DCM in Dobermans
Dilated Cardiomyopathy (DCM) is a disease of heart muscle that results in a decreased ability of the heart to pump blood. The prognosis for DCM is often poor, with a less than 50% survival rate one year after clinical signs develop, unless a reversible underlying cause is identified. There is no available cure for Dilated Cardiomyopathy, current techniques focus on extending survival time as long as possible. However the focus of this clinical trial is to evaluate a potential curative treatment for cardiomyopathy in the Doberman Pinscher.
About Dilated Cardiomyopathy
Dilated cardiomyopathy (DCM) is a very common form of heart disease in dogs. Only degenerative valve disease (also called mitral valve disease or endocardiosis or mitral insufficiency) and in some places heartworm disease are more common. It was not until the 1970s, when echocardiography began to be performed in veterinary institutions, that dilated cardiomyopathy could be diagnosed non-invasively with any certain degree of accuracy. The reported prevalence in dogs is approximately 0.5%.
Based upon a national database of dogs presented to veterinary schools in North America, we know that 5.8% of the Doberman Pinschers that were seen at a school had DCM, 5.6% of the Irish Wolfhounds presented had DCM. 3.9% of the Great Danes, 3.4 percent of the Boxers and 2.6% of the St. Bernards. In general, the dogs are middle age (4-10 years of age) with Males being over-represented (2:1). 70-80% of the Dobermans with congestive heart failure due to DCM are male and in a recent paper describing the disease in Dalmatians, all of the affected animals were male. This does not mean that female dogs are not affected by DCM, on the contrary, Dr. O’Grady at the University of Guelph found no sex predilection for Dobermans with subclinical (Asymptomatic or occult) DCM.
Familial and Genetic Influences
The general feeling is that most cases of DCM have a familial or genetic basis. This is based upon the observation of a higher prevalence in purebred dogs, in certain breeds and within certain families.
There are also strong indications in other breeds such as the Doberman, where DCM can affect more than 50 percent of family members. In Portuguese Water Dogs DCM appears to be autosomal recessive and in English Cocker Spaniels it is associated with a particular immune deficit. An autosomal dominant mode of transmission has been proposed for the Newfoundlands with DCM.
Taurine In the late 1980s taurine deficiency was recognized as the cause of dilated cardiomyopathy in the majority of cats with DCM. Since then investigators in the field have found a relationship between taurine deficiency and DCM in certain breeds such as Cocker Spaniels, Golden Retrievers and Newfoundlands.
Dogs with preclinical disease may go several years without clinical signs, so the diagnosis does not imply immediate risk of morbidity or mortality. Once the dogs become symptomatic, standard therapies for treatment of the heart failure and/or cardiac arrhythmias should be instituted. Nonetheless, the prognosis for Dobermans with DCM is poor.
Unless a reversible underlying cause is identified (e.g. taurine deficiency, primary tachyarrhythmia), the prognosis for DCM is often poor once overt clinical disease (CHF) develops, with most survival times being in months. The median survival time in a large retrospective study with mostly clinically significant dogs was 19 weeks, with one-year and two-year survival rates of 28% and 14%, respectively. In the Doberman, one-year survival rates of 10% or less have been reported, and treatment with triple therapy yielded a median survival time of 130 days.
Treatment of dilated cardiomyopathy is quite variable and depends upon the severity of the problem as well as the predominating symptom (e.g. fainting vs. coughing). The treatment may include things such as a moderately sodium restricted diet, diuretics, cardiac glycosides, nitrates, ACE inhibitors and various antiarrhythmic agents. Taurine and carnitine may also be added.
- A diagnosis of DCM and previous evidence of congestive heart failure which has been controlled with medical management.
- A circulating neutralizing antibody titer to the virus vector of less than 1:20
- Owner agreement to authorize participation with informed consent and collection of the heart following euthanasia or death from any cause.
- Clear of extra-cardiac disease, congenital heart disease or primary mitral valvular disease
Procedures covered by the study include bloodwork, ECH, and ECG. Enrolled patients also receive repeat screenings at no cost. The value of the study procedure is estimated at $5,000. The cardiology exam ($200) is NOT covered by the study, nor is the cost of thoracic radiographs if not provided by referring veterinarian.
At enrollment, an antibody titer, hematology and biochemistry panel will be used for screening purposes. Dogs will undergo a 3-minute electrocardiogram (ECG), a complete echocardiogram (ECHO) and the owners will complete a quality of life questionnaire. In order to participate in the study, dogs fulfilling the requirements will be randomly assigned to one of two groups: the placebo arm (cardiac injection with saline) or the gene therapy group (cardiac injection with the virus vector: AAV2/6-ARC-s100a1). Standard medical management for DCM and congestive heart failure will continue throughout the study in all dogs. Saline instead of empty virus will be used as the placebo so that control dogs can undergo gene delivery if the treatment group demonstrates a significant improvement compared to the placebo group. Owners will need to commit to re-evaluations at 2, 4, 6, 9, and 12 months at the University of Florida following therapy.
1. Department of Small Animal Clinical Sciences, University of Florida
2015 SW 16th Ave, Gainesville, FL 32608
Chief Medical Officer, DVM, DACVIM
Dr. David Bruyette received his Doctor of Veterinary Medicine degree from the University of Missouri. Subsequently, he completed an internship at Purdue University and residency in internal medicine at the University of California-Davis. He was a staff internist at the West Los Angeles Veterinary Medical Group and a member of the Department of Comparative Medicine at Stanford University. Dr. Bruyette was an Assistant Professor and Head of Internal Medicine at Kansas State University and Director of the Analytical Chemistry Laboratory at Kansas State. He was most recently, Medical Director of the VCA West Los Angeles Animal Hospital, one of the largest 24-hour emergency/specialty practices in the country. Dr. Bruyette is a diplomate of the American College of Veterinary Internal Medicine and a member of the Endocrine Society.