RHEUMATIC HEART DISEASE FROM VALVULAR FIBROSIS TO EMERGING PHARMACOLOGICAL STRATEGIES

Abstract

Rheumatic heart disease (RHD) is a chronic, progressive valvular disorder and an important cause of cardiovascular morbidity and premature mortality, particularly in low- and middle-income countries. It develops as a long-term consequence of acute rheumatic fever following group A Streptococcus infection and involves recurrent inflammation and progressive structural damage to cardiac valves. Despite effective antibiotic treatment and secondary prophylaxis, established valvular disease may progress to leaflet thickening, commissural fusion, chordal shortening, fibrosis, stenosis, and regurgitation. Current management focuses mainly on preventing recurrent infection, controlling cardiac complications, and correcting advanced valvular lesions. However, no established pharmacological therapy specifically prevents or reverses rheumatic valvular fibrosis. Emerging understanding of inflammatory and fibrotic valve remodeling has stimulated interest in disease-modifying approaches targeting profibrotic signaling, inflammatory mediators, oxidative stress, extracellular-matrix remodeling, valvular interstitial cells, endothelial-to-mesenchymal transition, calcification, and regulatory microRNAs. This review highlights current management and emerging pharmacological strategies aimed at limiting progressive valvular damage and improving long-term outcomes in RHD.