Terminology of Myocardial and Endocardial Diseases

The myocardium is the middle layer of the heart wall and is predominantly composed of cardiac muscle. A spectrum of acquired, developmental, and idiopathic disorders causes acute or chronic forms of cardiac disease with myocardial involvement. Inflammatory disease of the myocardium, termed myocarditis, includes infectious and autoimmune disorders. In contradistinction to the adult age group, myocardial ischemia is rare in children. Causes of myocardial ischemia in children include vasculitis (e.g., Kawasaki disease), thromboembolism, cardiac surgery, and coronary artery anomalies. Imaging techniques that evaluate myocardial perfusion and viability include stress echocardiography, coronary angiography, single-photon emission computed tomography (SPECT) scintigraphy, positron emission tomography, and perfusion MRI.¹

The term cardiomyopathy is nonspecific in that it applies to any disorder that involves the cardiac muscle. There are various classification schemes for cardiomyopathy. Primary, or idiopathic, cardiomyopathy refers to heart muscle disease of unknown cause or related to a genetic abnormality (e.g., arrhythmogenic right ventricular dysplasia), whereas the secondary form has a known underlying cause (e.g., infective myocarditis, chronic hypertension, or vasculitis) or is associated with a systemic disorder (e.g., muscular dystrophy). Some practitioners reserve the term cardiomyopathy for those conditions in which there is a structural or functional abnormality of the myocardium that is not associated with coronary artery disease, hypertension, valvar heart disease, congenital heart disease, or pulmonary vascular disease.

Cardiomyopathy can also be divided into acute and chronic forms. The World Health Organization classifies chronic cardiomyopathies into dilated, hypertrophic, and restrictive categories. Dilated cardiomyopathy is the most common variety; this is characterized by impaired systolic function and poor ventricular contractility. Dilated cardiomyopathy is most often caused by infective myocarditis or exposure to myocardial toxins. Ventricular wall thickening in the less common hypertrophic form of cardiomyopathy can cause systolic outflow obstruction or impaired diastolic filling. Hypertrophic cardiomyopathy frequently has a genetic basis. Restrictive cardiomyopathy is the least-common variety. Grossly impaired ventricular filling causes poor diastolic function. Restrictive cardiomyopathy can be idiopathic or caused by disorders that lead to cellular infiltration of the myocardium, such as glycogen storage disease.

The endocardium is the endothelial lining membrane of the heart and the underlying connective tissue bed. Because the cardiac valves are predominantly endocardial structures, valvar dysfunction is a common manifestation of endocardial diseases. Endocardial involvement is an important component of many diseases that also affect the myocardium. The most common acquired endocardial disease is endocarditis, which is inflammation of the endocardium. Endocarditis is most often caused by infection, but noninfectious varieties such as rheumatic fever are also common (Table 10-1).

Idiopathic Dilated Cardiomyopathy

Idiopathic dilated cardiomyopathy occurs because of structural and functional abnormalities of the myocytes, possibly related to an immunological abnormality. Histological examination shows interstitial fibrosis within the myocardium and hypertrophy of myofibrils. This is most often a sporadic disorder, although unusual familial cases have been reported. There is generalized cardiac dilation, frequently accompanied by some degree of hypertrophy. These changes cause impaired systolic function of both ventricles. More than half of patients with idiopathic dilated cardiomyopathy present before the age of 2 years.²

Manifestations of heart failure usually constitute the initial clinical presentation of idiopathic dilated cardiomyopathy. Idiopathic dilated cardiomyopathy is among the most common causes of congestive heart failure in young children. Patients may exhibit tachypnea, tachycardia, and fatigue. Some patients present because of the effects of cardiac dysrhythmias. The prominent end-systolic ventricular volumes in patients with dilated cardiomyopathy make these children susceptible to intracardiac thrombosis, which can lead to pulmonary and systemic emboli.

Chest radiographs of children with dilated cardiomyopathy typically show substantial cardiomegaly (Figure 10-1). Pulmonary venous congestion and pulmonary edema are common (Figure 10-2). Echocardiography shows dilation to be most pronounced in the left atrium and left ventricle (Figure 10-3). There is global left ventricular (LV) dysfunction; the ejection fraction is diminished. These patients may have mitral regurgitation. Intracavitary thrombi are sometimes visualized during sonographic evaluations. MR imaging is an alternative technique to measure the ejection fraction and delineate regional wall motion abnormalities in patients with dilated cardiomyopathy. MR also documents the pattern of associated myocardial thickening.^3,4

Endocardial Fibroelastosis

Endocardial fibroelastosis refers to severe, diffuse, thickening of the ventricular endocardium. Endocardial fibroelastosis can occur as a primary idiopathic cardiac lesion or, more frequently, in association with a congenital heart disease. Primary endocardial fibroelastosis is further classified into dilated (most common) and contracted (restrictive) types. Endocardial fibroelastosis is characterized pathologically by diffuse endocardial thickening and clinically by manifestations of myocardial dysfunction. Histological examination shows invasion of the endocardial and subendocardial regions by fibroelastic tissue. There is hyperplasia of collagen, smooth muscle, and elastic fibers within the endocardium.⁵

A common mechanism of endocardial fibroelastosis is myocardial damage that causes persistently increased ventricular wall tension and secondary mitral regurgitation. In patients with endocardial fibroelastosis as a result of a congenital heart lesion, the pathophysiology usually includes ventricular hypertrophy, disrupted myocardial oxygen supply, and resultant endocardial thickening. A viral etiology (e.g., mumps) is suggested in some instances of of this condition.⁶ Although generally occurring as a sporadic disorder, familial cases account for up to 10% of children with endocardial fibroelastosis. The frequency of this disorder in siblings of an affected child is approximately 4%. Reported inheritance patterns of familial endocardial fibroelastosis include X-linked recessive, autosomal dominant, and autosomal recessive varieties.^2,7–9

In patients with dilated primary endocardial fibroelastosis, there is marked enlargement of the heart. The left atrium and left ventricle are disproportionately dilated. There is diffuse thickening of the LV endocardium; thickening is most pronounced in the outflow tract. The papillary muscles and cordae tendineae are involved, preventing appropriate mitral valve closure. Endocardial thickening is also present, to varying degrees, in the left atrium, right ventricle, and right atrium. The ventricular wall thicknesses are usually normal.

The secondary form of dilated endocardial fibroelastosis can occur in association with aortic stenosis, aortic atresia, aortic coarctation, ventricular septal defect, anomalous origin of the left coronary artery from the pulmonary artery, carnitine deficiency, various myocardial injuries, and several metabolic disorders. The endocardial thickening often has a more focal character in patients with the secondary form.

The contracted type of primary endocardial fibroelastosis is rare. While the endocardium of the left ventricle is thickened, this chamber is normal in size or is hypoplastic. The atria and the right ventricle are dilated and the myocardium of the right ventricle is hypertrophied. The secondary form of contracted endocardial fibroelastosis most often occurs in association with hypoplastic left heart syndrome.¹⁰

The most common clinical presentation of endocardial fibroelastosis is that of unexplained heart failure in an infant or young child. Common symptoms include dyspnea, tachypnea, irritability, and mild cyanosis. Congestive heart failure is progressive, and can lead to death within weeks of the initial presentation. Patients with endocardial fibroelastosis usually present during infancy, most often during the first 6 months of life (80%). The prevalence of primary endocardial fibroelastosis has diminished markedly in recent years.^11,12

The radiographic features of endocardial fibroelastosis include marked cardiomegaly and manifestations of congestive heart failure. In some patients, substantial cardiac enlargement is present from birth; while in others, the heart initially appears normal and enlargement occurs during the first several weeks or few months of life. Dilation of the left ventricle and left atrium usually predominates. Left-lower-lobe atelectasis because of enlargement of the left atrium is common. With the rare contracted form, the left ventricle is small or normal in size, while the other cardiac chambers are dilated. In patients with congestive heart failure, pulmonary vascular congestion and pulmonary edema are present.

Echocardiography confirms the pattern of cardiac chamber dilation in patients with endocardial fibroelastosis. Left ventricular function is poor and the ejection fraction is reduced. There is abnormal mitral valve motion; mitral regurgitation is common. The endocardial thickening can sometimes be demonstrated with echocardiography as prominent echogenicity along the endocardial surface of the left ventricle.¹³ Cine MR and catheter angiocardiography of endocardial fibroelastosis demonstrate a poorly functioning dilated left ventricle.^14,15

Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy is an uncommon genetic disease that causes myocardial hypertrophy. The myocardium in these patients is thickened and hypercontractile. There is variation in the hereditary pattern and genetic alterations, indicating that hypertrophic cardiomyopathy represents a group of related disorders. Most often, there is an autosomal dominant pattern of inheritance, with variable penetrance. Approximately 45% of cases represent new mutations. Mutations in various chromosomes have been reported in patients with hypertrophic cardiomyopathy, typically leading to abnormal sarcomere proteins. The mutations cause abnormal myocyte stresses and impaired function that eventually lead to hypertrophy and fibrosis. Histological examination of the thickened myocardium in patients with hypertrophic cardiomyopathy shows abnormally short and thick myofibrils in a disordered pattern.

The peak age range for the presentation of pediatric hypertrophic cardiomyopathy is 5 through 15 years. The estimated prevalence in children is 5:1,000,000. There are various systemic disorders that sometimes occur in association with hypertrophic cardiomyopathy, usually with a clinical presentation during infancy. These include Noonan syndrome, Beckwith-Wiedemann syndrome, glycogen storage disease type IIA, defects of fatty acid oxidation (e.g., carnitine deficiency) and mitochondrial diseases.^16–20

The pattern of myocardial thickening in hypertrophic cardiomyopathy varies substantially between patients. In approximately 70% of patients, the myocardial thickening is asymmetric, with predominant involvement of the septum. In 25% of patients, the septal hypertrophy is asymmetric. When the upper portion of the septum is predominantly involved, obstruction of the LV outflow tract can cause sudden death. Right ventricular hypertrophy occurs in 15% to 20% of patients. Atrial wall hypertrophy is an occasional finding. Left atrial dilation is common.

Hypertrophic cardiomyopathy causes impaired relaxation of the ventricular myocardium during diastole. Manifestations of congestive heart failure can occur despite a normal or elevated ejection fraction. Some patients have findings of myocardial ischemia despite patent coronary arteries. The initial clinical presentation of hypertrophic cardiomyopathy in children is most frequently a result of a murmur in an otherwise healthy patient. Many cases are discovered because of a positive family history. Common symptoms include exertional dyspnea (90% of symptomatic patients), angina and syncope. Auscultation demonstrates a harsh midsystolic murmur. With substantial cardiac involvement, manifestations of congestive heart failure may develop. In general, this disorder follows a more rapid and severe course when presenting during infancy than in older children. The overall risk for sudden cardiac death in children with hypertrophic cardiomyopathy is approximately 6%; most deaths are a result of myocardial ischemia or an arrhythmia.

Nearly all children with hypertrophic cardiomyopathy have radiographically demonstrable cardiomegaly, usually of moderate severity. Cardiac enlargement is predominantly caused by LV hypertrophy and left atrial dilation. Pulmonary vascular congestion and pulmonary edema are unusual in these patients, unless there is severe progressive disease.

Echocardiography is usually diagnostic in patients with suspected hypertrophic cardiomyopathy. Myocardial wall thickening is easily demonstrated with this technique (Figure 10-4). Asymmetrical septal hypertrophy is indicated by a septal thickness-to-posterior wall thickness ratio of at least 1.3. Myocardial thickening is indicated when the LV wall thickness is equal to or greater than 1.3 cm. In those patients with LV outflow obstruction, color Doppler shows turbulent flow through a dynamic subaortic stenosis. Mitral insufficiency is common in these patients. Mild aortic regurgitation is present in approximately one-third of patients with hypertrophic cardiomyopathy.^21,22

Thallium-201 SPECT scintigraphy of patients with hypertrophic cardiomyopathy shows myocardial thickening. The LV cavity is usually small. Reversible perfusion defects sometimes occur, most often in patients with a history of syncope; this finding is a risk factor for sudden death. The detection of ischemia is complicated by the occurrence of inhomogeneous hypertrophy.^23,24 Dynamic imaging of the heart with gated blood pool scintigraphy shows the LV cavity to be relatively small during diastole and markedly diminished in size during systole.

Cardiac MR of patients with hypertrophic cardiomyopathy provides important anatomic and functional information. Cross-sectional MR images demonstrate the distribution and severity of myocardial wall thickening (Figure 10-5). MR is superior to echocardiography for the detection of apical LV hypertrophy. As with gated scintigraphy, cine MR shows lack of appropriate diastolic ventricular relaxation and filling. Forceful contraction during systole nearly obliterates the LV cavity. Most often, the degree of wall thickening at the hypertrophic site diminishes somewhat during systole and thickening becomes more pronounced at the nonhypertrophic sites. In those patients with LV outflow tract obstruction, cine MR angiography demonstrates the dynamic nature of the narrowed outflow tract. The regional character of myocardial involvement in patients with hypertrophic cardiomyopathy can be assessed with “myocardial tagging” MR. Delayed contrast enhancement, usually with a patchy character, within the abnormal myocardium can occur as a result of fibrosis.^25–29

Idiopathic Restrictive Cardiomyopathy

Restrictive cardiomyopathy is the least common of the primary cardiomyopathies. This disorder is characterized by markedly reduced diastolic ventricular compliance. The ventricular chambers are usually normal in size or mildly dilated. Histological examination shows fibrosis throughout the deep layers of the myocardium and within the endocardium. The clinical manifestations are similar to those of constrictive pericarditis, with peripheral edema, jugular venous engorgement, and ascites.^30,31

Chest radiographs of children with idiopathic restrictive cardiomyopathy show normal heart size or mild cardiomegaly. Echocardiography and cine MR sometimes demonstrate reduced ventricular contraction, although systolic contraction is normal in many patients. Dynamic imaging shows subnormal ventricular filling during diastole. Compromised ventricular filling causes some degree of atrial enlargement. In contrast to constrictive pericarditis, ventricular septal motion is not paradoxic. Likewise, MR shows no evidence of pericardial thickening (i.e., the pericardium is <3 mm thick).^3,32–35

Endomyocardial Fibrosis

Endomyocardial fibrosis is a restrictive cardiomyopathy. Although rare in most parts of the world, this disorder accounts for up to 20% of fatal instances of heart failure in children in the tropical regions of Africa. Endomyocardial fibrosis apparently is immunologically mediated. There are two forms of this disorder: the endemic tropical form and a sporadic variety that occurs throughout the world. The sporadic form often occurs as a part of an eosinophilic syndrome.

The pathological findings of endomyocardial fibrosis include marked fibrous endocardial thickening (predominantly along the inflow tract) and layering of organized thrombus within one or both of the ventricular cavities that leads to progressive obliteration. Physiologically, restricted ventricular filling and atrioventricular valvular incompetence characterize this disorder. Systemic embolization is uncommon. Peripheral eosinophilia is usually absent. The most common clinical manifestations of endomyocardial fibrosis are dyspnea and chest pain. This disorder is more common in adolescents and young adults than in other age groups. There is a male predilection.^30,31

Atrial enlargement in patients with endomyocardial fibrosis may be sufficient to cause cardiomegaly on chest radiographs. Ventricular wall thickening and pericardial effusion contribute to the prominent cardiac silhouette. The ventricular wall thickening is documented with echocardiography or MR. One or both ventricles can be involved. Organized thrombus is present in the ventricular cavity. There is apical obliteration of the ventricular cavity during systole. Left ventricular contraction is usually normal. Papillary muscle involvement can result in diminished motion of the mitral and tricuspid valves.^36,37

Löffler Endocarditis

Löffler endocarditis is a rare form of restrictive cardiomyopathy that shares many of the features of endomyocardial fibrosis, but tends to occur as a more acute process. This disorder is slightly more common in males than in females. It occurs in patients of all ages. The pathophysiology involves infiltration of the heart with eosinophils. There is also infiltration of other tissues, including the bone marrow. Patients with Löffler endocarditis have the sporadic form of endocardial fibrosis. The left ventricle is the site of greatest involvement. The LV cavity may become filled with thrombus that organizes into fibrotic layers. Systemic embolization is common. Patients may suffer heart failure, fever and manifestations of systemic emboli. Laboratory examination often indicates hypereosinophilia.

Echocardiography of patients with Löffler endocarditis demonstrates subnormal ventricular contraction and organized thrombus within the ventricular cavity. Cardiac MR demonstrates biventricular cavity obliteration (especially the apices) by thickened ventricular walls. There is late contrast enhancement of the subendocardial layer. Chest radiographs show nonspecific mild cardiomegaly, atrial enlargement, and, in some patients, pulmonary vascular congestion.³⁰

Noncompaction Cardiomyopathy

Noncompaction cardiomyopathy (also termed persistence of spongy myocardium) is a very rare cardiomyopathy that is characterized by the persistence of prominent ventricular trabeculations. Presumably, this occurs as a consequence of fetal arrest of normal compaction of the loose interwoven meshwork of the developing endomyocardium. This is a heterogenous, but predominantly genetic, disorder. Mutations in sarcomere genes are responsible for many cases. Echocardiography shows a layered myocardial wall, consisting of a thin compacted epicardial layer and an abnormal thick noncompacted endocardial layer. The endocardium contains numerous prominent trabeculations and deep recesses that communicate with the LV cavity. These patients may present because of arrhythmias or manifestations of heart failure. The clinical onset can occur at any time from birth through adolescence.^38–41

Arrhythmogenic Right Ventricular Dysplasia

Arrhythmogenic right ventricular dysplasia (ARVD; arrhythmogenic right ventricular cardiomyopathy; arrhythmogenic cardiomyopathy) is a cardiomyopathy that is characterized by fatty or fibrofatty infiltration of a portion of the right ventricular myocardium. Left ventricular involvement can occur, particularly with progressive disease. ARVD is associated with various ventricular arrhythmias. This disorder is an important potential cause of sudden death in children and young adults, including athletes. ARVD accounts for 3% to 4% of deaths during sporting activities, and 5% of sudden cardiac deaths in individuals younger than age 65 years. The mean patient age at presentation is 30 years. The male-to-female ratio is 3:1.^42–47

ARVD is a familial disorder with an autosomal dominant inheritance. Naxos disease is an autosomal recessive form that includes palmoplantar keratoses and woolly hair. Phenotypic expression of ARVD is variable. The pathogenesis apparently involves disrupted differentiation of cardiac progenitor cells, resulting in differentiation into adipocytes. The most common mutations are in DSP, JUP, PKP2, DSG2, and DSC2, which encode the desmosomal proteins desmoplakin, plakoglobin, plakophilin 2 (PKP2), desmoglein 2 (DSG2), and desmocollin 2 (DSC2), respectively. Mutations of TMEM43 and TGFβ3 (transforming growth factor β3) have been identified in some patients. Desmosomes are intercellular adhesion junctions. Some desmosomal proteins fulfill roles both as structural proteins in cell-to-cell adhesion junctions and as signaling molecules. The pathogenesis of ARVD likely is a combination of altered cellular biomechanical behavior at the gap junction and altered signaling. Patients with these mutations can have arrhythmias prior to the development of histological evidence of myocyte loss or fibrofatty replacement. However, the predominant cause of arrhythmias appears to be dispersion of myocytes by fibrofatty replacement.^48–53

The predominant site of pathology in the early phase of ARVD is between the anterior aspect of the infundibulum, the right ventricular (RV) apex, and the inferior or diaphragmatic aspect of the right ventricle; this is termed the “triangle of dysplasia.” Progression to diffuse RV disease is common. Left ventricular involvement is also common with advanced disease. There are also variants in which LV involvement predominates throughout the course of the disease.

All patients with ARVD have fatty replacement of myocardium. The amount of associated fibrous tissue varies between patients. Most commonly, there is segmental loss of myocardium of the RV free wall, with replacement by fibrofatty tissue. Histological examination suggests that the destructive process proceeds from the subepicardium centrally, such that residual myocardium is confined to the inner subendocardial layer. The ventricular wall is thinned (<3 mm) and replaced with fibrofatty tissue. The abnormal tissue borders on, and is embedded in, strands or sheets of cardiac myocytes. An inflammatory infiltrate is present in many patients. The fibrofatty replacement occasionally involves a portion of the left ventricle or the ventricular septum in addition to the right ventricle.⁵⁴

Isolated fatty replacement of the right ventricle is a more benign process than true ARVD. In these patients, the thickness of the RV wall can be normal or prominent. The involved portion of the myocardium is partially or nearly completely replaced by fatty tissue. Histological examination does not show myocyte atrophy or inflammation, as is demonstrated in the fibrofatty form of ARVD. Fibrous tissue replacement is lacking. The LV wall and the septum are spared.⁵⁵

Adipose tissue is sometimes present in the myocardium of normal individuals, particularly those with morbid obesity. Fat replacement, therefore, is not a sine qua non for the diagnosis of ARVD. Fat replacement of the RV myocardium without fibrosis may represent a distinct entity that is associated with relatively low arrhythmogenicity; the term fat dissociation syndrome has been proposed for these patients. Histological studies suggest that true ARVD most often has minimal fat replacement of myocardium, in conjunction with fibrosis and degeneration of myocytes within the areas of fibrosis. The fatty replacement primarily occurs at the epicardial border of the RV free wall, with infiltration inward toward the endocardium. There is replacement of bundles of myocyte fascicles.^55–57

ARVD constitutes a wide clinical spectrum that ranges from asymptomatic isolated premature ventricular beats to sustained ventricular tachycardia, ventricular fibrillation, and sudden cardiac death. In some patients, the clinical findings change with time. Many patients are completely asymptomatic until the first presentation with cardiac arrest. This asymptomatic early period is termed the concealed phase. During the electrical phase, patients experience symptomatic arrhythmias. Potential symptoms include palpitations, fatigue, syncope, and chest pain. Progression to diffuse myocardial involvement can lead to biventricular heart failure. Recognition of the hereditary nature of this disorder has led to the frequent diagnosis of asymptomatic individuals who have an affected family member. Treatment options include avoidance of strenuous exercise, antiarrhythmic medications, catheter ablation, implantable cardioverter defibrillator placement, and cardiac transplantation.

Physical examination, electrocardiographic findings, and cardiac imaging may be normal or nonspecific in patients with ARVD, particularly early in the course of the disease. Particularly in children, cardiac MR is often normal despite the presence of multiple clinical features of the condition. Endomyocardial biopsy is also unreliable for the diagnosis because this does not provide a full-thickness sampling of the myocardium and the patchy distribution of the lesion may lead to sampling error. The only truly diagnostic gold standard is gross pathology from hearts removed during transplantation or from postmortem examinations. In consideration of the diagnostic uncertainties, a task force comprised of members of the European Society of Cardiology and the International Society and Federation of Cardiology established standardized criteria for the diagnosis of ARVD. Table 10-2 summarizes the task force recommendations. Imaging studies serve an important role in the diagnostic evaluation of these patients.^58,59

The original task force system is highly specific for the diagnosis, but lacks sensitivity. In 2010, a new international task force proposed modified criteria to improve the diagnostic yield. Among the alterations to the criteria are specific rules for MRI findings for the “global or regional dysfunction and structural alterations” category. The major criterion is met if MRI demonstrates: (a) regional RV akinesia or dyskinesia or dyssynchronous RV contraction and (b) the ratio of RV end-diastolic volume to body surface area is ≥110 mL/m² for males or ≥100 mL/m² for females or the RV ejection fraction is ≤40%. The minor criterion is met if MRI shows: (1) regional RV akinesia or dyskinesia or dyssynchronous RV contraction and (2) a ratio of RV end-diastolic volume to body surface area of ≥100 to <110 mL/m² for males or ≥90 to <00 mL/m² for females or an RV ejection fraction of >40% to ≤45%. Note that MRI demonstration of RV wall thinning or fatty infiltration of the myocardium is not recognized to be of diagnostic value by this system.⁶⁰

The classic echocardiographic features of ARVD include focal or global RV enlargement, one or more RV aneurysms during diastole, and dyskinetic areas in the inferior-basal region below the tricuspid valve. Careful evaluation may show evidence of focal RV wall thinning. With severe disease, tricuspid or mitral valve prolapse may be present. In most patients with ARVD, however, the findings are relatively subtle and frequently are nonspecific; normal echocardiography does not exclude the diagnosis.⁶¹

MR imaging is generally considered the best noninvasive imaging technique for the diagnosis of ARVD, although the sensitivity, specificity, and accuracy are not well established, largely because of the lack of a practical diagnostic standard for comparison. Among the established criteria for the diagnosis of ARVD, MR imaging provides information on the following: (a) fatty infiltration of the RV myocardium (major criterion; however, the current task force standards require biopsy confirmation); (b) fibrofatty replacement, with diffuse thinning of the RV myocardium (major criterion); (c) aneurysms of the right ventricle and RV outflow tract (major criterion); dilation of the right ventricle and RV outflow tract (major criterion with severe, minor criterion when mild); (d) global systolic dysfunction (major criterion); (e) regional contraction abnormalities (minor criterion); and (f) global diastolic dysfunction (minor criterion).⁶²

The most important tissue abnormality that can be detected with imaging studies in patients with ARVD is fatty replacement of the RV free wall, usually best demonstrated with black blood spin-echo MR images. The accurate identification of fat within the myocardium is often challenging since the right ventricle is a relatively thin structure and the affected portion of the myocardium may be quite small. In addition, a variety of artifacts can cause the projection of high signal intensity onto the myocardium. Comparison of the findings on conventional high-resolution T1-weighted spin echo images to those obtained with a fat-suppressed technique is frequently helpful.^63,64 Delayed (10-minute) contrast-enhanced MR images may show abnormal increased signal intensity within the dysplastic tissue. Cine MR images (e.g., bright blood true fast imaging with steady-state precession) may show abnormal RV wall motion, both during systole and diastole. Transient aneurysms may be present. The involved portion of the right ventricle frequently lacks normal systolic thickening and contraction.^65–67

Because fat can be present in the myocardium of normal individuals, this finding alone is not specific for the diagnosis of ARVD and should be considered in the entire clinical context. This finding is most suspicious when the fatty replacement is transmural or is associated with diffuse thinning of the RV myocardium. Fibrotic degeneration cannot be distinguished from normal myocardium on standard T1-weighted images. A chemical shift selective breath hold cine technique is particularly helpful to detect dysplasia that is not associated with fatty signal abnormality.^56,62,65

Although MR is generally considered the standard imaging technique for patients with suspected ARVD, many of the features can also be demonstrated with helical CT or electron-beam CT. Fat of sufficient quantity within the ventricular wall causes diminished attenuation. The right ventricle can be somewhat dilated and the RV wall may have a scalloped appearance.^68,69

Gated blood-pool SPECT scintigraphy can be utilized to evaluate wall motion abnormalities in patients with ARVD and to quantify ventricular ejection fractions. Some of these patients have substantial compromise of RV ejection fraction. The right ventricle may be dilated. Segmental RV wall motion disorders can occur, as well as nonsynchronized contraction of the right and left ventricles.⁷⁰

Myocarditis

Myocarditis is an inflammatory process of the heart muscle, characterized pathologically by a cellular infiltrate in the myocardium that predominantly consists of mono-nuclear cells. Myocarditis most often is related to infection, usually with a virus. Myocarditis is a rare potential complication of many common viral infections, such as those involving influenza virus, coxsackievirus (B3 and B4 are most common), echovirus, adenoviruses (types 2 and 5 are most common), mumps virus, measles virus, herpes simplex virus, HIV, and rubella virus. Infection with coxsackie B virus can result in a severe form of myocarditis in neonates. Toxoplasmosis can involve the myocardium in infants. Multifocal myocarditis can occur in patients with Rocky Mountain spotted fever (Rickettsia rickettsii). Chagas disease (Trypanosoma cruzi) is a common cause of myocarditis in Central America and South America. Noninfectious forms of myocarditis can also occur, including autoimmune and toxin-mediated processes. The most common noninfectious causes of myocarditis are systemic lupus erythematosus, polyarteritis nodosa, Kawasaki disease, dermatomyositis, and scleroderma. Toxins that can affect the myocardium include chemotherapeutic agents such as doxorubicin. Myocarditis can accompany idiopathic acute pericarditis.

Acute infectious myocarditis can occur in children of any age. There is often a history of a recent upper respiratory tract infection. The clinical course ranges from a very mild abnormality to one of rapid progression culminating in fulminant cardiac dysfunction. The diagnosis of myocarditis is suggested when sudden cardiac failure and/or arrhythmias develop after a febrile flu-like illness. Common findings include fever, sinus tachycardia, pallor, mild cyanosis, and a gallop rhythm. Although there is considerable variation between patients, the clinical manifestations of myocarditis tend to be less severe in older children than in infants. Chronic forms of myocarditis can present with chronic congestive heart failure, dysrhythmias, and cardiomegaly.

Myocardial failure in patients with myocarditis is sometimes transient, while in other patients it is progressive and chronic in the form of dilated cardiomyopathy. About one-third of children with cardiomyopathy develop unremitting cardiac failure that is fatal or necessitates cardiac transplantation. Predictive factors for a poor outcome that can be evaluated at the time of diagnosis include an ejection fraction of less than 30%, a shortening fraction of less than 15%, LV dilation, moderate to severe mitral regurgitation, older age, cardiac arrest, and ventricular arrhythmia.^71,72

The radiographic features of myocarditis vary substantially between patients. Cardiomegaly is usually present (Figure 10-6). However, heart size is often normal in children who develop sudden symptoms as a result of a myocarditis-induced dysrhythmia. When myocarditis leads to congestive heart failure, radiographs show pulmonary edema in addition to cardiomegaly. The radiographic or sonographic demonstration of dystrophic calcification within the heart of a patient with myocarditis is a sign of severe myocardial damage and indicates a poor prognosis.⁷³

Myocardial dysfunction in children with myocarditis is readily evaluated with echocardiography. In those patients with congestive heart failure, echocardiography shows increases in the LV end-diastolic and end-systolic diameters and decrease in the LV shortening fraction. The ejection fraction is diminished. The left atrium is usually somewhat dilated. There is widespread asynergic motion of the LV free wall. Functional MR provides similar information. T2-weighted MR sequences may show abnormal increased signal intensity in the myocardium because of edema.⁷⁴

Scintigraphy with ⁶⁷gallium or ^99mtechnetium-labeled leukocytes shows intense uptake within the inflamed myocardium in patients with acute myocarditis. This finding aids in the differentiation of myocarditis from cardiomyopathy without active inflammation. Other nuclear medicine techniques that are sometimes helpful in the care of children with acute myocarditis include ²⁰¹thallium perfusion imaging to detect myocardial ischemia or infarction, and ^99mtechnetium-pyrophosphate imaging for the diagnosis of acute myocardial infarction.^75–77

Infective Endocarditis

Infective endocarditis refers to an infection of the endocardium, the valves, and the related structures. Many types of organisms are associated with endocardial infections, although bacteria are most common. Although structurally normal hearts can develop infective endocarditis, the majority of these patients have a predisposing cardiac abnormality. Endocardial surfaces that have been damaged by previous surgery, trauma (e.g., central venous catheterization), or inflammation (e.g., rheumatic fever) are susceptible to colonization by circulating microorganisms. Approximately half of patients with prosthetic cardiac valves develop infective endocarditis within 1 year of the surgery. Turbulent blood flow associated with various congenital heart diseases can cause endocardial surface changes that increase susceptibility to infection. In the pediatric and neonatal populations, the frequency of infective endocarditis is increasing because of improved survival of high-risk children and the widespread use of central venous catheters.

Approximately 3 in 4 cases of infective endocarditis are caused by streptococcal and staphylococcal species. Viridans streptococcus is the single most common group of organisms. Various Gram-negative and fungal organisms are occasionally responsible. The initial infection typically occurs by way of colonization of a noninfectious thrombotic vegetation at the site of an endothelial defect. Colonization of the vegetation stimulates additional platelet and fibrin deposition. Infected vegetations may be solitary or multiple, and range in size from less than 1 mm to several cm in diameter. The vegetations of infective endocarditis are composed of a complex meshwork of organisms, platelets, and fibrin that adhere to the damaged endocardium. Dislodgment of friable vegetations can lead to distant septic embolization to sites such as the brain, lungs, and kidneys. Vegetations infected with Candida albicans, Haemophilus species, and Staphylococcus aureus are particularly prone to embolization.⁷⁸

Endocardial damage and frequent episodes of bacteremia are the key factors in the pathogenesis of infective endocarditis in neonates. The major causes of endocardial damage in neonates are central catheter-induced trauma and hypoxic damage to the endocardium from sepsis or hypotension. Endocardial damage can also be related to a cardiac anomaly, such as a ventricular septal defect; however, the majority of neonates with infective endocarditis have otherwise normal hearts.^79–81

In addition to septic embolization, other potential complications of infective endocarditis include rupture of the cordae tendineae, valve-ring microabscesses, and fistula formation to the pericardial space (leading to a pericardial empyema). With extensive focal destruction, perforation can occur. Infection can also cause focal weakening of the myocardium, leading to an aneurysm of the ventricle or of the sinus of Valsalva. Spread of infection from a right-heart lesion can cause pulmonary artery mycotic aneurysms.⁸²

The clinical manifestations of infective endocarditis are frequently vague and insidious. Fever and fatigue are the most common early complaints. Other potential findings are also nonspecific; these include splenomegaly, weight loss, respiratory symptoms, petechiae, arthralgias, abdominal complaints, and headache. Ocular and cutaneous signs of microemboli are uncommon in children. Clinical examination may demonstrate a new or changing murmur. Approximately 90% of these patients have positive blood cultures. Other common laboratory findings include elevations of C-reactive protein and the erythrocyte sedimentation rate.

Chest radiographs of children with infective endocarditis are frequently normal or demonstrate nonspecific manifestations of an underlying congenital heart disease. If the infection is severe enough to cause cardiac dysfunction, radiographs may show cardiomegaly, pulmonary vascular congestion and pulmonary edema. If endocarditis involves the right heart, septic emboli can lead to multiple foci of nodular consolidation in the lungs.

The vegetations of infective endocarditis usually can be visualized with echocardiography (Figure 10-7). In some instances, the transesophageal technique is required for a complete examination, particularly when a right-sided lesion is suspected. Cross-sectional imaging with MR or CT is useful for selected patients, particularly when there is evidence of a mycotic aneurysm.⁸³

HIV and AIDS

Cardiac abnormalities in children with HIV infection and AIDS are important determinants of morbidity and mortality. Manifestations of cardiac dysfunction are uncommon in infants and young children with HIV infection, but occur with substantial frequency in older children and can cause or contribute to a fatal outcome. Myocarditis is a common cause of LV dysfunction in patients with HIV infection. The most common responsible organisms are adenoviruses and Cytomegalovirus. Other potential cardiac lesions in these patients include dilated cardiomyopathy, pericardial effusion, infective endocarditis, arteriopathy, cardiac rhythm disturbances, and cardiac malignancy.^84,85

Kawasaki Disease

Kawasaki disease (mucocutaneous lymph node syndrome) is an acute vasculitis that is a common form of acquired heart disease in children. Approximately 80% of cases of Kawasaki disease occur in children younger than 5 years of age. The peak incidence is between 13 and 24 months of age. Kawasaki disease is uncommon in infants younger than 7 months of age and rare in those younger than 3 months of age. Children of Asian ancestry are much more likely to develop Kawasaki disease than are those of other racial backgrounds. The frequency of this disorder in Japan is 100 to 200 per 100,000 children younger than 5 years of age. In the United States, 6 to 15 per 100,000 children develop Kawasaki disease prior to their fifth birthday. The peak age at onset is somewhat lower in Japan (6 to 12 months) than in Europe and United States (18 to 24 months). The male-to-female ratio is 1.5:1. Boys with this disease have a slightly higher mortality rate than girls. The overall mortality rate for properly treated Kawasaki disease is 0.3%.^86–90