Cocker Spaniel Dilated Cardiomyopathy

Dilated cardiomyopathy is reported in both American and English cocker spaniels. The disease is not common and cocker spaniels are more likely to develop heart failure due to mitral valve endocardiosis than cardiomyopathy. However, when cardiomyopathy is present, it is likely to start as a left ventricular disease that develops into biventricular failure.

An association between the development of DCM and decreased plasma taurine levels has been reported in some American cocker spaniels with dilated cardiomyopathy. ³ Plasma taurine levels (normal range:44-224 nmol/ml) should be evaluated to help guide therapeutic interventions and prognosis. Supplemental taurine (500 mg q 12h, PO) may be started while waiting for the results of the plasma levels and should be continued if the level is low. Additional treatment should be given as needed for heart failure, arrhythmias, etc. If taurine deficiency is documented, significant improvement may be observed with supplementation in 3-4 months. If taurine deficiency is not identified as the etiology of the DCM, the prognosis is poorer, but progression is fairly slow and the dog may be kept comfortable on heart failure medications for some time.

Recognition & Clinical Management

Kathryn M. Meurs, DVM, PhD, Diplomate ACVIM (Cardiology)
The Ohio State University

Dilated cardiomyopathy (DCM) is a syndrome characterized by impaired myocardial function (systolic +/- diastolic), ventricular dilation and frequently, tachyarrhythmias. In the dog, specific breed predispositions exist and the Doberman pinscher, Great Dane, Scottish deerhound, and Irish wolfhound appear to be over represented. This discussion will emphasize breed specific findings and newer developments in the understanding of etiologies, clinical presentation, diagnosis, screening and treatment for canine DCM as well as arrhythmogenic cardiomyopathy in the Boxer.

Etiology

The etiology of canine DCM is unknown in many cases. The development of DCM is likely to be a multifactorial process that could involve nutritional, familial and infectious agents. In some cases, there is evidence of a specific nutritional or familial link.^1-5

Nutritional

In 1991, a family of Boxers with dilated cardiomyopathy (historically known as Type III Boxer cardiomyopathy) was identified as having a myocardial L-carnitine deficiency.² Affected dogs demonstrated some reversal of disease with L- carnitine supplementation.² However, affected dogs eventually died from their heart disease, even while on supplementation. L-carnitine deficiency does not appear to be the cause of DCM in the majority of Boxers, or in other breeds. However, it is still considered a potential etiology for Boxers with DCM and supplementation should be considered for these rare cases.

Some American Cocker Spaniels have been reported to develop DCM associated with low taurine levels.³ Taurine supplementation may result in reversal of the disease and a significantly better prognosis. Although taurine does not appear to be associated with the development of DCM in other commonly affected breeds, it is still occasionally reported in unique presentations of DCM and measurement of levels may be considered in atypical breeds.

Familial

A genetic etiology has been strongly suggested in several breeds of dogs including the Doberman pinscher, Great Dane and Boxer and should be suspected in other breeds with a strong breed predisposition.^2,4,5 The mode of inheritance has not been determined in the Doberman pinscher, but a strong male predisposition in the Great Dane suggests an X-linked mode of inheritance.⁵

Diagnosis

Clinical presentation

This is an adult onset disease with a clinical presentation that may be as subtle as a gradual development of exercise intolerance and weight loss. However, more commonly the early signs of the disease are overlooked and the disease is not diagnosed until congestive heart failure develops and the patient presents with coughing, respiratory distress and occasionally, ascites. It would appear that the early stages of DCM are difficult to diagnose unless a clinician maintains a high level of suspicion for dogs that are of an at-risk breed and annual screening is performed.

Physical examination

A soft systolic murmur and/or gallop rhythm (S₃) may be ausculted at the left apex. In some cases, this may be the first sign of the disease. A tachyarrhythmia may be noted. Although canine DCM is predominantly a left ventricular disease, biventricular involvement and failure with jugular venous distension and ascites is frequently noted, particularly in the giant breeds.

Electrocardiography

Left atrial and ventricular enlargement and sinus tachycardia, atrial fibrillationor ventricular tachyarrhythmias are common.

Radiography

Left atrial and ventricular enlargement with or without pulmonary venous distension and pulmonary oedema may be observed

Figure 1a and 1b.

Lateral and ventrodorsal radiographs of a Great Dane with dilated cardiomyopathy. Note the left atrial and ventricular enlargement, pulmonary venous congestion and pulmonary oedema.

Figure 1a	Figure 1b.

 Echocardiography

The diagnosis of DCM in the symptomatic dog is easily determined by echocardiography. Left atrial and ventricular dilation with systolic dysfunction (decreased fractional shortening, ejection fraction and shortening area) and increased end-systolic volume are evident and often severe. Unfortunately, the diagnosis of the affected dog in the occult (asymptomatic) stage is much more difficult and will be discussed below.

Figure 2.

M-mode echocardiogram of the left ventricle from a Doberman pinscher with dilated cardiomyopathy. The left ventricle is dilated and has decreased systolic function. Note the decreased systolic motion of the interventricular septum and left ventricular free wall.

Adult Doberman pinschers with greater than 50 ventricular premature complexes (VPCs) per 24 hours, or couplets or triplets are suspect for the development of DCM.⁷ Owners should be advised that since this is an adult onset disease with variability in the age of onset, screening tests should be performed annually.

Prognosis

Dilated cardiomyopathy in the Doberman pinschers is a very malignant form of DCM in comparison to the disease in other breeds. Once clinical signs have developed, death usually occurs due to heart failure or sudden death within 6 months, therapy is palliative at best.

Giant Breed Dilated Cardiomyopathy

Giant breed dilated cardiomyopathy is used to characterize DCM in the Irish Wolfhound, Great Dane, Scottish Deerhound and Newfoundland dog, among others. Dilated cardiomyopathy in these breeds is more commonly a progressive biventricular disease and may present with ascites.

A high percentage of affected dogs present with atrial fibrillation. In some cases, atrial fibrillation may develop before any other evidence of underlying myocardial disease (chamber enlargement or systolic dysfunction). These dogs should be carefully followed for the development of DCM.

Screening

Occasional cases of familial disease in the Great Dane, Newfoundland and Irish wolfhound have been identified. In the Great Dane, it is most likely an X-linked disease. Sons of affected females are at high risk of developing the disease; daughters of affected fathers are likely to be silent carriers. Since it is adult onset, all dogs should be screened annually with echocardiography. Dogs with atrial fibrillation without other evidence of cardiomyopathy should probably be withheld from until it can be determined if they will develop DCM.

Treatment OF DCM

Asymptomatic dogs with ventricular dilation/dysfunction (occult)

Two types of therapy have been under investigation for treatment of occult DCM, ACE inhibitors and beta-blockers. Administration of ACE inhibitors (enalapril, 0.25-0.5 mg/kg q12hr) has been shown to slow the progression to heart failure in the Doberman pinscher.⁹ Since ACE inhibitors are generally well tolerated, this treatment is recommended for dogs of other breeds at this stage and provides additional support for the practice of screening at risk dogs (perhaps with a family history) to allow any intervention. Administration of beta-blockers at this stage is still being evaluated. The addition of low dose beta-blockers to the treatment of human patients with DCM and stable heart failure has demonstrated a reduction in both mortality and morbidity.¹⁰ However, many human patients with DCM cannot tolerate even very low doses of beta-blockers and demonstrate rapid cardiac decompensation. The use of beta-blockers for the canine patient with DCM has not yet been well studied and a consensus opinion on use of these drugs for our patients is not yet available. Beta-blockers might be considered for the patient with occult disease, but they should be very carefully monitored and should not be given once there is evidence of fluid retention and heart failure until it is very well stabilized. The optimal beta-blocker for this purpose appears to be carvedilol because of its effects on both alpha and beta-receptors. It cannot be over emphasized that the addition of beta-blockers in our DCM patients should be done very cautiously with gradual increases in dosing after a two-week period and careful monitoring of heart rate, blood pressure and symptomology.

Dogs with heart failure

Symptoms of heart failure should be alleviated with furosemide (1-3 mg/kg, q8-12h) and ACE inhibitors (enalapril, 0.25-0.5 mg/kg, q12h, orally). As heart failure becomes more refractory, the addition of spironolactone (1-2 mg/kg, q12h, orally) should be considered for aldosterone blocking affects. Digoxin may be added when the heart failure becomes refractory or atrial fibrillation is observed. Dogs with DCM and chronic heart failure often develop weight loss and cardiac cachexia. Fish oil supplementation has been shown to decrease cardiac cachexia in some cases.¹¹ It may be dosed at 40 mg/kg EPA and 25 mg/kg DHA . For easy dosing, most 1.0 gm capsules contain 180 mg EPA and 120 mg DHA.¹²

Arrhythmogenic right ventricular cardiomyopathy in the Boxer

Historically, boxers that presented with syncope and ventricular arrhythmias were diagnosed with dilated cardiomyopathy because some of the dogs eventually developed left ventricular dilation and heart failure. However, the majority of affected boxers suffer primarily from ventricular arrhythmias as a result of right ventricular myocardial disease. In some cases, the disease can advance to involve the interventricular septum and left ventricular free wall, left ventricular dilation and systolic dysfunction may result. This disease appears to have more similarities with arrhythmogenic right ventricular cardiomyopathy (ARVC) in human beings than with true dilated cardiomyopathy. This disease is now frequently being referred to as boxer ARVC.

History

The most common presenting complaint is one of syncope with brief (1-2 minutes) episodes of collapse, with quick recovery. The episodes may be associated with excitement. Less frequently, a dog may present with signs of left or biventricular heart failure.

Physical Examination

Many affected Boxers have a completely normal physical exam.However,arrhythmias may be ausculted. In a small percentage of cases (those dogs which really have ventricular dilation and systolic dysfunction), a systolic murmur and/or gallop (S₃) may be ausculted at the left apex and infrequently, signs of right heart failure (ascites and jugular venous distension) may be observed.

Electrocardiography

A 2-5 minute electrocardiogram is frequently normal in the affected Boxer; however, VPCs may be present singly, in pairs and in runs of paroxysmal ventricular tachycardia. The VPCs typically have a wide, upright QRS in leads I, II, III, and AVF, consistent with the right ventricular origin of this arrhythmia. The arrhythmia may be quite intermittent and in some cases, ventricular arrhythmias can cause syncope but may not be observed on the ECG in the clinic; in these cases, a 24-hour Holter monitor should be performed to evaluate for arrhythmias.

Figure 5.

This is an example of ventricular tachycardia that was detected by Holter monitoring in a Boxer that was screened for arrhythmogenic right ventricular cardiomyopathy. At the end of the electrocardiogram, the dog converts to a sinus arrhythmia.

Interpretation of the Holter results can sometimes be challenging because strict criteria for this diagnosis do not exist. However since it is unusual for a normal dog to have any VPCs in a 24-hour period, the observation of > 100 VPCs, or periods of couplets, triplets or runs of ventricular tachycardia are abnormal. Supraventricular premature complexes may be seen but not frequently.

Radiography

Thoracic radiographs are usually normal. However, in the small number of cases with left ventricular dilation and systolic dysfunction, generalized cardiomegaly with pulmonary oedema and/or pleural effusion may be noted.

Echocardiography

Left ventricular dimensions and contractility are usually normal. Eventually, a small percentage of cases may show left ventricular dilation and systolic dysfunction.

Screening

This is a familial, adult onset disease that appears to be inherited as an autosomal dominant trait. Since this disease appears to present as an electrical abnormality, any screening efforts should be based on annual Holter monitoring and possibly, annual echocardiography. As mentioned above, clear criteria for affected status are still being determined and day to day variability of arrhythmias exist, so owners should be encouraged to screen annually rather than put emphasis on a single Holter reading.

Treatment

Asymptomatic dogs with ventricular tachyarrhythmias

If an arrhythmia is detected on routine examination, a Holter monitor should be performed to evaluate for the frequency and complexity of the arrhythmia. Although a strict relationship between the development of symptoms and the number of VPCs does not exist, treatment is generally started if > 1000 VPCs/24 hours, runs of ventricular tachycardia or evidence of the R on T phenomenon exist. Owners should be advised that ventricular antiarrhythmics have the potential for proarrhythmic effects and that treatment is not known to decrease risk of sudden death.

Dogs with syncope

Dogs with syncope and ventricular arrhythmias are started on treatment. There are two choices for treatment that are well tolerated and have been shown to decrease VPC number and complexity, sotalol (1.5-3.5 mg/kg, q 12hr, orally) and the combination of mexiletine (5-8 mg/kg, q 8hr, orally) and atenolol (12.5 mg/DOG, q12h, orally). ¹³ It is likely that there is individual variation for drug response and if a poor response is observed with one drug, a different one may prove to more effective. Ideally, a Holter monitor would be placed before starting therapy and repeated two to three weeks after starting therapy to demonstrate the effect of therapy. Significant day-to-day variation in VPC number exists and a therapeutic effect is likely to exist if at least an 85% reduction in VPC number while on medication is observed.

Dogs with systolic dysfunction and heart failure

If echocardiography demonstrates significant systolic dysfunction and ventricular dilation, treatment as stated above for DCM is indicated. Additionally, supplementation with L-carnitine should be given (50 mg/kg, q8-12h, orally).

Prognosis

Sudden death is always possible. However, many dogs may live for years on antiarrhythmics without symptoms, some of these may develop ventricular dilation and systolic dysfunction.

References

1.  Harpster N: Boxer cardiomyopathy. In: Kirk RW,ed. Current Veterinary Therapy VIII. Philadelphia, PA,WB Saunders, 1983, pp 329-337.

2.  Keene B, Panciera DP, Atkins CE, et al. Myocardial L- carnitine deficiency in a family of dogs with dilated cardiomyopathy. J Am Vet Med Assoc 198:647-650,1991.

3.  Kittleson MD, Keene BW, Pion P, et al. Results of the multicenter spaniel trial (MUST): Taurine- and carnitine- responsive dilated cardiomyopathy in American Cocker Spaniels with decreased plasma taurine concentration. J Vet Intern Med 11:204-211, 1998.

4.  Hammer TA, Venta PJ, Eyster GE. The genetic basis of dilated cardiomyopathy in Doberman pinschers. Anim Gen 27:101-119,1996.

5.  Meurs KM, Miller MW, Wright NA. Clinical features of dilated cardiomyopathy in Great Danes and results of a pedigree analysis: 17 cases (1990-2000). J Am Vet Med Assoc 218:729-732,2001.

6.  O'Grady MR, Horne R. Occult dilated cardiomyopathy: An echocardiographic and electrocardiographic study of 193 asymptomatic Doberman Pinschers. Proceedings of the 10th annual ACVIM Forum 795-795,1998.

7.  Calvert CA, Jacobs G, Smith D, et al. Long -term ambulatory electrocardiographic (Holter) recordings in overtly healthy Doberman pinschers with normal echocardiograms. J Am Vet Med Assoc 216:34-39, 2000

8.  Freeman LM, Michel KE, Brown DJ, et al. Idiopathic dilated cardiomyopathy in Dalmations: Nine cases (1990-1995). J Am Vet Med Assoc 209:1592-1596,1996.

9.  O'Grady MR. DCM in Doberamn pinschers: Lessons learned the first decade of study. Proceedings of the 20th annual ACVIM Forum 114-115,2002.

10. Stevenson LW. Beta-blockers for stable heart failure. New Engl J Med 346:1346-1347,2002.

11. Freeman LM, Rush JE, Kehayias JJ, et al. Nutritional alterations and the effect of fish oil supplementation in dogs with heart failure. J Vet Intern Med 12:440-448,1998.

12. Freeman LM. Interventional nutrition for cardiac disease. Clin Techniques in Small Animal Pract 13: 232-237,1998.

13. Meurs KM, Spier AW, Wright NA, et al. Comparison of the effects of four antiarrhythmic treatments for familial ventricular arrhythmias in Boxer's Am Vet Med Assoc 221:522-527,2002.

Kathryn M. Meurs, DVM, PhD, Diplomate ACVIM (Cardiology)
The Ohio State University