Rheumatic Heart Valve Disease Pathophysiology and Underlying Mechanisms

Abstract

Rheumatic heart valve disease (RHVD) is a post-infectious sequel of acute rheumatic fever resulting from an abnormal immune response to a streptococcal pharyngitis that triggers valvular damage. RHVD is the leading cause of cardiovascular death in children and young adults, mainly in women from low and middle-income countries. It is known that long-term inflammation and high degree of fibrosis leads to valve dysfunction due to anatomic disruption of the valve apparatus. However, since public and private investments in RHVD studies are practically inexistent the number of publications is scarce. This disease shows different natural history and clinical presentations as compared to other degenerative heart valve diseases. Although more than five decades passed after the pioneering studies on the pathogenesis of RHVD, it is still unclear how self-tolerance mechanisms fail in this disease, and how humoral and cellular inflammatory responses are interconnected. Despite that pathological mechanisms have been already proposed for RHVD, none of them are able to explain the preferential involvement of the mitral valve. This review focuses on pathophysiology and underlying mechanisms of RHVD.

Proinflammatory Matrix Metalloproteinase-1 Associates With Mitral Valve Leaflet Disruption Following Percutaneous Mitral Valvuloplasty

“…Inflammation and its impact on mitral leaflet tissue integrity has been shown in several fibrocalcific valvopathy studies ( 5 , 24 – 26 ). The evidence supports that inflammation is as mediator of pathological valve remodeling ( 25 , 27 ).…”

“…Patients with severe MS show substantial collagen and elastin leaflet changes, and thus an altered MV leaflet architecture ( 5 , 18 ). Although we could not find differences in MV leaflet collagen orientation and composition in patients who had leaflet tearing vs. no tearing, we found a distinct layered composition of tissue lacking collagen alternating with fibrous tissue in MVs excised from RHD patients from both groups.…”

“…Despite high technical expertise and cumulative experience with PMV, the incidence rate of severe MR has not decreased ( 2 , 3 ). As the rheumatic MS disease process can cause distinct structural valvular derangements, the pattern of extracellular leaflet matrix changes and thickening may predict the risk of MR following PMV ( 4 , 5 ).…”

“…The MV leaflets are covered by endothelium and composed of three layers of specialized extracellular matrix (ECM) containing heterogeneous valvular interstitial cells ( 7 , 8 ). Rheumatic heart disease leads to a substantial changes in MV leaflet architecture due to alteration of its matrix and cellular components ( 5 ). Inflammation and subsequent ECM remodeling are likely compromising the physiologic range of leaflets tissue properties increasing the tearing risk during PMV balloon inflation.…”

Collagen Fibrillogenesis in the Mitral Valve: It’s a Matter of Compliance

“…Presence of inflammatory cells, such as macrophages and neutrophils, releasing a cytokine storm is likely to stimulate VIC to overexpress fibrillar collagens. Unfortunately, RHD continues to be a global problem that is completely preventable [32].…”