim of predicting the risk of HT, thereby having appropriate treatment measures. Many factors have been proposed as positive indicators for HT prognosis. Some factors have high prognostic value, some have low prognostic value. In general, depending on the region and existing conditions, people have been, are and continue to find prognostic factors suitable for their patient groups. However, currently in Vietnam, studies on HT prognosis, especially using the HAT score in acute ischemic stroke patients receiving revascularization treatment are still limited. Therefore, we conducted this study with the aim of finding valuable factors to help predict HT in acute ischemic stroke patients receiving revascularization treatment.

Research Objects

Patients with acute ischemic stroke treated for recanalization at the Department of Cerebrovascular Diseases, People's Hospital 115 during the study period from December 2022 to February 2023 who meet the disease selection criteria will be included in the study.

Disease Selection Criteria       

• Patients diagnosed with acute stroke that meets the clinical diagnostic criteria of the World Health Organization.
• There is a computed tomography (CT) scan or magnetic resonance imaging (MRI) of the brain confirming acute ischemic stroke.
• Hospitalization within 24 hours after symptom onset.
• Patients treated with thrombolysis and/or endovascular intervention.

Exclusion Criteria:

• Patients with cerebral infarction who were transferred to surgery later.
• Patients with associated traumatic brain injury.
• Patients without a second imaging (CT scan or brain MRI) within 24 ± 6 hours after treatment intervention.
• Patients with unsatisfactory imaging.
• Patients who did not agree to participate in the study.

Research Methods

Research Design: Cross-sectional, descriptive, analytical, and prospective with longitudinal follow-up.

Sampling Technique: Non-probability

Sample Size: 220 cases

Data Collection Method       

• Within 24 hours of admission, patients were asked for their medical history, clinical and paraclinical information as necessary.
• Brain CT scan within the first 24 hours of admission, repeat the second time (brain CT scan or MRI) after 24 ± 6 hours after recanalization treatment.
• Brain HT assessment based on imaging within 24 ± 6 hours after recanalization treatment.
• Each patient has a research medical record, with a medical record number and saved in SPSS software.

Data Collection Tools: Including a questionnaire and a results recording table.

Data Processing: SPSS 22.0 software.

Data Analysis: The first step is univariate analysis, using Chi-square or Fisher test for qualitative variables and t-student test for quantitative variables. The second step is multivariate analysis, using logistic regression analysis to find variables that are independently correlated with HT when there are other variables present. ROC curve is used to determine sensitivity, specificity as well as find the best cut-off point of HAT scale for HT [5].

The study sample included 220 patients, with an average age of 63. Males accounted for 63.6%.

Clinical and Paraclinical Characteristics in the Study Sample

Table 1: Clinical and paraclinical characteristics in the study sample.

Characteristics of the Scales in the Research SampleTable 2:

Characteristics of the scales in the research sample.

Revascularization Treatments

Table 3: Revascularization treatments.

Rate of Hemorrhagic Transformation in the Study Sample

Table 4: Rate of hemorrhagic transformation in the study sample.

Classification of Hemorrhagic Transformation on Brain CT Scan According to ECASS 2

Figure 1: Classification of hemorrhagic transformation according to ECASS 2.

After univariate analysis, we identified HAT (< 2 and ≥ 2), NIHSS (< 15 and ≥ 15), ASPECT (< 8 and ≥ 8) and 11 other variables correlated with HT after 24 hours of revascularization intervention in patients with acute cerebral infarction, including: Age (< 60 and ≥ 60), smoking, hypertension, valvular heart disease, diabetes, heart rate (< 100 and ≥ 100), diastolic blood pressure (< 90 mmHg and ≥ 90mmHg), and conscious disorder. Cerebral artery hyperdense sign, blood glucose (≤ 11.1 mmol/L and > 11.1 mmol/L), red blood cells (≤ 5400000 and > 5400000). All 14 variables were fully surveyed on 220 patients in the study sample. Multivariate analysis was conducted for these 14 variables using binary logistic regression (enter method and forward conditional method). We found that cerebral artery hyperdense sign and HAT scale were 2 independent prognostic factors for HT.

Table 5: Regression analysis results using the Enter method.

Table 6: Results of regression analysis using the forward conditional method.

Selecting the HAT Cutoff Point for Hemorrhagic Transformation

Figure 2: ROC curve of HAT for hemorrhagic transformation.

Through the above graph and through calculating the highest Youden index, we determined the best cut-off point of HAT to be 2 and also determined the sensitivity to be 94.3%; specificity to be 90.8%; positive predictive value (HT) to be 91.1%.

Discussion of Hemorrhagic TransformationFrom the infarct site or outside the infarct site, blood spots or blood clots appear, called HT infarcts. Thus, in these patients, there is both ischemic stroke and hemorrhagic stroke. Often, large, symptomatic cerebral hemorrhages worsen the outcome of the stroke. There are clinical, paraclinical and treatment factors that increase the risk of cerebral hemorrhage after ischemic stroke. However, there are also cases where there are no risk factors for cerebral hemorrhage but HT still appears, due to excessive reperfusion or damage to the blood-brain barrier... In this study, we studied the rate, classification and correlation between clinical and paraclinical factors, some scales with HT.Our study results recorded a HT rate of 15.9%, similar to the results of Masaya Enomoto (15.2%) [6], Craig S Anderson (16.1%) [7]. Our HT rate results were also higher than the results of Georgios Trivgoulis (9.3%) But much lower than the results of Thang Huy Nguyen (33.6%), Peter J. Mitchell (21.5%), Katinka R. Van Kranendonk (46.4%) [8-11]. Unlike us, Georgios Trivgoulis et al. only selected patients with cerebral artery embolism with thrombolysis, while Thang Huy Nguyen et al., Peter J. Mitchell et al. only selected patients with large vessel embolism within the 6-hour window, Katinka R. V. K. et al. selected patients with both venous thrombolysis and/or endovascular intervention but the treatment window was 6 hours from the onset of the disease and HT was determined by machine.Among HT, we recorded the proportions of HT types according to ECASS 2 as: HI1 (14.5%), HI2 (17%), PH1 (31.4%), PH2 (37.1%). Meanwhile, author Katinka R. Van Kranendonk et al. recorded the proportions as: HI1 (34.2%), HI2 (32%), PH1 (16.2%), PH2 (17.6%). Compared to us, Katinka R. Van Kranendonk et al. had a higher HI proportion and conversely, a lower PH proportion. In addition to sampling errors, is there a difference in the technique of determining HT by machine and by hand? Another issue that needs to be discussed is symptomatic HT, because this classification has an impact on the adverse outcome of stroke. Not only parenchymal hematoma (PH) has symptomatic HT but also hemorrhagic infarction (HI) has symptomatic HT. We know that, in addition to the impact of the volume of the hemorrhage, there is also the impact of the infarct lesion as well as the midline shift that causes adverse clinical symptoms of stroke [11,12]. We determined symptomatic HT according to ECASS criteria. Our study results recorded a rate of symptomatic HT of 5.5%, similar to the results of Georgios Trivgoulis et al. (5.6%) and not statistically different (p>0.05) compared to the results of Overt A. Berkhemer et al. (7.7%) [12], Masaya Enomoto et al. (2.3%) [6]. Studies have shown that the rate of symptomatic HT is low, which is good news for patients with acute ischemic stroke who are treated with revascularization.

Discuss Factors Associated With Hemorrhagic Transformation

After univariate analysis, we identified 14 variables correlated with HT after 24 hours of revascularization intervention in patients with acute ischemic stroke as presented in the results section. Reviewing previous studies, we found that some domestic and foreign studies also found univariate factors associated with HT such as Michael Mazya (age), Zhihong Zhao (smoking), Magdy Selim (hypertension), Nicholas Ngiam (valvular heart disease), Masaya Enomoto (diabetes), Mikhail N. Kalinin (heart rate), Jie Li (Conscious disorder), Jie Zhang (Cerebral artery hyperdense sign), Elena Spronk (blood glucose), Jiacheng Sun (polycythemia), Elisabeth B. Marsh (NIHSS), Georgios Tsivgoulis (HAT), Nguyen Hai Anh (ASPECT) [6,8,13-23].Conducting multivariate analysis for these 14 variables using binary logistic regression, we determined that cerebral artery hyperdense sign and HAT are 2 independent prognostic factors for HT. Reviewing previous studies on HT prognosis with multivariate analysis, we found that the number of independent prognostic variables identified by the authors is different. For example, the Masaya Enomoto study6 had diabetes as an independent prognostic factor, Elisabeth B. Marsh (Kidney function, infarct volume), Taha Nisar (early cerebral infarction signs, mean blood pressure, blood glucose, HAT), Mikhail N. Kalinin1 (ASPECT, NIHSS, INR, atrial fibrillation, male, heart rate, cerebral artery hyperdense sign), Xiaozan Chang (Age, atrial fibrillation, NIHSS, time of stroke onset, thrombolysis drugs, early cerebral infarction signs) [7,24-26]. Thus, depending on the study design as well as the selection of variables included in the survey, each study has different independent HT prognostic variables. Our results further strengthen the independent prognostic role of cerebral artery hyperdense sign, especially the HAT score for HT. Together with the results of previous studies, we contribute to enriching the field of HT prognosis after ischemic stroke. Depending on the region with different conditions, different factors are applied for HT prognosis, contributing to solving clinical problems as well as evaluating the effectiveness of new treatment methods.

In patients with acute ischemic stroke treated with recanalization, the mean NIHSS was 12.3; mean ASPECT was 9.4 and mean HAT was 1.1. The rates of recanalization treatments: venous thrombolysis was 25.5%; endovascular intervention was 60.4%; bridging treatment was 14.1%. The rate of HT was 15.9%; of which symptomatic cerebral hemorrhage was 5.5%. There are 14 univariate factors associated with HT after 24 ± 6 hours of revascularization treatment in patients with acute ischemic stroke: HAT, NIHSS, ASPECT, age, smoking, hypertension, valvular heart disease, diabetes, heart rate, diastolic blood pressure, conscious disorder, cerebral artery hyperdense sign, blood glucose, and red blood cells. Cerebral artery hyperdense sign and especially HAT are 2 independent prognostic factors for HT. HAT ≥ 2 predicts patients with HT with a sensitivity of 94.3%; specificity of 90.8%; area under the curve of 96.5% and positive predictive value of 91.1%.

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