Conjugated bile acids are elevated in severe calcific aortic valve stenosis.

Abstract

Introduction: Calcific aortic valve stenosis (CAVS) is a disease associated with significant morbidity and mortality in the aging population. Recently, bile acids have been shown to play a significant role in many disease processes, and untargeted metabolomic analyses of CAVS patient valves has shown a disrupted bile acid pathway.

Aim: We aimed to understand the changes in human valvular bile acids in relation to CAVS severity.

Methods: A total of 100 human aortic valves were collected from patients undergoing aortic valve replacement surgery. Bile acids were quantified by ultrahigh performance liquid chromatography coupled to tandem mass spectrometry.

Results: Patients with mild aortic stenosis (AS) showed a distinct valvular bile acid composition compared to moderate and severe AS groups, with five bile acids being significantly elevated in patients with moderate and severe AS. These included norcholic, nordeoxycholic, glycodeoxycholic, glycocholic and taurodeoxycholic acid. When classified by calcification score, five species were significantly different between mild and severe AS groups; four bile acids were similar when stratified based on AS severity. Using k means clustering we were able to distinguish valve severity by their bile acid composition. Grouping bile acids by conjugation and by primary versus secondary revealed that conjugated primary and secondary bile acids were significantly increased in stenotic valves compared to the mild AS group.

Conclusion: Conjugated bile acids are significantly elevated in the valvular tissue of patients with severe calcific aortic stenosis. These findings suggest a potential link between liverand gut microbiome physiologyand bile acid pathways in contributing to the pathophysiology of valvular stenosis.