BASIC DETERMINANTS OF MYOCARDIAL HYPERTROPHY: A Review of Molecular Mechanisms¹

The essential cardiac response to a fixed increase in hemodynamic load is an increase in cardiac mass. If the load increase is neither too severe initially nor indefinitely progressive, cardiac stress is renormalized, and compensated hypertrophy ensues. But hypertrophic compensation is often abrogated by progressively abnormal contractile performance per unit mass of myocardium, even when function at the organ level is maintained by the mass increase itself. That is, even when hypertrophy is appropriate to the load imposed, and in a manner analogous to dystrophic growth of skeletal muscle, specific phenotypic changes occurring during this growth response render compensation imperfect such that congestive heart failure ensues. This fact, and the fact that the presence of deleterious phenotypic changes in hypertrophied myocardium is critically dependent on the type of hemodynamic load imposed, mandates that cardiac hypertrophy be understood on the most basic level as a growth process if early, definitive interventions to prevent congestive heart failure following pathological hemodynamic overloads are to be realized.