Is Load-Induced Ventricular Hypertrophy Ever Compensatory?

Abstract

When muscle is subjected to increased workload, it grows by means of a cellular process called hypertrophy. When one lifts weights, skeletal muscle hypertrophies in a manner that increases muscle strength and work capacity. When cardiac muscle is exposed to increased workload demand, it, too, hypertrophies. When the increase in workload stems from physiological stress such as exercise, the now hypertrophied myocardium is strengthened. Similarly, when the heart “lifts weights” as a result of increased afterload (eg, hypertension, aortic stenosis), it hypertrophies. However, considerable evidence suggests that this hypertrophied heart is weaker, not stronger. Furthermore, a large body of preclinical evidence points to the fact that this afterload-triggered heart growth is not required to maintain ventricular size and contractile performance even in the face of persistently increased load. This fact, which has yet to be tested in large animals, begs the question of the concept of compensatory hypertrophy, an issue we explore here. It is important to emphasize that we are referring exclusively to disease stress-triggered heart growth, not the unequivocally beneficial myocardial hypertrophy that occurs with exercise. In the 1890s, Woods1 proposed that the left ventricle (LV) could be modeled according to the law of Laplace. Whereas it was apparent from the outset that the LV violates the first principle assumptions of the law, including spherical shape and homogeneous wall characteristics, a simplified model emerged in which wall stress is directly proportional to LV pressure and radius and inversely proportional to wall thickness. Today, this represents the simplest model proposed …