This article ©1996 by Denise Mankin, DVM, and is reprinted with the permission of the author. All Rights are Reserved.
SAS - What it is, and Why Breeder Should be Concerned
by Denise Mankin DVM
Recently, many people in the fancy learned about a relatively new problem of increasing importance in the breed: SAS or subvalvular aortic stenosis. Sub aortic stenosis is the second most common canine heart malformation and is defined as an "obstruction of the left ventricular outflow tract that ranges in severity from an incomplete fibrous ridge to a fibromuscular tunnel", and lies just under the aortic valve. This lesion causes turbulence in the blood as it crosses the aortic valve, and creates a murmur in most of the affected dogs. The lesion truly develops postnatally, unlike other congenital/hereditary heart disease, with the earliest detectable lesions found in extensive breeding studies performed on Newfoundland dogs being three to four weeks of age, making "congenital" somewhat of a misnomer in the case of SAS. The subaortic lesion progresses with maturity, and heart murmurs can be detected as early as six to eight weeks of age, or develop as late as three to four years of age in the milder cases.
Most of our information on SAS, including inheritance of the defect, has come from colony breeding studies on Newfoundland dogs. Information from this breed is identical to the clinical features observed in other breeds with SAS, such as Rottweilers and Golden retrievers, and would be considered relevant to our breed until proven otherwise. The mode of transmission found in the Newfoundland dog breeding studies suggests an autosomal dominant gene trait with variable expression or penetrance, with the variability probably due to modifying gene factors. This makes the true mode of inheritance complex, and presents a more challenging problem in eliminating the defect from the population of dogs.
To help understand the complex genetics of SAS, here is a quick genetics primer:
Mendelian genetics describes a simple genetic trait as having a pair of genes (termed "genotype", with each single gene being called an "allele") that dictates the physical expression of the gene. The location of the gene is called the "locus", with multiple sites taking the plural form as "loci". The physical expression of the gene pair is often observable, giving us the traits that we visually see, feel, or hear (the observed traits being called the "phenotype"). What we see as the phenotype may not clearly indicate all the underlying genes that the dog is carrying for the trait, explaining why we sometimes see an inherited trait expressed in offspring of normal parents. With "dominant" gene expression, the dominant allele becomes the observed phenotype irregardless of what the other allele in the pair contains. With "recessive" gene expression, both alleles of the pair must be the recessive gene type for the observed trait to be seen as the phenotype. There are sometimes a hierarchy of allele types, with a relative dominance/recessive "ladder".
With a dominant gene trait that has variable expression, it is generally understood that the variability may be due to complex gene factors that exist at other loci (i.e. locations). It is often considered that the variability comes from multiple genes that modify the expression of a major dominant gene (or small number of major dominant genes), having a cumulative effect. Although not yet directly shown in SAS, the more severe the defect, the more the cumulative affect is. Regardless of the severity of the case, any affected SAS animal can produce a degree of severity in its offspring because of the dominant genetics of the disease.
Subaortic stenosis has been graded in Newfoundlands based on postmortem exam: Grade 1 is the mildest form, with raised white nodules occurring in the area under the aortic valve; Grade 2 is intermediate, with a fibrous ridge occurring that partially encircles the outflow tract; Grade 3 is the most severe form, with a fibrous band encircling the entire outflow tract just under the aortic valve, and may also cause changes in the mitral valve complex. The mildest lesions create the most frustrating problem for breeders. While 95% of all cardiac defects cause a heart murmur, the Grade 1 lesion of SAS does not always create enough change in blood flow to cause a clinically detectable heart murmur. In studies performed on Newfoundlands, it was found that ausculation (stethosope exam), cardiac catheterization, and echocardiography (ultrasound), the most technologically advanced methods to detect and define heart murmurs, failed to reliably detect some, if not most, of the mildly affected dogs, as determined by postmortem exam. The Grade 2 lesions are often associated with soft cardiac murmurs and minimal changes in the pressure gradient across the aortic valve. The Grade 3 lesions are usually associated with the more severe clinical signs, including moderate to severe murmurs, exercise intolerance, syncope (fainting), congestive heart failure, and sudden death. The importance of this clinical data is clear - while the genetic makeup for SAS may truly be present in a dog, the actual detection of subaortic stenosis becomes difficult in mild cases, with definitive diagnosis of the true carrier depending on postmortem exams. This makes genetic counseling for this genetic trait fraught with error and leaves breeders frustrated.
Medical therapy for SAS can also be frustrating. For mild cases, therapy is usually not indicated, as affected dogs are usually asymptomatic and can live a full and productive life. The only exception would be prophylactic antibiotics for potential bacterial problems, such as dental procedures, surgery, and wounds due to the established risk of endocarditis (bacterial colonization of the heart valves), causing damage to the valves and potentially worsening the severity of the clinical signs. For moderate to severe cases of SAS, therapy is limited to medicines aimed at decreasing the clinical symptoms, such as those associated with congestive heart failure, but the benefits of the therapy are minimal and many of these dogs may develop acute heart arrhythmias as a result of heart muscle ischemia and sudden death.
So, what do breeders do to try to decrease the incidence of subaortic stenosis? First of all, we must realize the limitations of our current diagnostics in recognizing mildly affected dogs, but also realize that most affected animals will be identified in a comprehensive program of screening. Pursuit of such a program of screening and definitively diagnosing heart murmurs coupled with genetic counseling will result in a decrease in the incidence of the defect in a few generations. This includes screening all breeding stock and retaining those free of the defect, and carefully screening all offspring for the defect and eliminating parents which have produced affected offspring. Dr. Don Patterson describes a program for breeders working to decrease the frequency of SAS.
A Conservative Program to Screen Dogs for Discrete Subaortic Stenosis (see reference1)
1). Most, but not all, discrete subaortic lesions will produce a murmur, and it is reasonable to use ausculation as the main screening method. Some very mildly affected defects will go undetected, but neither are these likely to be detected by ultrasound or catheterization.
2). Because the lesion develops postnatally, screening should not be begun until 6-8 weeks of age. Pups with murmurs should be examined by more definitive methods, as needed, to make a diagnosis. Moderate to severe subaortic stenosis can be diagnosed by this age. Pups with mild lesions may not be distinguishable from those with innocent flow murmurs.
3). Pups with low grade murmurs and no other evidence of heart disease should be reexamined at 12-14 weeks of age. If the murmur disappears, the pup can be considered clear of clinically significant congenital heart disease. However, if there are close relatives with subaortic stenosis, it is prudent not to use such animals for breeding stock or use them only if their offspring are carefully screened for congenital heart disease. Discontinue breeding such dogs if they produce pups with confirmed subaortic stenosis.
4). Pups with a low grade murmur that persists beyond 12 weeks should be reexamined by more definitive methods to make an accurate diagnosis. If echocardiography or cardiac catheterization and angiocardiography are used, it should be possible to reduce the number of false positives. Pups that have a persistent murmur consistent with subaortic stenosis, but have no evidence of a congenital heart defect after further studies can be considered clear of a clinically significant lesion, but a very mild lesion cannot be ruled out. Such animals should not be used for breeding unless there are other compelling reasons for it. If bred, the offspring of such dogs should be carefully screened for evidence of congenital heart disease and breeding discontinued if any affected pups are produced.
The Orthopedic Foundation for Animals, or OFA, has recently opened a voluntary Open Registry for the certification of hearts against congenital cardiac disease. The recommendations given by OFA is that breeding stock be examined by ausculation at 12 months of age or older, preferably by a board certified Cardiologist, or an Internal Medicine specialist who has received advanced training in the area of congenital heart disease. The OFA fee is $15.00 and no charge is made for recertification at a later age. The certification number will indicate the age of certification, and the level of expertise of the examiner designated by a letter. Evaluation of dogs under 12 months of age is possible, and OFA will issue a provisional certificate for a $10.00 fee. For SAS, it has been recommended by cardiologists that reevaluation of breeding animals be performed at a minimum of 1, 2, 4, and 6 years of age due to the late onset of some of the murmurs associated with the defect. It is also highly recommended that dogs with congenital heart disease also be submitted to OFA for completeness of data collection and to assist with the analysis of inheritance within the breed. It will also be of assistance to those who have found SAS within their lines, by allowing the opportunity to seek out bloodlines that are relatively free of the defect through an open database.
Anyone seeking more information on the OFA Congenital Heart Disease Registry, and any of their other services (such as the Thyroid Registry), can contact them at Orthopedic Foundation for Animals, 2300 E. Nifong Blvd., Columbia, MO 65201-2856, or telephone at 573/442-0418.
1. Genes and the Heart: Congenital Heart Disease. Donald F. Patterson DVM, DSc, Diplomate ACVIM; 1991 Academy of Veterinary Cardiology Proceedings, as presented in conjunction with the 58th Annual Meeting of the AAHA and the Ontario Veterianary Medical Association Meeting, April 13-14, 1991, Toronto, Ontario, Canada.
2. The Genetics and Pathology of Discrete Subaortic Stenosis in the Newfoundland Dog. R.L. Pyle VMD, MS, D.F. Patterson DVM, DSc, S. Chacko DVM, PhD, American Heart Journal, Vol. 92, No. 3, pp. 324-334, September 1976.
3. CVT Update: Canine Subvalvular Aortic Stenosis. Linda B. Lehmkuhl and John B. Bonagura, Kirk's Current Veterinary Therapy, Volume XII, 1994.
4. OFA Congenital Heart Disease Registry: General Procedures. Orthopedic Foundation for Animals, 1996.