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Vitamin K Antagonists: Insufficient Aid for Embolism and Risky for Intracranial Hemorrhage

Elena Zapata-Arriaza, MD
@ElenaZaps

Meinel TR, Kniepert JU, Seiffge DJ, Gralla J, Jung S, Auer E, et al. Endovascular Stroke Treatment and Risk of Intracranial Hemorrhage in Anticoagulated Patients. Stroke. 2020;51:892–898.

Symptomatic intracranial hemorrhage (sICH) involves a potential complication in patients treated with rtpa or mechanical thrombectomy (MT), which influences functional and vital prognosis of ischemic stroke patients. Patients under oral anticoagulation (OAC) suffer higher risk of sICH per se; however, the association of mentioned oral treatment with recanalization therapies (IV fibrinolysis or MT) may increase cerebral bleeding. This is the aim of Dr. Meinel and colleagues, among others, like mortality and sICH risk in MT patients under OAC, sensitivity analysis with patients with confirmed therapeutic anticoagulation activity, and finally the presentation of a meta-analysis about the topic.

The authors performed a retrospective, multicenter non-randomized observational study to investigate safety and efficacy of a market-release neurothrombectomy device, including their data in the BEYOND-SWIFT registry. Patients were grouped according to their OAC intake prior to admission: Group 1: VKA (vitamin K antagonist); Group 2: DOACs (Direct oral anticoagulants); Group 3: No OAC. The primary endpoint was sICH rate (according to ECASS II (European Co-Operative Acute Stroke Study-II) criteria). The secondary endpoints were technical efficacy and all-cause mortality at 3 months.

Article Commentary: “Machine Learning–Enabled Automated Determination of Acute Ischemic Core From Computed Tomography Angiography”

Muhammad Taimoor Khan, MD

Sheth SA, Lopez-Rivera V, Barman A, Grotta JC, Yoo AJ, Lee S, et al. Machine Learning–Enabled Automated Determination of Acute Ischemic Core From Computed Tomography Angiography. Stroke. 2019;50:3093–3100.

As a vascular neurology fellow, an understanding of the automated tools available for immediate diagnosis of large vessel occlusion (LVO), estimation of core and penumbra in the context of treatment decision making has become critical in the era of endovascular therapy. In the article “Machine Learning–Enabled Automated Determination of Acute Ischemic Core From Computed Tomography Angiography,” the authors developed, validated, and reported a deep learning method called “DeepSymNet” that evaluates for ischemic core volume using computed tomography angiogram (CTA) source images. The study included patients with acute ischemic stroke and stroke mimics with CTA and CT perfusion (CTP) using the RAPID software and trained their algorithm against RAPID CTP determinations of ischemic core.

From 297 included patients, 224 (75%) had acute ischemic stroke, of which 179 (60%) had large vessel occlusion. The mean RAPID CTP based ischemic core volume was 23±42 cc. DeepSymNet learned to identify vessels on CTA, detect LVO autonomously and ischemic core of less than or equal to 30 cc and 50 cc with AUC 0.88 and 0.90 (ischemic core ≤30 mL and ≤50 mL) to CTP-RAPID ischemic core volume both in early, 0 to 6 hours and late 6-24 hours time windows. (AUCs 0.90 and 0.91, ischemic core ≤50 mL).

Article Commentary: “Mechanical Thrombectomy in the Era of the COVID-19 Pandemic: Emergency Preparedness for Neuroscience Teams”

Gurmeen Kaur, MBBS
@kaurgurmeen

Nguyen TN, Abdalkader M, Jovin TG, Nogueira RG, Jadhav AP, Haussen DC, et al. Mechanical Thrombectomy in the Era of the COVID-19 Pandemic: Emergency Preparedness for Neuroscience Teams: A Guidance Statement From the Society of Vascular and Interventional Neurology. Stroke. 2020.

With the COVID-19 pandemic taking more than 50,000 lives in the United States, emergency medical services are being forced to change their triage policies in order to ensure safety of both the patients and the health care personnel involved.

Stroke and STEMI triage systems are among the first to be affected, especially because there is some evidence for the increased incidence of acute ischemic strokes in COVID-19 patients, secondary to the hypercoagulability.

The Society of Vascular and Interventional Neurology has issued a guidance statement highlighting practices that all institutes should be incorporating into their routine stroke workflow — pre-, intra- and post-mechanical thrombectomy. These guidelines serve as pointers that can be used to modify our existing protocols. Because we are going to continue to see the effect of COVID-19 through the summer, especially in highly impacted states like New York, Massachusetts and Illinois, and there is also a potential second wave predicted for fall and winter 2020, it is prudent that all centers adopt these best practice guidelines in their daily stroke triage and workflow.

Determining Prognosis of Intracerebral Hemorrhage by Imaging: Wait (24 Hours) and See

Raffaele Ornello, MD

Lun R, Yogendrakumar V, Demchuk AM, Aviv RI, Rodriguez-Luna D, Molina CA, et al. Calculation of Prognostic Scores, Using Delayed Imaging, Outperforms Baseline Assessments in Acute Intracerebral Hemorrhage. Stroke. 2020;51:1107–1110.

The prognosis of intracerebral hemorrhage (ICH) is poor, and it is hard to identify factors which can predict a good or bad outcome. Besides, ICH is usually a fast-progressing clinical picture, in which early and delayed imaging may show completely different pictures.

The multicenter, prospective, observational cohort of the PREDICT study (Prediction of Hematoma Growth and Outcome in Patients With Intracerebral Hemorrhage Using the CT-Angiography Spot Sign) included 280 patients with a 90-day case-fatality of 25%. The study assessed the predictive accuracy for 90-day mortality of the ICH Score, FUNC Score, and modified ICH Score using imaging data at initial presentation and at 24 hours. Analyses were performed using receiver operating characteristic curves. Compared with early imaging, brain imaging performed 24 hours after ICH onset significantly improved the accuracy of prognostic scores; in detail, the area under the curve increased from 0.78 to 0.82 for ICH score, from 0.76 to 0.84 for FUNC Score, and from 0.74 to 0.82 for modified ICH score. The study findings are limited by the absence of complete 24-hour clinical data. Nevertheless, the study points out that waiting 24 hours from symptom onset might improve the prediction of ICH prognosis.

A possible consequence of this study is that early withdrawal of ICH care might be unjustified, as physicians can provide reliable estimates of patients’ prognosis only after several hours from ICH onset. More interventions in the hyperacute phase of ICH might be needed, and several studies suggest the efficacy of such early interventions. Waiting 24 hours before withdrawing care might be a viable option in ICH.

Article Commentary: “Antiplatelet Therapy vs Anticoagulation Therapy in Cervical Artery Dissection”

Muhammad Rizwan Husain, MD
@RIZWANHUSAINMD

Markus HS, Levi C, King A, Madigan J, Norris J, for the Cervical Artery Dissection in Stroke Study (CADISS) Investigators. Antiplatelet Therapy vs Anticoagulation Therapy in Cervical Artery Dissection: The Cervical Artery Dissection in Stroke Study (CADISS) Randomized Clinical Trial Final Results. JAMA Neurol. 2019;76:657-664.

Cervical artery dissection (CAD) has an annual incidence of about 2.9% per 100,000, though that seems to be under-reported, as many patients usually do not present for evaluation or undergo routine vessel imaging for local symptoms like pain or headache. At the same time, even though CAD accounts for about 1-2% of total ischemic strokes, it can be the cause of up to 25% of strokes in the young population.

The Cervical Artery Dissection in Stroke Study (CADISS) is the only prospective randomized clinical trial to date that evaluated if there was a reduction in subsequent stroke in patients treated with either antiplatelet or anticoagulation. It also looked at the presence of arterial recanalization between the two groups.

Evolocumab as Part of the Armory for Stroke Prevention

Lina Palaiodimou, MD

Giugliano RP, Pedersen TR, Saver JL, Sever PS, Keech AC, Bohula EA, et al; on behalf of the FOURIER Investigators. Stroke Prevention With the PCSK9 (Proprotein Convertase Subtilisin-Kexin Type 9) Inhibitor Evolocumab Added to Statin in High-Risk Patients With Stable Atherosclerosis. Stroke. 2020.

Alberts MJ, Thompson PD. PCSK9 (Proprotein Convertase Subtilisin-Kexin Type 9) Inhibition and Stroke Prevention: Another Step Forward. Stroke. 2020.

During the last decades, stroke primary and secondary prevention has been significantly improved by systematic lipid control. Ever since the first description of low-density lipoprotein cholesterol (LDL-C) as a stroke risk factor, published guidelines have been suggesting increasingly lower LDL-C values as the target levels. According to the most recent Guidelines on Management of Blood Cholesterol, when evaluating patients with very high atherosclerotic cardiovascular disease (ASCVD) risk, it is recommended to preserve LDL-C values up to a threshold of 70 mg/dl (Grundy, 2019). In order to achieve such a therapeutic target, clinicians should use high-intensity statins with co-administration of ezetimibe when needed. In the case that LDL-C control is proven to be inadequate, even under the combination of high-intensity statin and ezetimibe, a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor should be considered as an add-on therapy.     

Evolocumab is a monoclonal antibody that binds to and inhibits PCSK9 and is a very potent lipid-lowering drug. It has been approved as an adjunctive LDL-C lowering therapy for adults with established ASCVD and is administered as a subcutaneous injection either every two weeks (140mg) or once monthly (420mg). Administration of evolocumab, as the experimental arm of the FOURIER study, proved to be effective in lowering LDL-C levels below current targets and was beneficial for ASCVD patients (Sabatine, 2017). The study population consisted of patients with a history of myocardial infarction, non-hemorrhagic stroke, or symptomatic peripheral artery disease, and also had additional characteristics for high ASCVD risk. The primary end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization.

By |April 21st, 2020|clinical|0 Comments

Endovascular Thrombectomy With Improved Reperfusion Leads to Long-Term Public Health and Societal Cost Benefits

Melissa Trotman-Lucas, PhD
@TrolucaM

Kunz WG, Almekhlafi MA, Menon BK, Saver JL, Hunink MG, Dippel DWJ, et al. Public Health and Cost Benefits of Successful Reperfusion After Thrombectomy for Stroke. Stroke. 2020;51:899–907.

The number of deaths due to stroke is 10 million per year globally, with a prevalence of 42 million. Large vessel occlusions (LVO) account for a third of all occlusive ischemic strokes and are the largest contributor to the morbidity and mortality associated with ischemic stroke. The evolution and use of endovascular thrombectomy (EVT) for these patients have transformed stroke treatment and care; clinical trials utilizing EVT demonstrated the benefits of this technique during post-stroke recovery, including reduced disability and improved outcome. In multiple countries, EVT has been adopted as the standard of care for LVO and is recommended for use where possible in other countries — limits come from availability of suitably trained staff and equipment.

Article Commentary: “Cerebral Blood Flow Predicts the Infarct Core”

Adeola Olowu, MD

Amukotuwa S, Straka M, Aksoy D, Fischbein N, Desmond P, Albers G, et al. Cerebral Blood Flow Predicts the Infarct Core: New Insights From Contemporaneous Diffusion and Perfusion Imaging. Stroke. 2019;50:2783–2789.

The purpose of this study was to assess if cerebral blood flow (CBF) from perfusion studies could accurately estimate infarct core size in ischemic stroke patients during acute stroke management for appropriate thrombectomy triage. Relative cerebral blood flow (rCBF) accuracy would be determined by comparing infarct size to DWI of MRI.

Imaging data was assessed from the DEFUSE 2 and SENSE 3 studies. DEFUSE 2 (Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evaluation) evaluated if MRI can be used to determine which patients would most likely benefit from endovascular reperfusion. SENSE 3 (Sensitivity Encoding) compared DWI and CT perfusion to reliably detect ischemic core tissue, at risk tissue, and tissue at risk of hemorrhagic transformation. Between the two studies, 119 patients had both DWI and perfusion studies within 24 hours of symptoms onset. 

Relative CBF (rCBF) was divided into 12 thresholds (0.20-0.44), and each of those thresholds were compared to the corresponding DWI. rCBF threshold of 0.32 provided the best prediction of infarct core estimate with DWI. When applying an infarct core limit of 70 mL for thrombectomy, approximately 94% of patients were correctly triaged to the appropriate therapy.

Figure 1. Coregistered diffusion-weighted imaging (DWI) and processed perfusion-weighted imaging (PWI) images from a 66-year old man who had an acute right MCA M1 segment occlusion.
Figure 1. Coregistered diffusion-weighted imaging (DWI) and processed perfusion-weighted imaging (PWI) images from a 66-year old man who had an acute right MCA M1 segment occlusion.

Educate and Empower EMS for Expedited Acute Stroke Treatment

Rohan Arora, MD

Gu H-Q, Rao Z-Z, Yang X, Wang C-J, Zhao X-Q, Wang Y-L, et al. Use of Emergency Medical Services and Timely Treatment Among Ischemic Stroke: Findings From the China Stroke Center Alliance. Stroke. 2019;50:1013–1016.

Despite the progress in stroke treatment protocols in the United States, the rate of tPA use remains low due to the inability of ischemic stroke patients to reach the hospital within the narrow therapeutic window. EMS plays a very crucial role in acute stroke care by decreasing prehospital delay and by providing prenotification for the stroke team activation, which leads to decrease in door-to-needle time.

Gu et al. analyzed data from the Chinese Stroke Centre Alliance for patients with ischemic stroke from 2015 to 2018 to study the pattern of EMS use, factors associated and its impact on prehospital delay and the treatment. Absolute standardized difference and multivariate logistic models were used. Of 560447 patients with ischemic stroke, only 12.5% used EMS for transportation to the hospital. EMS use was significantly less in the younger population, low income group, milder stroke symptoms, HTN, DM and PVD, while its use was significantly more in patients with history of CVD. Perhaps EMS education regarding stroke in the young might still be something to continually work on. EMS transport was significantly associated with less prehospital delay, shorter onset-to-door time, shorter door-to-needle time (if prenotification is sent) and more rapid treatment. The authors concluded that a low proportion of AIS patients using EMS could be due to lack of accessibility to EMS or lack of awareness for urgent stroke treatment.

What About Stroke Primary Prevention? Article Commentary on “Hypothetical Lifestyle Strategies in Middle-Aged Women and the Long-Term Risk of Stroke”

Grace Y. Kuo, MD, MS, BA

Jain P, Suemoto C, Rexrode K, Manson J, Robins J, Hernan M, et al. Hypothetical Lifestyle Strategies in Middle-Aged Women and the Long-Term Risk of Stroke. Stroke. 2020.

We are fortunate enough to be in an era in which we have multiple validated treatments for stroke care. However, with the decrease in overall stroke incidence and mortality, we are beginning to see a gender disparity in the disease of stroke. More women, particularly in the elderly populations, suffer from stroke than men. Although it may be due to longer life expectancy for women, it is still important to look for strategies to decrease this disparity. Prospective studies have found an inverse association between healthy lifestyles and strokes. However, as the natural history of the chronic conditions that lead to strokes occurs over decades, the actual effects of lifestyle interventions for primary prevention are difficult to study in randomized trials.

The article “Hypothetical Lifestyle Strategies in Middle-Aged Women and the Long-Term Risk of Stroke” is an attempt to understand the effects of dietary and non-dietary modifications on stroke risk by using longitudinal observational data in a hypothetical analysis to estimate the possible risk reduction of the interventions. Data was obtained from the Nurse’s Health Study (NHS), a database that was started in 1976 with 121,701 participants. In 1984, the participants were sent a food frequency questionnaire (FFQ), which was used as a basis for dietary pattern. Based on this survey, 59,727 participants were deemed eligible, after exclusion criteria of having pre-existing cardiovascular events (stroke, MI, angina, history of CABG) and cancer. Incomplete surveys or surveys with implausible responses were also excluded from analysis. 1986, the first follow-up year, was set as the baseline year to allow for adjustment for pre-baseline confounders. Every two years thereafter, participants were sent follow-up questionnaires. Participants were followed until their first diagnosis of stroke, death or June 2012.