Clinical outcome of idiopathic juvenile ventricular arrhythmias in 25 dogs.

INTRODUCTION/OBJECTIVES: Juvenile ventricular arrhythmias in the absence of structural heart disease have been characterized in a small number of canine breeds with limited long-term follow up. The objective of this study was to describe the clinical outcome of dogs with JVA presenting to a university teaching hospital. ANIMALS, MATERIALS, METHODS: Twenty five dogs, less than two years old with idiopathic ventricular arrhythmias were retrospectively identified via a medical record search. Young dogs with ventricular arrhythmias were excluded if they had structural heart disease, systemic illness, or an abnormal troponin (if performed). Electrocardiographic and Holter monitor data was evaluated for arrhythmia frequency and complexity at the time of diagnosis and over time. Long-term follow up was achieved through client and primary veterinarian contact. RESULTS: Breeds included German Shepherd (eight), Boxer (four), Great Dane (three), mixed breed (two) and one each of the following: Anatolian Shepherd, French Bulldog, golden retriever, Great Pyrenees, Labrador retriever, Shiloh Shepherd, miniature Poodle and Siberian Husky. The average age at diagnosis was 7.9 months (range, 2-22 months). The overall median survival was 10.96 years (range, 1.75-15.66 years). There was an average reduction in the number of ventricular beats by 86.7 % per year (P value -0.0257) based on Holter data. CONCLUSION: In most cases, idiopathic juvenile ventricular arrhythmias had a favorable long-term prognosis with reduced ectopy over time in this case series. Juvenile ventricular arrhythmias remains a diagnosis of exclusion but can be considered in a broader range of dog breeds than previously described.

Association of diet with clinical outcomes in dogs with dilated cardiomyopathy and congestive heart failure.

INTRODUCTION: Dilated cardiomyopathy (DCM) in dogs has been associated with feeding of grain-free (GF), legume-rich diets. Some dogs with presumed diet-associated DCM have shown improved myocardial function and clinical outcomes following a change in diet and standard medical therapy. HYPOTHESIS: Prior GF (pGF) diet influences reverse cardiac remodeling and clinical outcomes in dogs with DCM and congestive heart failure (CHF). ANIMALS AND METHODS: A retrospective study was performed with 67 dogs with DCM and CHF for which diet history was known. Dogs were grouped by diet into pGF and grain-inclusive (GI) groups. Dogs in the pGF group were included if diet change was a component of therapy. Survival was analyzed using Kaplan-Meier curves and the Cox proportional-hazards model. RESULTS: The median survival time was 344 days for pGF dogs vs. 253 days for GI dogs (P = 0.074). Statistically significant differences in median survival were identified when the analysis was limited to dogs surviving longer than one week (P = 0.033). Prior GF dogs had a significantly worse outcome the longer a GF diet was fed prior to diagnosis (P = 0.004) or if they were diagnosed at a younger age (P = 0.017). Prior GF dogs showed significantly greater improvement in normalized left ventricular internal diastolic diameter (P = 0.038) and E-point septal separation (P = 0.031) measurements and significant decreases in their furosemide (P = 0.009) and pimobendan (P < 0.005) dosages over time compared to GI dogs. CONCLUSIONS: Prior GF dogs that survived at least one week after diagnosis of DCM, treatment of CHF, and diet change had better clinical outcomes and showed reverse ventricular remodeling compared to GI dogs.

A review of the underlying genetics and emerging therapies for canine cardiomyopathies.

Cardiomyopathies such as dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are common in large breed dogs and carry an overall poor prognosis. Research shows that these diseases have strong breed predilections, and selective breeding has historically been recommended to reduce the disease prevalence in affected breeds. Treatment of these diseases is typically palliative and aimed at slowing disease progression and managing clinical signs of heart failure as they develop. The discovery of specific genetic mutations underlying cardiomyopathies, such as the striatin mutation in Boxer arrhythmogenic right ventricular cardiomyopathy and the pyruvate dehydrogenase kinase 4 and titin mutations in Doberman Pinschers, has strengthened our ability to screen and selectively breed individuals in an attempt to produce unaffected offspring. The discovery of these disease-linked mutations has also opened avenues for the development of gene therapies, including gene transfer and genome-editing approaches. This review article discusses the known genetics of cardiomyopathies in dogs, reviews existing gene therapy strategies and the status of their development in canines, and discusses ongoing challenges in the clinical translation of these technologies for treating heart disease. While challenges remain in using these emerging technologies, the exponential growth of the gene therapy field holds great promise for future clinical applications.

Prevalence of an angiotensin-converting enzyme gene variant in dogs.

BACKGROUND: Genetic heterogeneity of the canine angiotensin converting enzyme (ACE) gene is functionally important because the degree of aldosterone breakthrough with ACE-inhibitor therapy is greater in variant positive dogs compared to variant negative dogs, but the prevalence of the variant is not known. The purpose of this study was to determine ACE gene variant-positive prevalence in a population of 497 dogs of different breeds. RESULTS: Overall variant-positive prevalence was 31%, with 20% of dogs heterozygous and 11% of dogs homozygous. The variant was overrepresented in Irish Wolfhounds (prevalence 95%; P < .001), Dachshunds (prevalence 90%; P < .001), Cavalier King Charles Spaniels (prevalence 85%; P < .001), Great Danes (prevalence 84%; P < .001), and Bull Mastiffs (prevalence 58%; P = .02). Irish Wolfhounds were more likely to be homozygous than heterozygous (P < .001). CONCLUSIONS: Nearly one-third of dogs in this study were positive for a functionally important ACE gene variant, with wide prevalence variability between breeds. The clinical importance of high ACE gene variant-positive prevalence in some breeds requires further study because the highest prevalences were found in breeds that are predisposed to heart disease and therefore may be treated with ACE-inhibitors.

Absence of known feline MYH7 and MYBPC3 variants in a diverse cohort of cats with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common cause of heart disease in the domestic cat with a genetic predisposition in a few breeds. In the Maine Coon and Ragdoll breeds, two variants associated with the HCM phenotype have been identified in the cardiac myosin binding protein C gene (MYBPC3; p.Ala31Pro and p.Arg820Trp respectively), and a single variant has been identified in the myosin heavy chain gene (MYH7; p.Glu1883Lys) in one domestic cat with HCM. It is not known if these variants influence the development of HCM in other cohorts of the feline population. The objective of this study was to evaluate the presence of the known MYBPC3 and MYH7 variants in a population of cats with HCM. DNA was isolated from samples collected from non-Ragdoll and non-Maine Coon domestic cats diagnosed with HCM through the North Carolina State University College of Veterinary Medicine and genotyped for the three variants. One-hundred and three DNA samples from cats with HCM were evaluated from domestic shorthair, domestic longhair and purebred cats. All samples were wt for the MYBPC3 and MYH7 variants. Although this study was limited by its inclusion of cats from one tertiary hospital, the lack of these MYBPC3 and MYH7 variants in this feline HCM population indicates that the clinical utility of genetic testing for these variants may be isolated to the two cat breeds in which these variants have been identified. Further studies to identify the causative variants for the feline HCM population are warranted.

Myxomatous mitral valve disease in the miniature poodle: A retrospective study.

Myxomatous mitral valve disease (MMVD) is the most common cardiovascular disease in the dog. The natural history of the disease is wide ranging and includes patients without clinical signs as well as those with significant clinical consequences from cardiac arrhythmias, pulmonary hypertension and/or congestive heart failure. The factors that determine which dogs remain asymptomatic and which develop clinical disease are not known. Disease characteristics could be breed or family related; some breeds of dogs, particularly the Cavalier King Charles spaniels, develop MMVD at an early age. The purpose of this study was to retrospectively characterize MMVD in the miniature poodle, a commonly affected breed in which MMVD has not been well characterized. Thirty-two miniature poodles met the inclusion criteria. Mean age was 11±three years. Clinical signs included exercise intolerance, syncope and coughing. Eighteen dogs were classified as ACVIM Stage B1, 12 as stage B2, and two as stage C. Mean vertebral heart scale (VHS) was 10.2 (±standard deviation of 0.9); 15 of 28 dogs had a VHS <10.3. One dog had radiographic evidence of congestive heart failure. Mean diastolic left ventricle dimension normalized to body weight was 1.6 (±0.4) and mean systolic was 0.8 (±0.3). Mitral valve prolapse was subjectively classified as mild or moderate in 19 dogs and severe in two. In the miniature poodles reported here, MMVD appears to be a fairly late onset disease and often is a mild phenotype.

Evaluation of genes associated with human myxomatous mitral valve disease in dogs with familial myxomatous mitral valve degeneration.

Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is believed to be heritable in Cavalier King Charles spaniels (CKCS) and Dachshunds. Myxomatous mitral valve disease is a familial disease in human beings as well and genetic mutations have been associated with its development. We hypothesized that a genetic mutation associated with the development of the human form of MMVD was associated with the development of canine MMVD. DNA was isolated from blood samples from 10 CKCS and 10 Dachshunds diagnosed with MMVD, and whole genome sequences from each animal were obtained. Variant calling from whole genome sequencing data was performed using a standardized bioinformatics pipeline for all samples. After filtering, the canine genes orthologous to the human genes known to be associated with MMVD were identified and variants were assessed for likely pathogenic implications. No variant was found in any of the genes evaluated that was present in least eight of 10 affected CKCS or Dachshunds. Although mitral valve disease in the CKCS and Dachshund is a familial disease, we did not identify genetic cause in the genes responsible for the human disease in the dogs studied here.

Lymphocyte Subsets in the Adrenal Glands of Dogs With Primary Hypoadrenocorticism.

Primary hypoadrenocorticism, or Addison's disease, is an autoimmune condition common in certain dog breeds that leads to the destruction of the adrenal cortex and a clinical syndrome involving anorexia, gastrointestinal upset, and electrolyte imbalances. Previous studies have demonstrated that this destruction is strongly associated with lymphocytic-plasmacytic inflammation and that the lymphocytes are primarily T cells. In this study, we used both immunohistochemistry and in situ hybridization to characterize the T-cell subtypes involved. We collected postmortem specimens of 5 dogs with primary hypoadrenocorticism and 2 control dogs and, using the aforementioned techniques, showed that the lymphocytes are primarily CD4+ rather than CD8+. These findings have important implications for improving our understanding of the pathogenesis and in searching for the underlying causative genetic polymorphisms.

Genotype imputation in the domestic dog.

Application of imputation methods to accurately predict a dense array of SNP genotypes in the dog could provide an important supplement to current analyses of array-based genotyping data. Here, we developed a reference panel of 4,885,283 SNPs in 83 dogs across 15 breeds using whole genome sequencing. We used this panel to predict the genotypes of 268 dogs across three breeds with 84,193 SNP array-derived genotypes as inputs. We then (1) performed breed clustering of the actual and imputed data; (2) evaluated several reference panel breed combinations to determine an optimal reference panel composition; and (3) compared the accuracy of two commonly used software algorithms (Beagle and IMPUTE2). Breed clustering was well preserved in the imputation process across eigenvalues representing 75 % of the variation in the imputed data. Using Beagle with a target panel from a single breed, genotype concordance was highest using a multi-breed reference panel (92.4 %) compared to a breed-specific reference panel (87.0 %) or a reference panel containing no breeds overlapping with the target panel (74.9 %). This finding was confirmed using target panels derived from two other breeds. Additionally, using the multi-breed reference panel, genotype concordance was slightly higher with IMPUTE2 (94.1 %) compared to Beagle; Pearson correlation coefficients were slightly higher for both software packages (0.946 for Beagle, 0.961 for IMPUTE2). Our findings demonstrate that genotype imputation from SNP array-derived data to whole genome-level genotypes is both feasible and accurate in the dog with appropriate breed overlap between the target and reference panels.

Sudden death associated with QT interval prolongation and KCNQ1 gene mutation in a family of English Springer Spaniels.

BACKGROUND: A 5-year-old, healthy English Springer Spaniel died suddenly 4 months after delivering a litter of 7 puppies. Within 4 months of the dam's death, 3 offspring also died suddenly. HYPOTHESIS: Abnormal cardiac repolarization, caused by an inherited long QT syndrome, is thought to be responsible for arrhythmias leading to sudden death in this family. ANIMALS: Four remaining dogs from the affected litter and 11 related dogs. METHODS: Physical examination and resting ECG were done on the littermates and 9 related dogs. Additional tests on some or all littermates included echocardiogram with Doppler, Holter monitoring, and routine serum biochemistry. Blood for DNA sequencing was obtained from all 15 dogs. RESULTS: Three of 4 littermates examined, but no other dogs, had prolonged QT intervals with unique T-wave morphology. DNA sequencing of the KCNQ1 gene identified a heterozygous single base pair mutation, unique to these 3 dogs, which changes a conserved amino acid from threonine to lysine and is predicted to change protein structure. CONCLUSIONS AND CLINICAL IMPORTANCE: This family represents the first documentation in dogs of spontaneous familial QT prolongation, which was associated with a KCNQ1 gene mutation and sudden death. Although the final rhythm could not be documented in these dogs, their phenotypic manifestations of QT interval prolongation and abnormal ECG restitution suggested increased risk for sudden arrhythmic death. The KCNQ1 gene mutation identified is speculated to impair the cardiac repolarizing current IKs, similar to KCNQ1 mutations causing long QT syndrome 1 in humans.

Natural history of arrhythmogenic right ventricular cardiomyopathy in the boxer dog: a prospective study.

BACKGROUND: Boxer arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease that may result in sudden death or heart failure. HYPOTHESIS/OBJECTIVES: To prospectively study the natural history of Boxer ARVC. ANIMALS: 72 dogs (49 ARVC, 23 controls). METHODS: Boxers >1 year of age were recruited for annual reevaluation. CONTROLS were defined as being ≥6 years of age and having <50 ventricular premature complex (VPCs)/24 h. ARVC was defined as ≥300 VPCs/24 h in the absence of other disease. Dogs were genotyped for the striatin deletion when possible. Descriptive statistics were determined for age; VPC number; annual change in VPC number; and left ventricular (LV) echocardiographic dimensions. Survival time was calculated. RESULTS: Controls: median age of 7 years (range, 6-10); number of VPCs 12 (range, 4-32). Median time in study of 6 years (range, 2-9). Seventeen of 23 were genotyped (5 positive, 12 negative). ARVC: median age of diagnosis of 6 (range, 1-11). Median time in study 5 years (range, 3-8). A total of 33% were syncopal and 43/49 were genotyped (36 positive, 7 negative). Yearly change in VPCs was 46 (range, -7,699 to 33,524). Annual percentage change in LV dimensions was 0, and change in fractional shortening (FS%) was 2%. Two dogs had FS% <20%. Although ARVC dogs died suddenly, there was no difference in survival time between groups. ARVC median age of survival was 11 years, and for controls was 10 years. CONCLUSIONS/CLINICAL IMPORTANCE: Arrhythmogenic right ventricular cardiomyopathy is a disease of middle age and frequently is associated with the striatin deletion. Syncope occurs in approximately 1/3 of affected dogs; systolic dysfunction is uncommon. The prognosis in many affected dogs is good.

Identification of PDE5A:E90K: a polymorphism in the canine phosphodiesterase 5A gene affecting basal cGMP concentrations of healthy dogs.

BACKGROUND: Cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE5A) is the target of phosphodiesterase inhibitors such as sildenafil. Polymorphisms in the PDE5A gene that may predict response to therapy with sildenafil and nitric oxide, be linked to disease progression, and aid in risk assessment have been identified in human beings. Identification of polymorphisms in PDE5A could affect the physiologic actions of PDE5A and the effects of phosphodiestrase type 5 inhibitor drugs. HYPOTHESIS/OBJECTIVE: Functional polymorphisms exist in the canine PDE5A gene. Specific objectives were to identify PDE5A polymorphisms and evaluate their functional relevance. ANIMALS: Seventy healthy dogs. METHODS: The exonic, splice-site, 3' and 5' untranslated regions of the canine PDE5A gene were sequenced in 15 dogs and aligned with the canine reference sequence. Identified polymorphisms were evaluated in 55 additional, healthy, unrelated dogs of 20 breeds. Plasma was collected from 51 of these dogs and cGMP was measured. An unpaired t-test and one-way ANOVA with Dunnett's test of multiple comparisons were used to evaluate the effect of genotype on cGMP. RESULTS: A common exonic polymorphism was identified that changed glutamic acid to lysine and resulted in significantly lower cGMP concentrations in the group with polymorphism versus the wild type group (P = .014). Additionally, 6 linked single nucleotide polymorphisms in the 3' untranslated region were identified that did not alter cGMP concentrations. CONCLUSIONS AND CLINICAL IMPORTANCE: A polymorphism exists in the canine PDE5A gene that is associated with variable circulating cGMP concentrations in healthy dogs and warrants investigation in diseases such as pulmonary hypertension.

Association of dilated cardiomyopathy with the striatin mutation genotype in boxer dogs.

BACKGROUND: Myocardial disease in the Boxer dog is characterized by 1 of 2 clinical presentations, dilated cardiomyopathy (DCM) characterized by ventricular systolic dysfunction, dilatation and tachyarrhythmias, and arrhythmogenic right ventricular cardiomyopathy (ARVC) characterized by ventricular tachyarrhythmias, syncope, and sudden death. Boxer ARVC has been associated with a deletion in the striatin gene in some families. HYPOTHESIS/OBJECTIVES: We hypothesized that both presentations represent a single disease, and the development of DCM in the Boxer is associated with the striatin deletion. ANIMALS: Thirty-three adult Boxer dogs with DCM, 29 adult Boxer dogs with the striatin deletion and ARVC, and 16 Boxers without cardiac disease. METHODS: DNA samples were evaluated for the striatin deletion. Association of the deletion with the DCM phenotype was tested by a Fisher's exact test. T-tests were used to evaluate potential differences between the positive heterozygous and positive homozygous groups with DCM with regard to age, LVIDD, LVIDS, and FS%. RESULTS: Thirty of 33 dogs with DCM were positive for the striatin deletion. The striatin mutation and the homozygous genotype were strongly associated with the DCM phenotype (P < .001 and P = .005). There was no statistical difference between the heterozygous and homozygous groups with regard to age and echocardiographic measurements. CONCLUSIONS AND CLINICAL IMPORTANCE: This study demonstrates an association between DCM in the Boxer dog and the striatin mutation, particularly with the homozygous genotype. The observation that 3/33 dogs developed DCM and lacked the striatin mutation suggests that there is at least 1 other cause of DCM in the Boxer dog.

Identification of DNA variants in the canine beta-1 adrenergic receptor gene.

Beta-adrenergic receptor antagonists are utilized for the management of several cardiac diseases in the dog. In humans the beneficial effects of beta-adrenergic receptor antagonists are variable and are associated with a genetic variability in the beta one adrenergic receptor gene (ADRB1). To determine if DNA variants were present in the canine ADRB1 gene, DNA from five breeds of dogs was evaluated. Two deletions were identified within the region of the gene that encodes the cytoplasmic tail of ADRB1. The functions of this region are not well understood although it is important in differentiating subtypes of adrenergic receptors and may be associated with control of receptor downregulation. The functional consequences of these identified variants deserve further study.

Familial subvalvular aortic stenosis in golden retrievers: inheritance and echocardiographic findings.

OBJECTIVES: To describe the echocardiographic findings and pedigree analysis of golden retrievers with subvalvular aortic stenosis. METHODS: Seventy-three golden retrievers were evaluated by auscultation and echocardiography. A subcostal continuous-wave Doppler aortic velocity ê2·5 m/s and presence of a left basilar systolic ejection murmur were required for diagnosis of subvalvular aortic stenosis. Three echocardiographic characteristics were recorded: evidence of aortic insufficiency, subvalvular ridge or left ventricular hypertrophy. A disease status score was calculated by totalling the number of echocardiographic -characteristics per subject. RESULTS: Thirty-two of 73 dogs were affected and their aortic velocities were as follows: range 2·5 to 6·8 m/s, median 3·4 m/s and standard deviation 1·2 m/s. Echocardiographic characteristics of 32 affected dogs were distributed as follows: left ventricular hypertrophy 12 of 32, aortic insufficiency 20 of 32 and subvalvular ridge 20 of 32. Disease status score ranged from 0 to 3 with a median of 2. There was a statistically significant correlation between aortic velocity and disease status score (r=0·644, P<0·0001). Subvalvular aortic stenosis was observed in multiple generations of several families and appears familial. CLINICAL SIGNIFICANCE: Subvalvular aortic stenosis in the golden retriever is familial. Severity of stenosis correlates well with cumulative presence of echocardiographic characteristics (left ventricular hypertrophy, subvalvular ridge and aortic insufficiency).

Identification of beta-1 adrenergic receptor polymorphisms in cats.

In human beings, genetic polymorphisms within the beta-1 adrenergic receptor (ADRB1) gene have been associated with variable pharmacologic responses to beta blocker therapy. Beta-blockers are commonly given to cats with heart disease, particularly hypertrophic cardiomyopathy, a common cause of feline heart disease. We hypothesized that polymorphisms are present in the feline ADRB1 gene, which could result in an altered pharmacologic response to beta-blocker therapy. We sequenced the feline ADRB1 gene in 42 cats of five breeds. We identified three polymorphisms within the ADRB1 gene. Two polymorphisms did not change the amino acid produced and are unlikely to be clinically significant. A third polymorphism identified was an AA/CC substitution at the 830-831 base pair sites. This alteration changed the amino acid produced from proline to glutamine at position 277 and computer modeling predicts an altered protein structure. Further study is warranted to determine if this polymorphism alters response to beta blocker therapy.

Comparison of polymerase chain reaction with bacterial 16s primers to blood culture to identify bacteremia in dogs with suspected bacterial endocarditis.

BACKGROUND: Identification of the bacterial organism in dogs with endocarditis is challenging. Human studies have reported the utility of the polymerase chain reaction (PCR) to amplify and identify bacterial nucleic acid from infected valvular tissue and blood. HYPOTHESIS/OBJECTIVES: We hypothesized that PCR using primers designed to amplify the bacterial 16s gene would identify circulating bacteria in dogs with suspected bacterial endocarditis more consistently than standard blood culture techniques. ANIMALS: Eighteen dogs with suspected bacterial endocarditis based upon clinical and echocardiographic findings. Fifteen clinically normal dogs served as negative controls. METHODS: Prospective study of dogs evaluated for suspect endocarditis at 6 veterinary hospitals. A blood sample was drawn from all dogs and evaluated with both a single-sample PCR and standard 3-sample blood culture techniques. RESULTS: Blood culture identified noncontaminant bacteria in 6/18 study animals (33%) and 1 control dog; PCR identified noncontaminant bacteria in 7/18 study animals (39%). There were no study animals in which the 2 tests identified different bacteria (κ = 1.0). However, bacteria were identified by both techniques in only 2/18 study animals. When results from both PCR and blood culture were considered together, a noncontaminant bacterial organism was identified in 11/18 study animals (61%). CONCLUSION AND CLINICAL IMPORTANCE: The results of this study suggest that although single sample PCR with 16s primers was not more sensitive than blood culture for detection of bacteremia in dogs with suspect endocarditis, performing both techniques simultaneously did increase the likelihood of identification of bacteria in blood.

Temporal variability of ventricular arrhythmias in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is prevalent in the Boxer. There is little information on the temporal variability of ventricular arrhythmias within affected dogs. OBJECTIVE: To evaluate ambulatory electrocardiograms (AECG) from Boxers with ARVC for hourly variation in premature ventricular complexes (PVC) and heart rate (HR). ANIMALS: One hundred and sixty-two Boxer dogs with ARVC. METHODS: Retrospective, observational study of 1,181 AECGs collected from Boxer dogs at The Ohio State University from 1997 to 2004 was evaluated. The proportion of depolarizations that were PVCs was compared across each hour of the day, during six 4-hour periods of day, to the time after AECG application, and to the maximum and minimum HR. RESULTS: A lower proportion of PVCs was noted during early morning (midnight to 0400 hours) as compared with the morning (0800-1200 hours) and late (1600-2000 hours) afternoon (P= .012). There was no increase in PVC proportion in the 1st hour after AECG application as compared with all other hours of the day (P= .06). There was poor correlation between maximum (rho= 0.19) and minimum (rho= 0.12) HR and PVC proportion. CONCLUSIONS AND CLINICAL IMPORTANCE: The likelihood of PVC occurrence in Boxer dogs with ARVC was relatively constant throughout the day, although slightly greater during the hours of 0800-1200 and 1600-2000. A biologically important correlation with HR was not apparent. The role of autonomic activity in the modulation of electrical instability in the Boxer with ARVC requires further study.

Analysis of 8 sarcomeric candidate genes for feline hypertrophic cardiomyopathy mutations in cats with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats. Causative mutations have been identified in the Maine Coon (MC) and Ragdoll breed in the cardiac myosin binding protein C gene (MYBPC3). HCM is thought to be inherited in other breeds. HYPOTHESIS: That a causative mutation for HCM in the British Shorthair (BSH), Norwegian Forest (NWF), Siberian, Sphynx, or MC cats would be identified in the exonic and splice site regions of 1 of 8 genes associated with human familial HCM. ANIMALS: Three affected BSH, NWF, Siberians, Sphynx, 2 MC (without the known MC mutation), and 2 Domestic Shorthair cats (controls) were studied. METHODS: Prospective, observational study. Exonic and splice site regions of the genes encoding the proteins cardiac troponin I, troponin T, MYBPC3, cardiac essential myosin light chain, cardiac regulatory myosin light chain, alpha tropomyosin, actin, and beta-myosin heavy chain were sequenced. Sequences were compared for nucleotide changes between affected cats, the published DNA sequences, and control cats. Changes were considered to be causative for HCM if they involved a conserved amino acid and changed the amino acid to a different polarity, acid-base status, or structure. RESULTS: A causative mutation for HCM was not identified, although several single nucleotide polymorphisms were detected. CONCLUSIONS AND CLINICAL IMPORTANCE: Mutations within these cardiac genes do not appear to be the only cause of HCM in these breeds. Evaluation of additional cardiac genes is warranted to identify additional molecular causes of this feline cardiac disease.

Magnetic resonance imaging of right ventricular morphology and function in boxer dogs with arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a myocardial disease characterized by fibrofatty replacement of the right ventricle and ventricular tachyarrhythmias, reported most commonly in the Boxer dog. Although ARVC is characterized as a myocardial disease, the impact of the disease on the function of the right ventricle has not been well studied. OBJECTIVE: To noninvasively evaluate the function and anatomy of the right ventricle in Boxer dogs with ARVC. ANIMALS: Five adult Boxer dogs with ARVC and 5 healthy size-matched hound dogs. METHODS: Magnetic resonance imaging was performed on an ECG-gated conventional 1.5-T scanner using dark blood imaging and cine acquisitions. Images were evaluated by delineation of endocardial right and left ventricular contours in the end-diastolic and end-systolic phases of each slice. Right and left end-systolic and end-diastolic volumes were generated using Simpson's rule and ejection fraction was calculated. Images were evaluated for right ventricular (RV) aneurysms and wall motion abnormalities. Spin echo images were reviewed for the presence of RV myocardial fatty replacement or scar. RESULTS: RV ejection fraction was significantly lower in Boxers with ARVC compared with the controls (ARVC 34%+/- 11 control 53%+/- 10, P < .01). There was an RV aneurysm in 1 dog with ARVC but not in any of the controls. RV myocardial gross fatty changes were not observed in dogs of either group. CONCLUSIONS AND CLINICAL IMPORTANCE: These findings could be interpreted to suggest that arrhythmias and myocardial dysfunction precede the development of morphological abnormalities in dogs with ARVC.