Book excerpt: The progression of heart disease is associated with changes in the neurohumoral mechanisms that control cardiac function. The degree to which this neurohumoral remodeling occurs, even before overt signs of cardiac disease become manifest, is important for prognosis. To determine why some patients experience sudden death while others sustain life in the presence of severely compromised cardiac function, the neuronal control of cardiac electrical and mechanical events must be considered. Starting at the level of individual neurons and building upwards, this book describes the synergistic interactions that occur among intrathoracic and CNS feedback loops to permit precise control of regional cardiac behavior. On this basic science foundation, subsequent clinical chapters explore the remodeling that occurs in this system with aging, with the evolution of specific cardiac pathologies, and with the psychological concomitants of heart disease. Most importantly, these chapters provide unique insights into how specific therapies like beta-andrenergic receptor blockade not only affect cardiomyocytes directly but also mitigate the adverse neurohumoral changes that accompany disease processes, such as heart failure and essential hypertension. The paradigm advanced in this volume is that heart disease is a multifaceted phenomenon involving the interplay of neurohumoral, cardiomyocyte and structural elements, each of which depends on the other. With our cumulative understanding of these interdependent processes, new avenues for time-appropriate, targeted methods of treating heart diseases can be developed.