Influence of lifetime food restriction on causes, time, and predictors of death in dogs

OBJECTIVE: To describe effects of lifetime food restriction on causes of death and the association between body-mass characteristics and time of death in dogs. DESIGN: Paired-feeding study. ANIMALS: 48 dogs from 7 litters. PROCEDURES: Dogs were paired, and 1 dog in each pair was fed 25% less food than its pair mate from 8 weeks of age until death. Numerous morphometric and physiologic measures were obtained at various intervals throughout life. Associations of feeding group to time and causes of death were evaluated, along with important associated factors such as body composition components and insulin-glucose responses. RESULTS: Median life span was significantly longer for the group that was fed 25% less food, whereas causes of death were generally similar between the 2 feeding groups. High body-fat mass and declining lean mass significantly predicted death 1 year prior to death, and lean body composition was associated with metabolic responses that appeared to be integrally involved in health and longevity. CONCLUSIONS AND CLINICAL RELEVANCE: Results were similar to results of diet restriction studies in rodents and primates, reflecting delayed death from species- and strain-specific intrinsic causes. Clinicians should be aware that unplanned body mass changes during mid- and later life of dogs may indicate the need for thorough clinical evaluation.     

Life expectancy in a birth cohort of Boxers followed up from weaning to 10 years of age

OBJECTIVE: To determine mortality rate over time, risk factors for death, and heritability of life expectancy in Boxers. ANIMALS: 1,733 purebred Boxers born in The Netherlands between January 1994 and March 1995. PROCEDURE: Dogs were followed up from weaning (ie, 49 days of age) to 10 years of age through use of a written questionnaire sent to owners every 6 months. Mortality rate over time, risk factors potentially associated with death, and heritability of life expectancy were examined by use of a proportional hazards model based on the Weibull distribution. RESULTS: stimated mortality rate during the 10-year study period for this birth cohort of Boxers was 45%. The probability of surviving to 5 years of age was 88%; the probability of surviving to 10 years of age was 55%. Estimated effective heritability of life expectancy was 0.076, meaning that in this population, an estimated 76% of the observed variation in life expectancy could be attributed to genetic differences among dogs that were passed from parents to their offspring. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that cumulative incidence of death from weaning to 10 years of age among this birth cohort of Boxers was 45%. The estimated heritability of life expectancy suggested that life expectancy can be improved by use of selective breeding.     

Premature death, risk factors, and life patterns in dogs with epilepsy

BACKGROUND: Epilepsy in dogs is often difficult to medically control, resulting in premature death of dogs with epilepsy. However, the risks of premature death are not known. HYPOTHESIS: Dogs with epilepsy have an increased risk of premature death as compared to a general population of dogs. ANIMALS: Sixty-three dogs diagnosed with epilepsy between 1993 and 1996 were included in this study. METHODS: A prospective longitudinal study of the population was performed from the diagnosis of epilepsy until the time of euthanasia, death, or a maximum of 12 years to investigate mortality and risk factors. Information about sex, onset, type, frequency, and control of seizures, remission of epilepsy, death, cause of death, and owner's perspective was collected and analyzed. RESULTS: The median age at death of dogs was 7.0 years. The life span of dogs in which euthanasia or death was directly caused by their epileptic condition was significantly shorter as compared with epileptic dogs that were euthanized because of other causes (P = .001). The median number of years that a dog lived with epilepsy was 2.3 years. Females lived longer with epilepsy than males (P = .036). Seizure type (primary generalized versus focal seizures) was not significantly associated with survival time. The remission rate of epilepsy (spontaneous remission and remission with treatment) was 15%. CONCLUSION AND CLINICAL IMPORTANCE: The diagnosis of epilepsy implies an increased risk of premature death. The prognosis for dogs with epilepsy is dependent on a combination of veterinary expertise, therapeutic success, and the owner's motivation.     

Mortality of purebred and mixed-breed dogs in Denmark

Causes of death and age at death of 2928 dogs are reported from a questionnaire study among members of the Danish Kennel Club (DKC) in 1997. The dogs represented 20 breeds, 15 breed-groups and a group of mixed-breed dogs. The median age at death for all dogs in the study was 10.0 years. Mixed-breed dogs had a higher median age at death (11.0 years) than the entire population, but breeds like Shetland Sheepdog, Poodle and Dachshund exceeded this age (12 years). The Bernese Mountaindog, the group of Molossian types and the Sighthounds had the shortest life span with a median age at death of 7.0 years. Old age was the most frequent reported cause of death (20.8%) followed by cancer (14.5%), behavioural problems (6.4%) accidents (6.1%), hip dysplasia (4.6%), heart diseases (4.6%) and spinal diseases (3.9%). Breed-specific proportional mortalities with 95% confidence limits are given for the six most prevalent specific causes of death.     

The Natural Clinical History of Canine Congenital Subaortic Stenosis

The demographics and natural clinical history of canine congenital subaortic stenosis (SAS) were evaluated by retrospective analysis of 195 confirmed cases (1967 to 1991), 96 of which were untreated and available for follow-up evaluation. Of these, 58 dogs had left ventricular outflow systolic pressure gradients available for assessment of severity. All 195 dogs were used for demographic analysis. Breeds found to be at increased relative risk included the Newfoundland (odds ratio, 88.1; P < .001), Rottweiler (odds ratio, 19.3; P < .001), Boxer (odds ratio, 8.6; P < .001), and Golden Retriever (odds ratio, 5.5; P < .001). Dogs with mild gradients (16 to 35 mm Hg) and those that developed infective endocarditis or left heart failure were diagnosed at older ages than those with moderate (36 to 80 mm Hg) and severe (>80 mm Hg) gradients. Of 96 untreated dogs, 32 (33.3%) had signs of illness varying from fatigue to syncope; 11 dogs (11.3%) developed infective endocarditis or left heart failure. Exercise intolerance or fatigue was reported in 22 dogs, syncope in 11 dogs, and respiratory signs (cough, dyspnea, tachypnea) in 9 dogs. In addition, 21 dogs (21.9%) died suddenly. Sudden death occurred mainly in the first 3 years of life, primarily but not exclusively, in dogs with severe obstructions (gradient, > 80 mm Hg; odds ratio, 16.0; P < .001). Infective endocarditis (6.3%) and left heart failure (7.3%) tended to occur later in life and in dogs with mild to moderate obstructions. Left heart failure was uncommon in the absence of additional congenital defects or infective endocarditis. Dogs with mild obstructions lived longer than other groups and tended to remain asymptomatic. The majority of dogs with severe obstructions died before 3 years of age and had a high prevalence (8 of 15) of sudden death. The prognosis for long-term survival in dogs with untreated mild or moderate SAS is favorable (median survival, 30.5 and 51.1 months, respectively), while the prognosis for dogs with severe SAS is very poor (median survival, 18.9 months).     

Mortality related to general anaesthesia and sedation in dogs under UK primary veterinary care

ObjectivesTo quantify and explore risk factors in dogs seen at primary care UK veterinary clinics for general anaesthetic (GA)/sedative-related death overall, in addition to neuter-specific procedures.Study designA nested case-control study within UK primary care veterinary electronic patient record surveillance programme, VetCompass, including over 300 UK veterinary practices.AnimalsA total of 157,318 dogs undergoing GA/sedative events.MethodsCases included dogs undergoing GA/sedative events between January 2010 and December 2013 with GA/sedative-related death recorded within 48 hours or 2 weeks of the event. Controls were randomly selected from dogs undergoing GA/sedation that did not die within these time periods. Risks of GA/sedative-related death for all surgeries and neuter-specific surgeries were estimated. Demographic and clinical associations with GA/sedative-related death were reported as odds ratios following multivariable logistic regression modelling. Statistical significance was set at 5%.ResultsFrom 157,318 dogs with a GA/sedative event, there were 159 (0.10%) within 48 hours and 219 (0.14%) GA/sedative-related deaths within 2 weeks. Within 89,852 dogs that underwent a neuter surgery, there were eight GA/sedative related (0.009%). Greater age, poorer American Society of Anaesthesiologists health status scores and more urgent procedures were associated with greater odds of death. Compared with mixed breeds, Rottweilers and West Highland White Terriers had greater odds and Cocker Spaniels had lower odds of GA/sedative-related death.Conclusions and clinical relevanceThe overall risk for GA/sedative related death was relatively low, particularly among the subset of dogs undergoing castration or ovariohysterectomy surgery. Associations and risk estimates may assist shared decision-making in clinical practice and provide benchmarks for audit.     

Effects of diet restriction on life span and age-related changes in dogs

OBJECTIVE: To evaluate the effects of 25% diet restriction on life span of dogs and on markers of aging. DESIGN: Paired feeding study. ANIMALS: 48 Labrador Retrievers. PROCEDURES: Dogs were paired, and 1 dog in each pair was fed 25% less food than its pair-mate from 8 weeks of age until death. Serum biochemical analyses were performed, body condition was scored, and body composition was measured annually until 12 years of age. Age at onset of chronic disease and median (age when 50% of the dogs were deceased) and maximum (age when 90% of the dogs were deceased) life spans were evaluated. RESULTS: Compared with control dogs, food-restricted dogs weighed less and had lower body fat content and lower serum triglycerides, triiodothyronine, insulin, and glucose concentrations. Median life span was significantly longer for dogs in which food was restricted. The onset of clinical signs of chronic disease generally was delayed for food-restricted dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that 25% restriction in food intake increased median life span and delayed the onset of signs of chronic disease in these dogs.     

Causes of death or reasons for euthanasia in military working dogs: 927 cases (1993-1996)

OBJECTIVE: To determine causes of death or reasons for euthanasia in a population of military working dogs. DESIGN: Retrospective study. ANIMALS: 927 military working dogs. PROCEDURE: Records of all military working dogs that died during the period from 1993 to 1996 were evaluated for cause of death or reason for euthanasia by review of necropsy and histopathology reports, death certificates, and daily clinical treatment sheets. A single primary cause of death or euthanasia was determined. RESULTS: Although sexually intact male dogs were more numerous in the study population, castrated male dogs typically lived longer than spayed females or sexually intact males. Leading causes of death or euthanasia (76.3% of all dogs) were appendicular degenerative joint disease, neoplasia, spinal cord disease, nonspecific geriatric decline, and gastric dilatation-volvulus. Compared with German Shepherd Dogs, Belgian Shepherd Dogs were at increased risk for death attributable to neoplasia, behavior, and respiratory tract disease. German Shepherd Dogs had nearly twice the risk for death associated with spinal cord diseases, compared with Belgian Shepherd Dogs. CONCLUSIONS AND CLINICAL RELEVANCE: For most military working dogs, death or euthanasia results from a few diseases commonly associated with advanced age. Some breed differences in risk for these diseases may exist, which clinicians should consider in the procurement and long-term management of these dogs.     

Nutritional management of chronic renal disease in dogs and cats.

Chronic renal disease is a leading cause of death in dogs and cats. Recent clinical studies show that nutrition plays a key role in improving quality of life and life expectancy of these patients. Typical nutritional interventions include modifying the protein, phosphorus, and lipid concentrations. Nutritional therapy, however, does not simply mean changing the diet; consideration must also be given to ensuring adequate caloric intake and to the method of feeding. Monitoring the effects of the dietary therapy is also crucial to ensure that the patients are responding appropriately to the selected nutritional modifications. Nutritional management must be coordinated with medical management for long term successful treatment.     

Longevity of British breeds of dog and its relationships with sex, size, cardiovascular variables and disease

The results of a questionnaire provided data about owners' perceptions of the cause of death of over 3000 British dogs. The mean age at death (all breeds, all causes) was 11 years one month, but in dogs dying of natural causes it was 12 years eight months. Only 8 per cent of dogs lived beyond 15, and 64 per cent of dogs died of disease or were euthanased as a result of disease. Nearly 16 per cent of deaths were attributed to cancer, twice as many as to heart disease. Neutered females lived longer than males or intact females, but among dogs dying of natural causes entire females lived slightly longer. In neutered males the importance of cancer as a cause of death was similar to heart disease. Mongrels lived longer than average but several breeds lived longer than mongrels, for example, Jack Russells, miniature poodles and whippets. There was no correlation between longevity and cardiovascular parameters (heart rate, systolic, diastolic, pulse and mean arterial pressure, or the combination of heart rate and pulse pressure) but smaller dogs had longer lifespans. The results also include breed differences in lifespan, susceptibility to cancer, road accidents and behavioural problems as a cause of euthanasia.     

Evaluation of aging on muscle blood flow in conscious healthy dogs by duplex Doppler ultrasonography

According to a study conducted on a population of 9,248 subjects, cardiac diseases are the second most prevalent cause of death in the dog. During the last decades, a common scenario has been the increase on life expectancy of dogs. The exact relationship between the negative modifications of cardiovascular function and the development of specific cardiovascular diseases is difficult to ascertain, and also, the effect of age per se on vascular impedance is important. It may result in limited cardiovascular reserve under conditions of increase demand in senescent animals. To evaluate the effect of age on the peripheral vasculature specifically, the objective of this study was to compare parameters of the regional blood flow as well as compliance and resistance indexes in the femoral arterial system of younger and older conscious healthy dogs by duplex Doppler ultrasonography. The data were collected from 16 mixed-breed dogs divided into two groups: young and old healthy dogs. In all dogs Doppler spectra blood flow patterns of the femoral artery were triphasic. Significant differences were not found between the parameters measured for young and old groups. Despite this, the average value of femoral flow volume in the older group was approximately 50% lower than the younger group. This finding could play an important role in limiting exercise response with age. In order to validate these speculations, further studies should be performed in aged dogs.     

Mortality in north american dogs from 1984 to 2004: an investigation into age-, size-, and breed-related causes of death

Background: Anecdotal beliefs and limited research suggest variable patterns of mortality in age, size, and breed cohorts of dogs. Detailed knowledge of mortality patterns would facilitate development of tailored health‐maintenance practices and contribute to the understanding of the genetic basis of disease. Hypothesis/Objectives: To describe breed‐specific causes of death in all instances of canine mortality recorded in the Veterinary Medical Database (VMDB) 1 between 1984 and 2004. We hypothesized that causes of death, categorized by organ system (OS) or pathophysiologic process (PP), would segregate by age, body mass, and breed. Animals: 74,556 dogs from the VMDB for which death was the outcome of the recorded hospital visit. Methods: Retrospective study. Causes of death from abstracted VMDB medical records were categorized by OS and PP and analyzed by age, breed, and breed‐standard mass of dog. Results: Causes of death, categorized by OS or PP, segregated by age, breed, and breed‐standard mass. Young dogs died more commonly of gastrointestinal and infectious causes whereas older dogs died of neurologic and neoplastic causes. Increasing age was associated with an increasing risk of death because of cardiovascular, endocrine, and urogenital causes, but not because of hematopoietic or musculoskeletal causes. Dogs of larger breeds died more commonly of musculoskeletal and gastrointestinal causes whereas dogs of smaller breeds died more commonly of endocrine causes. Conclusions and Clinical Importance: Not all causes of death contribute equally to mortality within age, size, or breed cohorts. Documented patterns now provide multiple targets for clinical research and intervention.     

Association between the findings on magnetic resonance imaging screening for syringomyelia in asymptomatic Cavalier King Charles spaniels and observation of clinical signs consistent with syringomyelia in later life

A questionnaire-based study was used to investigate the association between the findings on magnetic resonance imaging (MRI) screening for syringomyelia (SM) in 79 asymptomatic Cavalier King Charles spaniels (CKCS) and the subsequent development of clinical signs consistent with SM in later life. Owners reported clinical signs consistent with SM in 13/79 (16%) dogs at the time of the questionnaire. A significantly greater proportion of CKCS with a syrinx visible on MRI screening showed clinical signs in later life (9/25, 36%) than dogs without a visible syrinx (4/54, 7%; odds ratio 6.9). Whether the findings of MRI screening can be used to indicate the likelihood of an asymptomatic CKCS developing clinical signs consistent with SM in later life warrants further prospective study in a larger cohort of dogs.     

A prospective study on canine hip dysplasia and growth in a cohort of four large breeds in Norway (1998-2001)

The study-objective was to measure the effect of weight and growth related parameters on the risk of development of Canine Hip Dysplasia (CHD). The hypothesis was that heavy and fast growing dogs of large sized breeds were at increased risk of development of CHD compared to lighter and slower growing dogs. A prospective cohort study was conducted among dogs of four large breeds: Newfoundland (NF), Leonberger (LEO), Labrador retriever (LR), and Irish wolfhound (IW). The dogs were privately owned with individualized nutrition and environment, and they were followed from birth and throughout the growth period until the official screening for CHD was performed. The study sample consisted of 501 dogs from 103 litters, with the breed distribution 125 NF, 180 LEO, 133 LR, and 63 IW. Because the dogs were clustered in litters a multivariable random effects logistic regression model was used to assess statistically significant growth-related risk factors for CHD. The estimated incidence risk of CHD was 36% in NF, 25% in LEO, 20% in LR, and 10% in IW. Based upon the final multilevel model it appears that the odds of CHD among both LR and IW (odds ratio (OR) 0.22) are about one-fifth of the odds for NF. The odds for LEO (OR 0.60) are not significantly different from NF. There appeared to be an inverse relationship between body weight at 3 months of age and odds of CHD, with an OR of 0.89 (P=0.044). The degree of clustering at the litter-level was high (22.6%) and highly significant (P<0.001). Findings failed to support the hypothesis that heavy and fast growing dogs from four large sized breeds were at increased risk for development of CHD. There might be other unmeasured environmental risk factors for CHD in this cohort of dogs, although the contribution of the genetic variance to the litter-level clustering also needs further investigation.     

Ureterocolonlc Anastomosis in Ten Dogs with Transitional Cell Carcinoma

Ureterocolonic anastomosis (UCA) was performed in 10 dogs with transitional cell carcinoma of the urinary bladder trigone or the urethra, or both. All grossly visible tumor was excised. All of the dogs recovered from anesthesia and surgery and had anal continence with no urine leakage. One dog died of undetermined causes 7 days after surgery. Nine dogs survived 1 to 5 months. The owners of eight of the dogs considered their dog's quality of life to be acceptable. Four dogs were euthanatized because of neurologic disease, three of which also had nausea and vomiting. The neurologic and gastrointestinal signs may have been caused by hyperammonemia, metabolic acidosis, and uremia. Blood ammonia levels were elevated in two dogs with neurologic signs. Hyperchloremic metabolic acidosis that was reversible with bicarbonate therapy was diagnosed in five dogs. All of the dogs were azotemic because of intestinal recycling of urea. Serum creatinine concentrations increased in four dogs after surgery. Drug-induced renal disease may have developed in two dogs. Pyelonephritis developed in five kidneys, two of which had outflow obstruction and two had bilateral hydroureteronephrosis before the UCA. In this small number of dogs, surgical excision of transitional cell carcinoma was not curative with six dogs having confirmed metastatic lesions at the time of death.     

A longitudinal study on diarrhoea and vomiting in young dogs of four large breeds

Background

Prospective studies to document the occurrence of canine diarrhoea and vomiting are relatively scarce in dogs, and the majority of published studies are based on information from clinical records. This study investigates the incidence risk of diarrhoea and vomiting as well as potential risk factors.

Methods

A cohort study of 585 privately owned dogs of four breeds: Newfoundland, Labrador retriever, Leonberger, and Irish wolfhound. The owners maintained a continuous log regarding housing, exercise, nutrition, and health of their dogs. Episodes of diarrhoea and vomiting were recorded in a consecutive manner in a booklet. The owners completed the questionnaires and reported information at three, four, six, 12, 18, and 24/25 months of age, called observational ages.Associations with potential risk factors for diarrhoea and vomiting were investigated in separate generalized estimating equation analyses.

Results

The incidence of both diarrhoea and vomiting was influenced by breed. Both diarrhoea and vomiting were relatively common in young dogs, occurring most frequently during the first months of life. After three months of age, the odds of diarrhoea were significantly lower when compared to the observational period seven weeks to three months (OR ranging from 0.31 to 0.70 depending on the period). More males than females suffered from diarrhoea (OR = 1.42). The occurrence of diarrhoea was more common in dogs that also experienced episode(s) of vomiting during the study period (OR = 5.43) and vice versa (OR = 5.50). In the majority of dogs episodes of diarrhoea and vomiting did not occur at the same time. Dogs in urban areas had higher odds (OR = 1.88) of getting diarrhoea compared to dogs living in rural areas. The occurrence of both diarrhoea and vomiting demonstrated a seasonal variation with higher incidence during the summer months.

Conclusion

Both diarrhoea and vomiting occurred most frequently during the first months of life. The incidence of diarrhoea and vomiting was significantly different between breeds. Diarrhoea occurred more frequently in males and in dogs living in urban areas. Also, a positive association between the occurrence of diarrhoea and vomiting in the same dog was found.     

Surgery alone or in combination with radiation therapy for treatment of intracranial meningiomas in dogs: 31 cases (1989-2002)

OBJECTIVE: To compare, for dogs with intracranial meningiomas, survival times for dogs treated with surgical resection followed by radiation therapy with survival times for dogs treated with surgery alone. DESIGN: Retrospective study. ANIMALS: 31 dogs with intracranial meningiomas. PROCEDURE: Medical records of dogs with histologic confirmation of an intracranial meningioma were reviewed. For each dog, signalment, clinical signs, tumor location, treatment protocol, and survival time were obtained from the medical record and through follow-up telephone interviews. RESULTS: Dogs that underwent tumor resection alone and survived > 1 week after surgery had a median survival time of 7 months (range, 0.5 to 22 months). Dogs that underwent tumor resection followed by radiation therapy had a median survival time of 16.5 months (range, 3 to 58 months). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that in dogs with intracranial meningiomas, use of radiation therapy as a supplement to tumor resection can significantly extend life expectancy.     

Epidemiologic factors, clinical findings, and vaccination status of rabies in cats and dogs in the United States in 1988. National Study Group on Rabies

Despite the availability of rabies vaccination through private veterinarians and government-sponsored rabies control programs, rabies was reported in an average of 338 cats and dogs per year from 1980 through 1987 in the United States. Information was collected on 90% of the 183 cats and 97% of the 119 dogs that were reported to have rabies in the continental United States in 1988. The median age of rabid cats and dogs was 1 year, and 81% were from rural areas. Compared with rabid cats, rabid dogs were more likely to have been male (66 vs 42%, odds ratio = 2.6), to have been kept as pets (84 vs 43%, odds ratio = 6.8), and to have had reported contact with wildlife before onset of illness (38 vs 14%, odds ratio = 3.8). Rabid cats accounted for a greater proportion of human rabies postexposure prophylaxis, bites to people, and exposures to other animals than did rabid dogs. Although the clinical signs of rabies varied, rabid cats were more likely than dogs to have had aggressive behavior (55 vs 31%, odds ratio = 2.8). In contrast, rabid dogs were more likely than cats to have had an illness consistent with a paralytic process. The median period between onset of illness and death was 3 days (range, less than 1 to 10) in rabid cats and dogs that were allowed to die of rabies. Vaccine failures were documented in 3 (1%) rabid animals (2 cats and 1 dog). All animals had received only a single dose of vaccine in their lifetime and were vaccinated when they were between 3 and 6 months old.     

Effect of benazepril on survival and cardiac events in dogs with asymptomatic mitral valve disease: a retrospective study of 141 cases

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) improve quality of life and extend the life span of dogs with naturally acquired ISACHC class II-III congestive heart failure (CHF). However, their effects on asymptomatic heart disease remain controversial. HYPOTHESIS: Benazepril (BNZ), an ACEI, could have beneficial effects at the asymptomatic stage of degenerative mitral valve disease (MVD). ANIMALS: Dogs with ISACHC class Ia MVD and moderate-to-severe mitral regurgitation (MR) assessed by the color Doppler mapping technique at entry (Day 0) were retrospectively included. METHODS: Dogs were assigned to the treated group (BNZ group) if they received BNZ (and no other cardiac medication) from Day 0 or to the untreated group (UT group) if they did not receive any cardioactive treatment until occurrence of CHF. RESULTS: A total of 141 dogs were included in the study, 66 in the BNZ group (dosage: 0.30 +/- 0.13 mg/kg) and 75 in the UT group. In the population (n = 93) including all breeds except Cavalier (CKC) and King Charles Spaniels (KC), median survival time to all causes of death in the BNZ group (n = 34, 3.3 years) was significantly longer than in the UT group (n = 59, 1.9 years) as was time to cardiac event (P < .05). Conversely, no effect of the BNZ treatment was observed in the CKC and KC population. CONCLUSIONS AND CLINICAL RELEVANCE: BNZ had beneficial effects in asymptomatic dogs other than CKC and KC affected by MVD with moderate-to-severe MR. Breed distribution should be taken into account for interpretation of clinical trials performed in dogs with cardiac disease.