Metabolic Drivers of Valve Calcification and Atrial Remodeling in Calcific Aortic Stenosis

AS, one of the most common forms of valvular heart disease, requiring intervention in aging populations in Europe and North America, has traditionally been viewed as a passive, degenerative condition. However, growing evidence supports a paradigm shift toward recognizing AS as an active metabolic and inflammatory disorder. This narrative review synthesizes experimental, translational, and clinical evidence published between 2015 and 2025 examining metabolic mechanisms linking valvular calcification and atrial remodeling in AS and discusses their clinical relevance in the context of transcatheter aortic valve replacement (TAVR). We discussed classical pathways involving mineral metabolism and vitamin signaling, alongside emerging roles of lipid oxidation, mitochondrial dysfunction, epigenetic regulation, and gut microbiome-derived metabolites. Further, metabolomic signatures associated with disease severity and post-TAVR outcomes were reviewed, highlighting the predominantly associative nature and current limitations of these data. Although valve replacement remains the only effective therapy for advanced AS, metabolic and multi-omics insights may improve future risk stratification and mechanistic understanding. Metabolomic profiling could be integrated at multiple points in the clinical pathway for aortic stenosis and TAVR—most promisingly for pre-procedural risk stratification. The present paper focuses on an integrative framework in which valvular calcification and atrial remodeling are viewed within a broader context of metabolic dysregulation. Future research should aim to translate molecular biomarkers into real-world diagnostics and targeted interventions.