Professor, Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Uppsala, Sweden
Depending on the morphological appearance and pathophysiology, cardiomyopathy in cats is frequently classified as hypertrophic (HCM), dilated (DCM), and restrictive (RCM). Unfortunately, many cases have overlapping features or do not fit into a particular category. This has given rise to the increasingly used classification “unclassified cardiomyopathy.” With the exception for taurine dependent feline DCM, it is currently not known if and how these different types of cardiomyopathy are related. HCM is currently the most commonly diagnosed form of feline cardiomyopathy. Primary HCM is identified as a hypertrophied nondilated left ventricle where the extent of hypertrophy is not attributable to other causes including systemic, congenital cardiac or infiltrative diseases. Interest in this disease has been twofold. Owners are particularly disturbed by incidence of sudden death and thromboembolic episodes that appear in apparently healthy cats. In turn, this has led to an interest of breeders to establish breeding programs aimed at reducing the incidence of HCM. Secondly, since HCM is an important disease in people, especially as a cause of sudden death in adolescents and young adults, there is an interest in feline HCM as a mode l for the human disease. This presentation is limited to genetic, diagnostic and breeding aspects of HCM in purebred cats in light of experiences of screening cats in Europe.
Genetic Testing and Classification of Disease
Familial hypertrophic cardiomyopathy (HCM) has been shown an inherited trait in some cat breeds, such as American Shorthair, Maine Coon, and Persian. The disease is suspected to be inherited also in other breeds, such as Sphynx. In American Shorthair and Maine Coon cats it has been shown that familial HCM is inherited as an autosomal dominant trait. Because of two studies, one in Maine Coon Cats and one in Ragdoll cats, genetic tests for the disease in both breeds are available to the public. The proportion of gene test positive cats appears to be very high in the Maine Coon population both in the USA and in Europe. The value of the genetic test in European Maine Coon cats has recently been questioned. Therefore, the presence of HCM has relied, still relies today, and will in the near future rely largely on characterization of the phenotype by use of echocardiography. Even in the future when effective genetic tests may be available, there may still be a need for screening cats using echocardiography, because other mutations may spread in cat families, either through propagation of an existing mutation, or through a spontaneous de novo gene mutation (i.e., the sire and dam are unaffected but the offspring have the mutation). Fortunately, the vast technical improvement over the years has led to better image quality and image acquisition, which facilitate detection of HCM in feline patients. Feline HCM used to be characterized as global thickening of all portions of the left ventricle often together with left atrial enlargement. With increasing knowledge of feline HCM and improved diagnostic methods, the disease is now considered to be characterized by a broad range of phenotypic patterns of left ventricular hypertrophy ranging from localized and relatively mild wall segment to the overall thickened classical type, and no single pattern can be considered characteristic for the disease. In localized forms, the entire interventricular septum or free wall or a region of them may be affected, the apex may be primarily affected, or the papillary muscles. Because of the heterogeneity, HCM is a diagnosis that should be made by examining several two-dimensional echocardiographic views and measuring wall thicknesses in diastole from the region of thickening on the two-dimensional images. A standard M-mode echocardiogram of the left ventricle (taken from immediately below the mitral valve) may miss regional wall thickening. The upper limit for left ventricular thickness has traditionally been set at a maximum of 5.5 mm and anything above 6 mm is thought to be evidence of concentric hypertrophy. This limit is conservative because a recent report indicates a narrower body-weight dependent reference interval. Because echocardiographic measurements are usually corrected for body size in dogs, it may be confusing that body size is not accounted for in cats. After all, some males may have a lean weight twice the weight of a small female, and pure breed cats have a body weight ranging between 2.5 kg to >10 kg. A recent report including almost 20,000 cats shows that the body weight does have a clinically relevant effect on the echocardiographic measurements in cats too, and should be taken into account when evaluating the wall thickness and other echocardiographic dimensions. It should be noted that a measure outside this range does not necessarily indicate that the cat has HCM. Measurements that fall outside this range may be caused by unusual phenotypes (such as false tendons and ectopic papillary muscles, etc.), and/ or by suboptimal quality of the examination and/ or acquisition. Other evidence of HCM is the presence of systolic anterior motion of the mitral valve (SAM). Not all cats which manifest HCM have SAM, but this abnormal motion of the mitral valve may be present in some cats before they have overt evidence of wall thickening.
Because of the great interest from breeders and veterinarians in Europe to reduce the incidence of HCM in purebred cats, extensive screening is currently undertaken using echocardiography. Breeds currently being screened include most of the popular breeds. Completely asymptomatic HCM cats have been diagnosed in cat families of these breeds in frequencies slightly less than previously reported in Maine coon cats. However, the experience from this screening is that, although, the diagnosis of moderate to severe HCM is often not controversial as long as the most common differential diagnoses, such as systemic hypertension and hyperthyroidism, have been ruled out, the diagnosis of HCM is much more difficult and controversial. Indeed, some of these cats were diagnosed with HCM, but many cats are classified as equivocal, which means that re-examinations are recommended to verify or refute HCM, and that breeding restrictions are recommended. The main problem for the examiner has been how to classify cats with lesser wall thickening, or only regional thickening, or slightly to moderately hypertrophied papillary muscles on the echocardiogram. Thus, there has been a problem distinguishing mild disease from unusual, but, presumably, normal phenotypes (regarding HCM). Indeed, the examination itself and the interpretation of some of the echocardiograms may very well be one of the most difficult examinations currently undertaken in veterinary cardiology. Because of the difficulty of the examination and multiple examiners, there have been cases where different examiners have classified a specific cat differently, although these cases have, so far, been very few. However, to distinguish mild to moderate disease from hypertrophy secondary to other abnormalities (such as hyperthyroidism, renal failure, dehydration, etc.) appears to have been less problematic.
For the individual cat that is neutered or not intended to be used for breeding, it may not be so important. These cats have a good-short term and possibly long term prognosis, because the chance that heart failure will develop in the near future is little, owing to minor influence of the hypertrophy on cardiac performance, and the chance for other complications such as arterial thromboembolism is small. However, for breeding purposes it is important that borderline cats (classified as equivocal or mild HCM) are eventually correctly diagnosed to reduce the overall incidence of overt disease. The breeders are, therefore, instructed to re-examine these cats and to submit their cat to post mortem and histopathologic examinations once it dies. The reasons are twofold. The importance of specific echocardiographic findings, such as slight to moderate papillary muscle hypertrophy, need to be evaluated longitudinally, and the breeder needs the information for planning future breeding. The additional information from the post-mortem and histopathological examination is important to verify or refute the diagnosis of HCM.
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