American Heart Association

Monthly Archives: January 2021

Can Women With Cerebral and Spinal Cavernous Malformations Safely Get Pregnant?

Muhammad Rizwan Husain, MD

Joseph NK, Kumar S, Brown Jr. RD, Lanzino G, Flemming KD. Influence of Pregnancy on Hemorrhage Risk in Women With Cerebral and Spinal Cavernous Malformations. Stroke. 2021;52:434–441.

In this entry, I discuss the publication by Nycole K. Joseph and colleagues regarding pregnancy and hemorrhagic risk with known cerebral and spinal cavernous malformations (CM). Previous studies have reported a hemorrhage risk as high as 11% in pregnant women with CM. However, those studies assumed that CM are congenital lesions, present throughout life, and that they contain both estrogen and progesterone receptors leading to their enlargement and potential rupture during pregnancy. However, over time, it has been demonstrated that CM are both acquired lesions and that they do not have, what was initially thought, the estrogen and progesterone receptors. The authors here have attempted to demonstrate how pregnancy influences the risk of hemorrhage in women of child-bearing age both in the pregnant and non-pregnant state, and included only those women with a known diagnosis of cerebral or spinal CM.

By |January 29th, 2021|clinical|0 Comments

Article Commentary: “Sex, Age, and Socioeconomic Differences in Nonfatal Stroke Incidence and Subsequent Major Adverse Outcomes”

Parneet Grewal, MD

Akyea RK, Vinogradova Y, Qureshi N, Patel RS, Kontopantelis E, Ntaios G, Asselbergs FW, Kai J, Weng SF. Sex, Age, and Socioeconomic Differences in Nonfatal Stroke Incidence and Subsequent Major Adverse Outcomes. Stroke. 2021;52:396–405.

Stroke is a leading cause of disability worldwide, and despite advances in management, mortality and disability rates remain high. This prospective population-based cohort study explores demographic variations in incidence of first ever non-fatal stroke and incidence of major adverse outcomes (composite major adverse cardiovascular events (MACE), recurrent stroke, cardiovascular (CVD)-related and all-cause mortality) after it. The data source of the study is UK Clinical Practice Research Datalink (CPRD), which collects de-identified patient data from data quality-assured GP practices across the UK. The cohort included patients aged 18 years and over who had first record of non-fatal stroke between January 1, 1998 and December 31, 2018. The patients were followed until they developed a major adverse outcome or left the original cohort for a mean follow up time of 1.81 years (SD: 2.78).

By |January 28th, 2021|clinical|0 Comments

Article Commentary: “Female Stroke: Sex Differences in Acute Treatment and Early Outcomes of Acute Ischemic Stroke”

Ericka Samantha Teleg, MD

Bonkhoff AK, Karch A, Weber R, Wellmann J, Berger K. Female Stroke: Sex Differences in Acute Treatment and Early Outcomes of Acute Ischemic Stroke. Stroke. 2021;52:406–415.

The new advances on stroke treatment, namely thrombolysis and mechanical thrombectomy, from year 2000 to 2018 allowed us to treat and improve stroke outcomes significantly in all age groups. Despite the reduction of stroke burden in many ways, this article highlights that women are expected to share a higher fraction of this burden, and, hence, it is necessary to address sex-specific characteristics in order to optimize acute ischemic stroke, namely in terms of stroke severity and administration of intravenous thrombolysis — there exists a gender specific difference in women having an increased stroke severity at onset and less uptake with IVT. Hence, the aim of this article is befitting as it analyzes 19 years of data of differences in symptom severity and disability upon admission, administration of acute ischemic treatments, in-hospital mortality and functional outcome at discharge in a large German stroke registry.

The study utilized data from the Stroke Registry Northwestern Germany. This registry was able to collect data from several hospital sites between January 1, 2000 and December 31, 2018. This brings about a heterogenous representative sample of the overall stroke population throughout a time that stroke advances were also evolving. Logistic regression models to estimate the effect of sex on the outcome were utilized. It is important that corresponding models were adjusted for covariates. The strength of the methodology is being able to delineate model adjustment for covariates through year periods, namely from year 2000 to 2009, and from year 2010 to 2018.

By |January 27th, 2021|clinical|0 Comments

Carotid Artery Stenting vs Endarterectomy: Are Risks Different in Women and Men?

Ammad Mahmood, MBChB

Howard VJ, Algra A, Howard G, Bonati LH, de Borst GJ, Bulbulia R, Calvet D, Eckstein H-H, Fraedrich G, Greving JP, et al. Absence of Consistent Sex Differences in Outcomes From Symptomatic Carotid Endarterectomy and Stenting Randomized Trials. Stroke. 2021;52:416–423.

Management of carotid artery stenosis has been approached differently in women and men since the 1990s following the NASCET criteria.1 More recently, trials comparing carotid artery stenting with endarterectomy have shown the modification of treatment effect by sex to be variable. The Carotid Revascularisation Endarterectomy vs Stenting Trial (CREST)2 suggested women receiving stenting were at higher periprocedural risk of stroke, myocardial infarction or death compared to men, though there was no difference in the primary endpoint (periprocedural risks above or ipsilateral stroke within 4 years). Conversely, the International Carotid Stenting Study (ICSS)3 suggested a borderline higher periprocedural risk for men undergoing stenting. 

This meta-analysis pooled data from four trials of carotid artery stenting vs endarterectomy — CREST, ICSS, Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S)4 and Stent-Protected Angioplasty versus Carotid Endarterectomy in Symptomatic Patients (SPACE).5 A total of 4754 patients, 1437 women (30%), were included. The majority of events were periprocedural (335/433). Combining periprocedural risk and risk of ipsilateral stroke thereafter, the risk for women of stenting versus endarterectomy was found to be significantly lower in EVA-3S, non-significantly lower in ICSS and non-significantly higher in both SPACE and CREST. Overall, they found heterogeneity and inconsistency between trials, making the pooling of data inappropriate to draw conclusions from. Pooled data showed a trend to higher risk of stenting which did not reach significance in women but did in men, with no significant difference between women and men. Similar results were seen when considering periprocedural risk alone.

By |January 26th, 2021|clinical|0 Comments

Age Excludes Women from Intracerebral Hemorrhage Trials

Saurav Das, MD  

Greige T, Norton C, Foster LD, Yeatts SD, Thornhill A, Griffin J, Wang J, Hrdlicka CM, Selim M, on behalf of the iDEF Investigators. Why Are Women Less Represented in Intracerebral Hemorrhage Trials? Stroke. 2021;52:442–446.

Despite a higher burden of intracerebral hemorrhage (ICH) in women, their enrollment in clinical trials is low. Given sex differences in pathophysiology and outcomes following ICH, disparities in enrollment limit the generalizability of trial results. In this study, Dr. Greige et al. examine the reasons for exclusion of women compared to men from the Intracerebral Hemorrhage Deferoxamine (iDEF) trial. The iDEF trial was a prospective, multicenter, randomized, placebo-controlled, double-blind, phase 2 trial that evaluated the use of deferoxamine mesylate versus placebo (saline) infusions in patients with ICH at 40 hospitals in Canada and the United States. The trial results were published in Lancet Neurology in May 2019.1 The screening log for all ICH patients found ineligible to participate in this study was reviewed to identify the reason for exclusion (of the 29 pre-defined reasons). Chi-square test was used to evaluate whether women and men differed with regard to reason for exclusion; adjustments for multiple testing were made during analyses. 

Characterizing Coronavirus and Stroke: A Review of “Acute Cerebrovascular Events in Hospitalized COVID-19 Patients”

Yasmin Aziz, MD

Rothstein A, Oldridge O, Schwennesen H, Do D, Cucchiara BL. Acute Cerebrovascular Events in Hospitalized COVID-19 Patients. Stroke. 2020;51:e219-e222.

The search for the association between coronavirus and stroke began months ago in China. Since that time, various studies from around the world have sought to identify the incidence of vascular complications from the virus. 

In this study from The University of Pennsylvania, the authors performed a retrospective observational study across three hospitals between March 15 and May 3 to evaluate the incidence and mechanism of stroke in patients with COVID-19. The authors first looked for hospital-admitted patients who tested positive for SARS-CoV2 and then filtered by patients who received head imaging (either CT or MRI). Mechanism was then determined by a stroke neurologist using TOAST classification criteria.

By |January 19th, 2021|clinical|0 Comments

Article Commentary: “Risk of Distal Embolization From tPA (Tissue-Type Plasminogen Activator) Administration Prior to Endovascular Stroke Treatment”

Walter Valesky, MD

Flint AC, Avins AL, Eaton A, Uong S, Cullen SP, Hsu DP, Edwards NJ, Reddy PA, Klingman JG, Rao VA, et al. Risk of Distal Embolization From tPA (Tissue-Type Plasminogen Activator) Administration Prior to Endovascular Stroke Treatment. Stroke. 2020;51:2697-2704.

The authors utilize a unique approach to weigh-in on a brewing controversy in acute ischemic stroke management: Is intravenous thrombolysis (IVT) beneficial in large vessel occlusion (LVO) in patients receiving endovascular therapy (EVT)? Rather than reporting on symptomatic intracranial hemorrhage, as is typical in studies evaluating IVT, these authors evaluated distal migration of clot that was subsequently not amenable to retrieval with EVT in patients treated with and without thrombolytics. The hypothesis being that IVT will reduce clot size to a point that it may be dislodged from a larger, more proximal vessel to embolize into a smaller caliber, more distal vessel and not be amenable to EVT.

For their evaluation, the authors utilized a retrospective record review of patients evaluated at the Kaiser Permanente healthcare system in Northern California undergoing EVT after presenting with symptoms of acute ischemic stroke. EVT was performed at one of two comprehensive stroke centers (CSC) in the area functioning as a receiving hospital for 19 other primary stroke centers (PSC). Patients were included whether they initially presented to the PSC and were transferred or if they presented directly to the CSC. Successful recanalization was defined as a modified thrombolysis in cerebral infarction (mTICI) scale of 2b/3.  

By |January 14th, 2021|clinical|0 Comments

Routine CT Perfusion Imaging as Therapeutic Decision Support in LVO: Too Much of a Good Thing?

Tolga D. Dittrich, MD

Lopez-Rivera V, Abdelkhaleq R, Yamal J-M, Singh N, Savitz SI, Czap AL, Alderazi Y, Chen PR, Grotta JC, Blackburn S, et al. Impact of Initial Imaging Protocol on Likelihood of Endovascular Stroke Therapy. Stroke. 2020;51:3055-3063.

Endovascular therapies (EVT) are a cornerstone of acute ischemic stroke therapy. CT- based perfusion imaging (CT-P), in addition to native CT and CT angiography, has become established in many clinics for the identification of patients with large vessel occlusions (LVO) who are eligible for EVT. But how does the choice of initial imaging protocol affect the probability of conducting EVT in patients with LVO?

A recent retrospective cohort study with four stroke centers has addressed this question. All four centers routinely performed native CT and CT angiography as part of the initial radiological assessment. The capacity to perform CT-P and EVT was present at all centers at all times. One participating center routinely performed additional CT-P with a high rate of usage (CTP-H), whereas the other three centers performed CT-P at a lower rate of usage (CTP-L) only at clinical discretion.

By |January 13th, 2021|clinical|0 Comments

Low-Dose Intravenous Alteplase in Stroke with Unknown Time Onset

Sohei Yoshimura, MD, PhD

Koga M, Yamamoto H, Inoue M, Asakura K, Aoki J, Hamasaki T, Kanzawa T, Kondo R, Ohtaki M, Itabashi R, et al. Thrombolysis With Alteplase at 0.6 mg/kg for Stroke With Unknown Time of Onset: A Randomized Controlled Trial. Stroke. 2020;51:1530–1538.

The guidelines of the American Heart Association/American Stroke Association recommend MRI to identify diffusion-positive FLAIR-negative lesions (DWI-FLAIR mismatch) for selecting patients who can benefit from IV alteplase in acute ischemic stroke (AIS) patients who awake with stroke symptoms or have unclear time of onset > 4.5 hours from last known well.1 The efficacy and safety of IV alteplase for these patients was revealed by the WAKE-UP trial.2

In the WAKE-UP trial, a favorable outcome defined by mRS 0 to 1 at 90 days was achieved in 53.3% in the alteplase group and 41.8% in the placebo group (adjusted odds ratio, 1.61; 95% confidence interval [CI], 1.09 to 2.36; P = 0.02). The trial was stopped early for lack of funding, and there was numerically more death (4.1% vs 1.2%, P=0.07) and significantly more symptomatic intracranial hemorrhage (sICH) (2.0% vs. 0.4%, P= 0.15). So, there still have been some concerns about safety of the therapy.

Risk of Distal Embolization from Intravenous Thrombolysis Prior to Endovascular Stroke Treatment: Does the Risk Outweigh the Benefits?

Setareh Salehi Omran, MD

Flint AC, Avins AL, Eaton A, Uong S, Cullen SP, Hsu DP, Edwards NJ, Reddy PA, Klingman JG, Rao VA, et al. Risk of Distal Embolization From tPA (Tissue-Type Plasminogen Activator) Administration Prior to Endovascular Stroke Treatment. Stroke. 2020;51:2697-2704.

Intravenous tissue-type plasminogen activator (IV tPA) and endovascular stroke treatment (EST) are considered standard-of-care for acute ischemic stroke. However, it is unclear whether there is a benefit to administrating IV tPA before EST in patients with large vessel occlusion who are eligible for both treatments. The need for IV tPA prior to EST has been further questioned by the results of the randomized DIRECT-MT trial, where EST alone was shown to be noninferior to IV tPA followed by EST.

Although IV tPA may improve early recanalization and reperfusion, there is concern for distal thrombus migration prior to EST, which may make the thrombus less accessible for endovascular retrieval. Data is scarce on how often this occurs. To address this issue, Flint et al performed a retrospective chart review of stroke cases in Kaiser Permanente Northern California’s Stroke EXPRESS program and examined the impact of IV tPA before EST on the rate of distal embolization, recanalization, and outcomes. The healthcare system comprises of 21 hospitals, two of which are comprehensive stroke centers, and is managed by a telemedicine program. All patients treated fully within the Kaiser Permanente Northern California system for both IV tPA and EST were included. Primary outcome was distal embolization, and secondary outcomes were angiographic (complete recanalization) and short- and long-term clinical improvements. Multivariable logistic regression was used to determine whether IV tPA with EST was associated with an increased risk of distal embolization compared to EST alone.

By |January 11th, 2021|clinical|0 Comments