Phenotypes of Patients with Intracerebral Hemorrhage, Complications, and Outcomes

Background: The objective of this study was to define clinically meaningful phenotypes of intracerebral hemorrhage (ICH) using machine learning. Methods: We used patient data from two US medical centers and the Antihypertensive Treatment of Acute Cerebral Hemorrhage-II clinical trial. We used k-prototypes to partition patient admission data. We then used silhouette method calculations and elbow method heuristics to optimize the clusters. Associations between phenotypes, complications (e.g., seizures), and functional outcomes were assessed using the Kruskal-Wallis H-test or chi 2 test. Results: There were 916 patients; the mean age was 63.8 +/- 14.1 years, and 426 patients were female (46.5%). Three distinct clinical phenotypes emerged: patients with small hematomas, elevated blood pressure, and Glasgow Coma Scale scores > 12 (n = 141, 26.6%); patients with hematoma expansion and elevated international normalized ratio (n = 204, 38.4%); and patients with median hematoma volumes of 24 (interquartile range 8.2-59.5) mL, who were more frequently Black or African American, and who were likely to have intraventricular hemorrhage (n = 186, 35.0%). There were associations between clinical phenotype and seizure (P = 0.024), length of stay (P = 0.001), discharge disposition (P < 0.001), and death or disability (modified Rankin Scale scores 4-6) at 3-months' follow-up (P < 0.001). We reproduced these three clinical phenotypes of ICH in an independent cohort (n = 385) for external validation. Conclusions: Machine learning identified three phenotypes of ICH that are clinically significant, associated with patient complications, and associated with functional outcomes. Cerebellar hematomas are an additional phenotype underrepresented in our data sources.