1. The identification of early markers for the impending development of Dilated Cardiomyopathy will provide an opportunity to intervene with newer medications with a view to aborting the progression of this disorder or at least its progression.

2. This project will provide an opportunity for the owners of Dobermans that live somewhat removed from a centre of Doberman cardiac research to take an active role in helping their own dog and helping to eradicate this devastating disorder in their breed.

3. In that this will be an intercontinental project, we will be able to determine if the incidence of dilated cardiomyopathy is less prevalent in several countries.  This will help select breeding stock.

BACKGROUND:

Dilated Cardiomyopathy (DCM) is an irreversible and universally fatal disorder in the Doberman Pinscher breed.  The COVE Study Trial demonstrated that DCM is more prevalent in the Doberman than in all other breeds of dogs combined.  Ongoing work at the University of Guelph has indicated that the prevalence of DCM ranges from 31% to 47% in the breed in this region, with only a slightly higher occurrence in the male gender.

In addition, we have demonstrated that death due to DCM occurs due to euthanasia, congestive heart failure or as sudden death.  Sudden death occurs when ventricular premature contractions become frequent and progress to ventricular fibrillation.  In one study, sudden death occurred as the very first symptom of DCM in 31% of Dobermans that were destined to develop DCM. And, finally we have demonstrated that if one starts an asymptomatic Doberman in the hidden stage of DCM (signs seen only by ultrasound, ECG, etc.) on an angiotensin converting enzyme (ACE) inhibitor, the prevalence of sudden death as the first sign of DCM is significantly reduced and the asymptomatic period is significantly prolonged. 

A Holter recording provides one with an opportunity to look for premature ventricular contractions over an extended time period, usually 24 hours.  In addition to looking for electrical irritability that is so prevalent early in DCM (during the asymptomatic period).  We can also use this test to determine heart rate variability and the signal average electrocardiogram (ECG). These two tests have been demonstrated to be of outstanding value in people to predict cardiac death, especially sudden death, and cardiac weakness. Although these tests can be determined without a Holter recording, most Dobermans cannot completely relax in a hospital environment to provide meaningful information (work from the University of Guelph and the University of Georgia). From the Holter we can select a period when the dog is relaxed, as when sleeping, and extract a segment of 20 minutes for analysis of heart rate variability and signal average ECG. And finally, a Holter can be placed on a dog and data obtained by owners far removed from a veterinary facility. Thus dogs from literally anywhere in the world could be entered into a study utilizing Holter recordings.

OBJECTIVES:

1. To determine the incidence and frequency of premature ventricular contractions in asymptomatic Doberman Pinschers.
2. To determine the relation between geographic region and the incidence and frequency of premature ventricular contractions in asymptomatic Doberman Pinschers.
3. To determine the relation between age, coat color, and gender and the incidence and frequency of premature ventricular contractions in asymptomatic Doberman Pinschers.
4. To determine the range of normality for heart rate variability and the signal average ECG for asymptomatic Doberman Pinschers.
5. To following these dogs for the rest of their lives to determine:

• The frequency of premature ventricular contractions that predict dogs destined to develop DCM or sudden death.
• The level of abnormality of heart rate variability that predicts dogs destined to develop DCM or sudden death.
• The level of abnormality of the signal average ECG that predicts dogs destined to develop DCM or sudden death.

1. To investigate newer therapies that have the potential to abort or retard the progression of occult DCM in the asymptomatic Doberman Pinscher.
2. To investigate newer therapies that have the potential to reduce the incidence of sudden death.
   

EXPERIMENTAL DESIGN:

This is a long-term study. We are familiar with such long-term efforts as demonstrated by our activities for the last 10 years of work with the natural history of DCM in Doberman Pinschers. We propose to identify groups of asymptomatic Dobermans whose owners are willing to allow us to Holter their dogs at least annually on a long-term basis. A Contact Person will then arrange to have the Holter placed on each dog in the group on successive days. After each dog in the group has been holtered, the collection of tapes, the Holter recorder, etc will be returned to the University of Guelph. The tapes will be analyzed in batches and the owners will receive a confidential report. We propose to begin with 5 Holter recorders and add more as demand increases. Presently, we have been contacted by groups from North America, Europe, South America and Australia/New Zealand interested in participating.

As some of these dogs will ultimately go on to develop overt congestive heart failure (CHF) or sudden death (SD), our goal is to be able to determine the frequency and type of premature ventricular contractions that were detected on the examinations prior to these unfortunate endpoints (CHF or SD) and the related time-frames. Similarly, the changes to the heart rate variability and signal average ECG tests will be monitored for dogs that move toward overt CHF or SD.

As markers of risk become apparent, the owners of these dogs will be offered participation in therapeutic trials to determine the ability of various medications to reduce the risk of overt DCM or sudden death.

 Note: We propose to seek owners of Dobermans with a long-term view and commitment, and not individuals that wish a one-time Holter examination. Also there would be a nominal fee of $75 US (except in Canada use Cdn$) for the first year and $65 thereafter, for each dog examined. This will serve to support an individual to analyze all these tapes, collate the data, and generate reports for the owners.