Rethinking Left Ventricular Noncompaction and Excessive Left Ventricular Trabeculation: Development, Genetics, and a...

Left ventricular noncompaction (LVNC) has long been treated as a distinct cardiomyopathy defined by excessive left ventricular trabeculation. Human developmental studies no longer support the classical arrest-of-compaction hypothesis and instead favor differential growth of the trabecular and compact layers. Excessive trabeculation is also observed in inherited and developmental cardiomyopathies, as a change accompanying other cardiac disease, in asymptomatic individuals, and reversibly in pregnancy and in athletes. Morphology alone is therefore insufficient to define a disease entity. This narrative, conceptual review re-examines ventricular wall formation, the mechanisms producing excessive trabeculation, genetic heterogeneity, and clinical phenotypes and shows that no single axis organizes LVNC unequivocally. Integrating these elements, excessive trabeculation is organized into three clinical pathophysiologic contexts: primary cardiomyopathy with hypertrabeculation, in which overt cardiomyopathy is not sufficiently explained by another underlying disease or by pathological hemodynamic loading; disease-associated hypertrabeculation; and hypertrabeculation without overt cardiomyopathy. The purpose of this organization is to isolate a candidate disease entity that can be tested, using the attribution step by which current definitions of hypertrophic and dilated cardiomyopathy are themselves constructed. The framework is built on three axes: category, descriptive phenotypic group, and risk modifiers. It is hypothesis-generating; operationalization, interobserver reproducibility, prospective outcomes and external validation remain to be realized.