Structural Remodeling in Rheumatic Heart Disease: Influence of Age and Gender in an Egyptian Cohort

Rheumatic heart disease (RHD) remains a significant cause of cardiovascular morbidity globally, with notable variability in disease progression linked to patient demographics. This study investigated age- and gender-related differences in structural and extracellular matrix (ECM) remodeling in valve tissues from an Egyptian cohort of 88 RHD patients (37 males and 51 females; mean age 38 years at operation), selected for histological analysis from a total of 601 valve replacement and 344 valve repair procedures. The examined cases included individuals who underwent aortic valve replacement (n=34), mitral valve replacement or repair (n=41), or double valve replacements (aortic and mitral valves) (n=13). Biopsies were examined histologically using Hematoxylin and eosin (n=88), Picrosirius Red (n=88), Elastin Van Gieson (n=38), and Alcian Blue (n=38), with quantitative analysis performed via Fiji software. Our results revealed a significant increase in collagen deposition in female valve tissue compared to male tissue, indicating extensive fibrotic remodeling in females. Elastin fibers were fragmented and dispersed throughout the entire leaflet in both genders equally. Additionally, Alcian Blue staining revealed glycosaminoglycans accumulation in both male and female RHD patients, with a higher index in females, further supporting enhanced ECM remodeling. Age-related analysis demonstrated a general increase in fibrotic content with advancing age across both genders. These findings suggest that both age and gender influence ECM dynamics and structural remodeling in RHD-affected valves, with females exhibiting more pronounced fibrotic and ECM changes. Understanding these biological differences is critical for developing gender-specific and age-adapted approaches to the clinical management of RHD.