Chronic Mitral Valve Fibrosis in Rheumatic Heart Disease: From Immune Trigger to Inflammatory and Mechanical Progression

Rheumatic heart disease is a chronic valvular disorder resulting from acute rheumatic fever, predominantly affecting the mitral valve and characterized by progressive fibrotic thickening. Although the initial insult is driven by autoimmune responses triggered by Group A <i>Streptococcus</i> infection, the sustained progression of valvular fibrosis involves a complex interplay of persistent immune activation, chronic inflammation, and, critically, long-term mechanical stress. Mechanical forces arising from altered hemodynamics and structural valve deformation perpetuate valvular interstitial cell activation, endothelial-to-mesenchymal transition, and extracellular matrix remodeling, thereby driving fibrosis even after acute inflammation resolves. Current therapeutic options to halt or reverse mitral valve fibrosis are limited, with surgical repair or replacement remaining the primary interventions for advanced disease. Advancing mechanistic understanding through physiologically relevant models, coupled with early diagnostic strategies and multitargeted antifibrotic approaches, holds promise for preserving valve function. Integrating molecular insights with scalable public health measures may ultimately mitigate the global burden of rheumatic heart disease and improve outcomes for affected populations.