H Bart Brouwers1, Yuchiao Chang2, Guido J Falcone1, Xuemei Cai3, Alison M Ayres4, Thomas W K Battey5, Anastasia Vashkevich4, Kristen A McNamara4, Valerie Valant5, Kristin Schwab4, Susannah C Orzell3, Linda M Bresette3, Steven K Feske3, Natalia S Rost1, Javier M Romero6, Anand Viswanathan7, Sherry H-Y Chou3, Steven M Greenberg4, Jonathan Rosand1, Joshua N Goldstein7. 1. Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston2Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston3Hemorrhagic S. 2. Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston. 3. Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston. 4. Hemorrhagic Stroke Research Group, Massachusetts General Hospital, Harvard Medical School, Boston4J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston. 5. Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston3Hemorrhagic Stroke Research Group, Massachusetts General Hospital, Harvard Medical School, Boston4J. Philip Kistler Stroke Research Center, Massachusetts Gen. 6. Neuroradiology Service, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston. 7. Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston3Hemorrhagic Stroke Research Group, Massachusetts General Hospital, Harvard Medical School, Boston4J. Philip Kis.
Abstract
IMPORTANCE: Many clinical trials focus on restricting hematoma expansion following acute intracerebral hemorrhage (ICH), but selecting those patients at highest risk of hematoma expansion is challenging. OBJECTIVE: To develop a prediction score for hematoma expansion in patients with primary ICH. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study at 2 urban academic medical centers among patients having primary ICH with available baseline and follow-up computed tomography for volumetric analysis (817 patients in the development cohort and 195 patients in the independent validation cohort). MAIN OUTCOMES AND MEASURES: Hematoma expansion was assessed using semiautomated software and was defined as more than 6 mL or 33% growth. Covariates were tested for association with hematoma expansion using univariate and multivariable logistic regression. A 9-point prediction score was derived based on the regression estimates and was subsequently tested in the independent validation cohort. RESULTS: Hematoma expansion occurred in 156 patients (19.1%). In multivariable analysis, predictors of expansion were as follows: warfarin sodium use, the computed tomography angiography spot sign, and shorter time to computed tomography (≤ 6 vs >6 hours) (P < .001 for all), as well as baseline ICH volume (<30 [reference], 30-60 [P = .03], and >60 [P = .005] mL). The incidence of hematoma expansion steadily increased with higher scores. In the independent validation cohort (n = 195), our prediction score performed well and showed strong association with hematoma expansion (odds ratio, 4.59; P < .001 for a high vs low score). The C statistics for the score were 0.72 for the development cohort and 0.77 for the independent validation cohort. CONCLUSIONS AND RELEVANCE: A 9-point prediction score for hematoma expansion was developed and independently validated. The results open a path for individualized treatment and trial design in ICH aimed at patients at highest risk of hematoma expansion with maximum potential for therapeutic benefit.
IMPORTANCE: Many clinical trials focus on restricting hematoma expansion following acute intracerebral hemorrhage (ICH), but selecting those patients at highest risk of hematoma expansion is challenging. OBJECTIVE: To develop a prediction score for hematoma expansion in patients with primary ICH. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study at 2 urban academic medical centers among patients having primary ICH with available baseline and follow-up computed tomography for volumetric analysis (817 patients in the development cohort and 195 patients in the independent validation cohort). MAIN OUTCOMES AND MEASURES: Hematoma expansion was assessed using semiautomated software and was defined as more than 6 mL or 33% growth. Covariates were tested for association with hematoma expansion using univariate and multivariable logistic regression. A 9-point prediction score was derived based on the regression estimates and was subsequently tested in the independent validation cohort. RESULTS:Hematoma expansion occurred in 156 patients (19.1%). In multivariable analysis, predictors of expansion were as follows: warfarin sodium use, the computed tomography angiography spot sign, and shorter time to computed tomography (≤ 6 vs >6 hours) (P < .001 for all), as well as baseline ICH volume (<30 [reference], 30-60 [P = .03], and >60 [P = .005] mL). The incidence of hematoma expansion steadily increased with higher scores. In the independent validation cohort (n = 195), our prediction score performed well and showed strong association with hematoma expansion (odds ratio, 4.59; P < .001 for a high vs low score). The C statistics for the score were 0.72 for the development cohort and 0.77 for the independent validation cohort. CONCLUSIONS AND RELEVANCE: A 9-point prediction score for hematoma expansion was developed and independently validated. The results open a path for individualized treatment and trial design in ICH aimed at patients at highest risk of hematoma expansion with maximum potential for therapeutic benefit.
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