Heart failure is a world-wide public health problem that affects 4.5 million patients in the United States, necessitates one million hospitalizations each year, and causes 300,000 deaths annually (reviewed in Cohn et al., 1997). Estimates of the annual healthcare expenditure on heart failure exceed $17 billion, costs that are expected to increase as the US population ages. Heart failure is a complex pathophysiologic condition that arises when myocardial performance is insufficient to adequately supply blood to other organs. This syndrome is a common complication that ensues from a wide variety of cardiovascular pathologies including coronary artery atherosclerosis, cardiomyopathy, valvular heart disease, or congenital malformations.

The failing human heart differs from normal in structure as well as in function. The normal heart is an efficient muscle that is exquisitely designed to serve both as pump and integrator of two independent vascular systems, the pulmonary and systemic circulations. Two thin-walled atria function as reservoirs for returning blood. In diastole (cardiac relaxation), blood from the atria enters the muscular ventricular chambers with little impedance. During cardiac contraction (systole), the right ventricle propels blood into the low-pressure pulmonary vascular beds where gaseous diffusion occurs, while the left ventricle ejects equivalent volumes throughout the much larger sized and greater resistance vessels of the systemic circulation. Commensurate with vascular load and resistance, the normal muscle mass of the left ventricle is greater than that of the right ventricle.