DCM In Doberman Pinschers: Lessons Learned In The First Decade Of Study
Guelph, Ontario, Canada
Michael O'Grady, DVM, MS, DACVIM
Dilated cardiomyopathy (DCM) continues to be the second most commonly encountered cause of acquired congestive heart failure in the dog. In addition, DCM is observed much more commonly in large breed dogs, in fact DCM is the most common cause of heart failure in the large breed dog. Of all large breed dogs, the Doberman Pinscher is afflicted with DCM more than any other breed in North America. In fact, in the COVE Trial, more Dobermans were observed with DCM than dogs of all other breeds combined.
Ongoing work at the University of Guelph is studying the natural history of DCM in the Doberman breed. To this end symptom free Dobermans are examined by physical examination, echocardiography, and electrocardiography once yearly. These studies have demonstrated that the likelihood of developing DCM in an asymptomatic Doberman is at least 41% for males and 31% for females. These studies have demonstrated that Dobermans progress through three phases on route to congestive heart failure (CHF) and death. The first phase is characterized by a morphologically and electrically normal heart in a symptom free Doberman. The second phase is characterized by evidence of morphologic (enlargement) or electrical (ventricular ectopy) derangement in an otherwise symptom free Doberman. This latter phase has been termed occult DCM. The third and final phase of heart disease is heralded by the onset of symptoms of respiratory embarrassment due to the presence of pulmonary edema, exercise intolerance due to reduced forward flow, and or syncope due to frequent ventricular ectopy. This phase has been termed overt DCM.
The so-called occult DCM phase has been of particular interest to us. This period of derangement prior to the onset of symptoms appears to last up to 4 years. We have been impressed with the lack of evidence of exercise intolerance in dogs with advanced systolic dysfunction in the occult phase of DCM. The presence of ventricular ectopy is more commonly encountered than evidence of ventricular enlargement, particularly in the very early stages of occult DCM. The age range for Dobermans we have diagnosed with occult DCM is 2 to 12 years. Although we have previously said that even the presence of 1 VPC on a 3 to 6-minute rhythm strip in a symptom free Doberman is strong evidence of occult DCM, we have now encountered several dogs with 1 to 2 VPCs per minute that never did go onto develop CHF or sudden death.
Whereas ACE inhibitor therapy administered to dogs with chronic mitral valve insufficiency during the symptom free period of their disease has failed to delay the progression to CHF, ACE inhibitors have been demonstrated to delay the progression of occult DCM to overt DCM in Dobermans by approximately one year. Furthermore, this effect is almost exclusive to the male gender. It still remains unclear why female Dobermans would not see a similar benefit.
Sudden death refers to unexpected death. We defined sudden death as unexpected death that occurred either during sleep in the absence of respiratory distress or within one hour of appearing stable whether in CHF or not. Sudden death occurred in 14% of our dogs enrolled and 38% of all cases of DCM. Sudden death occurred in 31% of symptom free Dobermans as the first symptom of DCM. Both genders were equally likely to manifest sudden death as the first symptom of DCM. Sudden death was observed to occur more commonly before the onset of CHF than after. Females were almost twice as likely to develop sudden death before the onset of CHF as opposed to after the onset of CHF. Males however were observed to manifest sudden death with equal frequency before and after the onset of CHF. In our dogs there is very rarely any observed episodes of syncope prior to the manifestation of sudden death.
Dogs that met our criteria for ventricular ectopy (> 1PVC/min) or left ventricular systolic enlargement (> 42 mm at end systole by M mode) were more likely to manifest sudden death as the first symptom of overt DCM than CHF. Whereas dogs that met our criteria for left ventricular enlargement at end diastole (> 49 mm on M mode) were more likely to manifest CHF than sudden death as the first symptom of overt DCM.
THE HOLTER RECORDING
We presume that most cases of sudden death occur due to the development of ventricular fibrillation. Although Dr. Calvert has observed bradycardia associated with syncope in several Dobermans, tachycardia is likely the more common substrate that precedes sudden death. Ventricular fibrillation likely follows a period of time characterized by the occurrence of both isolated VPCs and paroxysms of ventricular tachycardia.
Studies at the University of Guelph are examining the natural history of ventricular ectopy in symptom free Dobermans. We are attempting to enroll Dobermans throughout the globe that are symptom free and re-Holter these dogs once yearly. Our objective is to determine predictors of sudden death in symptom free Dobermans by the examination of the Holter recording. About 130,000 beats are detected on a 24-hour recording of a Doberman. We recently reviewed Holter recordings from 128 symptom free Dobermans (73 from Canada, 55 from US). 86 dogs had evidence of ventricular ectopy, 42 did not. The frequency of ventricular ectopic beats ranged from 0 to 1556/hr with a median of 0.09/hr. VPCs were significantly more likely to occur in older dogs than younger dogs. However there was no relation between the frequency of VPCs and the age of the dog for dogs with VPCs. Continued work at the University of Guelph is evaluating the role of antiarrhythmics such as sotalol to reduce the risk of sudden death in Dobermans at risk based on Holter results.
Work by Dr. Calvert indicated that 48% of symptom free Dobermans without echocardiographic evidence of occult DCM had no VPCs on 24-hour Holter. As the frequency of VPCs increased in a group of symptom free Dobermans and possessing normal echocardiographic studies the likelihood of developing DCM increased.
The Holter examination may be the most expedient method of screening symptom free Dobermans for DCM.
CONGESTIVE HEART FAILURE STATE
The average survival for Dobermans diagnosed with CHF is 80 to 90 days with diuretics and ACE inhibitors. Dr. Calvert reports a mean of 11 weeks with a median of 7.5 weeks for Dobermans with left sided CHF. Note that the average survival for non-Doberman breeds that develop CHF due to DCM is considerably long, 280 days. The one-year mortality rate for Dobermans with CHF is 95%. Dogs that develop atrial fibrillation or ascites in addition to pulmonary edema have a poorer prognosis, mean survival of 4-6 weeks with a median of 3 weeks. We have observed that 30-40% of Dobermans can be expected to develop atrial fibrillation.
Newer therapies for DCM in the Doberman have been evaluated. Dr. Sonya Gordon evaluated the role of VDD pacing to extend survival in Dobermans with CHF. She demonstrated that Dobermans with DCM and CHF failure were identical to a subset of people with systolic failure in that they failed to respond to dual chamber pacing. We also assessed the role of a neutral endopeptidase inhibitor (inhibited the degradation of the hormone ANP) to extend survival in Dobermans with CHF. Preliminary results suggested no benefit. Current studies at the University of Guelph are evaluating the efficacy of pimobendan and spironolactone to reduce morbidity and extend survival in Dobermans with CHF due to DCM. Too few dogs have been enrolled with spironolactone to assess its efficacy. However, preliminary evidence with pimobendan suggests that pimobendan will increase survival and reduce morbidity in Dobermans with DCM. We are particularly impressed with the ability of pimobendan to increase appetite and energy level of even the most depressed dogs. However, pimobendan may increase the risk of developing atrial fibrillation and ventricular ectopy. Continuing studies will shed light on this area.
Others are assessing the role of carvedilol, a third generation beta adrenergic blocking agent. Based on work in people there is every reason to believe that carvedilol and other beta blockers will increase survival in all dogs with DCM. Currently we are examining the ability of carvedilol to delay the progression to overt DCM in Dobermans with occult DCM. These dogs are receiving benazepril in addition to carvedilol. 20 dogs are enrolled to date in this trial.
Further work on the role of pharmacotherapy for both the occult stage and CHF stage of DCM is ongoing. The role of pimobendan, spironolactone, and carvedilol in particular will be assessed. The role of antiarrhythmic therapy to reduce the incidence of sudden death, both before the onset of CHF and after the onset of CHF, will be assessed. Both sotalol and amiodarone will be studied in these areas.
Continued diagnostic studies will help us identify dogs earlier in the occult stage of DCM to help assess earlier therapy. Continued work with Holter recordings with respect to the presence and complexity of VPCs and indices of heart rate variability will be assessed to predict risk of sudden death and overt DCM. Work with newer echocardiographic indices of diastolic function and hormonal assays will stratify dogs with the 3 stages of DCM and predict the risk of sudden death or CHF and predict therapeutic responders from non-responders.
Michael R. O'Grady, DVM, MS, DACVIM
Clinical Studies, University of Guelph
Ontario Veterinary College
Guelph, ONT N1G 2W1