Arrhythmogenic Right Ventricular Cardiomyopathy in Boxers
Myths and Misinformation
April, 2011

In May 2009, Dr. Kathryn Meurs announced to the Boxer fancy that she had discovered a genetic mutation strongly associated with ARVC in Boxers. In the two years that have followed, as breeders and cardiologists have discussed the mutation and a growing number of dogs have been tested, we have gained information about what this mutation means for our breed. Not surprisingly, along with information has come misinformation, misunderstanding, and mythology regarding the mutation. While some of this misinformation is harmless, some has the dangerous potential to increase the incidence of ARVC, setting us back 20 years in our efforts to elminate the disease from the breed. Following is a discussion of these myths and the reality of the situation.

ARVC-1 Negative dogs will not develop genetic ARVC

This is the most dangerous myth, because it discourages holtering which could lead to breeding affected dogs. The assumption would be true if the ARVC-1 gene were the only gene responsible for ARVC in Boxers, but at this point we cannot say that is the case. Dr. Meurs has stated from the very first announcement that it is possible, and even likely, that one or more other genes may cause ARVC. Multiple genes are responsible for ARVC in humans, and there is no reason to think the situation would be different for dogs. To quote the Washington State University Veterinary Cardiac Genetics Lab page on Boxer ARVC, of which Dr. Meurs was the Chair when she found the mutation:

In humans there are 8 different genes that can cause the development of ARVC. Each one, all by itself can lead to the development of ARVC. There are 141 DIFFERENT mutations in these 8 genes. Therefore, it is very likely that there is more than one mutation in the Boxer dog that may lead to the disease in some lines of dogs.

Dr. Meurs has stated, and continues to state, that while ARVC-1 negative dogs do not have the only known mutation associated with ARVC, they should not be considered free of the disease and should be holtered routinely, especially if they are to be used in breeding programs. Again from the WSU VCGL page:

This is a disease that primarily affects the electrical system of the heart so the best way to test for it is a 24 hour Holter monitor. Since the disease is adult onset and can start at varying ages, we recommend that Holtering be started at 3 years of age and repeated ANNUALLY.

Every Boxer diagnosed with confirmed ARVC has tested positive for the ARVC-1 mutation

Another potentially dangerous myth, which is also completely and utterly untrue. Four dogs in the original research project were diagnosed with ARVC, but negative for the ARVC-1 mutation. The researchers felt -- as is possible with any Boxer diagnosed with ARVC, regardless of genetic status -- that the disease in these four dogs was due to environmental factors, but it is also possible the disease was due to a different gene. We have numerous anecdotes of Boxers clearly affected with ARVC that are Negative for the ARVC-1 mutation, and which are not traditional candidates for environmental ARVC. In her October 2010 webinar, Dr. Meurs discusses an ARVC-1 Negative dog that clearly has ARVC, and reitereates that there may be other genetic causes, again noting the situation in humans and the multiple genes that can cause the disease. Evidence from the UK also contradicts this myth, as the incidence of ARVC in tested dogs appears to be independent of the presence of the ARVC-1 gene: the distribution of the gene is similar between their affected and non-affected groups. As Dr. Meurs has noted from the start, more research is needed -- but the evidence clearly shows this myth is just that, a myth.

Homozygous Positive Boxers will develop ARVC at a younger age than Heterozygous Positive Boxers

This is not a particularly dangerous myth, but it is a myth all the same. Dr. Meurs debunked this in her February, 2010 update to the fancy:

In our study we found that dogs that were homozygous for the mutation (2 copies of the abnormal gene) had a more severe form of the disease based on Holter findings. This DOES NOT mean that they develop it earlier, it means that when they do develop the VPCs they tend to have more of them.

A clear holter means the dog is clear of ARVC

Although not a new myth, this is a persistent one. It, too, can be potentially dangerous for the breed. A clear holter simply means the dog did not show signs of ARVC during that particular 24-hour period of time. The number of VPCs a dog has can vary by up to 85% from day to day, and ARVC is a late-onset disease, with symptoms typically appearing after the dog is 5 years or older. Repeated holtering is essential for weeding out affected dogs from breeding programs, and for determining where ARVC appears in older dogs retired from breeding.

The minimum age to holter is 3 years

Actually this is not a myth; Dr. Meurs recommends holters start at 3 years of age and be repeated annually. The rationale for this is that numerous things can cause VPCs, and VPCs in a dog younger than 3 years are less likely to be the result of ARVC. The American Boxer Club continues to recommend holtering breeding prospects beginning at 12 months of age, however. While the incidence of sudden early death has greatly decreased thanks to routine holtering, there is still the occasional Boxer that drops dead at 2-3 years of age. Since the ABC Code of Ethics permits breeding dogs that are younger than 3, by recommending holtering starting at 12 months there is a greater chance to identify these young affected dogs, and there will be two years of baseline readings before the dog is bred. An abnormal holter at these ages can also indicate an underlying problem that might not be detected otherwise.

A cardiologist must read the holter data or the results are invalid

This myth might have been started by cardiologists to combat the growing number of breeders who purchase their own holter monitors and send the tapes out to independent parties to be read. In most cases, however, it is a myth. A variation is that holter tapes must be read by humans, rather than machines. That one is semi-true; of course a machine reads the tapes in every case, but with most holter services a certified holter technician reviews the data the machine provides. This allows the technician to separate artifact -- which might be caused by adjustments to the unit, the dog coughing or barking, rubbing against furniture or walls, etc. -- from actual abnormal beats. The risk, then, is of an artificially inflated number of VPCs from a machine-only reading, as machines cannot discern artifact from VPCs. In the June 2009 webinar, Dr. Meurs noted that a low number of VPCs in a machine-read tape with 22-24 hours of readable beats is acceptable as a valid holter result. If you have a higher number of VPCs, then the data should certainly be reviewed by a human to determine if any artifacts are present.

Once again, most holter services -- including Dr. Meurs' service -- utilize skilled technicians to review the data for the standard service, with a cardiologist interpretation available for an additional fee. For dogs with low numbers of VPCs, this is a valid holter result. If the dog has a higher number of VPCs, or other abnormal beats, then a cardiologist consultation might be useful. A cardiologist can review the abnormal beats and try to determine whether they represent ARVC or some other disease process, and can develop a plan of treatment and follow-up, if necessary.

The ARVC-1 mutation is predictive of ARVC

Whether this statement is a myth is highly and hotly debated within the Boxer fancy. The statement is based in fact, but the phrasing is a simplified statement of that fact. Dr. Meurs stated in the October 2010 webinar that the gene is predictive for about 70% of Boxers who test positive for the mutation -- meaning, of course, that it is not predictive for about 30% of them. Unfortunately, at this point in time we have no way of knowing for which Boxers the gene is predictive and for which it isn't. Dogs that test positive for the ARVC-1 mutation may never develop ARVC (and, as above, dogs that test negative may). Again, more research is necessary and ongoing to determine what factors might influence whether a dog does or does not develop the disease.