Vaccine-Associated Anaphylactic Shock in a Springer Spaniel Dog with Arrhythmogenic Right Ventricular Cardiomyopathy.

A 5-year-old female Springer Spaniel dog was submitted for necropsy after sudden death following vaccination against Leptospira spp. Gross examination revealed a diffuse dark red discolouration of skeletal musculature, severe diffuse congestion of all the abdominal organs and a contracted spleen. Severe dilation and reduction in wall width was seen in the right ventricle and histological examination revealed multifocal replacement of the right ventricular myocardium by a large amount of fibrofatty tissue. Pathological changes were consistent with post-vaccinal anaphylactic shock in a dog with arrhythmogenic right ventricular cardiomyopathy (ARVC), a rare condition typical of Boxer dogs but not previously reported in Springer Spaniels. Canine vaccine-associated adverse events are discussed and ARVC is compared with the corresponding human cardiac condition.

Arrhythmogenic right ventricular cardiomyopathy in dogs.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease seen in dogs, cats, and humans. A common entity in Boxers and the related English bulldog, the disease is characterized by fatty or fibrofatty replacement of the myocardium, ventricular arrhythmias, and the potential for syncope or sudden death. In some individuals, concomitant left ventricular involvement results in systolic dysfunction and a progression to congestive heart failure. The clinical and pathological characteristics of ARVC share many similarities in dogs and humans, and Boxers serve as an important spontaneous model of the disease. Although multiple mechanisms have been implicated in the pathogenesis of ARVC, the disease is ultimately considered to be a disorder of the desmosome. Multiple causal genetic mutations have been identified in people, and over 50% of affected humans have an identifiable mutation in desmosomal proteins. To date, only a single genetic mutation has been associated with ARVC in Boxer dogs. Other as-yet-undiscovered genetic mutations and epigenetic modifiers of the disease are likely. Treatment of ARVC in dogs is focused on controlling ventricular arrhythmias and associated clinical signs. This article will review the pathophysiology, clinical diagnosis, treatment, and prognosis of ARVC in the dog.

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.

Arrhythmogenic right ventricular cardiomyopathy in Bulldogs: Evaluation of clinical and histopathologic features, progression, and outcome in 71 dogs (2004-2016).

OBJECTIVES: This study aimed to characterize the clinical and histopathological features of arrhythmogenic right ventricular cardiomyopathy (ARVC) in English Bulldogs, American Bulldogs, and Bulldog-type mixed breed dogs and assess affected Bulldogs for a striatin gene mutation previously reported in Boxers with ARVC. ANIMALS: Seventy-one Bulldogs fit the inclusion criteria. Genetic analysis was performed on five dogs. Cardiac post-mortem evaluations were performed on two dogs. METHODS: Medical records from a single veterinary cardiology group (CVCA) were retrospectively evaluated. Tissue and blood samples were submitted for histopathological analysis and genetic testing in select patients. RESULTS: Presenting complaints included syncope (38%), arrhythmia (81.7%), or murmur (34.2%) documented on examination. On presentation, congestive heart failure (CHF) was diagnosed in 22 (31%) dogs, and 58 (81.7%) had ventricular arrhythmias. On bivariable analyses, the two-dimensional (2D) left atrial-to-aortic root ratio (LA:Ao) was the only prognostic variable significantly associated with survival time. Dogs with 2D LA:Ao below the mean (1.41) had longer median survival to all-cause mortality (12 months; 95% confidence interval [CI] six-15 months) than those with 2D LA:Ao above the mean (four months; 95% CI two-six months; p=0.0384). Most dogs (54%) died from cardiac disease, with 42.1% experiencing sudden death. The median time from diagnosis to cardiac death was four months. CONCLUSIONS: Arrhythmogenic right ventricular cardiomyopathy affects Bulldogs with both arrhythmogenic and dilated-type phenotypes. Despite variable arrhythmia severity and predominantly right-sided involvement in many dogs, an increase in left atrial size was the only significant predictor of mortality in this sample of dogs.

Twenty-four-hour ambulatory (Holter) electrocardiographic findings in 13 cats with non-hypertrophic cardiomyopathy.

Detection and characterisation of cardiac arrhythmias in cats with hypertrophic cardiomyopathy (HCM) has already been documented in various studies. However, similar studies have not been reported for other forms of feline cardiomyopathy. The clinical records of 13 client-owned cats diagnosed with restrictive cardiomyopathy (RCM), arrhythmogenic right ventricular cardiomyopathy (ARVC) and non-specific cardiomyopathy (NSCM) that underwent Holter recording at the time of diagnosis were reviewed retrospectively. Eight cats had signs of congestive heart failure at presentation, one cat had a history of recurrent syncope and the remaining four cats were asymptomatic. The average heart rate was 138 ± 22 (range 97-181) beats per minute (bpm) with the lowest value (97 bpm) recorded in a cat with third degree atrioventricular block (3-AVB) and the highest value (181 bpm) observed in a cat with atrial fibrillation (AF). The median number of ventricular ectopic beats (VEB) over 24 h was 2031 (338-8305), mostly represented by single isolated VPCs (803, 123-2221). Cardiac pauses were observed in three cats, with the longest pause lasting more than 6 s. A survival analysis was not performed due to the small number of cats and limited follow-up information. Holter recording revealed cardiac arrhythmias in all 13 cats, while 8/13 cats (61.5%) had an unremarkable resting electrocardiogram (ECG). The average daily heart rate in these cats did not appear affected by the presence of heart failure, although periods of sinus arrhythmia were absent in all individuals.

Prognostic value of coupling interval, prematurity index and heart rate variability in Boxer dogs / Valor prognóstico do intervalo de acoplamento, índice de prematuridade e variabilidade da frequência cardíaca em cães da raça Boxer

Boxer dogs with arrhythmogenic right ventricular cardiomyopathy (ARVC) can experience sudden cardiac death regardless of presence/absence of clinical signs. The aims of this retrospective study were two-fold: 1) to investigate the coupling interval (CI) and prematurity index (PI) of ventricular arrhythmias (VA), and the heart rate variability (HRV) in Boxers, and 2) to evaluate their impact on overall survival time. The first 24-hour Holter 36 client-owned Boxer dogs meeting inclusion/exclusion criteria were evaluated for the number, morphology, site of origin, complexity, CI and PI, of ventricular premature complexes (VPCs), and time domain HRV. The effect on survival was assessed, considering the presence/absence of ventricular tachycardia (VT), and syncope. All-cause mortality was considered as the end-point, with median survival times being obtained by Kaplan-Meier analyses and compared by log-rank test. Polymorphic VPCs were more common in symptomatic dogs than asymptomatic. VPCs in dogs with VT were less premature, due to the influence of heart rate on PI despite comparable CI. The PI and mean heart rate (HRme) were significantly different between VT and non-VT dogs but did not discriminate adequately between groups as standalone tests. Median survival time was shorter in Boxer dogs with VT (463 vs 1645 days, HR: 4.31, P=0.03). The HRV parameters, SDNN and SDANN, were both associated with prognosis. The CI and PI were not demonstrated to be prognostic surrogates in Boxer dogs with VA. HRme≥112bpm is 100% sensitive but only 46% specific for detecting VT in Boxers on the 24-hour Holter. Presence of VT, SDNN≤245ms, or SDANN≤134ms at the time of the first 24-hour Holter was associated with a shorter survival.(AU)

Cães da raça Boxer com cardiomiopatia arritmogênica do ventrículo direito (CAVD) podem apresentar morte súbita independentemente da presença/ausência de sinais clínicos. Os objetivos desse estudo retrospectivo foram: 1) investigar o intervalo de acoplamento (IA) e o índice de prematuridade (IP) das arritmias ventriculares e a variabilidade da frequência cardíaca (VFC) em Boxers, e 2) avaliar o impacto de tais características sob o tempo de sobrevida global. O primeiro Holter de 24 horas de 36 Boxers selecionados para os critérios de inclusão/exclusão foram avaliados para o número, morfologia, local de origem, complexidade, IA e IP dos complexos ventriculares prematuros (CVPs) e da VFC no domínio do tempo. O efeito na sobrevida foi avaliado, considerado a presença/ausência de taquicardia ventricular (TV), e síncope. O desfecho final foi a mortalidade global, com o tempo de sobrevida mediano sendo obtido pela análise de Kaplan-Meier e comparado pelo teste de log-rank. CVPs polimórficos foram mais comuns em cães sintomáticos. Os CVPs em Boxers com TV foram menos prematuros, devido à influência da frequência cardíaca (FC) sobre o IP, apesar de IA comparáveis. O IP e a FC média diferiram entre os cães com TV e os sem, mas não discriminam adequadamente os grupos como variáveis isoladas. A sobrevida global foi menor nos cães com TV (463 dias vs 1645 dias, HR=4,31, P=0,03). Os parâmetros da VFC, SDNN e SDANN, foram associados ao prognóstico. O IA e o IP não possuem valor prognóstico em Boxers com arritmias ventriculares. A FC média ≥112bpm é 100% sensível, mas apenas 46% específica para detectar Boxers com TV no Holter de 24 horas. A presença de TV, SDNN≤245ms, ou SDANN≤134ms no momento do primeiro Holter de 24 horas estão associados a menor sobrevida global no Boxer.(AU)

Echocardiographic assessment of right ventricular systolic function in Boxers with arrhythmogenic right ventricular cardiomyopathy.

OBJECTIVES: To determine whether there are differences in measures of longitudinal right ventricular (RV) systolic function among Boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC) compared with healthy control Boxer dogs. To explore relationships between markers of RV systolic function and age, body weight, gender, arrhythmia frequency, and markers of left ventricular (LV) systolic function in Boxer dogs. ANIMALS: The study included 50 client-owned Boxer dogs. METHODS: This is a retrospective echocardiographic study. Tricuspid annular plane systolic excursion (TAPSE) and pulsed wave tissue Doppler imaging-derived systolic myocardial velocity of the lateral tricuspid annulus (S') were measured in healthy control Boxers (n = 18), Boxers with ARVC and normal LV systolic function (n = 19), and Boxers with ARVC and reduced LV systolic function (n = 13). RESULTS: Tricuspid annular plane systolic excursion (p=0.002) and S' (p=0.001) were significantly different between affected and control groups. Significant correlations were found between measures of left heart size and function and both TAPSE and S'. No correlations were found between RV function parameters and age, gender, or body weight in this fairly homogeneous, single-breed population. Receiver operating characteristic curve analysis revealed that both TAPSE and S' had an area under the curve of 0.77 in distinguishing healthy Boxers from those with ARVC. CONCLUSIONS: Tricuspid annular plane systolic excursion and S' are reduced in Boxers with ARVC. In contrast to prior studies evaluating these parameters in dogs of different breeds and body types, no correlation was found between markers of RV function and body weight in this population of Boxer dogs.

Genetic analyses in a bonobo (Pan paniscus) with arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder that may lead to sudden death and can affect humans and other primates. In 2012, the alpha male bonobo of the Milwaukee County Zoo died suddenly and histologic evaluation found features of ARVC. This study sought to discover a possible genetic cause for ARVC in this individual. We sequenced our subject's DNA to search for deleterious variants in genes involved in cardiovascular disorders. Variants found were annotated according to the human genome, following currently available classification used for human diseases. Sequencing from the DNA of an unrelated unaffected bonobo was also used for prediction of pathogenicity. Twenty-four variants of uncertain clinical significance (VUSs) but no pathogenic variants were found in the proband studied. Further familial, functional, and bonobo population studies are needed to determine if any of the VUSs or a combination of the VUSs found may be associated with the clinical findings. Future genotype-phenotype establishment will be beneficial for the appropriate care of the captive zoo bonobo population world-wide as well as conservation of the bobono species in its native habitat.

Clinical Features of English Bulldogs with Presumed Arrhythmogenic Right Ventricular Cardiomyopathy: 31 Cases (2001-2013).

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden death in people and boxer dogs that has recently been described in English bulldogs. The objective of this retrospective study was to describe the clinical characteristics of English bulldogs with presumed ARVC. The medical records were searched for English bulldogs examined between 2001 and 2013 with a clinical diagnosis of ARVC. The average age of the 31 dogs identified was 9.2 ± 1.6 yr (range 7-13 yr). Males were overrepresented by a factor of 2.9 to 1. At initial presentation, 5 dogs had subclinical arrhythmia, 10 dogs had clinical signs attributable to arrhythmia, and 16 dogs had congestive heart failure. Eighteen dogs (58%) had ventricular tachycardia and five (16%) also had supraventricular arrhythmias. Four dogs experienced sudden death, 2 dogs died from congestive heart failure, 11 dogs were euthanized for cardiac causes, and 2 dogs died or were euthanized for noncardiac causes. Kaplan-Meier analysis showed a median survival time of 8.3 mo. This is the first study to describe the clinical characteristics of a population of English bulldogs with presumed ARVC. Further studies are needed to better characterize the clinical features of the disease in this breed.

Arrhythmogenic Right Ventricular Cardiomyopathy in the Boxer Dog: An Update.

Arrhythmogenic right ventricular cardiomyopathy is an inheritable form of myocardial disease characterized most commonly by ventricular tachycardias, syncope, and sometimes systolic dysfunction and heart failure. A genetic mutation in the striatin gene has been identified in many affected dogs. Dogs with only one copy of the mutation (heterozygous) have a variable prognosis, with many dogs remaining asymptomatic or being successfully managed on antiarrhythmic drugs for years. Dogs that are homozygous for the mutation seem to have a worse prognosis.

Arrhythmogenic right ventricular cardiomyopathy in Boxer dogs: the diagnosis as a link to the human disease.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a myocardial disease with an increased risk for ventricular arrhythmias. The condition, which occurs in Boxer dogs, shares phenotypic features with the human disease arrhythmogenic cardiomyopathy (ACM) suggesting its potential as a natural animal model. However, there are currently no universally accepted clinical criteria to diagnose ARVC in Boxer dogs. We aimed to identify diagnostic criteria for ARVC in Boxer dogs defining a more uniform and consistent phenotype. METHODS AND RESULTS: Clinical records from 264 Boxer dogs from a referral veterinary hospital were retrospectively analysed. ARVC was initially diagnosed according to the number of ventricular premature complexes (VPCs) in the 24-hour-Holter-ECG in the absence of another obvious cause. Dogs diagnosed this way had more VPCs, polymorphic VPCs, couplets, triplets, VTs and R-on-T-phenomenon and syncope, decreased right ventricular function and dilatation in comparison to a control group of all other Boxer dogs seen by the Cardiology Service over the same period. Presence of couplets and R-on-T-phenomenon on a 24h-ECG were identified as independent predictors of the diagnosis. A diagnosis based on ≥100 VPCs in 24 hours, presence of couplets and R-on-T phenomenon on a 24h-ECG was able to select Boxer dogs with a phenotype most similar to human ACM. CONCLUSION: We suggest the diagnosis of ARVC in Boxer dogs requires two out of the three following criteria: presence of ≥ 100 VPCs, presence of couplets or R-on-T-phenomenon on a 24 h-ECG. This results in a uniform phenotype similar to that described in human ACM and may result in the adoption of the term ACM for this analogous condition in Boxer dogs.

Structural and molecular pathology of the atrium in boxer arrhythmogenic right ventricular cardiomyopathy.

OBJECTIVE: To investigate the expression and distribution of desmosomal and gap junction proteins of the intercalated disc in the atria of boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC). ANIMALS: Nineteen control dogs and 13 boxers with histopathologically confirmed ARVC. METHODS: Right and left atrial samples were examined using immunofluorescence and Western blots. The intercalated disc proteins investigated included total and phosphorylated connexin43 (Cx43 and pCx43), connexin45, connexin40, plakoglobin, plakophilin-2, desmoplakin, and N-cadherin. RESULTS: Histopathological changes characteristic of ARVC were present in the left or right atrium of 12 out of 13 boxers and were absent in all control dogs. When compared to the 19 control dogs, immunofluorescence analysis revealed a decrease in signal intensity for pCx43 and plakoglobin in the left (p = 0.03 and p = 0.014, respectively) and right atrium (p = 0.015 and p = 0.002, respectively) of affected boxers. Connexin43 and pCx43 Western blot band density was significantly decreased in the left (p = 0.025 and p = 0.027, respectively) and right atrium (p = 0.001 and p = 0.044, respectively) of affected boxers. CONCLUSION: Altered intercalated disc and gap junction proteins were identified in atrial myocardium of ARVC boxers, supporting atrial involvement as part of this disorder. Reduction in pCx43 in conjunction with histological changes could represent the substrate for atrial arrhythmias associated with ARVC. Furthermore, these findings detected in boxer dogs, lend support for the broader term, arrhythmogenic cardiomyopathy, as preferred nomenclature used to describe this disease in humans.

Valor prognóstico da variabilidade da frequência cardíaca e da eletrocardiografia ambulatorial em cães Boxer com cardiomiopatia arritmogênica do ventrículo direito / Prognostic value of heart rate variability and Holter monitoring in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy

A cardiomiopatia arritmogênica do ventrículo direito (CAVD) é uma importante causa de morte súbita em cães da raça Boxer. A validação de fatores prognósticos para essa doença auxiliaria na detecção de animais mais gravemente afetados e sua exclusão dos programas de reprodução. O objetivo deste estudo foi avaliar o valor prognóstico da presença de manifestações clínicas, dos índices de variabilidade de frequência cardíaca (VFC) e das arritmias supraventriculares ou ventriculares registradas à monitorização eletrocardiográfica com Holter na sobrevida de cães Boxer em diferentes estágios da CAVD. Essas variáveis foram analisadas, de forma prospectiva, em 69 cães Boxer, divididos em cinco grupos: cães Boxer controle (grupo CB, <50 VPC/24 horas, n=28), cães Boxer suspeitos (grupo SB, 50 a 300 VPC/24 horas, n=8), cães Boxer com CAVD (grupo ARVC, >300 VPC/24 horas, n=19), cães Boxer com CAVD e disfunção sistólica sem insuficiência cardíaca congestiva (grupo SDB sem ICC, n=6) e com ICC (grupo SDB com ICC, n=8). A análise estatística compreendeu teste ANOVA, correlação de Pearson e análise de riscos proporcionais de Cox. Comparando-se com o grupo CB, não foi encontrada diminuição nos índices de VFC nos grupos SB, ARVC ou SDB sem ICC; por outro lado, o grupo SDB com ICC apresentou diminuição desses índices. Não houve relação entre os índices de VFC e a morte de origem cardíaca; porém, a presença de síncopes com ou sem sinais clínicos de ICC e o número de episódios de taquicardia ventricular (TV) correlacionaram-se com a sobrevida dos animais. Estes resultados permitem concluir que a presença de sinais clínicos de ICC, a presença de síncopes e o número de TV ao Holter apresentam valor prognóstico de sobrevida em cães Boxer com CAVD.(AU)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden death in Boxer dogs. Validation of prognostic factors for this disease could help in detecting more severely affected animals and their exclusion from breeding programs. The aims of this study were to evaluate the prognostic significance of presence of symptoms, heart rate variability (HRV) indices and ventricular or supraventricular arrhythmias recorded by Holter monitoring on survival of Boxer dogs with ARVC at different stages. Symptoms, arrhythmias registered on Holter and five HRV indices were prospectively analyzed in 69 client-owned Boxer dogs divided into five groups: control Boxer dogs (CB group, <50 VPC/24 hours, n=28), suspicious Boxers (SB group, 50 to 300 VPC/24 hours, n=8), Boxers with ARVC (ARVC group, >300 VPC/24 hours, n=19), Boxers with ARVC and systolic dysfunction without congestive heart failure (SDB without CHF group, n=6) and with CHF (SDB with CHF group, n=8). Statistical analyses consisted of an ANOVA test, Pearson correlation and Cox's proportional hazards regression. Compared to the CB group, no decrease in HRV indices was found in SB, ARVCB or SDB without CHF groups; otherwise, SDB with CHF group had impaired indices. No relation was found between HRV indices and cardiac-related death, but the presence of syncopes with or without clinical signs of heart failure and number of ventricular tachycardia (VT), were correlated with survival. These results allow us to conclude that the presence of symptoms of heart failure, presence of syncopes and number of VT on Holter examination seem to have prognostic value in Boxer ARVC.(AU)

Cardiomiopatia arritmogênica do ventrículo direito em felino: relato de caso / Arrhythmogenic right ventricular cardiomiopathy in a feline: case report

Felino de 3,3kg, fêmea, oito anos de idade, castrada, sem definição racial, foi atendida no Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo (HOVET-USP), com histórico de dispneia, prostração, hiporexia e consequente emagrecimento progressivo, havia uma semana. Foram realizados exames de sangue: hemograma com contagem de plaquetas, função renal, função hepática e dosagens séricas de sódio e potássio, eletrocardiograma (ECG), radiografia torácica, ecoDopplercardiograma, e os resultados dos exames indicaram diagnóstico presuntivo de cardiomiopatia arritmogênica do ventrículo direito. O diagnóstico foi confirmado pela necropsia e pela constatação da presença de tecido fibroadiposo no miocárdio no exame histopatológico, possibilitando, assim, o relato do primeiro caso de cardiomiopatia arritmogênica do ventrículo direito, em gato, no Brasil.(AU)

A female 3.3kg feline, eight years-old, spayed, without racial definition, was submitted to the Veterinary Hospital of the School of Veterinary Medicine and Animal Science, São Paulo University (HOVET-USP) with dyspnea, prostration, hyporexia, and consequent progressive weight loss a week ago. Blood count with platelet count, renal and hepatic profiles, and serum sodium and potassium, chest radiography, electrocardiogram (ECG), and echocardiography were performed and diagnosis of arrhythmogenic right ventricular cardiomyopathy was assumed. The diagnosis was confirmed by necropsy findings and by the presence of fibro-fatty tissue infiltration observed in histopathology, thus featuring the first report of arrhythmogenic right ventricular cardiomyopathy in a cat in Brazil.(AU)

Arrhythmogenic right ventricular cardiomyopathy in a weimaraner.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) was diagnosed postmortem in a weimaraner dog. Syncope, ventricular arrhythmias, and sudden death in this patient combined with the histopathological fatty tissue infiltration affecting the right ventricular myocardium are consistent with previous reports of ARVC in non-boxer dogs. Arrhythmogenic right ventricular cardiomyopathy has not been previously reported in weimaraners.

Cardiomyopathie ventriculaire droite arythmogène chez un Weimaraner. Une cardiomyopathie ventriculaire droite arythmogène (CVDA) a été diagnostiquée post-mortem chez un chien Weimaraner. Une syncope, des arythmies ventriculaires et une mort soudaine chez ce patient, combinées à une infiltration histopathologique par du tissu adipeux affectant le myocarde droit, correspondent à des rapports antérieurs de CVDA chez des chiens autres que des Boxers. La cardiomyopathie ventriculaire droite arythmogène n'a pas été signalée antérieurement chez des Weimaraners.(Traduit par Isabelle Vallières).

Arrhythmogenic right ventricular cardiomyopathy coincided with the cardiac fibrosis in the inner muscle layer of the left ventricular wall in a boxer dog.

A 7-year-old female boxer dog died suddenly without any clinical signs. It was suspected that the dog had arrhythmogenic right ventricular cardiomyopathy (ARVC) due to ventricular premature complexes and ventricular tachycardia at 3 years of age. The final diagnosis of ARVC was confirmed by histological characteristics, such as loss of cardiocytes and fibrofatty replacement, occurring in the right and left ventricular walls. In the cardiocytes, non-lipid vacuoles were observed. Cardiac fibrosis and intimal thickening of the small arteries occurred without fatty replacement in the inner muscle layer including the papillary muscles of the left ventricular wall. This paper describes the pathomorphological details of an ARVC case with coincidental cardiac fibrosis in the inner muscle layer of the left ventricular wall.

A pedigree-based genetic appraisal of Boxer ARVC and the role of the Striatin mutation.

The objective of this paper was to investigate by pedigree-based genetic means the origins and inheritance of arrhythmogenic right ventricular cardiomyopathy (ARVC) in UK Boxers and assess the role of the proposed causal mutation in the gene, Striatin (STRN). All ARVC cases traced back to a small number of imported American dogs deriving from the group of Boxers studied by Harpster (1983) to define the disease, strongly suggesting that the disease is the same in the two countries. Dogs with and without the STRN mutation were found in both ARVC affected and normal Boxers showing that the mutation is not responsible for the disease. Evidence was found that the STRN mutation is, however, genetically linked with the gene responsible on the same chromosome. The linkage implies that the two genes can separate by meiotic recombination such that both ARVC-affected and ARVC-unaffected lines of dogs may carry either the STRN mutation or its wild-type allele. These have been found. Homozygotes for the STRN mutation tended to be severely affected at early ages, suggesting that there is an interaction between the known effects of the STRN mutation on the cardiomyocyte and ARVC.

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.

Time-domain signal-averaged electrocardiogram in healthy German Shepherd and Boxer dogs / Eletrocardiograma de alta resolução (ECGAR) no domínio do tempo em cães sadios das raças Pastor Alemão e Boxer

Signal-averaged electrocardiogram (SAECG) identifies ventricular late potentials (LP), low-amplitude electrical signals that are markers of slow cardiac conduction in fibrous myocardium, consisting in a predictive factor for sudden death in dogs at risk of sustained ventricular tachycardia. The aim of this study was to establish reference values of SAECG for German Shepherd and Boxer dogs. SAECG was performed in 19 German Shepherd and 28 Boxer client-owned dogs, and parameters analyzed were QRSd (duration of filtered QRS), LAS<40μV (duration of low-amplitude signals in terminal portion of filtered QRS) and RMS40 (root square of mean voltage over the last 40 milliseconds of filtered QRS), with two different filters (25-250 Hz and 40-250 Hz). Statistical analyses was achieved by T Student test (p<0.05) to identify differences between the two groups and between the values obtained with the two filters. No statistical difference was found in SAECG variables between the two breeds with the two different filters (p>0.05). Achieving normal values of SAECG in German Shepherd and Boxer dogs is important to further research late potentials in animals of these breeds with hereditary ventricular tachycardia or arrhythmogenic cardiomyopathy and identification of individuals at high risk of cardiac-related sudden death...

O eletrocardiograma de alta resolução (ECGAR) identifica os potenciais tardios (PT), sinais elétricos de baixa amplitude considerados marcadores de condução cardíaca lenta de áreas fibrosadas do miocárdio, cuja presença consiste em fator preditivo de morte súbita em cães com taquicardia ventricular sustentada. O objetivo deste estudo foi o estabelecimento de valores de referência para o ECGAR de cães Boxer (n=28) e Pastor Alemão (n=19). Os seguintes parâmetros do ECGAR foram analisados: dQRS (duração do QRS filtrado), LAS<40μV (duração dos sinais de baixa amplitude no final do QRS filtrado) e RMS40 (raiz quadrada da voltagem média do final do QRS filtrado), com dois tipos diferentes de filtro (25-250 Hz e 40-250 Hz). Análise estatística foi realizada por meio do teste T de Student (p<0,05) para identificar diferenças entre os dois grupos e entre os valores obtidos com os dois filtros. Não foram encontradas diferenças significativas entre as variáveis de ECGAR nas duas raças estudadas com os dois diferentes filtros (p>0,05). A obtenção dos valores de normalidade de ECGAR em cães dessas raças auxiliará na realização de futuras pesquisas de potenciais tardios em animais com taquicardia ventricular hereditária ou cardiomiopatia arritmogênica, bem como na identificação dos indivíduos com alto risco de morte súbita de origem cardíaca...