American Heart Association

Monthly Archives: August 2019

Clot Histology: A Possible Clue to the Etiology of Ischemic Stroke

Piyush Ojha, MBBS, MD, DM

Fitzgerald S, Dai D, Wang S, Douglas A, Kadirvel R, Layton KF, et al. Platelet-Rich Emboli in Cerebral Large Vessel Occlusion Are Associated With a Large Artery Atherosclerosis Source. Stroke. 2019;50:1907–1910.

Stroke accounts for approximately 10% of all deaths worldwide and leads to substantial long-term disability. The majority of the strokes are ischemic in origin. No identifiable cause is found in up to one-third of the patients after a standard evaluation, which limits the options for secondary stroke prevention. Mechanical thrombectomy has been found to be highly effective in patients with large vessel occlusions (LVO). In addition to the revascularisation, endovascular procedures have also created a unique opportunity to identify the likely stroke pathogenesis by providing thrombus material for further study. Emerging insights on various thrombus characteristics can not only provide valuable information that might be useful for guiding acute therapies, but also in optimizing secondary stroke prevention, as different components in the clot may respond to different pharmacological strategies.

Studies have tried to correlate thrombus histological composition and stroke pathogenesis. Sporns et al.1 observed that clots from a cardioembolic source had a higher proportion of fibrin/platelets and fewer red blood cells than noncardioembolic thrombi.

NLRP3 Inflammasome as a Therapeutic Target for Ischaemic Stroke: Are We Really There Yet?

Melissa Trotman-Lucas, PhD
@TroLucaM

Lemarchand E, Barrington J, Chenery A, Haley M, Coutts G, Allen JE, et al. Extent of Ischemic Brain Injury After Thrombotic Stroke Is Independent of the NLRP3 (NACHT, LRR and PYD Domains-Containing Protein 3) Inflammasome. Stroke. 2019;50:1232-1239.

Inflammation plays a key role in the fight against infection. However, following ischaemic brain injury, inflammation can play a very different role, exacerbating the severity of damage. Inflammation results in long lasting, ongoing damage from the onset of vessel blockage through to and during reperfusion of the ischaemic brain area. One possible player within the inflammation related post-stroke damage is the NLR family pyrin domain containing 3 (NLRP3) inflammasome. During ischaemic brain injury, NLRP3 senses multiple stroke-induced stimuli leading to the recruitment of the adaptor protein ASC (the apoptosis-associated speck-like pro-caspase-1) resulting in caspase 1 production leading to downstream IL-1β and IL-18 production and release. IL-1β is well-reported to have significant pro-inflammatory and pro-apoptotic effects during acute ischaemic stroke.   

A recent study by Lemarchand et al., published in Stroke, sought to determine the importance of NLRP3 to the damage occurring following ischaemic brain damage. Previous studies have reported associations between NLRP3 and an increase in the severity of ischaemic brain injury, leading to the suggestion that targeting NLRP3 could be a potential therapeutic avenue. These previous studies report NLRP3 inhibition to be protective during ischaemia, alongside data showing that mice deficient in NLRP3 show decreased damage when compared to WT counterparts. However, contrary to this, the group responsible for the paper discussed here have previously reported that ischaemic brain injury develops independent of the NLRP3 inflammasome in a rodent model of stroke, suggesting instead that the NLRC4 (NLR family, CARD containing 4) and AIM2 (absent in melanoma 2) inflammasomes contribute to the resulting brain injury, independent of NLRP3. Lemarchand et al. sought to categorically determine the role of NLRP3 in ischaemic stroke damage, using genetic and pharmacological inhibition of NLRP3. Furthermore, to increase the robustness of the data, the group utilized the FeCl3 (ferric chloride induced thrombosis) model of preclinical ischaemic stroke, where FeCl3 soaked strips are applied to the middle cerebral artery causing localized and immediate thrombus formation, a model that may have considerable clinical relevance.   

Narrowing the ESUS Concept: Left Atrial Volume Index as Indicator of Left Atrial Enlargement and its Relationship with Presence of AF in Stroke Patients

Reyes de Torres Chacon, MD

Jordan K, Yaghi S, Poppas A, Chang AD, Mac Grory B, Cutting S, et al. Left Atrial Volume Index Is Associated With Cardioembolic Stroke and Atrial Fibrillation Detection After Embolic Stroke of Undetermined Source. Stroke. 2019;50:1997–2001.

The concept of ESUS is still a broad field of study that includes multiple etiologies, including hidden atrial fibrillation (AF), among many others. The latest published studies of secondary prevention in patients with ESUS (NAVIGATE-ESUS, RESPECT-ESUS) have not demonstrated superiority of anticoagulation versus aspirin, probably due, among other reasons, to the etiological heterogeneity of the ESUS concept. The latest studies, still in development, such as ARCADIA or ATTICUS, seek to refine and reformulate the concept of ESUS using biomarkers of atrial pathology such as morphological (left atrial enlargement) or electrical changes (atrial high rate episodes, increased P-wave terminal force in V1 on ECG) as indicators of hidden atrial fibrillation in patients with ESUS.

Jordan et al. show that left atrial enlargement measured as left atrial volume indexed (LAVI) is a good biomarker of the presence of atrial fibrillation in stroke patients. The LAVI of 1020 patients admitted to their hospital after an ischemic stroke are prospectively analyzed and correlated with the etiological subtype, divided into three categories: cardioembolic stroke (CES), non-cardioembolic stroke (NCE), and ESUS. In addition, in the ESUS subtype, prolonged cardiac monitoring was performed in 24% of them, with a hidden AF detection rate of 18.2%.

By |August 27th, 2019|clinical|0 Comments

Is Triple Antithrombotic Therapy History?

Victor J. Del Brutto, MD

Knijnik L, Rivera M, Blumer V, Cardoso R, Fernandes A, Fernandes G, et al. Prevention of Stroke in Atrial Fibrillation After Coronary Stenting: Systematic Review and Network Meta-Analysis. Stroke. 2019;50:2125–2132

Approximately one-fourth of patients with atrial fibrillation (AF) have coronary artery disease (CAD), and a significant number of them undergo percutaneous coronary intervention (PCI) and stent placement. This clinical scenario represents a special circumstance in which a combined antithrombotic regimen with platelet anti-aggregation (to prevent stent thrombosis and myocardial ischemia) and anticoagulation (to prevent AF-related cardioembolic stroke) is warranted. Previously, in the absence of randomized controlled trials, guidelines supported the use of a Vitamin K antagonist (VKA) and dual antiplatelet (DAPT), especially when drug eluting stents were used. This regimen known as “triple therapy” has shown to have a fourfold risk of bleeding complications when compared to oral anticoagulation alone.

Author Interview: Prof. Kazuo Kitagawa, MD, PhD, on “Effect of Standard vs Intensive Blood Pressure Control on the Risk of Recurrent Stroke”

Prof. Kazuo Kitagawa
Prof. Kazuo Kitagawa

An interview with Prof. Kazuo Kitagawa, MD, PhD, Department of Neurology, Tokyo Women’s Medical University, Tokyo, Japan, about the optimal blood pressure goal for secondary stroke prevention.

Interviewed by Dr. Mohammad Anadani, MD, neurocritical care fellow, Washington University, St. Louis, MO.

They will be discussing the article “Effect of Standard vs Intensive Blood Pressure Control on the Risk of Recurrent Stroke: A Randomized Clinical Trial and Meta-analysis,” published in JAMA Neurology.

Dr. Anadani: First, I want to thank Prof. Kitagawa for agreeing to the interview. Prof. Kitagawa is the lead investigator of the RESPECT trial, which investigated the optimal blood pressure goal for secondary stroke prevention.

Could you please share with the readers the rationale behind the RESPECT trial and summarize the key findings of the trial?

Dr. Kitagawa: Although the SPRINT trial recently demonstrated that a systolic blood pressure (BP) target of <120 mmHg was superior to <140 mmHg for preventing vascular events, no evidence was published about what is the optimal blood pressure target in the secondary stroke prevention.

In the RESPECT Study that included 1263 patients with a history of stroke, intensive blood pressure control to less than 120/80 mmHg tended to reduce stroke recurrence compared with standard blood pressure control (<140/90 mmHg). When this finding was pooled with the results of prior trials of intensive blood pressure control for secondary stroke prevention in an updated systematic review, intensive blood pressure treatment significantly reduced stroke recurrence by 22%. In conclusion, intensive blood pressure control to less than 130/80 mmHg is recommended for secondary stroke prevention.

Racial and Ethnic Disparities in Thrombectomy for Acute Stroke

Rachel Forman, MD

Rinaldo L, Rabinstein AA, Cloft H, Knudsen JM, Rangel Castilla L, Brinjikji W. Racial and Ethnic Disparities in the Utilization of Thrombectomy for Acute Stroke: Analysis of Data From 2016 to 2018. Stroke. 2019

I was excited for the chance to review this article, as this topic is near and dear to my heart as someone who does community stroke education to help improve healthcare disparities in this area. From my experience in providing stroke education to more diverse communities, there is much less knowledge in terms of recognizing stroke symptoms and the importance of prompt care to be eligible for tPA and mechanical thrombectomy (MT).  Unfortunately, I was not surprised when I read the results of this paper. 

It has already been established that minority patients receive less MT; however, this study looked at updated data (2016-2018) to see if this still held true following the publication of multiple positive MT trials in 2015. MT has become increasingly utilized after a series of positive trials published in 2015 and is now the standard of care for treatment of stroke due to large vessel occlusion. For more information on these trials, the HERMES collaboration is a meta-analysis of five major trials in The Lancet, published in 2016. 

By |August 21st, 2019|clinical|0 Comments

Better is the Enemy of Good

Elena Zapata-Arriaza, MD
@ElenaZaps

García-Tornel A, Requena M, Rubiera M, Muchada M, Pagola J, Rodriguez-Luna D, et al. When to Stop: Detrimental Effect of Device Passes in Acute Ischemic Stroke Secondary to Large Vessel Occlusion. Stroke. 2019;50:1781–1788

The achievement of mTICI 3 after one pass, known as first pass effect, is clearly associated with better functional outcome, as compared with those patients with more passes needed to obtain full recanalization. But how many passes should we attempt before stop procedure? Or maybe we should pursue a good (TICI 2B) but not perfect recanalization, instead of seeking TICI 3, because such recanalization is more than enough for patient outcome?

These are some of the aims of this study, in addition to finding the relation between number of passes and recanalization degree and clinical outcome.

Can We Predict Post Thrombectomy Hematoma?

Elizabeth M. Aradine, DO

Boisseau W, Fahed R, Lapergue B, Desilles J-P, Zuber K, Khoury N, et al. Predictors of Parenchymal Hematoma After Mechanical Thrombectomy: A Multicenter Study. Stroke. 2019

Parenchymal hematoma (PH) is a potential complication of IV thrombolytics or mechanical thrombectomy; however, risk factors for hematoma after thrombectomy are still uncertain. PH after acute stroke intervention can increase morbidity and mortality. In this study, the authors retrospectively reviewed data from a registry of thrombectomy patients to identify variables to predict post thrombectomy PH. Patients presenting with an anterior circulation large vessel or intracranial carotid occlusion who had a thrombectomy from 2011-2016 were included. MRI or CT based brain and vessel imaging were used to select patients for thrombectomy and to calculate the ASPECT score. Post thrombectomy, a 24-hour brain image was routinely performed on all patients to evaluate for PH. PH was classified using the European Cooperative Acute Stroke Study (ECASS) criteria. 90-day post stroke outcome was assessed using the mRS. This data was compared to baseline patient characteristics including age, smoking status, hypertension, diabetes, admission NIHSS, and antiplatelet or anticoagulation use. Data on the presence of collateralization on angiogram and general anesthesia use was also recorded.

By |August 19th, 2019|clinical|0 Comments

Article Commentary: “Causes and Risk Factors of Cerebral Ischemic Events in Patients With Atrial Fibrillation Treated With Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention”

Yan Hou, MD, PhD

Paciaroni M, Agnelli G, Caso V, Silvestrelli G, Seiffge DJ, Engelter S, et al. Causes and Risk Factors of Cerebral Ischemic Events in Patients With Atrial Fibrillation Treated With Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention: The RENo Study. Stroke. 2019;50:2168–2174

Non–vitamin K antagonist oral anticoagulants (NOACs) are currently recommended as the stroke prevention for patients with nonvalvular atrial fibrillation (AF). Despite compliance with NOAC, patients with nonvalvular AF may still experience ischemic cerebrovascular events. The RENO study is a multicenter case-control study to identify the etiology and risk factors for ischemic events occurring during NOACs (dabigatran, apixaban, rivaroxaban, or edoxaban) therapy in patients with nonvalvular AF.

The study included 713 cases (641 ischemic strokes and 72 TIA) and 700 controls (patients did not experience cerebrovascular events). Cases who did not guarantee compliance or who had suspended NOAC at least 24 hours before the cerebrovascular event were excluded. Most strokes (64%) occurring during NOACs therapy were caused by cardioembolism, but about 30% of strokes were found due to non-cardioembolic etiology. Among the risk factors (age, sex, hypertension, diabetes mellitus, current cigarette smoking, hyperlipidemia, ischemic heart disease, peripheral artery disease, alcohol abuse, obesity, previous stroke/transient ischemic attack, creatinine clearance, duration of NOAC treatment, doses of NOACs, AF classification, CHA2DS2-VASc score, left atrial enlargement on echo), off-label low doses of NOACs (OR, 3.18), atrial enlargement (OR, 6.64), hyperlipidemia (OR, 2.40), and high CHA2DS2-VASc score (OR, 1.72 for each point increase) were associated with ischemic events. The reasons for prescribing low doses of NOAC included fear of bleeding, history of bleeding, concomitant antiplatelet therapy, recurrent falls, amyloid angiopathy, anemia, history of cancer, age, gastrointestinal discomfort, and hypertension or other causes. Low clearance of creatinine (OR, 0.98 for 1 mL/min increase) and high CHA2DS2-VASc score (OR, 1.35 for each point increase) were also found associated with prescription of low-dose NOACs.   

When More is More: The Benefit of Combination Therapy for Large Vessel Occlusion Ischemic Stroke

Charlotte Zerna, MD, MSc
@CharlotteZerna

Young-Saver DF, Gornbein J, Starkman S, Savel JL. Magnitude of Benefit of Combined Endovascular Thrombectomy and Intravenous Fibrinolysis in Large Vessel Occlusion Ischemic Stroke. Stroke. 2019

Little is known about the effect size of the combination of intravenous alteplase therapy (IVT) and endovascular therapy (EVT) compared to supportive treatment alone for patients with anterior circulation large vessel occlusion (LVO). At the time EVT was proven effective with the randomized controlled trials, IVT had already been the standard of care for almost 20 years and thus chosen as a comparator group. Since no randomized controlled trial data are available to compare IVT+EVT to supportive therapy alone, Young-Saver et al. chose to undertake a post-hoc analysis matching patients from the Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT-PRIME) trial with patients from the 2 National Institute for Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator (NINDS rt-PA) trials.

In the main analysis, a total of 240 patients (80 from the SWIFT-PRIME IVT+EVT group, 80 from the NINDS rt-PA Study IVT alone group, and 80 from the NINDS rt-PA Study placebo group) were 1:1 inverse variance matched for presenting National Institutes of Health Stroke Scale (NIHSS) score to identify NINDS rt-PA Study patients likely harboring LVOs and age since it is a strong determinant of outcome. The 90-day modified Rankin Scale (mRS) score was used as the outcome, analyzed both as an ordinal scale (shift across all 7 mRS levels) with ordinal logistic regression analysis and as a dichotomized outcome ( 0-1 vs. 2-6 and 0-2 vs. 3-6) using Fisher exact test.

By |August 14th, 2019|clinical|0 Comments