By Dr. Becker
A team of researchers has identified a gene mutation responsible for canine subvalvular aortic stenosis (SAS). The study, led by University of California, Davis veterinary cardiologist Joshua Stern appeared in the September 2014 edition of the journal Human Genetics.1
The researchers analyzed thousands of Newfoundland genes to identify the mutation associated with SAS. The mutation occurs in the phosphatidylinositol-binding clathrin assembly protein (PICALM) gene. Interestingly, according to Dr. Stern, this is the same gene mutation that has been linked to the development of plaque-like lesions in the brains of Alzheimer’s sufferers.
In addition to the gene analysis, the research team also conducted a pedigree analysis in a family of 45 Newfoundland dogs to look for inheritance patterns of the PICALM gene mutation. They were able to confirm that only one parent needs to carry the mutation to pass it to offspring, and not all dogs with the mutation develop the disease.
"Our hope now is that breeders will be able to make informed breeding decisions and avoid breeding dogs that harbor this mutation, thus gradually eliminating the disease from the Newfoundland breed," Stern said in a university news release.2
Subvalvular Aortic Stenosis
Subvalvular aortic stenosis (SAS) (frequently shortened to aortic stenosis or subaortic stenosis) is the most common type of inherited heart disease in Golden Retrievers, Newfoundlands, and Rottweilers.
The disease is characterized by a narrowing (stenosis) caused by a ridge or ring of abnormal tissue growth that inhibits blood flow from the heart to the aorta. The narrowing is classified as mild, moderate, or severe.
Sadly, seemingly healthy dogs with SAS can die suddenly, in part because even animals with severe stenosis may show no clear signs of illness. And often their owners don’t recognize that episodes of exercise intolerance, or fainting or collapsing from excitement are red flags for SAS.
Symptoms of SAS
In mild cases of subvalvular aortic stenosis, there are typically no observable clinical signs of disease.
In some moderate cases, and almost all severe cases of SAS, symptoms include difficulty breathing, weakness, fainting, and in extreme cases, sudden death. According to Cornell University College of Veterinary Medicine, we must “Realize that dogs with subaortic stenosis, even severe subaortic stenosis, may look perfectly healthy and active. These dogs generally do not realize that their hearts are compromised.”3
The median survival time for dogs with severe SAS who do not receive treatment is 19 months. For dogs receiving traditional treatment (beta-blockers), the median survival is 56 months. Most dogs with the severe form of the disease die before they reach 4 ½ years of age. Dogs with mild to moderate SAS usually do much better, with some living a normal lifespan.
Diagnosis involves a thorough physical exam, including using a stethoscope to listen for a heart murmur or irregular heartbeat. Your veterinarian will also want to know if your dog has displayed any of the symptoms typical of SAS.
Chest x-rays will be performed to check for fluid accumulation in the lungs. An electrocardiogram (ECG) may also be done to look at the electrical activity of the heart and check for arrhythmias.
An echocardiogram (cardiac ultrasound) is the diagnostic test of choice for SAS, because it allows your veterinarian or veterinary cardiologist to visualize the inside of the heart to assess the heart valves, blood flow patterns and velocity, extent of blockage, and severity of disease (mild, moderate, or severe), and other details of the heart’s structure and function.
In mild cases of the disease, treatment is not required. However, since subvalvular aortic stenosis can worsen as a young dog matures, animals with moderate to severe disease may require medication. To reduce the workload on the heart and avoid symptoms, these dogs should also be prevented from engaging in sudden bursts of activity or intense physical exertion.
Follow-up appointments with your veterinarian are important to monitor your pet’s progress, adjust treatment as necessary, and to insure your dog is as comfortable as possible. If medications are being given, periodic echocardiograms may be performed to customize the therapy as necessary.
If your dog is having trouble breathing or collapses, it’s important to get to your veterinarian or the local veterinary emergency clinic immediately, even if your dog recovers quickly from the collapse.
Though rare, SAS also occurs in human children, and one treatment option is surgery to remove the ridge or ring of abnormal tissue below the aortic valve. This procedure has been tried with dogs, but has not increased survival rates according to Dr. Stern of UC Davis. In addition, open-heart surgery for dogs is only available at a handful of centers worldwide.
Cutting Balloon Valvuloplasty: A Procedure with Promise for Dogs with Severe SAS
Several other types of surgical procedures and balloon catheterization procedures have been performed in dogs with SAS, with inconsistent results. However, more recently veterinarians at the University of Florida Veterinary Teaching Hospital have had some success with a technique using cutting balloon valvuloplasty for dogs with severe disease.
The procedure works like this, according to the Newfoundland Club of America:
“The cutting balloon is customized with four 2-millimeter microsurgical blades that are about five times sharper than conventional surgical blades.
As the deflated balloon is initially inserted through the carotid artery in the neck, the blades do not touch the arterial walls. When the balloon is inflated, the blades are forced open within the stenotic region, which cuts four incision-like slits into the obstruction.
The balloon is then deflated, removed, and replaced with a high-pressure balloon, which is inflated to forcibly dilate the stenotic region. The slits created by the blades are opened up with the high-pressure balloon. This combined technique has been evaluated for effectiveness in dilating the tough stenoses in dogs with severe SAS.”4
The first dog to undergo the procedure in 2009 was a 15 month-old Golden Retriever named Buddy with severe SAS. As of 2011, Buddy had reached a healthy weight and was still going strong, with plenty of energy and a good quality of life. He was also being given beta-blockers and an omega-3 supplement, which he’ll need for the rest of his life.
The UF veterinarians then conducted a study using the procedure with 14 additional dogs with severe SAS, including 4 Boxers, a French Mastiff, a German Shepherd Dog, 6 Goldens, a Rottweiler, and a Swiss Mountain Dog.
Three of the 14 dogs died between 9 and 25 months after the procedure due to SAS-related complications (sudden death or congestive heart failure). The researchers will monitor the remaining 11 dogs for the rest of their lives to evaluate their long-term survival and quality of life.
Veterinary hospitals across the US have started offering cutting balloon valvuloplasty to canine patients with severe SAS. The cost of the procedure ranges from $3,000 to $6,000 depending on the location and clinic, and the cost of follow-up care is not included in those numbers. Part of the expense is the balloons used in the procedure – they are highly specialized, not reusable, and were developed initially for human use.
Genetic Testing Is Now Available
Genetic testing for presence of the PICALM mutation is available through North Carolina State University’s College of Veterinary Medicine and the Veterinary Genetics Laboratory at the UC Davis School of Veterinary Medicine.
Going forward, now that scientists know one gene is responsible for SAS and which proteins are involved, they will be working to develop novel therapies to help treat dogs with the disease.
The researchers are also now studying the differences in severity of the disease, and the genetic basis of SAS in Golden Retrievers, Rottweilers, and other breeds.