Clinical-pathological correlations of BAV and the attendant thoracic aortopathies. Part 1: Pluridisciplinary perspective on their hemodynamics and morphomechanics.

Clinical BAV manifestations pertain to faulty aortic valve (AOV) function, the associated aortopathy, and other complications such as endocarditis, thrombosis and thromboembolism. BAV arises during valvulogenesis when 2 of the 3 leaflets/cusps of the AOV are fused together. Ensuing asymmetric BAV morphologies alter downstream ejection jet flow-trajectories. Based on BAV morphologies, ejection-flows exhibit different wall-impingement and scouring patterns in the proximal aorta, with excessive hydrodynamic wall-shear that correlates closely with mural vascular smooth muscle cell and extracellular matrix disruptions, revealing hemodynamic participation in the pathogenesis of BAV-associated aortopathies. Since the embryologic regions implicated in both BAV and aortopathies derive from neural crest cells and second heart field cells, there may exist a common multifactorial/polygenic embryological basis linking the abnormalities. The use of Electronic Health Records - encompassing integrated NGS variant panels and phenotypic data - in clinical studies could speed-up comprehensive understanding of multifactorial genetic-phenotypic and environmental factor interactions. This Survey represents the first in a 2-article pluridisciplinary work. Taken in toto, the series covers hemodynamic/morphomechanical and environmental (milieu intérieur) aspects in Part 1, and molecular, genetic and associated epigenetic aspects in Part 2. Together, Parts 1-2 should serve as a reference-milestone and driver for further pluridisciplinary research and its urgent translations in the clinical setting.