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HCM & The Persian Cat 2015
Photos copyrighted by the individual photographers
As Persian cat breeders we face a whole host of obstacles, the least of which is producing that perfect cat. Inheritance plays a role in so many factors, and it is often just a roll of the genetic dice that determines the outcome. Sometimes that outcome is devastating. One kitten may have the ideal head structure, but it fades to FIP (Feline Infectious Peritonitis). Another may have a dynamite body, but it has a severe cleft palate and dies from aspiration pneumonia. An older kitten could have become the next top show quality cat, but it dies in your arms from a heart problem. If we breed long enough, we will suffer the pain of a broken heart, both ours and that of some of our treasured feline companions. HCM (Hypertrophic Cardiomyopathy) is one such cause of this pain. Scientific Research in HCM In humans, researchers have discovered hundreds of mutations spread across a number of genes encoding for abnormal myocardial (heart muscle) proteins that cause HCM. In cats, it hasn’t seemed quite as complicated. However, to date, there are only two breeds that have had some success in locating genetic markers for HCM. It was because of the discovery of mutations in cardiac myosin binding protein C genes associated with HCM in Maine Coons (A31P) in 2005 and in the Ragdoll (C820T) in 2007, that a DNA test was subsequently developed for those breeds. The Ragdoll mutation is different from the mutation in Maine Coons, the latter of which has been found to be less definitive in predicting disease than the former. Time will tell as to the accuracy of R820W as a sole predictor of the presence of HCM in the Ragdoll breed. Maine Coon breeders have seen some cats develop HCM that tested negative for the A31P mutation, suggesting that there is more than one mutation responsible for HCM within the Maine Coon breed. Even though that mutation has been insufficient in determining all Maine Coon cats which have the potential for passing HCM, its discovery was a step in the right direction. It proved that each breed is unique regarding HCM. The Ragdoll and Maine Coon mutations are not found in other breeds, so it is known that if a mutation is responsible for HCM in Persians, it is a different mutation. Consequently, until a definitive genetic mutation, or set of mutations, is discovered in the Persian breed, we must get cardiac ultrasounds (echocardiograms) on our breeding cats to find those that have HCM and remove them from our breeding programs. Breeder Responsibility Cat breeders of any breed with historical documentation of HCM in that breed should be getting cardiac ultrasounds. There is nothing worse than getting a phone call or an email from a kitten buyer with the tragic news that their Himalayan or their Exotic or their Persian has just suddenly died, often without obvious signs. If breeders aren’t educating their clients about HCM, they will have no clue what symptoms may signify presence of the disease. They won’t know how critical their kitten or cat may be depending on the symptoms. And they won’t know when to begin testing for it. They also won’t know that a simple oral medication may offer their kitty a better quality of life. At this point, evidence of life extension is anecdotal and subjective. You will read in detail about one such anecdotal case involving CHF (congestive heart failure) in the “New Research” section of this article. His name is CH Donegal’s Irish Crème (aka Irish). Irish has survived four years beyond the average survival rate for a cat diagnosed with CHF (Congestive Heart Failure) due to HCM, which is typically two years or less. It could be tenacity, the medications (including Vetmedin), or both. It could also be cat to cat variability. Since his case, my veterinarian has treated several more CHF cats, adding Vetmedin to their treatment regimen when they have pleural effusion, cardiac dilation or both. They are also beating the odds, living well over two years and delaying that trip over the rainbow bridge. Could it be the Vetmedin? Time and more practical experience will tell, as it does with so many things regarding cats.
My seal lynx point, CH Donegal’s Tow the Line (aka Toby), is a perfect example of improvement in quality of life. He exhibited labored breathing when being bathed for a show. His show agent assumed it was just the stress of getting a bath. Let’s face it, not all cats are going to like being bathed. Because I knew that his sire, Ronan, was positive for HCM and I was becoming more aware of the signs for this disease and its dominant inheritance, Toby’s symptoms rendered cause for suspicion. His agent and I agreed that he should be tested for it. So Toby received his first cardiac ultrasound at sixteen months of age, earlier than the recommended two years of age. He was positive for HCM, with one cardiac chamber enlargement evident on ultrasound. My veterinarian started him on daily atenolol, a blood pressure medicine, even though his blood pressure was normal. Toby came back to live with me and showed no further signs of labored breathing, even with the stress of jumping repeatedly for a toy and chasing after his cat buddies. His ultrasound at four years of age showed a functional improvement in the heart’s activity. The chamber enlargement is still there. That won’t go away. But the medicine helped to slow his heart rate enabling him to handle stress better. Continuous stress is considered to be a contributor to hastening the development of HCM. Could this explain why some show cats reach a pinnacle in the show circuit, only to disappear and never be seen again? No matter how much a cat displays that he/she loves the attention it receives at cat shows, being in strange places with strange people is a stress. Bathing a cat is a stress, as is a trip to the vet and having surgery (spay/neuter). These are all stresses capable of exacerbating HCM and even possibly taking a cat over the edge. If we can’t prevent all the stressors, then we need to at least try and help our cats physically cope with that stress with medication when appropriate. Ideally, show cats with advanced cases of HCM should not continue to be shown for the cats’ health concerns. Testing for HCM At this time the only testing method available for Persian cats is cardiac ultrasound (aka echocardiogram). Baseline scans for HCM should begin at two years of age (recommended by veterinary cardiologists) unless symptoms present sooner. A heart murmur can be a sign of HCM, particularly if it wasn’t present on previous examinations. Kittens will sometimes present with a developmental murmur that goes away after six months of age or sooner. If a murmur is detected before that age, the kitten should be rechecked for the murmur after it reaches six months. A murmur that develops after that age should warrant further investigation with an echocardiogram to rule out HCM or some other cardiac abnormality. With that said, many cats with HCM will have no murmur and many cats with murmurs have normal hearts. So veterinarians can’t rely on detection of a murmur in adult cats to signify HCM. Cardiac ultrasound is still the only method of detection of this disease. An echo, as it is often called, uses sound waves to view the pumping activity of the heart, the size of the chambers, and wall thickness of the left ventricle (the large pumping chamber). It is not to be confused with an ECG or EKG which is an electrocardiogram that measures the electrical activity of the heart. It is important that cardiac ultrasounds be performed by someone well versed in diagnosing HCM, ideally by a veterinary cardiologist. A positive cardiac ultrasound should be considered definitive and those cats should be eliminated from the breeding program, at least until researchers have identified the mutation in Persians and developed a DNA test for it. This decision should be made with the caveats proposed in the following paragraph. Accuracy of the Test Cats that have HCM on ultrasound can be monitored by echocardiogram at six month to one year intervals (depending on severity of the HCM) for disease progression and medication requirements (e.g. your veterinarian may want to prescribe Plavix if the left atrium is severely enlarged). Breeding cats that do not have HCM on ultrasound should be retested by ultrasound at least every other year. HCM, even though it is genetic, is a disease that develops over time. Most commonly it shows up in the age range of two to three years, but it may not appear until six to seven years of age. So it is important to note that a negative HCM ultrasound on a young cat could in fact be a pending positive over time. You could say they are false negatives or hidden positives. The terminology is less important than the facts of the disease. Whatever the age of the cat that presents with cardiac changes, the disease can be mild and progress to severe or it can be mild and stay mild for the rest of the cat’s life. Many cats don’t develop CHF until they are over ten years of age, but some do much earlier (even as young as kittens). So the disease and its progression are highly variable. In discussing disease documentation and accuracy, it is important to cover past DNA testing issues. This may apply to a DNA test for HCM in Persian cats in the future as well as DNA testing of other diseases/traits in the past. An example of a “false” negative could be whether the DNA on a particular cat was sent correctly by the breeder. Buccal swabs could have been mixed up and therefore incorrectly labeled when multiple samples were taken simultaneously. Other examples of false negatives could have been made when a sample was documented by the laboratory as another cat’s sample, or if the laboratory used an inaccurate testing method. Testing is managed by humans and human error is possible. Many of us saw what happened at a laboratory years ago in contract the Cat Fanciers’ Association, when we received erroneous DNA test results. Many breeders are not aware that the coalition with that researcher (Dr. Melba Ketchum, DNA Diagnostics dba Catgenes) was dissolved and the DNA was sent to Ernest G. (Gus) Cothran, PhD at Texas A&M Veterinary Genetics Lab (www.catDNAtest.org). And it was this lab’s researcher, Dr. Cothran, who initiated the Persian HCM study that Donegal Cattery has contributed DNA to since 2008. Dr. Cothran has recently transferred that six year data accumulation to Kathryn Meurs, DVM, PhD, DACVIM (Diplomat, American College of Veterinary Medicine) who is doing the current genome sequencing study later referenced in this article. At the time of this writing, the DNA profile testing, which had been available online via the CFA web site, is currently unavailable while the lab installs new test testing modalities involving state of the art genetic testing. The new testing profile, available sometime in the spring of 2015, will offer cat DNA genotyping which will provide hundreds more markers than previously available. Symptoms of HCM According to Mark Kittleson, DVM, PhD, DACVIM most cats with HCM show no clinical signs of the disease. Some go into congestive heart failure (CHF), either building up fluid in their lungs (pulmonary edema) or around their lungs (pleural effusion). A few form a blood clot in their heart that dislodges and is then carried by blood flow to the large artery that supplies blood flow to the hind legs (saddle thromboembolus, sometimes referred to as saddle thrombosis). This results in sudden pain and hind leg paralysis, which may be temporary or permanent. A few die suddenly and are usually found after death has occurred. Other cats will have cardiac changes over a lifetime that never lead to symptoms and the cat will die from other organs that fail. My fourteen year old Himalayan succumbed to pancreatitis and liver failure. It was during the ultrasound of his abdomen that I requested we check his heart for the HCM study. He had tested normal a few years before that. He was positive for HCM. Typical symptoms of CHF are rapid and shallow, abdominal breathing (shortness of breath), lethargy or inactivity uncharacteristic for the age of the cat, and possibly exercise intolerance. HCM was considered a middle age disease in cats. With recent documentations of HCM in the veterinary community, it has become evident that HCM is no longer a respecter of age.
A beautiful, nine month old bicolor Exotic kitten named GC Ashlin Zots Charlotte’s Web of Mr. Whisker (aka Charlie) just succumbed to a sudden cardiac death due to HCM. You can read about Charlie on Facebook. Her breeder is going to great lengths to help us in this funding effort with continuous postings asking for donations to the Persian HCM Research Fund via Winn Feline Foundation, sending the researcher information on other grant possibilities, and establishing a GoFundMe account. She and Charlie’s owner couldn’t stand by silently and watch others go through this without offering to help. Their effort is called Charlie’s Hope for Hearts. Charlie’s premature death is the youngest case I’ve encountered and such a tragedy. Wake up breeding community. The effort to discover the mutation and subsequent test for Persian HCM began years ago. It’s past time to get on board. If a loss like Charlie’s doesn’t prompt you to say “Count me in,” what will it take? Treatment for HCM Different medications are given to cats with HCM depending on the heart structure, cardiac function, and the cat’s symptoms. A beta blocker (atenolol) may be used for cats which are asymptomatic, but, according to Dr. Kittleson, there is no proof it is beneficial and a recent study suggests it does not prolong survival. However, some cats have shown functional cardiac improvement anecdotally, as in the case of Toby. On the other end of the disease spectrum are cats with CHF. For them a diuretic is mandatory. An ACE inhibitor may also be prescribed. In certain cases, Vetmedin (pimobendan) may be added. At thirteen years old, my Himalayan cat, Irish, is currently a six year survivor of CHF on Vetmedin with enalapril (ACE inhibitor), and furosemide (diuretic, aka Lasix). He was diagnosed with CHF due to HCM and began this treatment combination in August of 2008. In 2014 potassium was added to his regimen because his potassium level was low. A retrospective ten year case study was done using Vetmedin for CHF in cats compared with a control group that did not receive it. It was reported in JAVMA September 1, 2014 and one of the investigators was Kathryn Meurs, DVM, PhD, DACVIM who just initiated the genome sequencing study for HCM in Persians in December, 2014. Here is the title of the article, its authors, and the abstract conclusion:
HCM Research Based upon the historical research in Maine Coons, Ragdolls, and humans, it has been postulated that HCM is primarily due to a genetic mutation with autosomal dominant genetic inheritance. Simplistically defined, it is mutations in genes that code for structural proteins. In the case of HCM, it is a structural protein that is part of the heart muscle that actually contracts (sarcomeres). This affects the structure of the heart over time. Current theory accounts for the heart muscle thickening in the following way. The heart tries to compensate for the defective sarcomeres by creating more sarcomeres (some of them defective unfortunately) which result in an increase in muscle tissue (i.e. thickening). This thickening of the heart muscle can eventually cause the heart to fail by either sudden cardiac arrest due to an abnormal heart rhythm or congestive heart failure. It is considered to be autosomal dominant but with incomplete penetrance, age-related penetrance, and variable expression. In laymen’s terms, it does not develop in all cats that have the mutation (incomplete penetrance), and can develop at various points in a cat’s life (age-related penetrance) with varying degrees of disease severity (variable expression). It typically strikes symptomatically in adult cats somewhere between two and twelve years of age. A few will have symptoms as kittens, less than one year of age. Only severe HCM results in CHF. Most cats that have a saddle thromboembolus also have severe HCM. Cats that die suddenly can have mild, moderate or severe HCM. All of these factors make HCM a challenging disease to diagnose and to study. Given its autosomal dominance, some predictions can be postulated for the statistical potential for inheritance in the Persian breed, which includes Himalayans. Further research will be required for a definitive predictive capability. We are familiar with this projected rate of inheritance with our experience with PKD (Polycystic Kidney Disease). Heterozygosity and homozygosity are also discussed in the following article.
NOTE: A portion of this article and its online reference is quoted below by permission. A simplified definition of heterozygous verses homozygous, for the purposes of this article, is that offspring will inherit a gene from each parent. If one parent has the HCM mutation and the other doesn’t, the offspring will be heterozygous. For example, on PKD genetic tests a cat is considered heterozygous when the results are listed as: -/+ or N/P. The minus sign and the N means that parent was negative for the PKD gene and couldn’t pass the disease to offspring. The positive sign and the P means that parent has the PKD gene and it passed the disease gene to the offspring being tested. Homozygous means it receives the disease gene from both parents (+/+ or P/P). So with HCM homozygous means that both parents have the HCM mutation. This is not a disease where cats can be carriers. They either have the mutation (or mutations) or they don’t. In a publication in May, 2004, three researchers authored a joint paper on this disease. The following reference discusses symptomatic expression of HCM and the need for breeder involvement in research efforts. Some of the information is outdated. Current research, according to Dr. Kittleson, has now identified over 1300 mutations in the human model.
NOTE: A portion of this article and its online reference is quoted below by permission.
Research Funding Winn Feline Foundation provides the predominance of feline research grants and is a non-profit organization. To issue a grant for a breed-related research study, there has to be a special breed fund that must raise a minimum of $15,000 within five years or the funds are transferred to the general fund. If that minimum is reached within the allotted timeframe, the money within that special fund may be awarded to a researcher in the form of a grant. The fund was established on August 14, 2013. As of March, 2015, the Persian HCM Fund goal was achieved, evidence that the importance of this disease is finally receiving some recognition in the Persian cat breeding community. More dollars translate to more cats being studied. Greater numbers of subjects provide the researcher a better chance at making that critical discovery to enable Persian breeders to one day test for HCM. So, the Persian HCM Fund needs donations until a grant is issued. New Research The original Persian HCM study with Ernest G. (Gus) Cothran, Jr., PhD at VIBS (Veterinary Integrated Biosciences, Texas A&M University), initiated in 2008 using buccal swabs for DNA, has been in a holding pattern for years due to a lack of funding. In the process of seeking sources for funding, my efforts led me to Maureen Walsh (now retired) of the Winn Feline Foundation. Her learning of this setback was the impetus for the establishment of the Persian HCM Fund. Dr. Olah also sensed my frustration with the lack of progress in the original study and made a phone call to Dr. Meurs on my behalf. I had a detailed conversation with her in early December, 2014 about the six year endeavor with Texas A&M. I told her about the scores of DNA and Ronan’s diseased heart which is banked at this research facility, most of which are from Himalayan cats and CPCs (colorpoint carriers). We now have a new window of hope. That conversation with Dr. Meurs led to a new coalition for Persian HCM research using state of the art genome sequencing that determines the complete DNA sequence of an organism's genome. The genome is the total amount of genetic information in the chromosomes of an organism, including its genes and DNA sequences. Sequencing is defined as the exact order of the bases that make up a strand of DNA. There have been a number of attempts at sequencing domestic cat DNA, but Cinnamon, an Abyssinian, was the first project to successfully map a domestic cat’s entire genome. The domestic cat serves as an excellent model for human disease, which is one reason why the National Human Genome Research Institute (NHGRI) initially authorized the cat genome sequencing project. Data and bloodwork were submitted on eight HCM (positive or borderline positive) cats to North Carolina State College of Veterinary Medicine, Center for Comparative Medicine and Translational Research between December, 2014 and January, 2015 to initiate Dr. Meurs’ Persian HCM study. Two colorpoint carriers and three Himalayans, including Irish who is Donegal’s first HCM cat, comprise the five HCM samples from Donegal Cattery. Three Persian HCM samples were submitted by Pelaqita Cattery. Of these eight samples, three submissions from Donegal and two from Pelaqita have been sent for genome sequencing. Dr. Meurs should receive the results at the end of spring, 2015. This is exciting, state of the art DNA research in cats. We have the minimum of five subjects required for the genome sequencing, but Dr. Meurs will welcome any HCM positive submissions we can provide for future sequencing as needed. This study will involve Himalayans as well as Persians that have no Himalayans documented in their five generation pedigree. And it will need funding to continue.
CH InTheWind Peadar Ronan of Donegal was the foundation cat who was discovered to be passing HCM to his offspring. His son, CH Donegal’s Irish Crème (aka Irish), was the first case of HCM diagnosed at Donegal Cattery, the first DNA contribution to Dr. Cothran’s research at Texas A&M in 2008, and one of the first three submissions to Dr. Meurs’ study at NC State in 2014. At the time of this writing, Irish (my six year CHF survivor) is still alive and giving “high fives” to visitors. We are just at the beginning phase of the genome sequencing study, so it is unknown whether or not Exotics will also be included. With this type of breed to breed comparative study, it is likely they will be requested at some point, especially since American Shorthairs have also been affected by HCM. If you have positive Exotics (cats with documented heart thickening by cardiac ultrasound due to a diagnosis of HCM) and would like to have them included, I will bring your offer before Dr. Meurs. If she decides to include them, I will let you know how to participate. It will involve 1-2ml. of blood in a purple top EDTA tube, wall thickness measurements from the cardiac ultrasound while the heart is in diastole, and a copy of the pedigree. Donations Project Ronan’s Big Heart was initiated as an education vehicle for HCM in Persian cats and served to establish the Persian HCM Research Fund. On March 13, 2015 the fund reached its required minimum of $15,000 from public donations. Funds will continue to accumulate until a grant can be issued for a research proposal at the end of 2015. When Winn Feline Foundation awards a grant, it is then matched somewhere between $5000 and $7500. The amount is determined by how much is available in the general fund at the time the grant is awarded. You can read about Project Ronan’s Big Heart by going to Winn Feline Foundation’s web site: http://www.winnfelinefoundation.org/ . To make a donation:
Facebook & Yahoo Groups If you would like to join the Facebook and/or Yahoo group for Persian HCM Research, you will be kept up to date on where we are in researching this disease and where we stand with the funding. To join the Yahoo group you will first have to enroll in Yahoo Groups. Then go to: https://ca.groups.yahoo.com/neo/groups/PersianCatsHCMresearch/info Similarly, for Facebook, you will have to have a profile on Facebook, then go to: https://www.facebook.com/groups/PersianCatHCMResearch/. If you are not a part of this potential for a solution by giving financially and/or participating in the research, then you are merely a part of the problem. We will all face HCM in our breeding programs eventually, just as we did with PKD. But if we get behind this research, and if it leads where the researchers hope it will lead (discovery of the genetic mutation or mutations with subsequent DNA test), we will one day be able to have the confidence that we are providing our clients, both pet buyers and breeders, Himalayan and other Persian kittens and cats with “healthy hearts,” not “broken hearts.”
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