Identification of host endotypes using peripheral blood transcriptomics in a prospective cohort of patients with endocarditis

Objectives To identify endotypes in patients with infective endocarditis. Methods Thirty-two consecutive patients with infective endocarditis were studied. Clinical data and a blood sample were collected at diagnosis, and RNA sequenced. Gene expression was used to identify two clusters, termed endocarditis endotypes (EE) 1 and 2. RNA sequencing was repeated after surgery. Transcriptionally active cell populations were identified by deconvolution. Differences between endotypes in clinical data, survival, gene expression and molecular pathways involved were assessed. Results 18 and 14 patients were assigned to EE1 and EE2 respectively, with no differences in clinical data. Patients assigned to EE2 showed an enrichment in genes related to T-cell maturation and a decrease in the activation of the STAT pathway, with higher counts of active T-cells and lower counts of neutrophils. Fourteen patients (9 in EE1 and 5 in EE2) were submitted to surgery. Surgery in EE2 patients shifted gene expression towards a EE1-like profile. In-hospital mortality was higher in EE1 (56% vs 14%, p=0.027) with a hazard ratio of 12.987 (95% confidence interval 3.356 – 50] after adjustment by age and sex. Conclusions Gene expression reveals two endotypes in patients with acute endocarditis, with different underlying pathogenetic mechanisms, response to surgery and outcome.