Sodium-Glucose Cotransporter-2 Inhibitors in Valvular Heart Disease: From Mechanistic Insights to Clinical...

Valvular heart disease encompasses a diverse group of hemodynamic disorders that are frequently associated with heart failure, recurrent hospitalizations, and substantial morbidity despite advances in transcatheter and surgical therapies. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as a cornerstone of cardiovascular and renal disease management, demonstrating consistent benefits across a broad range of patient populations. Beyond their established effects in heart failure, diabetes mellitus, and chronic kidney disease, accumulating evidence suggests that SGLT2 inhibitors may favorably influence key biological pathways involved in valvular heart disease, including inflammation, oxidative stress, fibrosis, endothelial dysfunction, and adverse cardiac remodeling. Preclinical and translational studies have provided mechanistic support for a potential role of SGLT2 inhibition in modifying valvular and myocardial disease processes. Emerging clinical evidence suggests possible benefits across several forms of valvular heart disease, including degenerative aortic stenosis, functional mitral regurgitation, tricuspid regurgitation, rheumatic mitral stenosis, and bioprosthetic valve degeneration. In addition, growing interest has focused on the integration of SGLT2 inhibitors into contemporary structural heart practice, particularly among patients undergoing transcatheter aortic valve replacement, transcatheter edge-to-edge repair, and other structural interventions. This narrative review summarizes the mechanistic rationale, current clinical evidence, and practical considerations surrounding the use of SGLT2 inhibitors in valvular heart disease and structural heart interventions. We discuss the strengths and limitations of the existing literature, identify important gaps in knowledge, and highlight future directions for research aimed at defining the role of SGLT2 inhibitors as an adjunctive therapy in structural heart disease.