Inhibition of hypertrophy, per se, may not be a good therapeutic strategy in ventricular pressure overload: other approaches could be more beneficial.

Abstract

Cardiac hypertrophy was initially defined by a directly observed increase in cardiac mass that was then assumed to be mainly linked to an increase in cardiomyocyte mass. When submitted to a physiological or pathological stress, the heart undergoes a process of remodeling that involves cardiomyocyte growth but also changes in other cell types: changes in intracellular and extracellular structure, protein expression, signaling pathways, energy metabolism, vascularization, and so forth. Although hypertrophy is only one manifestation of the multiparameter remodeling of the myocardium, progressively, this term has, by oversimplification, included all others aspects of the cardiac response to stress. Classically, hypertrophy induced by pressure overload was considered as adaptive via a decreased stress allowed by a thicker myocardium. The currently accepted concept is that of pathological hypertrophy with depressed ventricular function that leads to heart failure, as opposed to physiological hypertrophy induced by exercise, for example. In this view, hypertrophy development should be prevented during pressure overload. This was proposed 10 years ago in an editorial in Circulation .1 A large number of experimental studies have been published since then, and it appears that an evaluation of the results is necessary. Response by Schiattarella and Hill on p 1457 Many studies showed a beneficial effect of hypertrophy blockade. However, some studies showed the opposite. Before reviewing them in detail, we rapidly present the evolution over time of the concept of adaptive hypertrophy that varied during the last 30 years. This reminds us of some important elements of the previous facts and interpretations that were forgotten as new ones appeared. This also allows understanding of why inhibition of hypertrophy, per se, may not be the best therapeutic strategy in the management of pressure overload–induced hypertrophy. One of the first complete reports of the initiation and evolution of the hypertrophic process toward …