A possible predisposition to dilated cardiomyopathy in Huntaway dogs

AIM: To compare the prevalence of dilated cardiomyopathy (DCM) in New Zealand Huntaway dogs with the prevalence of DCM in other breeds of dog.

METHODS: The necropsy database at Massey University was used to identify cases of DCM diagnosed between January 1999 and March 2006. Dogs were considered to have DCM if echocardiographic, gross necropsy, or histological findings were consistent with this diagnosis. The prevalence in Huntaways was then compared with the prevalence observed in all breeds of dog, as well as the prevalence observed in large breeds of dog.

RESULTS: Twelve dogs were identified with DCM. One was diagnosed using echocardiography, while the other 11 were diagnosed by gross necropsy examination. The gross diagnosis of DCM was confirmed histologically in 6/11 dogs. The prevalence of DCM in Huntaways was significantly higher than the prevalence seen in all breeds of dog (p=0.008), and the prevalence in large breeds of dog (p=0.025). All four Huntaways diagnosed with DCM were male, and had an average age of 4 years. Three dogs presented with symptoms attributable to impaired heart function while one presented with symptoms of chronic renal failure. The duration of clinical symptoms prior to presentation ranged between 1 day and 3 weeks.

CONCLUSIONS: The results of this study suggest that Huntaways may be predisposed to the development of DCM. Although the increased prevalence in this breed was significant, only small numbers of affected Huntaways were identified, and additional cases are required to confirm these preliminary findings.

CLINICAL RELEVANCE: Huntaways are the most common working dog in New Zealand. The premature loss of a working dog is expected to have a significant economic impact on farmers. Further investigation of DCM in Huntaways may allow measures to reduce the prevalence in this breed.     

Carvedilol in dogs with dilated cardiomyopathy

BACKGROUND: Dilated cardiomyopathy (DCM) is characterized by reduced systolic function, heightened sympathetic tone, and high morbidity and mortality. Little is known regarding the safety and efficacy of beta-blocker treatment in dogs with DCM. HYPOTHESIS: Carvedilol improves echocardiographic and neurohormonal variables in dogs with DCM over a 4-month treatment period. METHODS: Prospective, placebo-controlled, double-blinded randomized study. Dogs with DCM underwent echocardiography, ECG, thoracic radiographs, and neurohormonal profiling, followed by titration onto carvedilol (0.3 mg/kg q12h) or placebo over a 4-week period and subsequently received 3 months of therapy. Primary study endpoints included left ventricular volume and function. RESULTS: Sixteen dogs received carvedilol and 7 received placebo. At study end, 13 carvedilol dogs and 5 placebo dogs were alive. There was no difference in the mean percentage change in left ventricular volume at end-diastole (LVVd), left ventricular end-systolic volume (LVVs), and ejection fraction (EF) between treatment groups, suggesting that both groups experienced similar amounts of disease progression. Carvedilol treatment did not result in significant changes in neurohormonal activation, radiographic heart size, heart rate, or owner perceived quality-of-life. Baseline B-type natriuretic peptide (BNP) predicted dogs in the carvedilol-treated group that maintained or improved their EF over the study duration. CONCLUSIONS AND CLINICAL IMPORTANCE: Carvedilol administration did not improve echocardiographic or neurohormonal indicators of heart function. The lack of effect may be related to severity of disease, carvedilol dose, or brevity of follow-up time. Statistical power of the present study was adversely affected by a high fatality rate in study dogs and small sample size.     

Prognostic indicators for dogs with dilated cardiomyopathy

The purpose of this study was to investigate the prognostic value of various clinical, ECG, echocardiographic, and Doppler echocardiographic variables in dogs with dilated cardiomyopathy. The relationship to survival of 11 variables was evaluated in 63 dogs. Studied variables were age at time of diagnosis, class of heart failure (HF), dyspnea, ascites, atrial fibrillation (AF), ejection fraction (EF), E-point septal separation, end-diastolic volume index, end-systolic volume index (ESV-I), and restrictive or nonrestrictive transmitral flow (TMF) pattern. Median survival time was 671 days (lower 95% confidence limit, 350 days). Survival curves showed that severity of HF, ascites, ESV-I greater than 140 mL/m2, EF less than 25%, and restrictive TMF pattern had a significant negative relation to survival time. Thirty-nine dogs with both sinus rhythm and AF presented adequate TMF recordings; in these dogs, after stratification by TMF pattern, the restrictive TMF pattern was the most important negative prognostic indicator. We conclude that in dogs with dilated cardiomyopathy the restrictive TMF pattern appears to represent a useful prognostic indicator. Class of HF, ascites, ESV-I, and EF are also useful indexes if an adequate TMF pattern is not recorded.     

Skeletal muscle extra-aortic counterpulsation in dogs with dilated cardiomyopathy

Skeletal muscle extra-aortic counterpulsation was performed in seven dogs with dilated cardiomyopathy. A left latisslmus dorsi dynamic descending thoracic aortomyoplasty was used as the autologous counterpulsator. Pulse train stimulation In diastole was used to initiate contraction and fibre type transformation. Two of the dogs died within 48 hours of surgery. The device was successfully activated in the five remaining dogs, but in one individual it failed within 48 hours of activation. Serial echocardiographic examinations of dogs in which the device functioned successfully (n=4) showed trends towards the decrease In the left ventricular systolic Internal dimension, left ventricular diastolic internal dimension, E-point to septal separation and left atrial diameter in systole seven to 14 days following the procedure, although these changes failed to persist in the long term. The results suggest that skeletal muscle for cardiac assistances such as extra-aortic muscle counterpulsation, might be a therapeutic option for dogs with cardiac failure due to dilated cardiomyopathy.     

Familial dilated cardiomyopathy of young Portuguese water dogs

A novel dilated cardiomyopathy (DCM) in 12 related Portuguese Water Dogs was identified by retrospective analysis of postmortem and biopsy case records. Male and female puppies born to clinically healthy parents typically died at 13 (+/- 7.3) weeks of age (range, 2-32 weeks) because of congestive heart failure. Puppies died suddenly without previous signs or with mild depression followed by clinical signs of congestive heart failure 1-5 days before death. There was no sex predilection. The hearts were enlarged and rounded, with marked left ventricular and atrial dilation. No other significant structural cardiac defects were noted. The histologic changes in the myocardium were diffuse and characterized by myofibers of irregular sizes separated by an edematous interstitium. The myofibers had multifocal swollen, cleared segments often involving perinuclear areas that contained granular, phosphotungstic-acid-hematoxylin-positive material consistent with mitochondria. There was loss of the cross-striation pattern, and intercalated discs were difficult to identify. There was no evidence of concurrent myocardial fibrosis; rare chronic inflammatory infiltrates were noted in one dog. Noncardiac skeletal muscles were not affected. The underlying cause is unknown. From the pedigree analysis, an autosomal recessive pattern of inheritance is suspected. Based on the histologic findings, this DCM is most likely due to an underlying molecular (biochemical or structural) defect. The early onset and rapid progression of the disease makes this a clinically distinctive form of canine DCM.     

Pathology of mucopolysaccharidosis IIIA in Huntaway dogs

Dogs with mucopolysaccharidosis (MPS) IIIA were bred within an experimental colony. As part of characterizing them as a model for testing therapeutic strategies for the analogous disease of children, a pathologic study was undertaken. By histology, there were variably stained storage cytosomes within neurons, including many that stained for gangliosides. On ultrastructure examination, these cytosomes contained either moderately dense granular material, tentatively interpreted as precipitated glycosaminoglycan; a variety of multilaminar bodies, interpreted as being associated with secondary accumulation of gangliosides; or a mixture of both types. In the liver, storage vesicles also contained excess glycogen as a secondary storage product. In various tissues, there were large foamy macrophages. In the brain, many of these were in juxtaposition with neurons, and, on ultrastructure examination, they contained storage cytosomes similar to those in neurons. However, the neuron in association with such a macrophage frequently showed little such material.     

Myocardial concentrations of fatty acids in dogs with dilated cardiomyopathy

OBJECTIVE: To compare myocardial concentrations of fatty acids in dogs with dilated cardiomyopathy (DCM) with concentrations in control dogs. SAMPLE POPULATION: Myocardial tissues from 7 dogs with DCM and 16 control dogs. PROCEDURE: Myocardial tissues were homogenized, and total fatty acids were extracted and converted to methyl esters. Myocardial concentrations of fatty acids were analyzed by use of gas chromatography and reported as corrected percentages. RESULTS: The amount of docosatetraenoic acid (C22:4 n-6) was significantly higher in myocardial samples from dogs with DCM (range, 0.223% to 0.774%; median, 0.451%), compared with the amount in samples obtained from control dogs (range, 0.166% to 0.621%; median, 0.280%). There were no significant differences between DCM and control dogs for concentrations of any other myocardial fatty acids. CONCLUSIONS AND CLINICAL RELEVANCE: Although concentrations of most myocardial fatty acids did not differ significantly between dogs with DCM and control dogs, the concentration of docosatetraenoic acid was significantly higher in dogs with DCM. Additional investigation in a larger population is warranted to determine whether this is a primary or secondary effect of the underlying disease and whether alterations in fatty acids may be a target for intervention in dogs with DCM.     

Echocardiographic evaluation of diastolic parameters in dogs with dilated cardiomyopathy

Echocardiography is a valuable tool for the evaluation of systolic and diastolic cardiac function. A high correlation between measurements of diastolic mitral inflow parameters analyzed with Doppler echocardiography and invasive methods makes the former valuable. The aim of this study was to ascertain if significant differences occur in diastolic myocardial parameters between dogs with no heart disease and dogs with subclinical or clinical dilated cardiomyopathy. Furthermore the aim of the study was to determine whether heart failure in dilated cardiomypathy is a result of systolic dysfunction alone or both systolic and diastolic dysfunction. Eleven parameters were analyzed: E wave, E-AT, E-DT, E time, A wave, A-AT, A-DT, A time, E+A time, E/A ratio, and IVRT. The study confirmed the value of noninvasive echocardiographic assessment of diastolic function in dogs with dilated cardiomyopathy. Significant differences were found in E wave, E-AT, E time, E/A ratio and IVRT between healthy dogs and dogs with dilated cardiomyopathy. All are characterized by a significant decrease compared to healthy dogs after taking into account age and body weight except for the E/A ratio, which significantly increased in value. There were no significant changes in any of the Doppler parameters for diastolic evaluation in subclinical cases of DCM. Advanced heart failure in dilated cardiomyopathy entails systolic and diastolic dysfunction.     

Progressive myelopathy and neuropathy in New Zealand Huntaway dogs

Aim: To investigate the nature and cause of a progressive ataxia in three 20-month-old Huntaway dogs that were litter mates.

Methods: Affected dogs were examined before they were humanely killed and submitted to necropsy. Selected formalin-fixed tissues were examined by light and electron microscopy.

Results: The lesions were those of axon and myelin degeneration within sensory, proprioceptive and motor tracts of the spinal cord and to a lesser degree some peripheral nerves.

Conclusion: A progressive myelopathy and neuropathy, tentatively described as a central-peripheral distal axonopathy, was present in all 3 dogs.The cause was not determined but was likely to be either genetic or nutritional.

Clinical relevance: In the early stages of this disease, careful examination maybe necessary to distinguish the signs of ataxia from orthopaedic disease such as hip dysplasia. Affected animals are unlikely to be of use as working dogs.     

A double-blind,randomized, placebo-controlled study of pimobendan in dogs with dilated cardiomyopathy

A double-blind, randomized, placebo-controlled study was conducted to examine the effect on heart failure class and survival of pimobendan, an oral calcium-sensitizing inodilator, in dogs with dilated cardiomyopathy (DCM). Pimobendan (0.3-0.6 mg/kg body weight/d) or placebo was administered to English Cocker Spaniels (CSs; n = 10) and Doberman Pinschers (DPs: n = 10) that had DCM in addition to background therapy of furosemide, enalapril, and digoxin. Addition of pimobendan to standard triple therapy was associated with a significant improvement in heart failure class, regardless of breed (P < .02, Mann-Whitney rank sum test). Overall, 8 of 10 animals in the pimobendan-treated group, and 1 of 10 animals in the placebo group improved their heart failure status by at least I modified New York Heart Association functional class after initial stabilization (P = .005, Fisher's exact test). Pimobendan had no significant effect on survival in the CSs (P = 0.77, log-rank test), but DPs treated with pimobendan had significantly longer survival times compared with placebo (P < .02, log-rank test), with a median survival time of 329 days in the pimobendan group compared with 50 days in the placebo group, and a hazard ratio of 3.4 (95% confidence interval 1.4-39.8). Pimobendan resulted in significant improvement in heart failure class when added to standard therapy in this group of dogs with DCM, and may have contributed to improved survival in DPs.     

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.     

Screening for the Mucopolysaccharidosis-IIIA gene in Huntaway dogs

Abstract

Extract

A single case of the inherited lysosomal storage disease known as mucopolysaccharidosis-IIIA (MPS-IIIA), due to a deficiency of the enzyme heparan sulphatase, was reported in an 18-month-old male Huntaway dog (Jolly et al 2000 Jolly, RD, Allan, FJ, Collett, MG, Rozaklis, T, Muller, VJ and Hopwood, JJ. 2000. Mucopolysaccharidosis IIIA (Sanfilippo syndrome) in a New Zealand Huntaway dog with ataxia. New Zealand Veterinary Journal, 48: 144–148. [Taylor &; Francis Online], [Web of Science ®] , [Google Scholar]). He had developed normally but when presented with a history of progressive ataxia over the preceding month, had a high stepping, prancing gait and difficulty in jumping into a utility vehicle. In addition, he had started to defaecate in his kennel. Following diagnosis of the enzyme deficiency, the mutant heparan sulphatase gene was sequenced and a PCR/restriction enzyme diagnostic test developed, based on the mutation. This is capable of detecting both homozygous and heterozygous individuals (Yogalingam et al 2000 Yogalingam, G, Pollard, T, Gliddon, B, Jolly, RD and Hopwood, JJ. 2001. Identification of a mutation causing mucopolysaccharidosis type IIIA in New Zealand Huntaway dogs. Genomics, 79: 150–153.  [Google Scholar]).     

Timing of left heart base descent in dogs with dilated cardiomyopathy and normal dogs.

The identification and assessment of myocardial failure in canine idiopathic dilated cardiomyopathy (DCM) is achieved using a variety of two-dimensional and Doppler echocardiographic techniques. More recently, the availability of tissue Doppler imaging (TDI) has raised the potential for development of new ways of more accurately identifying a disease phenotype. Nevertheless, TDI has not been universally adapted to veterinary clinical cardiology primarily because of the lack of information on its utility in diagnosis. We assessed the application of timing of left heart base descent using TDI in the identification of differences between DCM and normal dogs. The times from the onset of the QRS complex on a simultaneously recorded electrocardiograph to the onset (Q--S'), peak (Q--peak S'), and end (Q--end S') of the systolic velocity peak were measured in the interventricular septum (IVS) and the left ventricular free wall. The duration of S' was also calculated. The Q--S' (FW), Q--end S' (FW), and duration S' (FW) were correlated with ejection fraction in the diseased group (P < 0.05). In addition, Q--S', Q--peak S', Q--end S', and the peak S' velocity were prolonged in the diseased dogs at both the free wall and in the IVS (P < 0.01). The duration of S' was unaffected by disease status. These findings provide insight into the electromechanical uncoupling that occurs in canine DCM and identifies new TDI parameters that can be added to the range of Doppler and echocardiographic parameters used for detecting myocardial failure in the dog.     

Vasopressin, cortisol, and catecholamine concentrations in dogs with dilated cardiomyopathy

OBJECTIVE: To evaluate plasma concentrations and urinary excretion of vasopressin and cortisol and urinary excretion of catecholamines in dogs with dilated cardiomyopathy (DCM). ANIMALS: 15 dogs with clinical signs of DCM, 15 dogs with preclinical DCM, and 15 control dogs. PROCEDURE: Physical examinations, thoracic radiography, ECG, and echocardiography were performed on all dogs. Blood and urine samples were collected. RESULTS: Plasma concentration of vasopressin and the urine cortisol-to-urine creatinine ratio were significantly increased in dogs with clinical signs of DCM and dogs with preclinical DCM, compared with control dogs. Plasma vasopressin concentration was significantly higher in dogs with clinical signs of DCM, compared with dogs with preclinical DCM. Urine vasopressin-to-urine creatinine ratio was significantly increased in dogs with clinical signs of DCM, compared with dogs with preclinical DCM and control dogs. Urine epinephrine-to-urine creatinine ratio and urine norepinephrine-to-urine creatinine ratio were significantly increased in dogs with clinical signs of DCM, compared with control dogs. Plasma concentration of cortisol and urine dopamine-to-urine creatinine ratio did not differ significantly among groups. CONCLUSIONS AND CLINICAL RELEVANCE: According to this study, the neuroendocrine pattern is changed in dogs with preclinical DCM. These changes are even more pronounced in dogs with clinical signs of DCM. Analysis of concentrations of vasopressin, cortisol, and catecholamines may aid in identification of the clinical stages of DCM. These findings may also provide a basis for additional studies of the possible beneficial effects of vasopressin antagonists and beta-adrenergic receptor antagonists in the treatment of dogs with congestive heart failure and DCM.     

Therapeutic trial of granulocyte-colony stimulating factor for dilated cardiomyopathy in three dogs

Three dogs were presented to us for evaluation of cardiac problems. Electrocardiographic recordings revealed severe tachyarrhythmia and atrial fibrillation with ventricular tachycardia in 2 of the 3 dogs. The echocardiographic findings of the 3 dogs revealed markedly decreased fractional shortening and a marked increase in E-point septal separation. Based on the results of electrocardiographic and echocardiographic evaluation, the 3 dogs were diagnosed as dilated cardiomyopathy (DCM). The dogs were treated with conventional cardiac medication, but cardiac function did not improve and the clinical signs remained. We subsequently attempted treatment with granulocyte-colony stimulating factor (G-CSF; 10 microg/kg, subcutaneously). The specific purpose of G-CSF therapy for DCM was to improve cardiac function and a significant improvement in cardiac function was confirmed. The three dogs had no treatment side effects. This case report suggests that G-CSF might have therapeutic effects for medically refractory DCM in dogs.     

Evaluation of the phospholamban gene in purebred large-breed dogs with dilated cardiomyopathy

OBJECTIVE: To evaluate the role of the phospholamban gene in purebred large-breed dogs with dilated cardiomyopathy (DCM). ANIMALS: 6 dogs with DCM, including 2 Doberman Pinschers, 2 Newfoundlands, and 2 Great Danes. PROCEDURE: All dogs had clinical signs of congestive heart failure, and a diagnosis of DCM was made on the basis of echocardiographic findings. Blood samples were collected from each dog, and genomic DNA was isolated by a salt extraction method. Specific oligonucleotides were designed to amplify the promoter, exon 1, the 5'-part of exon 2 including the complete coding region, and part of intron 1 of the canine phospholamban gene via polymerase chain reaction procedures. These regions were screened for mutations in DNA obtained from the 6 dogs with DCM. RESULTS: No mutations were identified in the promoter, 5' untranslated region, part of intron 1, part of the 3' untranslated region, and the complete coding region of the phospholamban gene in dogs with DCM. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that mutations in the phospholamban gene are not a frequent cause of DCM in Doberman Pinschers, Newfoundlands, and Great Danes.     

Breed predisposition to congenital alacrima in dogs

Objective  To evaluate the clinical characteristics and breed predisposition of congenital alacrima in dogs.
Animals studied  Dogs with congenital keratoconjunctivitis sicca.
Procedures  A search of the medical records of the University of Tennessee Veterinary Teaching Hospital from 1974–2005 and the University of California–Davis Veterinary Teaching Hospital from 1986–2006 for dogs under 1 year of age with a diagnosis of keratoconjunctivitis sicca (KCS) was performed. These cases were further reviewed for dogs with a Schirmer's tear test I of ≤ 5 mm/min before 6 months of age, with no known causes for KCS, which did not respond to appropriate KCS therapy; these cases were considered to have congenital alacrima. These breeds were compared to all other breeds using the Fisher's exact test with correction for multiple comparisons.
Results  Congenital alacrima was identified in 19 dogs representing 11 breeds and mixed breeds. Yorkshire Terriers and Bedlington Terriers were statistically overrepresented compared to reference populations ( P  < 0.01 and P  = 0.04, respectively).
Conclusions  Yorkshire terriers are significantly at risk for congenital alacrima compared to other breeds. The significance of the increase in congenital alacrima in Bedlington Terriers in this study may not be clinically relevant and may be due to the small total number of dogs of this breed that presented to the both hospitals. Based on the poor response to therapy in humans with congenital alacrima, it may be prudent to offer guarded prognoses for KCS in juvenile Yorkshire terriers.