[How and to what extent has beta-blocker treatment been established for chronic heart failure?]

Over the past 20 years, the concept of chronic heart failure has changed. The activation of neurohumoral system is important in worsening the chronic heart failure. Therefore, it is reasonable to block the effect of the renin-angiotensin system and sympathetic nervous system on the heart for treatment of heart failure. Many studies have demonstrated that angiotensin converting enzyme (ACE) inhibitors reduce the level of angiotensin II and plasma norepinephrine, and improve long-term hemodynamics and survival in patients with chronic heart failure. However, despite the wide use of ACE inhibitors, the prognosis of chronic heart failure remains poor. Although beta-blockers can block the effect of sympathetic nervous system activity, these agents had not been used for the treatment of chronic heart failure because of its negative inotropic action. In 1975, Waagstein and associates described functional improvement in seven patients receiving beta-blockers. Subsequently, many workers have examined the therapeutic efficacy of beta-blockers in the treatment of chronic heart failure. Eleven studies reported the long-term effect of beta 1-selective beta-blocker without intrinsic sympathetic activity including metoprolol and bisoprolol, and 14 studies were performed using beta-blockers with vasodilator properties including bucindolol and carvedilol. These studies predominantly included patients with dilated cardiomyopathy, although some also included patients with ischemic heart disease. Most but not all of these studies showed beneficial effects on symptoms, hemodynamics and morbidity in both dilated cardiomyopathy and ischemic heart disease. Vasodilating beta-blockers may provide an additional useful effect compared to beta-blockers without vasodilator properties. However, direct comparisons between beta-blockers with and without vasodilator properties on clinical efficacy have not yet been made. The effect of beta-blockers on survival was investigated in five controlled trials. Although these studies suggested a beneficial effect of beta-blockers on survival in chronic heart failure, the effect has not yet been conclusively determined especially in patients with chronic heart failure due to ischemic heart disease. Some investigators are proposing the use of beta-blockers in chronic heart failure to ameliorate the harmful effect of excess sympathetic stimulation, but the exact mechanisms of beta-blockers are uncertain. Although a large number of studies have demonstrated the usefulness of beta-blocker treatment for chronic heart failure, many unsolved problems such as the exact mechanisms of beneficial effect, usefulness for ischemic heart disease, and the optimal agent and dose for treatment remain. Further studies are needed to establish this treatment.