American Heart Association

Monthly Archives: May 2019

ESOC 2019: Insights from the Large Clinical Trials Sessions, May 23 and 24

European Stroke Organisation Conference
May 22–24, 2019

Aristeidis H. Katsanos, MD, PhD

Thursday, May 23

In the first presentation of the second day of the Large Clinical Trials section, Dr. Hatem Wafa presented a study on the burden of stroke in Europe: 30-year projections of incidence, prevalence, deaths and disability-adjusted life years (DALYs). Dr. Wafa presented data on the epidemiological trends and demographic changes in stroke epidemiology across Europe, using data from the global burden of disease (GBD) between 1990 and 2017. Future trajectories up to 2047 were based on population projections and GDP prospects. Investigators found that the absolute burden of stroke increased between the years 1990 and 2017 and will continue to increase through 2047 in most EU countries. Lithuania was found to be the country with the largest increase in both stroke incidence (+0.48%) and prevalence (+0.7%), while Portugal was found to have the greatest reductions in both metrics (-1.57% and -1.3%, respectively). Stroke survivors are expected to increase by 27%, posing the need for more rehabilitation services and care homes.

In the presentation of a post-hoc analysis from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) trial on the interaction of blood pressure (BP) lowering and alteplase dose in thrombolysis-eligible acute ischemic stroke (AIS) patients, it was reported that in thrombolysis-treated AIS patients, low (0.6 mg/kg) vs. standard-dose alteplase (0.9 mg/kg) does not clearly modify the treatment effects of intensive (systolic BP<130-140mmHg) vs. guideline BP lowering (SBP<180mmHg) on the primary outcome of functional outcome, intracranial hemorrhage (ICH), death or serious adverse events. Investigators concluded that intensive BP lowering does not improve functional recovery or ICH risk with either low or standard-dose alteplase.

ESOC 2019 Session: Cerebral Small Vessel Disease

European Stroke Organisation Conference
May 22–24, 2019

Raffaele Ornello, MD

At the 5th European Stroke Organisation Conference, there was an interesting session on Thursday, May 23, about small vessel disease (SVD), a frequent cause of ischemic and hemorrhagic stroke.

Professor Leif Østergaard from Aarhus University presented the role of the alterations of capillary hemodynamics in the pathogenesis of SVD, while Professor Nikolaus Plesnila from the University of Munich discussed the role of pericytes in brain ischemia and neurodegeneration.

ESOC 2019 Session: Future Directions on Thrombolysis

European Stroke Organisation Conference
May 22–24, 2019

Lina Palaiodimou, MD

In general, this year’s European Stroke Organisation Conference was characterized by the presentation of numerous clinical dilemmas and highlighted the need for new research targeted to their resolution, which is most likely to be found on the ground of personalized medicine. The session “Future Directions on Thrombolysis” provided some insight about subjects regarding management of acute ischemic stroke that have perpetually troubled clinicians during everyday practice.

The first talk, by William Whiteley, confirmed safety and efficacy of intravenous thrombolysis using data from the analysis of pooled stroke thrombolysis trials. Specifically, it was confirmed that the proportional benefits of alteplase increase with earlier treatment, and this association is independent of age and stroke severity. There is, of course, an increased risk of death from intracerebral hemorrhage (ICH) in the alteplase treated patients, but there is no significant effect on other causes of early or later death. Among those patients treated earlier, there is a suggestion that the early hazard due to death from ICH may be compensated by a later benefit regarding death from any cause within 90 days. Whiteley finally concluded, presenting a well-intelligible graph, that the absolute balance of benefit versus risk depends chiefly on treatment delay and stroke severity.   

Johns Hopkins Stroke Dept. Live Blogs About “Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke”

Burton J. Tabaac, MD

Ma H, Campbell BCV, Parsons MW, Churilov L, Levi CR, Hsu C, et al. Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke. N Engl J Med. 2019; 380:1795-1803.

The following discussion is documented via “LIVE Blogging,” a Journal Club held at Johns Hopkins Hospital in Baltimore, Maryland, on May 14, 2019. The journal article presented is “Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke,” published in The New England Journal of Medicine on May 9, 2019. The Journal Club presentation and discussion was led by Dr. Rebecca Gottesman, a neurology professor, cerebrovascular specialist, and International Stroke Conference 2019 award recipient.

Current American Heart Association/American Stroke Association guidelines for ischemic stroke limit the time to initiate intravenous thrombolytic therapy to within 4.5 hours after the onset of stroke. Representatives from the EXTEND trial and collaborators from the University of Melbourne, Royal Melbourne Hospital, in Australia published an article that challenges this limit. By carefully selecting the appropriate patient population using advanced imaging, patients who have salvageable brain tissue beyond 4.5 hours may benefit from treatment via IV thrombolysis! The authors tested the hypothesis that “intravenous thrombolysis with alteplase initiated between 4.5 and 9.0 hours after stroke onset or on awakening with stroke symptoms (for which the time of onset was not known) would provide a benefit in patients who had a small core volume of cerebral infarction that was disproportionate to a larger area of hypoperfusion.”

This paradigm change to carefully select the appropriate patients who may benefit from therapy outside current guidelines parallels a similar historical trajectory to that of endovascular intervention in treating large vessel occlusion. For an epoch, the standard of care in approaching embolectomies relied on the patient presenting to clinical attention within 6 hours of onset and a favorable ASPECTS score on “dry” CT brain imaging. This limit was breached via conclusions drawn from the DAWN and DEFUSE 3 trials. By carefully selecting the appropriate patient population in concordance with advanced imaging (e.g., CTP, hyperacute MRI), offerable treatment was readily introduced to a much larger eligible patient population.

ESOC 2019 Session: Official Welcome & Large Clinical Trials

European Stroke Organisation Conference
May 22–24, 2019

Alan C. Cameron, MB ChB, BSc (Hons), MRCP

The 5th European Stroke Organisation Conference (ESOC 2019) has opened with a fantastic session in Milan on Wednesday! The conference was opened by ESO President Bart van der Worp, Conference Chair Jesse Dawson, and Chair of the Local Organising Committee Danilo Toni, who welcomed over 5,500 participants from 94 countries to the conference, which has doubled in size since inception over the last four years.

Ten landmark studies were presented at the official welcome. Key highlights include results from RESTART, which answers whether to start or avoid antiplatelet therapy after ICH in patients taking antiplatelets for the prevention of occlusive vascular disease. Remarkably, restarting antiplatelet therapy does not increase major haemorrhagic events. In contrast, restarting antiplatelet therapy may reduce recurrent ICH and protect against recurrent major vascular events. This provides reassuring evidence on restarting antiplatelet medication for secondary prevention of occlusive vascular disease in patients with ICH.

RESILIENT demonstrates the overwhelming efficacy of mechanical thrombectomy persists when implemented in the challenges of a developing country healthcare system such as Brazil. In this setting, thrombectomy decreases disability with a number needed to treat of only 6.6, has low complication rates and no increase in symptomatic ICH compared to medical therapy. We must now ensure the tremendous benefits of thrombectomy are available to more patients globally, including developing countries. 

Interview: Professor Dr. Hans-Christoph Diener on “Dabigatran for Prevention of Stroke after Embolic Stroke of Undetermined Source”

Professor Dr. Hans-Christoph Diener

Professor Dr. Hans-Christoph Diener

A conversation with Professor Dr. Hans-Christoph Diener, Faculty of Medicine at the University of Duisburg-Essen, on the recently published randomized clinical trials assessing the safety and efficacy of non-vitamin K oral anticoagulants (NOACs) in patients with embolic strokes of undetermined source (ESUS), and on the future of anticoagulation in the secondary prevention of cryptogenic cerebral ischemia.

Interviewed by Aristeidis H. Katsanos, Research Fellow at the Department of Neurology, Ruhr University of Bochum.

They will be discussing the paper “Dabigatran for Prevention of Stroke after Embolic Stroke of Undetermined Source,” published in the May 16, 2019 issue of the New England Journal of Medicine.

Dr. Katsanos: Can you please summarize for the readers of the blog the main hypothesis and findings of the RE-SPECT ESUS trial?

Prof. Diener: Patients with ESUS (embolic stroke of undetermined source) have high risk of recurrent stroke, and the risk of recurrent stroke per year is about 5%. We assume that the majority of these recurrent strokes have an embolic source. Therefore, oral anticoagulation should be superior to antiplatelet therapy in patients with ESUS.

Article Commentary: “Cerebral Ischemia in Patients on Direct Oral Anticoagulants”

Bahar M. Beaver, MD

Macha K, Marsch A, Siedler G, Breuer L, Strasser EF, Engelhorn T, et al. Cerebral Ischemia in Patients on Direct Oral Anticoagulants: Plasma Levels Are Associated With Stroke Severity. Stroke. 2019;50:873–879.

Although anticoagulation is standard of care for secondary prevention in patients with cardioembolic stroke and non-valvular atrial fibrillation (a-fib), we often see recurrent strokes in patients taking vitamin K antagonists (VKA) or direct oral anticoagulants (DOACs). This group of authors at the University Medical Center in Erlangen, Germany, performed an observational study using a patient registry in order to correlate oral anticoagulant activity and plasma levels with severity of ischemic stroke.

From the Erlangen Registry of Patients on Oral Anticoagulation (ER-NOAC), 460 patients with acute ischemic stroke while on oral anticoagulation for a-fib were selected from November 2014 to October 2017. Of these, 234 (50.9%) were on DOAC, and 226 (49.1%) were on VKA. Functional plasma levels were assessed in the patients on DOAC, and the results were broken down by low (<50 ng/ML), intermediate (50-100 ng/mL), and high (>100 ng/mL). For patients on VKA, the threshold INR was set at 1.7. From the 226 patients on VKA, 41.2% had an INR below 1.7. The investigators correlated the various lab findings to NIHSS at time of presentation.

Article Commentary: “Dual Antiplatelet Therapy Improves Functional Outcome in Patients With Progressive Lacunar Strokes”

Philip Chang, MD

Berberich A, Schneider C, Reiff T, Gumbinger C, Ringleb PA. Dual Antiplatelet Therapy Improves Functional Outcome in Patients With Progressive Lacunar Strokes. Stroke. 2019;50:1007–1009.

As neurologists, we have all encountered patients with mild lacunar stroke, confirmed on MRI to be a small subcortical lesion, especially if caught early on. However, some patients, despite a small stroke seen on early MRI having waxing and waning symptoms, for example going from complete plegia to a mild hemiparesis within the same hour. Why would this be the case? CHANCE and POINT enrolled patients of minor non-cardioembolic strokes, and proved that dual antiplatelet therapy was superior in reducing recurrent strokes in minor strokes with NIHSS<3. If one thinks about the enrollment criteria, this would likely leave small vessel disease, large vessel disease, and other/cryptogenic by TOAST criteria.

In my blog entries’ ongoing discussion on dual antiplatelet data, there has been a long story about likely success of dual antiplatelet therapy in stabilizing large artery atherosclerosis, both by transcranial doppler studies as well as a newly published study in Stroke, “Dual Versus Mono Antiplatelet Therapy in Large Atherosclerotic Stroke: A Retrospective Analysis of the Nationwide Multicenter Stroke Registry.” In my opinion, this likely drives a large portion of the effect size in CHANCE/POINT. However, early neurologic deterioration was not differentiated from early recurrent stroke in these trials, and a portion of the effect size may have been from dual antiplatelet treatment of lacunar strokes with early neurological deterioration, which likely includes entities such as “stuttering lacunar syndrome” or “capsular warning syndrome.”

Craniocervical Arterial Dissection: A Common Cause of Stroke in Childhood

Alejandro Fuerte, MD

Nash M, Rafay MF. Craniocervical Arterial Dissection in Children: Pathophysiology and Management. Pediatric Neurology. 2019

Craniocervical arterial dissection (CCAD) is a crucial emergency state causing 7.5% to 20% of all childhood arterial ischemic stroke (AIS) cases, with an annual incidence of all AIS estimated at 2.5 to 8 per 100,000 children per year. Childhood CCAD cases are often spontaneous or in association with head and neck trauma, both blunt injuries and hyperextension or manipulation of the neck. With spontaneous CCAD, at least 5% to 20% of children have an underlying risk factor, such as connective tissue diseases, genetic disorders, anatomic vascular variations or familial segregation. The clinical presentation of CCAD is non-differentiating from other causes of AIS aside from a history of head and neck trauma or pain. Magnetic resonance imaging is the preferred neuroimaging method, followed by cerebral catheter angiography as a gold standard definitive neurovascular imaging modality when initial vascular imaging reveals non-diagnostic findings.

For this review, the authors searched MEDLINE (2000 to 2018) for articles that contained patients aged less than 18 years with craniocervical arterial dissection, with the aim of analyzing their characteristics. Sixteen articles met the study criteria and reported 182 cases of craniocervical arterial dissection. 68% were male individuals, with an average of 8.6 years of age. From the 182 cases reviewed, 102 (56%) cases experienced concurrent or preceding trauma as the risk factor for dissection; 25% of these were associated with some type of contact sport or physical activity, and skull or spine fracture(s) was listed as a risk factor in 14%. Several risk factors were identified among the spontaneous dissection cases (mainly aberrant vertebral arcuate foramina).

Author Interview: Dr. Diogo Haussen, MD, and Dr. Thomas Madaelil, MD, on “Multimodality Imaging in Carotid Web”

Dr. Diogo Haussen, left, and Dr. Thomas Madaelil

Dr. Diogo Haussen, left, and Dr. Thomas Madaelil

A conversation with Dr. Diogo Haussen, MD (Assistant Professor of Neurology, Emory School of Medicine/Grady Memorial Hospital), and Dr. Thomas Madaelil, MD (Neurointerventional Fellow, Emory School of Medicine), on imaging and clinical significance of carotid web.

Interviewed by Sami Al Kasab, MD (StrokeNet fellow, University of Iowa Hospitals and Clinics).

They will be discussing the paper “Multimodality Imaging in Carotid Web,” published in Frontiers in Neurology.

Dr. Al Kasab: I read with great enthusiasm your recent article comparing different imaging modalities to diagnose a carotid web. Can you please summarize the key findings of your study, and how your results can be applied to our clinical practice?

Drs. Haussen and Madaelil: Thank you for your interest in our manuscript. Acute ischemic stroke is commonly a devastating condition, especially when occurring in young adults. Occasionally, we can get tangled when we cast wide nets for the diagnostic work-up in patients with cryptogenic stroke. Carotid web is a condition that can be overlooked when neurovascular studies are reviewed during this diagnostic work-up period, and it may actually be more common that previously thought. Our study is aimed to help shed light on the performance of different imaging modalities in the diagnosis of carotid web, which is particularly important since there were no previously published comparative studies. We observed that computed tomographic angiogram (CTA) shared very high rates of inter-rater agreement with digital subtraction angiogram (DSA), while the CTA agreement with ultrasonography was much more limited. Therefore, non-invasive multiplanar imaging modalities, such as CTA, should be considered in the evaluation of young patients with otherwise no identified stroke cause considering the possibility of an underlying carotid web.