COVID‐19 Infection Is Associated With Poor Outcomes in Patients With Intracerebral Hemorrhage

Background Patients with ischemic stroke and concomitant COVID‐19 infection have worse outcomes than those without this infection, but the impact of COVID‐19 on hemorrhagic stroke remains unclear. We aimed to assess if COVID‐19 worsens outcomes in intracerebral hemorrhage (ICH). Methods and Results We conducted an observational study of ICH outcomes using Get With The Guidelines Stroke data. We compared patients with ICH who were COVID‐19 positive and negative during the pandemic (March 2020–February 2021) and prepandemic (March 2019–February 2020). Main outcomes were poor functional outcome (defined as a modified Rankin scale score of 4 to 6 at discharge), mortality, and discharge to a skilled nursing facility or hospice. The first stage included 60 091 patients with ICH who were COVID‐19 negative and 1326 COVID‐19 positive. In multivariable analyses, patients with ICH with versus without COVID‐19 infection had 68% higher odds of poor outcome (odds ratio [OR], 1.68 [95% CI, 1.41–2.01]), 51% higher odds of mortality (OR, 1.51 [95% CI, 1.33–1.71]), and 66% higher odds of being discharged to a skilled nursing facility/hospice (OR, 1.66 [95% CI, 1.43–1.93]). The second stage included 62 743 prepandemic and 64 681 intrapandemic cases with ICH. In multivariable analyses, patients with ICH admitted during versus before the COVID‐19 pandemic had 10% higher odds of poor outcomes (OR, 1.10 [95% CI, 1.07–1.14]), 5% higher mortality (OR, 1.05 [95% CI, 1.02–1.08]), and no significant difference in the risk of being discharged to a skilled nursing facility/hospice (OR, 0.93 [95% CI, 0.90–0.95]). Conclusions The pathophysiology of the COVID‐19 infection and changes in health care delivery during the pandemic played a role in worsening outcomes in the patient population with ICH

Patent Foramen Ovale Closure Decreases the Incidence but Not the Size of New Brain Infarction on Magnetic Resonance Imaging An Analysis of the REDUCE Trial

Background and Purpose: Randomized patent foramen ovale closure trials have used open-label end point ascertainment which increases the risk of bias and undermines confidence in the conclusions. The Gore REDUCE trial prospectively performed baseline and follow-up magnetic resonance imaging (MRIs) for all subjects providing an objective measure of the effectiveness of closure.Methods: We performed blinded evaluations of the presence, location, and volume of new infarct on diffusion-weighted imaging of recurrent clinical stroke or new infarct (>3 mm) on T2/fluid attenuated inversion recovery from baseline to follow-up MRI at 2 years, comparing closure to medical therapy alone. We also examined the effect of shunt size and the development of atrial fibrillation on infarct burden at follow-up.Results: At follow-up, new clinical stroke or silent MRI infarct occurred in 18/383 (4.7%) patients who underwent closure and 19/177 (10.7%) medication-only patients (relative risk, 0.44 [95% CI, 0.24-0.81], P=0.02). Clinical strokes were less common in closure patients compared with medically treated patients, 5 (1.3%) versus 12 (6.8%), P=0.001, while silent MRI infarcts were similar, 13 (3.4%) versus 7 (4.0%), P=0.81. There were no differences in number, volumes, and distribution of new infarct comparing closure patients to those treated with medication alone. There were also no differences of number, volumes, and distribution comparing silent infarcts to clinical strokes. Infarct burden was also similar for patients who developed atrial fibrillation and for those with large shunts.Conclusions: The REDUCE trial demonstrates that patent foramen ovale closure prevents recurrent brain infarction based on the objective outcome of new infarcts on MRI. Only clinical strokes were reduced by closure while silent infarctions were similar between study arms, and there were no differences in infarct volume or location comparing silent infarcts to clinical strokes.Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00738894.</p

Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial

Background: Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. Methods: NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. Findings: Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22–1·36), and the risk was similar for those without known PFO (1·06; 0·84–1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51–8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69–4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24–0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity. Interpretation: Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted. Funding: Bayer and Janssen

Abstract 013: Infarct density: a novel imaging biomarker of long‐term functional outcome after endovascular thrombectomy

Introduction Endovascular thrombectomy (EVT) dramatically improves clinical outcomes, but the reduction in final infarct volume only accounts for 10‐15% of the treatment benefit. There is a clear need for imaging biomarkers that are strongly associated with long‐term functional outcome after EVT, both in clinical practice and clinical trial design (surrogate outcome measure). Here we aimed to quantify the relationship between functional outcome and a range of ADC thresholds on post‐EVT MRI. Methods A single‐center cohort of consecutive acute stroke patients with anterior circulation large vessel occlusion, successful recanalization via EVT (mTICI ≥ 2b), and MRI of the brain between 12 hours and 7 days after EVT was evaluated. Imaging was processed via RAPID software. Final infarct volume was based on the traditional ADC <620 threshold. Logistic regression quantified the association of lesion volumes and good functional outcome (90‐day modified Rankin Scale ≤ 2) at a range of lower ADC thresholds (<570, <520, and <470). Infarct density was calculated as the percentage of the final infarct volume below the ADC threshold with the greatest effect size. Univariate and multivariate logistic regression quantified the association between clinical/imaging variables and functional outcome. A receiver operating characteristics (ROC) analysis was used to calculated areas under the curve (AUC) with 95% confidence intervals for the final model. The Delong test compared this AUC with two additional models: (1) the final multivariate model without infarct density and (2) the final model without infarct density and final infarct volume. Results Of the 120 patients who underwent MRI after successful EVT, lesion volume based on the ADC threshold <470 had the strongest association with good outcome (OR: 0.81 per 10mL; 95% CI: 0.66–0.99). In a multivariate model, infarct density (volume <470/volume <620 * 100) was independently associated with good outcome (aOR 0.68 per 10%; 95% CI: 0.49–0.95). In the multivariate model, final infarct volume was no longer associated with outcome (aOR 0.98 per 10mL; 95% CI: 0.85–1.14). The ROC analysis of the multivariate model with only clinical variables (age, sex, and NIHSS) yielded a good ability to distinguish patients with good and bad outcome (AUC = 0.77; 95% CI: 0.69 – 0.84). Adding infarct volume improved classification performance (AUC = 0.82; 95% CI: 0.75 – 0.88), but this was further improved by adding infarct density (AUC = 0.84, 95% CI: 0.78 – 0.91); p=0.02 comparing all three AUCs (Figure 1). Conclusion The degree of tissue injury after EVT is topographically heterogeneous, and more profound tissue injury manifests as lower ADC values. Here, we operationalized the severity of infarct as infarct density, which is independently associated with long‐term clinical outcome and provides greater prognostic information than final infarct volume. This technique may hold value as a surrogate outcome measure in early phased clinical trials

Cerebral Blood Flow Response During Bolus Normal Saline Infusion After Ischemic Stroke

We quantified cerebral blood flow response to a 500 cc bolus of 0.9%% normal saline (NS) within 96 hours of acute ischemic stroke (AIS) using diffuse correlation spectroscopy (DCS). Materials and Methods: Subjects with AIS in the anterior, middle, or posterior cerebral artery territory were enrolled within 96 hours of symptom onset. DCS measured relative cerebral blood flow (rCBF) in the bilateral frontal lobes for 15 minutes at rest (baseline), during a 30-minute infusion of 500 cc NS (bolus), and for 15 minutes after completion (post-bolus). Mean rCBF for each time period was calculated for individual subjects and median rCBF for the population was compared between time periods. Linear regression was used to evaluate for associations between rCBF and clinical features. Results: Among 57 subjects, median rCBF (IQR) increased relative to baseline in the ipsilesional hemisphere by 17% (-2.0%, 43.1%), P< 0.001, and in the contralesional hemisphere by 13.3% (-4.3%, 36.0%), P < .004. No significant associations were found between ipsilesional changes in rCBF and age, race, infarct size, infarct location, presence of large vessel stenosis, NIH stroke scale, or symptom duration. Conclusion: A 500 cc bolus of .9% NS produced a measurable increase in rCBF in both the affected and nonaffected hemispheres. Clinical features did not predict rCBF response2811NINDSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [R01 NS060653]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P41-EB015893, R25 NS065745