Clinical Significance of Markers of Collagen Metabolism in Rheumatic Mitral Valve Disease

Abstract

BackgroundRheumatic Heart Disease (RHD), a chronic acquired heart disorder results from Acute Rheumatic Fever. It is a major public health concern in developing countries. In RHD, mostly the valves get affected. The present study investigated whether extracellular matrix remodelling in rheumatic valve leads to altered levels of collagen metabolism markers and if such markers can be clinically used to diagnose or monitor disease progression.MethodologyThis is a case control study comprising 118 subjects. It included 77 cases and 41 healthy controls. Cases were classified into two groups- Mitral Stenosis (MS) and Mitral Regurgitation (MR). Carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), total Matrix Metalloproteinase-1(MMP-1) and Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) were assessed. Histopathology studies were performed on excised mitral valve leaflets. A p value <0.05 was considered statistically significant.ResultsPlasma PICP and PIIINP concentrations increased significantly (p<0.01) in MS and MR subjects compared to controls but decreased gradually over a one year period post mitral valve replacement (p<0.05). In MS, PICP level and MMP-1/TIMP-1 ratio strongly correlated with mitral valve area (r = −0.40; r = 0.49 respectively) and pulmonary artery systolic pressure (r = 0.49; r = −0.49 respectively); while in MR they correlated with left ventricular internal diastolic (r = 0.68; r = −0.48 respectively) and systolic diameters (r = 0.65; r = −0.55 respectively). Receiver operating characteristic curve analysis established PICP as a better marker (AUC = 0.95; 95% CI = 0.91−0.99; p<0.0001). A cut-off >459 ng/mL for PICP provided 91% sensitivity, 90% specificity and a likelihood ratio of 9 in diagnosing RHD. Histopathology analysis revealed inflammation, scarring, neovascularisation and extensive leaflet fibrosis in diseased mitral valve.ConclusionsLevels of collagen metabolism markers correlated with echocardiographic parameters for RHD diagnosis.

Rheumatic heart disease in the modern era: recent developments and current challenges

“…Thus, a ubiquitous protein can become a self-antigen that contributes to an imbalance between collagen deposition and collagen degradation, culminating in subsequent fibrosis of the valve apparatus in RHD. Mitral valves of patients with RHD demonstrate higher deposition of collagens Type I and Type III, evidence of fibrosis, when compared to non-rheumatic mitral valve controls 48 .…”

Identification of atrial fibrillation-associated microRNAs in left and right atria of rheumatic mitral valve disease patients

“…Many RMVD patients are children living in developing countries (Marijon et al, 2012). With the advancement of molecular medicine, efforts have been made to identify molecular markers of disease for clinical applications (Ozer et al, 2009;Banerjee et al, 2014;Leão et al, 2014). However, few RMVD biomarkers are known.…”

Can percutaneous mitral balloon valvuloplasty reduce ongoing inflammation in patients with rheumatic mitral stenosis?

“…In acute RF, there are inflammation and edema of the leaflets; it has been believed that the repeated episodes of the carditis associated with RF are responsible for chronic rheumatic valve disease, characterized by the deposition of fibrous tissue [4,14]. On the other hand, the role of continuous inflammation has strongly been put forward by different studies of inflammation markers [4,[8][9][10][11][14][15][16][17][18][19][20][21][22][23]].…”