Is Left Ventricular Noncompaction a Trait, Phenotype, or Disease? The Evidence Points to Phenotype.

Abstract

The question is is left ventricular noncompaction (LVNC) a trait, phenotype, or disease? By trait, we refer to a discrete and measurable characteristic like eye color. The term phenotype expands this definition to include multiple observable traits derived from diverse genetic factors (genotype) and to recognize additional roles for the environment in shaping visible expression of a genetically defined trait. Pathological phenotypes, with their myriad signs, symptoms, diagnoses, and prognoses, are recognized as diseases and are most often associated with adverse clinical manifestations or need for medical or surgical intervention. See Article by Miller et al So where in this conceptual framework do we place LVNC? This is a well-debated topic1,2 and one that has been recently systematically and expertly reviewed in much greater depth than afforded by this editorial.1–4 Although LVNC has increasingly been recognized as a cardiomyopathy5—itself a term with clear disease connotations—mounting evidence now points to reclassification of LVNC as a distinct but not necessarily pathological phenotype. More specifically, the degree of compacted to noncompacted (NC) myocardium, by itself alone, does not seem to cause disease. Why phenotype rather than trait? Traits are considered to be genetically driven and not malleable by the environment. As defined above, genetics interacting with environment are best labeled as phenotype. Left ventricular (LV) morphology is not fixed for certain characteristics, including LV wall thickness or LV size. The former is well known to increase with severe hypertension or aortic stenosis, and the latter increases with volume overload from aortic insufficiency. With medical or surgical therapy, both conditions will regress. A similar paradigm has been observed with dilated cardiomyopathy—a disease phenotype associated with heart failure and arrhythmia for which the dilated or remodeled left ventricle will reverse remodel with appropriate medical therapy. Characteristics such …