Rheumatic Heart Disease: Inflammation, Immune Pathways, Valve Remodeling, and the Promise of SGLT2 Inhibitors.

Fiche publication

Date publication

juillet 2026

Journal

JACC. Basic to translational science

Auteurs

Membres identifiés du Cancéropôle Est :
Pr SCHINI-KERTH Valérie

Tous les auteurs :
Mai TA, Marchandot B, Hmadeh S, Nguyen HTT, Pham HM, Nguyen QN, Schini-Kerth V, Pibarot P, Morel O

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/42462285

Résumé

Rheumatic heart disease (RHD) remains the leading cause of acquired valvular heart disease in low- and middle-income countries, affecting an estimated 40 million individuals and disproportionately affecting children and young adults in endemic regions. No pharmacological intervention has been shown to modify valvular disease progression in established RHD. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated cardioprotective effects across multiple cardiovascular conditions, prompting interest in their potential applicability to RHD. This hypothesis-generating review synthesizes current evidence on the molecular and cellular pathology of RHD and evaluates the mechanistic plausibility of SGLT2 inhibitor effects in this context. Evidence derived largely from non-rheumatic valve disease and experimental models suggests that SGLT2 inhibitors may attenuate oxidative stress, inflammatory cytokine signaling, transforming growth factor-β-driven fibrosis, and mitochondrial dysfunction; processes implicated in valvular remodeling. Mechanotransduction cascades and osteogenic calcification pathways, characterized primarily in calcific aortic valve disease, are biologically plausible but remain uncharacterized in RHD tissue. Whether these mechanisms are operative within the postinflammatory, immune-mediated rheumatic valve environment remains uncertain and represents an important avenue for future research. Validation of SGLT2 expression in rheumatic valve tissue, mechanistic testing in etiologically relevant models, and early-phase clinical trials tailored to endemic health system realities are essential prerequisites before any therapeutic claims can be advanced. This review outlines the translational pathway needed to determine whether this hypothesis warrants clinical development.