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Inotropic agents in heart failure with reduced ejection fraction

Wilson S Colucci, MD
Section Editor
Stephen S Gottlieb, MD
Deputy Editor
Susan B Yeon, MD, JD, FACC


The positive inotropic agents, including digoxin, inamrinone (formerly known as amrinone), milrinone, and the beta adrenergic receptor agonists (table 1), have beneficial hemodynamic effects in patients with heart failure with reduced ejection fraction (HFrEF; also known as systolic HF) due primarily to a direct increase in cardiac output and, to a lesser extent, the ensuing reduction in neurohumoral activation, which causes an unloading of the heart via a reduction in the plasma levels of vasoconstrictors such as angiotensin II and norepinephrine. Inamrinone and milrinone also exert direct arterial and venous dilator actions that contribute to the overall hemodynamic effects of these drugs. Inotropic therapy is of potential value only in patients with decreased cardiac contractility. Those with HF with preserved ejection fraction (also known as diastolic HF) do not need inotropic support.

The efficacy of acute intravenous inotropic support is well established in patients with severe myocardial systolic dysfunction. However, the benefit of chronic administration of oral inotropic agents in ambulatory patients, with the exception of digoxin, remains unproven. On the contrary, available data suggest that the chronic use of many of these drugs may increase mortality. Digoxin is the only oral positive inotropic agent available for long-term ambulatory use.

An overview of therapy of HFrEF is presented separately. (See "Overview of the therapy of heart failure with reduced ejection fraction".)


Digoxin is the only safe and effective oral positive inotropic agent. Data supporting the efficacy of digoxin therapy in patients with heart failure (HF) with reduced ejection fraction are presented in detail elsewhere. An important finding is that the safety of digoxin is related to the serum digoxin level (figure 1) [1,2]. In addition to symptomatic benefit [3], digoxin appears to be safe at optimal serum concentrations of 0.5 to 0.8 ng/mL in men and 0.5 to 0.9 ng/mL in women, but to reduce survival at concentrations ≥1.2 ng/mL in both sexes (figure 1) [1,2]. It should also be recognized that digoxin has other actions, most importantly to modify autonomic tone, that may be as important, or even more important, than its effects on myocardial contractility in determining the drug's clinical effects during chronic administration. (See "Use of digoxin in heart failure with reduced ejection fraction".)

Use of digoxin is discussed separately. Our approach is consistent with the 2013 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guideline suggestion that digoxin may be considered for symptom relief in patients with left ventricular systolic dysfunction with symptoms of HF to reduce hospitalization [4].

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Literature review current through: Nov 2017. | This topic last updated: Nov 25, 2016.
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