Abstract 17374: Epigenetic Age Acceleration in Adult Congenital Heart Disease

Abstract

Introduction: DNA methylation (DNAm) changes reflect alterations in the immune response to cardiac surgery in older adults. However, whether adults with congenital heart disease (ACHD) who underwent palliative cardiac surgery during childhood experience epigenetic age acceleration (EAA) is unknown. Hypothesis: ACHD patients with Fontan(F) procedures would have advanced EAA compared to healthy adults. Methods: A case-control study in young adults (aged 20-30 years) with Fontan circulation at a tertiary ACHD hospital with age-matched healthy adults. DNAm were measured by the EPIC Array. EAAs were calculated by extracting residuals by regressing epigenetic ages on chronological age in linear regression models for four epigenetic clocks. DNAm-based cell type proportions and EAA differences between the two groups were tested by robust linear models (rlm) adjusted for age, sex, and self-reported ethnicity. Results: Thirteen Fontan patients (6 female: 7 male) were compared with 20 age-matched controls (15 female). The median age of the F group was 23 years, compared to 27 years in control. Both subgroups had a predominant white race and non-Hispanic ethnicity. The F group has lower B memory cells and naïve CD4+ cells than controls (adjusted p<0.05). The F group has statistically significant higher Grimage and Phenoage EAA than the controls (p<0.01). Conclusions: Patients who underwent the Fontan procedure experience advanced EAA at a young age. Future studies evaluating the key predictors that drive EAA difference is needed to understand the impact of chronic alteration of physiology.