Dilated and arrhythmogenic cardiomyopathy in dogs (Proceedings)

In this lecture we will discuss canine dilated (DCM) and arrhythmogenic cardiomyopathy (ARVC). We will pay particular attention to breed specific findings.

Canine Dilated Cardiomyopathy - DCM

Strictly speaking, dilated cardiomyopathy (DCM) is defined as an idiopathic functional abnormality of the myocardium causing systolic dysfunction and/or arrhythmias. Definitive breed predispositions exist. Even though the disease is referred to as DCM in each breed, there are important clinical and pathological differences between the breeds mentioned. Although Boxer dogs can get dilated cardiomyopathy, most Boxers develop Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), a very different disease.

Dilated cardiomyopathy is an adult onset disease, with the exception of the Portuguese Water Dog in which it is diagnosed between two and thirty-two weeks.

There appear to be two stages of DCM, an asymptomatic stage, referred to as occult, which may be detected by careful screening, and a stage at which symptoms appear, referred to as overt. There is some preliminary evidence that early recognition of the occult stage may slow progression of the disease therefore, being aware of early signs may be beneficial to patient management.

Clinical signs

Clinical signs may include coughing, dyspnea, tachypnea, syncope and occasionally, ascites.

Physical examination

A soft systolic murmur consistent with mitral valve regurgitation and/or a gallop rhythm (S3) may be ausculted at the left apex.

A tachyarrhythmia of sinus, supraventricular or ventricular origin may be noted. In some cases, a murmur or an arrhythmia may be the first signs of the occult form of the disease and should not be overlooked. Since primary valvular disease is relatively uncommon in large breed dogs, and the detection of DCM before the development of congestive heart failure (CHF) may be beneficial in the long-term management of the case, identification of a new murmur, gallop or tachyarrhythmia in suspect breeds should be considered a "red flag" and may warrant a thorough cardiac work-up. Although canine DCM is predominantly a left ventricular disease, biventricular involvement and heart failure with jugular venous distension and ascites is frequently noted, particularly in the giant breeds.

Electrocardiography

Many dogs with DCM have normal electrocardiograms but atrial and/or ventricular enlargement patterns (R > 3.5 mV Lead II for the left ventricle) may be noted. Sinus tachycardia, atrial fibrillation or ventricular arrhythmias are common. In some cases, ventricular tachyarrhythmias can develop before any ventricular dilation or systolic dysfunction. Routine Holter monitoring may help detect these.

Radiography

Dilated cardiomyopathy is a progressive myocardial disease. If the disease is diagnosed in the early stages, radiographic findings may be subtle. Therefore, depending on the stage of the disease, thoracic radiographs may be within normal limits or may indicate atrial and ventricular enlargement (typically left) with or without pulmonary venous distension and pulmonary edema. In some cases, biatrial and biventricular enlargement may be noted.

Echocardiography

Echocardiography is the diagnostic test of choice for diagnosing canine DCM and is also an important test for occult disease. Echocardiographic findings in the patient with overt disease should include left and sometimes right atrial and ventricular dilation and decreased contractility as characterized by shortening fraction (FS%). Typically the decrease in contractility is quite severe with decreased fractional shortening % (< 20%).

A differential diagnosis for DCM is severe atrioventricular (AV) valve disease since severe ventricular dilation and systolic dysfunction may be occasionally observed in these cases. Consideration of the breed of dog may be helpful in differentiating between DCM and AV valve disease since it is uncommon for many of the large breed dogs to develop significant primary valve disease. An exception to this may be the cocker spaniel, a breed that has a high incidence of primary valve disease, and also is at increased risk of DCM.

Biomarkers

Prohormone BNP is released when the ventricles are dilated, hypertrophic or subjected to increased wall tension. Levels of BNP (Idexx) have been shown be increased in dogs with congestive heart failure and can be used to help diagnose, or exclude a diagnosis of heart failure in dogs that presented for cough or dyspnea. At this point it has not yet been shown to be sensitive enough for detection of early disease.

Etiology

It is clear that several breeds appear to be over represented and some breeds seem to have unique characteristics of the disease that may suggest that this is unique disease for their breed. A familial form of DCM has now been identified in several breeds and is suspected in others. Occasionally, atypical breeds of dogs develop DCM. The etiology of the disease in these cases is unknown and external factors that can insult the myocardium including infectious organisms or nutritional imbalances should be considered.

Doberman pinscher DCM

Etiology

Dilated cardiomyopathy is a familial disease in the Doberman pinscher and appears to be inherited in an autosomal dominant fashion.

Generally affected dogs are mature adults (average 6.5 years) although it has been reported as young as 1 year.

Clinical signs

Most affected Doberman Pinschers present for an initial diagnosis of DCM already in left heart failure (cough, respiratory distress). Syncope and sudden death are reported frequently due to the presence of ventricular premature complexes (VPCs). Most affected Dobermans will die from congestive heart failure and/or euthanasia due to refractory heart failure, although about 30% are believed to die from sudden death secondary to a lethal ventricular tachyarrhythmia.

Screening for early (occult) DCM

Dilation of the ventricle may precede the development of systolic dysfunction and be an early indicator of DCM. It has been suggested that Doberman Pinschers with a left ventricular end diastolic dimension of greater than 4.6 centimeters and an end systolic dimension of 3.8 are at risk of developing DCM within a 1-2 year period. Caution- these numbers are based on average sized Dobermans (60-80 pounds) and may be less accurate if very large dogs (>100 pounds)

Additionally, Holter monitoring has been suggested to be a good screening device for this breed. Adult Dobermans with greater than 10 VPCs per 24 hours, or couplets or triplets are suspect for the development of DCM.

Since dilated cardiomyopathy is an adult onset disease with a variable age of onset, screening should be performed every year and ideally include both an echocardiogram and a Holter monitor. However, keep in mind that sometimes variations on the echocardiogram and Holter monitor can be due to other systemic diseases and if questionable should be repeated in 6 – 12 months

Prognosis

Affected Doberman pinschers have a poor prognosis. Once clinical signs have developed, death usually occurs due to heart failure or sudden death within 6 months, therapy is palliative at best. Preliminary work has suggested that starting enalapril when ventricular dilation has occurred but before CHF develops, may slow rate of progression. Additionally, treatment with pimobenden as discussed below may have a significant positive effect on survival (increase survival to many months) but is still not a cure.

Great Dane Cardiomyopathy

Dilated cardiomyopathy in the Great Dane is a familial disease and appears to be inherited in an X- linked recessive mode of inheritance.

Clinical Presentation

The Great Dane also typically starts with a left apical systolic murmur. However, there is some evidence to suggest that in some cases, the first sign of DCM is the development of atrial fibrillation, even before the development of left ventricular dilation and decreased systolic function. Additionally, Great Danes are much more likely to develop biventricular failure with ascites and jugular venous distension. Treatment for DCM and heart failure would be the same as for the Doberman pinscher. Although this is still a fatal heart disease, the prognosis is better than that for the Doberman pinscher.

Cocker Spaniel Cardiomyopathy

Cocker spaniels are at an increased risk of two forms of heart disease, endocardiosis (more common) and dilated cardiomyopathy. However since some of the cocker spaniels with dilated cardiomyopathy may be responsive to taurine and have an improved prognosis, differentiation is important. If the taurine level is low, supplementation may be useful at 250-500 mg orally twice a day. Taurine is a safe supplementation so it may be started while waiting for the results of the plasma or serum levels. However, it is important to start other cardiac and heart failure medications as discussed above. Generally the prognosis is better for Cocker Spaniel Cardiomyopathy than for some of the other breeds.

Taurine Related Cardiomyopathy

The development of dilated cardiomyopathy due to low taurine is much less common in the dog than in the cat since dogs have a much greater ability to synthesize taurine than cats. However, as mentioned above, a relationship between taurine and L-carnitine abnormalities and DCM has been previously described in the cocker spaniel. There have now been additional, reports of the development of DCM in the dog in which low blood or plasma levels of taurine have been documented. The dogs were all adult at the time of onset and were breeds that would be considered to be in the large breed dog groups. A common factor observed in several dogs that developed DCM and were determined to have low taurine was the feeding of a diet of a dry dog food with lamb meal, rice or both as the primary ingredient. It has been hypothesized that rice bran or whole rice products may result in decreased taurine levels in some dogs.

A diagnosis of taurine deficiency is indicated by a blood level of less than150 nmol/ml or plasma levels less than 40 nmol/ml. If taurine deficiency is suspected, taurine supplementation should be started while waiting for the results of the blood or plasma levels. Published doses for taurine supplementation appear to vary slightly, although 1000 mg/day (divided or once a day) appears to be a consistent recommendation. Additional cardiac medications should be provided as needed including inotropic support such as pimobenden and treatment of heart failure if needed as discussed below. Taurine deficient dogs with dilated cardiomyopathy appear to respond to supplementation fairly rapidly and improvement in echocardiographic measurement should be observed in 3 - 6 months. Ideally blood levels of taurine should be reevaluated in 1-2 months to confirm that the levels have increased.

Treatment Of The Dog With Occult (Asymptomatic) Dilated Cardiomyopathy

Administration of angiotensin converting enzyme (ACE) inhibitors may have some benefit for the dog with early ventricular dilation, with or without systolic dysfunction. The use of ACE inhibitors in the Doberman pinscher with ventricular dilation was found to prolong the amount of time before the onset of CHF. Although this study was limited to evaluation of Doberman pinschers, the use of ACE inhibitors for other breeds of dogs with occult DCM may be considered (Enalapril, 0.5 mg/kg orally twice a day).

Administration of beta-blockers to the dog in the occult stage of DCM for a cardioprotective effect is still being evaluated and is not without risk. Further studies are needed before this can be safely used for the majority of our patients.

Treatment Of The Dog With Dilated Cardiomyopathy And Congestive Heart Failure

Dogs with DCM and heart failure will benefit from inotropic support. Ideally, this would be with pimobenden, a phosphodiesterase III and V inhibitor with calcium sensitizing properties that acts as a positive inotrope as well as vasodilator (inodilator). Pimobenden has balanced vasodilatation and positive inotropic effects and has been shown to increase survival (median of 130 days versus a median of 14 days for the placebo in one study) in Doberman pinschers with DCM. Additionally, it appears to be a mild appetite stimulant. Generally, it is dosed at approximately 0.25mg/kg orally q12 hours.

Additional medications for heart failure such as ACE inhibitors (Enalapril, 0.5 mg/kg orally BID) and diuretics (Furosemide, 1-4 mg/kg orally q 6-8 hours) should be started as needed.

Nonspecific treatments including nutritional supplementation by switching to a diet which contains supplements like taurine, L-carnitine and fatty acids (Royal Canin, Early Cardiac EC) should be considered.

Treatment Of The Dog With Ventricular Arrhythmias

There is little consensus for the decision of when and how to treat ventricular arrhythmias in the dog with DCM. Rapid ventricular tachycardia, complex ventricular arrhythmias or the combination of ventricular arrhythmias, ventricular dilation and systolic dysfunction are thought to be associated with a higher risk of sudden cardiac death and to be indications for treatment, but this has not been well studied. Additionally, some dogs die suddenly without having any of these arrhythmias documented. If treatment is warranted, consideration might be given to the use of one of several ventricular antiarrhythmics. Sotalol, a combination beta-blocker and potassium channel blocker, may be beneficial in some cases, but should be used a bit more cautiously (Sotalol, low dose, 1.0 mg/kg BID) if systolic dysfunction is present. Mexiletine at a dose of 5-6 mg/kg, q8hr, orally can be very effective at decreasing the arrhythmia. In a small number of cases it can cause nausea but this can be significantly reduced if it is given with at least a small meal, so it should never be given on an empty stomach. Although the goals of treatment include decreasing the number of ventricular premature complexes, decreasing symptoms and decreasing the risk of sudden death, the ability of any antiarrhythmic to reach these goals has not been well studied.

Boxer Cardiomyopathy (CM)

There are two forms of myocardial disease in the boxer, DCM and Arrhythmogenic right ventricular cardiomyopathy (ARVC) (most common).

Dilated Cardiomyopathy (less common myocardial disease in the boxer)

Boxers with DCM present with similar clinical signs to other breeds (syncope, cough, dyspnea). They may have a soft left apical murmur, an arrhythmia and sometimes have biventricular heart failure (ascites, jugular venous distension). Diagnosis is confirmed by echocardiography.

CAUTION!!!- Many boxers have a left basilar systolic murmur, this is more suggestive of a potential aortic stenosis or physiologic flow murmur than cardiomyopathy!

The treatment is similar to that in other breeds with DCM (as above) except that some Boxers with DCM may benefit from L- Carnitine (50 mg/kg orally three times a day) available at most health food stores) as well as possibly switching to a supplemented food such as Royal Canin early cardiac EC.

Arrhythmogenic Right Ventricular Cardiomyopathy

The more common form of boxer myocardial disease is arrhythmic and is named Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC). This is a familial (autosomal dominant) disease in the boxer.

The classical presentation is an adult boxer with VPCs. The dog may be asymptomatic, or symptomatic with episodes of syncope. The VPCs are typically wide and upright QRS in leads I, II, III, and AVF. The arrhythmia may be quite intermittent and in many cases, may require a 24 hour Holter monitor for documentation. Interpretation of the Holter results can sometimes be challenging because strict criteria for this diagnosis does not exist. However the observation of > 100 VPCs, or periods of couplets, triplets or runs of ventricular tachycardia are abnormal. A larger number of VPCs or a greater complexity of the arrhythmia (ventricular tachycardia, bigeminy, etc) has been associated with the development of clinical signs. Supraventricular premature complexes may be seen but not frequently, and are more commonly associated with the myocardial dysfunction form of the disease.

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.

Dogs with Syncope

Dogs with syncope and ventricular arrhythmias are generally started on treatment. Sotalol (1.5-2.0 mg/kg, q 12hr, orally) is well tolerated and have been shown to decrease VPC number and complexity. In some cases, sotalol and mexiletine (5-6 mg/kg, q 8hr, orally WITH FOOD) may be needed.

Prognosis

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