We have developed a novel automated drug delivery system for simultaneous control of systemic arterial pressure (AP), cardiac output (CO), and left atrial pressure (P(LA)) in acute heart failure. The circulatory equilibrium framework we established previously discloses that AP, CO, and P(LA) are determined by equilibrium of the mechanical properties of the circulation, i.e. pumping ability of the left heart, stressed blood volume and systemic arterial resistance. Our system directly controls the three mechanical properties with cardiovascular drugs including inotropes and vasodilators, thereby controlling AP, CO, and P(LA). Furthermore, by precisely controlling bradycardia and LV inotropy, our system enables to improve cardiac energetic efficiency while preserving AP, CO, and P(LA) within acceptable ranges. In conclusion, by directly controlling the mechanical properties of the heart and vessel, our automated system realizes comprehensive management of hemodynamics in acute heart failure.