Saturday, May 11, 2013

Heart disease in Great danes

Heart Disease in the Great Dane
 Cardiomyopathy and Congenital Disease.

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, triscuspid valve dysplasia--both potentially fatal valvular defect, aortic and subaortic stenosis (SAS)--other potentially fatal defects 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. It is largely males that are affected in this breed, with average age of onset of clinical symptoms seen at 5 years (3-7 years range typical). In an earlier paper in the JAVMA (Meurs, et al, Mar2001) concerning DCM, Dr. Meurs outlined the clinical features of DCM and offered some comments on potential inheritance of the disease. Preliminary data has suggested that DCM in the Great Dane is typically inherited in an X-linked recessive fashion. What this pattern of inheritance means is explained in the paragraph below, but essentially implicates the healthy dams of DCM sons because they are carriers. Recent research has not confirmed this pattern, and breeder anecdote offers two scenarios: one which supports the notion of X-linkage, another that suggests a possible "dominant" inheritance associated with a sire-to-son pattern. It's difficult to say if this means the Great Dane is dealing with two seperate forms of DCM, or perhaps the pattern of inheritance is simply multifactoral (and so both parents are involved in the inheritance of 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 result is a heart that fails to function effectively, and a distinctive pattern of measurements can be found for DCM via echocardiology. 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.
Cardiomyopapthy comes in several forms: hypertrophic cardiomyopathy (HCM) 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 it here...
The Great Dane is at risk for both congenital and adult-onset heart disease. So it's important that our dogs, especially our breeding stock, be examined for signs of heart disease. Although it might be the case that a simple auscultation by an expert would be able to offer a preliminary diagnosis of many congential forms of heart disease, it's generally recommend that breeding stock receive echocardiograms routinely (at least every 2 years beginning at age 2) for 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 an 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 screening exams on adult dogs are recommended for breeding stock in breeds like ours where adult-onset heart disease is found. So a one-time OFA Cardiac clearance is not an effective screening tool for such as DCM and SAS.

Permission to reprint as submitted for educational purposes is given.
Submitted by JP Yousha, Chair, H&W Committee, GDCA, updated 2009.

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