The North Central Newfoundland Club

Newfoundland Health Information - SAS Study

Funded by the North Central Newfoundland Club & The Ohio State University

 The North Central Newfoundland Club Inc. is pleased to announce that in partnership with The Ohio State University College of Veterinary Medicine, it is funding a study comparing a surgical procedure and drug therapy for treatment of SAS in Newfoundland dogs.

What is SAS ?

1. What is SAS?
Subvalvular aortic stenosis, also referred to as subaortic stenosis or SAS, is a common heart defect in dogs, especially Newfoundlands, Golden Retrievers, Rottweilers, and German Shepherds.

The heart anatomically is divided into 4 chambers separated by 4 valves. The 4 heart valves ensure that blood only flows in one direction through the heart. The aortic valve separates the main pumping chamber (left ventricle) from the aorta, a large blood vessel that carries blood from the heart to the body. In dogs with SAS, there is added tissue below the aortic valve (hence "subaortic"). This abnormal tissue creates an obstruction ("stenosis" is the scientific term) that the heart has to overcome to pump blood to the body. This stenosis makes the heart work harder than normal. A heart murmur is created by blood being pumped across the stenosis into the aorta.

2. What happens to dogs with SAS?
SAS comes in many grades of severity. We subdivide them into mild, moderate, and severe. Dogs with mild disease usually lead a normal life without complications. Dogs with severe disease may die suddenly or develop exercise intolerance, fainting, rear limb weakness, or fluid in the lungs (heart failure). Heart failure can cause coughing, rapid breathing, or shortness of breath. The course of dogs with moderate disease is hard to predict. All dogs with SAS are predisposed to heart valve infections (endocarditis).

3. How do dogs "get" SAS?
SAS is transmitted genetically. This has been studied in the Newfoundland breed; the mode of inheritance in this breed is either autosomal dominant with modifiers or polygenetic. Dogs with mild disease do not necessarily produce dogs with only mild disease, ie a dog with mild disease may sire a litter with severe disease. This defect develops very soon after birth (at approximately 3 weeks of age), and continues to worsen through maturity.

4. How is SAS diagnosed?
SAS is suspected based on a combination of physical examination findings including a heart murmur heard over the aortic valve. In dogs with a murmur, definitive diagnosis and assessment of severity requires echocardiography with Doppler. Echocardiography allows visualization of the 4 heart chambers and valves and the anatomy of the subaortic area. Doppler allows estimation of the pressure created in the heart by the obstruction. The degree of pressure elevation correlates with the disease severity. Some dogs with very mild disease are hard to distinguish from normal dogs even with this technology.

Radiographs of the heart and an electrocardiogram (ECG) are important in the evaluation of dogs with moderate to severe SAS but are usually normal in dogs with mild disease.

5. What should be done if my dog has mild disease?
These dogs should not be bred so castration or spaying is recommended. Due to the risk for heart valve infections, prophylactic antibiotics should be prescribed by a veterinarian for any potential bacteria exposure (dentals, skin infections, minor cuts or abrasions).

6. Can a dog with severe disease be treated?
Therapeutic options are limited. Surgery can be performed at some Universities, but it is expensive. Balloon catheter dilation can also be performed at some referral centers. This procedure involves passing a catheter with a balloon on the end down an artery in the neck. The balloon is centered across the stenosis and then inflated to open up the stenosis. This procedure helps to decrease the obstruction in some dogs. Medical therapy may be prescribed to try and decrease the work load of the heart (beta-blockers) or treat signs of heart failure once they develop.

7. How can I decrease the risk of transmitting this defect?
First, have all breeding animals listened to at maturity by a veterinarian. If no murmur is present, these adults do not have clinical SAS.

Second, have all litters listened to carefully. Timing of this exam is tricky; the older the puppy is at the time of examination, the better. Age is important because the defect is progressive early in life such that a murmur will be easier to detect in a 16 week puppy than an 8 week old puppy. Also, young puppies can have innocent murmurs (murmurs not caused by a heart defect). Innocent murmurs go away by 16 weeks of age. Innocent murmurs are difficult to differentiate from mild SAS. We recommend pups be at least 8 weeks old for screening; 12 weeks old is better, and 16 weeks old is ideal. If a pup is to be used for breeding, auscultation should be repeated as a mature adult (over 1 year of age). If pups with SAS are detected, have the sire and dam examined, and do not repeat breeding.

8. Are there undetectable carries of SAS?
Yes. A dog with no murmur may be a carrier of SAS. These dogs are not detectable at this time. Hopefully, future studies will identify a genetic marker that will lead to a rapid, noninvasive blood screening test for this defect and aid us in eliminating this heart breaking problem from so many wonderful breeds.

Prepared by Linda B. Lehmkuhl, DVM, DACVIM (Cardiology)
The Ohio State University
Veterinary Teaching Hospital

SAS Study Background

North Central Newfoundland Club to Fund SAS Study

This study, "Comparison of Balloon Valvuloplasty and Atenolol in the Treatment of Subaortic Stenosis in Newfoundland Dogs" will be conducted by Drs. Linda Lehmkuhl DVM, MSc and Kathym Meurs DVM, PhD from the College of Veterinary Medicine staff. Funding for the cost of the study, $19,886.00, will be contributed equally by NCNC and the State of Ohio Canine Research Fund through Ohio State Universtiy.

A group of from twelve to twenty Newfoundlands with comparable severity of SAS will be selected for this study. Comparable age and lack of complicating medical conditions will also be determining factors. All will have been diagnosed between twelve and twenty-six weeks of age using Doppler echocardiography. These Newfs will then be randomly assigned to one of two groups. The first will be put on a daily program of medication (atenolol - 25mg twice per day). Atenolol reduces the heart rate and work load on the heart. The second group will undergo a surgical procedure known as balloon valvuloplasty. In this procedure a catheter, with an inflatable cuff, is introduced by way of the carotid artery into the heart to the point of abnormal narrowing. The cuff is then inflated in an effort to dilate the narrowed area.

Thorough examinations of the study dogs, including physical exams, chest radiographs, Doppler echocardiography, and Holter monitoring (continuous 24 hour electrocardiogram recording in the home environment) will be performed at 6, 12, and 18 months.

While expensive, and not without some risk, balloon valvuloplasty, if successful over the long term, could be recomended for those dogs in which a long and productive life is anticipated. Daily drug therapy, with exercise restrictions, is less expenseive but requires daily intervention by the owner.

Funds for this study became available to NCNC because of the strong support we had, by Newfoundland lovers, when hosting the 1995 NCA National Specialty. Our membership felt strongly that a substantial portion of that income should be returned to the betterment of the breed. Towards that end a committee was established to make recommendations to the membership. Research proposals were solicited from eight Midwestern veterinary schools for studies addressing health problems of concern to Newfoundland owners. After careful evaluation, the decision was made to support this study since it appears to have the potential to benefit the breed in treatment of one of our most vexing problems within a relatively short period of time. Although balloon valvuloplasty has been studied before, to our knowledge this is the first study to directly compare it to drug therapy over an extended period of time. We hope future host clubs will consider similar support of Newfoundland research.

1996. Prepared by Bob Ohle

SAS Study Updates

North Central Newfoundland Club Funding SAS Study

December 18, 1998

We currently have finalized patient enrollment with 24 patients (15 are Newfoundlands). We were able to enroll 4 more patients than planned and still stay within our budget. This is great as it will increase our chance of detecting a difference in treatment effects if one exists (i.e. increased dog number will increase our statistical power). Also, this provides us a small cushion if any dogs are lost to follow-up through drop out. We have 12 dogs on each therapeutic arm of the trial (12 receiving beta blocker and 12 having been ballooned), and we are very pleased with the severity matching. Four dogs have died up to this point; two dogs in each treatment arm. Nine of the surviving dogs have passed their one year evaluation, and four of these have reached their 2 year follow-up.

As an outgrowth of this project, we have identified a very important feature of subaortic stenosis in Newfoundlands that we are only now fully appreciating. As part of our clinical study, numerous dogs were evaluated serially to determine whether their disease would progress. This was done because of our past experience that occasionally a dog may have progression of their disease with growth. If a dog with mild or moderate disease progressed to severe disease then therapy would be indicated and they could be enrolled in the clinical trial. This led us to the discovery that this disease is often DRAMATICALLY progressive in the first year of life in the Newfoundland. This has obvious importance to our ability as veterinarians to prognosticate for an individual dog as well as implications in our decisions to treat or not treat affected dogs.

We looked at a total of 23 Newfoundlands (many of the ones on the clinical trial plus a few others) that had pressure gradients determined more than one time before the age of 12 months. The pressure gradient is our best clinical indicator of severity. Dogs with mild disease (<50 mm Hg) do great without therapy. Dogs with severe disease (pressure gradient >100 mm Hg) die from their disease. Dogs with moderate disease have a variable outcome. Fifteen of these dogs had pressure gradients that progressed more than 25 mm Hg, and 7 had less than a 25 mm Hg change in their gradient. The change in pressure gradient in some dogs was as high as 123 mm Hg and averaged 50 mm Hg for the group of 23 dogs. These changes in gradient would definitely have important clinical implications! We are preparing a scientific abstract on this data for presentation at the American College of Veterinary Medicine Forum this Spring in Chicago as we believe this is a very important finding for the breed and we want our colleagues to realize this occurs. As always, your group will be acknowledged in this presentation.

Thanks for your continued support as we strive to improve the understanding and treatment of this devastating disease.

Linda Lehmkuhl, DVM, MS, DACVIM
Assistant Professor
Department of Veterinary Clinical Sciences
The Ohio State University

SAS Study Updates

North Central Newfoundland Club Funding SAS Study

December 14, 1999

We are currently still following the enrolled patients through the cardiology service at OSU. We ended up staying with 22 patients enrolled (we were going to do 20 initially but were able to do 2 more and stay in our budget. In last year's update it lists 24 patients but we were unable to severity match the last two patients so we stayed at 22). Of the 22 patients enrolled, 14 are Newfoundlands. We have 11 dogs on each therapeutic arm of the trial (11 receiving beta blocker and 11 having been ballooned), and we are pleased with the severity matching. Five dogs have died up to this point; three dogs on the beta blocker arm and two dogs on the balloon dialtion arm. Three of the surviving dogs are out over 3 years, 3 are out over two years, and the remaining 11 are all out over 1 year. One of the dogs has been partially lost to follow-up (this dog received it's one year follow-up visit, but then was given to a family in New Hampshire by the original owner). We will still be able to get a final outcome (survival data) but will not be able to get additional clinical data from this one dog.

We presented the abstract detailed in the December 1998 update letter (abstract attached) at the American College of Veterinary Internal Medicine this past Spring and it was very well received as this information is very important! Your group was acknowledged on the poster presentation of this project.

In terms of future publications, we have not finalized how we will divide this information up for publication (as that depends a little on the results), but most likely we will submit one paper on balloon dilation versus beta blockers (once we have final outcomes (survival times) on all enrolled patients; this could be a few years away if the treatments are helping!!), one detailing the progression of SAS in young Newfoundlands (as per abstract presented at ACVIM in the spring of this year), and one on Holter monitor (24 hour ambulatory ecg) results in dogs with SAS of varying severity (we have well over 100 Holters to date!).

Thanks for your continued support.

Linda Lehmkuhl, DVM, MS, DACVIM
Assistant Professor
Department of Veterinary Clinical Sciences
The Ohio State University

Journal of Veterinary Internal Medicine

Volume 13, May/June 1999

RETROSPECTIVE EVALUATION OF PRESSURE GRADIENT CHANGE IN YOUNG NEWFOUNDLAND DOGS WITH SUB-VALVULAR AORTIC STENOSIS. LB Lehmkuhl, C Cataldo, KM Meurs, TR Maxson, AW Spier, JC Bonagura. College of Veterinary Medicine, The Ohio State University, Columbus, OH.

Prognosis for dogs with subvalvular aortic stenosis (SAS) varies with lesion severity. Mild lesions may not compromise quality of life or longevity, but moderate to severe lesions often lead to syncope, exertional weakness, congestive heart failure, and sudden cardiac death. Doppler-derived peak left ventricular to aortic pressure gradient (PG) is the method most often used for quantifying severity of SAS. Gradients are often categorized as mild (PG <50 mmHg), moderate (PG > 50 and < 100 mmHg), or severe (PG > 100 mmHg). The purpose of this study was to determine the change in PG in young Newfoundlands with SAS.

Medical records from all Newfoundlands with SAS evaluated between July 1988 and July 1998 were reviewed retrospectively to identify untreated dogs examined by Doppler echocardiography at least twice during the first year of life. Twenty-three dogs (13 female, 10 male) were identified. Age at the initial exam ranged from 2 to 7 mos (median = 4 mos), wile age at the second exam ranged from 3 to 12 mos (median = 8 mos). The median PG increased from 56 mmHg (range, 25-210) at the first exam to 117 mmHg (range, 32-263) at the second exam. The median PG change from exam 1 to exam 2 was 48 mmHg ranging from a decrease of 60 mmHg to an increase of 123 mmHg. The PG increased by >25 mmHg in 15 dogs, decreased by >25 mmHg in 1 dog, and changed <25 mmHg in 7 dogs. The increment in PG affected severity classification in 16 (70%) of the dogs. Three dogs changed from mild to moderate, 8 dogs from moderate to severe, and 5 dogs from mild to severe.

This study documents the progressive nature of SAS in some Newfoundlands during the first year of life. The degree of disease progression is sufficient in some dogs to affect prognosis and therapeutic decisions.



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