Histomorphometric Analysis of Myocardial Fibrosis after Heart Transplantation

Abstract

Purpose Major components of the myocardial extracellular matrix are collagen type I and type III. Furthermore, collagen type IV is located in the basement membranes. Continuous structural remodeling of the collagenous matrix results in an excessive accumulation of collagen fibrils and therefore in pathologic myocardial fibrosis. Functional consequences are related to an increase in myocardial stiffness. The phenomenon of collagen turnover in heart transplant recipients has not yet been studied. The aim of the study was to evaluate collagen type III and IV in endomyocardial biopsy specimens (EMB) after heart transplantation (HTx) and to analyze the prognostic value of immunohistochemistry staining compared to the Sirius-red staining of fibrosis used routinely. Methods and Materials In total, 274 EMB of 77 patients who underwent HTx between 2003 and 2006 (66 men, mean age at HTx 49 years) were evaluated on the date of HTx=FU0, and 4 weeks=FU1, 1 year=FU2, 3 years=FU3 and 5 years=FU4 post-HTX. Computer-based histomorphometrical analyses were compared. The rates of collagen III and IV and myocardial fibrosis were measured in an area of 1mm2 for each EMB. Results The rate of collagen III increased continuously, while fibrosis demonstrated a fluctuating course (FU0: 13.0 vs 8.59%, FU1: 11.94 vs 7.87%, FU2: 12.0 vs 8.47%, FU3: 12.19 vs 6.95%, FU4: 16.17 vs 7.9%, p 20%) was associated with more fibrosis (10-19.9%, FU2: p=0.02, FU4: p Conclusions The rate of collagen III and IV increases significantly more than the rate of fibrosis in the long term post-HTx. The consequences of the collagenous remodeling for the contractile functionality of the myocardium of HTx recipients remain unclear and need to be evaluated.