Sarcomere Mutations in Cardiomyopathy, Noncompaction, and the Developing Heart

n this issue of Circulation, Klaassen and colleagues1 describe mutations in the genes encoding myosin heavy chain (MHC), cardiac actin, and troponin T in patients with left ventricular noncompaction (LVNC). LVNC, defined as excessive and unusual trabeculation of the mature left ven- tricle, is thought to reflect a developmental failure of the heart to form fully the compact myocardium during the later stages of cardiac development. Previously, mutations in sarcomeric genes have been linked extensively to the development of hypertrophic cardiomyopathy (HCM) and dilated cardiomy- opathy (DCM). The finding of similar, but not identical, mutations in patients with LVNC suggests a continuum of cardiomyopathy that includes LVNC and further supports the essential role for normal sarcomere function during cardiac development. Article p 2893 Noncompaction of the ventricular myocardium is charac- terized by a spongy morphological appearance of the myo- cardium occurring primarily in the left ventricle and most evident in the apical portion.2 Noncompaction often is visu- alized as deep recesses within the thickened apex, and these sinusoids communicate with the ventricular cavity. During heart development, the myocardium is initially trabeculated during a period before coronary artery development and is thought to be an adaptation to provide blood flow to the developing myocardium. The development of the coronary vasculature is associated temporally with the loss of trabec- ulae and the full maturation of the compact myocardium. Between embryonic weeks 5 and 8, the trabeculae regress as the compact myocardium develops from base to apex. Iso- lated LVNC is defined as occurring in the absence of other cardiac structural malformation. Nonsyndromic LVNC refers to the absence of other extracardiac developmental disorders. In 2006, the American Heart Association scientific statement on classification of cardiomyopathies reclassified LVNC as its own disease entity.3