Genetic Welfare Problems of Companion Animals

Boxer

Arrhythmogenic Right Ventricular Cardiomyopathy

Related terms: cardiomyopathy, primary idiopathic myocardial failure, DCM

Outline: Boxers are genetically predisposed to a form of heart disease that can result in cardiac insufficiency (a weakening of the muscles of the heart that may cause fainting or sudden death) or heart failure (that causes progressive breathing difficulties and leads to death). These effects are due to the heart beat abnormalities that occur in this disease. It causes discomfort and distress which can be severe and, depending on the form of the disease, these may affect the animal for weeks or months. In one study about 50% of Boxers tested were found to be positive for the gene that causes the disease. A genetic test is available.

Summary of Information

(for more information click on the links below)

1.  Brief description

Cardiomyopathy is disease of the heart muscle. In arrythmogenic right ventricular cardiomyopathy (ARVC) there are irregular heartbeats. The severity of this disease in Boxers varies, and can range from individuals who have occasional abnormal heart rhythms but show no signs of disease, to others that have episodes of collapsing or an inability to exercise normally. A few will die suddenly (Basso et al 2004, Baumwart et al 2005). In some affected animals there is congestive heart failure of the kind more commonly seen in other breeds of dogs with cardiomyopathy, in which a build up of fluid in the body, especially the lungs, occurs (Meurs & Spier 2009, Martin et al 2010). The signs typically associated with this latter form are episodes of syncope (fainting), sudden death, or other signs of heart failure. In a study by Basso et al (2004) of dogs of various breeds, including 23 Boxers, 40% of the Boxers died suddenly, 52% had had episodes of fainting and 13% had other signs of heart failure.

Typically, in ARVC in Boxers there is abnormal electrical activity in the heart ventricles: an electrocardiography (ECG) examination will reveal an abnormal heartbeat pattern described as ventricular premature complexes (VPCs). When single abnormal heartbeats occur they will be not be noticed, unless the dog is connected to an ECG machine. If there are frequent abnormal beats then the dog may not be able to exercise well due to an inability to increase its heart rate as is normally required during exercise. If there is a run of abnormal beats then the resulting inadequate blood flow to the brain may cause collapse or fainting and, if this persists, then death will rapidly occur.

Some Boxers with ARVC also have dilated cardiomyopathy (DCM). It is not known whether both conditions, in these cases, have the same underlying cause or not, but evidence from MRI (magnetic resonance imaging) suggests that the function of the right ventricle is affected by ARVC even when the heart looks normal on ultrasound examination – that is when there is no apparent DCM (Baumwart et al 2009).

Boxers may be affected by this disease at any age in adulthood (Basso et al 2004, Baumwart et al 2005; http://www.cvm.ncsu.edu/vhc/csds/vcgl/Boxer-arvc.html) but the incidence of the disease increases with age (Stern et al 2010). The average age at which ECG abnormalities are first detected is six years (http://www.cvm.ncsu.edu/vhc/csds/vcgl/Boxer-arvc.html). A gene has been found that is associated with at least some cases of Boxer ARVC and a test is available to detect this. The gene is associated with the proteins that hold cardiac muscle cells together. It is an autosomal dominant gene and it has been suggested that the disease is more severe in homozygous individuals (those in which both copies of the gene are of the mutant form) (http://www.cvm.ncsu.edu/vhc/csds/vcgl/Boxer-arvc.html).

2.  Intensity of welfare impact    

Boxers with ARVC generally have a period of subclinical disease during which there are no (or only slight) health and welfare problems. There may be some welfare problems in these dogs if they suffer from episodes of weakness or collapse as a result of the disease that are unnoticed by their owners.

As the disease progresses, some affected dogs can die within hours to days from congestive heart failure that does not respond to treatment, and survival for more than a few months is unusual. Depending on which side of the heart is failing, different symptoms will be seen. Left sided heart failure leads to fluid build up in the lungs that makes breathing difficult and also causes coughing. As fluid accumulates, breathing becomes an increasing struggle and the dog may die from, what is effectively, drowning in its own body fluids. The disease causes serious discomfort as a result of coughing, breathing difficulties and associated complications, although affected dogs are often euthanased before the final stages are reached. Right sided heart failure causes breathing problems because of fluid build up inside the pleural cavity (the space between the lungs and the inside of the rib cage). Affected dogs are likely to feel ill and may faint, collapse and die suddenly.

There may also be adverse welfare impacts associated with the veterinary examinations, hospitalisations and medications associated with treatment of the disease: for example one drug used to treat ARVC, mexiletine can cause anorexia and gastrointestinal disease (Meurs & Spier 2009) although treatment can be relatively benign (Smith et al 2007).

3.  Duration of welfare impact

The mean survival time of dogs (of all breeds) with ARVC after presentation to a cardio-respiratory referral centre was found to be 19 weeks in one study (Martin et al 2009). The duration of the period when welfare impacts are likely to occur is likely therefore to be of this magnitude. Once Boxers show signs of heart failure, their life expectancy is likely to be poor and there is likely to be significant but variable suffering in all the affected dogs.

Some dogs with occasional abnormal beats due to ARVC, but without DCM, may live for years with few signs other than intermittent fainting and this may be considered a lesser welfare problem but its significance is difficult to evaluate. Medical treatment is available that is probably effective in reducing the incidence of fainting episodes (Meurs et al 2002).

4.  Number of animals affected

As a breed, Boxers predisposition to this particular heart disease is well attested (Harpster 1991, Meurs 1999, Basso et al 2004, Meurs & Spier 2009). Stern et al (2010) performed Holter monitoring on 301 clinically normal Boxers between the ages of 1 and 16 years and found that about 23% of these dogs had more than 90 ventricular premature complexes (VPCs – abnormal heart beat patterns – see ‘Clinical and pathological effects’) in 24 hours. These dogs might be considered to have currently asymptomatic ARVC.

Some initial results of genetic testing for the disease are available on the North Carolina State University website (http://www.cvm.ncsu.edu/vhc/csds/vcgl/boxer-arvc.html). These show that of the first 1690 dogs tested for the mutant gene associated with the disease 53% were negative, 41% were positive heterozygotes (one normal gene and one mutant) and 6% were positive homozygotes (two mutant genes).

5.  Diagnosis

Although the condition would be suspected in a Boxer with signs of fainting, other causes of this are possible (Thomason et al 2008; http://www.cvm.ncsu.edu/vhc/csds/vcgl/boxer-arvc.html) and the diagnosis rests on examination using ultrasound and ECG and, particularly, the 24-hour Holter monitoring.

6.  Genetics

There is strong evidence for a genetic influence in the occurrence of ARVC in Boxers. It is suspected to be an autosomal dominant genetic condition with incomplete penetration (Basso et al 2004, Meurs et al 2007; http://www.cvm.ncsu.edu/vhc/csds/vcgl/boxer-arvc.html). A genetic test is available from North Carolina Stare University (http://www.cvm.ncsu.edu/vhc/csds/vcgl/boxer-arvc.html).

7.  How do you know if an animal is a carrier or likely to become affected?

The gene that has been discovered to be associated with ARVC in Boxers is dominant, which means that only one copy of the gene is needed for an animal to show signs of the disease. However, the gene does have incomplete penetration, which means that not all animals with the gene will develop the disease and the severity of the disease varies. Also, the age of onset of the disease is often beyond the end of the normal breeding age. It is possible therefore for animals that show no signs of the disease to pass it on to their offspring. Clearly, it is important to detect those carrying the gene prior to the onset of clinical signs. However, the usefulness of the currently available genetic test (http://www.cvm.ncsu.edu/vhc/csds/vcgl/boxer-arvc.html) is limited because it appears that other genes can be involved also.

A screening test, based on 'Holter' monitoring for irregular heart beats, has been suggested by Meurs and Spier (2009). This involves counting the number of VPCs (abnormal heartbeats, see ‘Clinical and pathological effects’ below) seen in a 24 hour period: 0-50 is considered normal; 51-100 is indeterminate and a repeat examination in 6-12 months is advised; 100-300 is suspicious and the advice is not to breed from these dogs and to repeat the test; 300-1000 is likely to be an affected individual; >1000 is an affected individual.

8. Methods and prospects for elimination of the problem

One problem with testing for ARVC is that most affected dogs show no signs until they are six years old and they may be used for breeding prior to this (http://www.cvm.ncsu.edu/vhc/csds/vcgl/boxer-arvc.html). The currently available genetic test is very valuable but it detects only one of the genes that can cause the disease.

No formal schemes based on Holter monitoring of heart beats are in operation as far as we are aware but the heart beat test, proposed above by Meurs and Spier (2009), is recommended for detection of asymptomatic animals so that they can be excluded from breeding. This should be used in combination with the currently available genetic test. The two tests compliment each other. Holter (heart beat) monitors are not directly available in most practices, but in the UK a scheme exists for their hire and for analysis of results via any veterinary surgeon (http://www.holtermonitoring.co.uk), and some of these monitors are available from Boxer breeders clubs.

A scheme based on the currently available genetic test is being run at the North Carolina State University and owners may elect to have the genetic test result included on a public register - http://www.cvm.ncsu.edu/vhc/csds/vcgl/boxer-tr.html. This scheme recommends that the test result is taken into account when deciding on use of an individual dog for breeding but that other considerations are important. This is consistent with the concept of selecting breeding animals on the basis of their breeding value. Breeding value takes into account available genetic information and the presence/absence of other diseases with a genetic influence both in the individual and its relatives. Breeding from individuals that are genetically healthy and which have normal siblings and whose parents' siblings are normal is recommended as these individuals have the greatest chance of carrying a low load for genetic conditions in general (Bell 2010).

For further details about this condition, please click on the following:
(these link to items down this page)

• Clinical and pathological effects
• Intensity of welfare impact
• Duration of welfare impact
• Number of animals affected
• Diagnosis
• Genetics
• How do you know if an animal is a carrier or likely to become affected?
• Methods and prospects for elimination of the problem
• Acknowledgements
• References

1. Clinical and pathological effects

Cardiomyopathy is disease of the heart muscle. In arrythmogenic, right ventricular cardiomyopathy there are irregular heartbeats. Although some affected Boxers have these abnormal rhythms only occasionally and show no signs of disease, others have episodes of collapsing or are unable to exercise normally. A few may die suddenly (Basso et al 2004, Baumwart et al 2005). In some affected animals there is congestive heart failure of the kind more commonly seen in other breeds of dogs with cardiomyopathy, with a build up of fluid in the body, especially the lungs (Meurs & Spier 2009, Martin et al 2010). The signs typically associated with this latter form are episodes of syncope (fainting), sudden death or other signs of heart failure. In the study by Basso et al (2004) of dogs of various breeds, including 23 Boxers, 40% of the Boxers died suddenly, 52% had had episodes of fainting and 13% had other signs of heart failure.

The heart is a four-chambered pump which is divided into left and right sides. Each side has two chambers. Blood enters into the thin-walled upper chambers (atria) and flows from these into the larger, lower chambers (ventricles). The ventricles have thick walls of muscle. Between the atria and the ventricles are valves that prevent blood flowing backwards. On contraction, blood is pumped from the ventricles into the major blood vessels. There are also valves at the junction of the ventricles and these blood vessels that prevent backward flow.

The right side of the heart receives blood from the whole of the body other than the lungs, via the venae cavae. This blood accumulates in the right atrium and during a heart beat it flows past the tricuspid valve into the right ventricle and then, as this ventricle contracts (squeezes), the blood is pumped through the pulmonary valves into the pulmonary arteries that take it onto the lungs (for  oxygenation).

Oxygenated blood from the lungs returns to the left atrium of the heart via the pulmonary veins.  During the heart beat it flows past the mitral valve into the left ventricle. Then, as the left ventricle contracts, it is pumped through the aortic valves into the aorta and on into the other major arteries which carry it around the body to perform its various function including delivery of oxygen and nutrients and transport of heat and metabolic products.

The left side of the heart has to pump blood around the entire body, but the right side only has to supply the lungs. The muscles of the left ventricle have to be much stronger, and thus thicker, than those of the right.

The contraction of the heart muscles is induced by an electronic impulse. Normally this starts in an area of the upper heart called the sinoatrial node and spreads out in a set and controlled manner causing the various parts of the heart to contract in order. First the atria contract and then the impulse travels down to the ventricles and they are caused to contract. The process can go awry if there is disease that prevents passage of the electrical impulse at any point in the pathway, or if there is disease somewhere in the heart that generates another pulse. Although normally the pacemaker is the sinoatrial node, all areas of the heart muscle have the capacity to act as a pacemaker and to generate an electric pulse which will cause activity in the local muscle and that may spread around the heart. Disturbances to the electrical control system result in abnormal contractions and when these occur  the heart  is unlikely to work properly as a pump and either forward or backward (or both) heart failure will occur. Typically in Boxer ARVC, abnormal electrical activity is generated in the ventricles, and the resulting electrical patterns - seen on ECG examination - are called ventricular premature complexes (VPCs). Single abnormal heart beats are not apparent unless the dog is connected to an ECG machine. If there are frequent abnormal beats then owners may notice that the dog is unable to exercise normally, this is due to the dog losing the capacity to increase its heart rate in response to the demands of exercise. If there is a run of abnormal beats then inadequate blood flow to the brain will result in collapse or fainting and, if inadequate supply persists, death will rapidly occur.

In some Boxers with ARVC, the heart becomes abnormal in shape, increases in size, and the atria and ventricles become larger within thinner muscle walls. This is termed dilated cardiomyopathy (DCM). The consequences of this depend on which parts of the heart dilate, how rapidly and severely, on whether or not the valves are affected, and the degree to which conduction of electrical activity is interfered with.

A thin heart wall contracts poorly so the heart may fail to empty. This has a ‘dam-like’ effect and prevents blood entering the heart normally. This is backward or congestive heart failure. When the left side of the heart is affected, the increased blood pressure caused by the ‘damming’ of the blood forces fluid out of the circulatory system and into the surrounding tissues resulting in fluid build up in the lungs (pulmonary oedema). When the right side is affected, fluid builds up in the body and usually accumulates in the chest cavity (pleural fluid), the abdomen (ascites), or in the body tissues generally (oedema).

The pathology of ARVC has been described and a definitive diagnosis can only be made by detecting the characteristic changes in a sample of heart muscle taken either via a biopsy (which is not usually considered necessary) or after death. These changes are replacement of heart muscle by fatty tissue or a combination of fatty and fibrous tissues (Basso et al 2004). The underlying biochemical abnormalities that cause this have been investigated (Oyama et al 2008) and genes that alter proteins associated with the connections between heart muscle cells have been found to be abnormal in Boxers with ARVC (http://www.cvm.ncsu.edu/vhc/csds/vcgl/Boxer-arvc.html).

Examination with a stethoscope may reveal a heart murmur, but most Boxers with ARVC do not have murmurs (they are caused by abnormally turbulent blood flow and usually indicate the presence of a structural abnormality of the heart). In DCM they may occur due to abnormal valves allowing backflow of blood. However, such structural abnormalities are usually absent in Boxer ARVC (Meurs & Spier 2009). Some affected dogs have a rapid heart rate. 

Electrocardiography (ECG) to record the electrical activity of the heart is usually carried out in dogs without sedation or anaesthesia and can provide information about the presence of heart disease. The typical abnormality seen in ARVC is the presence of VPCs but these have to be interpreted with caution as a few VPCs can occur in some dogs unaffected with the condition (Meurs et al 2001a, Meurs & Spier 2009).

Also, some affected individuals may have only occasional episodes of irregular heart beat. These dogs may faint during episodes but may appear completely normal when being subsequently examined. ECGs usually record electrical activity for a few minutes only and can miss problems that occur infrequently (Wess et al 2010). A more sensitive test is to record the ECG over an extended period using a Holter monitor. This is a particularly valuable way of investigating ARVC in Boxers as sporadic dysrhythmia (abnormal heart beat rhythm) during a 24-hour recording is often the first, or only, detectable sign of the disease. That VPCs are the cause of fainting can only be determined if the dog actually has a fainting episode when attached to the Holter. This rarely occurs and, in practice, ARVC is diagnosed when more than 100 VPCs are seen within the 24 hours if there are runs of repeated VPCs or additional abnormalities (Meurs & Spier 2009).

The most powerful tool for examining the structure of the heart is ultrasonography. This enables measurement of the thickness of the heart muscle; the size of each chamber, and the position and movement of each valve. With colour-flow ultrasonography it is also possible to measure the speed and direction of blood flow in the heart and the great vessels.

Some Boxers develop ARVC alone whilst, in others, DCM is also found. Whether both conditions are the result of the same underlying problem or whether DCM has a different cause, is not known. Evidence from MRI (magnetic resonance imaging) suggests that function of the right ventricle is affected in the presence of ARVC even when the heart looks normal on ultrasound exam (Baumwart et al 2009).

Genetic factors are certainly very important in predisposing to the disease but the mechanisms are complicated and currently unclear (http://www.cvm.ncsu.edu/vhc/csds/vcgl/Boxer-arvc.html). ARVC and DCM are known to have genetic causes in humans and other breeds of domestic animals (but DCM can also be caused by other factors including: nutritional deficiencies, drug side effects, viral infection and possibly hormonal imbalance, and autoimmune disease (Calvert & Meurs 2000, Rishniw 2004, Buse et al 2008). In humans ARVC is associated with genes that cause an abnormality in proteins found in the desmosomes (structures that anchor cells together) of the cardiac muscle cells. A gene that causes an abnormality in the desmosome protein striatin has been discovered in Boxers (Meurs et al 2009).

Boxers may be affected by ARVC at any age in adulthood (Bosse et al 2004, Baumwart et al 2005, http://www.cvm.ncsu.edu/vhc/csds/vcgl/Boxer-arvc.html) but the incidence of disease increases with age (Stern et al 2010). The average age at which ECG abnormalities are first detected is six years (http://www.cvm.ncsu.edu/vhc/csds/vcgl/Boxer-arvc.html). A gene associated with at least some cases of Boxer ARVC has been found and a test for this gene is available. It has an autosomal dominant inheritance pattern. This means that animals with just one copy of the mutant gene may develop the disease. However, observations suggest that the disease is more severe in homozygous animals (those with two copies of the mutant gene).

Return to top

2. Intensity of welfare impact

Boxers with ARVC generally have a period of subclinical disease during which there are no (or only slight) welfare problems. The average duration of this subclinical phase is unknown and Holter testing is the only way to detect the presence of ARVC in these individuals. There may be some welfare problems in these dogs if they suffer from episodes of weakness or collapse as a result of the disease that are are unobserved by their owners.

As the disease progresses, some affected dogs can die in hours to days from congestive heart failure that does not respond to treatment and survival for more than a few months is unusual. Depending on which side of the heart is failing, different symptoms will be seen. Left sided heart failure leads to fluid build up in the lungs causing breathing difficulties and coughing. As fluid accumulates, breathing becomes an increasing struggle and, unless it can be treated or the dog is euthanased, it may die from what is, in effect, drowning in its own body fluids. This is likely to be associated with severely unpleasant feelings (discomfort, distress).Right sided heart failure can also cause problems breathing because of fluid build up inside the pleural cavity.

In ARVC welfare is generally most likely to be compromised by feelings of malaise and discomfort due to breathing difficulties and inability to perform normal exercise and behaviour. Investigations for heart disease, failure and treatments may also have adverse effects on welfare associated with  the veterinary examinations, hospitalisations and medications associated with treatment of the disease: for example, mexiletine, a drug used to treat ARVC, can cause anorexia and gastrointestinal disease (Meurs & Spier 2009), although treatment can be relatively benign (Smith et al 2007).

In the future the implantation of cardioverter-fibrillators may be used, as is currently done for humans with similar problems and the welfare implications of such treatments that will deliver defibrillating shocks to a conscious dog have yet to be evaluated (Nelson et al 2006).

Return to top

3. Duration of welfare impact

The mean survival time of dogs (of all breeds) with ARVC after presentation to a cardio-respiratory referral centre in one study was found to be 19 weeks (Martin et al 2009). The duration of the period when welfare impacts are likely to occur is likely therefore to be of this magnitude. Once Boxers show signs of heart failure, their life expectancy is likely to be poor and there is likely to be significant but variable suffering in all the affected dogs.

Some dogs with occasional abnormal beats due to ARVC but without DCM may live for years with few signs other than intermittent fainting and this may be considered a lesser welfare problem but its significance is difficult to evaluate. Medical treatment is available that is probably effective in reducing the incidence of fainting episodes (Meurs et al 2002).

Return to top

4. Number of animals affected

As a breed, Boxers predisposition to this particular heart disease is well attested (Harpster 1991, Meurs 1999, Basso et al 2004, Meurs & Spier 2009). However, we are not aware of any data on the proportion of animals that develop the disease. Stern et al (2010) performed Holter monitoring on 301 clinically normal Boxers between the ages of 1 and 16 years and found that about 23% of these dogs had more than 90 ventricular premature complexes (VPCs – abnormal heart beat patterns – see ’Clinical and pathological effects’)  in 24 hours. These dogs might be considered to have currently asymptomatic ARVC (strict guidelines for making this diagnosis have not been established).

However, two factors suggest that the proportion of affected animals is likely to be much higher (at least in this population of Boxers in the USA). One is that clinically affected animals were excluded from the study. The second is that the average number of VPCs in normal dogs of all breeds is two per 24 hours (Meurs et al 2001a) but only 30% of the clinically normal Boxers examined by Stern et al (2010) had fewer than two VPCs (but, on-the-other-hand, VPCs can also be caused by conditions other than ARVC, and these were not ruled out).

Some initial results of genetic testing for the disease are available on the North Carolina State University website (http://www.cvm.ncsu.edu/vhc/csds/vcgl/boxer-arvc.html). These show that of the first 1690 dogs tested for the mutant gene associated with the disease 53% were negative, 41% were positive heterozygotes (one normal gene and one mutant) and 6% were positive homozygotes (two mutant genes). This test probably does not detect all the mutations that cause Boxer ARVC. The extent to which these findings in the USA reflect the world population is unknown.  Nor are the proportions of heterozygous and homozygous dogs that go on to develop the disease known but the indications are that these are quite high.

Return to top

5. Diagnosis

Although the condition would be suspected in a Boxer showing the signs outlined above (Thomason et al 2008; http://www.cvm.ncsu.edu/vhc/csds/vcgl/boxer-arvc.html), the diagnosis rests on examination using ultrasound and ECG and, particularly, 24-hour Holter monitoring.  The diagnosis can only be definitively confirmed by microscopic examination of heart muscle and this is not considered necessary clinically. Failure to detect abnormalities on ECG does not rule out the condition (Wess et al 2010).  Sometimes repeated Holter monitoring is necessary (Meurs et al 2001b, Spier & Meurs 2004, Scansen et al 2009).

A genetic test is available for identification of animals that carry the mutant gene. 

Return to top

6. Genetics

There is strong evidence for a genetic influence in the occurrence of ARVC in Boxers. It is suspected to be an autosomal dominant genetic condition with incomplete penetration (Basso et al 2004, Meurs et al 2007; http://www.cvm.ncsu.edu/vhc/csds/vcgl/Boxer-arvc.html). Autosomal dominant conditions affect both sexes equally and all individuals with the gene are at risk of developing the condition. Whether they do so may depend on the actions of other genes and environmental factors. (http://www.cvm.ncsu.edu/vhc/csds/vcgl/Boxer-arvc.html).

A genetic test is available from the North Carolina Stare University (http://www.cvm.ncsu.edu/vhc/csds/vcgl/boxer-arvc.html). This detects normal and mutant versions of one gene that is associated with an abnormality of the desmosome protein, striatin, that connects cardiac muscle cells together (Meurs et al 2009). In humans there are eight genes associated with ARVC, and more than 100 mutations of these are known. It is thought likely that different mutations are important in different individuals. It is probable that various mutations likewise cause ARVC in Boxers and that their frequencies in populations vary around the world (http://www.cvm.ncsu.edu/vhc/csds/vcgl/boxer-arvc.html).

Return to top

7. How do you know if an animal is a carrier or likely to become affected?

The gene that has been discovered to be associated with ARVC in Boxers is dominant, which means that only one copy of the gene is needed for an animal to show signs of the disease. However, it has incomplete penetration, which means that not all animals with the gene develop the disease and, for those that do, the severity of the disease varies. Also, the age of onset of the disease is often beyond the end of the normal breeding age. It is possible therefore for animals that show no signs of the disease to pass it on to their offspring. Clearly, it is important to detect those carrying the gene prior to the onset of clinical signs. The currently available genetic test (http://www.cvm.ncsu.edu/vhc/csds/vcgl/boxer-arvc.html) may not be perfect, because it appears that other genes can be involved also in some cases, but it makes sense to use it and to only breed from animals that do not have the mutant gene.

A screening test, based on 'Holter' monitoring for irregular heart beats, has been suggested by Meurs and Spier (2009). This involves counting the number of VPCs (abnormal heartbeats, see ‘Clinical and pathological effects’ above) seen in a 24 hour period: 0-50 is considered normal; 51-100 is indeterminate and a repeat exam in 6-12 months is advised; 100-300 is suspicious and the advice is not to breed from these dogs and to repeat the test; 300-1000 is likely to be an affected individual; >1000 is an affected individual.

Return to top

8. Methods and prospects for elimination of the problem

One problem with testing for ARVC is that most affected dogs show no signs until they are six years old and they may be used for breeding prior to this (http://www.cvm.ncsu.edu/vhc/csds/vcgl/boxer-arvc.html). The currently available genetic test is of some value but it detects only one, not all, of the genes that can cause the disease.

No formal schemes based on Holter monitoring of heart beats are in operation as far as we are aware. However, the heart beat test proposed above by Meurs and Spier (2009), is recommended for detection of asymptomatic animals so that they can be excluded from breeding. This should be used in combination with the currently available genetic test. The two tests compliment each other. Holter (heart beat) monitors are not directly available in most practices, but in the UK a scheme exists for their hire and for analysis of the results via any veterinary surgeon (http://www.holtermonitoring.co.uk), and some of these monitors are available from Boxer breeders clubs.

A scheme based on the currently available genetic test is being run at the North Carolina State University and owners may elect to have the genetic test result included on a public register at http://www.cvm.ncsu.edu/vhc/csds/vcgl/boxer-tr.html. This scheme recommends that the test result is taken into account when deciding on use of an individual dog for breeding but that other considerations are important. This is consistent with the concept of selecting breeding animals on the basis of their breeding value. Breeding value takes into account available genetic information and the presence/absence of other diseases with a genetic influence both in the individual and its relatives. Breeding from individuals that are genetically healthy and which have normal siblings and whose parents' siblings are normal is recommended as these individuals have the greatest chance of carrying a low load for genetic conditions in general (Bell 2010).

Return to top

9. Acknowledgements

UFAW is grateful to Rosie Godfrey BVetMed MRCVS and David Godfrey BVetMed FRCVS for their work in compiling this section

Return to top

10. References

Basso C, Fox PR, Meurs KM, Towbin JA, Spier AW, Calabrese F, Maron BJ and Thiene G (2004) Arrthythmogenic right ventricular cardiomyopathy causing sudden death in Boxer dogs: a new animal model of human disease. Circulation 109: 1180

Baumwart RD, Meurs KM, Atkins CE, Bonagura JD, DeFrancesco TC, Keene BW, Koplitz S, Luis Fuentes V, Miller MW, Rausch W and Spier AW (2005) Abnormalities in Boxers with cardiomyopathy and left ventricular systolic dysfunction: 48 cases (1985–2003) Clinical, echocardiographic, and electrocardiographic. Journal of the American Veterinary Medical Association226: 1102-1104

Baumwart RD, Meurs KM and Raman SV (2009) Magnetic Resonance Imaging of Right Ventricular Morphology and Function in Boxer Dogs with Arrhythmogenic Right Ventricular Cardiomyopathy. Journal of Veterinary Internal Medicine 23: 271–274

Bell JS (2010) Genetic Testing and Genetic Counselling in Pet and Breeding Dogs. World Small Animal Veterinary Association World Congress Proceedings

Buse C, Altmann F, Amann B, Hauck SM, Poulsen Nautrup C, Ueffing M, Stangassinger M and Deeg CA (2008) Discovering novel targets for autoantibodies in dilated cardiomyopathy. Electrophoresis 29: 1325–1332

Calvert CA and Meurs KM (2000) CVT update: Doberman pinscher occult cardiomyopathy. In: Bonagura JD ed. Kirk’s Current Veterinary Therapy XIII pp756 W.B. Saunders: Philadelphia.

http://www.cvm.ncsu.edu/vhc/csds/vcgl/Boxer-arvc.html accessed 16.6.2011

Harpster N (1991) Boxer cardiomyopathy. Veterinary Clinics of North America Small Animal Practice 21: 989

Martin MWS, Stafford Johnson MJ and Celona B (2009) Canine dilated cardiomyopathy: a retrospective study of signalment, presentation and clinical findings in 369 cases. Journal of Small Animal Practice 50: 23–29

Martin MWS, Stafford Johnson MJ, Strehlau G and King JN (2010) Canine dilated cardiomyopathy: a retrospective study of prognostic findings in 367 clinical cases. Journal of Small Animal Practice 51: 428–436

Meurs KM and Spier AW (2009) Cardiomyopathy in Boxer dogs. In: Bonagura JD and Twedt DC (eds) Kirk’s Current Veterinary Therapy XIV pp797 W.B. Saunders: Philadelphia

Meurs KM, Spier AW, Miller MW, Lehmkuhl L and Towbin JA (1999) Familial ventricular arrhythmias in Boxers. Journal of Veterinary Internal Medicine 13: 437-9

Meurs KM, Spier AW, Wright NA and Hamlin RL (2001a) Use of ambulatory electrocardiography for detection of ventricular premature complexes in healthy dogs. Journal of the American Veterinary Medical Association 218: 1291–1292

Meurs KM, Spier AW, Wright NA and Hamlin RL (2001b) Comparison of in-hospital versus 24-hour ambulatory electrocardiography for detection of ventricular premature complexes in mature Boxers. Journal of the American Veterinary Medical Association 218: 222–224

Meurs KM, Spier AW, Wright NA, Atkins CE, DeFrancesco TC, Gordon SG, Hamlin RL, Keene BW, Miller MW and Moise NS (2002) Comparison of the effects of four antiarrhythmic treatments for familial ventricular arrhythmias in Boxers. Journal of the American Veterinary Medical Association 221: 522–52

Nelson OL, Lahmers S, Schneider T and Thompson P (2006) The Use of an Implantable Cardioverter Defibrillator in a Boxer Dog to Control Clinical Signs of Arrhythmogenic Right Ventricular Cardiomyopathy. Journal of Veterinary Internal Medicine 20: 1232–1237

Oyama MA, Reiken S, Lehnart SE, Chittur SV, MeursKM, Stern J and arks AR (2008) Arrhythmogenic right ventricular cardiomyopathy in Boxer dogs is associated with calstabin2 deficiency. Journal of Veterinary Cardiology 10: 1-10

Meurs KM, Mauceli E, Acland G and Lindblad-Toh K (2009) Genome-Wide Association Identifies a Mutation for Arrhythmogenic Right Ventricular Cardiomyopathy in the Boxer Dog American College of Veterinary Internal Medicine Proceedings 2009

Rishniw (2004) Systolic myocardial failure. VIN Associate http://www.vin.com/Members/Associate/Associate.plx?DiseaseId=56 accessed 16.6.2011

Scansen B, Meurs K, Spier A, Koplitz S and Baumwart R (2009) Temporal Variability of Ventricular Arrhythmias in Boxer Dogs with Arrhythmogenic Right Ventricular Cardiomyopathy. Journal of Veterinary Internal Medicine 23: 1020–1024

Smith CE, Freeman LM, Rush JR, Cunningham SM and Biourge V (2007) Omega-3 Fatty Acids in Boxer Dogs with Arrhythmogenic Right Ventricular Cardiomyopathy. Journal of Veterinary Internal Medicine 21: 265–273

Spier AW and Meurs KM (2004) Evaluation of spontaneous variability in the frequency of ventricular arrhythmias in Boxers with arrhythmogenic right ventricular cardiomyopathy. Journal of the American Veterinary Medical Association 224: 538-541

Stern JA, Meurs KM, Spier AW, Koplitz SL and Baumwart RD (2010) Ambulatory electrocardiographic evaluation of clinically normal adult Boxers. Journal of the American Veterinary Medical Association 236: 430–433

Thomason J, Kraus M, Surdyk K, Fallaw T and Calvert C (2008) Bradycardia-Associated Syncope in 7 Boxers with Ventricular Tachycardia (2002–2005). Journal of Veterinary Internal Medicine 22: 931–936

Wess G, Schulze A, Geraghty N and Hartmann K (2010) Ability of a 5-Minute Electrocardiography (ECG) for Predicting Arrhythmias in Doberman Pinschers with Cardiomyopathy in Comparison with a 24-Hour Ambulatory ECG. Journal of Veterinary Internal Medicine 24: 367–371

http://www.holtermonitoring.co.uk/) accessed 16.11.2011

© UFAW 2011

Credit for main photo above:

By Corporalen (Own work) [Public domain], via Wikimedia Commons