HCM gene testing- are we wasting our time?

I had a really interesting chat with my breeder when I picked up Dudley about HCM - it's something I'm really interested in as I research muscular dystrophy-associated cardiomyopathies. She suggested that breeders concentrate far too much on breeding from 'HCM gene -ve' animals instead of looking at family history- i.e. how long did the cat's parents, grandparents etc. live? She made the very valid point that the 'HCM gene' we all test for is only one of what is likely to be a whole gamut of other genes which elevate the risk of HCM. She regularly checks her breeders by echo although she still states HCM gene status on her website, because the public demand it. I would like to get other breeder's opinions here- do you feel the 'general public' demand an HCM negative status although it is not entirely useful? Does genetic testing make for lazy breeders, i.e. is HCM -ve status viewed as a 'one stop' guarantee of a healthy heart making breeders less vigilant about family history and less like to use more qualitative information available to them. To me, if the known HCM gene is indeed a risk factor then I want to know about it, but I am not so naive as to believe that being negative for this gene eliminates the risk of my cat having HCM- in fact, Sylvie had HCM n/n parents but has a heart murmur.... It occured to me that within the MC breeder community there must be an untapped wealth of information about the strength of association of HCM with the so called 'HCM gene'! Someone needs to do a large scale study!

There have been a couple of relatively small studies to look at the outcome of HCM positive MCs. I will have to look them up because I cannot seem to find the papers on my machine right now, and the better one is hard to find online I believe. If you do related research, you should be able to find them. Primary author to search on is Kittleson and also of course Meurs (for older papers).

I have read these papers carefully as we have a heterozygous female, who is now nearing age six. She was echoed at four years by a vet cardiologist and showed no heart changes. One of our breeders has a hetero male who was around eight I think when our Allie was echoed (done together), and he has definite heart changes (though no symptoms).

More recent paper showed outcomes for hetero cats being mixed, some have clear HCM changes and others do not.. Study was not to be able to say if any hetero cats live a normal lifespan without health issues, though. Outcomes for homozygous cats generally have been shown as dire: virtually absolute early death sentence (some before age two as I recall).

The only reason to be breeding hetero cats, in my opinion, is if this is required for genetic diversity or some particular quality that one can get only from HCM positive MCs. Having had a cat that was ill with HCM for several years and died from it, there is no way in the world that I would ever spend a fairly large sum of money to buy a cat that I knew had a risk factor for this disease. Yes, the one known HCM mutation is hardly the only factor in health, but it is a very unpleasant disease for both the cat and the owner, so why would you not want to do as much as possible to eliminate that risk? Makes no sense to me! Also, the HCM gene test is hardly the only genetic and other type of health test that responsible breeders are doing (e.g., echo tests, PKD testing).

Potential owners of mutation-positive MCs should also be aware that there are no good treatments for HCM in cats. Current best practice (at least in US) is not to do any treatment on symptomless cats regardless of heart structural changes seen on echo. Generally the primary treatment once symptoms develop (congestive heart failure) is diuretics. My understanding from vet cardiologists (as of a couple of years ago at least) was that none of the other treatments that have been recommended (beta blockers and calcium channel blockers) have been shown to extend lifespan. Having said that, our MC mix lived four years post congestive heart failure, which is considered an extremely long period of time. He was on a calcium channel blocker the entire time. Cardiologist told me it wouldn't be helping him. I asked her how he had then managed to live so long post CHF not using diuretics for most of the time. She could not say. So, unfortunately, we see that little is really known about treating HCM in cats. I can tell you that Karma's last few hours of life were horrible for him and us.

HCM, has been a huge problems across the worlds cats, wiping out very young cats for generations.

The HCM Gene test which is what a lot of breeders use is not conclusive proof that there is no HCM as they are testing only on one known gene.

The best test is the Echo test but there is not really much point in testing a cat under 2 years old as the heart changes so much, the best time to test is after 3, but then you can be more hopeful if you have got your cat to that age its either clear or only has a mild case so hardly detectable.

However knowing the parents and grandparents are clear is also an added advantage. Most of my breeding stock I have 10 generations of and then some which are now pets and still alive so I would hope this is good and conclusive..

However a very good friend of mine had her girl tested by echo at 4 years old, and she was clear, she is now 9 years old and has HCM.. so what that is all about I do not know, her vets conclusion is the test was not clear in the first place.

In Europe the rule is simple cats have to be tested and these tests have to be shown if the cat is to be used at stud, or queens sold for breeding, however most pets owners are now asking to see the tests. Especially if they have lost a pet from this disease.

Responsible breeders should and do test that their cats are clear from all the known diseases, like HCM, PKD, PL PRA. before they breed off them.

Most of the UK breeders specially with the British short-hairs do not test for HCM but do test for PKD??

My Mainecoon breeding stock have been both gene tested and Echo tested and are Clear my 2 new girls will also be Echo tested when they are old enough, they have been gene tested and are clear, but not having the luxury of having information on their parents has made this a worrying time for us.

My British are tested for HCM and PKD. and My Abyssinians for PKD, PL and PRA.

Its a lot of money to lay out when you are testing and for the HCM and the eye test for the Abyssinians its a hell of a drive, my other tests I have them done at UCL, the peace of mind it gives to me is worth the money you pay out!

I have recently brought in new cats from the UK and also France and I was very impressed with the way forward for a lot of good and dedicated breeders, you might pay a little more for the breed cats but they come fully tested, and also blood typed and colour tested for the know colours like cinnamon- chocolate and colour pointed gene ( British Sh- Abyssinians - Somalis)


We can only hope that people both breeders and pet owners ask before they buy their pedigree pet cats, to see the documentation that comes with them just seeing on the breeders website HCM N/N. I believe is not proof enough!

I did all my homework when I bought Jet li and Aphrodite and Athene.. and the breeders of all my cats gave me photo copies of not only the parents but the grand parents etc etc .I could have just bought any cats and bred off them there was many for sale when I was looking, but I have never done this with my British and Abyssinians so I was not about to get sloppy with my daughters Mainecoons.

Ask to see the paperwork and tests before you buy saves a lot of heart ache later on down the line!

If we only breed off healthy cats we can then only improve the breed!

Here is the abstract of the most recent HCM paper I am aware of, directed specifically at hetero MCs:

J Vet Intern Med 2009;23:91–99

P r o s p e c t i v e Ec h o c a r d i o g r a p h ic an d T i s s u e D o p p l e r Im a g i n g
Scr eening o f a Popul ation of Maine C oon Cats T ested f or the A31P
Mu t a t i o n i n t h e M y o s i n - B i n d i n g P r o t e i n C G e n e :
A S p e c i fi c An a l y s i s of the H ete roz ygous Status

C. Carlos Sampedrano, V. Chetboul, J. Mary, R. Tissier, M. Abitbol, F. Serres, V. Gouni, A. Thomas, and J.-L. Pouchelon

Background: A mutation in the sarcomeric gene coding for the myosin-binding protein C gene has been identified in a
colony of Maine Coon cats with hypertrophic cardiomyopathy (MyBPC3-A31P mutation). However, the close correlation
between genotype and phenotype (left ventricular hypertrophy [LVH] and dysfunction) has never been assessed in a large pop-
ulation, particularly in heterozygous (Hetero) cats.

Objectives: To investigate LV morphology and function with echocardiography and tissue Doppler imaging (TDI) in a
population of Maine Coon cats tested for the MyBPC3-A31P mutation with focus on Hetero animals.

Animals: Ninety-six Maine Coon cats.

Methods: Prospective observational study. Cats were screened for the MyBPC3-A31P mutation and examined with both
echocardiography and 2-dimensional color TDI.

Results: Fifty-two out of 96 cats did not have the mutation (wild-type genotype, Homo WT), 38/96 and 6/96 were
Hetero- and homozygous-mutated (Homo M) cats, respectively. Only 11% of Hetero cats (4/38) had LVH and 29% (10/34) of
Hetero cats without LVH were >4 years old (4.1–11.5 years). LVH was also detected in 2 Homo WT cats (4%). A significantly
decreased (P < o .05) longitudinal E/A (ratio between early and late diastolic myocardial velocities) in the basal segment of
the interventricular septum was observed in Hetero cats without LVH (n = 34) compared with Homo WT cats without LVH
(n = 50), thus confirming that the Hetero status is associated with regional diastolic dysfunction (P < o .05).

Conclusions: The heterozygous status is not consistently associated with LVH and major myocardial dysfunction. More-
over, Homo WT cats can also develop LVH, suggesting that other genetic causes might be implicated.

This is quite a bit more positive paper about hetero MCs than the earlier papers. This paper did not follow cats to see when they died, though, it just looked for evidence of HCM-related heart changes at some (not very old) ages. Real question is average lifespan of clear (homo WT) vs. hetero M vs. homo M cats. This would be a very expensive undertaking with no financial benefits to any sort of drug company, so unlikely to ever be carried out.

Yes it is a shame that research is always profit driven......I would also be interested in how diet and obesity affects outcome for feline HCM! But that's another story, and another piece of research that wont get done. Although the cat food industry might be interested.....

NCarver- it is indeed encouraging that heterozygous status was not strongly associated with LVH, although as you say, some of the cats weren't massively old. I'm really sorry to hear about your cat which died through HCM- I only hope that Sylvester's murmur does not worsen (my boss suggested I put him on beta blockers early, but he is only drawing from experience with humans.... but then it seems like this is all the information we have).

Hi Catlover,what grade murmur has Sylvie got,my daughters MC had one picked up at a pretty early age,it stayed at grade 1 for several years & has now gone to grade two,she is 11.5ysr old,full of life & in no need of medication yet,I know there are lots of causes of heart murmurs in cats,some cardiac,some non cardiac but at the momen it seems as if it is a MC then it must be HCM related.As a matter of interest{all my cats are pet neuters} I swabbed three of them,all came from different breeders & they all came back as negatives,the eldest one is 13.5yrs & she is the mother of the above cat.
It is going to be very interesting to see over the next few years what the outcome of this is,especially if another gene is isolated....

My ancient moggie Barney has a grade 6 murmour, but no vet has said it needs treatment. How much of a worry should it be anyway?

They can be a very big worry,some causes are really dangerous to the animal,some are dangerous if not treated accordingly,some just carry on with life & no medication,obviously its all down to the cause, but if Barney is happy & enjoying life & your vet hasn't suggested him going on medication then he must be happy that Barney is coping.....

Quote:

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Originally Posted by jckkerrison

Hi Catlover,what grade murmur has Sylvie got,my daughters MC had one picked up at a pretty early age,it stayed at grade 1 for several years & has now gone to grade two,she is 11.5ysr old,full of life & in no need of medication yet,I know there are lots of causes of heart murmurs in cats,some cardiac,some non cardiac but at the momen it seems as if it is a MC then it must be HCM related.As a matter of interest{all my cats are pet neuters} I swabbed three of them,all came from different breeders & they all came back as negatives,the eldest one is 13.5yrs & she is the mother of the above cat.
It is going to be very interesting to see over the next few years what the outcome of this is,especially if another gene is isolated....

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The vet didn't say, just commented on it then said 'but then he seems a bit stressed by being here, his heart is going like the clappers'. I assume therefore that it is fairly low grade- having now met the breeder it sounds like he didn't have a murmur when vet checked by her as a kitten. I guess all I can do at the moment is make sure he has a stress-free life. Dudley is a bit of a stressor and has definitely made him more active playing 'chase me chase me', but hopefully having company will be good for him in the long run!

Quote:

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Originally Posted by Catlover

I'm really sorry to hear about your cat which died through HCM- I only hope that Sylvester's murmur does not worsen (my boss suggested I put him on beta blockers early, but he is only drawing from experience with humans.... but then it seems like this is all the information we have).

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Though his passing was of course very sad, we did manage to give him almost four years of great and actually quite healthy life. Every time I think about his last few hours, though, it is very hard not to get upset. If we had known that nothing would work and how much he would suffer we would have had him put down immediately, but we and the vets assumed he could be pulled through the incident (which came quite out of the blue, with no warning signs). Some cats with HCM just pass suddenly and with little/no pain. Others, though, go into CHF or throw clots and suffer greatly at the end.

At various points and in various combinations, Karma was on diuretic, beta-blocker, and calcium channel blocker. We eventually reduced him to just the calcium channel blocker, as that was what seemed to make him feel best. Beta-blocker definitely reduced his energy levels. As far as I know, though, best practice for vet cardiologists in US is still not to do any treatment at all on unsymptomatic cats as they do not believe any treatments slow progression or prolong life. We are still planning on having our hetero girl Allie echoed at least every two years so that we know the condition of her heart and thus might have better warning about any symptoms that develop. In a sense, though, it is pointless as nothing would be done based just on the echo results.

As already stated, some murmurs could be quite benign and some could indicate a serious problem. The only way to know for certain is to have an echocardiogram done by what in the US is called a "board certified veterinary cardiologist." Not sure what analog would be in UK. In the US vet cardiologists can be hard to find unless you live in a very big city. Our experience with even "radiologist specialist vets" has not been good, and I would never recommend spending the money with such a vet. I would probably give it a while and see what happens on vet next visit. Certainly not all murmurs are HCM and not all HCM cats even have murmurs.

Hi catlover,yep stress & infection are two of the main causes that the vet picks up heart murmurs from in both cats & dogs but when the animal improves then the murmur more often than not disappears,if stress related it is normally in the younger animal but as they get used to coming in although they still hate it the stress levels must reduce as the murmur very often is no longer audible.
Oh what a worry having pets is,you wouldn't be without them but....!

The most recent study is out of France:

Prevalence of the MYBPC3-A31P mutation in a large ... [J Vet Cardiol. 2010] - PubMed result

Abstract

OBJECTIVES: The MYBPC3-A31P mutation has been identified in the USA in a colony of Maine Coon cats with an autosomal dominant hypertrophic cardiomyopathy (HCM). The objectives of this prospective study were: 1) to evaluate the prevalence of this mutation in a large feline population from Europe; 2) to compare these data with the prevalence of HCM in the Maine Coon breed.

ANIMALS AND METHODS: 1) 3757 cats from different breeds including 2744 Maine Coon cats were screened for the mutation. 2) 164/2744 Maine Coon cats were subjected to echocardiography (Echo-Group, mean age = 2.6 years [0.3-11.5]).

RESULTS: 1) In the whole study population, the mutation was only found in Maine Coon cats (prevalence = 41.5%), except for one British Longhair cat. 2) 55/164 (34%) cats from the Echo-Group carried the mutation while only 12/164 (7%; 5/48 heterozygous, 5/7 homozygous mutated, 2/109 homozygous wild-type cats) showed HCM. MYBPC3-A31P was associated with a significant increased risk of HCM (relative risk = 9.91).

CONCLUSION: The MYBPC3-A31P mutation is highly prevalent in Maine Coon cats in Europe and appears to be breed specific with potential marginal events. Young unaffected mutated cats and affected homozygous wild-type cats illustrate the phenotypic and etiological heterogeneity of feline HCM, as demonstrated in humans.
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There was an extremely elevated incidence of HCM in Maine Coons homozygous for the mutation - 71%.

Thanks Ekimmel for taking the time to post. Unfortunately I'm finding it hard to decipher this information. What is a 'marginal event'? How do I know if my cat is mutated, or does that not matter? Could you explain the conclusion? Sorry for being a bit thick... but, help!

Nice to see some new research, and thanks for the post.

Quote:

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Originally Posted by Howlinbob

Unfortunately I'm finding it hard to decipher this information. What is a 'marginal event'? How do I know if my cat is mutated, or does that not matter? Could you explain the conclusion? Sorry for being a bit thick... but, help!

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Let me take a shot at the above questions from reading the abstract...

The researchers assembled a population of 3757 European cats of which 2744 were Maine Coons.

They screened these cats for the known HCM mutation and found only one non-MC cat that tested positive. 41.5% of the MCs had the mutation (abstract does not say fraction with one copy, heterozygous, vs. two copies, homozygous). So this is largely a MC-specific health issue.

164 of the MCs were screened by echocardiogram to look for evidence of heart changes indicative of HCM. 55 (34%) of the echoed MCs had the mutation. Only 12 of the 164 cats showed evidence of HCM changes, broken down as follows: 5/48 heterozygous, 5/7 homozygous mutated, 2/109 homozygous wild-type cats (wild-type means free of the mutation).

So here the probability of MCs free of the mutation showing HCM changes was less than 2%, while the probability for hetero MCs was 10%, but for homo mutated cats it was 71%!

So again we see that homozygous MCs--those with two copies of the MYBPC3 mutation--are virtually certain to undergo structural changes of the heart consistent with HCM. How many of these will show symptoms and how many will die prematurely was not addressed by this study.

Hetero MCs fared much better, though I note that the median age of the echoed population of cats was stated as 2.6, which is quite young. If it was more like 5, we might have seen the hetero percentage be much higher (and the homo group be much smaller due to them having died!).

What does this tell a person thinking of buying a MC? In my opinion it tells them quite clearly that if they want to buy a MC that has the best chance to live a long and healthy life, they should absolutely avoid getting a kitten that was homozygous for the mutation, and most likely also avoid a hetero kitten.

The only thing I found surprising here was the claim that over 40% of European MCs carry the mutation. That makes buying from breeders that do not do HCM testing pretty risky.

As for how you can find out about your own cat, well ideally your breeder could tell you. However it is possible to have your cats tested with a simple mouth swab. Here is the original lab that does it (run by the person that discovered the mutation):
Cat DNA Tests from the VCGL at the College of Veterinary Medicine

Other labs now do the testing as well, though whether they are as reliable is probably an open question.