DESCRIPTION

Cardiomyopathy (CM) is defined as dysfunction of the ventricular myocardium that cannot be explained by congenital heart disease or abnormal loading conditions. Impairment in systolic function, diastolic function, or both can occur. It can be classified based on structural and functional abnormalities:

• Dilated CM (DCM): depressed systolic function with ventricular dilation secondary to suboptimal myocardial systolic shortening. DCM predominantly involves the left ventricle (LV).
• Hypertrophic CM (HCM): excessive hypertrophy of the LV that is not secondary to load conditions, such as aortic stenosis or hypertension. HCM often has hyperdynamic systolic function.
• Restrictive CM (RCM): a rare disease characterized by noncompliant myocardium. There is normal or decreased volume of both ventricles associated with biatrial enlargement, no ventricular hypertrophy, impaired ventricular filling with restrictive physiology, and normal systolic function.
• LV non-compaction CM (LVNC): characterized by the failure of normal LV compaction during fetal life, leading to numerous ventricular trabeculations and deep intertrabecular recesses

EPIDEMIOLOGY

Overall incidence of CM is 1.1 to 1.5 cases per 100,000 children annually.

ETIOLOGY

The etiologies of cardiomyopathies can be separated into the following categories:

• Molecular genetic causes: Pediatric CMs are genetically heterogeneous and typically involve mutations in the genes encoding the sarcomere-binding proteins, Z-band, nuclear membrane, desmosome, mitochondrial, and calcium-handling proteins.
• Congenital myopathies (Duchenne muscular dystrophy and Becker muscular dystrophy)
• Inflammatory causes (myocarditis)
• Tachycardia arrhythmias
• RASopathies (Noonan syndrome)
• Inborn errors of metabolism (carnitine palmitoyltransferase [CPT] II deficiency, Pompe disease)
• Idiopathic

RISK FACTORS

GENERAL PREVENTION

• Patients undergoing cardiotoxic chemotherapy, like doxorubicin, should receive cardioprotective strategies like dexrazoxane. In addition, there is evolving evidence on early initiation of medications like angiotensin-converting enzyme inhibitors (ACE-i) for primary prevention of cardiotoxicity.
• There is strong evidence to suggest that all patients with Duchenne muscular dystrophy start an ACE-i or angiotensin receptor blocker (ARB) by age 10 years to delay the onset of CM.
• Patients with familial history of CM should be screened regularly as the disease may be diagnosed early. Prompt initiation of guideline-directed medical therapy (GDMT) may occasionally help in recovery of cardiac function.

PATHOPHYSIOLOGY

• DCM: inadequate systolic function with a low cardiac index (hypoperfusion) and a high central venous pressure (systemic congestion). There can be left atrial (LA) hypertension and pulmonary hypertension (PH) from left heart dysfunction.
• HCM: Diastolic dysfunction and LV outflow tract obstruction are the most problematic and lead to LA hypertension and compromised cardiac output, especially with activity.
• RCM: Diastolic dysfunction over time leads to LA hypertension and PH. There can also be RV dysfunction and hepatic venous congestion.
• LVNC: Incomplete myocardial compaction results in subendocardial ischemia and inadequate systolic function. There is also a risk of stroke due to frequent thrombus formation in deep intertrabecular recesses.

COMMONLY ASSOCIATED CONDITIONS

CM is most commonly identified in otherwise healthy children but can be associated with:

• DCM: neuromuscular disorders (16%), inborn errors of metabolism (4%), neuromuscular disorders (9%), familial (5%), or rarely with malformation syndromes (1%)
• HCM: neuromuscular disorders (9%), inborn errors of metabolism (9%), or malformation syndromes (9%)
• RCM: In some tropical regions, endomyocardial fibrosis associated with RCM is common.
• LVNC: inborn errors of metabolism, pulmonary stenosis, septal defects, aneuploidies, copy number mutations (22q11 deletion), neuromuscular disorders and other genetic syndromes (e.g., Marfan, Sotos)