The Influence of Beta Blocker Therapy on the Hemodynamic Response to Inotrope Infusion in Patients With Acute Decompensated Heart Failure

Background:

First-line management of chronic heart failure includes beta blockers and angiotensin converting enzyme (ACE) inhibitors, as these agents have been shown to have significant benefits on morbidity and mortality in large clinical trials. Therefore, a substantial number of patients with chronic heart failure are receiving chronic beta blocker therapy, most commonly metoprolol succinate and carvedilol. However, despite significant advancements in the treatment of chronic heart failure, the natural history of the disease remains progressive and many patients develop acute decompensations requiring hospitalization. In the setting of acute decompensated heart failure, the use of inotropic agents may be required for hemodynamic support. The two most widely used inotropes are dobutamine and milrinone. Dobutamine primarily acts as a beta-1 receptor agonist with some effects on beta-2 and alpha-1 receptors. Milrinone is a phosphodiesterase III inhibitor, thus inhibiting the breakdown of cyclic adenosine monophosphate. As such, milrinone works at a site that is distal to beta receptors and may be less influenced by chronic beta blocker therapy. As such, one may speculate that the presence of a beta blocker would influence the hemodynamic response to dobutamine, but to a much lesser extent to milrinone, if at all.

Two small studies have assessed the hemodynamic response to dobutamine in the presence and absence of beta blocker therapy in patients with chronic heart failure. In addition, one of these studies assessed the response to enoximone, another phosphodiesterase III inhibitor. Both studies demonstrated that metoprolol did not significantly affect the hemodynamic response to dobutamine infusion, including its effect on cardiac index, heart rate, stroke volume, and systemic vascular resistance. Conversely, carvedilol was shown to have significant inhibitory effects on cardiac index, heart rate, and stroke volume during dobutamine infusion. In addition, carvedilol appeared to increase mean arterial pressure at higher doses of dobutamine. In the setting of an enoximone infusion, metoprolol increased the cardiac index and stroke volume responses, while maintaining other hemodynamic parameters. There was no significant difference in the hemodynamic response to enoximone infusion in the presence of carvedilol.

Why This Study is Needed:

Published studies that assessed the hemodynamic response to inotropes in the presence and absence of beta blockers included less than 50 patients combined. As such, the replication of their results is warranted in order to use this data to drive changes in clinical practice. Additionally, and equally as important, no study has been published, to the best of our knowledge, which has assessed the hemodynamic response to milrinone in the presence of metoprolol. . Although enoximone is a phosphodiesterase III inhibitor and is theoretically similar to milrinone, it is not approved for use in the United States, thus making it difficult to extrapolate these findings to milrinone. Lastly, the severity of illness in patients included in current literature does not reflect individuals who will receive the most benefit from therapy i.e. patients with acute decompensated heart failure.