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.     

Omega-3 fatty acids in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy

BACKGROUND: Omega-3 fatty acids have been shown to reduce arrhythmia in animal models and people. These effects have not been studied in dogs with spontaneously occurring arrhythmia. HYPOTHESIS: Fish oil will reduce the frequency of ventricular arrhythmia in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy (ARVC). ANIMALS: Twenty-four Boxers with ARVC were included in this study. METHODS: Asymptomatic Boxers not receiving antiarrhythmic medications were evaluated with echocardiogram and electrocardiogram. Dogs with at least 1 ventricular premature contraction (VPC) received 24-hour ambulatory electrocardiography (AECG) recordings. Dogs with > 95 VPCs in 24 hours were randomized to 1 of 3 treatments: (1) Fish oil, 2 g; (2) Flax oil, 2 g; or (3) sunflower oil, 2 g (Control group), for 6 weeks. Investigators and owners were blinded to the treatment groups. All baseline measurements were repeated after the 6-week supplementation. RESULTS: There were no differences at baseline for age, sex, blood pressure, weight, echocardiographic measurements, or VPCs. Median number of VPCs in 24 hours for all dogs was 543 (range, 96-40,063) at baseline and 193 (range, 6-14,825) after 6 weeks of supplementation. VPCs/24 h were reduced for the Fish oil group (baseline median = 397 [range, 249-10,587]; 6-week median = 162 [range, 16-3,781]; P = .02), but not for the Flax oil (P = .58) or Control (P = .48) groups. CONCLUSIONS AND CLINICAL IMPORTANCE: These data suggest that fish oil, but not flax oil, supplementation for 6 weeks reduces arrhythmia in Boxers with ARVC and that it could be useful in treating this common disease. Further studies are needed to determine optimal dose and duration of treatment.     

Arrhythmogenic right ventricular cardiomyopathy associated with severe left ventricular involvement in a cat

An 8-year-old, 4 kg, intact female, domestic shorthaired cat was referred for tachypnea and pleural effusion. A 24-h Holter recording showed numerous polymorphic ventricular premature complexes with left and right bundle branch block morphology. Echocardiographic examination revealed right atrial and ventricular dilation. The right ventricular free wall was thin and aneurysmal. The cat died 10 days after initiation of antiarrhythmic therapy. Gross and histopathological findings were consistent with arrhythmogenic right ventricular cardiomyopathy (ARVC) associated with severe left ventricular involvement.     

Arrhythmogenic right ventricular cardiomyopathy in two cats

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease characterised by infiltration of the myocardium by adipose and fibrous tissue. The disease is an important cause of sudden death in humans, but has rarely been described in animals. This report describes ARVC in two cats with right-sided congestive heart failure. One cat had also experienced previous episodes of syncope. Standard six-lead and 24-hour (Holter) electrocardiogram recording revealed complete atrioventricular block and multiform ventricular ectopics in both cats, with the addition of ventricular tachycardia, ventricular bigeminy and R-on-T phenomenon in one of them. On echocardiography, the right ventricle and atrium were massively dilated and hypokinetic. The survival times of the cats were three days and 16 days following diagnosis. Histopathology in one case revealed fibro-fatty infiltration of the myocardium, predominantly affecting the right ventricular free wall.     

Arrhythmogenic right ventricular cardiomyopathy in a dog

An 8-month-old Labrador retriever bitch was evaluated for sudden-onset, progressive abdominal distension. Physical examination revealed an exaggerated inspiratory effort, severe ascites, bilateral jugular vein distension, and hypokinetic femoral arterial pulses. Thoracic auscultation detected tachycardia with muffled heart sounds, without audible cardiac murmurs. Thoracic radiographs identified severe right ventricular enlargement and pleural effusion. The electrocardiogram was consistent with incomplete right bundle branch block or right ventricular enlargement. Echocardiography demonstrated severe right ventricular and atrial dilation, secondary tricuspid regurgitation, and thinning and hypocontractility of the right ventricular myocardium. Left heart chamber sizes were slightly decreased, with normal left ventricular contractility. A diagnosis of arrhythmogenic right ventricular cardiomyopathy was reached, based on the characteristic clinical, electrocardiographic, radiographic and echocardiographic findings, and the exclusion of other causes of isolated right ventricular failure. Treatment effected good control of clinical signs, until acutely decompensated congestive right heart failure led to euthanasia after 4 months. Arrhythmogenic right ventricular cardiomyopathy is a well-described clinical entity in humans, and has previously been documented in 3 male dogs. The condition is characterised by progressive fibro-adipose replacement of right ventricular myocardium, while the left ventricle usually remains unaffected. It should be considered a differential diagnosis in any young dog presented with isolated right heart failure, syncope, or unexplained ventricular tachyarrhythmias. This article reports the 1st case of arrhythmogenic right ventricular cardiomyopathy in a female dog, and highlights its echocardiographic features.     

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.     

Arrhythmogenic right ventricular dysplasia/cardiomyopathy in a Siberian husky

A seven-month-old male Siberian husky was presented with a recent history of anorexia, hindlimb weakness and syncope. Physical examination revealed severe tachycardia, tachypnoea and dyspnoea. Mucous membranes were pale and femoral pulses were weak. An electrocardiogram showed sustained ventricular tachycardia with a left bundle branch block configuration. Thoracic radiographs revealed slight right ventricular enlargement and two-dimensional echocardiography revealed mild right ventricular dilation at the cardiac apex and some hyperechogenic areas on the right side of the interventricular septum. Administration of intravenous lignocaine converted the ventricular tachycardia to sinus rhythm. The maintenance antiarrhythmic therapy consisted of oral procainamide and propranolol. Three weeks later the dog died suddenly. On postmortem examination, the right ventricular free wall was very thin at the apex, infundibulum and caudal aspect of the right ventricular parietal wall, similar to the 'triangle of dysplasia' of human patients. Histopathological examination revealed replacement of several areas of right ventricular free wall myocardium with connective tissue and fat. The right atrium and left ventricle were less severely affected by the same lesions. The clinical and pathological findings are similar to those reported in young people with arrhythmogenic right ventricular dysplasia/cardiomyopathy.     

Pathological features of arrhythmogenic right ventricular cardiomyopathy in middle-aged dogs

The hearts of four dogs (a 4-year-old Shetland sheepdog, a 4-year-old Labrador retriever, a 5-year-old English Bulldog, and a 6-year-old Dalmatian; three males and one female), that had died suddenly and had been clinically diagnosed as having arrhythmogenic right ventricular cardiomyopathy (ARVC), were studied post mortem. At the cut surface, all four hearts showed mild to moderate hypertrophy of the left and right ventricular free walls and ventricular septum, with grayish-white tissue replacement of the myocardium to various degrees. Histologically, all had typical right ventricular features of ARVC and morphological evidence of left ventricular and ventricular septal involvement. Two main histological patterns were identified: a fatty type (two cases) and a fibrofatty type (two cases). With either type, myocardial replacement by fatty or fibrofatty tissue were detected in both ventricles, but were more severe in the right ventricle, where they usually became transmural. Furthermore, this myocardial replacement was more severely seen in the epimyocardium and midmyocardium; the endomyocardium was less severely affected. On the basis of the present observation, it is evident that, in dogs, the disease process of ARVC affects both the right and left ventricles, although the striking pathological feature is right ventricular involvement. The pathological evidence of biventricular involvement in these canine cases of ARVC may represent a wider spectrum of the disease than has previously been recognized, suggesting that, in dogs, this disease should no longer be considered as limited to the right ventricle.     

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.

Taurine status in normal dogs fed a commercial diet associated with taurine deficiency and dilated cardiomyopathy

Taurine (Tau) deficiencies have been associated with the feeding of commercial lamb-meal and rice diets to dogs. We hypothesized that the poor digestibility of some lamb-meals may limit sulphur amino acids availability for Tau synthesis and/or increase of Tau degradation in the gut. Growing dogs were fed either a lamb-meal-based (Diet A) or poultry by-product-based (Diet B) commercial diet. Plasma, whole blood and urinary Tau were measured for 22 weeks. Plasma and whole blood Tau concentrations were similar between the groups throughout the study. Urinary excretion of Tau in dogs fed diet A was 3.2 times greater than that from dogs fed Diet B, suggesting greater renal reabsorption and the need for conservation of Tau in the Diet A group. Food restriction affected Tau status as indicted by a positive correlation of food intake and urinary Tau. Dogs fed Diet A were given antibiotics to inhibit bacterial activity in the gut. Increases in breath hydrogen, indicative of increased bacterial activity, correlated negatively with urinary Tau. Urinary Tau increased by 54% when methionine (Met) was supplemented to Diet A, supporting the suggestion of a low bioavailability of sulphur amino acids and/or an increased fecal loss of Tau in dogs consuming Diet A.     

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.     

Desmosomal gene evaluation in Boxers with arrhythmogenic right ventricular cardiomyopathy

OBJECTIVE: To sequence the exonic and splice site regions of the 4 desmosomal genes associated with the human form of familial arrhythmogenic right ventricular cardiomyopathy (ARVC) in Boxers with ARVC and identify a causative mutation. ANIMALS: 10 unrelated Boxers with ARVC and 2 unaffected Labrador Retrievers (control dogs). PROCEDURES: Exonic and splice site regions of the 4 genes encoding the desmosomal proteins plakophilin-2, plakoglobin, desmoplakin, and desmoglein-2 were sequenced. Sequences were compared for nucleotide sequence changes between affected dogs and the published sequences for clinically normal dogs and between affected dogs and the control dogs. Base-pair changes were considered to be causative for ARVC if they were detected in an affected dog but not in unaffected dogs, and if they involved a conserved amino acid and changed that amino acid to one of a different polarity, acid-base status, or structure. RESULTS: A causative mutation for ARVC in Boxers was not identified, although single nucleotide polymorphisms were detected in some affected dogs within exon 3 of the plakophilin-2 gene; exon 3 of the plakoglobin gene; exons 3 and 7 of the desmoglein-2 gene; and exons 6, 14, 15, and 24 of the desmoplakin gene. None of these changed the amino acid of the respective protein. CONCLUSIONS AND CLINICAL RELEVANCE: Mutations within the desmosomal genes associated with the development of ARVC in humans do not appear to be causative for ARVC in Boxers. Genomewide scanning for genetic loci of interest in dogs should be pursued.     

Myocardial L-carnitine deficiency in a family of dogs with dilated cardiomyopathy

Dilated cardiomyopathy in a family of dogs was found to be associated with decreased myocardial L-carnitine concentrations, when compared with those in control dogs. In 2 affected dogs, treatment with high doses of L-carnitine was associated with increased myocardial L-carnitine concentration and greatly improved health and myocardial function. Withdrawal of L-carnitine supplementation from these dogs resulted in development of myocardial dysfunction and clinical signs of dilated cardiomyopathy.     

Systolic anterior motion of the mitral valve associated with right ventricular systolic hypertension in 9 dogs

ObjectivesTo describe the zoographic and echocardiographic characteristics of canine patients in which systolic anterior motion of the mitral valve (SAM) was identified in association with right ventricular systolic hypertension (RVSH).Animals, materials and methodsMedical records and digitally recorded echocardiographic examinations were reviewed for RVSH and two-dimensional (2DE) or M-mode echocardiographic evidence of SAM.ResultsSAM was identified in association with RSVH in 9 patients; 5 had pulmonic stenosis, 2 had tetralogy of Fallot and 2, pulmonary hypertension. Relative to body weight, the end-diastolic and end-systolic left ventricular dimensions were subnormal in all patients. Hyperdynamic left ventricular systolic performance was identified in 8 of 9 patients.In 5 of the 9 patients, SAM was mild or moderate in degree. Left ventricular outflow tract (LVOT) obstruction and mitral valve regurgitation were documented by Doppler studies in only 3 of the 4 patients with marked SAM. However, late systolic acceleration within the LVOT was recorded in 2 additional patients for whom peak velocities were normal.ConclusionsIn the cases described here, the presence of SAM is likely explained by alterations in left ventricular geometry and function associated with diminished pulmonary venous return together with sympathetic activation resulting from subnormal stroke volume. Although the hemodynamic consequences were apparently minor, the association of SAM with right-sided heart disease might be of interest to those engaged in the practice of veterinary echocardiography.     

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 (ρ= 0.19) and minimum (ρ= 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.     

Nervous syndrome in dogs possibly associated with thiamine deficiency

A 2 1/2-year-old Cavalier King Charles Spaniel bitch was examined because of recurring episodes of lameness and joint swelling over a period of 2 years. Clinical examination, radiography, serology, joint-fluid analysis and histopathology of the joint capsule led to a diagnosis of idiopathic, non-infectious, non-erosive arthritis. Combination therapy with prednisolone, cyclophosphamide and azothioprine produced a rapid improvement in the dog's condition.

The features of this disease and its relationship to rheumatoid arthritis and systemic lupus erythematosis are discussed.     

Assessment of heart rate variability in Boxers with arrhythmogenic right ventricular cardiomyopathy

OBJECTIVE: To assess heart rate variability (HRV) in Boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC), assess the ability of HRV analysis to identify differences in Boxers on the basis of severity of their arrhythmia, and evaluate the use of HRV to determine whether persistently high sympathetic tone is present in these dogs. DESIGN: Prospective study. ANIMALS: 24 Boxers with ARVC and 10 clinically normal non-Boxer dogs. PROCEDURE: Boxers were categorized as dogs with congestive heart failure (CHF), dogs with < or = 2 ventricular premature complexes (VPCs)/24 h (designated unaffected), or dogs with > 1,000 VPCs/24 h (designated affected). Ambulatory electrocardiography (24 hours) was performed in each dog. Recordings were analyzed for HRV variables at a commercial laboratory; differences in HRV variables among groups were compared with 1-way ANOVA. RESULTS: Compared with control non-Boxer dogs and Boxers without CHF (affected and unaffected Boxers), HRV was reduced in Boxers with CHF. No differences in HRV variables were detected between affected and unaffected Boxers. Inconsistent differences were identified between the control dogs and Boxers without CHF that had various degrees of arrhythmias. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that persistently high sympathetic tone is not a consistent feature of ARVC. Differences in some HRV variables between Boxers without CHF and control dogs suggest that Boxers may have different autonomic control of heart rate, compared with that of clinically normal non-Boxer dogs. The usefulness of HRV analysis appears limited to Boxers with ARVC that have systolic dysfunction and CHF.