Katrina Hannah Dizon Ignacio

Background and aims: It is unclear if stroke occurring after cardiac procedures is more severe than stroke associated with cardiac conditions without procedures. We compared in-hospital acute ischemic stroke patients admitted with a cardiac diagnosis who did versus did not undergo cardiac procedures. Methods: In this retrospective cohort study, we analyzed adults with in-hospital stroke admitted with a primary cardiac diagnosis in Alberta (2018–2022). Patients were categorized into no prior cardiac procedure, cardiac procedure, or cardiac surgery within 30 days of stroke diagnosis. Multivariable logistic regression was used to assess associations between exposure groups and outcomes. Results: Among 499 patients (median age 70 years IQR [62–77], 36.7% women), 116 (23.2%) underwent a cardiac procedure, and 227 (45.5%) underwent cardiac surgery prior to stroke diagnosis. Median time from procedure to stroke diagnosis was 1.75 days (IQR 0.87–3.83). In-hospital mortality was 34.6%, 24.1% and 22.5% in patients with no prior procedure, cardiac procedures and cardiac surgery, respectively. After adjustment for age, sex, facility level and comorbidities, no significant differences were observed in mortality (cardiac procedure vs no procedure: aOR 0.73, 95% confidence interval (CI) 0.40–1.33; cardiac surgery vs no procedure: aOR 0.78, 95% CI 0.42–1.45). Among procedural patients, strokes recognized ≥2 days post-procedure were associated with higher mortality (2–7 days: OR 2.31, [1.18–4.52]; 8–30 days: OR 3.23, [1.59–6.59]). Conclusions: Adjusted mortality did not differ by cardiac procedural status, although residual confounding is possible. Later stroke recognition after cardiac procedures was associated with higher mortality, identifying a high-risk monitoring window.

Background: To determine whether computed tomography (CT) thrombus characteristics modify the effect of intravenous (IV) thrombolysis type (tenecteplase vs alteplase) on outcomes. Methods: This is a secondary analysis of the Alteplase compared to Tenecteplase (AcT) trial. Patients with visible intracranial occlusions on thin-slice baseline imaging were included. Key thrombus characteristics assessed by CT imaging were hyperdense artery sign, thrombus length, residual flow, clot burden score, and occlusion site. Multivariable analyses were performed to test for interactions between thrombolysis type and thrombus characteristics on clinical and angiographic outcomes. Results: Of 1577 patients, 939 met inclusion criteria; 479 (51.0%) received tenecteplase and 460 (49.0%) alteplase. Among the 498 patients (53.0%) treated with endovascular thrombectomy (EVT), angiographic outcomes were comparable between treatment groups. A significant interaction was observed between thrombolysis type and thrombus length; longer thrombi were associated with reduced likelihood of modified Rankin Scale (mRS) 0–1 with alteplase (adjusted odds ratio (aOR) per 1 mm increase, 0.97 (95% confidence interval (CI): 0.95–1.00)), but not with tenecteplase (aOR: 1.00 (95% CI: 0.98–1.02); interaction p = 0.04). Similarly, the presence of residual flow within the thrombus was associated with higher odds of mRS 0–2 in the alteplase group (aOR: 2.00 (95% CI: 1.25–3.20)), but had no significant effect in the tenecteplase group (aOR: 0.93 (95% CI: 0.62–1.41); interaction p = 0.01). No other significant interactions between thrombus characteristics and thrombolysis type were identified. Conclusion: In the AcT trial, alteplase appeared less effective with longer thrombi and those lacking residual flow, whereas IV tenecteplase showed more consistent effectiveness across thrombus characteristics. These findings require confirmation in future prospective studies.

Background: Venous thrombosis and venous thromboembolism (VTE) are important causes and complications of stroke. They may complicate acute stroke as deep venous thrombosis or pulmonary embolism (DVT/PE), contribute causally to ischemic stroke through paradoxical embolism from a patent foramen ovale (PFO), or present directly as cerebral venous thrombosis (CVT). Despite shared pathophysiological features and overlapping antithrombotic strategies, these conditions are typically considered separately, fragmenting evidence and limiting the exchange of concepts. Purpose: We therefore convened experts across both stroke neurology and thrombosis medicine fields to examine these conditions under a unifying venous theme and define priorities for future clinical trials. Methods: Thirty-two stroke and thrombosis clinicians and researchers identified research priorities across three domains: prevention of VTE after stroke, secondary prevention after PFO-related stroke, and acute and long-term management of CVT. Structured discussions were guided by the PICO (Population, Intervention, Comparison, Outcome) framework, followed by a Delphi survey to establish consensus. Priority questions centered on the balance between thrombosis prevention and bleeding risk and the optimal timing, duration, and choice of DVT/PE prophylaxis after stroke; the optimal antithrombotic strategy for patients awaiting or forgoing PFO closure; and, for CVT, the role of endovascular therapy in severe disease and the optimal duration of secondary prevention (Graphical Abstract). Across domains, the group prioritized pragmatic and platform trial designs, integration with international registries to address the rarity of CVT, and patient-oriented outcomes that extend beyond functional recovery. Conclusions: By considering these venous conditions together and bridging stroke and thrombosis disciplines, this work defines priority questions to address persistent evidence gaps, harmonize practice, and improve patient-centered outcomes.

Background: With the increasing use of tenecteplase, it is important to understand its safety compared with alteplase. We aimed to determine the incidence, predictors, and functional impact of serious adverse events (SAEs) in patients treated with alteplase versus tenecteplase. Methods: This is a post hoc analysis of the AcT (Alteplase Compared to Tenecteplase) trial, a phase 3 multicenter randomized controlled trial that randomized 1577 ischemic patients with stroke (2019–2022) into tenecteplase versus alteplase presenting P =0.002) and higher endovascular treatment rates (50.2% versus 29.2%; P <0.001) than those without SAEs. Nervous system disorders were the most common SAE (58.2%), including stroke worsening (26.7%) and intracranial hemorrhage (25%). No significant differences were observed in SAE distribution by thrombolytic. Patients with SAEs had higher 90‐day modified Rankin Scale scores (median, 4 versus 2; odds ratio [OR], 3.93 [95% CI, 2.78–5.56]). Independent predictors of SAEs included baseline National Institutes of Health Stroke Scale (per SD increase: OR, 1.2 [95% CI, 1.0–1.5]), large‐vessel occlusion (OR, 1.6 [95% CI, 1.1–2.5]), Alberta Stroke Program Early Computed Tomography Score (per point increase: OR, 0.9 [95% CI, 0.8–1.0]), and cerebral atrophy (per point increase: OR, 1.5 [95% CI, 1.1–1.9]). Conclusions: Our study found no difference between rate or type of SAEs by thrombolytic type, supporting the safety of tenecteplase. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT03889249.

Background: The Alberta Stroke Program Early CT Score (ASPECTS) and CT angiography (CTA) Collateral Score (CS) are routinely used to estimate ischemic core burden and collateral status in acute ischemic stroke due to large vessel occlusion, but suffer from limited reliability. Whether automated CT perfusion (CTP) maps improve scoring consistency remains unclear. Objectives: To assess the reliability of these scores on non-contrast computed tomography (NCCT) and CTA among numerous raters, with and without access to automated perfusion maps, and their correlations with endovascular thrombectomy (EVT) decisions. Methods: Twenty-nine clinicians independently rated 60 imaging cases from 30 late-window stroke patients with large vessel occlusion, each presented twice: once using NCCT and CTA alone (‘non-CTP cases’), and once with the addition of perfusion maps (‘CTP cases’). Twenty-eight raters (97%) completed the survey twice. Inter- and intra-reliability was assessed using Gwet’s AC1/2 coefficients (κ _G ). Correlations with EVT decisions were evaluated using Cramer V. Results: Inter-rater reliability for ASPECTS was substantial and similar between non-CTP (κ _G = 0.65, 95% CI: 0.53 to 0.78) and CTP cases (κ _G = 0.64, 95% CI: 0.51 to 0.77). CS showed an almost perfect reliability in both scenarios (κ _G = 0.82 and 0.83). Intra-rater agreement was at least substantial. Dichotomizing ASPECTS as 0-2/3-10 improved reliability to almost perfect. ASPECTS strongly correlated with EVT decisions (V=0.80), whereas CS showed moderate correlation (V=0.56), both remaining similar with the addition of CTP (V=0.75 and 0.54, respectively). Conclusion: Automated perfusion imaging did not improve the reliability of ASPECTS or CS. Strong reliability was achieved with NCCT and CTA alone.

Introduction: Fast delivery of intravenous thrombolysis (IVT) and transportation to a comprehensive stroke center (CSC) are paramount for primary stroke centers (PSCs). We investigated outcomes and workflow times of patients treated with IVT at PSCs. Methodology: This is a secondary analysis of the AcT trial, a multicenter, phase-3, randomized, controlled, noninferiority trial comparing tenecteplase with alteplase in patients with acute ischemic stroke within 4.5 hours of onset. We compared baseline characteristics, imaging and clinical outcomes at 90 days, and workflow times between PSCs and CSCs. Results: Of 1577 patients enrolled in the trial, 99 (6.27%) were treated at PSCs and 1,478 (93.72%) at CSCs. Both groups had similar age, proportion of females, baseline NIHSS and presence of LVO. The proportion of patients achieving excellent functional outcome at 90 days was higher in PSCs compared to CSCs (mRS 0-1: 48.48% versus 35.01%, adjusted IRR, 1.42 [CI 95%, 1.04–1.95]). Patients at PSCs had longer door-to-needle times (median, 56.5 [42–70] versus 35 [27–47] minutes, p < 0.001). In the 24 patients transferred to CSCs, the needle-to-puncture time was more favorable for tenecteplase compared to alteplase (median, 35.5 [21–58] versus 52 [18–74] minutes, p < 0.001). Conclusions: Our findings suggest that patients treated at PSCs may achieve outcomes comparable to those treated at CSCs, despite differences in workflow efficiency. These results should be interpreted cautiously, as this is a hypothesis-generating analysis, and observed differences may reflect multiple factors, including site-level practices, referral patterns and workflow characteristics.

BACKGROUND: With the increasing use of tenecteplase for acute ischemic stroke, it is important to determine its safety in young adults. We aimed to characterize the clinical characteristics and imaging findings of young adults (≤45 years) in the AcT trial (Intravenous Tenecteplase Compared With Alteplase for Acute Ischaemic Stroke in Canada) and to compare their safety and efficacy outcomes. METHODS: This is a secondary analysis of the AcT trial, a phase 3 pragmatic multicenter registry-linked randomized controlled trial. We describe clinical and imaging characteristics of young adults with acute ischemic stroke. Logistic regression adjusted for sex and stroke severity was performed to assess safety and efficacy outcomes between the tenecteplase and alteplase arms. RESULTS: Of the 1577 enrolled patients, 68 (4.31%) were ≤45 years. Of 53 patients with available comorbidity data, 33 (62.26%) had no comorbidities. Hypertension was the most common comorbidity (n=8, 15%), whereas cardiac pathologies were observed in a smaller proportion (n=4, 7.5%). Intracranial atherosclerosis was identified in 7 patients (10%) and carotid or vertebral artery dissection in 6 patients (9%). Safety outcomes, including mortality, intracranial hemorrhage, and serious adverse events, were similar between the tenecteplase and alteplase arms. Excellent functional outcome (modified Rankin Scale score 0–1) at 90 days was better in the tenecteplase arm (84.72% versus 45%; adjusted odds ratio, 6.55 [95% CI, 1.89–22.71]). CONCLUSIONS: The majority of young adults presenting with acute ischemic stroke did not have any traditional risk factors for stroke at presentation. Safety outcomes were similar between the tenecteplase and alteplase arms. Although functional outcomes were observed to be better in the tenecteplase arm, these findings are exploratory and should be interpreted cautiously, given the study’s limited sample size and lack of adjustment for key confounders. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03889249.