Phenotyping hypertrophy: eschew obfuscation.

Abstract

Everyone thinks they know what “cardiac hypertrophy” is: a reactive increase in cardiac size/myocardial mass in response to hemodynamic stress that, in humans, predisposes to early death.1 Yet, the term “hypertrophy” has become one of the most misused and inaccurate terms in the cardiovascular basic science literature because of its nonspecificity and, as typically used, lack of mechanistic implication. “Hypertrophy” (noun and verb), derived from Greek hyper (above, more than normal) and trophe (nutrition), is defined as “the enlargement or overgrowth of an organ or part due to an increase in size of its constitute cells.”2 The normal heart is “normal,” and hypertrophy is, by definition, “not normal.” Therefore, normal maturational development at the organ level is not “hypertrophy” (verb) and does not result in cardiac “hypertrophy” (noun), although the cells do “hypertrophy” (verb). (Perhaps the term “eutrophy” is more appropriate to describe maturational development.) Likewise, in many genetic in vivo experimental models, the term “cardiac hypertrophy” has too often been loosely applied to any observed cardiac enlargement, frequently with such modifiers as “physiological” or “pathological.”3 Herein, we reflect on the appropriate meanings of terms and criteria that can be used to more accurately describe cardiac enlargement and myocardial growth, with the anticipation that rigorous mechanistic description of such phenotypes will result in a more coherent appreciation of the parallel and redundant processes that result in “myocardial hypertrophy.” The widespread use of the term “hypertrophy” to describe one or a few specific pathophysiological conditions is a holdover from the earliest scientific work on cardiac response to stress, in which cardiac enlargement was largely assumed to be the result of increased cardiomyocyte size and was qualitatively predictable based on the nature of the provocative stimulus.4 Hence, morphogenic changes in the heart were classified by the nature of …