American Heart Association

Monthly Archives: January 2022

Article Commentary: “Sex Differences in Presentation of Stroke: A Systematic Review and Meta-Analysis”

Farah Aleisa, MD

Ali M, van Os HJA, van der Weerd N, Schoones JW, Heymans MW, Kruyt ND, Visser MC, Wermer MJH. Sex Differences in Presentation of Stroke: A Systematic Review and Meta-Analysis. Stroke. 2021.

In the literature, women do worse after stroke than men, mortality and severe stroke are higher among women, and atypical clinical presentation of acute stroke could explain the higher rate of misdiagnosis in women. Interestingly, a previous cohort study indicated that women who presented with a transient ischemic attack (TIA) or minor stroke more frequently received a diagnosis of stroke mimic compared with men with similar symptomatology; at the same time, stroke recurrence rate within 90 days of stroke onset were similar in both men and women, raising the possibility of sex biases in diagnosing acute stroke. Here, we will go through a systematic analysis of different acute stroke presentations between men and women.

By |January 31st, 2022|clinical|Comments Off on Article Commentary: “Sex Differences in Presentation of Stroke: A Systematic Review and Meta-Analysis”
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Article Commentary: “Sex Difference and Rupture Rate of Intracranial Aneurysms”

Isabella Canavero, MD

Zuurbier CCM, Molenberg R, Mensing LA, Wermer MJH, Juvela S, Lindgren AE, Jääskeläinen JE, Koivisto T, Yamazaki T, Uyttenboogaart M, et al. Sex Difference and Rupture Rate of Intracranial Aneurysms: An Individual Patient Data Meta-Analysis. Stroke. 2022.

A higher prevalence of both intracranial aneurysms and aneurysmal subarachnoid hemorrhage (aSAH) in women than in men has been reported by many studies. However, female sex has not been identified as an independent risk factor in rupture rate of intracranial aneurysms according to the PHASES score, which is a validated scoring system that takes into account both patient- and aneurysm-related features, including geographic location, hypertension, age, history of aSAH, aneurysm size and location.

By hypothesizing a different prevalence of patient- or aneurysm-related risk factors for rupture (including the PHASES score, smoking, and a positive family history for aSAH) among sexes, Zuurbier and colleagues performed a pooled analysis of individual patient data from nine prospective cohort studies, examining about 10000 patients, to assess if sex is an independent risk factor for rupture.

By |January 28th, 2022|clinical, hemorrhage|Comments Off on Article Commentary: “Sex Difference and Rupture Rate of Intracranial Aneurysms”
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Article Commentary: “Sex-Related Differences in Outcomes After Endovascular Treatment of Patients With Late-Window Stroke”

Vignan Yogendrakumar, MD MSc
@VYogendrakumar

Bala F, Casetta I, Nannoni S, Herlihy D, Goyal M, Fainardi E, Michel P, Thornton J, Power S, Saia V, et al. Sex-Related Differences in Outcomes After Endovascular Treatment of Patients With Late-Window Stroke. Stroke. 2022.

To date, differences in clinical outcomes between males and females undergoing endovascular therapy (EVT) within the early time window have not been observed. Outcome data in the late window (> 6 hours from symptom onset) stratified by sex remains limited. To that effect, Bala and colleagues sought to use data from the SOLSTICE Consortium to investigate potential differences in outcomes between males and females undergoing EVT in the late window.

The SOLSTICE Consortium is an individual-patient level analysis of data from select registries and clinical trials. Patient selection for EVT in the late window was based on collateral or perfusion imaging. Outcomes evaluated in this analysis include functional independence (mRS ≤ 2), mRS shift, mortality at 90 days, and symptomatic intracranial hemorrhage.

By |January 27th, 2022|clinical, treatment|Comments Off on Article Commentary: “Sex-Related Differences in Outcomes After Endovascular Treatment of Patients With Late-Window Stroke”
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Are Young Women at Higher Risk of Ischemic Stroke Than Their Male Counterparts?

Csilla Manoczki, MD

Leppert MH, Burke JF, Lisabeth LD, Madsen TE, Kleindorfer DO, Sillau S, Schwamm LH, Daugherty SL, Bradley CJ, Ho PM, Poisson SN. Systematic Review of Sex Differences in Ischemic Strokes Among Young Adults: Are Young Women Disproportionately at Risk? Stroke. 2022;53:319–327.

Historically, stroke epidemiological studies have reported a higher rate of incident strokes in men than women, regardless of age. In the last decade, increasing evidence suggest that there may be more complexity to this “gender gap”, including a shift towards increased incidence of ischemic strokes in younger women.

In this systematic review of 16 population-based studies with nearly 70,000 patients included between 2008 and 2021, stroke incidence rate ratios for women/men in adults younger than age 45 years were calculated and standardized for each study. Combined incidence rate ratios were estimated for three age groups (≤35, 35-45, ≤45 years), and by ischemic stroke vs. all stroke types. Overall effect on the estimates was calculated by the study weights based on variability of the incidence rate ratios.

By |January 26th, 2022|clinical|Comments Off on Are Young Women at Higher Risk of Ischemic Stroke Than Their Male Counterparts?
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How Does Risk of Stroke Following Childbirth Differ Based on Hypertensive Disorder of Pregnancy Subtype? How Does Risk Change Over Time for Hemorrhagic and Ischemic Stroke?

Hannah Roeder, MD, MPH

Hung S-K, Lee M-S, Lin H-Y, Chen L-C, Chuang C-J, Chew C-H, Yu B-H, Yang H-J, Hsu F-C, Chiou W-Y. Impact of Hypertensive Disorders of Pregnancy on the Risk of Stroke Stratified by Subtypes and Follow-Up Time. Stroke. 2022.

Hypertensive disorders of pregnancy (HDP) are a common obstetric complication and are associated with an increased risk of vascular disease later in life. Hung et al. investigate whether the four subtypes of HDP (1. chronic hypertension (HTN), 2. chronic HTN with superimposed preeclampsia, 3. preeclampsia/eclampsia, and 4. gestational HTN) lead to different patterns of subsequent ischemic and hemorrhagic stroke.

 The authors employed the Taiwan National Health Insurance Research Database to identify pregnancies in women aged 18 to 45 years old (without a prior history of stroke) between the years 2000 and 2017. Exact matching (of age, delivery method, gestation number, hospital level, delivery season, geographic area, income, and co-morbidities) was employed to recruit HDP patients and controls in a 1:4 ratio. Firstly, 17,588 women with HDP were initially identified, but after exact matching 13,617 were included. Adjusted hazard ratios for ischemic and hemorrhagic stroke were calculated, and a stratified analyses of stroke risk for the four HDP subtypes were performed. The authors also stratified risk by follow-up time after childbirth.

By |January 25th, 2022|clinical|Comments Off on How Does Risk of Stroke Following Childbirth Differ Based on Hypertensive Disorder of Pregnancy Subtype? How Does Risk Change Over Time for Hemorrhagic and Ischemic Stroke?
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Targeting Pro-Inflammatory Neuronal Death After Intracerebral Hemorrhage Improves Neurological Deficits in Mice

Kristina Shkirkova, BSc

Yan J, Xu W, Lenahan C, Huang L, Wen J, Li G, Hu X, Zheng W, Zhang JH, Tang J. CCR5 Activation Promotes NLRP1-Dependent Neuronal Pyroptosis via CCR5/PKA/CREB Pathway After Intracerebral Hemorrhage. Stroke. 2021.

Intracerebral hemorrhage (ICH) is the most debilitating stroke subtype, resulting in higher mortality and disability than ischemic stroke. The mechanism of vessel rapture results in blood leaking into the brain tissue, leading not only to physical damage to the surrounding tissue, but also triggering a severe acute inflammatory response in the brain. Acute inflammation is driven by several inflammatory cytokines and inflammasomes that initiate cellular pathways of pyroptosis that ultimately result in neuronal death. 

In this study, the authors focused on a neuronal cell death pathway that involves C-C chemokine receptor 5 (CCR5), which is located in the cell membrane and regulates leukocytes transport in the cells. Using mice with induced IHC, the authors targeted deactivation of this receptor to reduce the inflammatory response in the brain using an antagonist agent to CCR5. After 1 hour of induced ICH in mice, CCR5 antagonist treatment resulted in reduced number of neuronal cells undergoing degeneration and death at 24 and improved neurological motor and sensorimotor functioning at 24 and 72 hours. CCR5 antagonist treatment also significantly increased protein kinase A (PKA) and cAMP response element binding protein (CREB) levels.

By |January 21st, 2022|basic sciences|Comments Off on Targeting Pro-Inflammatory Neuronal Death After Intracerebral Hemorrhage Improves Neurological Deficits in Mice
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Mortality and Pediatric Stroke

Kevin O’Connor, MD

Sundelin HEK, Walås A, Söderling J, Bang P, Ludvigsson JF. Long-Term Mortality in Children With Ischemic Stroke: A Nationwide Register-Based Cohort Study. Stroke. 2021.

Having recently explored post-stroke epilepsy in children, Sundelin et al. now examine mortality following pediatric stroke (<18 years of age). They identified children who had an ischemic stroke (n=1,327) along with matched controls (n=13,269) using several registers of the Swedish population (1969-2016). Of the 1,327 pediatric strokes, 343 (25.8%) were perinatal strokes and 984 were (74.2%) ischemic, which also included cerebral venous sinus thrombosis (CVST) as it could not be differentiated from ischemic stroke in the registers.

Pediatric ischemic stroke was associated with increased mortality beyond one week of follow-up from stroke (HR=10.8 [95% CI, 8.1–14.3]). Mortality remained increased past one year (HR=7.7 [95% CI, 5.6–10.7]) and past 20 years (HR=3.9 [95% CI, 2.1–7.1]). The highest risk for mortality was between one week and 6 months (HR=43.3 [95% CI, 17.8–105.3]). Overall mortality risk was elevated for both perinatal stroke (≤28 days; HR=7.0 [95% CI, 3.4–14.7]) and childhood stroke (>28 days of age; HR=11.6 [95% CI, 8.5–15.8]) without a statistically significant difference between the two. Notably, females (HR=16.7 [95% CI, 10.2–27.4]) had a statistically significant (P=0.03) higher mortality risk than males (HR=8.5 [95% CI, 6.0–12.1]).

By |January 20th, 2022|clinical, outcomes, prognosis|Comments Off on Mortality and Pediatric Stroke
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Advanced ML Algorithms: The Future of CT Perfusion?

Arooshi Kumar, MD
@ArooshiK

Bathla G, Liu Y, Zhang H, Sonka M, Derdeyn C. Computed Tomography Perfusion–Based Prediction of Core Infarct and Tissue at Risk: Can Artificial Intelligence Help Reduce Radiation Exposure? Stroke. 2021;52:e755–e759.

It is well accepted that advanced CT perfusion (CTP) technology can help select patients who could benefit from endovascular treatment (EVT).1 However, CTP imaging is arterial input dependent, requires higher radiation than CT angiography, and utilizes timely and costly post-processing software.2,3 Authors Bathla et al. in this study explored if a machine learning algorithm, a convolutional neural network, which establishes complex relationships between many layers of visual imagery, could estimate cerebral blood flow and area-at-risk similar to the standard arterial dependent prediction method (RAPID).

Retrospective CTP data from 57 patients was split into training/validation (60%/40%) sets. The authors devised and validated separate U-net models, allowing for imaging segmentation, to predict core infarct (CBF) and tissue at risk (Tmax). Once trained, the full sets of 28 input images were sequentially reduced to equitemporal 14, 10, and 7 time points (tp) to further investigate if suboptimal arterial capture could be overcome by this predictive algorithm. The averaged structural similarity index measure (SSIM), a measure of similarity between two images, between the model-derived images and true perfusion maps was compared. For reference, the higher the SSIM, the better the reconstruction technique.

By |January 12th, 2022|clinical|Comments Off on Advanced ML Algorithms: The Future of CT Perfusion?
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Chemical Thrombolysis Disparities in the United States

Kevin O’Connor, MD

Suolang D, Chen BJ, Wang NY, Gottesman RF, Faigle R. Geographic and Regional Variability in Racial and Ethnic Disparities in Stroke Thrombolysis in the United States. Stroke. 2021;52:e782–e787.

Disparities in the administration of IV thrombolysis (IVT) have previously been reported, but Suolang et al. report regional disparities in the administration of IVT based on race/ethnicity. They examined IVT administration in 47,031 (8.6%) of 545,509 patients diagnosed with acute ischemic stroke between 2012 and 2018 according to nine United States Census Bureau regions (see Figure 2B below). Race/ethnic groups comprised White, Black, Hispanic, Asian/Pacific Islander, as well as Native American and Other.

Figure 2. Regional variability in intravenous thrombolysis (IVT) disparities for all racial/ethnic minority groups.
Figure 2. Regional variability in intravenous thrombolysis (IVT) disparities for all racial/ethnic minority groups. B, Green areas indicate no disparity, that is, no IVT underutilization compared with White people (odds ratio [OR], ≥1); green-yellow checkered areas indicate no statistically significant disparity (OR, <1, but 95% CI including 1); yellow areas indicate a disparity (i.e., lower use) comparable to the national average (OR and 95% CI <1 but not significantly below the national average); and the red areas indicate a disparity below the national average (OR and 95% CI <1 and statistically significantly below the national average). NIS indicates National Inpatient Sample.
By |January 10th, 2022|clinical|Comments Off on Chemical Thrombolysis Disparities in the United States
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Investigating Suspected Cardioembolic Strokes

Kevin O’Connor, MD

Bhat A, Mahajan V, Chen HHL, Gan GCH, Pontes-Neto OM, Tan TC. Embolic Stroke of Undetermined Source: Approaches in Risk Stratification for Cardioembolism. Stroke. 2021;52:e820-e836.

Embolic strokes of undetermined source (ESUS) account for about a fifth of all ischemic strokes and comprise pathologies including cardioembolic sources, undiagnosed malignancy, and arteriogenic emboli. There is no single strategy for investigating suspected cardioembolic strokes, and initiating empiric anticoagulation for these patients may result in more harm than benefit.

Cardiac monitoring — whether implanted or external — is an important part of a cardioembolic workup, but the ideal timeframe for monitoring is unclear. In the CRYSTAL AF trial, the median time for atrial fibrillation (AF) detection via implanted cardiac monitor (ICM) was 8.4 months. A meta-analysis of ICM use in patients monitored for AF reported detection rates of 5% for <6 months, 26% for 12-24 months, and 34% for >24 months of monitoring. Although prolonged monitoring appears beneficial, the utility may be limited by patient adherence, accurate interpretation of captured rhythms, and patient cost.

By |January 7th, 2022|clinical|1 Comment
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