Clinical significance of markers of collagen metabolism in rheumatic mitral valve disease
Tanima Banerjee, Somaditya Mukherjee, Sudip Ghosh, Monodeep Biswas, Santanu Dutta, Sanjib Pattari, Shelly Chatterjee, Arun Bandyopadhyay, Tanima Banerjee, Somaditya Mukherjee, Sudip Ghosh, Monodeep Biswas, Santanu Dutta, Sanjib Pattari, Shelly Chatterjee, Arun Bandyopadhyay
Abstract
Background: Rheumatic 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.
Methodology: This 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.
Results: Plasma 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.
Conclusions: Levels of collagen metabolism markers correlated with echocardiographic parameters for RHD diagnosis.
Conflict of interest statement
Competing Interests: The authors have declared that no competing interests exist.
Figures
References
- Marijon E, Mirabel M, Celermajer DS, Jouven X (2012) Rheumatic Heart Disease. Lancet 379: 953–964.
- GuilhermeL, Köhler KF, Postol E, Kalil J (2011) Genes, autoimmunity and pathogenesis of rheumatic heart disease. Ann Pediatr Cardiol 4: 13–21.
- Eisenberg MJ (1993) Rheumatic heart disease in the developing world: prevalence, prevention, and control. Euro Heart J 14: 122–128.
- World health organization(2004) 2001 Report of a WHO Expert Consultation. Geneva,13–19.
- Steer AC, Carapetis JR (2009) Prevention and treatment of rheumatic heart disease in the developing world. Nat Rev Cardiol 6: 689–698.
- World Health Organization (2011) Projections of mortality and burden of disease, 2004–2030; standard DALYs (3% discounting, age weights) -baseline scenario; 2008; WHO regions.
- Kadir IS, Barker TA, Clarke B, Denley H (2004) Grötte GJ (2004) Recurrent acute rheumatic fever: a forgotten diagnosis? Ann ThoracSurg 78: 699–701.
- Carabello BA (2005) Modern management of mitral stenosis. Circulation 112: 432–7.
- López B, González A, Díez J (2010) Circulating biomarkers of collagen metabolism in cardiac diseases. Circulation 121: 1645–1654.
- QuerejetaR, López B, González A, Sánchez E, Larman M, et al. (2004) Increased collagen type I synthesis in subjects with heart failure of hypertensive origin: relation to myocardial fibrosis. Circulation 110: 1263–1268.
- Querejeta R, Varo N, López B, Larman M, Artiñano E, et al. (2000) Serum carboxy-terminal propeptide of procollagen type I is a marker of myocardial fibrosis in hypertensive heart disease. Circulation 101: 1729–1735.
- López B, Querejeta R, González A, Sánchez E, LarmanM, et al (2004) Effects of loop diuretics on myocardial fibrosis and collagen type I turnover in chronic heart failure. J Am Coll Cardio l43: 2028–2035.
- MartosR, Baugh J, LedwidgeM, O'Loughlin C, Conlon C, et al. (2007) Diastolic heart failure: evidence of increased myocardial collagen turnover linked to diastolic dysfunction. Circulation 115: 888–895.
- Banerjee T, Mukherjee S, Biswas M, Dutta S, Chatterjee S, et al. (2012) Circulating carboxy-terminal propeptide of type I procollagen is increased in rheumatic heart disease Int J Cardiol. 156: 117–119.
- Reményi B, Wilson N, Steer A, Ferreira B, Kado J, et al. (2012) World Heart Federation criteria for echocardiographic diagnosis of rheumatic heart disease—an evidence-based guideline.Nat Rev Cardio. 19: 297–309.
- Ganau A, Devereux RB, Roman MJ, de Simone G, Pickering TG, et al. (1992) Patterns of left ventricular hypertrophy and geometric remodelling in essential hypertension. J Am Coll Cardiol 19: 1550–1558.
- Lancellotti P, Moura L, Pierard LA, Agricola E, Popescu BA, et al. (2010) European Association of Echocardiography Recommendations for the assessment of valvular regurgitation.Part2:mitral and tricuspid regurgitation(native valve disease). Eur J Echocardiogr 11: 307–32.
- Ghose Roy S, Mishra S, Ghosh G, Bandyopadhyay A (2007) Thyroid hormone induces myocardial matrix degradation by activating matrix metalloproteinase-1. Matrix Biol 26: 269–279.
- Zhang H, Sun L, Wang W, Ma X (2006) Quantitative analysis of fibrosis formation on the microcapsule surface with the use of picro-sirius red staining, polarized light microscopy, and digital image analysis. J Biomed Mater Res A76: 120–125.
- Hara M, Noiseux N, Bindokas V P (2005) High resolution optical imaging of infarction in intact organs. Biotechniques 39: 373–376.
- Yeghiazarians Y, Zhang Y, Prasad M, Shih H, Saini S, et al. (2009) Injection of bone marrow cell extract into infarcted hearts results in functional improvement comparable to intact cell therapy. Mol Ther 17: 1250–1256.
- Marijon E, Ou P, Celermajer DS, Ferreira B, Mocumbi AO, Jani D, Paquet C, Jacob S, Sidi D, Jouven X (2007) Prevalence of rheumatic heart disease detected by echocardiographic screening. N Engl J Med 357: 470–476.
- Marijon E, Ou P, Celermajer DS, Ferreira B, Mocumbi AO, et al. (2008) Echocardiographic screening for rheumatic heart disease. Bull World Health Organ 86: 84.
- Narula J, Kaplan EL (2001) Echocardiographic diagnosis of rheumatic fever. Lancet 358: 2000.
- Brand A, Dollberg S, Keren A (1992) The prevalence of valvular regurgitation in children with structurally normal hearts: a colour Doppler echocardiographic study. American Heart Journal 123: 177–180.
- McCarthy KP, Ring L (2010) RanaBS (2010) Anatomy of the mitral valve: understanding the mitral valve complex in mitral regurgitation. Eur J Echocardiogr 11: i3–i9.
- Walker GA, Masters KS, Shah DN, Anseth KS, Leinwand LA (2004) Valvularmyofibroblast activation by transforming growth factor-beta: implications for pathological extracellular matrix remodelling in heart valve disease. Circ Res 95: 253–260.
- Khan R, Sheppard R (2006) Fibrosis in heart disease: understanding the role of transforming growth factor-beta in cardiomyopathy, valvular disease and arrhythmia. Immunology 118: 10–24.
- Leong SW, Soor GS, Butany J, Henry J, Thangaroopan M, et al. (2006) Morphological findings in 192 surgically excised native mitral valves. Can J Cardiol 22: 1055–1061.
- González A, López B, QuerejetaR, Díez J (2002) Regulation of myocardial fibrillar collagen by angiotensin II.A role in hypertensive heart disease? J Mol Cell Cardiol 34: 1585–1593.
- Rabkin E, Aikawa M, Stone JR, Fukumoto Y, Libby P, et al. (2001) Activated interstitial myofibroblasts express catabolic enzymes and mediate matrix remodeling in myxomatous heart valves. Circulation 104: 2525–2532.
- Boldt A, Wetzel U, Lauschke J, Weigl J, Gummert J, et al. (2004) Fibrosis in left atrial tissue of patients with atrial fibrillation with and without underlying mitral valve disease. Heart 90: 400–405.
- Gaasch WH, Meyer TE (2008) Left ventricular response to mitral regurgitation: implications for management. Circulation 118: 2298–2303.
- Marciniak A, Claus P, Sutherland GR, Marciniak M, Karu T, et al. (2007) Changes in systolic left ventricular function in isolated mitral regurgitation.A strain rate imaging study. Eur Heart J 28: 2627–2636.
- Lorell BH, Carabello BA (2000) Left ventricular hypertrophy: pathogenesis, detection, and prognosis. Circulation 102: 470–479.
Source: PubMed