Diseases of the Myocardium

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Chapter 433 Diseases of the Myocardium

The extremely heterogeneous groups of heart muscle diseases that are associated with structural and/or functional cardiac dysfunction (cardiomyopathy) are important causes of morbidity and mortality in the pediatric population. Certain anatomic and physiologic conditions such as congenital heart disease, hypertension, and coronary artery disease may result in heart muscle dysfunction, but are distinct from the conditions presented in this chapter. Several classification schemes have been formulated in an effort to provide logical, useful, and scientifically based etiologies for the cardiomyopathies. Insight into the molecular genetic basis of cardiomyopathies has increased exponentially and it is likely that etiologic classification schemes will continue to evolve.

Table 433-1 classifies the cardiomyopathies based on their anatomic (ventricular morphology) and functional pathophysiology. Dilated cardiomyopathy, the most common form of cardiomyopathy, is characterized predominantly by left ventricular dilation and decreased left ventricular systolic function (Fig. 433-1). Hypertrophic cardiomyopathy demonstrates increased ventricular myocardial wall thickness, normal or increased systolic function, and often, diastolic (relaxation) abnormalities (Table 433-2). Restrictive cardiomyopathy is characterized by nearly normal ventricular chamber size and wall thickness with preserved systolic function, but dramatically impaired diastolic function leading to elevated filling pressures and atrial enlargement (see Fig. 433-3). Arrhythmogenic right ventricular cardiomyopathy and left ventricular non-compaction are characterized by specific morphologic abnormalities and heterogeneous functional disturbances.


Dilated Cardiomyopathy (DCM)
Neuromuscular diseases Muscular dystrophies (Duchenne, Becker, limb girdle, Emery- Dreifuss, congenital muscular dystrophy, etc.), myotonic dystrophy, myofibrillar myopathy
Inborn errors of metabolism Fatty acid oxidation disorders (trifunctional protein, VLCAD), carnitine abnormalities (carnitine transport, CPTI, CPTII), mitochondrial disorders (including Kearns-Sayre syndrome), organic acidemias (propionic acidemia)
Genetic mutations in cardiomyocyte structural apparatus Familial or sporadic DCM
Genetic syndromes Alstrom syndrome, Barth syndrome (phospholipid disorders)
Ischemic Most common in adults
Chronic tachyarrhythmias  
Hypertrophic Cardiomyopathy (HCM)
Inborn errors of metabolism Mitochondrial disorders (including Friedreich ataxia, mutations in nuclear or mitochondrial genome), storage disorders (glycogen storage disorders, especially Pompe; mucopolysaccharidoses; Fabry disease; sphingolipidoses; hemochromatosis; Danon disease)
Genetic mutations in cardiomyocyte structural apparatus Familial or sporadic HCM
Genetic syndromes Noonan, Costello, cardio-faciocutaneous, Beckwith-Wiedemann syndrome
Infant of a diabetic mother Transient hypertrophy
Restrictive Cardiomyopathy (RCM)
Neuromuscular disease Myofibrillar myopathies
Metabolic Storage disorders
Genetic mutations in cardiomyocyte structural apparatus Familial or sporadic RCM
Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
Genetic mutations in cardiomyocyte structural apparatus Familial or sporadic ARVC
Left Ventricular Noncompaction (LVNC) X-linked (Barth syndrome), autosomal dominant, autosomal recessive, mitochondrial inheritance, or sporadic LVNC
Sporadic LVNC
Systemic Inflammatory Disease Systemic lupus erythematosus (SLE), infant of mother with SLE, scleroderma, Churg-Strauss vasculitis, rheumatoid arthritis, rheumatic fever, sarcoidosis, dermatomyositis, periarteritis nodosa, hypereosinophilic syndrome (Löffler syndrome), acute eosinophilic necrotizing myocarditis, giant cell myocarditis
Nutritional Deficiency Beriberi (thiamine deficiency), kwashiorkor, Keshan disease (selenium deficiency)
Drugs, Toxins Doxorubicin (Adriamycin), cyclophosphamide, chloroquine, ipecac (emetine), sulfonamides, mesalazine, chloramphenicol, alcohol, hypersensitivity reaction, envenomations, irradiation, herbal remedy (blue cohosh)
Coronary Artery Disease Kawasaki disease, medial necrosis, anomalous left coronary artery from the pulmonary artery (ALCAPA), other congenital coronary anomalies (anomalous right coronary, coronary ostial stenosis), familial hypercholesterolemia
Hematology-Oncology Anemia, sickle cell disease, leukemia
Endocrine-Neuroendocrine Hyperthyroidism, carcinoid tumor, pheochromocytoma


Cox GF, Sleeper LA, Lowe AM, et al: Factors associated with establishing a causal diagnosis for children with cardiomyopathy, Pediatrics 4:1519–1531, 2006.

Elliott P, Andersson B, Arbustini E, et al: Classification of the cardiomyopathies: a position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases, Eur Heart J 29:270–276, 2008.

Hershberger RE, Lindenfeld J, Mestroni L, et al: Genetic evaluation of cardiomyopathy—a Heart Failure Society of America practice guideline, J Card Fail 15:83–97, 2009.

Judge DP: Use of genetics in the clinical evaluation of cardiomyopathy, JAMA 302:2471–2476, 2009.

Maron BJ, Roberts WC, Arad M, et al: Clinical outcome and phenotypic expression in LAMP2 cardiomyopathy, JAMA 301:1253–1258, 2009.

Maron BJ, Towbin JA, Thiene G, et al: Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention, Circulation 113:1807–1816, 2006.

Mocumbi AO, Fereira MB, Sidi D, et al: A population study of endomyocardial fibrosis in a rural area of Mozambique, N Engl J Med 359:43–48, 2008.

Morita H, Rehm HL, Menesses A, et al: Shared genetic caused of cardiac hypertrophy in children and adults, N Engl J Med 358:1899–1908, 2008.

Paul M, Zumhagen S, Stallmeyer B, et al: Genes causing inherited forms of cardiomyopathies: a current compendium, Herz 34:98–109, 2009.

Scaglia F, Towbin JA, Craigen WJ, et al: Clinical spectrum, morbidity, and mortality in 113 pediatric patients with mitochondrial disease, Pediatrics 114:925–931, 2004.

433.1 Dilated Cardiomyopathy


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.

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.