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.     

Syncope secondary to transient atrioventricular block in a German shepherd dog with dilated cardiomyopathy and atrial fibrillation

This case report describes transient atrioventricular block as the etiology for syncopal events in a 6-year-old male German shepherd dog with atrial fibrillation and dilated cardiomyopathy. The arrhythmia diagnosis was obtained via Holter monitoring. Medical treatment with a sustained-release preparation of theophylline, as an additive to the standard congestive heart failure treatment (benazepril, furosemide and pimobendan) may have contributed to temporary remission of the syncopal events. However, the congestive heart failure progressed and the dog was euthanized. Veterinarians should be aware of the possibility of transient atrioventricular block causing syncope in dogs with DCM and AF and should be careful in empirically lowering the ventricular response rate if these dogs present with syncopal episodes.     

Effect of pimobendan on case fatality rate in Doberman Pinschers with congestive heart failure caused by dilated cardiomyopathy

BACKGROUND: Despite traditional therapy of a diuretic, angiotensin converting enzyme inhibitor, digoxin, or a combination of these drugs, survival of dogs with dilated cardiomyopathy (DCM) is low. Pimobendan, an inodilator, has both inotropic and balanced peripheral vasodilatory properties. HYPOTHESIS: Pimobendan when added to conventional therapy will improve morbidity and reduce case fatality rate in Doberman Pinschers with congestive heart failure (CHF) caused by DCM. ANIMALS: Sixteen Doberman Pinschers in CHF caused by DCM. METHODS: A prospective randomized, double-blind, placebo-controlled study with treatment failure as the primary and quality of life (QoL) indices as secondary outcome variables. Therapy consisted of furosemide (per os [PO] as required) and benazepril hydrochloride (0.5 mg/kg PO q12h) and dogs were randomized in pairs and by sex to receive pimobendan (0.25 mg/kg PO q12h) or placebo (1 tablet PO q12h). RESULTS: Pimobendan-treated dogs had a significant improvement in time to treatment failure (pimobendan median, 130.5 days; placebo median, 14 days; P= .002; risk ratio = 0.35, P= .003, lower 5% confidence limit = 0.13, upper 95% confidence limit = 0.71). Number and rate of dogs reaching treatment failure in the placebo group precluded the analysis of QoL. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan should be used as a first-line therapeutic in Doberman Pinschers for the treatment of CHF caused by DCM.     

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.     

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.     

The potential role of myocardial serotonin receptor 2B expression in canine dilated cardiomyopathy

Serotonin signalling in the heart is mediated by receptor subtype 2B (5-HTR2B). A contribution of serotonin to valvular disease has been reported, but myocardial expression of 5-HTR2B and its role in canine dilated cardiomyopathy (DCM) is not known. The aim of the present study was to investigate myocardial 5-HTR2B mRNA expression in dogs with DCM and to correlate results with expression of markers for inflammation and remodelling. Myocardial samples from eight healthy dogs, four dogs with DCM, five with cardiac diseases other than DCM and six with systemic non-cardiac diseases were investigated for 5-HTR2B mRNA expression using quantitative PCR (qPCR). The results were compared to mRNA expression of selected cytokines, matrix metalloproteinases (MMP) and tissue inhibitors of matrix metalloproteinase (TIMP). Laser microdissection with subsequent qPCR and immunohistochemistry were employed to identify the cells expressing 5-HTR2B.The myocardium of control dogs showed constitutive 5-HTR2B mRNA expression. In dogs with DCM, 5-HTR2B mRNA values were significantly greater than in all other groups, with highest levels of expression in the left ventricle and right atrium. Myocytes were identified as the source of 5-HTR2B mRNA and protein. A significant positive correlation of 5-HTR2B mRNA with expression of several cytokines, MMPs and TIMPs was observed. The findings suggest that serotonin might play a role in normal cardiac structure and function and could contribute to myocardial remodelling and functional impairment in dogs with DCM.     

A prospective genetic evaluation of familial dilated cardiomyopathy in the Doberman pinscher

BACKGROUND: The Doberman Pinscher is one of the most common breeds of dogs to develop dilated cardiomyopathy (DCM), a primary heart muscle disorder characterized by myocardial dysfunction, cardiac arrhythmias, and congestive heart failure. In the Doberman Pinscher, the disease is typically adult onset, and a familial etiology has been suggested. HYPOTHESIS: DCM in the Doberman Pinscher, is a familial disease linked to a specific genetic marker. ANIMALS: The study comprised an extended family of Doberman Pinschers with a history of DCM. METHODS: Participating dogs were prospectively evaluated over an 8-year period. Phenotype of participating dogs was determined by annual echocardiography and ambulatory electrocardiography, and the pedigree was evaluated to determine a specific mode of inheritance. Three hundred seventy-two microsatellite markers were selected and genotyped to cover the 38 autosomal chromosomes. Phenotyping, genotyping, and pedigree information was entered into a database, and parametric, 2-point analysis was performed. Markers were considered to be linked to the development of DCM if the logarithm of odds LOD score was >/= 3.0. RESULTS: An autosomal dominant mode of inheritance was defined by the appearance of the disease in multiple generations, equal gender representation (P = .973) and male-to-male transmission. A maximum LOD score of 1.31 was obtained for I marker on chromosome 20, a score not high enough to be associated with DCM. CONCLUSION: DCM in the Doberman Pinscher is a familial disease inherited as an autosomal dominant trait. The causative gene(s) responsible for this condition remain unresolved. Association studies by means of array technology may provide new insights into gene identification.     

Plasma endothelin-1 immunoreactivity in normal dogs and dogs with acquired heart disease

We sought to measure plasma endothelin-1 (ET-1) concentrations in normal dogs and to compare them with those measured in dogs with acquired heart disease with or without pulmonary edema. A sandwich enzyme-linked immunosorbent assay kit was validated and used to measure ET-1 immunoreactivity in plasma samples obtained from 32 normal dogs and 46 dogs with either dilated cardiomyopathy (DCM, n = 27) or degenerative valvular disease (CDVD, n = 19) with (n = 30) or without (n = 16) overt congestive heart failure (CHF). Plasma ET-1 concentrations (geometric mean, 95% confidence interval of geometric mean) were 1.17 (1.04-1.32) fmol/mL in the 32 normal control dogs, 1.25 (0.981-1.60) fmol/mL in 16 dogs with DCM (n = 9) or CDVD (n = 7) without CHF, and 2.51 (2.10-3.01) fmol/mL in 30 dogs with DCM (n = 18) and CDVD (n = 12) with CHE Plasma immunoreactivity of ET-1 was significantly higher in dogs with CHF in comparison with normal dogs (P < .001) and dogs with heart disease without CHF (P < .001). No significant difference was found between normal dogs and dogs with heart disease but without CHF (P > .05). Significant correlations were between plasma ET-I concentrations and left atrial:aortic ratio (P < .0001, r2 = .39), left ventricular internal dimension at end-diastole indexed to aortic diameter (P < .0001, r2 = .30) or body surface area (BSA) (P = .0071, r2 = .10), and left ventricular internal dimension at end-systole indexed to aortic diameter (P = .0003, r- = .17) or BSA (P = .0008, r2 = .15).     

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.     

Prospective study of dilated cardiomyopathy in dogs eating nontraditional or traditional diets and in dogs with subclinical cardiac abnormalities

BackgroundRecent studies have investigated dogs with presumed diet‐associated dilated cardiomyopathy (daDCM), but prospective studies of multiple breeds are needed.Hypothesis/ObjectivesTo evaluate baseline features and serial changes in echocardiography and cardiac biomarkers in dogs with DCM eating nontraditional diets (NTDs) or traditional diets (TDs), and in dogs with subclinical cardiac abnormalities (SCA) eating NTD.AnimalsSixty dogs with DCM (NTD, n = 51; TDs, n = 9) and 16 dogs with SCA eating NTDs.MethodsEchocardiography, electrocardiography, and measurement of taurine, cardiac troponin I, and N‐terminal pro‐B‐type natriuretic peptide were performed in dogs with DCM or SCA. Diets were changed for all dogs, taurine was supplemented in most, and echocardiography and cardiac biomarkers were reassessed (3, 6, and 9 months).ResultsAt enrollment, there were few differences between dogs with DCM eating NTDs or TDs; none had low plasma or whole blood taurine concentrations. Improvement in fractional shortening over time was significantly associated with previous consumption of a NTD, even after adjustment for other variables (P = .005). Median survival time for dogs with DCM was 611 days (range, 2‐940 days) for the NTD group and 161 days (range, 12‐669 days) for the TD group (P = .21). Sudden death was the most common cause of death in both diet groups. Dogs with SCA also had significant echocardiographic improvements over time.Conclusions and Clinical ImportanceDogs with DCM or SCA previously eating NTDs had small, yet significant improvements in echocardiographic parameters after diet changes.     

Clinical, echocardiographic, and neurohormonal effects of a sodium-restricted diet in dogs with heart failure

The use of low-sodium diets in dogs with heart failure is common practice, but randomized, double-blind studies have not been conducted to examine the benefits or problems with this approach. The purpose of this study was to determine the effects of a low-sodium diet on clinical, echocardiographic, and neurohormonal parameters in dogs with heart failure. Dogs with stable chronic heart failure were fed exclusively a low-sodium (LS) and a moderate-sodium (MS) diet for 4 weeks each in a randomized, double-blind, crossover design. At days 0, 28, and 56, echocardiography and thoracic radiography were performed, and blood was analyzed for electrolytes and neurohormones. Fourteen dogs completed the study (9 with chronic valvular disease and 5 with dilated cardiomyopathy). Electrolyte abnormalities were common during the study, and serum sodium and chloride concentrations decreased significantly on the LS diet. Neurohormones did not change significantly between diet groups. Maximum left atrial (P = .05) and standard left atrial (P = .09) size decreased on the LS diet. For dogs with chronic valvular disease, vertebral heart score (P = .05), left ventricular internal dimension in diastole (P = .006) and systole (P = .02), standard left atrial dimension (P = .03), maximum left atrial dimension (P = .02), end-diastolic volume index (P = .02), and end-systolic volume index (P = .04) decreased significantly on the LS diet compared to the MS diet. Although analysis of these data suggests some benefits of a low-sodium diet, future studies with improved study design are needed to further evaluate the advantages and disadvantages of sodium restriction in dogs with heart failure.     

Total bilirubin is an independent predictor of death in dogs with degenerative valvular disease and dilated cardiomyopathy

IntroductionThere is little published regarding the association between canine cardiovascular disease and the hepatic system. The objective of the study was to evaluate the relationship between hepatic parameters, survival, and disease stages of dogs with either dilated cardiomyopathy (DCM) or degenerative valvular disease (DVD).Animals, materials, and methodsRetrospective study analyzing hepatic parameters in dogs with DVD or DCM in American College of Veterinary Internal Medicine stage B or C and healthy control dogs. Associations between liver parameters, type and stage of disease, and survival were investigated.ResultsNinety-nine dogs were included in the study: 61 DVD, 22 DCM, and 16 controls. Differences in liver parameter concentrations between DCM, DVD, and disease stages were found. Univariate analysis identified alanine aminotransferase (P < 0.001), aspartate aminotransferase (P = 0.02), and total bilirubin (P = 0.005) as predictors of mortality. In the multivariate analysis, total bilirubin remained an independent predictor of mortality.ConclusionsThe observed differences between DCM, DVD, and disease stages are likely consistent with disease-specific hemodynamics and progression of disease. This and the role of total bilirubin as an independent predictor for mortality indicate that in dogs with DVD and DCM the cardiovascular–hepatic interaction might be of relevance for disease progression and outcome, as reported for humans with cardiac disease. Further studies into the role of hepatic function in canine cardiac disease are required.     

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.     

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.     

Evaluation of risk and clinical outcome of mast cell tumours in pug dogs

Mast cell tumours (MCT) are common in dogs and characterized by diverse biologic behaviour. Our objective was to evaluate the risk of MCT in pugs and to describe the clinical behaviour of MCT in this breed. Data obtained from the Veterinary Medicine Database demonstrate significantly increased frequency of MCT in pugs compared with other dogs (OR = 2.28, 95% CI = 1.81–2.86). The medical records for 25 purebred pugs with a histologic diagnosis of MCT were reviewed. Multiple cutaneous tumours were documented in 14 (56 %) of the dogs. Histologic review of 64 tumours from these dogs confirmed that most tumours (94%) were low to intermediate grade. Sixty‐four per cent of these dogs are still living, while only three dogs (12%) have died due to mast cell disease. A median survival time has not been reached. The median follow‐up time is 660 days from the diagnosis of the first MCT. We conclude that MCT in pugs are relatively benign, despite the presence of multiple cutaneous tumours in most cases. Multiple tumours in breeds with predisposition to MCT may indicate separate primaries rather than advanced stage disease.     

Retrospective review of congenital heart disease in 976 dogs

Background: Knowledge of epidemiology is important for recognition of cardiovascular malformations. Objective: Review the incidence of congenital heart defects in dogs in Italy and assess breed and sex predispositions. Animals: Nine hundred and seventy‐six dogs diagnosed with congenital heart disease (CHD) of 4,480 dogs presented to Clinica Veterinaria Gran Sasso for cardiovascular examination from 1997 to 2010. Methods: A retrospective analysis of medical records regarding signalment, history, clinical examination, radiography, electrocardiography, echocardiography, angiography, and postmortem examination was performed. Breed and sex predisposition were assessed with the odds ratio test. Results: CHD was observed in 21.7% of cases. A total of 1,132 defects were observed with single defects in 832 cases (85%), 2 concurrent defects in 132 cases (14%), and 3 concurrent defects in 12 cases (1%). The most common defects were pulmonic stenosis (PS; 32.1%), subaortic stenosis (SAS; 21.3%), and patent ductus arteriosus (20.9%), followed by ventricular septal defect (VSD; 7.5%), valvular aortic stenosis (AS; 5.7%), and tricuspid dysplasia (3.1%). SAS, PS, and VSD frequently were associated with other defects. Several breed and sex predispositions were identified. Conclusions and Clinical Relevance: The results of this study are in accordance with previous studies, with slight differences. The breed and sex predilections identified may be of value for the diagnosis and screening of CHD in dogs. Additionally, the relatively high percentage of concurrent heart defects emphasizes the importance of accurate and complete examinations for identification. Because these data are from a cardiology referral center, a bias may exist.     

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.