Treatment of heart failure: state of the art and prospectives.

Heart failure is unique among the major cardiovascular disorders in that it alone is increasing in prevalence while there has been a striking decrease in other conditions. Some of this can be attributed to the aging of the U.S. and European populations. The ability to salvage patients with myocardial damage is also a major factor, as these patients may develop progression of left ventricular dysfunction due to deleterious remodelling of the heart. This process involves structural and conformational changes in the heart characterized by pathological hypertrophy and fibrosis. The net effect is deterioration in cardiac function and the onset of heart failure. Neurohormonal activation is known to be a major factor in promoting cardiac remodelling. Increased neurohormone levels systemically and within the heart lead to increased load on the heart. Many neurohormones involved also directly act as growth factors on cardiac myocytes and fibroblasts. Due to its central role in remodelling, neurohormonal activation has emerged as an inviting target for therapeutic interventions. The use of agents to block the renin-angiotensin-aldosterone and sympathetic nervous systems has been shown to inhibit (and sometimes even reverse) cardiac remodelling and to improve the clinical course of patients with cardiac dysfunction. Neurohormonal activation is known to be widespread and there is evidence that additional agents such as endothelin and tumour necrosis factor-alpha (TNFalpha) may be involved in the remodelling process. Clinical trials evaluating the effects of blocking these agents are currently under way and should soon provide important information about therapy.