New concepts in the pathophysiology of heart failure: beneficial and deleterious interaction of endogenous haemodynamic and neurohormonal mechanisms.

During most of the last 50 years, physicians have viewed heart failure primarily as an oedematous disorder, in which fluid retention occurs because the heart cannot pump adequate quantities of blood to the kidneys. This conceptual model led to the successful utilization of diuretics for heart failure, but it failed to permit physicians to recognize that heart failure is a chronic progressive disorder that impairs both the quality and quantity of life, even when oedema is adequately controlled. To accommodate this new understanding, a new model has been developed, in which the development and progression of heart failure is viewed as resulting from the interplay of haemodynamic and neurohormonal mechanisms. Both mechanisms support the inotropic state of the heart following an injury to the myocardium, but when sustained for long periods, their ability to augment cardiac contractility wanes, and, instead, these same mechanisms act to enhance ventricular wall stress, thereby impairing ventricular performance. As the heart-failure state evolves, endogenous mechanisms that are normally activated to control wall stress become exhausted, and peripheral vasoconstriction and sodium retention develop. Unopposed activation of haemodynamic stresses and neurohormonal systems leads to further destruction of the myocardium and progression of the underlying disease. The acceptance of this haemodynamic-neurohormonal model has led to the development of vasodilators and neurohormonal antagonists that have been shown to be useful alone, or when added to diuretics, in the treatment of heart failure.