Clinical phenotypes of embolic strokes of undetermined source

Background and purpose: The embolic stroke of undetermined source (ESUS) represents a heterogeneous clinical entity. The aim of this study was to investigate whether distinct clinical phenotypes may be identified in the ESUS population. Methods: We retrospectively identified consecutive patients hospitalized for acute ischemic stroke who met the ESUS diagnostic criteria. Baseline characteristics and diagnostic workup findings were collected. Hierarchical cluster analysis was carried out to classify clinical features and identify different groups of ESUS patients. Results: One hundred twenty-seven patients with a mean age of 68.6 (12.5) years were included. Three main clusters were identified. The first cluster associated young age, male sex, presence of patent foramen ovale, and posterior circulation infarct. The second phenotype linked hypertension, severe stroke, left atrial cardiopathy, diabetes mellitus, and involvement of multiple vascular territories. The third cluster gathered smoking, dyslipidemia, ipsilateral vulnerable sub-stenotic carotid plaque, and infarct of anterior vascular territory. Conclusions: Distinct clinical phenotypes have been identified within the ESUS population, which may supply clues to the underlying pathogenic mechanisms.