Effects of neurohormonal antagonism on symptoms and quality-of-life in heart failure

Increased mortality and reduced functional capacity are the two main characteristics of chronic heart failure. Activation of the renin-angiotensin and sympathetic systems has a primary role in the progressive worsening of heart failure and increased mortality of patients. In addition, both systems may be important in the pathogenesis of exercise intolerance, although there is only a weak relationship between neurohormonal activation and exercise capacity. While neurohormonal antagonists, such as angiotensin-converting enzyme (ACE) inhibitors and beta-blockers, consistently improve the prognosis of patients with heart failure, their effects on exercise tolerance have often been less significant. This problem has been emphasized by the introduction of beta-blockers for the therapy of heart failure. Beta blockade results in a significant improvement in left ventricular function during rest and exercise. However, the reduction in chronotropic response to exercise as well as the metabolic changes caused by these agents in skeletal muscle may result in an apparent lack of change in maximal functional capacity. This effect is particularly important with the new third generation non-selective beta-blockers. The pronounced anti-adrenergic activity of these compounds accounts for their greater negative chronotropic effect and relates to the lack of improvement in peak oxygen consumption (VO2). Submaximal exercise testing can be used to assess changes induced by these agents. However, even the six-minute walk test may act as an almost maximal test in patients with advanced heart failure: moreover, the measurement of submaximal exercise duration may be sensitive enough to detect changes in single-centre trials, but not in multicentre trials. To date, direct assessment of symptoms by both patient and physician is still the most sensitive tool to monitor changes in functional status with non-selective beta-blockers. Thus, an accurate method of measuring patients' symptoms, in addition to the clinical examination, is still necessary when neurohormonal antagonists are used in patients with chronic heart failur