Etiology and Epidemiology

Dilated cardiomyopathy (DCM), the most common form of cardiomyopathy in children, is the cause of significant morbidity and mortality as well as a common indication for cardiac transplantation. The etiologies are diverse. Unlike adult patients with dilated cardiomyopathy, ischemic etiologies are rare in children, although these include anomalous origin of the left coronary artery from the pulmonary artery, premature coronary atherosclerosis (homozygous type II hypercholesterolemia), and coronary inflammatory diseases, such as Kawasaki disease. It is estimated that up to 50% of cases are genetic, including some with metabolic causes (see Table 433-1). Although the most common etiology of dilated cardiomyopathy remains idiopathic, it is likely that undiagnosed familial/genetic conditions and myocarditis predominate. The annual incidence of DCM in children younger than 18 yr is 0.57 cases per 100,000 per year. Incidence is higher in males, African Americans, and in infants less than 1 yr old.

Pathogenesis

The pathogenesis of the ventricular dilation and altered contractility seen in dilated cardiomyopathy varies depending on the underlying etiology. Genetic abnormalities of several components of the cardiac muscle including sarcomere protein, the cytoskeleton, and the proteins that bridge the contractile apparatus to the cytoskeleton, have been identified in autosomal dominant and X-linked inherited disorders. Dilated cardiomyopathy can occur following viral myocarditis and, although the primary pathogenesis varies from direct myocardial injury to viral-induced inflammatory injury, the resulting myocardial damage, ventricular enlargement, and poor function likely occur by a final common pathway similar to that which occurs in genetic disorders.

In 20-50% of cases, the DCM is familial with autosomal dominant inheritance most common (see Table 433-2). Duchenne and Becker muscular dystrophies (Chapter 601.1) are X-linked cardiomyopathies that account for 5-10% of familial dilated cardiomyopathy cases. These dystrophinopathies result in an abnormal sarcomere-cytoskeleton connection, causing impaired myocardial force generation, myocyte damage/scarring, chamber enlargement, and altered function.

Mitochondrial myopathies, like the muscular dystrophies, may present clinically with a predominance of extra cardiac findings and are inherited in a recessive or mitochondrial pattern. Disorders of fatty acid oxidation present with systemic derangements of metabolism (hypoketotic hypoglycemia, acidosis, liver dysfunction), some with peripheral myopathy and neuropathy, and others with sudden death or life-threatening cardiac arrhythmias

Anthracycline cardiotoxicity (doxorubicin [Adriamycin]) on rare occasion causes acute inflammatory myocardial injury, but more classically results in dilated cardiomyopathy and occurs in up to 30% of patients given a cumulative dose of doxorubicin exceeding 550 mg/m². The risk of toxicity appears to be exacerbated by concomitant radiation therapy.

Clinical Manifestations

Although more prevalent in patients less than 1 yr of age, all age groups may be affected. Clinical manifestations of dilated cardiomyopathy are most commonly those of congestive heart failure, but can also include palpitations, syncope, and sudden death. Irritability or lethargy can be accompanied by additional nonspecific complaints of failure to thrive, nausea, vomiting, or abdominal pain. Respiratory symptoms (tachypnea, wheezing, cough, or dyspnea on exertion) are often present. Uncommonly, patients may present acutely with pallor, altered mentation, hypotension, and shock. Patients can be tachycardic with narrow pulse pressure and have hepatic enlargement, and rales or wheezing. The precordial cardiac impulse is increased and the heart may be enlarged to palpation or percussion. Auscultation may reveal a gallop rhythm in addition to tachycardia and occasionally murmurs of mitral or, less commonly, tricuspid insufficiency may be present. The presence of hypoglycemia, acidosis, hypotonia, or signs of liver failure suggests an inborn error of metabolism. Neurologic or skeletal muscle deficits are associated with mitochondrial disorders or muscular dystrophies.

Laboratory Findings

Electrocardiographic screening reveals atrial or ventricular hypertrophy, nonspecific T-wave abnormalities, and occasionally atrial or ventricular arrhythmias. The chest x-ray demonstrates cardiomegaly and may reveal pulmonary vascular prominence or pleural effusions. The echocardiogram is often diagnostic, demonstrating the characteristic findings of left ventricular enlargement, decreased ventricular contractility, and occasionally a globular (remodeled) left ventricular contour (see Fig. 433-1). Right ventricular enlargement and depressed function are occasionally noted. Echo Doppler studies can reveal evidence of pulmonary hypertension, mitral regurgitation, or other structural cardiac or coronary abnormalities.

Additional testing should include CBC, renal and liver function tests, CPK, cardiac troponin I, lactate, plasma amino acids, urine organic acids, and an acylcarnitine profile. Additional genetic and enzymatic testing may be useful (see Table 433-2). Cardiac catheterization and endomyocardial biopsy are not routine but may be useful in patients with acute dilated cardiomyopathy. Biopsy samples can also be assessed for the presence of mononuclear cell infiltrates, myocardial damage, storage abnormalities, and viral infection or genomes. It is important to consider screening of 1st-degree family members utilizing echocardiography and ECG.

Prognosis and Management

The 1- and 5-yr rates of death or need for transplantation in patients diagnosed with DCM is 31% and 46%, respectively. Independent risk factors at DCM diagnosis for subsequent death or transplantation include older age, congestive heart failure, lower left ventricular fractional shortening z score, and underlying etiology. Dilated cardiomyopathy is the most common cause for cardiac transplantation in pediatric and adult studies.