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stabilizes. In such patients, positive inotropic agents, whose effects are mediated independently of the beta-receptor (e.g., a phosphodiesterase inhibitor such as milrinone) may be preferred. Once stabilized, the beta-blocker should be reintroduced to reduce the subsequent risk of clinical deterioration.

Risks of treatment

Initiation of treatment with a beta-blocker may lead to adverse reactions requiring attention and management.

Initiation of therapy with a beta-blocker can cause fluid retention, which is usually asymptomatic, being primarily detected by an increase in body weight, but occasionally may become sufficiently marked to worsen the symptoms of HF78. Patients with fluid retention before treatment are at greatest risk of fluid retention during treatment, and thus, physicians should ensure that patients are not volume overloaded before a beta-blocker is initiated. Furthermore, physicians should monitor patients closely for increases in weight and for worsening signs and symptoms of HF and should augment the dose of diuretic if weight increases whether or not other signs or symptoms of worsening HF are present. The occurrence of fluid retention or worsening HF is not generally a reason for the permanent withdrawal of treatment. Such patients generally respond favorably to intensification of conventional therapy, and once treated, such patients remain excellent candidates for long-term treatment with a beta-blocker.

Treatment with a beta-blocker can be accompanied by feelings of general fatigue or weakness. In many cases, the sense of lassitude resolves spontaneously within several weeks without treatment, but in some patients, it may be severe enough to limit increments in dose or require the withdrawal of treatment. Complaints of fatigue can generally be managed by a reduction in the dose of the beta-blocker (or the accompanying diuretic), but treatment should be discontinued if the syndrome of weakness is accompanied by evidence of peripheral hypoperfusion.

The slowing of heart rate and cardiac conduction produced by beta-blockers is generally asymptomatic and thus generally requires no treatment. However, if the bradycardia is accompanied by dizziness or lightheadedness or if second- or third-degree heart block occurs, physicians should decrease the dose of the beta-blocker. Physicians should also consider the possibility of the pharmacological interaction with other drug, which, being capable of inducing in their turn bradycardia or heart block, should be discontinued first. In selected patients developing symptomatic bradycardia or cardiac blocks despite the low doses of beta-blockers, the benefits of beta-blocker administration may be sufficiently important to consider cardiac pacing (implantation of a pacemaker).

Beta-blockers, especially those that also block alpha-1-receptors, such as carvedilol, can produce hypotension, which is usually asymptomatic, but may produce dizziness,

78 Effects of metoprolol CR in patients with ischemic and dilated cardiomyopathy: the randomized evaluation of strategies for left ventricular dysfunction pilot study. Circulation 2000;101:378-84.

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