The Birman Heart Fund

Lois Wilkie did a talk at the Birman Cat Club Show in 2015 and you can download the recording below

Recording
Transcript

Sending samples
Frequently Asked Questions

How to help our Researcher

Update from Lois Wilkie from the 2016 AGM
Funding Report May 2016

BIRMAN CARDIOMYOPATHY RESEARCH UPDATE

Spring 2017

Over the past 18 months the study’s investigators have screened 162 Birmans for heart disease. They found a high prevalence of cardiomyopathy (heart muscle disease) in Birman cats (10%). Birman cats seem to be affected by several different types of cardiomyopathy, such as hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC). However, HCM was the most common type of cardiomyopathy in their population, affecting nearly 7% of the Birman cats that they screened. This type of cardiomyopathy causes thickening of the walls of the heart. 

HCM was most commonly diagnosed in adult cats (median age of 8.4 years), as previously described in other feline HCM studies. This means that cats may develop HCM later in life and a normal heart scan at a young age does not exclude the possibility of a cat developing HCM at a later stage. Serial heart scans and exclusion of HCM in previous generations is required to properly exclude this disease. 

Heart murmurs appear to be more common in Birmans with cardiomyopathy (heart muscle disease) than in healthy cats. Although heart murmurs are not always a reliable indication of heart disease in other breeds, the investigators findings suggest that any Birman cat with a heart murmur should be investigated further for heart disease with echocardiography. In cases of HCM, the septal wall of the heart was most commonly thickened, which is typical of humans with inherited HCM. Males were more frequently affected with HCM in their study population (82% of the HCM cats were male), as repeatedly shown in feline and human HCM studies. Eleven Birmans that died of heart disease were submitted for pathological analysis, and similarly to the heart scan results they found evidence of different forms of cardiomyopathy, including HCM, RCM, ARVC and dilated cardiomyopathy (DCM). In humans, these types of cardiomyopathy are usually associated with different genetic mutations, but occasionally one genetic mutation can cause multiple types of disease. They have identified families of Birmans that include cats with HCM and RCM, and cats with HCM and ARVC. It is possible that there is more than one mutation in these families, but it is also possible that one mutation in a Birman family can result in different types of cardiomyopathy. 

The investigators have also investigated blood tests that can help identify cats with heart disease (cardiac ‘biomarkers’). Levels of these cardiac biomarkers are increased in the bloodstream when the heart chamber walls are under strain (shown by the biomarker ‘NT-proBNP’) or when heart muscle cells are damaged (shown by the biomarker ‘troponin-I’). These biomarkers do not appear to be helpful in all breeds when screening for cardiomyopathy, but they do appear to be helpful in Birmans. As there is an overlap in biomarker levels between healthy and affected cats, biomarkers will not be reliable enough to act as the sole test in screening breeding cats. Biomarkers may be useful however in determining which cats should be investigated further with echocardiography. Early diagnosis of more severely affected cats will allow cats to be started on treatment to reduce the risk of blood clots (‘aortic thromboembolism’), which is a devastating and often fatal complication of cardiomyopathy. 

They have built a large bank of stored samples for DNA from screened Birmans and Birmans with severe heart disease. This will allow them to proceed to the next stage of their studies, where they will look for genetic differences in Birmans with cardiomyopathy compared with healthy Birmans. Their hope is that by identifying genetic differences it may be possible to produce a gene test for cardiomyopathy in Birmans. The extended period of screening was necessary in order to gather data in old and affected Birman cats (for example, 41 cats ≥9 years old were screened). Considering the age-dependent penetrance of HCM, these subpopulations of cats are of extreme importance to better define the true cardiac phenotype/s in this breed and to conduct more reliable genomic studies. Collecting these valuable samples was only achievable by traveling around the UK and targeting cats for screening from families with a history of cardiomyopathy or old cats from relatively unaffected lines. By being so rigorous about demanding samples from only clearly affected or clearly unaffected cats, their genomic studies have been delayed. However, improving the quality of the samples should improve the reliability of the genetic testing. They are now ready to proceed with our targeted gene testing. A 12- month no-cost extension has been requested by the investigators to complete the project. The necessary genomic sequencing and analysis of the samples collected will be performed during this time period. 

The investigators would also like to make the following appeal:

Ribonucleic acid (RNA) is a molecule that has essential roles regulating gene expression. Examining RNA in the hearts of normal compared with affected Birmans may be an important part of determining the underlying genetic mutation. Since RNA is unstable, it is essential that a storage reagent ‘RNAlater’ is used to stabilize the RNA in tissue samples and preserve the gene expression profile.  

If any cat that was scanned as affected, or normal aged 9 or older, dies or is put to sleep for any reason, RNA from their heart would be extremely useful. If you think that you would like to participate in this phase of the research, if or when the time comes, please contact the RVC research team now so that they can send RNAlater to your veterinary practice. 

By Lois Wilkie

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SCANNING DAY

A Scanning Day has been arranged by the RVC and Birman owners, for people unable to travel to the RVC. It is to be held at� Mappleborough Green Village Hall, on �20th July 2016. Mappleborough Green is just south of the M42 and handy for the Midlands and Birmingham areas.

Scanning will be free but some costs will be involved as below.
Cats over 8 years will need to have prior blood tests at their own vet to eliminate diseases which can mimic cardiomyopathy for example Thyroid and blood problems.
Your vet will know these tests as PCV/TP and T4.Costs vary from vet to vet.
The used blood or pellet, will be needed by the research team for genetic analysis and will need to be sent by your vet to the Royal Veterinary College FAO The Birman Cardiomyopathy Study, Clinical investigation Centre, Hawkshead Lane, North Mymms, Hatfield, AL9 7TA.

The scanning procedure will involve
A microchip check.........a micro chip is not essential but much prefered
Blood pressure check for cats 8 years or older
Complete heart scan...echocardiography...by a board certificatated cardiologist.
Blood test for cardiac biomarkers
NT-proBNP and Tim for affected cats.
A written report or owners and their vets, otherwise all results are confidential.

The scanning will take about 15 - 20 minutes, with the cat lying on its side, gently restrained by the owner and the vet. Sedation is not needed.
We are hoping to run an appointment system to minimise waiting and stress.

To book a place please contact either myself Anne Madden panjandrum@ntlworld.com�or Heather Horton. at�namrib@yahoo.co.uk


Testing offer from our Researcher

We would like to offer free of charge cardiomyopathy screening to those Birmans that cannot travel to our hospital in Hertfordshire. To facilitate this, we propose a two week period in January where we will travel to screen Birmans at locations suggested by breeders.

To qualify for this screening, cats must meet the following criteria:

- Closely (within 4 generations) related to a cat that has died suddenly, been diagnosed with heart failure (fluid build-up in or around the lungs) or had an ATE (clot, usually to the back legs ‘saddle thrombus’)
- Had quantitative cardiac biomarkers (blood test) measured at their own veterinary practice with an NT-proBNP reading that suggests cardiomyopathy is likely
- Been diagnosed with cardiomyopathy and is being treated, therefore cannot risk the stress of travel
- Is 10 years or older and has no history of heart disease in their lines (within 5 generations)

If a breeder/owner would like a large group of their cats scanned, at least some cats must meet the above criteria. We will scan cats within a group that do not meet the requirements, as long as they are 2 years or older – please contact Lois directly.

To ensure we maximise this opportunity, we would suggest that several ‘hot spots’ are chosen that are central to a cluster of breeders, therefore multiple groups of cats can be screened over the course of our stay in that location.

If you are interested in this offer please email Lois: lwilkie@rvc.ac.uk with the following information:

- Preferred/suggested location
- Suitability of location to host screening e.g. local vet practice has agreed to lend a consult room for the day
- Number of cats you would like to bring
- Do they meet the criteria, and how?
- Pedigree names and date of birth/age of cats

We look forward to seeing as many of you as possible in January.

Thank you once again for your ongoing support and dedication.

Lois Wilkie
December 2015


The Birman Heart fund was started after the Birman Cat Club Committee received letters from breeders and owners about cardiac problems in the breed. The committee contacted Veterinary Specialists who confirmed that the problem was increasing within the breed.

At this time no one was raising awareness of the problem and no research was planned. The Birman committee voted to fund raise to remedy this. They have since been joined by the S & SW Birman Cat Club, the N. Birman Cat Club, and the Birman Welfare and Rescue. They have also received encouragement from the Birman BAC and the Cats Welfare Trust.

Protecting breeders

In order to protect breeders and the breed as a whole from unwelcome publicity the supporting clubs have concentrated on holding seminars, publishing information in the magazine, in leaflets and on their web sites. It was felt that a high profile campaign using public media would exaggerate the problem and give rise to acrimonious gossip. It could discourage sales and give the impression that the Birman Cat was less healthy than other breeds.

The money raised

The fund has raised over £3000 to date. Although this money is at present held in The Birman Heart Research Account, it is not Birman Cat Club money, but is held in trust on behalf of the donors until it can be handed over for research.

Some of the major donors have specified that the funds go direct to a UK college, and these conditions will have to be honoured. The RVA has been mentioned, as donors are aware that research into similar problems is already being done there, and it was intimated that they would be prepared to carry out research into the Birman cat.

Now that the RVA is in a position to begin research, having applied for a donation from the WINN Foundation, we are able to hand over funds to them for this research. Direct communication and steps are being taken with the RVA to do this without impacting the current WINN support or ongoing research plans.

The clubs will continue to fundraise for this cause, and look forward to help from members and Birman owners.

How to help our Researcher with some information

Birman cats are predisposed to heart muscle disease (cardiomyopathy), which can take a range of forms: hypertrophic (HCM), where the walls of the heart are too thick; restrictive (RCM), where the walls of the heart are too stiff; dilated (DCM) where there is thinning and weakening of the heart muscle and (arrhythmogenic) right ventricular (ARVC), where the right side of the heart may be replaced by fat and scar tissue. It is currently not clear whether HCM, RCM, DCM and ARVC represent different diseases with different causes, or whether these cardiomyopathies are part of the spectrum of one disease with one genetic cause.  This is a crucial question that must be answered before a genetic mutation can be identified.

We have been studying Birmans with cardiomyopathy using a combination of cardiac ultrasound (echocardiography), pathology and pedigree analysis, so that we can tease out the features of these heart muscle diseases. Since the start of the study we have screened 21 cats with echocardiography and had 3 cats presented for necropsy examination and pathology. We have also received DNA samples from one cat who was screened elsewhere and died of cardiomyopathy.

Pedigree analysis is underway and we have found families of Birmans with multiple members affected by more than one type of cardiomyopathy, therefore are gaining confidence that we are dealing with one disease.  At the end of the July 2015 we have the opportunity to begin our first round of genetic testing, using Next-Generation Sequencing (NGS).  In order to do this, we recently made an appeal for Birmans 7 years or older (ideally 10 years or older) with no family history of cardiomyopathy that do not have high blood pressure (hypertension) or an overactive thyroid gland (hyperthyroidism). These older, normal cats will form our ‘control’ group with which we will compare the DNA of cats with cardiomyopathy in the hope of finding the genetic mutation(s) responsible for cardiomyopathy in this breed.

We continue to offer free of charge screening at the Queen Mother Hospital for Animals in Hertfordshire, which includes:

  • Physical examination
  • Blood pressure measurement
  • Complete heart scan by a board-certified cardiologist
  • Blood test for cardiac biomarkers (NT-proBNP and hsTnI), hormones released into the blood if the heart is under stress or being actively damaged.
  • Full written report to both owner and vet

You can book your cat in by emailing lwilkie@rvc.ac.uk

We are very grateful to everyone who has donated personally, through Breed Clubs, the Birman Heart Foundation and WINN.  Without you this research would not be possible!