The prevalence and phenotypic progression of hypertrophic cardiomyopathy in domestic cats of New Zealand : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Veterinary Science at Massey University, Manawatū, New Zealand

Abstract

Hypertrophic cardiomyopathy (HCM) is considered the most common heart disease in domestic cats (𝘍𝘦𝘭𝘪𝘴 𝘤𝘢𝘵𝘪𝘴). However, the prevalence of HCM in the general feline population is unknown outside the United Kingdom and United States of America. Furthermore, the cause of HCM is unknown in most cats, and the pattern of disease progression is markedly heterogeneous, so much so that some cats will die due to HCM within months of diagnosis, but many live for many years without developing any clinical signs.

To describe the prevalence of HCM in New Zealand and better understand the pattern of disease progression, five studies were conducted. The aims of these five studies were to 1) describe the prevalence of feline HCM in New Zealand, 2) describe the pattern of HCM phenotypic development, 3) describe the HCM phenotypic progression with a specific focus on the subtype of HCM where the blood flow is obstructed due to systolic anterior motion of the mitral valve (SAM), 4) describe the influence of psychological or physiologic stress as an environmental cause of feline HCM, and 5) investigate the pattern of HCM disease progression and a potential genetic cause of HCM in Sphynx cats in New Zealand.

Prospective screening of non-purebred cats in the Centre of Feline Nutrition, which serves as a convenience sample of the general feline population in New Zealand, showed that 15.2% (95% confidence interval: 9.5-22.4%) had echocardiographic evidence of subclinical HCM. However, a retrospective review of the 10-year mortality data showed that only 3.8% (95% confidence interval: 1.2-8.6%) cats died due to complications of HCM, highlighting that many cats with HCM do not develop evidence of heart disease.

Serial echocardiography of cats in the Centre of Feline Nutrition revealed that the anterior mitral valve leaflet increased in length by median 0.5 mm per year (95% CI: 0.4-0.7 mm per year, 𝘗 <0.001), prior to developing HCM in cats. The anterior mitral valve leaflet length did not further increase in cats that had already developed HCM. Additionally, the left ventricular wall thickness increased both in cats with HCM, median 0.4 mm per year (95% CI: 0.2-0.5 mm per year, 𝘗 <0.001) and in cats without HCM, median 0.5 mm per year (95% CI: 0.4-0.7 mm per year, 𝘗 <0.001).

Some of the cats with HCM gained SAM over time, while some lost SAM over time, highlighting that SAM is a labile process in feline HCM. In a retrospective study of 60 cats with HCM from two referral centres over a median 2.1 years of follow-up (minimum 1.0 years; maximum 5.9 years), the yearly incidence of gain or loss of SAM in cats with HCM was 8%. Cats with SAM at the initial diagnosis were more likely to develop congestive heart failure than cats without SAM at the initial diagnosis.

Cat-Stress-Score and hair cortisol concentration are proposed markers of psychological or physiologic stress. To determine a possible role of stress in the development of feline HCM, both markers were measured in a case-control study of 20 cats (10 with subclinical HCM and 10 without HCM) that were matched by sex, neuter status, and age. Neither of these markers were associated with the diagnosis of subclinical HCM in this study, suggesting that psychological or physiologic stress is not a cause of HCM in cats.

Prospective screening of Sphynx cats owned by breeders and pet owners revealed that subclinical HCM was common in Sphynx cats with a prevalence of 40% (95% confidence interval: 28.1-53.2%). A variant in the ALMS1 gene (𝘈𝘓𝘔𝘚1:ENSFCAG00000008756:c.7384G>C;p.[G2462R]) had been previously suggested to be a potential cause of HCM in Sphynx cats. However, while the allelic frequency of 𝘈𝘓𝘔𝘚1 was found to be high at 70.9% in the population of Sphynx cats in New Zealand, the presence of 𝘈𝘓𝘔𝘚1 gene variant was not associated with HCM. This suggests that the 𝘈𝘓𝘔𝘚1 gene variant is unlikely to be the sole determining factor in the development of HCM and that testing for this variant is unlikely to be a successful way to reduce HCM in this cat breed.