Hieronder informatie van Dr Nicole Van Israël
DVM, CESOpht, CertSAM, CertVC, Diplomate ECVIM-CA (Cardiology), MSc, MRCVS
Diplomate of the European College of Veterinary Internal Medicine
European Specialist in Veterinary Cardiology
MSc in Congenital Cardiology
c/o ACAPULCO
Animal CardioPulmonary Consultancy
Masta 11, BE-4970 Stavelot Belgium
http://acapulco-vet.be/definitions/echocardiographie.htm?lng=nl

Overerving: polygenisch bij de CKCSen Teckels, bij de andere rassen weten we dat niet. MVD is multifactorieel, het is dus veel meer dan de genen...
Kruisingen zijn altijd beter maar ook straathonden ontwikkelen MVD. Het is nl vnl een degenerative ziekte zoals de naam het zegt met een
genetische predispositie.

Canine Mitral Valve Disease: From Genetics Through Screening Programs, to Practical Breeding Advice 24th ECVIM-CA Congress, 2014
Jens Häggström1; Simon Swift2; Lisbeth H. Olsen3 Swedish University of Agricultural Science, Uppsala, Sweden; 2Small Animal
Clinical Sciences, University of Florida, Gainesville, FL, USA; 3University of Copenhagen, Frederiksberg, Denmark

Introduction

Myxomatous mitral valve disease (MMVD) usually affecting the mitral valve is the most common cause of cardiac disease in dogs, being responsible for 75–80% of all canine cardiac disease. Progressive myxomatous degeneration of the mitral and/or tricuspid valve leads to thickening of the valve
leaflets, incompetence, and a clinically detectable systolic murmur. The loudness of the murmur is related to the severity of the disease. Initially
the regurgitant volume is small, but as the disease progresses, the volume increases, resulting in a volume overload of the left atrium and left
ventricle. In some dogs, heart failure or sudden death can occur. In several countries, the Cavalier King Charles spaniel (CKCS) has been shown
to have a high incidence and an earlier onset of the disease than other breeds. A survey in the UK suggested that 43% of CKCS die from heart
disease.1 Animal insurance data between 1995–2006 shows that Cavalier King Charles Spaniels have one of the highest cause-specific mortality,
accounting for 37% of the total mortality in dogs < 10 years of age, a number that is only higher in the Irish Wolfhound.2 In fact, there are only a few other breeds that have a cause-specific mortality for any disease that can match this number. Furthermore, the total mortality caused by heart disease is higher than this, because dogs die or become euthanased either as a direct consequence of the heart condition or as an indirect consequence. Genetic analysis has suggested an inherited basis for the disease and breeding from dogs that develop murmurs later in life produces puppies that develop murmurs later in life.3,4 A polygenic trait has been proposed, and recently 2 loci have been identified.5 The disease is highly heritable, and selection against the disease should be successful. As a result, several breed schemes have been developed across Europe to try to help guide breeders. Schemes are present in Sweden, the UK, and Denmark.

Swedish Breed Scheme

A national breeding program, which accounts for age and ancestral background, was started in Sweden in 2001 with the intention to reduce the
prevalence of MR attributable to MMVD in CKCS. The basis of this program is a central register, handled by the Swedish Kennel Club, a functioning
system of dog identification (such as ear tattoo or microchips), and submission of data to the registry. The results are from examinations performed once a year, starting from the age of 2 years. The annual examination consists of cardiac auscultation only, but approved examiners are restricted to those specialised in small animal practice according to the rules set by the Swedish Veterinary Association. Dogs may be evaluated provided they are not sedated or have signs of other disease that may have haemodynamic effects, such as anaemia, conduction disturbances (excluding 1st- and 2nd-degree AV block), fever, or conditions that are associated with increased blood volume (i.e., pregnancy). Dogs with suspected thoracic, pleural, and pulmonary or pericardial disease may not be evaluated. Breeders are recommended not to use dogs younger than 2 years or dogs that developed a heart murmur before the age of 4 years, or dogs descending from a parent that developed a heart murmur before that age. Thus, a breeder may use a dog older than 2 years,

but younger than 4 years if the dog's parents were free from heart murmurs at the age of 4 years. The submission of results from the examination is mandatory if the breeder wants to register the offspring in the Swedish Kennel Club (and thereby participate with the offspring in major dog shows).

The programme is designed on the principle that the registry is open to the public, thereby stimulating the breeders to use healthy dogs, rather than prohibiting them from using certain dogs for breeding. The experiences in Sweden over 30 years of other breeding programmes have proved that this strategy gives best compliance and, thereby, best results. The age limit of 4 years recommended by the programme derives from epidemiological research in CKCS. This age limit was estimated to exclude approximately 20% of the dogs from breeding and is aimed at excluding dogs with a premature form of MMVD, but at the same time keeping the number of males and females available at an appropriate level to ensure genetic variation. Although the number of animals required for maintaining genetic variation is considerably lower, it is not advisable to exclude more than approximately 30% of the dogs from breeding due to a single disease in a population with the size of the CKCS in Sweden. The practice of breeding purebred dogs involves, in itself, selection of dogs to maintain certain qualities, and, in addition, dogs are excluded from breeding due to the presence of other diseases. Therefore, the age limit was chosen to not be too high in the beginning of the program, but it may later be raised with improving MMVD status in the breed.

Unfortunately, an early analysis of the Swedish scheme did not detect a significant effect on age of development of murmurs in 6-year-old dogs between 2007 and 2009; however, the follow-up period in the study was short in addition to several other study limitations.

UK Breed Scheme

The UK Cavalier King Charles Spaniel Club began gathering data of the incidence of murmurs in 1991, and in 1997, breeding guidelines were proposed. These suggested that dogs should be examined for the presence or absence of a murmur consistent with degenerative valvular disease. Dogs used for breeding should be over 5 years before they developed a murmur. As many breeders want to use younger dogs, dogs over 2½ and free from a murmur could be used if their parents were over 5 before they developed a murmur. Dogs were presented at shows or at their local vets, and any vet could complete the certification. The use of general practitioners (GP) vets was based on a desire to encourage participation, as there were few cardiologists in the UK in the early 1990s. Breeders were encouraged to have their dogs examined by cardiologists who were defined as veterinary surgeons with further qualifications in cardiology (RCVS Certificate or Diploma). As the importance of the status of a dog at 5 became apparent, a list of dogs examined by cardiologists and found to be free of murmurs at 5 years was published. The certificates were entered on a database for analysis. Between 1991 and 2010, a total of 16,887 examinations were performed on 8860 dogs. Sixty-five percent of the examinations were performed in bitches, and 35% in male dogs. GP vets performed approximately 60% of the examinations, and cardiologists performed the remaining 40%. However, over time the percentage of dogs examined by cardiologists increased from 25% to 78%. Multivariate models showed male dogs developed murmurs at a younger age than females, and cardiologists detected murmurs in younger dogs than GP vets.7 Hence, it became necessary to compare dogs and bitches examined by GP vets and cardiologists separately. Comparing 4 quartile time periods, there was a significant increase in the median age at which 50% of bitches will be murmur free determined by GP vets (over 1991–1995 and 2006–2010) (p = 0.001). Although this trend was seen for cardiologists and for male dogs examined by GP vets, it was not significant.

A subanalysis was performed in the 2006–2010 quartile of dogs over 3 years. Their pedigrees were traced to establish if the breeding guidelines had been followed and the effect on murmur age incidence. A total of 790 dogs were identified, but only 31 (4%) had followed the breeding advice. No difference in age of onset of the murmur could be identified.

Danish Breed Scheme

The Danish Cavalier King Charles Spaniel Club began gathering data of the incidence of murmurs due to MMVD in the 1990s, and in 2001 a mandatory breed scheme was started in collaboration with the Danish Kennel Club and University of Copenhagen. Dogs were approved for breeding from 1½ years of age, and they needed to be reexamined at 4 years if they wanted to continue breeding. From 2007, males also needed to be reexamined at 6 years if they want to continue breeding after this age. The cardiac examinations consist of auscultation (mitral regurgitation murmur grade 1–6) and echocardiography of the mitral valve. The degree of mitral valve prolapse (MVP) was evaluated as no (grade 0), mild (grade 1), moderate (grade 2), or severe (grade 3).8,9 Auscultation and echocardiography were performed by 7 trained veterinarians (5 GP with special training in auscultation and echocardiography) and two experienced cardiovascular veterinary researchers (one was substituted in 2004). One of the cardiovascular researchers with special interest in MMVD evaluated the degree of MVP offline in all dogs. Dogs with mitral regurgitation murmur more than 2 and/or severe MVP (MVP = 3) were excluded from breeding. Dogs with grade 2 murmurs were excluded if they have moderate or severe MVP (MVP grade 2 or 3).

From 2002 to 2011, 997 CKCS were examined in the breed scheme. Some of the dogs were examined up to 4 times, resulting in a total of 1380 examinations. Five to 12 percent of the examined dogs were excluded from breeding each year. The risk of having a murmur in 2010–2011 compared to 2002–2003 was estimated using linear regression analysis (exact condition binary logistic regression), adjusting for repeated measurements.10 In 2010–2011, dogs were estimated to have 71% reduced risk of having a murmur due to MMVD than dogs in 2002–2003 if they were a product of the breed scheme (p = 0.0017).10 A dog was defined as a product of the breed scheme if both parents where

approved by the Danish breed scheme. The reduced risk of having a murmur did not reach statistical significance (OR 1.71; p = 0.06) if non-products of the breed scheme (for example, imported dogs with parents with unknown cardiac status) were included in the analysis.10 The conclusion of this first evaluation of the mandatory Danish breed scheme based on auscultation and echocardiography reported a significant reduction in the prevalence of MMVD in CKCS over an 8- to 10-year period.

Conclusions

The schemes suggest that it is possible to increase the age at which CKCS develop murmurs by selectively breeding from dogs that develop murmurs later in life. The Danish scheme seems to result in a much more effective improvement than the UK and Swedish schemes. The main differences between the breed schemes are the diagnostic tools, numbers and training of examiners, mandatory or voluntary participation, and use of information regarding parental cardiac status. The Danish scheme uses echocardiography

as well as auscultation, while the Swedish and UK schemes rely on auscultation alone, and the Danish and Swedish schemes are mandatory (if the breeder wants to have the dog registered in the National Kennel Club), while the UK scheme is voluntary. In addition, the Danish scheme is based on relative few trained examiners but does not include parental information compared to the UK and Swedish schemes. Echocardiography allows confirmation of the diagnosis, but experienced cardiologists can detect murmurs in 89% of dogs with mitral regurgitant jets in excess of 30% of the left atrial area.11 Thus, echocardiography will detect dogs at an early stage of MMVD than auscultation, but the potential benefit of this (in terms of offspring cardiac status) has not yet been evaluated. Further studies are needed to evaluate the benefit of including echocardiography and parent cardiac information in breed schemes aiming at reducing the prevalence of MMVD in CKCS.

Conflict of Interest Statement

Jens Häggström has received research funding from the Swedish Science Council, the Swedish Research Council Formas, Boehringer-Ingelheim, Ceva Sante Animale, Agria Insurance Ltd, the Swedish Kennel Club, the AKC Canine Health Foundation, and Animeda. He has also undertaken paid consultancies for Boehringer-Ingelheim, Oasmia, Animeda, and the European School of Advanced Veterinary Studies (ESAVS).

Simon Swift has received research funding from the UK Cavalier King Charles Club.

Lisbeth Olsen has received research funding from The Danish Council for Independent Research, Ceva Sante Animale, Novo Nordisk A/S, Boehringer-Ingelheim, Agria Insurance Ltd, the Danish Kennel Club, the Cavalier Club in Denmark, and the AKC Canine Health Foundation.

References

1. www.thekennelclub.org.uk/download/1533/hscavalierkingcharlesspaniel.pdf; 2006 (VIN editor: This link could not be accessed as of 6-24-14.)

2. Egenvall A, et al. Heart disease as a cause of death in insured Swedish dogs younger than 10 years of age. J Vet Intern Med. 2006;20:894–903.

3. Swenson L, et al. Relationship between parental cardiac status in cavalier King Charles spaniels and prevalence and severity of chronic valvular disease in offspring. J Am Vet Med Assoc. 1996;208:2009–2012.

4. Lewis T, et al. Heritability of premature mitral valve disease in cavalier King Charles spaniels. Vet J. 2011;188:73–76.

5. Madsen MB, et al. Identification of 2 loci associated with development of myxomatous mitral valve disease in cavalier King Charles spaniels. J. Hered. 2011;102(Suppl.1):S62–67.

6. Lundin T, et al. Evaluation of the Swedish breeding program for cavalier King Charles spaniels. Acta Vet Scand. 2010;52:54.

7. Swift. ACVIM Proceedings; 2013.

8. Pedersen HD, et al. Observer variation in the two-dimensional echocardiographic evaluation of mitral valve prolapse in dogs. Vet Radiol Ultrasound. 1996;37(5):367–372.

9. Reimann MJ, et al. R-R interval variations influence the degree of mitral regurgitation in dogs with myxomatous mitral valve disease. Vet J. 2014;199:348–354.

10. Birkegaard, et al. ACVIM Proceedings; 2013.

11. Pedersen HD, et al. Auscultation in mild mitral regurgitation in dogs: observer variation, effects of physical maneuvers, and agreement with color Doppler echocardiography and phonocardiography. J Vet Intern Med. 1999;13:56–64.