Pathology of End-stage Remodeling in a Family of Cats with Hypertrophic Cardiomyopathy

Abstract

Abstract. End-stage hypertrophic cardiomyopathy (ES-HCM), affecting 5-10% of human hypertrophic cardiomyopathy (HCM) patients, is characterized by relative thinning of the ventricular walls and septum with dilation of the ventricular lumen, decreased fractional shortening, and progression to heart failure. C. J. Baty and others recently documented similar progressive changes to ES-HCM in a family of four cats through serial echocardiograms. At the time of heart failure, these cats exhibited changes similar to those exhibited by human ES-HCM patients. Our objectives were to describe the pathologic alterations associated with ES-HCM and investigate the pathogenesis in three of the four cats. Grossly, there was left atrial dilation with relative thinning of the interventricular septum (IVS) and left ventricular free wall (LVFW). The left atrium contained large thrombi in two of the three cats, and all three cats died following thromboembolization of the aortic bifurcation. Histologically, all three cats had subendocardial and myocardial fibrosis, predominantly of the IVS and LVFW, and one cat had acute, multifocal, myocardial infarcts with mononuclear inflammatory cell infiltrates. The pathogenesis of ES-HCM is uncertain, but theories implicate occlusion of the coronary blood flow by thickening of the coronary vessels, coronary vascular thromboembolism or coronary vessel spasm, apoptosis of myocytes, and myocardial hypertrophy beyond the ability of the vasculature to supply blood. Apoptosis assays did not reveal any apoptotic myocytes. Considering the hypercoagulative state of these cats, coronary vascular thromboembolism could be a major contributing factor. We cannot exclude apoptosis or coronary vessel spasm on the basis of the data presented.

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

“…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.…”

“…End-stage hypertrophic cardiomyopathy (ES-HCM) is the dilated phase of HCM. It is characterized by relative dilation of the ventricular chambers, relative thinning of the ventricular walls, marked left atrial dilation and variable myocardial scarring, with consequent decreased ventricular contractility often closely followed by congestive heart failure (Baty et al, 2001;Cesta et al, 2005).…”

“…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.…”

Evaluation of Feline Cardiomyopathies

“…Progressive dilation of the LV and left atrium (LA) as well as a reduction of the SF were observed. Subendocardial and myocardial fibrosis, as well as multifocal infarcts, was present in three of these cats, indicating that ischemic phenomena were involved in the remodeling process [11]. Echocardiographically, the presence of thin and hypocontractile myocardial areas adjacent to still hypertrophied segments characterizes remodeling ( Figure 13-3 and Video 13-10).…”

Cardiomyopathies in Animals

“…Histologic findings based on hematoxylin and eosin (HE) staining and other specific markers revealed several abnormalities including multifocal myocardial interstitial fibrosis, myofiber disarray, diffuse myocyte hypertrophy with or without scattered individual cell necrosis, and arteriosclerosis in papillary muscles in the LV wall, interventricular septum, and intramural coronary artery [10,37]. Recent evidence showed remodeling of the myofibrils and interfibrillar mitochondria, sarcolemmal remodeling with depletion of the subsarcolemmal mitochondria, changes of Z-disc morphology, myofibrillar degeneration, and endomysial fibrosis based on electron microscopic examination [10].…”