Therapeutic strategies and neurohormonal control in heart failure.

Neurohormonal activation is one of the major determining factors in the process of transition from asymptomatic ventricular dysfunction to end-stage heart failure, in the prognosis of heart failure, and in the efficacy and, hence, choice and timing of pharmacological therapy. Although various counteracting hormonal systems are involved, emphasis in terms of functionality is on vasopressor and growth-promoting systems. In contrast, ANF and N-terminal proANF probably have a significant prognostic value, even at an early stage. The focus of heart failure therapy is moving from measures aimed at improving cardiac function to ones that concentrate on modulating neuroendocrine changes during failure and their effects on intrinsic peripheral and cardiac alterations. Although ACE inhibition undoubtedly constitutes a major step forward in this approach, alternative ways to modulate neurohormonal activation pharmacologically are needed. Several such novel approaches are being developed, including angiotensin receptor antagonists, dopaminergic stimulation, neutral endopeptidase inhibition, aldosterone antagonism and beta blockade. In addition to their positive inotropic properties digitalis glycosides may act as neurohormonal modulators. Finally, the realization that several well-established forms of heart failure therapy may aggravate neuroendocrine stimulation demands careful consideration as to whether such agents are really necessary, and underlines the desirability of co-administering neurohormonal modulating therapy.