February 7, 2010
Veterinary cardiology research projects are gaining interest and funding from human medical associations and animal alike.
Morris Animal Foundation lists 17 cardiac grants it has awarded for canine and feline cardiac research in the last two years alone. All colleges of veterinary medicine dedicate time and resources to carrying out the research, allowing the specialty of cardiac medicine to reach new heights.
Mitral valve disease and dilated cardiomyopathy (DCM) are the most common canine heart diseases, while hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy are the most common heart diseases found in cats, says Mark A. Oyama, DVM, Dipl. ACVIM (cardiology). Researchers are investigating these and other cardiac diseases to identify the cause of disease–whether a genetic role exists, how to diagnose earlier and how to most effectively treat the diseases.
“For many diseases we suspect or have shown a congenital or heritable predilection such as feline HCM, Boxer DCM, but many other causes of disease is largely unknown,” says Dr. Oyama, an associate professor at the University of Pennsylvania School of Veterinary Medicine.
Because genetics plays such a large role in breed-specific cardiac disease, Washington State University created the canine cardiac genetic lab and is studying boxer, golden retriever, Rottweiler and Doberman heart diseases. Recently, Kathryn M. Meurs, DVM, Dipl. ACVIM (cardiology), discovered a mutant gene in the boxer breed that causes cardiomyopathy, a heart disease that can be fatal in animals and humans.
“This detection will help avoid breeding boxer dogs with the mutation,” says Bryan Slinker, DVM, Ph.D., dean of WSU's College of Veterinary Medicine. “This also provides an extraordinary advancement to the study of human heart diseases resulting from electrical conduction defects and the resulting heart muscle changes that occur."
Much of the veterinary cardiac research conducted focuses on how and why the animal is suffering from the specific heart disease. According to American College of Veterinary Internal Medicine cardiology specialists, an estimated 10 percent of dogs presenting to primary care veterinary practices have heart disease. Of those presentations, Chronic Valvular Heart Disease (CVHD), the most commonly diagnosed heart disease in dogs, accounts for about 75 percent of cases seen by veterinary practices.
Guidelines for the treatment of CVHD were created by an ACVIM cardiology panel in an effort to develop screening programs for the presence of CVHD in at-risk dogs. The goal of the guidelines is to identify interventions that can decrease the incidence of disease development and identify symptomatic dogs so medical treatment can be given earlier. The ACVIM hopes veterinarians use the panel’s suggestion as a standard when treating CVHD patients.
While humans can sometimes prevent heart disease through a healthy diet, no such correlation exists for dogs, specialists say. After a diagnosis is made, nutrition plays a role in controlling the disease but has no known preventive capabilities.
“The only canine heart disease that is preventable is heartworm disease,” says Clarke Atkins, DVM, Dipl., ACVIM (cardiology). Dr. Atkins is the Jane Lewis Seaks Distinguished Professor of Companion Animal Medicine at North Carolina State University.
“In 2001 25 million dogs were diagnosed with the disease and I suspect that’s just the tip of the iceberg,” Atkins says. “Several years later, in 2007, another poll was taken and the incidence had gone up, not down, despite very effective monthly prevention. The problem with this disease is that owners are not compliant. They don’t see the need to give medication when the animal isn’t sick, or they purchase the preventive but forget to give it, or give it irregularly. A vaccine may help improve this common cardiac disease, but so far there isn’t one commercially available.”
Diet can, however, lead to cardiac issues in cats. Dilated cardiomyopathy comes secondary to taurine deficiency but is reversible with taurine supplementation if treated early. The cat’s prognosis worsens if there is extensive permanent change in the myocardium. This disease, however, is less common in the owned-cat population since Paul Pion, DVM, Dipl. ACVIM (cardiology), discovered the cause of the problem in 1987 and the cure. Commercial cat food manufacturers have since altered their formulas and the deficiency is almost completely absent.
Though pacemaker implantation isn’t common in dogs, the number of dogs that could benefit from the procedure is great. About two permanent pacemaker surgeries are performed each month on dogs at the University of Florida.
Amara Estrada, DVM, Dipl. ACVIM (cardiology), is researching the best implantation site for the pacemaker in a dog’s heart. Currently, the most common spot is from the jugular vein to the right ventricle.
“We are hoping to find a more natural position in which to place the pacemaker,” Dr. Estrada says. “We have 16 dogs in the trial now and hope to have at least 30 before concluding the study. We are looking at the immediate and long-term differences in cardiac function as it relates to pacemaker placement. The results will allow veterinarians to place pacemakers in the optimal location to extend and improve patients’ lives.”
The placement possibilities include the right ventricle, left ventricle, both ventricles and the atrium.
Estrada began researching uses of stem cell therapy in Dobermans with asymptomatic dilated cardiomyopathy (DCM) in December 2009 from a $72,000 grant from the National Doberman Research Foundation. She says she hopes to eventually have funding to study all canine breeds suffering from the disease.
“We use an isolated population of cells from a dog called mesenchymal stem cells that do not undergo immune detection,” Estrada says. “We store aliquots of cells for each individual patient and will evaluate the efficacy of the adult stem cell transplantation into the dilated, failing myocardium of DCM dogs.”
Estrada’s goal is to provide the groundwork for a new treatment option for these patients.
Teresa DeFrancesco, DVM, Dipl. ACVIM (cardiology), Dipl. ACVECC, is studying asymptomatic HCM cats undergoing clinical treatment using atenolol to determine whether early medical therapy improves the outcome. Dr. DeFrancesco, an associate professor at North Carolina State University, started enrolling patients in January for the MAF-funded study.
“Part of the dilemma is we don’t know how to delay disease progression in cats that are identified as having HCM,” DeFrancesco says. “There is no study to date about atenolol, and the median survival time for diagnosed cats is four to seven years, so it’s hard to convince an owner to pill a cat for five years in part of a trial when the pill might be a placebo. This trial offers a potentially more positive outcome because all of the CM cats will receive the drug on trial.”
Potential patients were identified by sending letters to nearby veterinarians who could refer clients whose cats fit the description. DeFrancesco is interested in cats 1 to 10 years old who have a heart murmur. The cats are screened to see whether they qualify. Those with atrial enlargement are especially attractive for the study.
The cats’ asymptomatic HCM will be evaluated partly using a collar excelometer that measures vertical and horizontal movements.
“Cardiac biomarkers via blood tests will show the severity of disease,” DeFrancesco says. “Owner questionnaires will also be used to provide information. We hope to have 60 cats total in this study–30 healthy cats will serve as the baseline and 30 HCM cats will be evaluated pre- and post-treatment. The main thrust of this research is to detect disease earlier and reveal a more effective treatment.”
Cornell University researcher Bruce Kornreich, DVM, Dipl. ACVIM (cardiology), is looking at mitral valve thickening from endocarditis in dogs–primarily found in Cavalier King Charles Spaniels.
“We are looking at the disease at the molecular mechanism level,” Dr. Kornreich says. “We want to get as many dogs as possible in this basic science study. We’ll be looking at the strains of cultures of valvular cells and comparing them to normal cells.”
Kornreich says the research is propelled by an interest in better understanding the disease so it can be treated more efficiently.
One of Atkins’ research projects looked at the potential pharmaceutical impact on heart failure in dogs, using six healthy adult male beagles. He wanted to determine what drug or combination of drugs activates the Renin-angiotensin-aldosterone system (RAAS), a hormone system that helps regulate long-term blood pressure and volume in the body. In the past, ACE inhibitors alone have been the most useful treatment of the disease.
Each dog received amlodipine used to treat both heart failure and hypertension, (0.57 mg/kg b.i.d.) for six days, followed by amlodipine (0.57 mg/kg b.i.d.) and enalapril (0.57 mg/kg b.i.d.) for four days. Blood pressure, heart rate, serum chemistries and urinary aldosterone excretion, as a measure of RAAS activation, were compared with baseline values.
The animals’ blood pressure fell by about 7 percent with amlodipine (P = 0.05) and 7 percent further with the combination of amlodipine and enalapril (P < 0.01). Blood urea nitrogen increased with the combination (P < 0.05). RAAS activation, based on 24-hour urinary aldosterone excretion and by aldosterone:creatinine ratio, was increased by approximately threefold (P < 0.05) with amlodipine administration. This effect was weakened by enalapril, so much that aldosterone excretion was no longer different from that observed under control conditions, though values for 24-hour aldosterone excretion did not return to pretreatment levels.
“The research showed that while amlodipine is a useful drug, it does not activate RAAS and therefore should be accompanied by the use of some drug which blunts RAAS such as an ACE-I,” Atkins says.
Karsten Schober, DVM, Ph.D., of Ohio State University, recently completed research on noninvasive predictions of congestive heart failure in dogs. Dr. Schober initially was interested in determining whether cardiac ultrasound–Doppler echocardiography–could predict congestive heart failure. He wanted to reduce the high radiation levels that patients and staff were exposed to when the 20 to 40 films were taken to make a diagnosis.
“We tested 70 dogs in this study and we found Doppler is a very reliable way of diagnosing the disease,” Schober says. “At home, owners could monitor the animal’s respirations. If the respiration rate went below a certain number, we could determine the dog did have the disease. We had owners track their dogs’ respirations and by comparing their findings to traditional methods of diagnosis we found this way of monitoring CHF was much less invasive for early detection and disease monitoring.”
Schober says a new use for sildenafil (Viagra), helps reduce artery pressure when used with L-arginine in dogs with pulmonary disease. As much as 80 to 90 percent of dogs with mitral valve disease also have pulmonary disease.
“I am conducting an ongoing clinical trial using these drugs,” Schober says. “About one-third of all dogs responded well to this treatment, which is better than drugs used for treatment in the past. Owners say the dogs seem to feel better. We are hoping these drugs can extend the animals’ lives and the quality of life.”
Specialists say evidenced-based medicine has become the standard, and owners’ willingness to pursue treatments means cardiology research will continue to have a strong industry presence.
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