Hypertrophic cardiomyopathy in cats—It used to be so simple!

Since the description of feline hypertrophic cardiomyopathy in the early 1970s, substantial effort has gone into the characterization of the disease (Atkins 1992, Liu 1970, Liu 1981, Lord 1974). The various names that have been applied to this condition reflect one of the outstanding characteristics of the disease—heterogeneity. Primary hypertrophic cardiomyopathy is identified as a hypertrophied non-dilated left ventricle where the extent of hypertrophy is not attributable to other causes including systemic, congenital heart or infiltrative diseases. Interest in this disease has been twofold. Since the drastic reduction of feline dilated cardiomyopathy with recognition of the significance of taurine deficiency, hypertrophic cardiomyopathy (HCM) is the most commonly diagnosed form of feline cardiomyopathy. Thus, it is an important disease in cats and continues to be a diagnostic and a therapeutic challenge for the veterinarian. 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 involved in breeding of purebred cats 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 the feline HCM as a model for study of the human disease (Liu 1980, Liu 1993).

Since the first description of HCM, a genetic background of the disease has been suspected as the disease may occur, although not exclusively, as familiar disease in some instances, such as in Maine Coon cats (Kittleson 1999). In this breed, it has been shown that HCM is inherited as an autosomal dominant trait (Kittleson 1999). This has led to extensive search for a genetic or a biochemical marker depicting the presence of HCM; but what first appeared to be comparably easy, turned out to be considerably more complicated. As the feline HCM has many similarities with human familiar HCM with regard to inheritance pattern, clinical presentation and histopathologic changes, there was an initial hope that findings in people could be extrapolated to cats. However, at present, over 125 mutations in nine genesencoding sarcomeric proteins (β myosin heavy chain, α-tropomyosin, troponin I, troponin T, myosin light chains, myosin binding protein C, α-cardiac actin and titin) are known to cause familiar HCM in people (Towbin 2000). Although mutations in some of the genes coding for these proteins in cats have been found, none of these have hitherto been shown linking to feline HCM. Recently, Meurs and co-workers found that myomesin, a sarcomeric protein, is reduced or absent in the myocardium of Maine Coon cats affected with familiar HCM (Meurs 2001). These findings support the fact that familiar HCM in cats is a disease of the sarcomere, and paves a possible way to tests for early diagnosis in breeding programs in future.

In the absence of genetic tests to diagnose the disease, the presence of disease today, and in the near future, relies largely on the characterization of the phenotype using echocardiography. Fortunately, the vast technical improvement over the years has led to better image quality and image acquisition (frame rate), which facilitate detection of HCM in feline patients. The frame rate is especially important when examining the cats because of the heart rate in feline patients. From the beginning, feline HCM was characterized as the global thickening of all the 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 (Bright 1992, Fox 1995, Liu 1981), and no single pattern can be considered a characteristic of the disease. In localized forms, the entire interventricular septum or free wall or a region of them may be affected, the apex or the papillary muscles being primarily affected (Fox 1995). Because of the heterogeneity, HCM is a diagnosis that should be made by examining several two-dimensional (2-D) echocardiographic views, and by measuring the wall thicknesses in diastole from the region of thickening on the 2-D 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 is 5.5 mm, and anything above 6 mm is believed to be an evidence of concentric hypertrophy (Fox 1995). Other evidence of HCM is the presence of systolic anterior motion (SAM) of the mitral valve. Not all cats with manifest HCM have SAM, but this abnormal motion of the mitral valve may be present in some cats before they have evidence of wall thickening, whereas others have SAM only as the manifestation of the disease (Fox 1995).

At present, 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. However, the diagnosis of HCM is much more difficult and controversial in cats with lesser wall thickening or only regional thickening on an echocardiogram. To distinguish either mild disease from normal, or mild to moderate disease from hypertrophy secondary to other abnormalities is often not easy in individual cases. In the clinical situation examining an old cat with suspected hypertrophy, the decision must first be taken whether hypertrophy is present or not. Then the causes for hypertrophy other than HCM must be ruled out before the diagnosis is established.

Is it important to detect mild to moderate HCM in asymptomatic adult cats? In cases of cats that are either 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 (Kittleson 1998), 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 the occurrence of other complications, such as arterial thromboebolism, is small. However, for breeding purposes, it may be important to detect these asymptomatic individuals to reduce the overall incidence of overt disease. Currently, screening of certain breeds, such as Maine Coon cats, has been initiated and this will lead to increased demands on the examiners to distinguish diseased cats from the healthy ones. In the absence of exact criteria for the disease and there being many examiners, there will be subjectivity and variation in interpreting findings. Nevertheless, it is important, like any breeding program, that healthy individuals are not excluded due to false positive diagnosis. Actually, this is more important than allowing a few diseased individuals to breed.