Exploration of Mediators Associated with Myocardial Remodelling in Feline Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) affects both humans and cats and exhibits considerable interspecies similarities that are exemplified by underlying pathological processes and clinical presentation to the extent that developments in the human field may have direct relevance to the feline disease. Characteristic changes on histological examination include cardiomyocyte hypertrophy and interstitial and replacement fibrosis. Clinically, HCM is characterised by significant diastolic dysfunction due to a reduction in ventricular compliance and relaxation associated with extracellular matrix (ECM) remodelling and the development of ventricular hypertrophy. Studies in rodent models and human HCM patients have identified key protein mediators implicated in these pathological changes, including lumican, lysyl oxidase and TGF-ß isoforms. We therefore sought to quantify and describe the cellular location of these mediators in the left ventricular myocardium of cats with HCM and investigate their relationship with the quantity and structural composition of the ECM. We identified increased myocardial content of lumican, LOX and TGF-ß2 mainly attributed to their increased expression within cardiomyocytes in HCM cats compared to control cats. Furthermore, we found strong correlations between the expressions of these mediators that is compatible with their role as important components of cellular pathways promoting remodelling of the left ventricular myocardium. Fibrosis and hypertrophy are important pathological changes in feline HCM, and a greater understanding of the mechanisms driving this pathology may facilitate the identification of potential therapies.

Immunohistological Evaluation of Von Willebrand Factor in the Left Atrial Endocardium and Atrial Thrombi from Cats with Cardiomyopathy.

Aortic thromboembolism (ATE) occurs in cats with cardiomyopathy and often results in euthanasia due to poor prognosis. However, the underlying predisposing mechanisms leading to left atrial (LA) thrombus formation are not fully characterised. von Willebrand Factor (vWF) is a marker of endothelium and shows increased expression following endothelial injury. In people with poor LA function and LA remodelling, vWF has been implicated in the development of LA thrombosis. In this study we have shown (1) the expression of endocardial vWF protein detected using immunohistofluorescence was elevated in cats with cardiomyopathy, LA enlargement (LAE) and clinical signs compared to cats with subclinical cardiomyopathy and control cats; (2) vWF was present at the periphery of microthrombi and macrothrombi within the LA where they come into contact with the LA endocardium and (3) vWF was integral to the structure of the macrothrombi retrieved from the atria. These results provide evidence for damage of the endocardial endothelium in the remodelled LA and support a role for endocardial vWF as a pro-thrombotic substrate potentially contributing to the development of ATE in cats with underlying cardiomyopathy and LAE. Results from this naturally occurring feline model may inform research into human thrombogenesis.

Time spent with cats is never wasted: Lessons learned from feline acromegalic cardiomyopathy, a naturally occurring animal model of the human disease.

BACKGROUND: In humans, acromegaly due to a pituitary somatotrophic adenoma is a recognized cause of increased left ventricular (LV) mass. Acromegalic cardiomyopathy is incompletely understood, and represents a major cause of morbidity and mortality. We describe the clinical, echocardiographic and histopathologic features of naturally occurring feline acromegalic cardiomyopathy, an emerging disease among domestic cats. METHODS: Cats with confirmed hypersomatotropism (IGF-1>1000ng/ml and pituitary mass; n = 67) were prospectively recruited, as were two control groups: diabetics (IGF-1<800ng/ml; n = 24) and healthy cats without known endocrinopathy or cardiovascular disease (n = 16). Echocardiography was performed in all cases, including after hypersomatotropism treatment where applicable. Additionally, tissue samples from deceased cats with hypersomatotropism, hypertrophic cardiomyopathy and age-matched controls (n = 21 each) were collected and systematically histopathologically reviewed and compared. RESULTS: By echocardiography, cats with hypersomatotropism had a greater maximum LV wall thickness (6.5mm, 4.1-10.1mm) than diabetic (5.9mm, 4.2-9.1mm; Mann Whitney, p<0.001) or control cats (5.2mm, 4.1-6.5mm; Mann Whitney, p<0.001). Left atrial diameter was also greater in cats with hypersomatotropism (16.6mm, 13.0-29.5mm) than in diabetic (15.4mm, 11.2-20.3mm; Mann Whitney, p<0.001) and control cats (14.0mm, 12.6-17.4mm; Mann Whitney, p<0.001). After hypophysectomy and normalization of IGF-1 concentration (n = 20), echocardiographic changes proved mostly reversible. As in humans, histopathology of the feline acromegalic heart was dominated by myocyte hypertrophy with interstitial fibrosis and minimal myofiber disarray. CONCLUSIONS: These results demonstrate cats could be considered a naturally occurring model of acromegalic cardiomyopathy, and as such help elucidate mechanisms driving cardiovascular remodeling in this disease.

Asymptomatic Hypertrophic Cardiomyopathy: Diagnosis and Therapy.

Hypertrophic cardiomyopathy (HCM) affects 15% of cats, and prevalence increases with age. Although many cats with HCM have normal life expectancy, some cats die suddenly, or develop congestive heart failure or arterial thromboembolism (ATE). High-risk cats can be recognized by left atrial enlargement on echocardiography, which can be missed on physical examination, as a heart murmur is often absent. Alternatively, plasma biomarkers can be measured as an initial screening test; echocardiography is indicated in cats with plasma NT-probrain natriuretic peptide concentrations exceeding 100 pmol/L. High-risk cats should be treated with clopidogrel to reduce the risk of ATE.

MEDICAL MANAGEMENT OF DILATED CARDIOMYOPATHY IN LIVINGSTONE FRUIT BATS ( PTEROPUS LIVINGSTONII).

Eleven cases of dilated cardiomyopathy have been diagnosed and treated in captive Livingstone fruit bats ( Pteropus livingstonii) in the United Kingdom over the past 7 yr. All but one case received treatment with a diuretic plus an angiotensin-converting enzyme inhibitor (ACEI), and, or pimobendan. One case is still under treatment with pimobendan alone, following diagnosis before onset of clinical signs. Diuretic treatment consisted of furosemide at a dose rate of 0.5-5 mg/kg, one to three times daily, and, or spironolactone at a dose rate of 1-4 mg/kg, once or twice daily. When used, the ACEI imidapril was given at a dose rate of 0.24-0.38 mg/kg q 24 hr, and pimobendan at a dose rate of 0.2-0.5 mg/kg bid. This report is intended to provide anyone seeking to medically manage heart failure in Pteropus species, particularly P. livingstonii, with a review of drugs and doses that have been used.

Familial cardiomyopathy in Norwegian Forest cats.

Norwegian Forest cats (NFCs) are often listed as a breed predisposed to cardiomyopathy, but the characteristics of cardiomyopathy in this breed have not been described. The aim of this preliminary study was to report the features of NFC cardiomyopathy based on prospective echocardiographic screening of affected family groups; necropsy findings; and open-source breed screening databases. Prospective examination of 53 NFCs revealed no murmur or left ventricular (LV) outflow tract obstruction in any screened cat, though mild LV hypertrophy (defined as diastolic LV wall thickness ≥5.5mm) was present in 13/53 cats (25%). Gross pathology results and histopathological sections were analysed in eight NFCs, six of which had died of a cardiac cause. Myocyte hypertrophy, myofibre disarray and interstitial fibrosis typical of hypertrophic cardiomyopathy were present in 7/8 cats, but endomyocardial fibrosis suggestive of restrictive cardiomyopathy was also present in the same cats. Pedigree data analysis from 871 NFCs was supportive of a familial cardiomyopathy in this breed.