Inotropes and beta-blockers: is there a need for new guidelines?

Beta-adrenergic blocking agents are standard treatment for patients with mild-to-moderate heart failure. When patients receiving beta-blockers decompensate they often need treatment with a positive inotropic agent. The beta-agonist dobutamine may not produce much increase in cardiac output during full-dose beta-blocker treatment and may increase systemic vascular resistance via alpha-adrenergic stimulation. In contrast, phosphodiesterase inhibitors (PDEIs) such as milrinone or enoximone retain full hemodynamic effects during complete beta-blockade because the site of action of PDEIs is beyond the beta-adrenergic receptor and because beta-blockade reverses some of the desensitization phenomena that account for the attenuation of PDEI response in heart failure related to upregulation in G(alphai). Inotrope-requiring subjects with decompensated heart failure who are undergoing long-term therapy with beta-blocking agents should be treated with a type III-specific PDEI, not a beta-agonist such as dobutamine.