ACVIM consensus statement guidelines for the classification, diagnosis, and management of cardiomyopathies in cats

Cardiomyopathies are a heterogeneous group of myocardial disorders of mostly unknown etiology, and they occur commonly in cats. In some cats, they are well-tolerated and are associated with normal life expectancy, but in other cats they can result in congestive heart failure, arterial thromboembolism or sudden death. Cardiomyopathy classification in cats can be challenging, and in this consensus statement we outline a classification system based on cardiac structure and function (phenotype). We also introduce a staging system for cardiomyopathy that includes subdivision of cats with subclinical cardiomyopathy into those at low risk of life-threatening complications and those at higher risk. Based on the available literature, we offer recommendations for the approach to diagnosis and staging of cardiomyopathies, as well as for management at each stage

Classification of feline hypertrophic cardiomyopathy-associated gene variants according to the American College of Medical Genetics and Genomics guidelines

INTRODUCTION: The correct labeling of a genetic variant as pathogenic is important as breeding decisions based on incorrect DNA tests can lead to the unwarranted exclusion of animals, potentially compromising the long-term health of a population. In human medicine, the American college of Medical Genetics (ACMG) guidelines provide a framework for variant classification. This study aims to apply these guidelines to six genetic variants associated with hypertrophic cardiomyopathy (HCM) in certain cat breeds and to propose a modified criterion for variant classification. METHODS: Genetic samples were sourced from five cat breeds: Maine Coon, Sphynx, Ragdoll, Devon Rex, and British Short- and Longhair. Allele frequencies were determined, and in the subset with phenotypes available, odds ratios to determine the association with HCM were calculated. In silico evaluation followed with joint evidence and data from other publications assisting in the classification of each variant. RESULTS: Two variants, MYBPC3:c.91G > C [A31P] and MYBPC3:c.2453C > T [R818W], were designated as pathogenic. One variant, MYH7:c.5647G > A [E1883K], was found likely pathogenic, while the remaining three were labeled as variants of unknown significance. DISCUSSION: Routine genetic testing is advised solely for the MYBPC3:c.91G > C [A31P] in the Maine Coon and MYBPC3:c.2453C > T [R818W] in the Ragdoll breed. The human ACMG guidelines serve as a suitable foundational tool to ascertain which variants to include; however, refining them for application in veterinary medicine might be beneficial

Classification of feline hypertrophic cardiomyopathy-associated gene variants according to the American College of Medical Genetics and Genomics guidelines

IntroductionThe correct labeling of a genetic variant as pathogenic is important as breeding decisions based on incorrect DNA tests can lead to the unwarranted exclusion of animals, potentially compromising the long-term health of a population. In human medicine, the American college of Medical Genetics (ACMG) guidelines provide a framework for variant classification. This study aims to apply these guidelines to six genetic variants associated with hypertrophic cardiomyopathy (HCM) in certain cat breeds and to propose a modified criterion for variant classification.MethodsGenetic samples were sourced from five cat breeds: Maine Coon, Sphynx, Ragdoll, Devon Rex, and British Short- and Longhair. Allele frequencies were determined, and in the subset with phenotypes available, odds ratios to determine the association with HCM were calculated. In silico evaluation followed with joint evidence and data from other publications assisting in the classification of each variant.ResultsTwo variants, MYBPC3:c.91G > C [A31P] and MYBPC3:c.2453C > T [R818W], were designated as pathogenic. One variant, MYH7:c.5647G > A [E1883K], was found likely pathogenic, while the remaining three were labeled as variants of unknown significance.DiscussionRoutine genetic testing is advised solely for the MYBPC3:c.91G > C [A31P] in the Maine Coon and MYBPC3:c.2453C > T [R818W] in the Ragdoll breed. The human ACMG guidelines serve as a suitable foundational tool to ascertain which variants to include; however, refining them for application in veterinary medicine might be beneficial

The genetic basis of hypertrophic cardiomyopathy in cats and humans

Mutations in genes that encode for muscle sarcomeric proteins have been identified in humans and two breeds of domestic cats with hypertrophic cardiomyopathy (HCM). This article reviews the history, genetics, and pathogenesis of HCM in the two species in order to give veterinarians a perspective on the genetics of HCM. Hypertrophic cardiomyopathy in people is a genetic disease that has been called a disease of the sarcomere because the preponderance of mutations identified that cause HCM are in genes that encode for sarcomeric proteins (Maron and Maron, 2013). Sarcomeres are the basic contractile units of muscle and thus sarcomeric proteins are responsible for the strength, speed, and extent of muscle contraction. In people with HCM, the two most common genes affected by HCM mutations are the myosin heavy chain gene (MYH7), the gene that encodes for the motor protein β-myosin heavy chain (the sarcomeric protein that splits ATP to generate force), and the cardiac myosin binding protein-C gene (MYBPC3), a gene that encodes for the closely related structural and regulatory protein, cardiac myosin binding protein-C (cMyBP-C). To date, the two mutations linked to HCM in domestic cats (one each in Maine Coon and Ragdoll breeds) also occur in MYBPC3 (Meurs et al., 2005, 2007). This is a review of the genetics of HCM in both humans and domestic cats that focuses on the aspects of human genetics that are germane to veterinarians and on all aspects of feline HCM genetics

Investigation into the use of plasma NT-proBNP concentration to screen for feline hypertrophic cardiomyopathy.

To evaluate the utility of feline NT-proBNP plasma concentration [NT-proBNP] as a screening tool for cats with subclinical hypertrophic cardiomyopathy (HCM).Forty adult Maine Coon or Maine Coon crossbred cats from the feline HCM research colony at the University of California, Davis were studied. All cats had previously been genotyped as heterozygous or negative for the A31P myosin binding protein C (MYBPC) mutation. Echocardiograms were performed to assess the severity of HCM in each cat. Blood samples were collected for evaluation of [NT-proBNP].In these cats with severe HCM, [NT-proBNP] was significantly elevated (P<0.0001) when compared to all other groups of cats and an [NT-proBNP]>44pmol/L accurately predicted the presence of severe HCM. However, [NT-proBNP] was not increased in cats with moderate or equivocal HCM when compared to normal cats. Cats heterozygous for the MYBPC mutation had a significantly elevated [NT-proBNP] when compared to cats without the A31P mutation (P=0.028).Measurement of [NT-proBNP] has a high sensitivity and specificity as a means of detecting severe HCM in cats, but it is not sensitive for the identification of moderate HCM as judged by the evaluation of Maine Coon and Maine Coon cross cats in our colony. Consequently, we conclude that this test cannot be used to screen cats for the presence of mild to moderate HCM

Investigation into the use of plasma NT-proBNP concentration to screen for feline hypertrophic cardiomyopathy.

To evaluate the utility of feline NT-proBNP plasma concentration [NT-proBNP] as a screening tool for cats with subclinical hypertrophic cardiomyopathy (HCM).Forty adult Maine Coon or Maine Coon crossbred cats from the feline HCM research colony at the University of California, Davis were studied. All cats had previously been genotyped as heterozygous or negative for the A31P myosin binding protein C (MYBPC) mutation. Echocardiograms were performed to assess the severity of HCM in each cat. Blood samples were collected for evaluation of [NT-proBNP].In these cats with severe HCM, [NT-proBNP] was significantly elevated (P<0.0001) when compared to all other groups of cats and an [NT-proBNP]>44pmol/L accurately predicted the presence of severe HCM. However, [NT-proBNP] was not increased in cats with moderate or equivocal HCM when compared to normal cats. Cats heterozygous for the MYBPC mutation had a significantly elevated [NT-proBNP] when compared to cats without the A31P mutation (P=0.028).Measurement of [NT-proBNP] has a high sensitivity and specificity as a means of detecting severe HCM in cats, but it is not sensitive for the identification of moderate HCM as judged by the evaluation of Maine Coon and Maine Coon cross cats in our colony. Consequently, we conclude that this test cannot be used to screen cats for the presence of mild to moderate HCM

Philosophical Trends in Health Education: Implications for the 21st Century

The purpose of this study was to explore five health education philosophies: cognitive based, decision-making, behavior change, freeing/functioning, and social change. This was done in order to ascertain if there is a single dominant philosophy ascribed to by health educators, and discover any variations in philosophical preferences between health education academicians and practitioners. The Health Education Philosophy Inventory (HEPI) was designed to answer these questions. Through a series of vignettes and a rank order exercise, HEPI determined both philosophical preference within educational settings and philosophical beliefs. Data were collected from a nationwide random sample of health education professionals through a mailed survey. Total response rate of usable inventories was 48.3 percent. Content analysis determined the philosophical preference in educational settings was behavior change, followed by freeing/functioning. The stated philosophical preferences in the rank order exercise was decision-making. Statistically significant differences (p = .0059) were noted between academicians and practitioners in their choices in educational settings, yet stated philosophical beliefs were identical. Recommendations emanating from the study included future studies to be conducted to verify the findings. Philosophical preferences of health educators who work in settings other than community and university, i.e., school, worksite, and clinical, need be investigated