The purposes of this study were to evaluate Boxers with ventricular arrhythmias (abnormal heart beats which arise in the ventricular regions or lower chambers of the heart) to determine whether this trait runs in families of Boxers, and, if so to determine the mode of inheritance.
A wide spectrum of ventricular arrhythmias, including single PVCs, PVCs which occur together in couplets, and sudden attacks of extremely rapid heart beats (tachycardia) are frequently detected in Boxers.
The observation that abnormal heart rhythms occur in Boxer families has been observed by Harpster (1991); Keene, Pancera and Atkins (1991); and Goodwin and Cattiny (1995). In 1983, closely related Boxers in New England were observed to have a high prevalence of abnormal heart rhythms (Harpster 1983). A few breeding lines seemed to be commonly affected and affected littermates were identified. In 1991, a family of Boxers with a deficiency of L-carnitine and arrhythmias was reported and subsequently a family of Boxers with arrhythmias was observed by Keene et al and Goodwin and Cattiny. Unfortunately [in these articles] strong evidence supporting a familial basis of inheritance for this disorder and an understanding of the pattern of inheritance is lacking. in these studies In our study we describe 2 families of Boxers with abnormal heart rhythms (PVCs) and provide evidence that familial ventricular arrhythmias (FVA) is inherited in Boxers as an autosomal dominant trait.
Families of Boxers were recruited for evaluation at the College of Veterinary Medicine at The Ohio State University and Texas A & M University. Complete cardiac studies were conducted on the dogs in the study. Dogs were rejected from the study if they had other existing heart disease as determined by an echocardiogram. For the purposes of the study dogs were considered to be affected with FVA if a 24-hour Holter monitor detected 50 or more PVC's. In addition, the pattern of inheritance was also evaluated statistically using a strict criterion (i.e., that a normal Boxer should not have any PVCs over a 24 hour period) and a more lenient criterion (i.e., that up to 500 PVCs are normal in a Boxer.)
Pedigrees were analyzed for a pattern of inheritance. Autosomal dominant, autosomal recessive , and X-linked patterns were considered the most likely modes of inheritance.
The mode of inheritance was considered to be autosomal dominant if the following conditions were met:
The offspring of the affected individuals have a 50% statistical chance of being affected .
Autosomal recessive was defined by
X-linked recessive inheritance was defined by
X-linked dominant inheritance was defined by
Two affected parents cannot produce an un affected female with either type of X-linked inheritance.
Complete cardiovascular examinations were performed on 82 dogs from 6 extended families. Of all dogs evaluated, only 6 dogs had no PVCs detected on the Holter monitor. All dogs evaluated had normal cardiac function. Four of the families were missing important family members and could not be used to determine the pattern of inheritance. The two most complete families were used for determining inheritance patterns. (Fig. 1)
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Table 1. Results of the clinical evaluation (electrocariogram, echocardiogram, Holter monitor) of Boxer families A and B. A paroxysm of PVCs was defined as a run of 3 in a row.
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Character of Arrhythmias |
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Multiform singlets, paroxysms of PVCs |
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Monomorphic singlets, couplets |
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Multiform singlets, bigeminy |
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Multiform singlets, trigeminy |
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Multiform singlets |
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Multiform singlets, triplets |
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Monomorphic couplets,triplets |
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Multiform singlets, couplets, bigeminy |
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Multiform singlets, couplets |
Family A
Three males and one female were evaluated and called affected with FVA under the parameters of the study (greater than 50 PVCs in a 24 hour period). A 5th dog (A5) had a history of syncope (temporary loss of consciousness due to a deficiency of blood to the brain) but died suddenly before a Holter test could be performed. Arrhythmias could be detected by auscultation (listening to the heart with a stethoscope) in four of the dogs. Abnormal arrhythmias ranged from 0 in the unaffected female to 4,894 in one of the affected females. The arrhythmias varied from single PVCs to sudden bursts of PVCs. Heart dimensions and function were normal in all dogs.
Two males and six females were evaluated. None of the dogs had had syncope. In a physical examination none of the dogs had arrhythmias that were detected by stethoscope. The number of PVCs in a 24 hour Holter monitor test ranged from 12 to 1,558. Heart dimensions and heart function were normal in all dogs.
Autosomal recessive and an X-linked pattern of inheritance were ruled out during pedigree evaluation. Autosomal recessive inheritance was ruled out because the trait did not skip generations and affected individuals produced unaffected individuals. An X-linked pattern of inheritance was ruled out because there was an equal number of affected males and females and two affected individuals produced an unaffected female.
The pattern of inheritance was determined to be autosomal dominant because affected individuals occurred in every generation, the disease affected approximately as many males as females, and affected parents were able to produce unaffected female dogs.
Even altering the criteria using stricter criteria (0 PVCs in a 24 hour period) and more lenient criteria (greater than 500 PVCs in a 24 hour period) the autosomal dominant pattern of inheritance was determined to be the pattern of inheritance of FVA.
This report describes 2 families of Boxers with a significant presence of abnormal heart rhythms in individual Boxers within the family. Boxer cardiomyopathy has been defined as a physical condition in which there are an abnormal number of PVCs, episodes in which the dog loses consciousness (syncope), and sudden death (Harpster 1983, 1991). Three different types of cardiomyopathy have been described:
It is possible that dogs progress from Type I to Type III cardiomyopathy but there is no data to support this at the current time.
The dogs in the study had normal heart dimensions and blood flow values as determined by an echocardiogram. Because the Boxers in the study seemed to have a primarily electrical disorder rather than a disorder affecting the heart muscle, the authors prefer to refer to the condition described in the study as having FVA (Familial Ventricular Arrhythmias).
Fifty PVCs in a 24-hour period was defined as determining an affected dog for the purposes of the study. This value was chosen after consideration of what constitutes a normal canine 24-hour Holter test, but 50 PVCs as a value for determining an affected dog is still controversial. It may be that even a single PVC is abnormal in a healthy dog. On the other hand, a small number of PVCs may be normal in a healthy dog, particularly in an older dog. (Hall 1991, Ulloa 1995, Moise 1995). Twenty-four-hour ambulatory electrocardiographic evaluation (Holter monitor test) of 228 research Beagles by Ulloa and others documented PVCs in approximately 20% of the dogs. However, in all but 4 dogs the total number of PVCs per day was no more than 9 PVCs. The four dogs with greater than 9 PVCs possibly had cardiac disease. A similar study of 16 healthy dogs of various breeds demonstrated an average of 7 and a range of 0 to 52. PVCs over a 24 hour period. However, this study included 3 Boxers possibly affected with FVA. If these Boxers are excluded, the average number of PVCs per day was only 2. Some breed variation may exist and certain breeds (including Boxers) normally may have a higher number of PVCs per 24 hours. Alternatively, all Boxers with PVCs may be affected with FVA. The choice of 50 PVCs per 24 hours seems to be appropriate because our dogs either had very few (0-16) or many PVCs (112-4,894). To avoid errors based on the classification of dogs as affected or unaffected, the pattern of inheritance was reevaluated using strict and lenient criteria. The pattern of inheritance still was determined to be autosomal dominant by exclusion of autosomal recessive and X-linked patterns of inheritance.
One hazard of evaluating the inheritance of an adult-onset disease is that apparently unaffected dogs eventually may develop the disease. Very little information is available on the age of onset of ventricular arrhythmias in Boxers. One way to increase the likelihood of evaluating affected dogs is to evaluate only mature adult littermates. In family A, the members of the family (A2, A3 that determined the pattern of inheritance were 6 years of age at the time of diagnosis. In family B, the critical members (B5, B6, B7) were 8 years of age. Although it seems unlikely that dog B6 (at 8 years of age) still may become affected, continued follow-up will be imperative for a more completed understanding of this disease.
The syndrome of FVA in Boxers may lead to frequent syncopal episodes, which may or may not be well controlled with antiarrhythmic therapy. Additionally and very importantly, FVA can cause sudden death. The likelihood that FVA is inherited as an autosomal dominant trait justifies recommending careful screening of breeding animals of a mature age and consideration of removal of affected dogs from breeding programs.
Aortic stenosis &endash; Occurs when two of the three flaps that comprise the aortic valve fuse together. This fusion narrows the opening to the aorta, thus restricting the blood flow out of the left ventricle into the aorta. Symptoms and signs of this condition include exercise intolerance, fainting, and a systolic murmur (a murmur or slight noise heard when the heart contracts.) There is no known relationship between aortic stenosis and Boxer cardiomyopathy.
Arrhythmia &emdash;; An erratic heartbeat. This occurs when the electrical impulses are no longer originating from the sinus node (or normal pacemaker) and proceeding in a predictable pattern through the various areas of the heart to ensure a predictable rhuthmic contraction of the heart muscle. Prolonged arrhythmias can compromise the pumping function of the heart. Symptoms associated with arrhythmias include fatigue, exercise intolerance, weakness, dizziness, fainting, or palpitations. Arrhythmias can come and go, or they can be constant and incessant, and thus so can their symptoms.
Bigeminy &emdash; Every other beat is a couplet (two successive PVC's.)
Cardiac conduction system &endash; Specialized heart tissues that carry the electrical impulses which cause the heart muscle to contract.
Congestive heart failure &endash; A condition in which the heart does not pump enough blood to satisfy the needs of the body.
Couplet -- Two consecutive PVC's.
Echocardiography - Ultrasonic examination of the heart. During the examination the dog lies on a soft padded table. The cardiologist places a hand held microphone-like instrument called a transducer on the dog's chest. The transducer emits high frequency sound waves that neither we nor out pets can hear. These sound waves are reflected back to the transducer from the heart. The ultrasound machine translates the sound waves into a picture viewed on a monitor.
ECG (electrocardiogram) - A graphic representation of the electrical impulses of the heart.
Ectopic beat &emdash; A premature heartbeat due to a contraction impulse from an abnormal source in either the atria (upper chambers of the heart), or the ventricles (lower chambers) of the heart.
Histopathology - The study of pathology of cells and tissues.
Holter monitor &emdash; A portable device that records an ECG over a 24 hour period. It is the size of a portable tape recorder and has wires that connect to pads (electrodes) that are put on a dog's chest. These electrodes transmit the electrical impulses of the heart to the monitor and the impulses are recorded on an audiocassette tape in the monitor.
L-carnitine - A naturally occurring compound in the body synthesized from the amino acids lysine and methionine. Supplementaion with large quantities of l-carnitine was found to improve the contractile functions of the hearts of two sibling Boxer dogs with dilated cardiomyopathy and resultant congestive heart failure.
Myocardium &emdash; The specialized muscle tissue of the heart which is able to contract repeatedly without fatiguing.
PVCs (Premature Ventricular Contractions) - "Extra" heartbeats occurring out of sync with the normal regular rhythm of the heart. PVCs may cause no symptoms at all or may be felt as a "irregular" heartbeat or as the sensation of a "hard heartbeat". They may arise from a single ectopic focus (uniform) or several (multifocal) foci. The origin of the PVC is an irritable focus in either ventricle. This focus stimulates an electrical impulse that overrides the normal conduction pathway and causes the ventricle to contract earlier than normal. These beats occur before the ventricle fills completely, therefore, the amount of blood that is pumped per beat is reduced.
Syncope - Temporary loss of consciousness due to a deficiency of blood to the brain
Systolic --; The contraction phase of the heart cycle.
Systolic murmur - A heart murmur that occurs between the first and second heart sounds, during the contraction phase of the heart cycle.
Tachycardia &emdash;A rapid heart rate, usually signified by a pulse over 100 beats per minute
Trigeminy -- Every third beat is a PVC.
Triplet -- Three consecutive PVCs.
Ventricle - The right and left ventricles are the two muscular lower chambers of the heart. The right ventricle pumps oxygen-poor blood received from the right atrium out to the lungs through the pulmonary artery. The left ventricle pumps oxygen-rich blood received from the left atrium out to the body through the aorta.
Ventricular fibrillation &emdash;A ventricular arrhythmia in which there is complete absence of effective ventricular contraction, and a common cause of sudden death.
Ventricular tachycardia &emdash;Rapid heart rhythm, originating in the ventricle, during which rapid contractions prevent the heart from adequately filling with blood between beats.