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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 post-mortem 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 post-mortem 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 post-mortem exams. This makes genetic
counselling 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 counselling 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)
-
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.
-
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.
-
Pups with
low grade murmurs and no other evidence of heart disease
should be re-examined 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.
-
Pups with
a low grade murmur that persists beyond 12 weeks should
be re-examined 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 re-certification 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 re-evaluation 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.
References:
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.
by Denise Mankin DVM |
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