A pathobiologic classification of aortic stenosis: Moving beyond the degenerative–bicuspid–rheumatic paradigm

BackgroundAortic stenosis is traditionally categorised as degenerative calcific, congenital bicuspid, or rheumatic. Contemporary molecular biology, multimodality imaging, and transcatheter valve therapy demonstrate that aortic stenosis represents a spectrum of mechanistically distinct diseases converging upon a shared haemodynamic endpoint. A four-category pathobiologic classification is proposed linking disease mechanism to operative strategy and procedural risk stratification.MethodsA narrative mechanistic review was performed using contemporary international guidelines, foundational biological studies, and key clinical series. Pathophysiology, characteristic imaging phenotype, and procedural implications were integrated into a clinically applicable framework for use by multidisciplinary heart valve teams.ResultsAortic stenosis arises via common downstream pathways - valve interstitial cell activation, inflammation, extracellular matrix remodelling, and mineralisation - through mechanistically distinct initiating processes. Four phenotypes are identified: (a) congenital structural-biomechanical disease; (b) fibro-calcific inflammatory-osteogenic disease; (c) autoimmune/inflammatory valvulitis; and (d) metabolic/mineralisation-associated disease. Each demonstrates characteristic anatomical morphology, rate of haemodynamic progression, and differential suitability for transcatheter or surgical intervention.ConclusionsAortic stenosis is a final common phenotype of multiple distinct biological processes. A pathobiologic classification improves procedural planning, risk stratification, and therapeutic selection in the era of transcatheter valve therapy, and supports precision-based individualised patient management.