American Heart Association

Monthly Archives: August 2020

Navigating Major Bleeding and Embolic Strokes of Undetermined Source

Kevin O’Connor, MD

Mikulík R, Eckstein J, Pearce LA, Mundl H, Rudilosso S, Olavarría VV, Shoamanesh A, Chamorro Á, Martí-Fàbregas J, Veltkamp R, et al. Frequency and Predictors of Major Bleeding in Patients With Embolic Strokes of Undetermined Source: NAVIGATE-ESUS Trial. Stroke. 2020;51:2139-2147.

About a third of ischemic strokes are categorized as being cryptogenic. Embolic strokes of unknown source (ESUS) represent a subset of these cryptogenic strokes. Clinicians are often faced with choosing between an anticoagulant and a platelet antiaggregant as one component of secondary prevention in patients having an ESUS. The NAVIGATE-ESUS trial provides data on the frequency and predictors of major bleeding in ESUS patients based on antithrombotic therapy choice, which can help inform treatment decisions.

NAVIGATE-ESUS was an international, double-blind, phase III trial that included 7213 participants from 31 countries who were randomized to receive rivaroxaban 15 mg once daily or aspirin 100 mg once daily. Sites were in Europe, East Asia, North America, and Latin America. The primary outcome of this analysis was major bleeding. Clinically-relevant nonmajor bleeding (CRNMB) was excluded for several reasons: CRNMB determinations were not determined centrally, whereas there was centralized adjudication of major bleeding events; intracranial bleeding was not considered to be a CRNMB; and analysis of independent predictors of major bleeding and CRNMBs such as epistaxis requiring medical attention would have been potentially spurious. NAVIGATE-ESUS was terminated before targeted enrollment was completed after an interim analysis found increased bleeding among rivaroxaban-treated participants, but no reduction in recurrent stroke.

By |August 31st, 2020|clinical|0 Comments

A Collateral Dialogue: Addressing Neuroanatomy of Posterior Circulation in Basilar Artery Occlusion

Saurav Das, MD

Kwak HS, Park JS. Mechanical Thrombectomy in Basilar Artery Occlusion: Clinical Outcomes Related to Posterior Circulation Collateral Score. Stroke. 2020;51:2045–2050.

The successful endovascular treatment (EVT) trials for large vessel occlusion (LVO) strokes have excluded patients with basilar artery occlusion (BAO). Recently, the results of the Basilar Artery International Collaboration Study (BASICS) were presented at the European Stroke Organization (ESO-WSO) virtual platform. The results, even though underpowered to show significant benefits of EVT <6 hours of BAO, were effective in patients with moderate to severe deficits (NIHSS > 10). The trial results have shifted the spotlight to the distinction in the neuro-anatomy of posterior-circulation vessels and collateral circulation in this part of the brain, etio-pathological mechanisms involved in large vessel disease in the posterior circulation, as well as appropriate patient selection based on symptom severity and time window from symptom onset. In this blog, I will discuss a retrospective study from South Korea relevant to this topic that was published in the July issue of Stroke.

In this study, the authors present data from 81 patients with acute BAO treated with EVT using manual aspiration or stent retriever at their institute in South Korea over a period of eight years from 2012 to 2019. Posterior circulation collaterals were graded using the Basilar Artery on CT Angiogram (BATMAN) score and posterior circulation collateral score (PC-CS). Both these scoring systems have a maximum possible score of 10 points. 64% of these patients achieved TICI 2b or 3 recanalization within a median time of 5.5 hours from symptom onset, and 37% of patients had good functional outcomes defined by a 3-month modified Rankin scale ≤ 2. When compared to patients with poor outcomes, the ones with favorable outcomes had lower baseline NIHSS (15 vs 7.5, p<0.01), a greater proportion of distal BAO (20% vs 63%,  p<0.01), and better posterior circulation collateral scores (5 vs 6,  p<0.01). The authors also compared these groups on a timeline of < 3hrs, 3-6 hrs, 6-12 hrs, and >12 hrs from symptom onset. Interestingly, the time to recanalization from symptom onset was not significantly different between the groups. Receptor operating characteristic (ROC) curve analysis for collateral scores yielded the highest area under the curve with a cut-off score of 6 for both BATMAN and PC-CS. Using these cut-offs, multivariate analysis revealed that NIHSS score <15 (odds ratio 8.49, P=0.004), PC-CS ≥6 (odds ratio 3.79, P=0.042), and distal BAO (odds ratio 3.67, P=0.035) were independent predictors of good clinical outcomes.

Figure 1. Schematic illustration of collateral scores.

IV Thrombolysis for CRAO: Time is Vision?

Song J. Kim, MD

Mac Grory B, Nackenoff A, Poli S, Spitzer SM, Nedelmann M, Guillon B, Preterre C, Chen CS, Lee AW, Yaghi S, et al. Intravenous Fibrinolysis for Central Retinal Artery Occlusion: A Cohort Study and Updated Patient-Level Meta-Analysis. Stroke. 2020;51:2018–2025.

Patients presenting with complete retinal artery occlusion (CRAO), often first evaluated by ophthalmologists, are advised to seek emergent neurological evaluation. On the receiving end, even when the patient arrives within the typical thrombolysis window of <4.5 hours, some vascular neurologists may demur on offering reperfusion therapy owing to : 1) lack of robust evidence with regards to outcomes, and 2) absence of a comprehensive ophthalmological evaluation in excluding other non-ischemic differentials. 

To address the above, Mac Grory and co-authors developed a protocol for a rapid evaluation of CRAO including a dilated ophthalmologic evaluation and other work-up, ruling out mimics such as optic neuritis, giant cell arteritis, and retinal detachment. Barring any contraindications, patients received tPa if CRAO was deemed the most likely diagnosis, with visual acuity of less than 20/200 in the affected eye and presenting within 4.5 hours of symptom onset. Over a 10-year time span, 112 were diagnosed with acute CRAO. They were subsequently included in a retrospective observational analysis on post-tPa visual outcomes, as well as an updated subject-level meta-analysis expanding upon the authors’ 2015 study.

By |August 24th, 2020|clinical|0 Comments

Article Commentary: “Clot-Based Radiomics Predict a Mechanical Thrombectomy Strategy for Successful Recanalization in Acute Ischemic Stroke”

Aurora Semerano, MD

Hofmeister J, Bernava G, Rosi A, Vargas MI, Carrera E, Montet X, Burgermeister S, Poletti P-A, Platon A, Lovblad K-O, Machi P. Clot-Based Radiomics Predict a Mechanical Thrombectomy Strategy for Successful Recanalization in Acute Ischemic Stroke. Stroke. 2020;51:2488–2494.

Tools for predicting the success or the failure of reperfusion treatments in the acute setting of ischemic stroke are useful both to assist treatment decision-making and to guide the selection of the best device and reperfusion strategy. Multiple biomarkers and models, including clinical, biochemical, and radiological parameters, are currently under investigations with this purpose. Recently, multimodal analyses of the occlusive clot are receiving growing interest for the potential predictive value on reperfusion outcomes.

Hofmeister et al.(1) addressed this important issue in their recent article in Stroke. More specifically, the authors aimed at identifying the radiomic features of the occlusive clot on pre-treatment non-contrast CT scan, which may predict both first-attempt successful reperfusion with thromboaspiration (defined by modified Treatment in Cerebral Ischemia, mTICI 2b-3) and the number of maneuvers required to achieve successful reperfusion.

Ticagrelor: Is It Here to Stay?

Elena Zapata-Arriaza, MD

Johnston SC, Amarenco P, Denison H, Evans SR, Himmelmann A, James S, Knutsson M, Ladenvall P, Molina CA, Wang Y, for the THALES Investigators. Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA. N Engl J Med. 2020;383:207-217.

Without urgent treatment, the risk of major stroke in the week after a transient ischemic attack (TIA) or minor stroke can be as high as 10%. Some studies have shown that the combination of aspirin (ASA) plus Clopidogrel reduces the risk of stroke and other major ischemic events. Given the limitations in Clopidogrel due to hepatic conversion and the high resistance rates, Ticagrelor emerges as an interesting alternative, not dependent on metabolic activation.

With the aim of testing the effect of Ticagrelor and aspirin combination on stroke prevention, Johnston et al performed this randomized, placebo-controlled, double-blind trial involving patients who had had a mild-to-moderate acute noncardioembolic ischemic stroke, with a NIHSS≤5 or TIA, and who were not undergoing thrombolysis or thrombectomy. The patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive a 30-day regimen of either Ticagrelor (180-mg loading dose followed by 90 mg twice daily) plus aspirin (300 to 325 mg on the first day followed by 75 to 100 mg daily) or matching placebo plus aspirin. The primary outcome was a composite of stroke or death within 30 days. Secondary outcomes were first subsequent ischemic stroke and the incidence of disability within 30 days. The primary safety outcome was severe bleeding.

By |August 17th, 2020|clinical|0 Comments

The Future of Stroke in Europe: The Good and Bad News

Raffaele Ornello, MD

Wafa AH  Wolfe CDA, Emmett E, Roth GA, Johnson CO, and Wa Y. Burden of Stroke in Europe: Thirty-Year Projections of Incidence, Prevalence, Deaths, and Disability-Adjusted Life Years. Stroke. 2020;51:2418–2427.

Making projections about the future of stroke is important, due to the high burden of the disease in the general population and especially among the elderly. However, it is hard to provide accurate estimates due to the high number of variables to take account of.

In the present study, which used data from the Global Burden of Diseases 2017, the authors considered two variables, namely time and GDP per capita, to estimate variations in stroke incidence, prevalence, mortality, and disability-adjusted life years (DALYs) lost from 2017 to 2047 in 28 European countries. The authors’ statistical model predicted a slight increase (+3%) in stroke incidence, a striking 27% increase in stroke prevalence, fewer deaths (-17%) and DALYs lost (-33%).

By |August 14th, 2020|clinical|0 Comments

Tackling a Long Overdue Problem: The Eyes Have It

Richard Jackson, MD

Mac Grory B, Nackenoff A, Poli S, Spitzer MS, Nedelmann M, Guillon B, Preterre C, Chen CS, Lee AW, Yaghi S, et al. Intravenous Fibrinolysis for Central Retinal Artery Occlusion: A Cohort Study and Updated Patient-Level Meta-Analysis. Stroke. 2020;51:2018–2025.

Mac Grory et al. have published data that all stroke neurologists on call have been waiting for. In hospital systems where there are ophthalmologists taking calls, usually the neurologist on call for stroke gets the stroke code page for acute onset loss of vision or the patient is referred to the ER for a diagnosis of CRAO for evaluation. There is an ensuing debate between the on-call neurologist and ER physician about what to do for this patient. As neurologists, we are taught that the eye is an extension of the brain, and infarcts to the eye are technically infarcts to the brain. However, there is no data on whether or not thrombolysis with alteplase is efficacious. The ophthalmologists cite a lack of efficacy in trials and only one randomized trial with a small sample of 25 that showed no benefit when treated with standard dose 0.9mg/kg IV-tPA but within 24 hours of onset. An even more difficult situation arises in the primary stroke centers that do not have ophthalmologists on call where the neurologist on call for stroke has to make a decision based on clinical judgement. Both of these scenarios usually end in poor visual acuity for the patient after medical treatment with monotherapy or dual therapy antiplatelet with or without permissive hypertension and statin treatment.

By |August 10th, 2020|clinical|0 Comments

Infection as a Risk Factor for Stroke Recurrence

Elena Zapata-Arriaza, MD

Xu J, Yalkun G, Wang M, Wang A, Wangqin R, Zhang X, Chen Z, Mo J, Meng X, Li H, et al. Impact of Infection on the Risk of Recurrent Stroke Among Patients With Acute Ischemic Stroke. Stroke. 2020;51:2395–2403.

The association of immune changes after stroke and infection appearance has been widely evidenced recently. Inflammatory cascade occurring during infection may promote platelet, endothelial and coagulation changes triggering subsequent cerebrovascular events. Xu J et al. aim to investigate whether infection increases the short- and long-term risk of recurrent stroke in patients hospitalized due to acute ischemic stroke (AIS).

For the purpose, data were derived from ischemic stroke patients in 2 stroke registries (CSCA study and CNSR III study) realized in China. These registries recorded the medical data during hospitalization and finished 1-year follow-up. Associations of infection (pneumonia or urinary tract infection) during hospitalization with recurrent stroke in the short (during hospitalization) and long term (since 30 days to 1 year after stroke onset) were analyzed. The primary outcome was recurrent stroke, and secondary outcomes included the recurrence of ischemic stroke, intracerebral hemorrhage, hemorrhagic transformation, myocardial infarction, combined vascular events (including recurrent stroke, myocardial infarction, and vascular death), and all cause death. In the CSCA, the authors conducted multivariate logistic regression models to investigate the association of infection with in-hospital outcomes. To keep consistency and confirm the finding in the CSCA, the association of infection with in-hospital outcomes in the CNSR-III was analyzed using logistic regression models.

By |August 5th, 2020|clinical|0 Comments

Impact of COVID-19 on Stroke Workflow: Assessment from Comprehensive Hospitals in Connecticut

Shashank Shekhar, MD, MS

Jasne AS, Chojecka P, Maran I, Mageid R, Eldokmak M, Zhang Q, Nystrom K, Vlieks K, Askenase M, Petersen N, et al. Stroke Code Presentations, Interventions, and Outcomes Before and During the COVID-19 Pandemic. Stroke. 2020.

Stroke management requires quick and timely evaluation by medical personnel and transfer to a primary stroke center to provide appropriate medical care. The American Heart Association/American Stroke Association recently revised the stroke guidelines in 2019 to reflect the recent advancement in clinical research to clinical practice. However, after the COVID-19 pandemic started in the United States in January 2020, the whole medical system came under severe strain. Around 72% of United States adults were no longer going to public places, including hospitals, to avoid COVID-19 exposure.

This study estimates this decline in stroke volume in the Comprehensive Stroke Centers (CSC) in Connective and eventually aims to increase public awareness. The aims of the study were: compare the volume of stroke codes before and during the COVID-19 local spread; describe the demographics and clinical characteristics of patients presented with acute stroke-like symptoms during this pandemic; and find the association between the onset of the pandemic and acute stroke metrics and outcomes.

This study is a retrospective pre and during event cohort analysis and was approved by the Yale-New Haven Hospital (YNHH) Institutional Review Board with a waiver of informed consent. The date was including from pre-pandemic cohort and pandemic cohort from 2019 and corresponding months in 2020. The number of stroke codes at three hospitals was analyzed from January 1 to April 28, 2020, and compared from the previous year.