Dilated cardiomyopathy in the dog

Dilated cardiomyopathy (DCM) is an idiopathic disease of the myocardium and is the most common acquired cardiac disorder in dogs (13.6%). It is characterized by progressive dilatation, mainly of the left ventricle, although also of the right ventricle in some cases, which leads to severe systolic dysfunction followed by diastolic dysfunction, with consequent congestive heart failure. DCM mainly affects some large breeds of dog (Doberman, Great Dane, Newfoundland, Boxer, Cocker) and is rare in mongrels. Dobermans are affected by DCM more than any other breed and account for about 50% of all cases of DCM in dogs. Various studies have demonstrated that from 20% to 30% of apparently healthy adult Dobermans have signs of preclinical DCM, showing echocardiographic abnormalities or disorders of cardiac rhythm.

AETIOLOGY

In order to make a diagnosis of idiopathic DCM, the presence of heart, lung or metabolic diseases that could produce the same cardiac picture must be excluded. The cause of DCM in dogs remains unknown and is probably related to the concomitant occurrence of various factors. Nevertheless, there appears to be transmission of the condition within families in some breeds, suggesting a genetic cause. This resembles the situation in human medicine, with intrafamily transmission of numerous genetic mutations seeming to be the most common cause of DCM, accounting for 20% to 50% of cases of DCM in humans. The most commonly observed type of genetic transmission is autosomal dominant: this form of transmission has been described in the Irish wolfhound, Newfoundland and Doberman. An X-linked form has been described in the Golden retriever, German hound and Great Dane.

HISTOLOGY

Two histological models of DCM have been found in dogs. The model of attenuated wavy fibres is more common and has been described in many medium-sized to giant breeds of dog. These lesions have also been observed in healthy dogs and those with asymptomatic DCM and, therefore, seem to be early lesions during the evolution of the disorder.  Histologically, there is a significant thinning of myocytes which become wave-shaped. This deformation is probably due to changes in the cells’ structural proteins, such as actin, desmin and dystrophin.

The second model is the fatty infiltration-degenerative type of DCM. This is found less commonly and is typical of Boxers and Dobermans. It is characterized by myocardial cell lysis, degeneration of myofibrils, vacuolisation and atrophy of myocytes with large areas of fibrosis and fibro-adipose infiltration. In Boxers these histopathological changes mirror those found in arrhythmogenic right ventricular cardiomyopathy, suggesting possible diagnostic errors in this breed.

Both histological models give rise to the same clinical picture and histological studies are useful only for determining the aetiology and pathophysiology of the DCM.

PATHOPHYSIOLOGY

DCM is characterized by systolic dysfunction related to compromised myocardial contractility. The loss of contractility causes a reduction in cardiac output and an increase in end-systolic volume, with consequent activation of neurohormonal compensatory mechanisms such as the renin-angiotensin-aldosterone system (RAAS), catecholamines, natriuretic factors and cytokines. The left ventricle undergoes eccentric hypertrophy with a consequent reduction in compliance and diastolic dysfunction. The increase in left ventricular diastolic pressure inevitably causes an increase in atrial pressure and then congestive left heart failure. The heart failure does, however, often also involve the right chambers of the heart.

Given the marked eccentric ventricular hypertrophy, the annulus of the mitral valve becomes dilated leading to functional mitral regurgitation which causes a further volume overload.

Dogs with DCM often develop arrhythmias. Atrial fibrillation is a frequent complication associated with atrial dilatation. Ventricular arrhythmias are frequent in Boxers and Dobermans, already in the preclinical stage of DCM. These arrhythmias can sometimes cause sudden death.

CLINICAL DIAGNOSIS

Signalment
Large to giant breeds are most frequently affected by DCM. The disease usually becomes clinically evident in adulthood except in Portuguese water dogs in which the clinical signs can appear before 12 weeks of age.

Clinical findings

Two stages of the disease can be identified: a preclinical (or occult) stage in which there are no evident signs and a second symptomatic (or overt) stage.

In the preclinical stage the only signs present may be ventricular arrhythmias, particularly in Dobermans and Boxers.

In the symptomatic stage the dog may have breathlessness or dyspnoea, cough, exercise intolerance, syncope and weight loss. Clinical examination may reveal clear signs of left heart failure (pulmonary rales, crackles) or right heart failure (raised jugular venous pressure, ascites). At auscultation there may be low intensity (I-III/VI) systolic mitral murmurs and in some cases a diastolic gallop rhythm can be heard as a result of a third heart sound (S3). The presence of atrial fibrillation or ventricular arrhythmias can be detected as an irregular heart rhythm associated with a lack of a pulse.

Laboratory investigations

A biochemical and haematological screen is essential in order to exclude other causes of cardiac dilatation or concomitant disorders. Results of routine biochemical and haematological analyses are normal in most dogs with DCM, although an increase in the level of urea in the blood may be found, indicating prerenal hyperuraemia related to the low cardiac output.

Markers of cardiac function, such as natriuretic factors (in particular B-type natriuretic peptide, BNP) and troponin I, can be evaluated. The production of BNP, stimulated by the stretching of myocardial fibres, tends to increase in subjects with left ventricular dysfunction. However, at present assays of this peptide are not sufficiently sensitive to enable a diagnosis of DCM to be made on the basis of levels of BNP. On the other hand, an increase in troponin I concentrations in patients with suspected DCM could indicate other causes of ventricular dilatation and hypokinesia, such as myocarditis and myocardial infarction.

ELECTROCARDIOGRAPHY

It is essential to carry out an electrocardiogram in patients with DCM in order to determine whether there are arrhythmias. The most commonly detected arrhythmias are atrial fibrillation, premature ventricular contractions and ventricular tachycardia.

HOLTER MONITORING

Holter monitoring is useful in Boxers and Dobermans to detect subjects with occult DCM. It has been seen that in these breeds animals having more than 50 premature ventricular beats in 24 hours are at risk; Dobermans can manifest the disease within a few months or up to a few years later, while Boxers can develop overt DCM within 3-4 years. Ventricular ectopic beats are also common in other breeds (Weimaraner and Great Dane), but there are no guidelines for identifying subjects at risk of DCM.

RADIOLOGICAL EXAMINATIONS

In subjects with manifest DCM, chest radiographs in both latero-lateral and dorso-ventral projections show marked enlargement of the cardiac shadow; the enlargement may be generalised or localised to a single sector. In Dobermans the alterations to the cardiac shadow may not be proportional to the real pathological situation given the conformation of the thorax in this breed (Fig. 1). X-rays may also reveal typical radiographic signs of left or biventricular congestive heart failure, such as venous congestion, interstitial or alveolar oedema, pleural effusion and, in the abdomen, ascites.

ECHOCARDIOGRAPHY

Echocardiography is currently the most sensitive diagnostic investigation for confirming the presence of DCM. The diagnosis of heart failure with systolic and diastolic dysfunction, typical of DCM, requires the use of two-dimensional (2D) and one-dimensional motion-mode (M-mode) echocardiography. A Doppler echocardiographic study is also important in order to exclude the presence of other congenital or acquired cardiac disorders that can produce a clinical picture similar to that of DCM.

Two-dimensional echocardiographyshows the hypertrophy of the ventricles, predominantly the left one, and reduced movements of the ventricular wall and septum (Figs. 2 and 3). The ventricular walls show lack of thickening in systole and there may be akinetic or dyskinetic segments as a result of ischaemia. The left ventricle loses its normal shape and becomes spherical. This change in ventricular geometry can be evaluated by calculating the sphericity index, i.e. the ratio between the length and diameter of the left ventricle. A ratio less than 1.65 is suggestive of increased ventricular sphericity.

The assessment of systolic function includes both subjective and objective evaluations, with the latter being made through the measurement of numerical parameters. The most widely used parameters include fractional shortening and ejection fraction. A fractional shortening of less than 20-25% in predisposed breeds can raise a diagnostic suspicion of DCM, while a value between 15-20% indicates moderate disease and a value below 15% is considered to reflect severe DCM. An ejection fraction below 40% is defined as pathological (Fig. 4). These echocardiographic indices are, however, dependent on cardiac load. Furthermore, the ejection fraction is a measure of volume calculated starting from a two-dimensional image and, therefore, subject to a certain approximation which may be more or less relevant depending on the technique used for the measurement. Systolic and diastolic volumes are also indices of systolic and diastolic dysfunction, respectively. They can be calculated in relation to body surface area, giving values of the end-systolic volume index (ESV-i) and end-diastolic volume index (EDV-i), expressed in ml/m². Cornell recently developed a formula to relate ventricular diameters to body weight. Finally, systolic dysfunction and increased ventricular diastolic pressure cause reduced excursion of the leaflets of the mitral valve which is associated with an increased  E-point-septal-separation (EPSS) (Fig. 5).

A Doppler assessment of transmitral flow can provide prognostically important information on diastolic function; a restrictive pattern of transmitral flow is associated with a poor prognosis.

Tissue Doppler imaging

Tissue Doppler imaging can be used to detect early changes in left ventricular contractility. Patients with DCM develop systolic and diastolic asynchrony both between the left ventricle and the right ventricle and between the various regions of the interventricular septum and the free wall of the left ventricle. Furthermore, a prolongation of the pre-ejection period, shortening of the left ventricular ejection time and a decrease in the velocity of circumferential fibre shortening can be seen.

Strainand strain rate are parameters derived from Doppler measurements which reflect myocardial deformation. Specific software is needed to calculate these parameters. Although this software can be used with most echocardiographic instruments, the long time needed to analyse the data and the pronounced intra- and inter-operator variability mean that these parameters are rarely used in routine clinical practice. In the future, strain could be a useful parameter for making an early diagnosis of occult DCM.

TREATMENT

The basic treatment for animals with clinical signs of DCM is that for heart failure and includes diuretics, ACE-inhibitors and positive inotropes. However, the therapeutic choices depend on the clinical condition  of the subject and the severity of the signs.

In the preclinical phase the aim of treatment is to slow the progression of the disease. Studies have been conducted on the use of ACE-inhibitors or b-blockers in asymptomatic patients; however, from those published in the literature, there are no convincing data on the efficacy of these treatments in patients with occult DCM.

Diuretics
Most dogs with DCM present with congestive heart failure. In these cases, diuretics can play an important role in stabilising the patients’ clinical condition.

• Furosemide: this is the most widely used diuretic and is prescribed at very different doses (from 2 to 4 mg/kg every 8 to 24 hours). In some dogs a low dose treatment (0.5-2 mg/kg b.i.d. or t.i.d.) can be effective. The dose of furosemide can be decreased if this diuretic is combined with ACE-inhibitors and positive inotropes.
• Spironolactone: this is an aldosterone antagonist and a potassium-sparing diuretic. It is used, before introducing an ACE-inhibitor, in subjects on chronic treatment with furosemide in order to counteract the potassium loss that can occur in animals taking this latter diuretic. It has been found that a standard dose (2-4 mg/kg b.i.d.) does not cause a notable increase in diuresis in healthy dogs. However, it is introduced in chronic treatment to counteract the phenomenon of “aldosterone escape” (an alternative pathway of aldosterone formation independent of the activity of the RAAS and, therefore, not responsive to suppression by ACE-inhibitors). It is advisable to monitor serum potassium levels in order to intervene if these should increase excessively.
• Thiazides:  in animals with signs of congestive heart failure it may be necessary to increase the dose of furosemide gradually or add another diuretic, such as a thiazide (e.g. hydrochlorothiazide 2-4 mg/kg b.i.d.).

ACE-inhibitors
ACE-inhibitors act by inhibiting the formation of angiotensin II, which induces vasoconstriction, fluid retention and the production of aldosterone. ACE-inhibitors have important effects in DCM: studies reported in the veterinary literature have shown that enalapril and benazepril improve the quality of life of patients, increase the mean survival time and delay progression to heart failure.

Digoxin
Digoxin is a drug that was historically used in the treatment of heart failure for its positive inotropic and negative chronotropic properties. As a positive inotrope it has been replaced by drugs with a stronger effect on contractility (e.g. pimobendan); however, its negative chronotropic effect is still of wide utility, particularly in dogs presenting with atrial fibrillation. Given that digoxin is eliminated mainly through the kidneys, renal function should be determined before starting treatment with this cardiac glycoside. Digoxin is administered every 12 hours (at a dose of 0.003-0.005 mg/kg or, in very large dogs, 0.2-0.25 mg/m²) and serum levels must be monitored regularly because accumulation of the drug in the blood (digoxinaemia) can produce signs of toxicity (loss of appetite, vomiting, diarrhoea and neurological signs). If these signs appear, or if renal function is impaired, in the presence of high serum levels of digoxin, it may be necessary to reduce the daily dose or administer the drug on alternate days until treatment suspension.

Pimobendan
Pimobendan is defined as an inodilator because of its dual properties of positive inotropy and vasodilatation. It is a drug that increases the affinity of myofibrils for calcium without increasing oxygen consumption by the cardiac muscle cells. Furthermore, its effect of inhibiting phosphodiesterases 3 and 5 causes peripheral vasodilatation and partial dilatation of the pulmonary vasculature. It has been demonstrated that treatment with this drug in combination with digoxin, an ACE-inhibitor and furosemide significantly prolongs the mean survival of dogs with DCM.

Other treatments

Cocker spaniels (English and American) can develop a form of DCM related to taurine deficiency. In these subjects, whether with occult or clinically manifest DCM, it is worth giving dietary supplementation with taurine (250-500 mg b.i.d.). In some cases, this supplementation can lead to complete remission of the DCM.

Suggested readings

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