American Heart Association

Monthly Archives: October 2020

Emergent Large Vessel Occlusions Strokes in the Time of the Pandemic: A Look at the COVID-19 ELVO Profile

Ericka Samantha Teleg, MD

Majidi S, Fifi JT, Ladner TR, Lara-Reyna J, Yaeger KA, Yim B, Dangayach N, Oxley TJ, Shigematsu T, Kummer BR, et al. Emergent Large Vessel Occlusion Stroke During New York City’s COVID-19 Outbreak: Clinical Characteristics and Paraclinical Findings. Stroke. 2020;51:2656–2663.

This article aimed to report observations of emergent large vessel occlusion (ELVO) ischemic strokes during the time of COVID-19 in one of the most affected cities in the United States, New York City. The association of strokes, prevalence and mechanisms are important to be investigated at this time as it is known that the virus invades cells and adheres to angiotensin converting enzyme 2 receptors that are distributed throughout the body, including the endothelium.

The timeline of this retrospective observational study is important as they highlight the 3-week period (March 21 to April 12, 2020) when hospitalizations and deaths due to COVID-19 were at their peak. Interestingly, in their exploratory analysis, the authors compared the study population with ELVO patients from March 20, 2020 backward to even include the entire year of 2019 (pre-pandemic). This is one of the most important strengths of this observational study, as it explores the potential cause-effect associations between COVID-19 and ELVO.

By |October 19th, 2020|clinical|0 Comments

What’s in a Name? Updated Classification of Patent-Foramen Ovale-Associated Strokes

Saurav Das, MD

Elgendy AY, Saver JL, Amin Z, Boudoulas KD, Carroll JD, Elgendy I, Grunwald IQ, Gertz ZM, Hijazi ZM, Horlick EM, et al. Proposal for Updated Nomenclature and Classification of Potential Causative Mechanism in Patent Foramen Ovale–Associated Stroke. JAMA Neurol. 2020;77:878-886.

We saw a 59-year-old patient with diabetes, hypertension, hyperlipidemia, coronary artery disease with multiple bypass surgeries but no known history of atrial fibrillation (AFib), and extensive smoking history in office. The patient was admitted to the ICU with recurrent episodes of hemorrhagic shock from gastro-intestinal bleeds requiring embolization of gastric artery and subsequently exploratory laparotomy within a 1-month period. He developed wedge-shaped strokes involving bilateral middle cerebral artery territories during one of these hospitalizations. Subsequently, stroke work-up revealed mild atherosclerosis in the head and neck vessels, and a transthoracic echocardiogram showed a significant large patent foramen ovale (PFO) with right to left shunt without any evidence of straddling thrombus, atrial septal aneurysm, or left atrial enlargement. He was found to have deep vein thrombosis in bilateral lower extremities and had an inferior vena cava filter placed. The question then arises how strongly we attribute the strokes to PFO and if this patient will benefit from PFO closure. In this context, I read the recent update on nomenclature and classification of PFO-associated strokes published in JAMA Neurology by the PFO-Associated Stroke International Working Group, and I will discuss the salient points in this blog post.

By |October 16th, 2020|clinical|0 Comments

Pre-Clinical Evidence of the Neuro-Recovery Effects of Vascular Endothelial Growth Factor-Activating Glycosaminoglycan Sugar

Lin Kooi Ong, PhD

Chan SJ, Esposito E, Hayakawa K, Mandaville E, Smith RAA, Guo S, Niu W, Wong PT-H, Cool SM, Lo EH, Nurcombe V. Vascular Endothelial Growth Factor 165-Binding Heparan Sulfate Promotes Functional Recovery From Cerebral Ischemia. Stroke. 2020;51:2844–2853.

Angiogenesis and neurogenesis are crucial processes for brain recovery after stroke. While the brain has the capacity to form new cerebral blood vessels and to generate new neurons from neural stem cells after stroke, these self-repair mechanisms are limited. Therefore, strategies to promote brain restorative processes beyond the endogenous recovery are highly desirable. In this study, Chan and colleagues demonstrated that an exogenously applied heparan sulfate with increased affinity for vascular endothelial growth factor was able to enhance angiogenesis and neurogenesis within the peri-infarct regions, as well as to promote neurological recovery after experimental stroke.

The team first purified heparan sulfate variant 7, a glycosaminoglycan sugar which has increased affinity for vascular endothelial growth factor, and tagged the molecule with fluorescent dye. The team experimentally induced stroke in rats using transient middle cerebral artery occlusion, and then they delivered heparan sulfate (or placebo) into the right lateral ventricle of the brain at day 4 after experimental stroke. The rats were assessed for neurological deficits, and rats treated with heparan sulfate showed a modest improvement in the modified neurological score 7 days after treatment (heparan sulfate vs placebo; 7.3±0.4 vs 8.8±0.5). Furthermore, the team tracked the distribution of the fluorescent tagged heparan sulfate and found the signals co-localized with endothelial cells (Collagen IV) and in neural stem cells (Nestin) within the peri-infarct regions. Histology analysis showed that heparan sulfate treatment enhances angiogenesis and neurogenesis (by approximately 3 to 7 folds) within the peri-infarct regions, without compromising the blood brain barrier integrity. The team also performed a series of cell culture studies and demonstrated that the heparan sulfate most likely stimulates vascular endothelial growth factor signaling.

Choosing the Path During Acute Stroke Treatment: Direct Transfer to Angio-Suite Versus Computed Tomography-Transit

Alejandro Rodríguez-Vázquez, MD

Pfaff JAR, Schönenberger S, Herweh C, Ulfert C, Nagel S, Ringleb PA, Bendszus M, Möhlenbruch MA. Direct Transfer to Angio-Suite Versus Computed Tomography–Transit in Patients Receiving Mechanical Thrombectomy: A Randomized Trial. Stroke. 2020;51:2630–2638.

Time is one of the most important elements when it comes to determining the efficacy of mechanical thrombectomy (MT) in acute stroke. The usual pathway across specialized stroke centers for initial evaluation of patients with suspected stroke includes a stop for neuroimaging like a multimodal-CT after the first clinical examination and before treatment. On the other hand, stroke imaging could be acquired directly in the angio-suite via flat-panel CT. There are some articles which defend this method as a faster and better way in terms of outcome to proceed with MT. However, this was not the subject of a clinical trial until now.

This was a prospective, single-center, parallel-group, open-label investigator initiated randomized trial in which the authors compare workflow metrics according to a CT-transit (CTT) pathway versus a direct transfer to the angio-suite (DTAS) pathway before MT. Both pathways include a non-contrast CT and a CT-angiography, plus a perfusion-CT (CTT) or a parenchymal blood volume imaging (DTAS) when presenting after 4.5 hours of symptom onset. The primary outcome of the study was time from stroke imaging to groin puncture. Other workflow metrics like admission to imaging or imaging to reperfusion time were also assessed, as well as final reperfusion and clinical outcome. The study included patients with an acute stroke secondary to a large vessel occlusion of the carotid territory with a National Institutes of Health Stroke Scale >7 and modified Rankin Scale 0-3 which undergo MT after a complete evaluation. In addition, intravenous thrombolysis (IVT) was performed if treatment criteria were fulfilled. Patients which required intubation between neuroimaging and groin puncture were excluded in order to minimize the mode of sedation bias. Wake-up strokes were also excluded because MRI was the preferred imaging method.

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

Article Commentary: “Safety of Anticoagulation in Patients Treated With Urgent Reperfusion for Ischemic Stroke Related to Atrial Fibrillation”

Song J. Kim, MD

Giustozzi M, Acciarresi M, Agnelli G, Caso V, Bandini F, Tsivgoulis G, Yaghi S, Furie KL, Tadi P, Becattini C, et al. Safety of Anticoagulation in Patients Treated With Urgent Reperfusion for Ischemic Stroke Related to Atrial Fibrillation. Stroke. 2020;51:2347–2354.

While the optimal timing of initiating or resuming anticoagulation in patients with acute strokes is said to be generally within 3-14 days, a treating neurologist may pause to consider the impact of recent IV thrombolysis or mechanical revascularization. Pharmacological thrombolysis carries an increased risk of brain hemorrhage, and reperfusion injury is a concern in the latter group of patients. At the same time, these potential adverse events must be weighed against the risk of recurrent thromboembolic events while anticoagulation is being held.

To address this issue, Giustozzi et al. set out to examine the incidence of both ischemic and hemorrhagic events in patients receiving anticoagulation following reperfusion therapies, as compared to untreated patients. The authors tapped into the RAF and RAF-NOAC datasets, which are prospective observational studies of patients receiving anticoagulation following stroke due to non-valvular atrial fibrillation. Primary outcome was the composite of any ischemic strokes and symptomatic intracranial hemorrhages, as well as other systemic embolism and bleeding events at 90 days. Furthermore, the authors conducted a multivariate logistic regression models to identify independent predictors of increased risk for the primary outcomes.

By |October 13th, 2020|clinical|0 Comments

Machine Learning as a Tool for Etiological Investigation in Stroke Medicine

Aurora Semerano, MD

Kamel H, Navi BB, Parikh NS, Merkler AE, Okin PM, Devereux RB, Weinsaft JW, Kim J, Cheung JW, Kim LK, et al. Machine Learning Prediction of Stroke Mechanism in Embolic Strokes of Undetermined Source. Stroke. 2020;51:e203–e210.

In 2014, when the concept of embolic stroke of undetermined source (ESUS) was proposed,1 confidence existed that ESUS could represent a single entity which would have benefitted from a unified treatment. However, after two randomized clinical trials did not show benefit of direct oral anticoagulation for secondary prevention of ESUS patients,2,3 it is now common opinion that these patients rather represent a heterogeneous population and are likely to benefit from tailored, personalized therapies. Today, ESUS represents a useful definition to identify patients deserving extended diagnostic workup, while prevention therapy for these patients remains elusive, and clinical stroke recurrence is still an issue. Both subgroup analyses from the above-mentioned clinical trials and new research studies have been developed or are ongoing, to better understand the pathophysiology of ESUS and help in patient selection.

In such a phenotypically heterogeneous population, one big effort is to identify patient subsets with a single or group of underlying mechanisms likely to respond to an established treatment. With this right purpose of uncover the “hidden structure” in a complex scenario, the recent study from Kamel et al.4 employs a machine learning approach. Firstly, a supervised machine-learning algorithm was developed to distinguish cardioembolic versus non-cardioembolic strokes in a population of 1083 patients with known stroke etiology, by entering data about demographics, comorbidities, vitals, laboratory results, and echocardiograms. After the learning process, the system finally resulted to distinguish cardioembolic from non-cardioembolic strokes with excellent accuracy (area under the curve, AUC=0.85).

Chaos About Treatment of Chaotic Heartbeat in Elderly Patients

Nurose Karim, MD

Okumura K, Akao M, Yoshida T, Kawata M, Okazaki O, Akashi S, Eshima K, Tanizawa K, Fukuzawa M, Hayashi T, et al. Low-Dose Edoxaban in Very Elderly Patients with Atrial Fibrillation. N Engl J Med. 2020.

Treatment of atrial fibrillation (AF) in the elderly population has always been challenging. Fragile age, multiple comorbidities, and fall risk put them as a red flag whenever a decision to anticoagulate them is made. Edoxaban is a direct oral factor Xa inhibitor. Studies have been done comparing low dose Edoxaban with warfarin and have found Edoxaban once-daily regimens noninferior to warfarin with respect to the prevention of stroke or systemic embolism and have been associated with significantly lower rates of bleeding and death from cardiovascular causes.1

The Edoxaban Low-Dose for EldeR CARE AF patients (ELDERCARE-AF) study is a phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study comparing the safety and efficacy of once-daily edoxaban 15 mg versus placebo in Japanese patients with NVAF ≥80 years of age who are considered ineligible for standard oral anticoagulant therapy.2

Article Commentary: “Young Women Had More Strokes than Young Men in a Large, United States Claims Sample”

Gurmeen Kaur, MBBS

Leppert MH, Ho PM, Burke J, Madsen TE, Kleindorfer D, Sillau S, Daugherty S, Bradley CJ, Poisson SN. Young Women Had More Strokes than Young Men in a Large, United States Claims Sample. Stroke. 2020.

Ekker MS, de Leeuw F-E. Higher Incidence of Ischemic Stroke in Young Women Than in Young Men: Mind the Gap. Stroke. 2020.

Strokes are a leading cause of disability in the United States. This is especially important for strokes in the young because those are individuals at the peak of their economic and professional productivity.

In this paper by Leppert et al., using PharMetrics, a commercial administrative database, the authors report very interesting findings. There is a higher incidence of strokes in young women between the ages of 25-34 years. The risk of new diagnosis of stroke is higher in men from ages 45-74 years, and there is no significant difference in the incidence rates among men and women at both extremes of age. This is contrary to the existing literature which shows that while the stroke incidence rate is higher in men even at older age, after the age of 85 years significantly more women suffer strokes than men because of the higher life expectancy in women.

By |October 8th, 2020|clinical|0 Comments

Article Commentary: “Blacks Are Less Likely to Present With Strokes During the COVID-19 Pandemic: Observations From the Buckle of the Stroke Belt”

Abdullah Ibish, MD

Cummings C, Almallouhi E, Al Kasab S, Spiotta AM, Holmstedt CA. Blacks Are Less Likely to Present With Strokes During the COVID-19 Pandemic: Observations From the Buckle of the Stroke Belt. Stroke. 2020.

In the midst of the COVID-19 pandemic and a national climate of social unrest following the aftermath of the George Floyd killing, the authors highlight a particular racial disparity as it pertains to predominantly Black communities. In their study of South Carolina patients from March 2019 to February 2020, the authors demonstrated a lower percentage of Black patients presenting with strokes during the pandemic for unclear reasons. We know from data from the REGARDS study (Reasons for Geographic And Racial differences in stroke), standard vascular risk factors alone were higher amongst Black persons, however only accounting for up to 40% of stroke incidences amongst White and Black patients.1 The remaining 60% of other stroke incidences remained unclear.

Moreover, recent studies have highlighted disproportionate cases of COVID-19 morbidity and mortality as it relates to minority communities, particularly Black patients.2,3 In this study, the investigators evaluated retrospective data, utilizing both pre- and post-COVID-19 pandemic stroke cases of over 5852 patients spanning March 2019 to February 2020 in South Carolina. This analysis included over 27 centers via a comprehensive tele-stroke network in South Carolina and assessed a myriad of different baseline characteristics as highlighted in their Table 1. Between the two groups (pre- and post-COVID-19 pandemic), there was a higher percentage of patients receiving intravenous tPA during the pandemic (15.5% versus 12.5% p=0.0037), and the number of thrombectomies per week was lower during the pandemic. Notably, however, there was a lower percentage of Black patients presenting via tele-stroke consultations during the pandemic (13.9% vs 29% prior to COVID-19 pandemic, p<0.001).

By |October 7th, 2020|clinical|0 Comments

The Effects of Age on Traditional Risk Factors for Stroke

Wern Yew Ding, MBChB

Ahmed A, Pinto Pereira SM, Lennon L, Papacosta O, Whincup P, Wannamethee G. Cardiovascular Health and Stroke in Older British Men: Prospective Findings From the British Regional Heart Study. Stroke. 2020.

I read with interest the cohort study by Ahmed and colleagues, which sought to evaluate the influence of cardiovascular health on stroke risk. The authors used data from the British Regional Heart Study to identify men with no prior history of cardiovascular disease at baseline who were then re-examined 20 years later. Cardiovascular health was assessed using 7 traditional health metrics, including smoking status, body mass index, level of physical activity, dietary patterns, total cholesterol, blood pressure, and fasting glucose. Outcome data comprised of fatal and non-fatal stroke.

At baseline, there was a total of 7274 men with a mean age of 50 years. As highlighted by the authors, blood pressure was the only parameter at both baseline and 20-year follow-up that was consistently associated with stroke risk in this population. Better levels of physical activity and smoking status at baseline were related to reduced stroke risk, but similar results were not observed using data from 20-year follow-up when the mean age was 69 years. Overall, the authors concluded that stroke prevention strategies should prioritize blood pressure control and other risk factors.