Feline hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is a common cause of sudden death in cats that is characterised by thickening of the ventricular walls. At postmortem heart weight is a reliable proxy of cardiac size with heart:body weight (BW) ratios in excess of 4.2 g/kg BW indicating a large heart; most cases of HCM show ratios in excess of 5 g/kg BW. Hypertrophic cardiomyopathy may present in various ways including congestive heart failure, aortic thromboembolism or sudden death with no premonitory signs. Reports suggest a familial predisposition in Persian, American Shorthair, Maine Coon and Ragdoll cats with specific gene mutations identified in Maine Coon and Ragdolls. Male cats are overrepresented and typically the idiopathic form of HCM is seen in young to middle aged adults. The pathology of HCM is characterised by a generalised or focal thickening of the myocardium offen with dilatation of the left atrium, cardiomyocyte hypertrophy, some interstitial fibrosis and mixed inflammatory cell aggregates. The pathophysiology of the myocardial injury is unclear, with developmental issues (gene mutations), toxicities, inflammatory processes and myocardial infarction suggested. There is an association between HCM in the older cat and hyperthyroidism. Mediators of inflammation and remodelling are present in the cats myocardium, and there is a recognised shift from a pro-inflammatory state in younger cats to a pro-fibrotic state as cats age. Their role in causing morphological changes in feline hearts was studied by Kitz et al (2019). They compared the hearts of 18 cats with HCM, with those from 18 control cats. Histological features of HCM (cardiomyocyte disarray and degeneration, leukocyte infiltration, and interstitial fibrosis) were observed in 83% of the HCM cases with patchy to disseminated multifocal loss and/or degeneration of cardiomyocytes, collagen deposition with moderate numbers of fibrocytes, increased interstitial cellularity associated with the presence macrophage and blood vessel proliferation.
In 44% of HCM cases focal areas comprised of cardiomyocyte degeneration encircling densely packed collagen bundles with fibroblasts and macrophages. Lymphocytes were not more numerous in the myocardium of cats with HCM compared to the control population. In cats with HCM, various pro-inflammatory and re-modelling cytokines (chemical messengers) were up-regulated compared to the control cats.
Feline HCM is a disease associated with cardiomyocyte necrosis and the development of granulation tissue (increases in interstitial macrophages, blood vessels and interstitial collagen). The stimulus for its development is unclear and its pathophysiology is complex and likely to be multifactorial. This article by Kitz et al (2019) contributes interesting information on the role inflammation and fibrosis play in its development. They had previously reported that the normal cats heart has the capacity to produce a range of inflammatory and remodelling mediators, and that there is shift from a proinflammatory state in the younger cat to a remodelling or pro-fibrotic state as the cat ages. The authors note that the increase in interstitial cells was not associated with an increase in overall cell numbers, which they took to suggest as indicating a reduction in the number of cardiomyocytes due to injury and loss. These focal lesions of myocyte loss were considered by the authors to be infarct-like lesions with disorderly arranged granulation tissue and that the presence of dying cardiomyocytes at the edge of these lesions suggested active expansion of the area of damage. These focal infarcts were present mainly in the thicker areas of the left ventricle and interventricular septum and their random distribution suggests an ischaemic cause. They were not able to identify the underlying basis of the infarcts, but their presence in the thicker regions of the myocardium suggests possible histological issues relating to blood supply. Inflammation that develops due to chronic antigenic stimulation (ie chronic viral infection) does not appear to be a cause of HCM and nor is it involved in perpetuating disease. Rather, the infiltrate of macrophages is a secondary process responsible for driving fibrosis and remodelling after myocardial injury has occurred. This recruitment and proliferation of interstitial macrophages is stimulated by locally produced factors (cytokines) in the myocardium. The local release of mediators by activated macrophages and cardiomyocytes promotes fibroplasia to maintain structural integrity and neovascularisation to promote blood flow; this is granulation tissue. The authors speculate that hypoxia and thus cardiomyocyte degeneration may develop secondary to individual cardiomyocyte issues (ie individual cellular issues such as mitochondrial problems) or compromise of blood flow to a large; hypoxic environments can induce a macrophage-driven inflammatory response. The authors speculate that as young male cats are primed to produce pro-inflammatory compounds, these might result in cardiomyocyte damage when triggered, or that susceptible cats might persistently produce more cytokines, predisposing cardiomyocytes to injury even after mild hypoxic events that in other cats would not be an issue. As cats age, there is a reduced ability to react to injury and repair the myocardium, which with continued disease progression, may result in more pronounced myocardial damage.