Bicuspid aortic-valve (BAV) is the most common congenital malformation. Complications include aortic stenosis and regurgitation, endocarditis, aortic dilatation and dissection. Although BAV is associated with early valve degeneration, its pathophysiology remains unknown.

The objective of this study was to examine at clinical, histological and molecular levels, a cohort of BAV patients with pure aortic regurgitation (AR-BAV).

From 2011 to 2018, patients with BAV were prospectively included. We performed histological and transcriptomic analysis of explanted BAV and compared differences between characteristics of prolapsed leaflet and non-prolapsed leaflet, using a normal tricuspid valve leaflet at reference. Aortic-valves from patients with long term left ventricular assist device (LVAD) were used as a model of acquired aortic regurgitation.

A total of 350 patients with BAV were included. Among 316 patients (90%) with dysfunctional BAV, 66 (21%) presented severe AR-BAV. Mechanism of AR was prolapse in 37 patients (56%). Histologically, analysis of 2 explanted AR-BAV showed disorganization of extracellular matrix, loss of laminar structure and proteoglycans accumulation on prolapsed leaflet. Inversely, trilaminar structure of the non-prolapsed aortic leaflet was preserved. Transcriptomic analysis revealed upregulation of genes involved in extracellular matrix homeostasis and downregulation of endothelial cell markers on the prolapsed leaflet. The aortic-valve LVAD analysis found histological and molecular results similar to those described in BAV prolapsed leaflet and was associated with occurrence AR.

AR-BAV is a mood of BAV dysfunction that occurs in young male subjects, as a consequence of myxomatous degeneration similar to that described in mitral valve prolapse. LVAD model suggests that altered hemodynamic environment could account for the acquired nature of valve degeneration.