Abstract 15298: Epidemiology and microRNA Predictors of Infection After Heart Transplantation

Abstract

Background: Infection rates are high in heart transplant (HT) patients due to the need for immunosuppressive medication. MicroRNAs (miR) are non-coding RNAs, that regulate gene expression and are promising biomarkers for identifying patients at risk for infection. Hypothesis: MiR profiles can identify HT patients who are at increased risk for developing an infection. Methods: HT patients who were prospectively enrolled from 2015-2018 had miR-sequencing performed. Incident infection after HT hospital discharge along with the epidemiologic characteristics of the infection were collected from the EMR. An opportunistic infection (OI) is an infection which is less virulent in a healthy host but can cause severe disease in those immunosuppressed. A time-to-event analysis was performed using miR expression at two weeks post-HT in multivariable modeling, and the Benjamini-Hochberg procedure was used to correct for false discovery. Results: The cohort included 46 patients with a median age of 56 years (IQR: 49, 62), 33% (N=15) were Female sex, 41% (N=19) were Black, and 80% (N=37) were supported with an LVAD prior to HT. Post-HT infection occurred in 59% of patients (N=27) and median time to infection was 341 days (IQR: 85, 859). Hospitalization was required in 56% (N=15) of infections. Respiratory tract and OIs were the most common infection type (Figure A). The most common microorganisms implicated were CMV (28%) and SARS-COV-2 (19%) (Figure B). After correction for false discovery, we identified 15 miRs associated with infection risk. The 5 miRs with strongest effect size and their corresponding hazard ratios include: miR-21 2.5(95% CI: 1.3, 4.7), miR-130b 8.6 (95%CI: 1.9, 39.3), miR-192 0.3 (95%CI: 0.1, 0.6), miR-218 2.6 (95%CI: 1.3, 5.1) and miR-484 0.3 (95%CI: 0.1, 0.7). Conclusion: While the burden of post-HT infections is high and contributes to patient morbidity, novel plasma miRs can potentially play a role in identifying patients at risk for infections after HT.