Cardiovascular Safety of COVID-19 Vaccination in Patients With Cancer: A Self-Controlled Case Series Study in Korea.

BACKGROUND: Cancer patients have an increased risk of cardiovascular outcomes and are susceptible to coronavirus disease 2019 (COVID-19) infection. We aimed to assess the cardiovascular safety of COVID-19 vaccination for cancer patients in South Korea. METHODS: We conducted a self-controlled case series study using the K-COV-N cohort (2018-2021). Patients with cancer aged 12 years or older who experienced cardiovascular outcomes were identified. Cardiovascular outcomes were defined as myocardial infarction, stroke, venous thromboembolism (VTE), myocarditis, or pericarditis, and the risk period was 0-28 days after receiving each dose of COVID-19 vaccines. A conditional Poisson regression model was used to calculate the incidence rate ratio (IRR) with 95% confidence interval (CI). RESULTS: Among 318,105 patients with cancer, 4,754 patients with cardiovascular outcomes were included. The overall cardiovascular risk was not increased (adjusted IRR, 0.99 [95% CI, 0.90-1.08]) during the whole risk period. The adjusted IRRs of total cardiovascular outcomes during the whole risk period according to the vaccine type were 1.07 (95% CI, 0.95-1.21) in the mRNA vaccine subgroup, 0.99 (95% CI, 0.83-1.19) in the ChAdOx1 nCoV-19 vaccine subgroup, and 0.86 (95% CI, 0.68-1.10) in the mix-matched vaccination subgroup. However, in the analysis of individual outcome, the adjusted IRR of myocarditis was increased to 11.71 (95% CI, 5.88-23.35) during the whole risk period. In contrast, no increased risk was observed for other outcomes, such as myocardial infarction, stroke, VTE, and pericarditis. CONCLUSION: For cancer patients, COVID-19 vaccination demonstrated an overall safe profile in terms of cardiovascular outcomes. However, caution is required as an increased risk of myocarditis following COVID-19 vaccination was observed in this study.

Coagulation Factor Expression and Composition of Arterial Thrombi in Cancer-Associated Stroke.

BACKGROUND: Cancer is associated with an increased risk of stroke. Tumor cells activate platelets, induce a coagulation cascade, and generate thrombin. The composition of thrombi may reflect the mechanism of thrombosis, aiding the determination of the treatment strategy. Here, we investigated the composition and expression of coagulation factors in the thrombi of patients with cancer-associated stroke. METHODS: Patients with stroke who underwent endovascular thrombectomy between September 2014 and June 2020 and whose cerebral thrombi were obtained were divided into those with cancer-associated stroke (cancer group) and propensity score-matched patients without cancer (control group), using 1:1 matching based on age and sex. Immunohistochemistry was performed of the thrombi, and the composition and expression of coagulation factors were compared between groups. RESULTS: Among the 320 patients who underwent endovascular thrombectomy and who had thrombi obtained, this study included 23 patients with cancer and 23 matched controls. In both groups, the median age was 65 years, and 12 patients (52.2%) were men. Platelet composition was significantly higher in the cancer group than in the control group (median [interquartile range], 51.3% [28.0%-61.4%] versus 9.5% [4.8%-14.0%]; P<0.001). Among coagulation factors, thrombin (26.2% [16.2%-52.7%] versus 4.5% [1.3%-7.2%]; P<0.001) and tissue factors (0.60% [0.34%-2.06%] versus 0.37% [0.22%-0.60%]; P=0.024) were higher and factor X was lower (1.25% [0.39%-3.60%] versus 2.33% [1.67%-4.48%]; P=0.034) in the cancer group. There was a positive correlation between thrombin and platelets in the cancer group (r=0.666; P=0.001) but not in the control group (r=-0.167; P=0.627). CONCLUSIONS: Cerebral thrombi in patients with cancer-associated stroke showed higher proportions of platelets, thrombin, and tissue factors, suggesting their key roles in arterial thrombosis in cancer and providing a therapeutic perspective for preventing stroke in patients with cancer-associated stroke.

Cancer Prediction With Machine Learning of Thrombi From Thrombectomy in Stroke: Multicenter Development and Validation.

BACKGROUND: We aimed to develop and validate machine learning models to diagnose patients with ischemic stroke with cancer through the analysis of histopathologic images of thrombi obtained during endovascular thrombectomy. METHODS: This was a retrospective study using a prospective multicenter registry which enrolled consecutive patients with acute ischemic stroke from South Korea who underwent endovascular thrombectomy. This study included patients admitted between July 1, 2017 and December 31, 2021 from 6 academic university hospitals. Whole-slide scanning was performed for immunohistochemically stained thrombi. Machine learning models were developed using transfer learning with image slices as input to classify patients into 2 groups: cancer group or other determined cause group. The models were developed and internally validated using thrombi from patients of the primary center, and external validation was conducted in 5 centers. The model was also applied to patients with hidden cancer who were diagnosed with cancer within 1 month of their index stroke. RESULTS: The study included 70 561 images from 182 patients in both internal and external datasets (119 patients in internal and 63 in external). Machine learning models were developed for each immunohistochemical staining using antibodies against platelets, fibrin, and erythrocytes. The platelet model demonstrated consistently high accuracy in classifying patients with cancer, with area under the receiver operating characteristic curve of 0.986 (95% CI, 0.983-0.989) during training, 0.954 (95% CI, 0.937-0.972) during internal validation, and 0.949 (95% CI, 0.891-1.000) during external validation. When applied to patients with occult cancer, the model accurately predicted the presence of cancer with high probabilities ranging from 88.5% to 99.2%. CONCLUSIONS: Machine learning models may be used for prediction of cancer as the underlying cause or detection of occult cancer, using platelet-stained immunohistochemical slide images of thrombi obtained during endovascular thrombectomy.

Impact of statin treatment on cardiovascular risk in patients with type 1 diabetes: a population-based cohort study.

BACKGROUND: Cardiovascular disease (CVD) is a major complication in type 1 diabetes mellitus (T1D) patients. Previous studies have suggested that statins may be helpful for prevention of CVD in T1D, but there are limited data on the role of statins in T1D. We investigated the relationship between statin treatment and cardiovascular risk in T1D patients using a population-based cohort. METHODS: We conducted a retrospective cohort study using the Korean nationwide health insurance database from January 2007 to December 2017. This study included 11,009 T1D patients aged ≥ 20 years without a prior history of CVD. The primary outcome was a composite development of stroke or myocardial infarction. Statin use during follow-up was treated as a time-varying variable. We performed a multivariable time-dependent Cox regression analysis adjusting for sex, age, type of insurance, hypertension, renal disease, and use of antiplatelets and renin-angiotensin-aldosterone system inhibitors. RESULTS: During the mean follow-up of 9.9 ± 3.7 years of follow-up, 931 T1D patients (8.5%) suffered primary outcome. Statin treatment was associated with a reduced risk of the primary outcome (adjusted hazard ratio, 0.76; 95% confidence interval 0.66-0.88; p < 0.001). Statin use led to decreased risks of ischemic stroke and myocardial infarction, but was not related to hemorrhagic stroke. We also found that the risk of cardiovascular events decreased as the cumulative exposure duration of statins increased. CONCLUSIONS: Statin use was associated with a lower risk of cardiovascular events in T1D patients. Further prospective studies are needed to confirm the potential role of statins in prevention of CVD in patients with T1D.

Lobeglitazone, a novel thiazolidinedione, for secondary prevention in patients with ischemic stroke: a nationwide nested case-control study.

INTRODUCTION: Ischemic stroke patients with diabetes are at high risk for recurrent stroke and cardiovascular complications. Pioglitazone, a type of thiazolidinedione, has been shown to reduce cardiovascular complications in patients with ischemic stroke and type 2 diabetes (T2D) or insulin resistance. Lobeglitazone is a novel thiazolidinedione agent that improves insulin resistance and has similar glycemic efficacy to pioglitazone. Using population-based health claims data, we evaluated whether lobeglitazone has secondary cardiovascular preventive effects in patients with ischemic stroke and T2D. METHODS: This study has a nested case-control design. From nationwide health claims data in Korea, we identified patients with T2D admitted for acute ischemic stroke in 2014-2018. Cases were defined who suffered the primary outcome (a composite of recurrent stroke, myocardial infarction, and all-cause death) before December 2020. Three controls were selected by incidence density sampling for each case from those who were at risk at the time of their case occurrence with exact matching on sex, age, the presence of comorbidities, and medications. As a safety outcome, we also evaluated the risk of heart failure (HF) according to the use of lobeglitazone. RESULTS: From the cohort of 70,897 T2D patients with acute ischemic stroke, 20,869 cases and 62,607 controls were selected. In the multivariable conditional logistic regression, treatment with lobeglitazone (adjusted OR 0.74; 95% CI 0.61-0.90; p = 0.002) and pioglitazone (adjusted OR 0.71; 95% CI 0.64-0.78; p < 0.001) were significantly associated with a lower risk for the primary outcome. In a safety outcome analysis for HF, treatment with lobeglitazone did not increase the risk of HF (adjusted OR 0.90; 95% CI 0.66-1.22; p = 0.492). CONCLUSIONS: In T2D patients with ischemic stroke, lobeglitazone reduced the risk of cardiovascular complications similar to that of pioglitazone without an increased risk of HF. There is a need for further studies on the cardioprotective role of lobeglitazone, a novel thiazolidinedione.

Intensive vs Conventional Blood Pressure Lowering After Endovascular Thrombectomy in Acute Ischemic Stroke: The OPTIMAL-BP Randomized Clinical Trial.

Importance: Optimal blood pressure (BP) control after successful reperfusion with endovascular thrombectomy (EVT) for patients with acute ischemic stroke is unclear. Objective: To determine whether intensive BP management during the first 24 hours after successful reperfusion leads to better clinical outcomes than conventional BP management in patients who underwent EVT. Design, Setting, and Participants: Multicenter, randomized, open-label trial with a blinded end-point evaluation, conducted across 19 stroke centers in South Korea from June 2020 to November 2022 (final follow-up, March 8, 2023). It included 306 patients with large vessel occlusion acute ischemic stroke treated with EVT and with a modified Thrombolysis in Cerebral Infarction score of 2b or greater (partial or complete reperfusion). Interventions: Participants were randomly assigned to receive intensive BP management (systolic BP target <140 mm Hg; n = 155) or conventional management (systolic BP target 140-180 mm Hg; n = 150) for 24 hours after enrollment. Main Outcomes and Measures: The primary outcome was functional independence at 3 months (modified Rankin Scale score of 0-2). The primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and death related to the index stroke within 3 months. Results: The trial was terminated early based on the recommendation of the data and safety monitoring board, which noted safety concerns. Among 306 randomized patients, 305 were confirmed eligible and 302 (99.0%) completed the trial (mean age, 73.0 years; 122 women [40.4%]). The intensive management group had a lower proportion achieving functional independence (39.4%) than the conventional management group (54.4%), with a significant risk difference (-15.1% [95% CI, -26.2% to -3.9%]) and adjusted odds ratio (0.56 [95% CI, 0.33-0.96]; P = .03). Rates of symptomatic intracerebral hemorrhage were 9.0% in the intensive group and 8.1% in the conventional group (risk difference, 1.0% [95% CI, -5.3% to 7.3%]; adjusted odds ratio, 1.10 [95% CI, 0.48-2.53]; P = .82). Death related to the index stroke within 3 months occurred in 7.7% of the intensive group and 5.4% of the conventional group (risk difference, 2.3% [95% CI, -3.3% to 7.9%]; adjusted odds ratio, 1.73 [95% CI, 0.61-4.92]; P = .31). Conclusions and Relevance: Among patients who achieved successful reperfusion with EVT for acute ischemic stroke with large vessel occlusion, intensive BP management for 24 hours led to a lower likelihood of functional independence at 3 months compared with conventional BP management. These results suggest that intensive BP management should be avoided after successful EVT in acute ischemic stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT04205305.

Impact of Renal Function on Short-Term Outcome After Reperfusion Therapy in Patients With Ischemic Stroke.

BACKGROUND: A high and low estimated glomerular filtration rate (eGFR) could affect outcomes after reperfusion therapy for ischemic stroke. This study aimed to determine whether renal function based on eGFR affects mortality risk in patients with ischemic stroke within 6 months following reperfusion therapy. METHODS: This prospective registry-based cohort study included 2266 patients who received reperfusion therapy between January 2000 and September 2019 and were registered in the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) study or the Yonsei Stroke Cohort. A high and low eGFR were based on the Chronic Kidney Disease Epidemiology Collaboration equation and defined, respectively, as the 5th and 95th percentiles of age- and sex-specific eGFR. Occurrence of death within 6 months was compared among the groups according to their eGFR such as low, normal, or high eGFR. RESULTS: Of the 2266 patients, 2051 (90.5%) had a normal eGFR, 110 (4.9%) a low eGFR, and 105 (4.6%) a high eGFR. Patients with high eGFR were younger or less likely to have hypertension, diabetes, or atrial fibrillation than the other groups. Active cancer was more prevalent in the high-eGFR group. During the 6-month follow-up, there were 24 deaths (22.9%) in the high-eGFR group, 37 (33.6%) in the low-eGFR group, and 237 (11.6%) in the normal-eGFR group. After adjusting for variables with P<0.10 in the univariable analysis, 6-month mortality was independently associated with high eGFR (hazard ratio, 2.22 [95% CI, 1.36-3.62]; P=0.001) and low eGFR (HR, 2.29 [95% CI, 1.41-3.72]; P=0.001). These associations persisted regardless of treatment modality or various baseline characteristics. CONCLUSIONS: High eGFR as well as low eGFR were independently associated with 6-month mortality after reperfusion therapy. Kidney function could be considered a prognostic factor in patients with ischemic stroke after reperfusion therapy.

Proton Pump Inhibitors and Risk of Cardiovascular Disease: A Self-Controlled Case Series Study.

INTRODUCTION: We investigated cardiovascular risk due to proton pump inhibitor (PPI) treatment using a self-controlled case series (SCCS) study design, a type of case-only design and an approach to overcome between-person confounding in which individuals act as their own control. METHODS: We conducted an SCCS study using the National Health Insurance Service-Health Screening cohort in Korea (2002-2015). The cohort included 303,404 adult participants without prior cardiovascular events, who were followed up until December 2015. The primary outcome was a composite of stroke or myocardial infarction. The SCCS method estimated the age-adjusted incidence rate ratio between periods with and without exposure to PPI among patients with primary outcomes. As sensitivity analysis, conventional multivariable Cox proportional regression analyses were performed, which treated the exposure to PPI and H2 blocker during follow-up as time-dependent variables. RESULTS: In the SCCS design, 10,952 (3.6%) patients with primary outcomes were included. There was no association between PPI exposure and primary outcome (incidence rate ratio 0.98, 95% confidence interval [CI] 0.89-1.09). In the time-dependent Cox regression analyses, both PPI (adjusted hazard ratio 1.36, 95% CI 1.24-1.49) and H2 blocker (adjusted hazard ratio 1.46, 95% CI 1.38-1.55) were associated with an increased risk of the primary outcome. DISCUSSION: Negative findings in the SCCS design suggest that association between increased cardiovascular risk and PPI, frequently reported in prior observational studies, is likely due to residual confounding related to conditions with PPI treatment, rather than a true relationship.

Immediate and Long-Term Outcomes of Reperfusion Therapy in Patients With Cancer.

Background and Purpose: Patients with acute stroke are often accompanied by comorbidities, such as active cancer. However, adequate treatment guidelines are not available for these patients. The purpose of this study was to evaluate the association between cancer and the outcomes of reperfusion therapy in patients with stroke. Methods: We compared treatment outcomes in patients who underwent reperfusion therapy, using a nationwide reperfusion therapy registry. We divided the patients into 3 groups according to cancer activity: active cancer, nonactive cancer, and without a history of cancer. We investigated reperfusion processes, 24-hour neurological improvement, adverse events, 3-month functional outcome, and 6-month survival and related factors after reperfusion therapy. Results: Among 1338 patients who underwent reperfusion therapy, 62 patients (4.6%) had active cancer, 78 patients (5.8%) had nonactive cancer, and 1198 patients (89.5%) had no history of cancer. Of the enrolled patients, 969 patients received intravenous thrombolysis and 685 patients underwent endovascular treatment (316 patients received combined therapy). Patients with active cancer had more comorbidities and experienced more severe strokes; however, they showed similar 24-hour neurological improvement and adverse events, including cerebral hemorrhage, compared with the other groups. Although the functional outcome at 3 months was poorer than the other groups, 36.4% of patients with active cancer showed functional independence. Additionally, 52.9% of the patients with determined stroke etiology showed functional independence despite active cancer. During the 6-month follow-up, 46.6% of patients with active cancer died, and active cancer was independently associated with poor survival (hazard ratio, 3.973 [95% CI, 2.528­6.245]). Conclusions: In patients with active cancer, reperfusion therapy showed similar adverse events and short-term outcomes to that of other groups. While long-term prognosis was worse in the active cancer group than the nonactive cancer groups, not negligible number of patients had good functional outcomes, especially those with determined stroke mechanisms.

Clinical prognosis of isolated anterior cerebral artery territory infarction: a retrospective study.

BACKGROUND: Isolated anterior cerebral artery territory (ACA) infarction is a rare phenomenon, and is known to have distinctive clinical features. Little is known regarding the clinical prognosis of isolated ACA territory infarction with associated factors, and its impact on dwelling and job status. We investigated the short- and long-term outcomes of anterior cerebral artery (ACA) territory infarction, and the associated factors involved in the development of the distinctive symptoms. METHODS: This retrospective study in a prospective cohort of acute ischaemic stroke patients included consecutively enrolled patients with isolated ACA territory infarction. We investigated the functional status using the modified Rankin scale (mRS) score at discharge, three months' post-discharge, and one-year post-discharge. We also investigated the occlusion site of the ACA (proximal vs. distal); presence of distinctive symptoms of ACA territory infarction including behaviour changes, indifference, aphasia, and urinary incontinence; and the effect of these symptoms on dwelling and job status one year after discharge. RESULTS: Between April 2014 and March 2019, 47 patients with isolated ACA territory infarction were included. Twenty-nine patients (61.7 %) had good outcomes (mRS ≤ 2) at discharge; however, the mRS score increased at three months (40; 85.1 %, p < 0.001) and one year (41; 87.2 %) post-discharge. Occlusion of the ACA proximal segment was independently associated with the development of distinctive symptoms (adjusted odds ratio, 17.68; 95 % confidence interval: 2.55-122.56, p < 0.05). Twenty-one (48.8 %) patients with good outcomes at one year experienced a change in dwelling status and job loss; 20 (95.2 %) of them had distinctive ACA territory symptoms with proximal ACA occlusion. CONCLUSIONS: Short- and long-term outcomes of isolated ACA territory infarction were favourable. However, proximal segment occlusion was associated with the development of distinctive symptoms, possibly related to future dwelling and job status.

Predicting Endovascular Treatment Outcomes in Acute Vertebrobasilar Artery Occlusion: A Model to Aid Patient Selection from the ASIAN KR Registry.

Background The decision to perform endovascular treatment (EVT) for stroke related to vertebrobasilar occlusion (VBO) remains controversial. Purpose To identify preprocedural predictors of good outcomes and to develop a model to aid patient selection for VBO. Materials and Methods For this retrospective study using a Korean multicenter registry, a predictive model for good outcomes (modified Rankin scale score, 0-2) was generated based on a derivation sample of patients with VBO (January 2011-February 2016). Preprocedural parameters, including onset-to-puncture time, infarct volume, occlusion type as a surrogate marker of intracranial atherosclerotic stenosis-related occlusion or embolic occlusion (truncal-type occlusion vs branching site occlusion), and collateral status, were analyzed. Continuous variables were dichotomized based on receiver operating characteristic analysis. Multiple logistic regression analysis was performed to generate a predictive model. The model was internally validated with the bootstrap method and was externally validated with a single-center sample (April 2016-December 2018). Results A predictive model was generated from 71 patients (mean age, 67 years ± 11 [standard deviation]; 41 [58%] men) and was externally validated in 32 patients (mean age, 72 years ± 13; 19 [59%] men). The composite of initial DW imaging volume of less than 10 mL (odds ratio [OR], 19.3; 95% confidence interval [CI]: 3.0, 126.4; P = .002), onset-to-puncture time of less than 8 hours (OR, 8.7; 95% CI: 1.8, 42.0; P = .007), and branching-site occlusion (OR, 6.1; 95% CI: 1.5, 26.0; P = .01) could be used to predict good outcomes, with a median area under the receiver operating characteristic curve of 0.86 (interquartile range [IQR], 0.77-0.95; bootstrap optimism-corrected C statistic, 0.837) in the derivation sample and 0.78 (IQR, 0.62-0.95) in the validation sample. Results failed to show an association between collateral status and outcome (P = .67). Conclusion When selecting patients with vertebrobasilar occlusion for endovascular treatment, the combination of onset-to-puncture time of less than 8 hours, initial infarct volume of less than 10 mL, and presence of branching-site occlusions is indicative of a good outcome. © RSNA, 2020 Online supplemental material is available for this article.

Histological features of intracranial thrombi in stroke patients with cancer.

The histological features of thrombus in stroke patients with cancer are not well known. Using immunohistochemical staining of thrombi retrieved during mechanical thrombectomy in stroke patients, thrombus compositions were compared between 16 patients with active cancer, 16 patients with inactive cancer, and 16 patients without any history of cancer. The active cancer group showed higher platelet and lower erythrocyte fractions than the inactive cancer or the control group. Four patients with vegetation showed very high platelet and low erythrocyte fractions. Patients with cryptogenic etiology in the active cancer group showed a similar pattern to those with vegetation. These findings may aid the determination of treatment strategies in cancer-associated stroke. ANN NEUROL 2019.

Local tirofiban infusion for remnant stenosis in large vessel occlusion: tirofiban ASSIST study.

BACKGROUND: Compared with embolic occlusions, intracranial atherosclerotic stenosis (ICAS)-related large vessel occlusions (LVOs) often require rescue treatment following mechanical thrombectomy (MT). Herein, we hypothesized that local tirofiban infusion can be effective and safe for remnant stenosis in LVO during endovascular treatment and can improve clinical outcomes. METHODS: This observational multicenter registry study (January 2011 to February 2016) included patients with ICAS who underwent endovascular treatment for LVO within 24 h after stroke onset. An underlying fixed focal stenosis at the occlusion site observed on cerebral angiography during and after MT was retrospectively determined as a surrogate marker of ICAS. Procedural and clinical outcomes were compared between the tirofiban and non-tirofiban groups. RESULTS: Of 118 patients, 59 received local tirofiban infusion. Compared to the non-tirofiban group, patients were older (non-tirofiban group versus tirofiban group; median, 63 years vs. 71 years, p = 0.015) and the onset-to-puncture time was longer (median, 275 min vs. 395 min, p = 0.036) in the tirofiban group. The median percent of residual stenosis prior to rescue treatment tended to be higher in the tirofiban group (80 [71-86] vs. 83 [79-90], p = 0.056). Final reperfusion success (modified Treatment In Cerebral Ischemic 2b-3) was more frequent (42.4%vs. 86.4%, p = 0.016) and post-procedure parenchymal hematoma type 2 and/or thick subarachnoid hemorrhages were less frequent (15.3%vs. 5.1%, p = 0.068) in the tirofiban group. The frequency of favorable outcomes 3 months after endovascular treatment (modified Rankin Scale 0-2) was significantly higher in the tirofiban group (32.2% vs. 52.5%, p = 0.025), and tirofiban administration was an independent predictor of favorable outcomes (odds ratio, 2.991; 95% confidence interval, 1.011-8.848; p = 0.048). CONCLUSIONS: Local tirofiban infusion can be a feasible adjuvant treatment option for patients with ICAS-LVO.

Immediate effects of first-line thrombectomy devices for intracranial atherosclerosis-related occlusion: stent retriever versus contact aspiration.

BACKGROUND: Although stent retriever (SR) is recommended as a frontline device of endovascular treatment (EVT) for embolic large artery occlusion causing acute ischemic stroke, contact aspiration (CA) device showed similar efficacy in the recent trials. However, the efficacy of the both devices as first-line therapy for intracranial atherosclerotic stenosis (ICAS)-related large vessel occlusion has not yet been established. Therefore, we compared the immediate effects and final outcomes of SR and CA as first-line devices for treating ICAS-related occlusions. METHODS: We retrospectively analyzed the data of patients who underwent EVT for acute ischemic stroke from the registry of three Korean hospitals. Patients with ICAS-related occlusion who were treated within 24 h of onset of the symptoms were included. We investigated immediate reperfusion performance, immediate safety outcomes, and 3-month clinical outcomes for the two first-line devices. RESULTS: Of the 720 registered patients, 111 were eligible for this study. Forty-nine patients (44.1%) used SR and 62 (55.9%) used CA as the first-line device. Achieving successful reperfusion immediately after first-line thrombectomy was more frequent in the SR group than that in the CA group (77.6% vs. 43.5%, p = 0.001), with fewer additional rescue treatments (12.2% vs. 59.7%, p < 0.001). The incidence of iatrogenic dissection or rupture was lower in the SR group than that in the CA group (8.2% vs. 29.0%, p = 0.012). After additional rescue treatments, however, the final successful reperfusion rate did not differ between the two groups (SR 87.8% vs. CA 77.4%, p = 0.247), and there was no significant difference in the 3-month good outcomes (modified Rankin Scale, p = 0.524). CONCLUSIONS: First-line SR thrombectomy showed higher immediate reperfusion and less vessel injury for ICAS-related occlusions than CA. However, there was no significant difference in the final reperfusion status or 3-month outcomes from additional rescue treatments.

Short-Term Outcome of Ischemic Stroke Patients With Systemic Malignancy.

Background and Purpose- Recent guidelines have suggested the potential benefit of intravenous thrombolysis in stroke patients with systemic malignancy who have a reasonable life expectancy of >6 months. However, it is difficult to determine which patients with cancer will have a life expectancy of >6 months. Therefore, we identified the factors associated with 6-month mortality in patients with acute ischemic stroke and systemic malignancy. Methods- Consecutive stroke patients with systemic malignancy were retrospectively analyzed. We classified the patients into 3 groups: the nonactive cancer, active nonmetastatic cancer, and metastatic cancer groups. We compared the baseline characteristics and 6-month survival rates. Results- Of the 468 ischemic stroke patients with systemic malignancy during an 8-year period, 223 patients had nonactive cancer, 105 patients had active nonmetastatic cancer, and 140 patients had metastasis. During the 6-month follow-up, 122 patients (26.1%) died (nonactive cancer group [7.2%, 16/223], active nonmetastatic cancer group [11.4%, 12/105], and metastatic cancer group [67.1%, 94/140]). Multivariate Cox regression analysis revealed that the presence of metastasis (hazard ratio, 4.527; 95% CI, 2.175-9.422) was independently associated with 6-month mortality. However, the active nonmetastatic cancer group exhibited similar 6-month mortality to the nonactive cancer group (hazard ratio, 0.711; 95% CI, 0.282-1.795). Gastric/esophageal cancer and pancreatic cancer were also independently associated with 6-month mortality (hazard ratio, 2.068 and 2.389, respectively). Conclusions- In stroke patients with active cancer, the presence of metastasis and the cancer type were crucial factors associated with 6-month mortality.

Ischemic Diffusion Lesion Reversal After Endovascular Treatment.

Background and Purpose- Several studies have reported partial reversal of diffusion-weighted imaging (DWI) lesions after acute stroke reperfusion treatment. However, factors associated with DWI reversal have not yet been systematically investigated. We evaluated the factors associated with DWI reversal after endovascular treatment (EVT). Methods- We retrospectively analyzed consecutively encountered patients with acute ischemic stroke who underwent EVT at 3 comprehensive stroke centers in Korea from January 2011 to February 2016. Patients who received EVT within 24 hours of anterior circulation infarction and had both baseline and follow-up DWIs were included. DWI reversal was defined as a decrease in DWI volume from baseline to follow-up. We compared the characteristics and outcomes between patients with and without DWI reversal and assessed independent factors associated with DWI reversal. Results- Of 720 patients encountered during the time period, 404 patients (56.1%) met the study criteria, with 63 patients (15.5%) showing DWI reversal after EVT. The mean time interval between baseline and follow-up DWI was 4.7±2.4 days. Mean baseline DWI volumes of patients with and without DWI reversal were 30.1±36.7 versus 22.0±30.7 mL ( P=0.106), and follow-up DWI volumes were 17.8±24.9 versus 68.7±77.5 mL ( P<0.001). Patients with DWI reversal showed better functional outcomes at 3 months than those without DWI reversal (modified Rankin Scale [interquartile range], 1 [0-3] versus 2 [1-4]; P=0.001). In a multivariate analysis, complete reperfusion (odds ratio, 1.954; 95% CI, 1.063-3.582) and shorter time from baseline DWI to final reperfusion (odds ratio, 0.991; 95% CI, 0.983-0.998) were independently associated with DWI reversal. Conclusions- Complete reperfusion and shorter imaging time to recanalization were independently associated with DWI reversal among patients with acute ischemic stroke who received EVT.

Balloon Guide Catheter Is Beneficial in Endovascular Treatment Regardless of Mechanical Recanalization Modality.

Background and Purpose- Based on its mechanism, the use of balloon guide catheters (BGCs) may be beneficial during endovascular treatment, regardless of the type of mechanical recanalization modality used-stent retriever thrombectomy or thrombaspiration. We evaluated whether the use of BGCs can be beneficial regardless of the first-line mechanical endovascular modality used. Methods- We retrospectively reviewed consecutive acute stroke patients who underwent stent retriever thrombectomy or thrombaspiration from the prospectively maintained registries of 17 stroke centers nationwide. Patients were assigned to the BGC or non-BGC group based on the use of BGCs during procedures. Endovascular and clinical outcomes were compared between the BGC and non-BGC groups. To adjust the influence of the type of first-line endovascular modality on successful recanalization and favorable outcome, multivariable analyses were also performed. Results- This study included a total of 955 patients. Stent retriever thrombectomy was used as the first-line modality in 526 patients (55.1%) and thrombaspiration in 429 (44.9%). BGC was used in 516 patients (54.0%; 61.2% of stent retriever thrombectomy patients; 45.2% of thrombaspiration patients). The successful recanalization rate was significantly higher in the BGC group compared with the non-BGC group (86.8% versus 74.7%, respectively; P<0.001). Furthermore, the first-pass recanalization rate was more frequent (37.0% versus 14.1%; P<0.001), and the number of device passes was fewer in the BGC group (2.5±1.9 versus 3.3±2.1; P<0.001). The procedural time was also shorter in the BGC group (54.3±27.4 versus 67.6±38.2; P<0.001). The use of BGC was an independent factor for successful recanalization (odds ratio, 2.18; 95% CI, 1.54-3.10; P<0.001) irrespective of the type of first-line endovascular modality used. The use of BGC was also an independent factor for a favorable outcome (odds ratio, 1.40; 95% CI, 1.02-1.92; P=0.038) irrespective of the type of first-line endovascular modality used. Conclusions- Regardless of the first-line mechanical endovascular modality used, the use of BGC in endovascular treatment was beneficial in terms of both recanalization success and functional outcome.

Thrombus Volume as a Predictor of Nonrecanalization After Intravenous Thrombolysis in Acute Stroke.

Background and Purpose- We investigated whether measuring the volume and density of a thrombus could predict nonrecanalization after intravenous thrombolysis. Methods- This study included a retrospective cohort to develop a computed tomography marker of thrombus for predicting nonrecanalization after intravenous thrombolysis and a prospective multicenter cohort for validation of this marker. The volume and density of thrombus were measured semiautomatically using 3-dimensional software on a baseline thin-section noncontrast computed tomography (1 or 1.25 mm). Recanalization was assessed on computed tomography angiography or magnetic resonance angiography immediately after intravenous thrombolysis or conventional angiography in patients who underwent further intra-arterial treatment. Nonrecanalization was defined as a modified Thrombolysis in Cerebral Infarction grade 0, 1, 2a. Results- In the retrospective cohort, 162 of 214 patients (76.7%) failed to achieve recanalization. The thrombus volume was significantly larger in patients with nonrecanalization than in those with successful recanalization (149.5±127.6 versus 65.3±58.3 mm3; P<0.001). In the multivariate analysis, thrombus volume was independently associated with nonrecanalization ( P<0.001). The cutoff for predicting nonrecanalization was calculated as 200 mm3. In the prospective multicenter validation study, none of the patients with a thrombus volume ≥200 mm3 among 78 enrolled patients achieved successful recanalization. The positive and negative predictive values were 95.5 and 29.4 in the retrospective cohort 100 and 23.3 in the prospective validation cohort, respectively. The thrombus density was not associated with nonrecanalization. Conclusions- Thrombus volume was predictive of nonrecanalization after intravenous thrombolysis. Measurement of thrombus volume may help in determining the recanalization strategy and perhaps identify patients suitable for direct endovascular thrombectomy.

Number of Stent Retriever Passes Associated With Futile Recanalization in Acute Stroke.

Background and Purpose- Stent retriever (SR) thrombectomy has become the mainstay of treatment of acute intracranial large artery occlusion. However, it is still not much known about the optimal limit of SR attempts for favorable outcome. We evaluated whether a specific number of SR passes for futile recanalization can be determined. Methods- Patients who were treated with a SR as the first endovascular modality for their intracranial large artery occlusion in anterior circulation were retrospectively reviewed. The recanalization rate for each SR pass was calculated. The association between the number of SR passes and a patient's functional outcome was analyzed. Results- A total of 467 patients were included. Successful recanalization by SR alone was achieved in 82.2% of patients. Recanalization rates got sequentially lower as the number of passes increased, and the recanalization rate achievable by ≥5 passes of the SR was 5.5%. In a multivariable analysis, functional outcomes were more favorable in patients with 1 to 4 passes of the SR than in patients without recanalization (odds ratio [OR] was 8.06 for 1 pass; OR 7.78 for 2 passes; OR 6.10 for 3 passes; OR 6.57 for 4 passes; all P<0.001). However, the functional outcomes of patients with ≥5 passes were not significantly more favorable than found among patients without recanalization (OR 1.70 with 95% CI, 0.42-6.90 for 5 passes, P=0.455; OR 0.33 with 0.02-5.70, P=0.445 for ≥6 passes). Conclusions- The likelihood of successful recanalization got sequentially lower as the number of SR passes increased. Five or more passes of the SR became futile in terms of the recanalization rate and functional outcomes.

Rescue Stenting for Failed Mechanical Thrombectomy in Acute Ischemic Stroke: A Multicenter Experience.

BACKGROUND AND PURPOSE: Effective rescue treatment has not yet been suggested in patients with mechanical thrombectomy (MT) failure. This study aimed to test whether rescue stenting (RS) improved clinical outcomes in MT-failed patients. METHODS: This is a retrospective analysis of the cohorts of the 16 comprehensive stroke centers between September 2010 and December 2015. We identified the patients who underwent MT but failed to recanalize intracranial internal carotid artery or middle cerebral artery M1 occlusion. Patients were dichotomized into 2 groups: patients with RS and without RS after MT failure. Clinical and laboratory findings and outcomes were compared between the 2 groups. It was tested whether RS is associated with functional outcome. RESULTS: MT failed in 148 (25.0%) of the 591 patients with internal carotid artery or middle cerebral artery M1 occlusion. Of these 148 patients, 48 received RS (RS group) and 100 were left without further treatment (no stenting group). Recanalization was successful in 64.6% (31 of 48 patients) of RS group. Compared with no stenting group, RS group showed a significantly higher rate of good outcome (modified Rankin Scale score, 0-2; 39.6% versus 22.0%; P=0.031) without increasing symptomatic intracranial hemorrhage (16.7% versus 20.0%; P=0.823) or mortality (12.5% versus 19.0%; P=0.360). Of the RS group, patients who had recanalization success had 54.8% of good outcome, which is comparable to that (55.4%) of recanalization success group with MT. RS remained independently associated with good outcome after adjustment of other factors (odds ratio, 3.393; 95% confidence interval, 1.192-9.655; P=0.022). Follow-up vascular imaging was available in the 23 (74.2%) of 31 patients with recanalization success with RS. The stent was patent in 20 (87.0%) of the 23 patients. Glycoprotein IIb/IIIa inhibitor was significantly associated with stent patency but not with symptomatic intracranial hemorrhage. CONCLUSIONS: RS was independently associated with good outcomes without increasing symptomatic intracranial hemorrhage or mortality. RS seemed considered in MT-failed internal carotid artery or middle cerebral artery M1 occlusion.