Etiology and Pathophysiology

DCM is an idiopathic disease characterized by poor myocardial contractility, with or without arrhythmias. A genetic basis is thought to exist for idiopathic DCM, especially in breeds that have a high prevalence or a familial occurrence of the disease. Large and giant breeds are most commonly affected, including Doberman Pinschers, Great Danes, Saint Bernards, Scottish Deerhounds, Irish Wolfhounds, Boxers, Newfoundlands, Afghan Hounds, and Dalmatians. Some smaller breeds such as Cocker Spaniels and Bulldogs are also affected. The disease in rarely seen in dogs that weigh less than 12 kg. In at least some Great Danes, DCM appears to be an X-linked recessive trait. An autosomal dominant inheritance pattern was found in Boxers with ventricular arrhythmias (discussed in more detail later in this chapter); however, a rapidly fatal familial DCM affecting very young Portuguese Water Dogs shows an autosomal recessive inheritance pattern. Doberman Pinschers appear to have the highest prevalence of DCM; although a genetic basis is suspected, the inheritance pattern is not clear.

Various biochemical defects, nutritional deficiencies, toxins, immunologic mechanisms, and infectious agents may be involved in the pathogenesis of DCM in different cases. Impaired intracellular energy homeostasis and decreased myocardial adenosine triphosphate (ATP) concentrations were found in myocardial biochemical studies of affected Doberman Pinschers. DCM as an entity probably represents the end-stage of different pathologic processes or metabolic defects involving myocardial cells or the intercellular matrix rather than a single disease. Idiopathic DCM has also been associated with prior viral infections in people. However, on the basis of polymerase chain reaction (PCR) analysis of myocardial samples from a small number of DCM-affected dogs, viral agents do not seem to be commonly associated with DCM in this species.

Decreased ventricular contractility (systolic dysfunction) is the major functional defect in dogs with DCM. Progressive cardiac chamber dilation (remodeling) develops as systolic pump function and cardiac output worsen and compensa tory mechanisms become activated. Poor cardiac output can cause weakness, syncope, and ultimately, cardiogenic shock. Increased diastolic stiffness also contributes to the development of higher end-diastolic pressures, venous congestion, and congestive heart failure (CHF). Cardiac enlargement and papillary muscle dysfunction often cause poor systolic apposition of mitral and tricuspid leaflets with valve insufficiency. Although severe degenerative atrioventricular (AV) valve disease is not typical in dogs with DCM, some have mild to moderate valvular disease, which exacerbates valve insufficiency.

As cardiac output decreases, sympathetic, hormonal, and renal compensatory mechanisms become activated. These mechanisms increase heart rate, peripheral vascular resistance, and volume retention (see Chapter 3). Chronic neurohormonal activation is thought to contribute to progressive myocardial damage, as well as to CHF. Coronary perfusion can be compromised by poor forward blood flow and increased ventricular diastolic pressure; myocardial ischemia further impairs myocardial function and predisposes to arrhythmia development. Signs of low-output heart failure and right- or left-sided CHF (see Chapter 3) are common in dogs with DCM.

Atrial fibrillation (AF) often develops in dogs with DCM. Atrial contraction contributes importantly to ventricular filling, especially at faster heart rates. The loss of the “atrial kick” associated with AF reduces cardiac output and can cause acute clinical decompensation. Persistent tachycardia associated with AF probably also accelerates disease progression. Ventricular tachyarrhythmias also occur frequently and can cause sudden death. In Doberman Pinschers serial Holter recordings have documented the appearance of ventricular premature contractions (VPCs) months to more than a year before early echocardiographic abnormalities were noted. Once left ventricular (LV) function begins to deteriorate, the frequency of tachyarrhythmias increases. Excitement-induced bradyarrhythmias have also been associated with low-output signs in Doberman Pinschers.

Dilation of all cardiac chambers is typical in dogs with DCM, although left atrial (LA) and LV enlargement usually predominate. The ventricular wall thickness may appear decreased compared with the lumen size. Flattened, atrophic papillary muscles and endocardial thickening are described. Concurrent degenerative changes of the AV valves are generally only mild to moderate, if present at all. Histopathologic findings include scattered areas of myocardial necrosis, degeneration, and fibrosis, especially in the left ventricle. Narrowed (attenuated) myocardial cells with a wavy appearance may be a common finding. Inflammatory cell infiltrates, myocardial hypertrophy, and fatty infiltration (mainly in Boxers and some Doberman Pinschers) are inconsistent features.

Clinical Findings

The prevalence of DCM increases with age, although most dogs presented with CHF are 4 to 10 years old. Males appear to be affected more often than females. However, in Boxers and Doberman Pinschers there may be no gender predilection once dogs with occult disease are included. Cardiomyopathy in Boxers is described in more detail later (see p. 134). Male Doberman Pinschers generally show signs at an earlier age than females.

DCM appears to develop slowly, with a prolonged preclinical (occult) stage that may evolve over several years before clinical signs become evident. Occult DCM often is recognized through the use of echocardiography. Some giant-breed dogs with mild-to-moderate LV dysfunction are relatively asymptomatic, even in the presence of AF.

Clinical signs of DCM may appear to develop rapidly, especially in sedentary dogs in which early signs may not be noticed. Sudden death before CHF signs develop is relatively common. Presenting complaints include any or all of the following: weakness, lethargy, tachypnea or dyspnea, exercise intolerance, cough (sometimes described as “gagging”), anorexia, abdominal distention (ascites), and syncope (see Fig. 1-2). Loss of muscle mass (cardiac cachexia), accentuated along the dorsal midline, may be severe.

Physical examination findings vary with the degree of cardiac decompensation. Dogs with occult disease may have a normal physical exam. Others have a soft murmur of mitral or tricuspid regurgitation or an arrhythmia. Dogs with advanced disease and poor cardiac output have increased sympathetic tone and peripheral vasoconstriction. A consequence is mucous membrane pallor and slowed capillary refill time. The femoral arterial pulse and precordial impulse are often weak and rapid. Uncontrolled AF and frequent VPCs cause an irregular and usually rapid heart rhythm, with frequent pulse deficits and variable pulse strength (see Fig. 4-1). Signs of left- and/or right-sided CHF include tachypnea, increased breath sounds, pulmonary crackles, jugular venous distention or pulsations, pleural effusion or ascites, and/or hepatosplenomegaly. Heart sounds may be muffled in association with pleural effusion or poor cardiac contractility. An audible third heart sound (S₃ gallop) is a classic finding, although it may be obscured by an irregular heart rhythm. Systolic murmurs of mitral or tricuspid regurgitation that are soft to moderate in intensity are common.

Diagnosis

Treatment

Long-Term Therapy

Chronic inotropic therapy for dogs with DCM traditionally consisted of oral digoxin, but pimobendan now offers several advantages over digoxin (see p. 65). Pimobendan (Vetmedin, Boehringer Ingelheim) is a phosphodiesterase III inhibitor that increases contractility through a Ca⁺⁺-sensitizing effect; the drug also has vasodilator and other beneficial effects. Digoxin, with its neurohormonal modulating and antiarrhythmic effects, may still be useful and can be given with pimobendan. Digoxin is indicated in dogs with AF to help slow the ventricular response rate. It can also suppress some other supraventricular tachyarrhythmias.

If digoxin is used, it is generally initiated with oral maintenance doses. Toxicity seems to develop at relatively low dosages in some dogs, especially Doberman Pinschers. A total maximum daily dose of 0.5 mg is generally used for large and giant-breed dogs, except for Doberman Pinschers, which are given a total maximum dose of 0.25 mg/day to 0.375 mg/day. Serum digoxin concentration should be measured 7 to 10 days after digoxin therapy is initiated or the dose is changed (see p. 66). Dogs with AF and a ventricular rate exceeding 200 beats/min can be cautiously given digoxin IV (see Box 3-1) or twice the oral maintenance dose on the first day to more rapidly achieve effective blood concentrations. However, the use of IV or rapid oral diltiazem is probably safer (see p. 81). If oral digoxin alone has not significantly reduced the heart rate after 36 to 48 hours, a β-blocker or diltiazem may be added (see Table 4-2). Because these agents can have negative inotropic effects, a low initial dose and gradual dosage titration to effect or a maximum recommended level is advised. Heart rate control in dogs with AF is important. A maximum ventricular rate of 140 to 150 beats/min in the hospital (i.e., stressful) setting is the recommended target; lower heart rates (e.g., ∼100 beats/min or less) are expected at home. Because accurate counting of heart rate by auscultation or chest palpation in dogs with AF is difficult, an ECG recording is recommended. Femoral pulses should not be used to assess heart rate in the presence of AF.

Furosemide is used at the lowest effective oral dose and at consistent time intervals for long-term therapy (see Table 3-3). Hypokalemia and alkalosis are uncommon sequelae, unless anorexia or vomiting occurs. Potassium supplements may be given if hypokalemia is documented. However, these should be used cautiously if an ACEI and/or spironolactone (see Table 3-3 and p. 62) are also being administered to prevent hyperkalemia, especially if renal disease is present.

Spironolactone is thought to be useful for chronic therapy because of its aldosterone-antagonist, as well as potential diuretic, effects. Increased aldosterone production develops as a component of neurohormonal activation in heart failure, but ACEIs do not fully suppress this. Aldosterone is known to promote cardiovascular fibrosis and abnormal remodeling and as such contributes to the progression of cardiac disease. Therefore spironolactone is advocated as adjunctive therapy in combination with an ACEI, furosemide, and pimobendan/digoxin for chronic DCM therapy.

An ACEI should be used in the chronic treatment of DCM. Angiotensin-converting enzyme inhibition can attenuate progressive ventricular dilation and secondary mitral regurgitation. ACEIs have a positive effect on survival in both people and dogs with myocardial failure. These drugs minimize clinical signs and increase exercise tolerance. Enalapril or benazepril are used most extensively, but other ACEIs have similar effects.

The pure arteriolar dilator hydralazine can also improve cardiac output and exercise tolerance, as well as help reduce congestion; however, it can precipitate hypotension and reflex tachycardia, and it tends to exacerbate neurohormonal activation. Hydralazine can be used in combination with a nitrate in dogs that do not tolerate an ACEI. Hydralazine or amlodipine (see Table 3-3) could also be useful as adjunct therapy for dogs with refractory CHF, although arterial blood pressure should be carefully monitored in such animals. Any vasodilator must be used cautiously in dogs with a low cardiac reserve because of the increased potential for hypotension. Therapy is initiated at a low dose; if this is well-tolerated, the next dose is increased to a low maintenance level. The patient should be evaluated for several hours after each incremental dose, ideally by blood pressure measurement. Signs of worsening tachycardia, weakened pulses, or lethargy also can indicate the presence of hypotension. The jugular venous PO₂ can be used to estimate directional changes in cardiac output; a venous PO₂ >30 mm Hg is desirable.

A number of other therapies may be useful in certain dogs with DCM, although additional studies are needed to define optimal recommendations. These include omega-3 fatty acids, l-carnitine (in dogs with low myocardial carnitine concentrations), taurine (in dogs with low plasma concentrations), long-term β-blocker therapy (e.g., carvedilol or metoprolol), and possibly others (see Chapter 3, p. 69). Several palliative surgical therapies for DCM have been described in dogs but are not widely used.

Monitoring

Many dogs can be maintained fairly well for a variable time with chronic oral therapy. Owner education regarding the purpose, dosage, and adverse effects of each drug used is also important. Monitoring the dog’s resting respiratory (and heart) rate at home helps assess how well the patient’s CHF is controlled. Periodic reevaluation is important, but the time frame depends on the animal’s status. Visits once or twice a week may be needed initially. Dogs with stable heart failure can be rechecked every 2 or 3 months. Serum electrolyte and creatinine (or BUN) concentrations, an ECG, pulmonary status, blood pressure, serum digoxin concentration, body weight, and other appropriate factors can be evaluated, and therapy adjusted as needed.

Prognosis

The prognosis for dogs with DCM is generally guarded to poor. Historically, most dogs do not survive longer than 3 months after the clinical manifestations of CHF, although approximately 25% to 40% of affected dogs live longer than 6 months if initial response to therapy is good. The probability of survival for 2 years is estimated at 7.5% to 28%. However, the advent of newer therapies may change this bleak picture. Pleural effusion and possibly ascites and pulmonary edema have been identified as independent indicators of poorer prognosis.

Sudden death may occur even in the occult stage, before heart failure is apparent. Sudden death occurs in about 20% to 40% of affected Doberman Pinschers. Although ventricular tachyarrhythmias are thought to precipitate cardiac arrest most commonly, bradyarrhythmias may be involved in some dogs.

Doberman Pinschers with occult DCM often experience deterioration within 6 to 12 months. Dobermans in overt CHF when initially presented generally do not live long, with a reported median survival of less than 7 weeks. The prognosis is worse if AF is present in dogs with CHF. Most symptomatic dogs are between 5 and 10 years old at the time of death.

In each case, however, it is reasonable to assess the animal’s response to initial treatment before pronouncing an unequivocally dismal prognosis. Early diagnosis may help prolong life; further cardiac evaluation is indicated for dogs with a history of reduced exercise tolerance, weakness, or syncope or in those in which an arrhythmia, murmur, or gallop sound is detected.

Clinical Findings

Signs may appear at any age, but the mean age is reportedly 8.5 years (range <1-15 years). The most consistent clinical finding is a cardiac arrhythmia. When CHF occurs, left-sided signs are more common than ascites or other signs of right-sided heart failure. Many Boxers also develop a mitral insufficiency murmur.

The radiographic findings are variable; many Boxers have no visible abnormalities. Those with congestive signs generally show evidence of cardiomegaly and pulmonary edema. Echocardiographic findings also vary. Many Boxers have normal cardiac size and function; others show chamber dilation with reduced fractional shortening.

The characteristic ECG finding is ventricular ectopy. VPCs occur singly, in pairs, in short runs, or as sustained ventricular tachycardia. Most ectopic ventricular complexes appear upright in leads II and aVF. Some Boxers have multiform VPCs. There usually is an underlying sinus rhythm. AF is less common. Supraventricular tachycardia, conduction abnormalities, and evidence of chamber enlargement also are sometimes seen on ECG.

Twenty-four-hour Holter monitoring is often used as a screening tool for Boxer ARVC. It also is recommended to evaluate the efficacy of antiarrhythmic drug therapy. Frequent VPCs and/or complex ventricular arrhythmias are characteristic findings in affected dogs. However, an absolute number of VPCs/24-hour period that might separate normal from abnormal dogs is not (and may never be) clear. An arbitrary cut-off of >50 VPCs/24-hour period is often used to designate an abnormal frequency. However, there can be enormous variability in the number of VPCs between repeated Holter recordings in the same dog. Very frequent VPCs or episodes of ventricular tachycardia are thought to signal an increased risk for syncope and sudden death.

Treatment

Boxers with signs from tachyarrhythmias, but with normal heart size and LV function, are treated with antiarrhythmic drugs. Some asymptomatic dogs found to have ventricular tachycardia on Holter monitoring are also given an antiarrhythmic drug. The best regimen(s) and when to institute therapy are still not clear. Antiarrhythmic drug therapy that is apparently successful in reducing VPC number based on Holter recording may still not prevent sudden death. Sotalol, mexiletine with atenolol, amiodarone, or procainamide with atenolol have been advocated (see Chapter 4) because they might reduce the risk for sudden death from ventricular fibrillation, but further study is needed. Some dogs require treatment for persistent supraventricular tachyarrhythmias.

Therapy for CHF is similar to that described for dogs with idiopathic DCM. Myocardial carnitine deficiency has been documented in some Boxers with DCM and heart failure. Some of these dogs have responded to oral l-carnitine supplementation. Digoxin is used sparingly, if at all, when ventricular tachyarrhythmias are frequent.

Prognosis

The prognosis for affected Boxers is guarded. Survival is often <6 months in those with CHF. Asymptomatic dogs may have a more optimistic future, but the likelihood of developing serious arrhythmias is high. Sudden death is common, presumably from VPCs leading to ventricular fibrillation. The ventricular tachyarrhythmias may be refractory to drug therapy. Furthermore, even if most arrhythmias are suppressed, an increased survival is not assured.

Doxorubicin

The antineoplastic drug doxorubicin induces both acute and chronic cardiotoxicity. Histamine, secondary catecholamine release, and free-radical production appear to be involved in the pathogenesis of myocardial damage, which leads to decreased cardiac output, arrhythmias, and degeneration of myocytes. Doxorubicin-induced cardiotoxicity is directly related to the peak serum concentration of the drug; administering the drug diluted (0.5 mg/ml) over 20 to 40 minutes minimizes the risk of developing cardiotoxicity. Progressive myocardial damage and fibrosis have developed in association with cumulative doses of >160 mg/m² and sometimes as low as 100 mg/m². In dogs that have normal pretreatment cardiac function, clinical cardiotoxicity is uncommon until the cumulative dose exceeds 240 mg/m². It is difficult to predict whether and when clinical cardiotoxicity will occur. Increases in circulating cardiac troponin concentrations can be seen, but more work is needed to clarify the utility of this in monitoring dogs for doxorubicin-induced myocardial injury.

Cardiac conduction defects (infranodal AV block and bundle branch block) as well as ventricular and supraventricular tachyarrhythmias can develop in affected dogs. ECG changes do not necessarily precede clinical heart failure. Dogs with underlying cardiac abnormalities and those of breeds with a higher prevalence of idiopathic DCM are thought to be at greater risk for doxorubicin-induced cardiotoxicity. Recently, carvedilol has been shown to minimize or prevent the development of doxorubicin-induced cardiotoxicity in humans; we have had similar anecdotal experiences in dogs. Clinical features of this cardiomyopathy are similar to those of idiopathic DCM.

Other Toxins

Ethyl alcohol, especially if given intravenously for the treatment of ethylene glycol intoxication, can cause severe myocardial depression and death; slow administration of a diluted (20% or less) solution is advised. Other cardiac toxins include plant toxins (e.g., Taxus, foxglove, black locust, buttercups, lily-of-the-valley, gossypol), cocaine, anesthetic drugs, cobalt, catecholamines, and ionophores such as monensin.

l-carnitine

l-carnitine is an essential component of the mitochondrial membrane transport system for fatty acids, which are the heart’s most important energy source. It also transports potentially toxic metabolites out of the mitochondria in the form of carnitine esters. l-carnitine–linked defects in myocardial metabolism have been found in some dogs with DCM. Rather than simple l-carnitine deficiency, one or more underlying genetic or acquired metabolic defects are suspected. There may be an association between DCM and carnitine deficiency in some families of Boxers, Doberman Pinschers, Great Danes, Irish Wolfhounds, Newfoundlands, and Cocker Spaniels. l-carnitine is mainly present in foods of animal origin. DCM has developed in some dogs fed strict vegetarian diets.

Plasma carnitine concentration is not a sensitive indicator of myocardial carnitine deficiency. Most dogs with myocardial carnitine deficiency, diagnosed via endomyocardial biopsy, have had normal or high plasma carnitine concentrations. Furthermore, the response to oral carnitine supplementation is inconsistent. Subjective improvement may occur, but few dogs have echocardiographic evidence of improved function. Dogs that do respond show clinical improvement within the first month of supplementation; there may be some degree of improvement in echo parameters after 2 to 3 months. l-carnitine supplementation does not suppress preexisting arrhythmias or prevent sudden death. See p. 69 for supplementation guidelines.

Taurine

Although most dogs with DCM are not taurine deficient, low plasma taurine concentration is found in some. Low taurine, and sometimes carnitine, concentrations occur in Cocker Spaniels with DCM. Oral supplementation of these amino acids can improve LV size and function as well as reduce the need for heart failure medications in this breed. Low plasma taurine concentrations have also been found in some Golden Retrievers, Labrador Retrievers, Saint Bernards, Dalmatians, and other dogs with DCM. A normally adequate taurine content is found in the diets of some such cases, although others have been fed low-protein or vegetarian diets. The role of taurine supplementation is unclear. Although taurine-deficient dogs may show some echocardiographic improvement after supplementation, there is questionable effect on survival time. Nevertheless, measurement of plasma taurine or a trial of supplemental taurine for at least 4 months may be useful, especially in an atypical breed affected with DCM. (See p. 69 for supplementation guidelines.) Plasma taurine concentrations <25 (to 40) nmol/ml and blood taurine concentrations <200 (or 150) nmol/ml are generally considered deficient. Specific collection and submission guidelines should be obtained from the laboratory used.

Other Factors

Myocardial injury induced by free radicals may play a role in a number of diseases. Evidence for increased oxidative stress has been found in dogs with CHF and myocardial failure, but the clinical ramifications of this are unclear. Diseases such as hypothyroidism, pheochromocytoma, and diabetes mellitus have been associated with reduced myocardial function, but clinical heart failure is unusual in dogs secondary to these conditions alone. Excessive sympathetic stimulation stemming from brain or spinal cord injury results in myocardial hemorrhage, necrosis, and arrhythmias (brain-heart syndrome). Muscular dystrophy of the fasciohumoral type (reported in English Springer Spaniels) may result in atrial standstill and heart failure. Canine X-linked (Duchenne’s) muscular dystrophy in Golden Retrievers and other breeds also has been associated with myocardial fibrosis and mineralization. Rarely, nonneoplastic (e.g., glycogen storage disease) and neoplastic (metastatic and primary) infiltrates interfere with normal myocardial function. Immunologic mechanisms may also play an important role in the pathogenesis of myocardial dysfunction in some dogs with myocarditis.

Clinical Features

HCM is most commonly diagnosed in young to middle-age large-breed dogs, although there is a wide age distribution. Various breeds are affected. There may be a higher prevalence of HCM in males. Clinical signs of CHF, episodic weakness, and/or syncope occur in some dogs. Sudden death is the only sign in some cases. Ventricular arrhythmias secondary to myocardial ischemia are presumed to cause the low-output signs and sudden death. A systolic murmur, related to either LV outflow obstruction or mitral insufficiency, may be heard on auscultation. The systolic ejection murmur of ventricular outflow obstruction becomes louder when ventricular contractility is increased (e.g., with exercise or excitement) or when afterload is reduced (e.g., from vasodilator use). An S₄ gallop sound is heard in some affected dogs.

Diagnosis

Echocardiography is the best diagnostic tool for HCM. An abnormally thick left ventricle, with or without narrowing of the LV outflow tract area or asymmetrical septal hypertrophy, and LA enlargement are characteristic findings. Mitral regurgitation may be evident on Doppler studies. Systolic anterior motion of the mitral valve may result from dynamic outflow obstruction causes. Partial systolic aortic valve closure may be seen as well. Other causes of LV hypertrophy include congenital subaortic stenosis, hypertensive renal disease, thyrotoxicosis, and pheochromocytoma. Thoracic radiographs may indicate LA and LV enlargement, with or without pulmonary congestion or edema. Some cases appear radiographically normal. ECG findings may include ventricular tachyarrhythmias and conduction abnormalities, such as complete heart block, first-degree AV block, and fascicular blocks. Criteria for LV enlargement are variably present.

Treatment

The general goals of HCM treatment are to enhance myocardial relaxation and ventricular filling, control pulmonary edema, and suppress arrhythmias. A β-blocker (see p. 89) or Ca⁺⁺-channel blocker (see p. 91) may lower heart rate, prolong ventricular filling time, reduce ventricular contractility, and minimize myocardial oxygen requirement. β-blockers can also reduce dynamic LV outflow obstruction and may suppress arrhythmias induced by heightened sympathetic activity, whereas Ca⁺⁺-blockers may facilitate myocardial relaxation. Diltiazem has a lesser inotropic effect and would be less useful against dynamic outflow obstruction, especially in view of its vasodilating effect. Because β- and Ca⁺⁺-channel blockers can worsen AV conduction abnormalities, they may be relatively contraindicated in certain animals. A diuretic and ACEI are indicated if congestive signs are present. Digoxin should not be used because it may increase myocardial oxygen requirements, worsen outflow obstruction, and predispose to the development of ventricular arrhythmias. Exercise restriction is advised in dogs with HCM.

Etiology and Pathophysiology

Viral Myocarditis

Lymphocytic myocarditis has been associated with acute viral infections in experimental animals and in people. Cardiotropic viruses can play an important role in the pathogenesis of myocarditis and subsequent cardiomyopathy in several species, but this is not recognized commonly in dogs. The host animal’s immune responses to viral and nonviral antigens contribute to myocardial inflammation and damage.

A syndrome of parvoviral myocarditis was well-known in the late 1970s and early 1980s. It is characterized by a peracute necrotizing myocarditis and sudden death (with or without signs of acute respiratory distress) in apparently healthy puppies about 4 to 8 weeks old. Cardiac dilation with pale streaks in the myocardium, gross evidence of congestive failure, large basophilic or amorphophilic intranuclear inclusion bodies, myocyte degeneration, and focal mononuclear cell infiltrates are typical necropsy findings. This syndrome is uncommon now, probably as a result of maternal antibody production in response to virus exposure and vaccination. Parvovirus may cause a form of DCM in young dogs that survive neonatal infection; viral genetic material has been identified in some canine ventricular myocardial samples in the absence of classic intranuclear inclusion bodies.

Canine distemper virus may cause myocarditis in young puppies, but multisystemic signs usually predominate. Histologic changes in the myocardium are mild compared with those in the classic form of parvovirus myocarditis. Experimental herpesvirus infection of pups during gestation also causes necrotizing myocarditis with intranuclear inclusion bodies leading to fetal or perinatal death.

Bacterial Myocarditis

Bacteremia and bacterial endocarditis or pericarditis can cause focal or multifocal suppurative myocardial inflammation or abscess formation. Localized infections elsewhere in the body may be the source of the organisms. Clinical signs include malaise; weight loss; and, inconsistently, fever. Arrhythmias and cardiac conduction abnormalities are common, but murmurs are rare unless concurrent valvular endocarditis or another underlying cardiac defect is present. Serial bacterial (or fungal) blood cultures, serology, or PCR may allow identification of the organism. Bartonella vinsonii subspecies have been associated with cardiac arrhythmias, myocarditis, endocarditis, and sudden death.

Lyme Carditis

Lyme disease is more prevalent in certain geographic areas, especially the northeastern, western coastal, and north central United States, as well as in Japan and Europe, among other areas. The spirochete Borrelia burgdorferi (or related species) is transmitted to dogs by ticks (especially Ixodes genus) and possibly other biting insects. Third-degree (complete) and high-grade second-degree AV block have been identified in dogs with Lyme disease. Syncope, CHF, reduced myocardial contractility, and ventricular arrhythmias also are reported in affected dogs. Pathologic findings of Lyme myocarditis include infiltrates of plasma cells, macrophages, neutrophils, and lymphocytes, with areas of myocardial necrosis. These are similar to findings in human Lyme carditis. A presumptive diagnosis is made on the basis of the finding of positive (or increasing) serum titers or a positive SNAP test and concurrent signs of myocarditis, with or without other systemic signs. The findings from endomyocardial biopsy, if available, may be helpful in confirming the diagnosis. Treatment with an appropriate antibiotic should be instituted pending diagnostic test results. Cardiac drugs are used as needed. Resolution of AV conduction block may not occur in dogs despite appropriate antimicrobial therapy.

Protozoal Myocarditis

Trypanosoma cruzi, Toxoplasma gondii, Neosporum caninum, Babesia canis, and Hepatozoon canis are known to affect the myocardium. Trypanosomiasis (Chagas’ disease) has occurred mainly in young dogs in Texas, Louisiana, Oklahoma, Virginia, and other southern states in the United States. The possibility for human infection should be recognized; this is an important cause of human myocarditis and subsequent cardiomyopathy in Central and South America. The organism is transmitted by bloodsucking insects of the family Reduviidae and is enzootic in wild animals of the region. Amastigotes of T. cruzi cause myocarditis with a mononuclear cell infiltrate and disruption and necrosis of myocardial fibers. Acute, latent, and chronic phases of Chagas’ myocarditis have been described. Lethargy, depression, and other systemic signs, as well as various tachyarrhythmias, AV conduction defects, and sudden death, are seen in dogs with acute trypanosomiasis. Clinical signs are sometimes subtle. The disease is diagnosed in the acute stage by finding trypomastigotes in thick peripheral blood smears; the organism can be isolated in cell culture or by inoculation into mice. Animals that survive the acute phase enter a latent phase of variable duration. During this phase the parasitemia is resolved, and antibodies develop against the organism as well as cardiac antigens. Chronic Chagas’ disease is characterized by progressive right-sided or generalized cardiomegaly and various arrhythmias. Ventricular tachyarrhythmias are most common, but supraventricular tachyarrhythmias may occur. Right bundle branch block and AV conduction disturbances are also reported. Ventricular dilation and reduced myocardial function are usually evident echocardiographically. Clinical signs of biventricular failure are common. Antemortem diagnosis in chronic cases may be possible through serologic testing. Therapy in the acute stage is aimed at eliminating the organism and minimizing myocardial inflammation; several treatments have been tried with variable success. The therapy for chronic Chagas’ disease is aimed at supporting myocardial function, controlling congestive signs, and suppressing arrhythmias.

Toxoplasmosis and neosporiosis can cause clinical myocarditis in conjunction with generalized systemic infection, especially in the immunocompromised animal. The organism becomes encysted in the heart and various other body tissues after the initial infection. With rupture of these cysts, expelled bradyzoites induce hypersensitivity reactions and tissue necrosis. Other systemic signs often overshadow signs of myocarditis. Immunosuppressed dogs with chronic toxoplasmosis (or neosporiosis) may be prone to active disease, including clinically relevant myocarditis, pneumonia, chorioretinitis, and encephalitis. Antiprotozoal therapy may be successful.

Babesiosis can be associated with cardiac lesions in dogs, including myocardial hemorrhage, inflammation, and necrosis. Pericardial effusion and variable ECG changes are also noted in some cases. A correlation between plasma cardiac troponin I (cTnI) concentration and clinical severity, survival, and cardiac histopathologic findings was shown in dogs with babesiosis.

H. canis may involve the myocardium during part of its life cycle; this was found in dogs along the Texas coast. Infection occurs as a result of ingesting the organism’s definitive host, the brown dog tick (Rhipicephalus sanguineus). Clinical signs include stiffness, anorexia, fever, neutrophilia, and periosteal new bone reaction.

Other Causes

Rarely, fungi (Aspergillus, Cryptococcus, Coccidioides, Histoplasma, Paecilomyces), rickettsiae (Rickettsia rickettsii, Ehrlichia canis, Bartonella elizabethae), algaelike organisms (Prototheca sp.), and nematode larval migration (Toxocara sp.) cause myocarditis. Affected animals are usually immunosuppressed and have systemic signs of disease. Rocky Mountain spotted fever (R. rickettsii) occasionally causes fatal ventricular arrhythmias, along with necrotizing vasculitis, myocardial thrombosis, and ischemia. Angiostrongylus vasorum infection in association with immune-mediated thrombocytopenia has rarely caused myocarditis, thrombosing arteritis, and sudden death.

Clinical Findings and Diagnosis

Unexplained onset of arrhythmias or heart failure after a recent episode of infective disease or drug exposure is the classic clinical presentation of acute myocarditis. However, definitive diagnosis is difficult because clinical and clinicopathologic findings are usually nonspecific and inconsistent. A database including complete blood count, serum biochemical profile with creatine kinase activity, cardiac troponin concentration, thoracic and abdominal radiographs, and urinalysis are usually obtained. ECG changes could include an ST segment shift, T-wave or QRS voltage changes, AV conduction abnormalities, and various arrhythmias. Echocardiographic signs of poor regional or global wall motion, altered myocardial echogenicity, or pericardial effusion may be evident. In dogs with persistent fever, serial bacterial (or fungal) blood cultures may be useful. Serologic screening for known infective causes may or may not be helpful. Histologic criteria for a diagnosis of myocarditis include inflammatory infiltrates with myocyte degeneration and necrosis. Endomyocardial biopsy specimens are currently the only means of obtaining a definitive antemortem diagnosis, but if the lesions are focal, the findings may not be diagnostic.

Treatment

Unless a specific etiology can be identified and treated, therapy for suspected myocarditis is largely supportive. Strict rest, antiarrhythmic drugs (see Chapter 4), therapy to support myocardial function and manage CHF signs (see Chapter 3), and other support are used as needed. Corticosteroids are not proven to be clinically beneficial in dogs with myocarditis, and considering the possible infective cause, they are not recommended as nonspecific therapy. Exceptions would be confirmed immune-mediated disease, drug-related or eosinophilic myocarditis, or confirmed nonresolving myocarditis.