Defining hematoma expansion in intracerebral hemorrhage: relationship with patient outcomes

D Dowlatshahi, A M Demchuk, M L Flaherty, M Ali, P L Lyden, E E Smith, VISTA Collaboration, A Alexandrov, P W Bath, E Bluhmki, L Claesson, J Curram, S M Davis, G Donnan, H C Diener, M Fisher, B Gregson, J Grotta, W Hacke, M G Hennerici, M Hommel, M Kaste, K R Lees, P Lyden, J Marler, K Muir, R Sacco, A Shuaib, P Teal, N G Wahlgren, S Warach, C Weimar, D Dowlatshahi, A M Demchuk, M L Flaherty, M Ali, P L Lyden, E E Smith, VISTA Collaboration, A Alexandrov, P W Bath, E Bluhmki, L Claesson, J Curram, S M Davis, G Donnan, H C Diener, M Fisher, B Gregson, J Grotta, W Hacke, M G Hennerici, M Hommel, M Kaste, K R Lees, P Lyden, J Marler, K Muir, R Sacco, A Shuaib, P Teal, N G Wahlgren, S Warach, C Weimar

Abstract

Background: Hematoma expansion (HE) is a surrogate marker in intracerebral hemorrhage (ICH) trials. However, the amount of HE necessary to produce poor outcomes in an individual is unclear; there is no agreement on a clinically meaningful definition of HE. We compared commonly used definitions of HE in their ability to predict poor outcome as defined by various cutpoints on the modified Rankin Scale (mRS).

Methods: In this cohort study, we analyzed 531 patients with ICH from the Virtual International Stroke Trials Archive. Primary outcome was mRS at 90 days, dichotomized into 0-3 vs 4-6. Secondary outcomes included other mRS cutpoints and mRS "shift analysis." Sensitivity, specificity, and predictive values for commonly used HE definitions were calculated.

Results: Between 13% and 32% of patients met the commonly used HE definitions. All definitions independently predicted poor outcome; positive predictive values increased with higher growth cutoffs but at the expense of lower sensitivities. All HE definitions showed higher specificity than sensitivity. Absolute growth cutoffs were more predictive than relative cutoffs when mRS 5-6 or 6 was defined as "poor outcome."

Conclusion: HE robustly predicts poor outcome regardless of the growth definition or the outcome definition. The highest positive predictive values are obtained when using an absolute growth definition to predict more severe outcomes. Given that only a minority of patients may have clinically relevant HE, hemostatic ICH trials may need to enroll a large number of patients, or select for a population that is more likely to have HE.

Figures

Figure. Receiver operating characteristic (ROC) curve comparison
Figure. Receiver operating characteristic (ROC) curve comparison
ROC curves for percent growth and absolute growth (n = 531). FP = false positive; TP = true positive.

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Source: PubMed

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