Myocarditis is a pathologic process characterized by inflammation of the myocardium leading to cellular necrosis and myocardial dysfunction. Although often thought of as a viral or post-viral process, causes of myocarditis are numerous and include infectious (viral, bacterial, fungi, yeast, rickettsial, protozoal, and parasitic) as well as non-infectious (toxins, drugs, autoimmune diseases, and Kawasaki disease) etiologies.

Cardiomyopathy is a general term referring to diseases of the myocardium. Clinically and pathologically, cardiomyopathy can be divided into dilated, hypertrophic, and restrictive types. As myocarditis is a precursor to and one of the causes of dilated cardiomyopathy, the two will be considered together.

CLINICAL PRESENTATION

The presentation of a child with dilated cardiomyopathy (DCM) depends on the age of the patient and the acuteness of the illness. Aggressive acute viral myocarditis may present as cardiovascular collapse and cardiac arrest over a very short period of time. Other causes of DCM in general, and occasionally myocarditis as well, may have a more progressive subacute to chronic course. Unless the disease process progresses to the point of causing significant myocyte necrosis and myocardial dysfunction, clinical symptoms may be absent. A slow decrease in ventricular function over many months or years may go unnoticed, whereas a rapid drop in ventricular function over several days may result in severe heart failure and cardiovascular collapse, as compensatory mechanisms have not set in. However, the chronic stable patient has little cardiac reserve, and therefore an unrelated illness such as an upper respiratory infection may result in cardiac decompensation. The history of an antecedent viral infection in the child presenting with a new-onset DCM may not herald the initiation of cardiac disease, as it is possible that the viral illness merely unmasked the chronic compensated form of DCM.

The usual presentation of DCM is that of congestive heart failure and low cardiac output. Signs and symptoms of heart failure and low cardiac output in newborns and infants include fussiness, poor appetite, poor feeding, fever, listlessness, diaphoresis, and respiratory distress. Physical examination generally demonstrates a patient with tachypnea, tachycardia, cardiomegaly, and hepatomegaly with pallor or an ashen appearance. The older child and adolescent will generally have a history of a viral illness 7 to 14 days prior to presentation with myocarditis. Findings of poor appetite and abdominal pain due to hepatic congestion, lethargy, exercise intolerance, malaise, and fever may also be present. Findings of heart failure including jugular venous distention and rales as well as low cardiac output may be present on physical examination in an older child, whereas the findings of rales and jugular venous distention are often absent in the newborn and infant.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of DCM based on age is seen in Table 55-1. All attempts should be made to diagnose the treatable causes of cardiomyopathy such as structural heart disease, underlying arrhythmias, and vitamin deficiencies. Although structural heart defects and arrhythmias are not truly diseases of the myocardium, they are listed, as they may present similar to a DCM and must be considered in the evaluation of these children.

DIAGNOSTIC EVALUATION

Table 55-2 is a list of studies that may be performed in the evaluation of a patient with newly diagnosed DCM. The extent of evaluation will depend on initial findings of some of the more specific tests and history (e.g. a history of adriamycin administration or cocaine abuse likely point to the etiology). When identifiable causes are excluded or point to a familial or inherited disorder, family screening becomes important.

Chest X-Ray

A chest x-ray is often the first test done and is often performed for reasons other than suspicion of cardiomyopathy. Radiography demonstrates cardiomegaly and increased pulmonary venous markings with or without pulmonary edema or pleural effusion. The chest x-ray is often ordered because the child presents with some degree of respiratory distress.

Electrocardiogram

The electrocardiogram (ECG) is usually nonspecific but may show decreased QRS voltages and low voltage or inverted T waves in myocarditis. Q waves in lead I and aVL due to myocardial infarct are very suspicious of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). Ectopic beats should raise the suspicion of poorly controlled supraventricular tachycardia or ventricular arrhythmias, although in severe cardiac dysfunction, ventricular arrhythmias may occur secondary to the myocardial disease.

Echocardiogram

The echocardiogram establishes the diagnosis of a dilated poorly contracting left ventricle (Figure 55-1A, 1B), while at the same time should exclude all structural causes of left ventricular (LV) dysfunction (LV outflow tract obstruction and anomalous origin of the left coronary artery). Structural and treatable anomalies that cannot be excluded with certainty, such as ALCAPA, require further diagnostic testing. Although ventricular dysfunction is usually in the form of global hypokinesis, segmental wall motion abnormalities may be present. The evaluation should also search for the presence of a thrombus in the left atrium or ventricle (Figure 55-1C).

Pericardial and pleural effusions are not uncommon, and Doppler cardiography will often demonstrate mitral as well as tricuspid insufficiency. Right ventricular (RV) size and function may be spared early on but the RV may also dilate and demonstrate poor contractility as well. There may be secondary pulmonary hypertension arising from LV dysfunction. Doppler interrogation of the tricuspid regurgitation jet provides quantitation of RV systolic pressure.

Cardiac Catheterization

Catheterization is rarely undertaken as a diagnostic test unless it is utilized to obtain baseline hemodynamics, perform an endomyocardial biopsy, or exclude structural disease not eliminated by echocardiography.

Baseline hemodynamics are useful in evaluating right and LV filling pressures as a prognostic sign, even if only for the short term. Patients with poor ventricular function and low biventricular filling pressures usually respond well to medication symptomatically, even if they do not improve echocardiographically. Patients with extremely elevated biventricular filling pressures are less likely to do well over the short term.

Endomyocardial biopsy was previously used to make the diagnosis of myocarditis. A positive biopsy using the Dallas criteria¹ had been used to establish the diagnosis (although a negative biopsy did not exclude it), but the Dallas criteria are limited by variability of interpretation and low sensitivity.^2,3 Newer criteria based on immunoperoxidase staining seem to have greater sensitivity,⁴ as does testing the sample for viral genomes (PCR test).⁵ As myocarditis is a patchy non-homogenous infiltrate, it may be missed on random sampling of the right ventricle. Because the procedure is not without complication, especially in infants and young children, obtaining numerous samples to get a power value to diagnose 80% of myocarditis cases (17 samples) is unquestionably too dangerous and generally not performed to this extent.³ Currently, endomyocardial biopsy is considered on the basis of the likelihood of finding a specific treatable disorder⁶ (e.g. giant cell myocarditis).

MANAGEMENT

Viral myocarditis may rapidly deteriorate, follow a chronic course, or have progressive resolution. The old adage of a third, a third, and a third for those who get worse, stay the same, or get better still holds fairly true today. Patients with dilated cardiomyopathy of familial, idiopathic, or untreatable etiologies may have some improvement in LV function as well as symptomatology with medical therapy, but generally have a progressive deterioration over many years or may deteriorate rapidly to the point that medical therapy is no longer effective.

Medical Therapy

Acute medical therapy consists of sympathomimetic inotropic agents, often dobutamine (5–10 μg/kg/min) and if necessary dopamine (3–10 μg/kg/min) for maintenance of blood pressure. Practitioners try to avoid higher doses due to the negative effect on myocardial oxygen consumption and wall stress in the already decompensated heart. Patients requiring more support should be considered for mechanical support. Epinephrine is not used unless the child is in cardiovascular shock and the other medications are not effective at maintaining heart rate and blood pressure. For chronic oral inotropic therapy, digoxin is used (10 μg/kg/day divided BID, maximum starting dose 250 μg/day).

Vasodilation with milrinone and/or nesiritide is used in virtually all patients in the acute setting. Milrinone is a positive inotropic agent with vasodilatory and lusitropic effects (positive lusitropic effects are a more rapid phase of myocardial relaxation).⁷ The pharmacologic effect is seen rapidly with an initial loading infusion but also within 30 minutes of starting a continuous infusion without a loading dose.⁷ The infusion dose is 0.25 to 1.0 μg/kg/min with or without a loading dose of 50 μg/kg. Nesiritide, a brain (B-type) natriuretic peptide, has been shown to cause arterial and venous dilation, enhanced sodium excretion, and suppression of the renin-angiotensin-aldosterone and sympathic nervous systems.⁸ Although early reports demonstrated efficacy in the treatment of heart failure in adults^8,9 and preliminary evidence had been favorable in pediatric patients,¹⁰ it is not commonly used in pediatric centers as there has been little evidence to support improvement over milrinone. It is administered as a bolus infusion of 1 μg/kg followed by a continuous infusion of 0.01 to 0.03 μg/kg/min. The lower dose is usually adequate. For chronic oral therapy, angiotensin-converting enzyme (ACE) inhibitors are recommended in adults and children with heart failure.^11,12

The use of beta-blocking agents with their negative inotropic effects for the treatment of heart failure seems paradoxical. However, numerous well-controlled studies have demonstrated the effectiveness of beta-blocker therapy in reducing symptoms and improving survival when added to ACE inhibitors in adults.^13,14 Beta blockade in the intensive care unit is usually carried out with esmolol (50–250 μg/kg/min for heart failure, higher for supraventricular tachycardia), as it has a very short half-life. Chronic oral therapy is beneficial for children as well as adults.^13-16 One of the newest agents to gain widespread acceptance is carvedilol. It is a nonselective third-generation beta-blocking as well as alpha-adrenergic blocking agent, giving it vasodilatory properties as well.¹⁷ In addition to improving LV systolic performance, it also improves diastolic filling.¹⁸ A recent study in adults was stopped because there was a clear survival advantage in the carvedilol-treated group.^13,19 A double-blind placebo-controlled study in children failed to show efficacy, however, likely due to the small number of patients.²⁰ Nevertheless, based on the experience in adults as well as improvement in aspects of LV function in the above study, many cardiology practices are using carvedilol in infants and children.^16,17,20-22