Inotropes in the beta-blocker era

Beta-adrenergic blocking agents are now standard treatment for mild to mode rate chronic heart failure (CHF). However, although many subjects improve o n beta blockade, others do not, and some may even deteriorate. Even when su bjects improve on beta blockade, they may subsequently decompensate and nee d acute treatment with a positive inotropic agent. In the presence of full beta blockade, a beta agonist such as dobutamine may have to be administere d at very high (> 10 mu g/kg/min) doses to increase cardiac output, and the se doses may increase afterload. In contrast, phosphodiesterase inhibitors (PDEIs) such as milrinone or enoximone retain their full hemodynamic effect s in the face of beta blockade. This is because the site of PDEI action is beyond the beta-adrenergic receptor, and because beta blockade reverses rec eptor pathway desensitization changes, which are detrimental to PDEI respon se. Moreover, when the combination of a PDEI and a beta-blocking agent is a dministered long term in CHF their respective efficacies are additive and t heir adverse effects subtractive. The PDEI is administered first to increas e the tolerability of beta-blocker initiation by counteracting the myocardi al depressant effect of adrenergic withdrawal. With this combination, the s ignature effects of beta blockade (a substantial decrease in heart rate and an increase in left ventricular ejection fraction) are observed, the hemod ynamic support conferred by the PDEI appears to be sustained, and clinical results are promising. However, large-scale placebo-controlled studies with PDEIs and beta blockers are needed to confirm these results.