Effect of Heart Rate Variabilities on Outcome After Acute Intracerebral Hemorrhage: A Post Hoc Analysis of ATACH‐2

Background To explore how the clinical impact of heart rate (HR) and heart rate variabilities (HRV) during the initial 24 hours after acute intracerebral hemorrhage (ICH) contribute to worse clinical outcomes. Methods and Results In the ATACH‐2 (Antihypertensive Treatment in Intracerebral Hemorrhage 2) trial, the HR was recorded for every 15 minutes from baseline to 1 hour and hourly during the initial 24 hours post‐randomization. We calculated the following: mean, standard deviation, coefficient of variation, successive variation, and average real variability (ARV). Outcomes were hematoma expansion at 24 hours and unfavorable functional outcome, defined as modified Rankin Scale score 4 to 6 at 90 days. Of the 1000 subjects in ATACH‐2, 994 with available HR data were included in the analyses. Overall, 262 experienced hematoma expansion, and 362 had unfavorable outcomes. Increased mean HR was linearly associated with unfavorable outcome (per 10 bpm increase adjusted odds ratio [aOR], 1.31, 95% CI, 1.14–1.50) but not with hematoma expansion, while HR‐ARV was associated with hematoma expansion (aOR, 1.06, 95% CI, 1.01–1.12) and unfavorable outcome (aOR, 1.07, 95% CI, 1.01–1.3). Every 10‐bpm increase in mean HR increased the probability of unfavorable outcome by 4.3%, while every 1 increase in HR‐ARV increased the probability of hematoma expansion by 1.1% and unfavorable outcome by 1.3%. Conclusions Increased mean HR and HR‐ARV within the initial 24 hours were independently associated with unfavorable outcome in acute ICH. Moreover, HR‐ARV was associated with hematoma expansion at 24 hours. This may have future therapeutic implications to accommodate HR and HRV in acute ICH. Registration URL: https://www.clinicaltrials.gov ; Unique Identiﬁer: NCT01176565.

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Prehospital Transdermal Glyceryl Trinitrate for Ultra-Acute Intracerebral Hemorrhage

Stroke ◽

10.1161/strokeaha.119.026389 ◽

2019 ◽

Vol 50 (11) ◽

pp. 3064-3071 ◽

Cited By ~ 4

Author(s):

Philip M. Bath ◽

Lisa J. Woodhouse ◽

Kailash Krishnan ◽

Jason P. Appleton ◽

Craig S. Anderson ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Glyceryl Trinitrate ◽

Global Analysis ◽

Mass Effect ◽

Modified Rankin Scale ◽

Unique Identifier ◽

Serious Adverse Events ◽

Clinical Trial Registration ◽

Prehospital Treatment ◽

Acute Intracerebral Hemorrhage

Background and Purpose— Pilot trials suggest that glyceryl trinitrate (GTN; nitroglycerin) may improve outcome when administered early after stroke onset. Methods— We undertook a multicentre, paramedic-delivered, ambulance-based, prospective randomized, sham-controlled, blinded-end point trial in adults with presumed stroke within 4 hours of ictus. Participants received transdermal GTN (5 mg) or a sham dressing (1:1) in the ambulance and then daily for three days in hospital. The primary outcome was the 7-level modified Rankin Scale at 90 days assessed by central telephone treatment-blinded follow-up. This prespecified subgroup analysis focuses on participants with an intracerebral hemorrhage as their index event. Analyses are intention-to-treat. Results— Of 1149 participants with presumed stroke, 145 (13%; GTN, 74; sham, 71) had an intracerebral hemorrhage: time from onset to randomization median, 74 minutes (interquartile range, 45–110). By admission to hospital, blood pressure tended to be lower with GTN as compared with sham: mean, 4.4/3.5 mm Hg. The modified Rankin Scale score at 90 days was nonsignificantly higher in the GTN group: adjusted common odds ratio for poor outcome, 1.87 (95% CI, 0.98–3.57). A prespecified global analysis of 5 clinical outcomes (dependency, disability, cognition, quality of life, and mood) was worse with GTN; Mann-Whitney difference, 0.18 (95% CI, 0.01–0.35; Wei-Lachin test). GTN was associated with larger hematoma and growth, and more mass effect and midline shift on neuroimaging, and altered use of hospital resources. Death in hospital but not at day 90 was increased with GTN. There were no significant between-group differences in serious adverse events. Conclusions— Prehospital treatment with GTN worsened outcomes in patients with intracerebral hemorrhage. Since these results could relate to the play of chance, confounding, or a true effect of GTN, further randomized evidence on the use of vasodilators in ultra-acute intracerebral hemorrhage is needed. Clinical Trial Registration— URL: http://www.controlled-trials.com . Unique identifier: ISRCTN26986053.

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Advances in CT for prediction of hematoma expansion in acute intracerebral hemorrhage

Imaging in Medicine ◽

10.2217/iim.13.64 ◽

2013 ◽

Vol 5 (6) ◽

pp. 539-551 ◽

Cited By ~ 2

Author(s):

Thien J Huynh ◽

Sean P Symons ◽

Richard I Aviv

Keyword(s):

Intracerebral Hemorrhage ◽

Hematoma Expansion ◽

Acute Intracerebral Hemorrhage

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Hematoma Expansion following Acute Intracerebral Hemorrhage

Cerebrovascular Diseases ◽

10.1159/000346599 ◽

2013 ◽

Vol 35 (3) ◽

pp. 195-201 ◽

Cited By ~ 123

Author(s):

H. Bart Brouwers ◽

Steven M. Greenberg

Keyword(s):

Intracerebral Hemorrhage ◽

Hematoma Expansion ◽

Acute Intracerebral Hemorrhage

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Tranexamic Acid for Prevention of Hematoma Expansion in Intracerebral Hemorrhage Patients With or Without Spot Sign

Stroke ◽

10.1161/strokeaha.120.032426 ◽

2021 ◽

Author(s):

Christian Ovesen ◽

Janus Christian Jakobsen ◽

Christian Gluud ◽

Thorsten Steiner ◽

Zhe Law ◽

...

Keyword(s):

Computed Tomography ◽

Intracerebral Hemorrhage ◽

Tranexamic Acid ◽

Symptom Onset ◽

Odds Ratio ◽

Hematoma Expansion ◽

Spot Sign ◽

Main Trial ◽

Acid Versus ◽

Acute Intracerebral Hemorrhage

Background and Purpose: The computed tomography angiography or contrast-enhanced computed tomography based spot sign has been proposed as a biomarker for identifying on-going hematoma expansion in patients with acute intracerebral hemorrhage. We investigated, if spot-sign positive participants benefit more from tranexamic acid versus placebo as compared to spot-sign negative participants. Methods: TICH-2 trial (Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage) was a randomized, placebo-controlled clinical trial recruiting acutely hospitalized participants with intracerebral hemorrhage within 8 hours after symptom onset. Local investigators randomized participants to 2 grams of intravenous tranexamic acid or matching placebo (1:1). All participants underwent computed tomography scan on admission and on day 2 (24±12 hours) after randomization. In this sub group analysis, we included all participants from the main trial population with imaging allowing adjudication of spot sign status. Results: Of the 2325 TICH-2 participants, 254 (10.9%) had imaging allowing for spot-sign adjudication. Of these participants, 64 (25.2%) were spot-sign positive. Median (interquartile range) time from symptom onset to administration of the intervention was 225.0 (169.0 to 310.0) minutes. The adjusted percent difference in absolute day-2 hematoma volume between participants allocated to tranexamic versus placebo was 3.7% (95% CI, −12.8% to 23.4%) for spot-sign positive and 1.7% (95% CI, −8.4% to 12.8%) for spot-sign negative participants ( P heterogenity =0.85). No difference was observed in significant hematoma progression (dichotomous composite outcome) between participants allocated to tranexamic versus placebo among spot-sign positive (odds ratio, 0.85 [95% CI, 0.29 to 2.46]) and negative (odds ratio, 0.77 [95% CI, 0.41 to 1.45]) participants ( P heterogenity =0.88). Conclusions: Data from the TICH-2 trial do not support that admission spot sign status modifies the treatment effect of tranexamic acid versus placebo in patients with acute intracerebral hemorrhage. The results might have been affected by low statistical power as well as treatment delay. REGISTRATION: URL: http://www.controlled-trials.com ; Unique identifier: ISRCTN93732214.

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Commentary on Associations of Radiographic Small Vessel Disease with Acute Intracerebral Hemorrhage Volume, Hematoma Expansion, and Intraventricular Hemorrhage

Neurocritical Care ◽

10.1007/s12028-019-00884-4 ◽

2019 ◽

Vol 32 (2) ◽

pp. 361-362

Author(s):

Sarah E. Nelson

Keyword(s):

Intracerebral Hemorrhage ◽

Intraventricular Hemorrhage ◽

Small Vessel Disease ◽

Small Vessel ◽

Hematoma Expansion ◽

Vessel Disease ◽

Acute Intracerebral Hemorrhage ◽

Hemorrhage Volume

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Noncontrast Computed Tomography Signs as Predictors of Hematoma Expansion, Clinical Outcome, and Response to Tranexamic Acid in Acute Intracerebral Hemorrhage

Stroke ◽

10.1161/strokeaha.119.026128 ◽

2020 ◽

Vol 51 (1) ◽

pp. 121-128 ◽

Cited By ~ 8

Author(s):

Zhe Kang Law ◽

Azlinawati Ali ◽

Kailash Krishnan ◽

Adam Bischoff ◽

Jason P. Appleton ◽

...

Keyword(s):

Computed Tomography ◽

Clinical Outcome ◽

Intracerebral Hemorrhage ◽

Tranexamic Acid ◽

Hematoma Expansion ◽

Acute Intracerebral Hemorrhage ◽

Noncontrast Computed Tomography

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Hematoma Expansion Predictors: Laboratory and Radiological Risk Factors in Patients with Acute Intracerebral Hemorrhage: A Prospective Observational Study

Journal of Stroke and Cerebrovascular Diseases ◽

10.1016/j.jstrokecerebrovasdis.2019.04.038 ◽

2019 ◽

Vol 28 (8) ◽

pp. 2177-2186 ◽

Cited By ~ 5

Author(s):

Takwa H.M. Elkhatib ◽

Nahed Shehta ◽

Ahmad Awad Bessar

Keyword(s):

Risk Factors ◽

Observational Study ◽

Intracerebral Hemorrhage ◽

Prospective Observational Study ◽

Hematoma Expansion ◽

Radiological Risk ◽

Acute Intracerebral Hemorrhage

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Tranexamic acid for acute intracerebral hemorrhage growth predicted by spot sign trial: Rationale and design

International Journal of Stroke ◽

10.1177/1747493017694394 ◽

2017 ◽

Vol 12 (3) ◽

pp. 326-331 ◽

Cited By ~ 10

Author(s):

Liping Liu ◽

Yilong Wang ◽

Xia Meng ◽

Na Li ◽

Ying Tan ◽

...

Keyword(s):

High Risk ◽

Intracerebral Hemorrhage ◽

Tranexamic Acid ◽

Primary Outcome Measure ◽

Hematoma Expansion ◽

Spot Sign ◽

Double Blind ◽

Risk Patients ◽

Acute Intracerebral Hemorrhage ◽

Hemorrhage Volume

Rationale Acute intracerebral hemorrhage inflicts a high-economic and -health burden. Computed tomography angiography spot sign is a predictor of hematoma expansion, is associated with poor clinical outcome and is an important stratifying variable for patients treated with haemostatic therapy. Aims We aim to compare the effect of treatment with tranexamic acid to placebo for the prevention of hemorrhage growth in patients with high-risk acute intracerebral hemorrhage with a positive spot sign. Design The tranexamic acid for acute intracerebral hemorrhage growth predicted by spot sign (TRAIGE) is a prospective, multicenter, placebo-controlled, double-blind, investigator-led, randomized clinical trial that will include an estimated 240 participants. Patients with intracerebral hemorrhage demonstrating symptom onset within 8 h and with the spot sign as a biomarker for ongoing hemorrhage, and no contraindications for antifibrinolytic therapy, will be enrolled to receive either tranexamic acid or placebo. The primary outcome measure is the presence of hemorrhage growth defined as an increase in intracerebral hemorrhage volume >33% or >6 ml from baseline to 24 ± 2 h. The secondary outcomes include safety and clinical outcomes. Conclusion The TRAIGE trial evaluates the efficacy of haemostatic therapy with tranexamic acid in the prevention of hemorrhage growth among high-risk patients with acute intracerebral hemorrhage.

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Determinants and Prognostic Significance of Hematoma Sedimentation Levels in Acute Intracerebral Hemorrhage

Cerebrovascular Diseases ◽

10.1159/000442532 ◽

2015 ◽

Vol 41 (1-2) ◽

pp. 80-86 ◽

Cited By ~ 10

Author(s):

Shoichiro Sato ◽

Candice Delcourt ◽

Shihong Zhang ◽

Hisatomi Arima ◽

Emma Heeley ◽

...

Keyword(s):

Blood Pressure ◽

Intracerebral Hemorrhage ◽

Scale Score ◽

Controlled Trial ◽

Blood Pressure Reduction ◽

Prognostic Significance ◽

Logistic Regression Models ◽

Elevated Systolic Blood Pressure ◽

Acute Intracerebral Hemorrhage ◽

Post Hoc

Background: This study aimed at identifying the determinants and prognostic significance of a sedimentation level (fluid-blood level) in the hematoma among patients with acute intracerebral hemorrhage (ICH) who participated in the main Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Methods: Post-hoc analysis of the INTERACT2 dataset, a randomized controlled trial of patients with acute ICH with elevated systolic blood pressure (SBP), randomly assigned to intensive (target SBP <140 mm Hg) or guideline-based (<180 mm Hg) BP management. Patients with a sedimentation level at baseline assessment on CT, and modified Rankin Scale score at 90-day, were included in these analyses. Factors associated with a sedimentation level and its significance in relation to 90-day clinical outcomes were assessed in univariable and multivariable logistic regression models. Results: Of 2,065 participants, 19 (1%) had sedimentation level on baseline CT, which was independently associated with warfarin use (p = 0.006) and lobar ICH (p = 0.025). Sedimentation level was also associated with death or major disability at 90-day in both crude (84 vs. 53%; p = 0.014) and multivariable analyses adjusted for age, gender, Chinese region, warfarin use, baseline National Institutes of Health Stroke Scale score, onset to CT time, volume and location of ICH, intraventricular extension, and randomized intensive BP lowering (OR 3.94, 95% CI 1.01-15.37; p = 0.049). Conclusions: The presence of hematoma sedimentation level on baseline CT is associated with warfarin use and lobar location of ICH, and predicts a worse outcome. Although uncommon, sedimentation level is an easily detectable prognostic factor in acute ICH.

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