The clinical significance of neurohormonal activation.

Progressive heart disease after the onset of left ventricular dysfunction has typically been attributed to hemodynamic factors. As left ventricular function declines, decreased cardiac output and tissue hypoperfusion lead to compensatory increases in afterload, preload, and heart rate. The purpose of these compensatory responses is to increase cardiac output and maintain tissue perfusion; however, they may also create hemodynamic stress for the failing heart. However, this does not explain the progression of heart failure despite hemodynamic maintenance with pharmacologic therapy. Activation of neurohormonal systems that are essential for homeostasis in the normal heart plays a key role in the progression of heart failure. In acute heart failure, these systems have beneficial effects, but in chronic heart failure their activation produces deleterious effects by increasing the load on the left ventricle and promoting structural remodeling, which may further impair left ventricular function. The issue of neurohormonal activation is an important one in cardiovascular medicine, not only for patients with heart failure but also for patients with hypertension and ischemic heart disease when left ventricular dysfunction is present. As neurohormonal activation may play a pathogenic role in the long-term outcome of patients, interventions that have favorable hemodynamic but unfavorable neurohormonal effects can actually exacerbate cardiac disease and may increase cardiovascular morbidity and mortality. As neurohormonal activation appears to parallel the severity of heart failure, whether assessed according to symptoms or prognosis, an understanding of neurohormonal activation and its interaction with hemodynamic factors is essential for optimizing pharmacologic therapy for cardiovascular disease.