THE UK HEART CONTROL SCHEME FOR AORTIC STENOSIS, PRESENTED AT THE 2001 ABC

With heart disease at the forefront of many present-day American boxer breeders’ concerns, the ABC Health & Research Committee invited Dr. Bruce Cattanach, Bsc, PhD, DSc, FRS, to give a presentation at the 2001 ABC on the UK Heart Control Scheme for Aortic Stenosis.  Dr. Bruce Cattanach presents the UK Heart Control Scheme for Aortic Stenosis. Dr. Cattanach has been a noted breeder/exhibitor of boxers in England since 1949 under the Steynmere prefix. Ch. Steynmere Night Rider had a strong influence on boxer bloodlines in the UK, and English Ch. Steynmere Summer Gold - imported to the US as an adult - appears in many North American pedigrees through his descendents, Chs. Berena’s Gemini Splashdown and Tribute to Fa Fa. Dr. Cattanach is a geneticist by profession, and has specialized in the cause and analysis of genetic defects. Until his recent "semi-retirement," Dr. C. was Director of the Medical Research Council Mammalian Genetics Unit in the UK. He also worked on the genetic effects of radiation in the USA in the 1960s, and in fact, on his return to the UK in 1969 he took a Cherokee Oaks bitch back to the UK to found his present-day Steynmere breeding. Dr. Cattanach was instrumental in eradicating the crippling, hereditary, neurological disease, Progressive Axonopathy (PA), from the British boxer in the 1980s, and is currently working with British cardiologists and breeders to lessen the very widespread incidence of Aortic/Subaortic Stenosis in British bloodlines. At the end of Dr. C.’s talk, he received a standing ovation from the 200+ people who attended.  Dr. Cattanach has added a postscript to his ABC talk as a result of subsequent discussions of AS on the Showboxer-L e-mail list. The postscript also answers questions and issues raised during Dr. Cattanach’s presentation. It appears at the end of this article. Editor’s note: The following notes are taken from Slides used by Dr. Cattanach in the course of his presentation. These illustrate his main points. VZ THE UK HEART CONTROL SCHEME FOR AORTIC STENOSIS PRESENTED AT THE 2001 ABC BY DR. BRUCE CATTANACH  copyright 2001 Dr. Bruce M. Cattanach Slide 1 The Start/Initial Findings Slide 2 Actions Taken Slide 3 Tests for Aortic Stenosis (AS/SAS) Slide 4 Heart Murmurs, Doppler Blood Velocity and AS Slide 5 Selection of a Test System Slide 6 The UK Breed Council Breeding Control Scheme Slide 7 Summary of Results Slide 8 What Further Can Be Done? Slide 1 The start/initial findings: 1. Breeder reports to the Breed Council of heart associated deaths among young boxers in the late 1980s: some 30 cases had been reported over the two previous years. 2. A heart survey was conducted at the British Boxer Club’s 1990 championship show: About 30% of 125 dogs tested had heart murmurs of a type consistent with a heart disease known as aortic stenosis. The veterinary literature recognised the Boxer as a breed in which aortic stenosis occurred. The condition had a genetic basis -- it was inherited (data from a study of Newfoundlands). The Edinburgh cardiology group reported that about 45% of all cases of aortic stenosis across all breeds referred to the university were Boxers...and that the incidence had climbed greatly over the previous 10 years. Back to Top Slide 2  Actions taken: 1. A panel of three breeders was set up by the UK Boxer Breed Council. This included Dr. Cattanach as geneticist and a specially interested cardiologist, Virginia Luis Fuentes, from Edinburgh University. 2. The panel’s goal was to recommend a means of dealing with the problem. The following descriptions of the problem and the available diagnostic tests were given: Aortic Stenosis: A narrowing (stenosis) of the aorta: Typically, narrowing is below the valve, subaortic (SAS), but can locate above, or even affect the valve itself. The condition shows a range of effect: The severest form comprises a fibrous ring. 1. The ring narrows the aorta, increases blood velocity, and reduces blood supply to the body/brain. 2. The increased blood velocity causes noise, i.e., heart murmurs. 3. The redeuction in blood supply to the brain may lead to fainting and even death. Milder forms exhibit fibrous nodules or a roughening of the walls of the aorta. 1. Nodules/roughness cause turbulence in the blood flow. 2. Turbulence causes noise, i.e., minor heart murmurs. 3. No restriction of blood flow need occur. 4. Murmurs may have no functional significance. Back to Top Slide 3   Tests for Aortic Stenosis (AS/SAS): 1. Pathology (autopsy): As used in the Newfoundland research on inheritance. 2. Auscultation: Use of the stethoscope to assess the magnitude of murmurs. Cannot distinguish between AS and PS (Pulmonary Stenosis). 3. Phonocardiography: Use of this equipment to assess the magnitude of murmurs. Probably cannot distinguish between AS and PS. 4. Doppler echocardiography: Measures the velocity of blood flow attributable to narrowing (stenosis). May allow a visualisation of the abnormality that is causing the murmur. The classical tool for clinical (severe) cases. Back to Top Slide 4   Heart murmurs, Doppler blood velocity and AS: No murmur (Grade 0): May be considered free of AS (big question on that point)??? Doppler scan results of 0.8 - 1.4m/s (in non-AS breeds). Grade 1 murmurs: Described as "flow" murmurs. The dog is clinically normal (has no symptoms). The murmur has no functional significance (causes no impairment). A Doppler scan is likely to be under 2.00m/s. The dog may have a mild form of AS. Grade 2 murmurs: The dog is clinically normal. The murmur has no functional significance. The Doppler scan may range from about 1.7 - 2.5m/s Almost certainly some degree of AS/ Grade 3 murmurs: May be clinically significant. Functional problems are likely. The Doppler scan may range from about 2.0 - 3.0m/s. Clearly AS. Higher grade murmurs (4 - 6): Clinically significant AS. Functional problems expected/certain. Doppler scans up to 6.00m/s. Liable to fainting/sudden death at exercise. Back to Top Slide 5   Selection of a test system: Auscultation: Doppler Echocardiography: Advantages: Advantages: Simple/available in the UK. Economical. Allows whole kennels to be screened. Screens for all levels of AS. Distinguishes AS from PS. May firmly diagnose the condition (at more serious levels). Offers prognosis/evaluation. 2D echo may allow visualisation of abnormality. The veterinary tool of choice for diagnosis. Disadvantages: Disadvantages: Variable (at least one grade range). Does not distinguish AS from PS. Hypothetical risk of misdiagnosis. Limited availability. Costly. Limited application for whole kennels. Does not recognise most minor levels of AS. Can be variable (0.5m/s variability expected). NOTE: Good correlation between murmur grade and blood velocity with murmur grades 2 - 6 only. Auscultation screens for PHYSICAL abnormality. Doppler screens for FUNCTIONAL abnormality. Back to Top Slide 6  THE UK BREED COUNCIL BREEDING CONTROL SCHEME The Heart Panel made the following recommendations, which were accepted by the Breed Council: 1. Primary test system should be auscultation carried out only by cardiologists experienced in Boxer heart testing  on grounds of economy greater potential application believed greater sensitivity 2. Tests applicable only to dogs over 1 year old. 3. Grade 0 (murmur-free) and Grade 1 accepted as normal. 4. Retesting Grade 2s two or three times is recommended, and the "best" score is accepted. 5. In addition, for Grade 2 males, Doppler, as carried out only by experienced cardiologists, is suggested. A normal blood velocity is taken to be under 2.00m/s (too high, in Dr. Cattanach’s opinion). 6. Dogs with Grades 0 and 1, or with accepted Doppler blood velocities may have their names included in a Heart List, with owners’ permission. The Heart List is available to all in print format through UK breed clubs and is now on a web site ** Dr. Cattanach illustrated his talk with a graph showing the results of breeding dogs with different grade murmurs together and a table of the grades of dogs tested at shows from 1997 - 2000. The graph showed that the severity of heart murmurs in the progeny were dependent upon the severity of heart murmurs in the parents. The table showed the unfortunate effects of increasingly "tougher" and more standardised heart testing over the years. Both the graph and table may be viewed on the UK Heart List web site. ** Back to Top Slide 7  Summary of Results: 1. From a very high rate of referral of Boxers with severe clinical AS in the 1980s, there are now almost none -- across the whole country. 2. The incidence of dogs tested at shows and found to have Grade 3 and louder murmurs has now declined significantly. Therefore, selective breeding for dogs with minor or no murmurs, as detected by auscultation alone, is effective in reducing the incidences of clinical AS -- in Boxers. 3. It may be difficult to reduce the incidences of dogs with Grade 2 murmurs, due to the influence of untested parents, of pet dogs of unknown breeding coming to be tested, and the uncertainty about the genotype of murmur-free dogs. 4. Further veterinary and genetical research upon AS in Boxers is needed. Back to Top Slide 8  What further can be done? 1. Investigate the pathology of murmur-free and Grade 1 dogs. Do they have any pathological changes indicative of AS? 2. Re-test, by auscultation, Grade 0 dogs under rigorous conditions. Do any remain murmur-free? Perhaps re-test with other methods also, Doppler, 2D echo. Do we have any Boxers that are truly free of AS? 3. Investigate litters from matings of any genuine Grade 0/AS-free parents. Do genuine Grade 0/AS-free Boxers breed true? 4. Identify the litter sizes of dogs with/without murmurs. Questions 3 and 4 are genetic questions. The answers could indicate the mode of inheritance of AS. Back to Top Postscript to Dr. Cattanach’s ABC talk on the UK Heart Scheme I have just returned from a trip to find a mass of e-mail writings on my ABC heart talk. The volume has dropped sharply in recent days, and I hesitate to bring up the subject again, especially as my points all seem to have been recognised and some level of agreement reached. But several pertinent questions were asked and require answers and certain other issues perhaps should be emphasised again. So let me try and deal with these -- in sequence: Ques. 1. Has the severity of cases referred to vet schools changed since the breeding control scheme was introduced? Ans. - Only severe cases are ever referred to vet schools. Ques. 2. Has there been any change among the vets at vet schools in the UK? Ans. - There has been little or no change. In any case, almost all the results come from those selected vets who are experienced with Boxer heart testing. Ques. 3. Has there been any change in Boxer lifespan since the inception of the control scheme? Ans. - We have no information at all on that point. This needs an epidemiological study. Ques. 4. What pathology data exist? Ans. - The information available is very limited. The problem is that British Boxer breeders are reluctant to have hearts sent for pathology when their dogs die, despite the availability of forms that can arrange matters in advance of death (see the UK Heart web site). The drive (such as it is) has been focussed on checking what, if any, AS there is to be found in dogs which had been tested earlier and shown to have murmurs of different grades, notably the minor murmurs. My own dog, as shown in the last photo at ABC, had a Grade 1 murmur and a 1.7m/s Doppler velocity and was found to have minor changes consistent with AS at death from other causes (about 10 or 11). There have been others. So some Grade 1 dogs do have AS detectable on pathology. Ques. 5. How many dogs were involved in the breeding study? Ans. - About 2000 dogs contributed to the data. Most parents were Grade 1s and 2s, with a good number of Grade 0s and far fewer Grade 3s and 4s. Since data are approaching a point where they will be submitted for publication, I am reluctant to make every aspect public knowledge in advance. Ques. 6. Low grade murmurs have been found without Doppler evidence of obstruction and vice versa. Does this not call into question the validity of scoring heart murmurs? Ans. - Exceptions must always be expected. For example, a badly affected heart may be too weak to pump blood hard enough to cause a murmur, even through there is a narrowing of the aorta (stenosis). And the opposite is also true. Large hearts in fit dogs such as the racing greyhounds can pump blood rapidly and with few beats, and this results in spurious murmurs. Neither situation is expected with Boxers presented for examination at shows. Ques. 7. Isn’t Doppler the best test system? Ans. - Vets are understandably eager to say whether an individual dog is affected/clear, just as the owner is anxious to know. But from the breeder/genetics point of view one wants to know the broader picture for the majority of dogs. We need on average to identify the best. We do not need an absolutely perfect answer. All we need is a guide to which dogs are the best such that we have an opportunity for selective breeding. This is almost like selective breeding for show purposes. We don't ask judges to say what is perfect and then only breed from the perfect specimens. We don't even ask for the very best, the champions say. We all try to breed better from what we have, and with AS, the UK concept is to provide the estimation, or the assessment of the most normal. And, recognising that the scoring is never precise, we have flexibility built into the breeding recommendations so that there are no absolute dividng lines. The breeding control scheme provides recommendations that people can follow with whatever breeding stock they have got. Ques. 8. Is there really a correlation between loudness of murmurs and degree of obstruction? Ans. - Auscultation and Doppler measure somewhat different things. Auscultation measures physical abnormality and Doppler measures function. There should still be a relationship between the two scores, and I have the data to illustrate this point. The problem is that the relationship only holds true at higher grades. At the lower end, where velocities are normally somewhat variable, the Doppler scoring becomes meaningless. Murmurs are found further down the scale where Doppler is not sensitive enough to distinguish from normal. Maybe auscultation can confuse AS with PS (pulmonic stenosis), but then we don’t want PS either. Mis-diagnosis (PS for AS) is not a problem for breeders, but would be for genetic studies. So, let's say it again -- auscultation is more sensitive, cheaper, more easily attained, more readily repeated than Doppler. That it is variable is no special disadvantage, as Doppler is variable too. Ques. 9. Must not the gold standard for AS be based on pathology? Ans. - This is certainly true, but the old Newfoundland work, plus that of other researchers, established that all test systems relate to the pathological changes. Otherwise none would be used. Just an add on: A big difficulty as I tried to point out is that the same words are used to mean slightly different things. Is AS strictly only a narrowing, an obstruction, associated with an increased blood flow through the aorta; or is it also the lumps and bumps, the roughening of the aorta walls that do not restrict blood flow but are manifestations of AS nontheless? The cardiologists in the UK have recognised all to be the same thing. For me as a geneticist with a very different view from the vets, based on many studies with mouse mutants, this is exactly what I would expect -- a range of effects (irrespective of the exact mode of inheritance); and every single reader will recognise this themselves with everyday Boxer breeding. Take brindle/fawn; there is a range of brindle effect from near fawn (let's call this grade 1) through to reverse brindle (let's call it grade 6). We can all see this by looking, but if we could not do this directly but had to try and work out what was brindle and what was fawn from hair samples ( like the cardiologists working with ausculation, Doppler, 2D ultrasound, etc), we might conclude that lots of black hair means strong brindle, lesser amounts of black hair probably means brindle, but what about the least amount of black hair?? Some might conclude that such a dog is a light brindle. Others might conclude it is fawn. But there is black hair in the coat of fawns so the exact "diagnosis" is not clear. There is all sorts of scope for argument with an imprecise scoring system. What the UK system specifies is that we don't want the bad hearts (= reverse brindles) and we will encourage breeding from the best dogs, be they absolutely normal (= fawn) or grade 1s (= the lightest brindles). We all know that some lines tend to be dark brindles and others light brindles. We therefore can select for whatever we want. This applies to AS too. So, as the astute will have noticed, I presented the UK scheme, its rationale, its problems, etc., so that you in America, should you wish to do anything about AS, will see what we have tried to do, what has gone wrong, what we have had to do to fix things, and in total, avoid all the pitfalls that we met. The concept and types of problems apply to BCM as well. You don't at all have to follow the same route, but standardising the diagnosis across the country is one essential need, and setting up an agreed written protocol or guidelines for breeding, with flexibilty to meet different situations, is another. This applies, as far as I am concerned, across the whole spectrum of dog abnormalities, not just with regard to hearts. About your dog: The selective breeding is the key -- a fair system that everyone can use. You don't want to continue testing for the rest of time, do you? One might say that this is the case for PRA. PRA testing has been going on for 30 years or more. Bruce M Cattanach bcattanach@steynmere.freeserve.co.uk