Noncompaction Cardiomyopathy in Childhood

Noncompaction cardiomyopathy (NCCM), also called left ventricular noncompaction (LVNC), a classified form of cardiomyopathy, is a genetic disease characterized by excessive and unusual trabeculations within the mature left ventricle (LV). NCCM has been considered to be a developmental failure of the heart to form fully the compact myocardium during the later stages of cardiac development. Clinically and pathologically, NCCM is characterized by a spongy morphological appearance of the myocardium occurring primarily in the LV with the abnormal trabeculations typically being most evident in the apical and midlateral-inferior portions of the LV. The right ventricle (RV) may also be affected alone or in conjunction with the LV. In NCCM, in addition to the regional presence of prominent trabeculae and inter-trabecular recesses in the LV, thickening of the myocardium in 2 distinct layers composed of compacted and non-compacted myocardium is also classically noted. It may be associated with left ventricular dilation or hypertrophy, systolic and/or diastolic dysfunction, atrial enlargement, or various forms of congenital heart disease. The myocardium in NCCM may demonstrate normal or abnormal systolic or diastolic function and the size, thickness or function may change unexpectedly (“undulating phenotype”). Affected individuals are at risk of left or right ventricular failure, or both. Heart failure symptoms can be exercise-induced or persistent at rest, but many patients are asymptomatic. Chronically treated patients sometimes present acutely with decompensated heart failure. Other life-threatening risks are ventricular arrhythmias and atrioventricular block, presenting clinically as syncope, and sudden death. Genetic inheritance arises in at least 30–50% of patients, NCCM is thought to occur in approximately 1 per 7000 live births. It occurs in newborns, young children and adults, with the worst reported outcomes seen in infants, particularly those with associated systemic disease and metabolic derangement. In some families, a consistent phenotype of NCCM is seen in affected relatives but quite commonly individuals with features of NCCM are found in families where other affected relatives have typical hypertrophic cardiomyopathy, dilated cardiomyopathy, or restrictive cardiomyopathy. Mutations in ~15 genes have been implicated and include cytoskeletal, sarcomeric, and ion channel genes, with sarcomere-encoding genes being most common. In the case of NCCM with congenital heart disease, disturbance of the Notch or Wnt signaling pathways appear to be part of a “final common pathway” for this form of the disease. In addition, disrupted mitochondrial function and metabolic abnormalities have a causal role as well. Treatments focus on improvement of cardiac efficiency and reduction of mechanical stress in those with systolic dysfunction. Further, arrhythmia therapy and implantation of an automatic implantable cardioverter-defibrillator (ICD) for prevention of sudden death are mainstays of treatment when deemed necessary and appropriate. Patients with NCCM associated with congenital heart disease commonly require surgical or catheter-based interventions. Despite progress in diagnosis and treatment over the past 10–15 years, understanding of the disorder and outcomes continue to need further improvement.