Cardiomyopathies - The Merck Veterinary Manual

Cardiomyopathies

Cardiomyopathy is defined as any disease involving primarily and predominantly the heart muscle. The cardiomyopathies of animals are idiopathic diseases that are not the result of any systemic or primary cardiac disease. In animals (primarily dogs and cats), they have been classified as dilated cardiomyopathy, hypertrophic cardiomyopathy, and restrictive or unclassified cardiomyopathy. If a disease process has been identified as the cause of myocardial dysfunction, these are more correctly identified as secondary myocardial diseases or a descriptive term precedes the term cardiomyopathy (eg, taurine-responsive cardiomyopathy).

Dilated Cardiomyopathy:

This acquired disease is characterized by the progressive loss of cardiac contractility of unknown cause. Several forms of secondary dilated cardiomyopathy exist (eg, taurine deficiency in cats, doxorubicin- or parvovirus-induced). Dilated cardiomyopathy has a protracted subclinical phase in dogs, with clinical signs evident for a relatively short period of time. During the subclinical phase, compensatory mechanisms maintain normal hemodynamics. As cardiac contractile function is progressively lost, cardiac output decreases. Increased blood volume and pressure within the chambers causes them to dilate, most dramatically evident in the left atrium and left ventricle. The increased activation of the sympathetic nervous system and the RAAS, after an initial benefit, cause deleterious effects (see Compensatory Mechanisms). Excessive stimulation of the myocardium by the sympathetic nervous system may stimulate ventricular arrhythmias and myocyte death, while excessive activation of the RAAS causes excessive vasoconstriction and retention of sodium and water. Signs of CHF are then inevitable.

Dilated cardiomyopathy is one of the most prevalent acquired heart diseases of dogs, only surpassed by degenerative valve disease and, in some parts of the world, heartworm disease as a major cardiovascular cause of morbidity and mortality. It most commonly affects large-breed dogs and far less commonly small-breed dogs (with a few exceptions such as American Cocker Spaniels, Springer Spaniels, and English Cocker Spaniels). Doberman Pinschers, Boxers, Great Danes, German Shepherds, Irish Wolfhounds, Scottish Deerhounds, Newfoundland Retrievers, Saint Bernards, and Labrador Retrievers, among other large-breed dogs, are particularly at risk. The disease is typically seen in middle-aged dogs; males are affected more than females. The incidence in cats has decreased dramatically since the discovery in 1985 that taurine deficiency was responsible for most cases (taurine-responsive cardiomyopathy). Since then, taurine levels have been increased to acceptable levels in all commercial cat foods. Most cases today are not taurine responsive and reflect primary (or idiopathic) disease.

There is breed variation in the presenting history and clinical signs. Up to 35% of Boxers demonstrate episodes of weakness or collapse as the presenting clinical sign and most demonstrate no myocardial failure at the time of presentation. The syncope typically results from severe ventricular arrhythmias. In those Boxers that do not succumb to sudden death, signs of left-sided CHF (eg, cough, dyspnea) eventually develop as a result of myocardial failure. Doberman Pinschers typically develop concurrent and progressive ventricular arrhythmias along with progressive systolic dysfunction. As with Boxers, collapse and sudden death occur (in up to 20% of Doberman Pinschers), and signs of left-sided CHF eventually develop. Most Doberman Pinschers demonstrate evidence of myocardial failure at the time syncopal episodes are noted, in contrast to Boxers. In other breeds, such as Great Danes and Newfoundlands, sudden death and collapse are far less likely. Signs of right-sided CHF predominate, including weakness, exercise intolerance, pleural effusion, and ascites. Ascites was noted in 35% of Newfoundlands with dilated cardiomyopathy in one study. Cats with dilated cardiomyopathy typically present with severe signs of pleural effusion and dyspnea, and clinical signs are usually rapidly progressive and refractory to therapy.

A low-grade systolic murmur, best heard at the left cardiac apex, is usually present. A third heart sound or gallop heart sound is also frequently present, especially in cats. Femoral pulses may be weak, and an arrhythmia with associated pulse deficits may be noted. The arrhythmia is most commonly a result of ventricular ectopy, but supraventricular arrhythmias such as atrial fibrillation or atrial premature complexes can also be noted, especially in giant breeds. Ascites, dyspnea, or cough may also be noted depending on the type of heart failure that develops.

Blood work may demonstrate elevation of BUN, creatinine, and alkaline phosphatase, as well as a mild reduction in sodium. Thoracic radiographs typically demonstrate mild to marked generalized cardiomegaly. If heart failure is present, pulmonary edema is evident and the pulmonary veins are enlarged. Echocardiography is the ideal test to definitively diagnose dilated cardiomyopathy. There is a dramatic loss of cardiac contractility (evidenced by a reduced left ventricular fractional shortening) and an increase in left ventricular end-systolic diameter. Cardiac chambers, especially the left atrium and left ventricle, are dilated. Mitral or tricuspid insufficiency typically develops as progressive cardiac dilation results in separation of the valve leaflets. Abnormal ECG findings may include ventricular premature complexes and ventricular tachycardia (especially in Doberman Pinschers and Boxers), atrial fibrillation, and atrial premature complexes (especially giant breeds). There may be electrocardiographic evidence of left atrial enlargement (P mitrale or widened P waves) and left ventricular enlargement (tall and wide R waves). Conduction disturbances, such as left bundle-branch block, are uncommon but could indicate severe disease. The occurrence of ventricular premature contractions on a routine ECG in a presumed healthy Doberman Pinscher or Boxer is highly suggestive of cardiomyopathy.

The objectives of therapy are to control the congestive state (eg, with diuretics), improve contractility (eg, with digoxin or dobutamine), and reduce adverse effects of angiotensin II and other neurohormonal changes (eg, with ACE inhibitors). Taurine-responsive myocardial failure occurs in some breeds, particularly American Cocker Spaniels, Golden Retrievers, and Dalmatians, and in anecdotal reports, Welsh Corgis, Tibetan Terriers, and other breeds. In many of these breeds, taurine deficiency can be diagnosed by low plasma or whole blood levels. Response to taurine supplementation (which may take 2-4 wk) can be dramatic, many times obviating the need for other cardiac medications. Carnitine-responsive cardiomyopathy has been reported in Boxers and Doberman Pinschers. Dogs deficient in L-carnitine cannot be identified without an endomyocardial biopsy, however, and supplementation with L-carnitine may be cost prohibitive. Taurine is less expensive. Coenzyme Q₁₀ supplementation has resulted in significant improvements in humans with dilated cardiomyopathy in some small studies. The recommended dose is 30 mg, PO, tid. Administration of fish oil may reduce the severity of cardiac cachexia in patients with dilated cardiomyopathy.

CHF, which may be severe, should be treated as discussed under heart failure, Heart Failure: Overview. As pulmonary edema resolves, furosemide can be administered orally, with oxygen and nitroglycerin continued until clinical signs are controlled. Digoxin and an ACE inhibitor (eg, enalapril, benazepril) should be started. Antiarrhythmic therapy is frequently indicated, especially for Doberman Pinschers and Boxers with severe ventricular arrhythmias. Holter monitoring is the ideal method for evaluating both the severity of arrhythmias and therapy efficacy. In Boxers with severe ventricular arrhythmias without evidence of systolic dysfunction, sotalol (2 mg/kg, PO, bid) may be considered. Mexiletine (4-8 mg/kg, PO, bid-tid), can be added to sotalol if arrhythmia control is inadequate. Mexiletine is also useful in patients with ventricular arrhythmias and concurrent heart failure, as negative inotropy is less than with β-blocker therapy. β-Blockers are very effective at controlling ventricular arrhythmias; however, they must be used with extreme caution because the negative inotropic effects of most β-blockers (eg, atenolol) can predispose dilated cardiomyopathy patients to worsening CHF.

The prognosis is grave for cats with dilated cardiomyopathy (not taurine responsive), with a median survival time of 2 wk. Cats that are taurine responsive also have a high risk of death. However, patients that can be kept alive long enough for taurine to become effective (2-3 wk) have an excellent prognosis. Dogs that are taurine or carnitine responsive also have a fair to good prognosis once signs of CHF abate. The prognosis is poor in most Doberman Pinschers; ~25% die within 2 wk of presenting in heart failure, and 65% die within 8 wk. The prognosis in other breeds is better but remains guarded; 75% die within 6 mo of diagnosis. As expected, dogs with severe heart failure, particularly left-sided CHF, have a worse prognosis than those with milder signs or signs of right-sided CHF at presentation.

Hypertrophic Cardiomyopathy:

Feline hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy is characterized by primary concentric left ventricular hypertrophy resulting from an inherent myocardial disorder rather than pressure overload (such as caused by aortic stenosis), hormonal stimulation (such as hyperthyroidism or acromegaly), or other noncardiac disease. With severe disease, significant left ventricular hypertrophy develops; this results in a decrease in size of the left ventricular chamber, and consequently decreased left ventricular end-systolic diameter, sometimes to zero, as well as decreased left ventricular end-diastolic diameter and volume, resulting in reduced stroke volume and activation of the RAAS. Although contractility is not significantly impaired, the hypertrophied ventricular walls lose compliance and resist filling during diastole. Elevation of left ventricular end-diastolic pressure results in increased pressure within the left atrium, causing it to dilate; the pressure is then transmitted to the pulmonary veins, causing pulmonary edema and sometimes pleural effusion. Severe left atrial enlargement can develop, leading to left atrial thrombi and the potential for systemic thromboembolism. Mitral regurgitation also leads to left atrial dilation. This can develop secondary to an anterior displacement of the anterior mitral valve leaflet during ventricular systole, a phenomenon termed systolic anterior motion of the mitral valve. Gross pathology may include increased cardiac weight, left ventricular concentric hypertrophy, papillary muscle hypertrophy, left atrial enlargement, asymmetric septal hypertrophy, and a reduction in left ventricular chamber volume.

Hypertrophic cardiomyopathy is the most common primary heart disease diagnosed in cats but is rare in dogs. It is familial in certain breeds of cats such as Maine Coon cats and American Shorthairs. The disease occurs in cats from 3 mo to 17 yr of age, although most patients are middle aged; male cats are predisposed. The etiology is believed to be genetic mutations resulting in abnormalities of the sarcomeric proteins. Although not proved in cats, it has been documented in humans with this disease.

Affected patients may be asymptomatic or may have signs of acute dyspnea, collapse, or hindlimb paresis/paralysis. Cough is uncommon in cats with heart failure. Physical examination frequently demonstrates abnormal heart sounds, including soft to prominent systolic cardiac murmurs and gallop heart sounds. Increased respiratory sounds may suggest pulmonary edema, and decreased respiratory sounds may indicate pleural effusion. Pulses may be normal, weak, or absent if distal aortic thromboembolism has developed. Distal aortic embolization commonly leads to rear limb paresis or paralysis. Radiographically, there may be pronounced left atrial enlargement and variable left ventricular enlargement. The cardiac silhouette often appears relatively normal even in the presence of moderate left ventricular hypertrophy. Echocardiography allows confirmation of the diagnosis and assessment of additional therapy needed (eg, anticoagulants are most beneficial in cats with severe left atrial enlargement). Systolic anterior motion of the mitral valve, concentric left ventricular hypertrophy, or variable hypertrophy of other portions of the left ventricle such as papillary muscle hypertrophy or asymmetric septal hypertrophy can be noted. ECG abnormalities may include atrial premature complexes, ventricular premature complexes, and ventricular tachycardia. With severe atrial enlargement, atrial fibrillation may develop. Conduction disturbances such as left anterior fascicular block may also be noted.

Treatment is directed at controlling signs of CHF, improving diastolic function, and reducing the incidence of systemic thromboembolism. Furosemide administration, oxygen, and nitroglycerin administration should be considered when acute CHF is present. Diltiazem (7.5 mg, PO, tid), a calcium-channel blocker, improves diastolic function and may also reduce wall thickness and edema formation. Use of β-blockers such as atenolol (6.25-12.5 mg, PO, sid-bid) or propranolol may also be considered. Humans with hypertrophic cardiomyopathy have shown improvement in angina, dyspnea, and exercise intolerance when given β-blockers. If calcium channel blockers are ineffective, switching to β-blockers may be considered. ACE inhibitors may be considered in some cats (enalapril, 0.25-0.5 mg/kg, PO, sid), especially where CHF has developed and activation of the RAAS is a concern. Either aspirin (80 mg, PO, every third day) or warfarin (0.2-0.5 mg, PO, sid) may reduce the incidence of further thrombus formation in cats with thromboembolism or a propensity to develop thrombi (such as a large left atrium on echocardiographic examination). Efficacy has not been well documented, however. Prognosis is highly variable, with many mildly affected patients having a good longterm prognosis. Patients in CHF have a poorer prognosis, with a median survival time of 3 mo. Up to 20% of CHF patients survive for prolonged periods, however.

Restrictive/Unclassified Cardiomyopathy:

Restrictive cardiomyopathy is characterized by restrictive filling and reduced diastolic volume of either or both ventricles without significant ventricular hypertrophy or abnormalities of systolic function. The disease is seen in cats. Definitive documentation typically requires cardiac catheterization or specific abnormalities to Doppler mitral valve flow patterns that are not readily notable in cats. Although echocardiography can be variable, left atrial enlargement (usually severe) without significant left ventricular hypertrophy is common. Left atrial thrombi may be evident. Systolic function is usually preserved, but abnormalities of the mitral valve apparatus and papillary muscles may be noted. Doppler evaluation may demonstrate mitral regurgitation. Clinical signs and treatment are similar to those for hypertrophic cardiomyopathy (see above); however, prognosis seems to be worse, especially in patients with CHF. Unclassified cardiomyopathy includes patients with obvious abnormalities to the myocardium on echocardiography that do not clearly fit into any other category. It is also a disease of cats. The causes of restrictive cardiomyopathy and unclassified cardiomyopathy are unknown.