EFFECTS OF NEUROHORMONAL ANTAGONISM ON SYMPTOMS AND QUALITY-OF-LIFE IN HEART-FAILURE

Increased mortality and reduced functional capacity are the two main c haracteristics of chronic heart failure. Activation of the renin-angio tensin and sympathetic systems has a primary role in the progressive w orsening of heart failure and increased mortality of patients. In addi tion, both systems may be important in the pathogenesis of exercise in tolerance, although there is only a weak relationship between neurohor monal activation and exercise capacity. While neurohormonal antagonist s, such as angiotensin-converting enzyme (ACE) inhibitors and beta-blo ckers, consistently improve the prognosis of patients with heart failu re, their effects on exercise tolerance have often been less significa nt. This problem has been emphasized by the introduction of beta-block ers for the therapy of heart failure. Beta blockade results in a signi ficant improvement in left ventricular function during rest and exerci se. However, the reduction in chronotropic response to exercise as wel l as the metabolic changes caused by these agents in skeletal muscle m ay 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 o f these compounds accounts for their greater negative chronotropic eff ect and relates to the lack of improvement in peak oxygen consumption (VO2).Submaximal exercise testing can be used to assess changes induce d by these agents. However, even the six-minute walk test may act as a n almost maximal test in patients with advanced heart failure: moreove r, the measurement of submaximal exercise duration may be sensitive en ough to detect changes in singIe-centre trials, but not in multicentre trials. To date, direct assessment of symptoms by both patient and ph ysician is still the most sensitive tool to monitor changes in functio nal status with non-selective beta-blockers. Thus, an accurate method of measuring patients' symptoms, in addition to the clinical examinati on, is still necessary when neurohormonal antagonists are used in pati ents with chronic heart failure.