Myocardial
fibrosis can lead to
heart failure and act as a substrate for
cardiac arrhythmias. In
dilated cardiomyopathy diffuse interstitial reactive
fibrosis can be observed, whereas arrhythmogenic
cardiomyopathy is characterized by fibrofatty replacement in predominantly the right ventricle. The p.Arg14del mutation in the
phospholamban (PLN) gene has been associated with
dilated cardiomyopathy and recently also with arrhythmogenic
cardiomyopathy. Aim of the present study is to determine the exact pattern of
fibrosis and fatty replacement in PLN p.Arg14del mutation positive patients, with a novel method for high resolution systematic digital histological quantification of
fibrosis and fatty tissue in cardiac tissue. Transversal mid-ventricular slices (nā=ā8) from whole hearts were collected from patients with the PLN p.Arg14del mutation (age 48±16 years; 4 (50%) male). An in-house developed open source MATLAB script was used for digital analysis of Masson's trichrome stained slides (http://sourceforge.net/projects/fibroquant/). Slides were divided into trabecular, inner and outer compact myocardium. Per region the percentage of connective tissue, cardiomyocytes and fatty tissue was quantified. In PLN p.Arg14del mutation associated
cardiomyopathy, myocardial
fibrosis is predominantly present in the left posterolateral wall and to a lesser extent in the right ventricular wall, whereas fatty changes are more pronounced in the right ventricular wall. No difference in distribution pattern of
fibrosis and adipocytes was observed between patients with a clinical predominantly dilated and arrhythmogenic
cardiomyopathy phenotype. In the future, this novel method for quantifying
fibrosis and fatty tissue can be used to assess cardiac
fibrosis and fatty tissue in animal models and a broad range of human
cardiomyopathies.