Etiological and molecular determinants of atrial endomysial fibrosis: results from the CATCH ME consortium

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main source(s): CATCH ME: Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly Background We recently demonstrated that human atria, endomysial fibrosis causes conduction disturbances during atrial (AF), while overall connective tissue content (over-all fibrosis) has no effect. Etiological and molecular determinants are largely unknown. Methods quantified over-all using staining with WGA left (LA, n=95) right (RA, n=76) appendages sampled from a European cohort (CATCH ME) patients undergoing cardiac surgery. The contributions AF, heart failure (HF), sex, age, 4 principal components accounting for confounding clinical characteristics to were determined multivariate model. RNA sequencing was performed explore biological pathways associated two types fibrosis. Results Over-all moderately correlated (LA: r=0.69, RA: 0.61, both p<0.001) more pronounced RA than LA samples (p<0.001). In LA, persistent female HF independently fibrosis, only sex HF. Likewise, RA, AF not. Expression 18 genes univariately but 1 RA. There After correction relevant traits, BMP10 showed strongest association amongst coding (p=3.16E-04, LA). an independent validation (RACE V Tissue Bank Project, n=162 pts surgery), out 11 biomarkers reflecting inflammation, vascular dysfunction, or ischemia, plasma levels most strongly (p<0.001), not Conclusions Taken together, HF, main drivers atria. However, is whereas specific marker Our findings suggest distinct mechanisms involved development versus atria may provide explanation reported predictive value recurrences after ablation stroke.