Myocardial collagen deposition and inflammatory cell infiltration in cats with pre-clinical hypertrophic cardiomyopathy

Abstract

The histological features of feline hypertrophic cardiomyopathy (HCM) have been well documented, but there are no reports describing the histological features in mild pre-clinical disease, since cats are rarely screened for the disease in the early stages before clinical signs are apparent. Histological changes at the early stage of the disease in pre-clinical cats could contribute to an improved understanding of disease aetiology or progression. The aim of this study was to evaluate the histological features of HCM in the left ventricular (LV) myocardium of cats diagnosed with pre-clinical HCM. Clinically healthy cats with normal (n = 11) and pre-clinical HCM (n = 6) were identified on the basis of echocardiography; LV free wall dimensions (LVFWd) and/or interventricular septal wall (IVSd) dimensions during diastole of 6-7 mm were defined as HCM, while equivalent dimensions <5.5 mm were defined as normal. LV myocardial sections were assessed and collagen content and inflammatory cell infiltrates were quantified objectively. Multifocal areas of inflammatory cell infiltration, predominantly lymphocytes, were observed frequently in the left myocardium of cats with pre-clinical HCM. Tissue from cats with pre-clinical HCM also had a higher number of neutrophils and a greater collagen content than the myocardium of normal cats. The myocardium variably demonstrated other features characteristic of HCM, including arteriolar mural hypertrophy and interstitial fibrosis and, to a lesser extent, myocardial fibre disarray and cardiomyocyte hypertrophy. These results suggest that an inflammatory process could contribute to increased collagen content and the myocardial fibrosis known to be associated with HCM.

Biomarkers of Myocardial Fibrosis: Revealing the Natural History of Fibrogenesis in Fabry Disease Cardiomyopathy

“…Similar to our study, in HCM it has been shown that serum levels of PICP are elevated even in mutation carriers without LV hypertrophy, supporting a profibrotic state preceding development of overt cardiomyopathy . Moreover, a histologic study in cats with preclinical HCM showed an increase in myocardial collagen deposition . Furthermore, studies in murine models of HCM have shown upregulation of several extracellular matrix proteins (CTGF [connective tissue growth factor] and POSTN [periostin]) in the very early stage of the disease (prehypertrophic stage, with normal histologic findings) …”

Anatomopathological staging of feline hypertrophic cardiomyopathy through quantitative evaluation based on morphometric and histopathological data

“…Despite several anatomopathological studies on feline HCM (Liu et al, 1975(Liu et al, , 1981(Liu et al, , 1993Tilley et al, 1977;Liu and Tilley, 1980;Van Vleet et al, 1980;Van Vleet and Ferrans, 1986;Fox, 2003;Cesta et al, 2005;Kershaw et al, 2012;Khor et al, 2014), the quantitative parameters which allow the characterization of this myocardial disease in veterinary pathology are limited. Similarly to the standardized echocardiographic parameters previously established for diagnosis and classification of feline HCM (Migliorini, 2012), the present study aims to propose an original, complete and repeatable quantitative anatomopathological evaluation of gross and histopathological features of this myocardial disease.…”

“…A quantitative evaluation of myocardial fibrosis has already been described for feline HCM (Kershaw et al, 2012;Khor et al, 2014), but without evaluation of the repeatability of the measurement technique.…”

“…The fixed heart was externally examined and opened following the inflow and outflow tracts after transverse sectioning at the level of the middle third of the ventricles in order to evaluate all the cardiac structures. Heart transverse sectioning was chosen according to previous anatomopathological studies (Liu et al, 1981;Cesta et al, 2005;Kershaw et al, 2012;Khor et al, 2014). Transverse sections of myocardium involving the left ventricular (LV) free wall, the interventricular septum and the right ventricular (RV) free wall and other organs samples were routinely embedded in paraffin wax blocks.…”

“…Similarly to the quantitative assessment of left ventricular hypertrophy (Kershaw et al, 2012), myofiber disarray (Kershaw et al, 2012) and myocardial fibrosis (Kershaw et al, 2012;Khor et al, 2014) proposed for feline HCM, the aim of the present study is to provide an original, complete and repeatable quantitative anatomopathological evaluation of feline HCM features based on morphometric and histopathological data. Since ES-HCM is a clearly defined clinicopathological entity of this myocardial disease (Baty et al, 2001;Cesta et al, 2005), the present study also evaluates the possibility of staging its temporal evolution by a morphological differentiation of the phenotypes in the initial/ middle phase of the pathology from the end-stage ones based on anatomopathological findings only.…”