Digitalis-like steroids and related agents have been a mainstay in the treatment of congestive heart failure ever since the publication, in 1785, of Withering’s seminal monograph on foxglove. Heart failure refers to the clinical syndrome that results when the heart is unable to pump sufficient blood to keep up with the metabolic demands of the body. Congestive heart failure is characterized by excessive neuronal and hormonal-mediated fluid retention, expanded intravascular volume, high pulmonary and systemic venous pressures with consequent dyspnea (shortness of breath) on exertion, reduced exercise tolerance, and fatigue. Most heart failure patients also have impaired ventricular systolic function and depressed cardiac output; these are the patients most often treated with digitalis glycosides. These drugs are positive inotropic agents and enhance cardiac contraction. The “cardiotonic steroids” cause cardiac muscle to lose K+ and gain Na+ because they inhibit the Na+ pump (Na+,K+–ATPase), a plasma membrane protein, present in all cells. The Na+ pump uses the energy from ATP to extrude Na+ and …