Health Issues Dilated Cardiomyopathy

Dilated Cardiomyopathy

A variety of heart diseases are reported in the Great Dane. Among them are dilated
cardiomyopathy (DCM)--a progressive, life-threatening disease unfortunately not uncommon in the
Dane, and then a variety of congenital heart defects, to include: mitral valve defects, typically
stenosis--which is another serious and potentially fatal disorder, triscuspid valve dysplasia--another
potentially fatal valvular defect, subaortic stenosis (SAS)--another potentially fatal defect of
structure, patent ductus arteriosus (PDA)--a common congenital defect in dogs that is usually
correctable, and persistent right aortic arch (PRAA or VRA)--another congenital, correctable
defect.

Congenital heart defects, as Patterson (JSAP; 1989: Hereditary congenital heart defects in
dogs) noted "comprise probably the most common class of malformations found in dogs, occurring
with a frequency approaching 1% in animals presented to veterinary clinics. The frequency is
significantly higher among purebred dogs than in dogs of mixed breeding and specific anatomical
malformations occur with highest frequency in certain breeds. Genetic studies of patent ductus
arteriosus, pulmonic stenosis, subaortic stenosis, ventricular septal defect, tetralogy of Fallot and
persistent aortic arch have confirmed that these are specific heritable defects, the genes for which
are concentrated in a number of different breeds. Each of these defects is inherited in a complex
manner consistent with a polygenic basis."

The last two congenital defects listed above (PRAA & PDA) are reported sporadically in the
dog, with PDA being the most common canine congenital heart defect. Both are the result of fetal
structures which persist after birth, resulting in problems for the growing pup, so both are thought to
be "timing gene" defects. Both are correctable by surgery as noted. PDA shows a female
predominance in some breeds; in PRAA the persistent fetal structure essentially "strangles" the
esophagus, causing constriction of the esophagus with regurgitation, aspiration pneumonia and
dysphagia (poor eating ability), so can be confused with non-heart diseases such as megaesophagus.
Congenital valve defects result in reduced heart efficiency, and if severe are typically fatal in the
first year of life with the puppy likely demonstrating lethargy, poor appetite, even syncope
(fainting) and sudden death. SAS is a narrowing of a major area of blood flow, and although mild
cases may go undetected, a diagnosis of SAS often requires careful treatment & death may occur
regardless. All these congenital heart conditions can be the cause of "unthrifty" puppies and/or
sudden inexplicable death. All can have a "graded expression," meaning the defects of structure can
be mild, moderate, or severe, resulting in more or less obvious symptoms of disease. All are
considered to be inherited diseases. Generally all are associated with heart murmurs (of various
sorts), and an expert auscultation (exam with a stethoscope by a cardiologist or internist) can often
offer a preliminary diagnosis of congenital heart disease. The OFA Cardiac clearance exam and
registry is a suitable screening method for congenital heart disease.

Dilated cardiomyopathy (DCM) is in a different category. This is typically an adult-onset disease
and is progressive in nature, so signs of disease are not obvious for months and even years. In a
recent paper in the JAVMA (Meurs, et al, Mar2001) concerning DCM, Dr. Meurs outlines the
clinical features of DCM and offers some comments on potential inheritance of the disease. In our
breed the preliminary data suggest that DCM is typically inherited in an X-linked recessive fashion.
This means that usually unaffected, but carrier, dams pass on the defective X chromosome to
statistically 50% of their offspring. When this is a bitch pup, she will also be an unaffected carrier
like her dam. When this is a dog pup, he will suffer from DCM as an adult dog. This is because male
dogs only have one X chromosome; the other sex chromosome being the Y chromosome inherited
from their sire (which made them male). Affected males will produce 100% carrier daughters, as they
give this defective X chromosome to all their female offspring. Then these carrier daughters produce
again affected sons. However, when a disease is X-linked, the sons of an affected sire are NOT at
risk, as they do not inherit an X chromosome from their sires. Females can also be affected (i.e.
develop DCM), although this is more rare. With an X-linked recessive disease females have TWO
defective X-chromosomes. If used in a breeding program, such a bitch would produce 100% affected
sons and 100% carrier daughters bred to a clear dog. If an affected dog was used on a carrier bitch,
then 50% of the male pups would be affected, 25% of the female pups would also have DCM, with
the other 25% would be DCM carriers. So to summarize, X-linked recessive disorders are: seen with
much more frequency in males than in females, are a trait never transferred directly from father to
son, and have the appearance of skipping a generation because it's transmitted through carrier
females typically. DCM is obviously a serious enough disease that it's wise for breeders to learn
about the method of inheritance and they should track its progression through various generations,
thereby attempting to predict carrier status and thus reducing the number of potentially affected
dogs.

HCM (hypertrophic cardiomyopathy) is exceeding rare in dogs & typically not a primary disease
(i.e. it results from other disease). DCM and ACM (arrhythmogenic cardiomyopathy) are primary
heart diseases that are heritable in nature and involve the heart muscle. For a precise discussion of
DCM and it's relationship to ACM, another form of "cardio" that does occur in dogs and may
occur in the Great Dane, see:
http://www.vin.com/VINDBPub/SearchPB/Proceedings/PR05000/PR00034.htm

Also noteworthy is Dr. Kate Meurs current research into a potential marker gene for the disease in
our breed. Dr. Meurs is currently performing the first molecular evaluation of this disease in our
breed, and is evaluating the dystrophin gene as a potential candidate for a gene marker. Finding a
marker gene would mean that a simple blood test could be used to screen our breeding stock for
DCM. Dr. Meurs writes: "We are continuing to recruit dogs from families of Great Danes with a
history of dilated cardiomyopathy. We particularly need to evaluate affected dogs as well as their
family members. Additionally, we are in great need of healthy Great Danes that are at least 7 years
of age who could come to Ohio State for an echocardiogram and who would be willing to donate a
small blood sample. These animals will serve as "healthy controls" and their DNA will be compared
to the DNA from the affected animals."

The Great Dane is the second most common breed of dog afflicted with DCM. So it's important
that our dogs, especially our breeding stock, be examined for signs of DCM. Although it might be
the case that a simple auscultation by an expert would be able to offer a preliminary diagnosis of
DCM, it's generally thought that an ultrasound is required for a cardiomyopathy breeding
clearance. This exam ideally should include a full physical and a history, and be done by a competent
cardiologist. This generally takes up to an hour; the dog is examined, then the ultrasound performed
& taped (audio & visual) and the results interperlated. Radiographs (xrays) or other further tests
may be deemed necessary, particularly if the initial cardiac testing is for suspected illness &/or any
anomalies come up on the ultrasound/physical exams. A thorough exam screens for all gross heart
diseases & anomalies. Regular (annual?) screening exams on adult dogs are recommended for
breeding stock in breeds like ours where DCM is found. So a one-time OFA Cardiac clearance is
not an effective screening tool for DCM.

Cardiovascular diseases generally have their origin in the reduced effectiveness of the heart to
function as a blood pump. This requires of course muscle. In DCM, the smooth muscle of the heart,
the myocardium, fails to maintain it's contractility, and essentially gets "stretched out" so that the
heart enlarges. DCM literally means enlarged heart muscle disease. The details of why and how
exactly this occurs are currently unknown. However Dr. Meur's research on dystrophin points the
way to one potential explanation. Dystrophin is a membrane-associated protein that helps regulate
the integrity of the muscle cells; it fails to function properly in such diseases as muscular dystrophy,
and when dystrophin is absent, the muscle cells die. Duchenne muscular dystrophy (DMD) is an
X-linked disorder in humans. In DMD typically there are frame-shift & in-frame mutations (i.e. via
deletion) in the DNA. The result is a defective protein as the DNA made is a "nonsense" strand
or has portions that don't code for a useful dystrophin protein. Dr. Meurs will be speaking at our
2002 National Specialty on DCM and her research on our breed and will provide us with an update
of the evaluation of DCM in the Great Dane. All are encouraged to attend. Also Purina has
recently initiated a pamphlet on health and welfare issues in our breed. The first issue of this
GREAT DANE REVIEW (Jan2002) was devoted to the topic of DCM. It gives a nice
overview of the disease, it's diagnosis and treatment. With the cooperation of Purina, I have
arranged to have this pamphlet made available as a free handout in the educational room at the 2002
GDCA National Specialty. Dr. Meurs email is: meurs.1@osu.edu.