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.

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.

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.

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.