The human heart has a tremendous capacity to change its size and shape in response to external stimuli.1 During embryonic development and the postnatal state, the heart grows via hyperplasia (increase in cell number) and hypertrophy (increase in individual cell size). In the adult heart the predominant form of growth is via cellular hypertrophy, although recent data suggest that cardiomyocyte replication and replenishment is possible in the adult myocardium.2,3 Growth signals that occur in the setting of postnatal maturation, pregnancy, and endurance exercise can lead to physiologic hypertrophy, a process where the heart grows with preservation of overall structure and function. In contrast, stimuli such as mechanical overload, ischemia, diabetes, and sarcomeric protein mutations can lead to pathologic hypertrophy, a process where growth is associated with abnormalities in cardiac geometry, performance, tissue architecture, and cellular function. From a clinical standpoint, physiologic hypertrophy has no adverse sequelae, whereas pathologic hypertrophy is associated with increased risk of heart failure, arrhythmias, and death. In addition to its capacity for growth, the heart can shrink its mass in response to mechanical unloading or physical inactivity in a process termed cardiac atrophy. These phenotypic profiles have a robust dynamic range that approaches 100% and thus highlight the remarkable plasticity of the adult heart (Fig. 7-1).4 The application of contemporary biologic approaches is progressively elucidating the cellular and molecular pathways that drive cardiac hypertrophy, atrophy, and altered cardiac function.1 Precise definition of these pathways forms the foundation for novel heart-failure therapies.
Relative roles of cardiomyocyte hypertrophy, hyperplasia, and apoptosis in physiologic and pathologic cardiac hypertrophy along with the functional differences between compensated hypertrophy and heart failure.
Cardiac growth during normal development (also referred to as cardiac eutrophy) includes fetal cardiogenesis, postnatal cardiac growth, and the modest additional increase in heart size that evolves during senescence. The earliest stage of cardiac growth in utero is governed by a genetically determined developmental program which can occur in the absence of contractile activity. Subsequent fashioning of the developing heart is determined by an intricate interplay between genetic programs and mechanical forces. The fetal four-chambered mammalian heart attains an adult structural configuration in the second trimester, but continues to enlarge to maintain circulatory support for the growing embryo and juvenile.5 In rodents and other experimental models, fetal myocardial growth is largely a consequence of increasing number of cardiomyocytes (hyperplasia) until shortly after birth, after which cell division gradually subsides and cardiac mass increases almost entirely through enlargement of cardiomyocytes (hypertrophy).6 When hyperplasia subsides, many cells undergo a final round of karyogenesis (nuclear division) without cytokinesis (cell division) thereby producing a mixture of mononucleate and binucleate cardiomyocytes. Growth of the left ventricle exceeds that of the right ventricle during the early postnatal period as the mammalian heart transitions ...