# Sticky  Current thinking on HCM (2017)



## Ceiling Kitty

For anyone who is interested, I've attempted to summarise current scientific thinking on feline HCM based on the conferences I attended throughout 2017.

If anything doesn't make sense, you need something explaining or wish to discuss it more, just drop a line on the thread below.  It is quite heavy going!

*BACKGROUND AND GENETICS*

HCM in cats is defined as:
- a left ventricular diastolic wall thickness of around ≥6mm (though different cut offs exist depending on what study you read, personal thoughts of the specialist involved etc);
- myocyte disarray on histology.

Cats are increasingly being used as models for the study of human HCM.

Humans

>1400 genetic mutations have been identified in humans with HCM. Around 70% of these are found in the MYH7 and MYBPC3 genes. Most human mutations are 'private', which means they are unique to a single family.

The situation in humans is very complicated, with genetic testing also identifying thousands of single missense mutations that may or may not be relevant - these are known as 'variants of unknown significance'. In human medicine, patients receive genetic counselling prior to gene testing because of the complexity of interpreting their results.

Morever, in humans the genes associated with HCM have incomplete penetrance, meaning that the HCM genotype results in a wide range of phenotypes amongst affected individuals.

Cats

As of early 2018, specific genes have only been identified for the Maine Coon and Ragdoll breeds. Work to identify genes in Norwegian Forest Cats is ongoing as we speak.

Annotation of the feline genome in general is improving, especially with the work of Leslie Lyons in the States on her 99 Lives Project.
http://felinegenetics.missouri.edu/

The mutations identified in both Maine Coons and Ragdolls are, like a large proportion of humans, in the MYBPC3 (myosin binding protein C3) gene.

The mutation in Maine Coons is A31P. 22-42% of Maine Coons are positive for this gene mutation - but some Maine Coons with HCM DON'T have it.

The mutation in Ragdolls is R820W.

Work in Ragdolls (Borgeat, J Vet Cardiol 2014) has shown that homozygous cats are more severely affected, with a higher risk of sudden death and earlier onset of disease.
https://www.ncbi.nlm.nih.gov/pubmed/24906243

Like in humans, we can see mixed phenotypes within feline families. It is currently not clear whether these are the result of multiple mutations, or different expressions of a single mutation. It has also been shown that phenotype can change over time and with age in cats.

In addition, we know that Maine Coons homozygous for the A31P mutation have unusually reactive platelets and display vascular changes, which may increase their risk of developing thrombotic disease.

Aetiology

In humans, most HCM cases are due to the sarcomeric protein gene mutations discussed above, but systemic diseases, neuromuscular disease and glycogen storage diseases have also been highlighted as causes. Approximately 30% of human cases are of unknown cause.

In humans, any heart showing the HCM phenotype is HCM until proven otherwise. This is not necessarily the case in cats, amongst whom HCM 'phenocopies' are common.

Hyperthyroidism, hypertension, acromegaly and neoplastic infiltration (usually lymphoma) all cause a 'hypertrophic phenotype' in cats without known sarcomeric mutations and possibly no histological features. These cases may be reversible. Another example is the recently characterised transient myocardial thickening, which is discussed in more detail later.

We still don't know for certain how the mutation in contractile proteins causes hypertrophy. Haploinsufficiency is not suspected, but current thinking supports the 'poison polypeptide' hypothesis, which proposes that mutant sarcomeric proteins incorporate into cardiac myofibrils and act as dominant negative proteins.

Increased sensitivity of the cardiac muscle to calcium has been identified in homozygous Ragdolls.

There are multiple current 'unknowns' in feline HCM, which can have implications for screening protocols. For example, we don't know for certain whether the onset of left ventricular (LV) hypertrophy is age-related, or whether it can be influenced by environmental factors such as obesity or neutering. The same is true in human medicine, with little understood.

Prevalence of HCM

0.2% people (1 in 500)
15% cats
16% DSH, 26% pedigrees

*DIAGNOSIS*

Definitive diagnosis of feline HCM requires histology, which is not possible ante-mortem. Even so, there is poor consensus regarding the pathology to create a histological 'gold standard' classification.

The principle aim of diagnosis is to identify high-risk asymptomatic cats, who may need anti-thrombotic treatment due to a risk of developing aortic thromboembolism (ATE).

Dynamic auscultation

Feline heart murmurs are highly influenced by adrenaline. In the thesis linked below, which looked at heart murmurs in 103 outwardly healthy cats, 16% of the cats had a heart murmur at rest. This increased to 27% after a dynamic manoeuvre (lifting the cats quickly into the air at least twice).
https://vtechworks.lib.vt.edu/bitstream/handle/10919/43704/CPAIGE_THESIS.pdf?sequence=2&isAllowed=y

It is also known that inadvertent compression of the chest wall with a stethoscope can induce a DRVOTO (dynamic right ventricular outflow tract obstruction), which can cause a murmur.

It seems that chest auscultation techniques are more complex than simply placing the stethoscope in different places on the chest in identifying feline heart murmurs.

Echocardiography

Echocardiography is the most common method of diagnosis. LAE (left atrial enlargement) is a major predictor of symptomatic disease in high risk cats.

Unfortunately there are significant issues (which have been highlighted in studies) with poor inter-observer agreement - even amongst cardiac specialists - and even poor intra-observer agreement. It has not even been agreed across the profession that a LVDWT of 6mm is a suitable diagnostic criterion for HCM.

Better criteria are needed for the diagnosis and classification of feline HCM.
http://onlinelibrary.wiley.com/doi/10.1046/j.1439-0442.2003.00546.x/full
http://www.sciencedirect.com/science/article/pii/S1760273410000603

Electrocardiography

ECG testing is very important in humans, and is sometimes used to screen young athletes for HCM. It is a sensitive test, meaning that a normal ECG is a good indication of a healthy heart, but poorly specific (lots of false positives can result). Echocardiography is used as a follow-up for abnormal ECG traces in humans.

Currently, ECG seems less helpful in the cat. Some changes have been identified in cats with HCM, but at present we have no firm criteria for diagnosis.

Other imaging techniques

Cardiac MRI is important in humans, since it is more detailed than echo, can calculate LV mass and can identify myocardial fibrosis. However, is not useful in cats, as general anaesthesia is required in this species.

CT scanning may be possible without general anaesthesia, using the new 'mousetrap' devices, and is less stressful than echo.

Micro-CT is a new imaging modality in its infancy - not currently available in veterinary medicine, but a possible hope for the future. It is a CT scanning technique that is so detailed that it can examine the cardiac myofibres and myocytes on a microscopic level.

Strain rate imaging - an echo technique looking at deformation of the heart muscle - is also promising but very new in veterinary medicine at the moment.

Family history

Veterinary cardiologist Virginia Luis-Fuentes, who has done a lot of work in feline HCM, believes that we need to spend more time incorporating family history (where known) in screening for feline HCM, and she has collaborated with the PawPeds database to try and improve this.

Cardiac biomarkers

The use of NT-proBNP is controversial amongst veterinary cardiologists.

It was incorporated in JR Payne's recent 'CatScan' study, and found that it can identify high-risk cats but not low-risk cases, and cannot differentiate cats with HCM from those without HCM.
http://onlinelibrary.wiley.com/doi/10.1111/jvim.12215/full

A stepwise increase in mortality with increasing NT-proBNP has been shown in both humans and cats.

*TREATMENT*

There are very few new treatments for HCM in humans.

There is currently NO published evidence that ANY medication can delay the onset of signs in cats with subclinical HCM. In human medicine, there is evidence that ACE inhibitors can prevent the remodelling of myocardium, and may modify disease progression. No such benefit has been shown in Maine Coons.

Pimobendan is increasingly being used in feline congestive heart failure cases (unlicensed), and anecdotally seems to improve survival time and clinical response.

A promising new molecule, MYK-461 (no chemical name yet) is currently undergoing tests. MYK-461 is an inhibitor of sarcomere force output, which reduces the contractility of myocardial sarcomeres. It may reduce cardiac work without compromising systolic function.

In the following study, MYK-461 reduced contractility, eliminated systolic anterior motion of the mitral valve (SAM - see below) and relieved LVOT pressure gradients.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0168407

ATE

Following the FATCAT study a couple of years ago, clopidogrel (Plavix) is the current drug of choice for the prevention of ATE in cats with HCM, preferred to aspirin.
http://www.vet.cornell.edu/news/FatCatStudy.cfm

Other medications being worked on at the moment include direct thrombin anatgonists and factor Xa antagonists (a study comparing the latter with clopidogrel is ongoing).

It has been shown that clopidogrel attentuates ADP-mediated P-selectin expression (involved in platelet aggregation and thrombus formation) in the homozygous Maine Coons with increased platelet reactivity, this reducing ADP-induced platelet aggregation.
http://www.vetmed.ucdavis.edu/resea...Zeta_Research_Award_Nominatin_Ronald_Li-2.pdf

*SURVIVAL AND PROGNOSIS*

The median survival time reported in cats with HCM is approximately 13 years. This means that 50% of cats diagnosed with HCM were still alive at 13 years of age (and many will have lived longer). 50% died before they reached the age of 13 years.

Mortality due to HCM can occur at any age.

While a significant cause of feline mortality, it has been shown to be a less common cause of death than urinary tract disease, trauma and cancer.
https://www.ncbi.nlm.nih.gov/pubmed/19780926

Survival is worse in humans diagnosed under the age of 50 years. Over the age of 50, survival in HCM patients is no different to the general population. Whether or not a similar phenomenon exists in cats is currently not known.

*CARDIAC CHEST PAIN, MYOCARDIAL INFARCTION AND SAM/DLVOTO*

SAM - systolic anterior motion of the mitral valve.
DLVOTO - dynamic left ventricular outflow tract obstruction (generally caused by SAM).

SAM generally results from elongation of the mitral valve leaflet, abnormalities of the chordae tendine and enlargement of the papillary muscles. It can result from HCM, or may be a consequence of congenital mitral dysplasia. In humans, genetic mutations can cause these abnormalities as well as HCM.

DLVOTO is present in around 1/3 of humans and cats with HCM. It is considered a significant issue in humans, resulting in chest pain, breathlessness and some cases of sudden death. In cats, the outcome is generally much better than in humans, though it may be painful, and MAY be associated with an increased risk of myocardial infarction (heart attack).

Myocardial infarction, an extreme end point of ischaemia (tissue death due to interruption of the blood supply), is not uncommon in cats.

A degree of ischaemia may be present in HCM cats before we see infarction. The cardiac biomarker cTnI may be a marker of ischaemia. Myocardial infarction can manifest as sudden death, arrhythmia or syncope (fainting). In surviving cats, the affected myocardium is replaced with fibrous tissue and can appear thin even in cats with a previous history of HCM. The coronary vasculature is unusual in these cats, due to angiogenesis.

AliveCor is a mobile ECG monitor in human medicine, which may have future applications in feline medicine.

*TRANSIENT MYOCARDIAL THICKENING*

This is a relatively recent discovery in cats, backed up with very limited data at the moment (only one case series exists as of 2018).
http://onlinelibrary.wiley.com/doi/10.1111/jvim.14897/full

It is seen in young cats following an antecedent event (stress). There is sudden onset thickening of the myocardium - thought to be oedema of the muscle - with acute, low-output congestive heart failure. On bloodwork, cardiac troponin levels are high and reflective of severe acute muscle damage.

The myocardial thickening in these cases does not mean the cat has HCM, and may not indicate immediate euthanasia. They usually respond quickly (if they survive at all), but it can take several weeks for the myocardial thickening to resolve. It is usually not recurrent.

There is no way to distinguish transient myocardial thickening from true HCM on echo. Some cats will not survive the acute episode, even with intensive care.


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## Sacrechat

There is a research study currently underway on heart disease in Birmans. I have given permission for my cats medical records to be obtained from the University of Liverpool and will let them scan my cats if a day and location can be arranged not too far from where I live. I arranged to have bloods taken and sent to the researchers from one of my cats today. The other is not due another blood test just yet, but I will have his bloods sent to the study when it is time for his tests. Here's a link to the Birman Cat Club website with updates on research done and being done. http://www.birmancatclub.co.uk/heartfund.html


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## Ceiling Kitty

That's good to know @Sacremist, thanks!

If anyone is aware of any other genetic research for HCM in other breeds, please be sure to add it here!


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## stockwellcat.

Thank you for the above @Ceiling Kitty.

Can I ask something?
In December 2016 there was a publication in the Vet Times about a drug on trial in the US called MYK-461, was there any advancement on this drug at UC Davis? The drug from what I have read was showing real promise but there has been no updates. I tried emailing UC Davis and got no response.

Thanks your input would be greatly appreciated.

https://www.ucdavis.edu/news/new-drug-heart-disease-shows-promise-cats-and-humans/

http://science.sciencemag.org/content/351/6273/617

https://www.vettimes.co.uk/news/feline-heart-disease-treatment-shows-promise/

http://mrcvs.co.uk/en/news/15340/New-heart-disease-drug-offers-hope-for-cats-and-humans

http://www.2ndchance.info/MYK-461.htm

Here's the research article:
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0168407


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## stockwellcat.

Ceiling Kitty said:


> For anyone who is interested, I've attempted to summarise current scientific thinking on feline HCM based on the conferences I attended throughout 2017.
> 
> If anything doesn't make sense, you need something explaining or wish to discuss it more, just drop a line on the thread below.  It is quite heavy going!
> 
> *BACKGROUND AND GENETICS*
> 
> HCM in cats is defined as:
> - a left ventricular diastolic wall thickness of around ≥6mm (though different cut offs exist depending on what study you read, personal thoughts of the specialist involved etc);
> - myocyte disarray on histology.
> 
> Cats are increasingly being used as models for the study of human HCM.
> 
> Humans
> 
> >1400 genetic mutations have been identified in humans with HCM. Around 70% of these are found in the MYH7 and MYBPC3 genes. Most human mutations are 'private', which means they are unique to a single family.
> 
> The situation in humans is very complicated, with genetic testing also identifying thousands of single missense mutations that may or may not be relevant - these are known as 'variants of unknown significance'. In human medicine, patients receive genetic counselling prior to gene testing because of the complexity of interpreting their results.
> 
> Morever, in humans the genes associated with HCM have incomplete penetrance, meaning that the HCM genotype results in a wide range of phenotypes amongst affected individuals.
> 
> Cats
> 
> As of early 2018, specific genes have only been identified for the Maine Coon and Ragdoll breeds. Work to identify genes in Norwegian Forest Cats is ongoing as we speak.
> 
> Annotation of the feline genome in general is improving, especially with the work of Leslie Lyons in the States on her 99 Lives Project.
> http://felinegenetics.missouri.edu/
> 
> The mutations identified in both Maine Coons and Ragdolls are, like a large proportion of humans, in the MYBPC3 (myosin binding protein C3) gene.
> 
> The mutation in Maine Coons is A31P. 22-42% of Maine Coons are positive for this gene mutation - but some Maine Coons with HCM DON'T have it.
> 
> The mutation in Ragdolls is R820W.
> 
> Work in Ragdolls (Borgeat, J Vet Cardiol 2014) has shown that homozygous cats are more severely affected, with a higher risk of sudden death and earlier onset of disease.
> https://www.ncbi.nlm.nih.gov/pubmed/24906243
> 
> Like in humans, we can see mixed phenotypes within feline families. It is currently not clear whether these are the result of multiple mutations, or different expressions of a single mutation. It has also been shown that phenotype can change over time and with age in cats.
> 
> In addition, we know that Maine Coons homozygous for the A31P mutation have unusually reactive platelets and display vascular changes, which may increase their risk of developing thrombotic disease.
> 
> Aetiology
> 
> In humans, most HCM cases are due to the sarcomeric protein gene mutations discussed above, but systemic diseases, neuromuscular disease and glycogen storage diseases have also been highlighted as causes. Approximately 30% of human cases are of unknown cause.
> 
> In humans, any heart showing the HCM phenotype is HCM until proven otherwise. This is not necessarily the case in cats, amongst whom HCM 'phenocopies' are common.
> 
> Hyperthyroidism, hypertension, acromegaly and neoplastic infiltration (usually lymphoma) all cause a 'hypertrophic phenotype' in cats without known sarcomeric mutations and possibly no histological features. These cases may be reversible. Another example is the recently characterised transient myocardial thickening, which is discussed in more detail later.
> 
> We still don't know for certain how the mutation in contractile proteins causes hypertrophy. Haploinsufficiency is not suspected, but current thinking supports the 'poison polypeptide' hypothesis, which proposes that mutant sarcomeric proteins incorporate into cardiac myofibrils and act as dominant negative proteins.
> 
> Increased sensitivity of the cardiac muscle to calcium has been identified in homozygous Ragdolls.
> 
> There are multiple current 'unknowns' in feline HCM, which can have implications for screening protocols. For example, we don't know for certain whether the onset of left ventricular (LV) hypertrophy is age-related, or whether it can be influenced by environmental factors such as obesity or neutering. The same is true in human medicine, with little understood.
> 
> Prevalence of HCM
> 
> 0.2% people (1 in 500)
> 15% cats
> 16% DSH, 26% pedigrees
> 
> *DIAGNOSIS*
> 
> Definitive diagnosis of feline HCM requires histology, which is not possible ante-mortem. Even so, there is poor consensus regarding the pathology to create a histological 'gold standard' classification.
> 
> The principle aim of diagnosis is to identify high-risk asymptomatic cats, who may need anti-thrombotic treatment due to a risk of developing aortic thromboembolism (ATE).
> 
> Dynamic auscultation
> 
> Feline heart murmurs are highly influenced by adrenaline. In the thesis linked below, which looked at heart murmurs in 103 outwardly healthy cats, 16% of the cats had a heart murmur at rest. This increased to 27% after a dynamic manoeuvre (lifting the cats quickly into the air at least twice).
> https://vtechworks.lib.vt.edu/bitstream/handle/10919/43704/CPAIGE_THESIS.pdf?sequence=2&isAllowed=y
> 
> It is also known that inadvertent compression of the chest wall with a stethoscope can induce a DRVOTO (dynamic right ventricular outflow tract obstruction), which can cause a murmur.
> 
> It seems that chest auscultation techniques are more complex than simply placing the stethoscope in different places on the chest in identifying feline heart murmurs.
> 
> Echocardiography
> 
> Echocardiography is the most common method of diagnosis. LAE (left atrial enlargement) is a major predictor of symptomatic disease in high risk cats.
> 
> Unfortunately there are significant issues (which have been highlighted in studies) with poor inter-observer agreement - even amongst cardiac specialists - and even poor intra-observer agreement. It has not even been agreed across the profession that a LVDWT of 6mm is a suitable diagnostic criterion for HCM.
> 
> Better criteria are needed for the diagnosis and classification of feline HCM.
> http://onlinelibrary.wiley.com/doi/10.1046/j.1439-0442.2003.00546.x/full
> http://www.sciencedirect.com/science/article/pii/S1760273410000603
> 
> Electrocardiography
> 
> ECG testing is very important in humans, and is sometimes used to screen young athletes for HCM. It is a sensitive test, meaning that a normal ECG is a good indication of a healthy heart, but poorly specific (lots of false positives can result). Echocardiography is used as a follow-up for abnormal ECG traces in humans.
> 
> Currently, ECG seems less helpful in the cat. Some changes have been identified in cats with HCM, but at present we have no firm criteria for diagnosis.
> 
> Other imaging techniques
> 
> Cardiac MRI is important in humans, since it is more detailed than echo, can calculate LV mass and can identify myocardial fibrosis. However, is not useful in cats, as general anaesthesia is required in this species.
> 
> CT scanning may be possible without general anaesthesia, using the new 'mousetrap' devices, and is less stressful than echo.
> 
> Micro-CT is a new imaging modality in its infancy - not currently available in veterinary medicine, but a possible hope for the future. It is a CT scanning technique that is so detailed that it can examine the cardiac myofibres and myocytes on a microscopic level.
> 
> Strain rate imaging - an echo technique looking at deformation of the heart muscle - is also promising but very new in veterinary medicine at the moment.
> 
> Family history
> 
> Veterinary cardiologist Virginia Luis-Fuentes, who has done a lot of work in feline HCM, believes that we need to spend more time incorporating family history (where known) in screening for feline HCM, and she has collaborated with the PawPeds database to try and improve this.
> 
> Cardiac biomarkers
> 
> The use of NT-proBNP is controversial amongst veterinary cardiologists.
> 
> It was incorporated in JR Payne's recent 'CatScan' study, and found that it can identify high-risk cats but not low-risk cases, and cannot differentiate cats with HCM from those without HCM.
> http://onlinelibrary.wiley.com/doi/10.1111/jvim.12215/full
> 
> A stepwise increase in mortality with increasing NT-proBNP has been shown in both humans and cats.
> 
> *TREATMENT*
> 
> There are very few new treatments for HCM in humans.
> 
> There is currently NO published evidence that ANY medication can delay the onset of signs in cats with subclinical HCM. In human medicine, there is evidence that ACE inhibitors can prevent the remodelling of myocardium, and may modify disease progression. No such benefit has been shown in Maine Coons.
> 
> Pimobendan is increasingly being used in feline congestive heart failure cases (unlicensed), and anecdotally seems to improve survival time and clinical response.
> 
> A promising new molecule, MYK-461 (no chemical name yet) is currently undergoing tests. MYK-461 is an inhibitor of sarcomere force output, which reduces the contractility of myocardial sarcomeres. It may reduce cardiac work without compromising systolic function.
> 
> In the following study, MYK-461 reduced contractility, eliminated systolic anterior motion of the mitral valve (SAM - see below) and relieved LVOT pressure gradients.
> http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0168407
> 
> ATE
> 
> Following the FATCAT study a couple of years ago, clopidogrel (Plavix) is the current drug of choice for the prevention of ATE in cats with HCM, preferred to aspirin.
> http://www.vet.cornell.edu/news/FatCatStudy.cfm
> 
> Other medications being worked on at the moment include direct thrombin anatgonists and factor Xa antagonists (a study comparing the latter with clopidogrel is ongoing).
> 
> It has been shown that clopidogrel attentuates ADP-mediated P-selectin expression (involved in platelet aggregation and thrombus formation) in the homozygous Maine Coons with increased platelet reactivity, this reducing ADP-induced platelet aggregation.
> http://www.vetmed.ucdavis.edu/resea...Zeta_Research_Award_Nominatin_Ronald_Li-2.pdf
> 
> *SURVIVAL AND PROGNOSIS*
> 
> The median survival time reported in cats with HCM is approximately 13 years. This means that 50% of cats diagnosed with HCM were still alive at 13 years of age (and many will have lived longer). 50% died before they reached the age of 13 years.
> 
> Mortality due to HCM can occur at any age.
> 
> While a significant cause of feline mortality, it has been shown to be a less common cause of death than urinary tract disease, trauma and cancer.
> https://www.ncbi.nlm.nih.gov/pubmed/19780926
> 
> Survival is worse in humans diagnosed under the age of 50 years. Over the age of 50, survival in HCM patients is no different to the general population. Whether or not a similar phenomenon exists in cats is currently not known.
> 
> *CARDIAC CHEST PAIN, MYOCARDIAL INFARCTION AND SAM/DLVOTO*
> 
> SAM - systolic anterior motion of the mitral valve.
> DLVOTO - dynamic left ventricular outflow tract obstruction (generally caused by SAM).
> 
> SAM generally results from elongation of the mitral valve leaflet, abnormalities of the chordae tendine and enlargement of the papillary muscles. It can result from HCM, or may be a consequence of congenital mitral dysplasia. In humans, genetic mutations can cause these abnormalities as well as HCM.
> 
> DLVOTO is present in around 1/3 of humans and cats with HCM. It is considered a significant issue in humans, resulting in chest pain, breathlessness and some cases of sudden death. In cats, the outcome is generally much better than in humans, though it may be painful, and MAY be associated with an increased risk of myocardial infarction (heart attack).
> 
> Myocardial infarction, an extreme end point of ischaemia (tissue death due to interruption of the blood supply), is not uncommon in cats.
> 
> A degree of ischaemia may be present in HCM cats before we see infarction. The cardiac biomarker cTnI may be a marker of ischaemia. Myocardial infarction can manifest as sudden death, arrhythmia or syncope (fainting). In surviving cats, the affected myocardium is replaced with fibrous tissue and can appear thin even in cats with a previous history of HCM. The coronary vasculature is unusual in these cats, due to angiogenesis.
> 
> AliveCor is a mobile ECG monitor in human medicine, which may have future applications in feline medicine.
> 
> *TRANSIENT MYOCARDIAL THICKENING*
> 
> This is a relatively recent discovery in cats, backed up with very limited data at the moment (only one case series exists as of 2018).
> http://onlinelibrary.wiley.com/doi/10.1111/jvim.14897/full
> 
> It is seen in young cats following an antecedent event (stress). There is sudden onset thickening of the myocardium - thought to be oedema of the muscle - with acute, low-output congestive heart failure. On bloodwork, cardiac troponin levels are high and reflective of severe acute muscle damage.
> 
> The myocardial thickening in these cases does not mean the cat has HCM, and may not indicate immediate euthanasia. They usually respond quickly (if they survive at all), but it can take several weeks for the myocardial thickening to resolve. It is usually not recurrent.
> 
> There is no way to distinguish transient myocardial thickening from true HCM on echo. Some cats will not survive the acute episode, even with intensive care.


I see that studies have been carried out for Ragdolls and Maine coons but moggies also get HCM like my cat is a dsh and has HCM. Why hasn't studies been carried out in moggies?


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## Ceiling Kitty

@stockwellcat.

What I've written about MYK-461 above is all I know about it at the moment. It takes years for things to develop from initial tests into a useable product, and of course unfortunately not all substances make it that far.

Regarding the studies, the vast majority of them ARE in moggies.


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## Tigermoon

I have also helped in the research currently ongoing in birmans. We are hoping for a test in the nearish future. 
There is also research for HCM in persians taking place now.


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## stockwellcat.

Ceiling Kitty said:


> @stockwellcat.
> 
> What I've written about MYK-461 above is all I know about it at the moment. It takes years for things to develop from initial tests into a useable product, and of course unfortunately not all substances make it that far.
> 
> Regarding the studies, the vast majority of them ARE in moggies.


Thank you for answering my questions. I didn't realise moggies are included in the studies I just thought it was pedigree cats like those stated above. That's good news they are included.


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## stockwellcat.

I hope you don't mind me just giving a little update on MYK-461 @Ceiling Kitty?

I have had a reply from one of the researchers at UC Davis in the last 10 minutes via email.

This is the latest situation with MYK-461.


> MYK-461 is not in the clinical trial phase for client owned cats yet but we continue to research this compound with this hope in the future.


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## chillminx

Great post @Ceiling Kitty  . Very useful information for future reference.

I believe the question of making a thread into a 'sticky' may be rather a delicate matter, but on the basis that 'she/he who doesn't ask, never gets' could I please ask @lymorelynn if there is any possibility of this thread being made a sticky?


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## lymorelynn

chillminx said:


> Great post @Ceiling Kitty  . Very useful information for future reference.
> 
> I believe the question of making a thread into a 'sticky' may be rather a delicate matter, but on the basis that 'she/he who doesn't ask, never gets' could I please ask @lymorelynn if there is any possibility of this thread being made a sticky?


I'll have a look and see if there's room (after I made a mess of trying to tidy them up last year :Bag) 
I did think when I saw it this morning it was something worth keeping


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## Sacrechat

Just wanted to say that research being carried out in Birmans is being funded by the Birman Cat Club who raise money through Birman breeders and pet owners in the Birman loving community. I’m sure all research will ultimately help all cats.


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## TallulahCat

Thanks for this @Ceiling Kitty

My cat has HCM so this is interesting to read. He's part Ragdoll, obviously from a BYB (I got him as a rescue).


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## Bigsize9foot

My 7 month old male moggy (rescued) has just been diagnosed with HCM. The vet leads me to believe it is rare in a cat so young. 

We are awaiting the cardiologist scan to give us prognosis but they will just say “guarded” at the moment. I’m hoping for some survival figures like the ones above.


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## Tigermoon

Sacremist said:


> Just wanted to say that research being carried out in Birmans is being funded by the Birman Cat Club who raise money through Birman breeders and pet owners in the Birman loving community.


The club would like you to believe this, but it is not true.

I was sent this article today. It is about cardiomyopathy in humans but gives some rather interesting detail into what goes on within the heart of a sufferer.
https://theconversation.com/dilated...se-that-killed-george-michael-explained-74227


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## QOTN

I thought DCM and HCM are different. In DCM the heart is enlarged but in HCM the heart wall is thickened. Is this not true?


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## Rufus15

@Ceiling Kitty would you mind clarifying for me please, is the current school of thought that heart scans in Maine Coons are still beneficial to detect the onset of HCM or is gene testing and breeding from n/n parents the best option?


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## Tigermoon

Rufus15 said:


> @Ceiling Kitty would you mind clarifying for me please, is the current school of thought that heart scans in Maine Coons are still beneficial to detect the onset of HCM or is gene testing and breeding from n/n parents the best option?


Ideally you are should to do both as the gene test will only find the most gene responsible but there are probably others. Scans won't tell you if your cat is likely to get cardiomyopathy but it will tell you if there are any changes to the heart.


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## Rufus15

Tigermoon said:


> Ideally you are should to do both as the gene test will only find the most gene responsible but there are probably others. Scans won't tell you if your cat is likely to get cardiomyopathy but it will tell you if there are any changes to the heart.


This is partly my question - is there much point in the scan as you can breed from a cat that has a normal heart at 1 but an abnormal heart at 6, after they've had a number of litters. Ceiling Kitty said:



Ceiling Kitty said:


> It has not even been agreed across the profession that a LVDWT of 6mm is a suitable diagnostic criterion for HCM.


which as I understand it means that an echocardiogram is not an accurate form of diagnosis and, based on my experience in learning from long-term Maine Coon breeders, is not helpful when a cat displays late symptoms after producing litters.

So I wonder whether it's somewhat fruitless to scan.


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## Tigermoon

Rufus15 said:


> This is partly my question - is there much point in the scan as you can breed from a cat that has a normal heart at 1 but an abnormal heart at 6, after they've had a number of litters. So I wonder whether it's somewhat fruitless to scan.


A breeder who doesn't scan could be breeding from a cat with clear changes to the heart though couldn't they??? And cats have dropped dead at 9 months, 18 months, 2 years, 4 years ..... I therefore scan. At least I know that at the time I am breeding the cat wasn't showing anything that would be a cause for concern. Of course I have no gene test for my breeds. If I did I would test every breeding cat just as I do for PKD even though I know their parents are tested clear.


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## Rufus15

Tigermoon said:


> A breeder who doesn't scan could be breeding from a cat with clear changes to the heart though couldn't they??? And cats have dropped dead at 9 months, 18 months, 2 years, 4 years ..... I therefore scan. At least I know that at the time I am breeding the cat wasn't showing anything that would be a cause for concern. Of course I have no gene test for my breeds. If I did I would test every breeding cat just as I do for PKD even though I know their parents are tested clear.


It's unclear though whether Maine Coons suffer from HCM outside the known gene. It's unhelpful that we still have breeders who breed from carriers, so I expect that's skewing some results.


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## Tigermoon

Rufus15 said:


> It's unclear though whether Maine Coons suffer from HCM outside the known gene.


I think you can fairly safely say that no breed of cat will only suffer from one genetic cause for cardiomyopathy.


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## Bigsize9foot

I don’t know if it is of interest to anyone (being practical helps me) that our 8 month old dsh has just been diagnosed with HCM but because of his age they are querying if a faulty valve has caused the thickening of the heart muscle. I am really hoping it is that as it will improve his prognosis which at the moment is very poor. He is being treated by Glasgow Vet School which has a well respected cardiology unit. 
He has been started on the drug clopidogrel that you mention and goes back in a week for a rescan of his heart. I’m not sure if this thread is for us to share our experiences. Sorry if it’s not.


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## Ceiling Kitty

Rufus15 said:


> which as I understand it means that an echocardiogram is not an accurate form of diagnosis and, based on my experience in learning from long-term Maine Coon breeders, is not helpful when a cat displays late symptoms after producing litters.
> 
> So I wonder whether it's somewhat fruitless to scan.


It's the only practical method we have right now.

The precise cut-off for HCM is woolly - different cardiologists use different criteria, and we don't know whether there are any significant breed differences.

But this only becomes relevant in borderline cases - as a cat with a wall thickness of less than 4.5mm is not considered to have HCM whereas a cat with a wall thickness of 7.5mm almost certainly does - and a lot of cases will be that clear cut.

In the borderline cases, one could always rescan - which is usually in the plan in any case.



Rufus15 said:


> It's unclear though whether Maine Coons suffer from HCM outside the known gene. It's unhelpful that we still have breeders who breed from carriers, so I expect that's skewing some results.


They 1000% do - Maine Coons without the A31P mutation can and do still develop HCM.

We know that the A31P mutation isn't the only one. But it's the only one we know for this breed. Given that there are thousands of known mutations in humans, it stands to reason that the same applies to cats. But we only know two.



Bigsize9foot said:


> I don't know if it is of interest to anyone (being practical helps me) that our 8 month old dsh has just been diagnosed with HCM but because of his age they are querying if a faulty valve has caused the thickening of the heart muscle. I am really hoping it is that as it will improve his prognosis which at the moment is very poor. He is being treated by Glasgow Vet School which has a well respected cardiology unit.
> He has been started on the drug clopidogrel that you mention and goes back in a week for a rescan of his heart. I'm not sure if this thread is for us to share our experiences. Sorry if it's not.


Of course it's fine!

Hopefully he does not have HCM, and has ventricular hypertrophy secondary to a valve malformation. Have they said whether or not they are optimistic that his congestive heart failure is reversible?


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## Rufus15

@Ceiling Kitty thanks for clarifying, that's helpful. There seems to be so many different opinions on HCM just within the breeding community, so it's extremely helpful to know what the stance of the veterinary community is.


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## Bigsize9foot

They didn’t mention if the heart failure was reversible. Just that it would come back at some point. I took that to mean he was now not in heart failure. His lungs are clear for now. They did say (I think) only 10% chance of it being due to the heart valve. Maybe I’ll find out more next week assuming the lungs don’t start to fill again. Such an awful awful illness.


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## Sacrechat

Tigermoon said:


> The club would like you to believe this, but it is not true.
> 
> I was sent this article today. It is about cardiomyopathy in humans but gives some rather interesting detail into what goes on within the heart of a sufferer.
> https://theconversation.com/dilated...se-that-killed-george-michael-explained-74227


My friend is on the committee for the Birman Cat Club and I'm a member of the group that does fund raising for heart research, so I can tell you, you are wrong.


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## Tigermoon

Sacremist said:


> My friend is on the committee for the Birman Cat Club and I'm a member of the group that does fund raising for heart research, so I can tell you, you are wrong.


Ooops sorry to disillusion you. Yes the Club raised a very small amount but they refused to put any of it into the official research funding body (WINN Feline Foundation) which the researchers were being funded through. As a result the research was paid for by just a few breeders who put money directly into WINN, one of whom put in several thousand pounds. The same thing happened for the following two years, and this years research was paid for by Birman Rescue.


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## Paul Arenson

Thank you for this. A bit above me, but our Blackie was diagnosed (apparently incorrectly) with Hypertrophic Cardiomyopathy. Second opinion by cardiologist (Atsushi Hirakawa, Fukuoka, Japan) determined Restrictive Cardiomyopathy (lower left chamber is divided into two in lay people's terms). Prognosis up to a year for this 3-year old.


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## gskinner123

Copied from the British Shorthair Breed Advisory Committee page:

"I have just heard from David Connolly of the Royal Veterinary College regarding their HCM in British project. They are looking to make contact with the owners of British who have had a definitive diagnosis of HCM and who may sadly be reaching the end of their lives.
We understand that making contact with people who may be facing the loss of their much loved pets is difficult, but the RVC have a very real chance of finding these genes if we can provide the help they need.
People are welcome to contact the BSH BAC in the first instance or directly to David - email address -
[email protected]
Thank you"


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## OrientalSlave

Ceiling Kitty said:


> <snip>
> We know that the A31P mutation isn't the only one. But it's the only one we know for this breed. Given that there are thousands of known mutations in humans, it stands to reason that the same applies to cats. But we only know two.
> <snip>


Are the known mutations in cats the same as any known mutations in humans?


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## stockwellcat.

Just an update on MYK-461 which is now known as Mavacamten (formerly known as MYK-461).

https://hcmbeat.com/tag/myk-461/

https://www.streetinsider.com/dr/news.php?id=14217112&gfv=1

https://www.2ndchance.info/MYK-461.htm

The drug is in phase 3 of trials in humans but I am finding no advancement information in the trials with cats.


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## Sacrechat

Saad Ali said:


> what is this?


Hypertrophic cardiomyopathy, which is a disease of the heart. The left ventricle becomes enlarged slowing the flow of blood around the body and eventually resulting in death as the blood backs up into the lungs. Sometimes the back legs can go due to having a stroke.


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## cat11dog

.


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## Neo93

_*Quote: Increased sensitivity of the cardiac muscle to calcium has been identified in homozygous Ragdolls.*_

Hello and thank you for this interesting thread. Should we aim to feed our cats foods with lower calcium content? I have a ragdoll cat with a hole in the heart so of course I am worried about HCM. Is the calcium mentioned something to look out for in the diet or is it irrelevant?


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## chillminx

Neo93 said:


> _*Quote: Increased sensitivity of the cardiac muscle to calcium has been identified in homozygous Ragdolls.*_
> 
> Hello and thank you for this interesting thread. Should we aim to feed our cats foods with lower calcium content? I have a ragdoll cat with a hole in the heart so of course I am worried about HCM. Is the calcium mentioned something to look out for in the diet or is it irrelevant?


Has your Ragdoll been identified as being homozygous? Genes are inherited in pairs, and if a cat has two defective (mutated) genes (called a homozygous cat) this further increases the risk of HCM compared with a cat that has just one defective gene and one normal gene, i.e. a heterozygous cat.

You may find this article from Icat Care useful :

https://icatcare.org/advice/hypertrophic-cardiomyopathy-hcm-and-testing/


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## Neo93

No testing done as this was a BYB reject. The insurance doesn’t cover the heart as it was classified as a pre existing condition. The ultrasound cost about 1200. The walls had the right thickness but I’m still concerned about what you mentioned about calcium. Should I feed low calcium diet just in case?


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## QOTN

Neo93 said:


> _*Quote: Increased sensitivity of the cardiac muscle to calcium has been identified in homozygous Ragdolls.*_
> 
> Hello and thank you for this interesting thread. Should we aim to feed our cats foods with lower calcium content? I have a ragdoll cat with a hole in the heart so of course I am worried about HCM. Is the calcium mentioned something to look out for in the diet or is it irrelevant?


It would be a good idea to test your Ragdoll. Langford is the best lab for cat genetic testing. https://www.langfordvets.co.uk/diagnostic-laboratories/services/cat-genetic-testing/
If your cat is not homozygous you will not have to worry about calcium.


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## OrientalSlave

As well as testing your cat, remember that low calcium levels are dangerous in themselves. I would make sure he doesn't get too much calcium - for example by feeding raw chicken wings - and simply feed a good quality, balanced, diet. One DNA test costs £37.80, or £30.24 if you qualify for the breed society price. They will send you the swab and a freepost return envelope. They also have a PDF on the website you can print yourself for freepost.

I sent one away two weeks ago on the Monday, got the results by email on Thursday.


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## Neo93

OrientalSlave said:


> As well as testing your cat, remember that low calcium levels are dangerous in themselves. I would make sure he doesn't get too much calcium - for example by feeding raw chicken wings - and simply feed a good quality, balanced, diet. One DNA test costs £37.80, or £30.24 if you qualify for the breed society price. They will send you the swab and a freepost return envelope. They also have a PDF on the website you can print yourself for freepost.
> 
> I sent one away two weeks ago on the Monday, got the results by email on Thursday.


Thank you for the information. My cat is spayed so no breeding involved. I think all the test will do is stress me out. I don't think I have the stomach to do it. When I took my cat for the ultrasound it was the most stressful 1 hour of my life.


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## Tigermoon

Neo93 said:


> _*Quote: Increased sensitivity of the cardiac muscle to calcium has been identified in homozygous Ragdolls.*_
> 
> Hello and thank you for this interesting thread. Should we aim to feed our cats foods with lower calcium content? I have a ragdoll cat with a hole in the heart so of course I am worried about HCM. Is the calcium mentioned something to look out for in the diet or is it irrelevant?


A hole in the heart, or septal defect, has no relationship to HCM. There is no reason why your cat is any more likely to get HCM than any other cat based purely on having this defect.

You can test your ragdoll via swabbing to check if it has one of the genes identified as causing HCM in that breed, but it is not a guarantee as the test only covers two genes, and there are likely to be dozens.

Calcium is important for normal heart functioning and you absolutely should not be messing with the nutritional content of your cat's diet unless specifically told to do so by a veterinarian. You cannot prevent HCM by reducing calcium in the diet.


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## Linah4

Hi there! I've been doing some research on HCM and blood clots, because I think my late girl (RagdollX) suffered from this before she passed earlier this year. I came across a website that had some resources for treatments and found this patent that discusses HCM and ATE with a solution for dissolving blood clots. There was an independent research study done using Nattokinase and Rutin. Would be interesting to get your thoughts on this.

PS - I tried posting the link but its giving me a spam error.


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## blackislegirl

I am new here and found this thread. I have just lost my adored blue Bumese boy from an aortal blood clot. He suffered a blood clot affecting one hind leg 5 months ago. He recovered quickly and seemed to be doing well on his medication Iclopidogrel, Fortekor and furosemide.) Then on 15 Feb I found him collapsed in the garden. His back legs were paralysed, and I knew it was game over. It was 5 days before his 4th birthday. 

I am posting this as there seems to be no mention of Burmese in this thread. My boy had an echocardiogram after the first clot, which led to a diagnosis of unclassified CM. The prognosis was poor. I was advised to contact his breeder, and the consulting vet who did the scan said it was very likely an inherited condition. So I spoke to her, and she told me that there was now 'a question mark' over the father's bloodline. That was so sad to hear, and clearly she k knew nothing about it when she chose the stud.

Does anyone here know more about such bad heart disease in Burmese?


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## Leodog15

I had two cats (brother and sister of the same litter) who I lost both to this awful disease. Both showed some similar signs but also very different. The male was 10 years old, his began at first with an overactive thyroid. He always breathed fast but it became more noticeable and he began coughing. A heart scan confirmed HCM. This was new to us at the time but we travelled to Derby to see a heart specialist for him who did more in depth scans and provided medication to help. It was very difficult and he began open mouth breathing and we had to make the hardest decision to let him go.
Interestingly our female cat had been doing this strange thing for years where her legs would go all funny, her tail would fall to one side. We took her to the vet immediately the first time it happened and they weren't sure but said it was some kind of seizure. This only happened once every few months or something so they decided it wasn't worth treating. A year after losing our boy cat, she began coughing. We took no risk and instantly paid for a heart scan. When we got the results she said it was ok. We were relieved. But very quickly she began breathing fast and heavy and at one point even collapsed (only for a mili second). We went back to the vet and said are you sure it's not HCM as we've seen this before. They looked back at the scan results which stated there were signs of HCM. Hers progressed quickly with her heart rate reaching near 200 beats per minute and we had to say goodbye.
We later found out that the strange tilting to one side and her legs going funny was actually the blood not being able to pump around the body and possible clotting due to the HCM. I am determined to share these early signs, as even the vet didn't recognise this years prior, in the hope of catching this disease early. We need more research to help fight this.
This disease ripped us all apart twice. Both of our cats were of the same litter and had a heart murmur which was detected very young.


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