Added note, February 2006:
This series of articles outlines the progress and difficulties in establishing and applying an effective screening test for aortic stenosis. Evidence to show that heart murmurs attributable to aortic stenosis are inherited was obtained, and a reduction in the incidence of severe cases was ultimately reported by all cardiologists. Assessment of a decline in the incidence of dogs with more minor murmurs was confounded at least in part by increasingly rigorous grading. Collation of the results was terminated in 2004 although heart testing continued.
1.1 A number of heart conditions are known in the dog. These include aortic stenosis, pulmonic stenosis, cardiomyopathy, mitral valve degeneration and myocarditis. Mitral valve degeneration commonly occurs in Cavalier King Charles Spaniels but has not been reported in Boxers; myocarditis is caused by infections, such as parvo-virus, and therefore can occur in all breeds, but is known to be a cause of puppy deaths in Boxers. The remaining three conditions, notably aortic stenosis, have been found in Boxers and are the major cause of fainting and collapse, as well as sudden death generally ascribed to heart disease in the breed.
1.2 Aortic stenosis has been reported to occur with high frequencies in a number of breeds. Notably Newfoundlands and Golden Retrievers in North America. High incidences have also been observed in Boxers, however. At a recent (Oct. 1991) cardiovascular conference in Vienna, vets from various parts of the world were in agreement that exceptionally high incidences of aortic stenosis generally occur in the breed.
2. THE SITUATION IN THE U.K.
2.1 U.K. Boxers have also been recognised by the veterinary profession to be particularly subject to aortic stenosis. Moreover, there is some indication that the frequency of clinical cases (showing symptoms or dying) is rising. At Edinburgh Veterinary School, Boxers referred to the cardiology group have represented almost 40% of cases of aortic stenosis found across all breeds in recent years. Cambridge Veterinary School has also reported aortic stenosis (and cardiomyopathy) as a major problem in present-day Boxers. Furthermore, even Boxer breeders have become aware of unusually high incidences of heart-associated sudden deaths among Boxers over the last 5 or more years. Data has been collated on such deaths and reported to Breed Council at their meetings since 1987.
3. VETERINARY ASPECTS
3.1 Aortic stenosis is a heart abnormality in which fibrous tissue develops in or close to the aortic valve narrowing the aperture. Because of this narrowing (stenosis), the blood is forced through the valve faster and this results in a turbulence that can be heard on stethoscopic examination. Generally, there is a good correlation between degree of stenosis and volume of sound. The range of stenosis is wide; minor stenosis does not result in clinical effects; more major stenosis results in collapsing, especially with sudden exercise or even death.
3.2 Aortic stenosis may occur in very young (4 months) puppies when it may be so severe as to cause sudden death. More typically, it develops rapidly in dogs between 6 and 12 months of age after which progression may decline so that the condition probably does not worsen greatly with increasing age. The most severe cases therefore tend to develop clinical signs or die as young adults.
3.3 Pulmonic stenosis represents a narrowing of the pulmonic valve. The sound so caused cannot be clearly distinguished from that due to aortic stenosis by stethoscopic examination but can be distinguished by more sophisticated methods such as Doppler echocardiography (see 4.3). The clinical signs may be similar.
3.4 Cardiomyopathy is an entirely different form of heart disease. It is usually distinguished by irregular heart beats on stethoscopic examination and causes other clinical signs such as fluid on the lungs and abdomen, coughing and general lethargy. Port-mortem examination can confirm the cause of deaths due to aortic stenosis pulmonic stenosis, or cardiomyopathy, as well as myocarditis.
4. DIAGNOSIS OF AORTIC STENOSIS
4.1 STETHOSCOPIC EXAMINATION
4.1.1 Stethoscopic examination can be used as a method of screening for aortic stenosis. Specialist cardiologists are able to grade the sounds (heart murmurs) and this is now standardly done on a scale of I (minor) to VI (major). General veterinary practitioners may only detect louder murmurs.
4.1.2 As already indicated (3.3), murmurs attributable to stenosis of the pulmonic valve cannot be usually distinguished from those due to aortic stenosis; further testing is necessary to identify which valve is affected.
4.1.3 More importantly, purportedly innocent 'flow' murmurs can be confused with established stenosis murmurs. 'Flow' murmurs are commonly found in young puppies (-3 months) but usually disappear by 6 months of age. Their relationship, if any, to stenosis in adults is not known. However, 'flow' murmurs may also be heard in adult dogs when they are usually of mild degree (grade I). Typically, they are variable such that they may be heard on some occasions but not on others. While the significance of these adult 'flow' murmurs is not yet understood, 'flow' murmurs in Newfoundlands are associated with mild degree of fibrous tissue in the aorta, and it has been observed that 'flow' murmurs are rarely found in breeds that have low incidences of aortic stenosis.
4.1.4 The general conclusions are therefore that dogs which are free of heart murmurs (HM-free) are unlikely to have aortic (or pulmonic) stenosis; and those with minor murmurs which cannot be consistently heard ('flow' murmurs) are also unlikely to have any physical form of valvular stenosis.
4.1.5 Stethoscopic examination can also detect cardiomyopathy and myocarditis. Other systems, together with post-mortem examination findings can confirm diagnosis of these conditions.
4.2 ULTRASOUND SCANNING
4.2.1 This painless procedure, carried out without anaesthesia, enables the internal anatomy of the heart to be seen. A thickening of the heart walls or abnormality of the valves may be distinguished. Fibrous tissue in or close to the valves may be seen.
4.2.2 Both aortic and pulmonic stenosis may be distinguished in this test but minor degrees of affect may not be detectable.
4.3 DOPPLER ECHOCARDIOGRAPHY
4.3.1 This procedure is usually carried out concurrently with ultrasound scanning when equipment is available and is the most effective method of detecting and quantitating aortic (and pulmonic) stenosis. It does this by directly measuring the velocity of blood flow through the valves.
4.3.2 The accepted upper limit of normal blood velocity through the aortic valve is 1.5 metre/second; velocities ranging up to 2.0 metre/second are taken to correspond with 'flow' murmurs; but yet higher velocities are attributed to aortic stenosis. Maximal velocities are 6-7 metres/ second. With the highest velocities, life expectancy is usually short; with intermediate velocities, clinical signs may be seen in some dogs but not others. Doppler echocardiography serves as the key test for functional aortic stenosis.
4.4 POST-MORTEM EXAMINATION
4.4.1 Post-mortem examination remains the ultimate method of ascertaining the presence/absence of aortic stenosis (and other heart conditions). Even minor amounts of fibrous tissue can be detected.
5. RESULTS OF RECENT HEART SCREENING IN UK BOXERS
5.1 The screening clinics held at six shows over the period August 1990- August 1991 have revealed that, overall, 54% of Boxers tested were HM-free, 24% had Grade I murmurs, 16% had Grade II murmurs, and 5% and 1 % had Grade III and IV murmurs, respectively.
5.2 Very few of these dogs have yet been taken for follow-up ultrasound scanning and Doppler echocardiography. However, so far, all dogs with Grade I murmurs have been shown to have blood velocities within the normal to 'flow' ranges (up to 2.0 metres/sec). Evidence of aortic stenosis has been found in a major proportion of dogs with Grade II murmurs, and all but two dogs with Grade III murmurs have been shown to have abnormally high blood velocities consistent with aortic stenosis.
5.3 The observed high incidence of heart murmurs together with the direct evidence of aortic stenosis in the various veterinary schools confirms that aortic stenosis is a problem in UK Boxers, as elsewhere.
6. GENETIC ASPECTS
6.1 The inheritance of aortic stenosis has been investigated in Newfoundlands. In this breed the mode of inheritance appears as that of a dominant gene with variable expression, i.e. other genetic factors may be involved. If verified, the inheritance could be modelled on that of the dominance of the gene for brindle over its recessive form, red; although dominant to red, brindle shows a range of expression from minor degree, golden brindle to major degree, 'black' brindle. The variation in degree of aortic stenosis may be so understood.
6.2 On the basis of such a dominant inheritance, any dog carrying the gene for aortic stenosis (As) would be expected to transmit this gene to approximately half its progeny, irrespective of its own grade of murmur or level of stenosis. About half their progeny from crosses with HM- free dogs would therefore have some level of stenosis, whereas about 75% of the progeny from crosses between two As carriers (affected) would have some degree of affect. Both crosses could produce normal progeny, these occurring with frequencies of approximately 50% and 25%, respectively. Crosses between two carriers would also be expected to produce progeny carrying two doses of the As gene. Such dogs have not yet been identified; they might be so severely affected that the onset occurs very early - possibly even within a few days of birth.
6.3 A further important expectation for the dominant form of inheritance is that normal, HM-free dogs when mated together would produce only normal progeny. How true this will prove will depend upon the certainty with which normal dogs can be distinguished from those with the mildest degrees of stenosis. To date, amongst the very limited amount of Boxer breeding data available, affected dogs have always proven to have at least one affected, or potentially (heart murmur) affected parent.
6.4 It is still possible that aortic stenosis will show a multifactorial inheritance in Boxers, such as established for HD in a number of breeds. In this case, a less clear pattern of inheritance would be evident and it would be less unexpected for two unaffected (normal) parents to produce some affected pups. Nevertheless, as with HD, the least affected parents would, overall, be expected to produce fewer, less affected puppies.
6.5 Despite the possibility of a multifactorial inheritance, it might be noted that aortic stenosis in humans is generally regarded as showing something closer to a single gene, rather than a multifactorial inheritance. It has also been predicted that Golden Retrievers, which in North America show a high incidence of heart murmurs and established cases of aortic stenosis, will show the similar dominant-type of inheritance to that indicated in Newfoundlands. On the same basis, aortic stenosis not only may be expected to be inherited in Boxers, but a dominant-type mode of inheritance would seem most probable.
7. FUTURE RESEARCH NEEDS
7.1 For the breed as a whole, further heart screening at a series of shows throughout the country over a number of years is needed in order to monitor the situation and provide research information.
7.2 For individual breeders, regular heart screening clinics are necessary to allow them to conduct their own family studies and to identify HM- free dogs that can be used to produce sound, aortic stenosis free stock.
7.3 As no studies have yet been carried out upon 'normal' Boxer hearts, there is a clear need to evaluate HM--free dogs by ultrasound scanning and Doppler echocardiography. Edinburgh veterinary school (see list of diagnostic centres) has offered to examine such normal dogs for research purposes at no charge. Bristol (Langford) Veterinary School has also indicated a willingness to test a few normal dogs by the above methods. Breeder’s cooperation is required.
7.4 Much further information is needed to establish firmly the correlation between grade of murmur and velocity of blood flow and assess the meaning of those exceptions to the correlation that are detected. In particular, the significance of the lower grade murmurs and their distinction from 'flow' murmurs needs elucidation. It is therefore essential that additional animals with different grades of murmur be investigated by ultrasound scanning and Doppler echocardiography to provide substantive information on the variable levels of aortic stenosis. Such testing would also provide individual breeders with a quantitative assessment of the severity of any effect in their own dogs or, alternatively establish normality despite the existence of murmurs. Costs at Edinburgh have been set at £25, and £30 at Bristol. Cambridge and London (Dr Cobb) can undertake such testing as a service at a cost of about £80 (see list of diagnostic centres). Breeder cooperation is required.
7.5 Post-mortem evidence on the hearts of Boxers that have died of aortic stenosis (or other heart conditions) is as yet limited. There is therefore a need to have hearts of dogs that have died of any suspected heart condition sent to the veterinary schools for final diagnosis and direct evaluation of the degree of any aortic stenosis found. It would be particularly useful if the hearts of dogs which had screened for heart murmurs at any age could be made available. There would be no charge for such investigation at Edinburgh; costs elsewhere have yet to be determined. Breeder cooperation would be appreciated.
7.6 Post-mortem examination of the hearts of dogs that had previously been shown to the HM-free could also help characterise the normal Boxer heart. Such hearts are being sought by the veterinary schools, notably Edinburgh, for this purpose. Breeder cooperation would be appreciated.
7.7 The possibility exists that some early puppy deaths (within a few days of birth to a few weeks) might in some case be due to heart abnormality (Para 6.2). London Veterinary School (specifically Dr Brownlie) has expressed an interest in investigating such early puppy deaths.
7.8 Research upon the treatment of dogs suffering from aortic stenosis (and other heart conditions) is in progress in several of the veterinary schools, certainly in Edinburgh and in London (Dr Brownlie) where the work is being conducted in collaboration with Guys' Hospital Medical School. Owners of dogs with aortic stenosis therefore now have the opportunity of alleviating the disabling effects of the condition while incidentally contributing towards human medicine.
O'Grady, M.F. et a/. Canine congenital aortic stenosis: A review of the literature and commentary. Can. Vet. J. 30:811-815 (1989).
Patterson, D.F. Congenital defects of the cardiovascular system of dogs: Studies in comparative cardiology. Adv. Vet. Sci. Compo Med. 20:1-37 (1976).
Pyle, R.L. et a/. The genetics and pathology of discrete sub aortic stenosis in the Newfoundland dog. Am. Heart Jour. 92:324-334 (1976).