Classical inotropes and new cardiac enhancers

Abstract

Acute heat failure syndromes are a heterogenous group of conditions. Chronic heart failure exacerbations represent the vast majority of cases. Pathophysiologic mechanisms, such as hypotension with peripheral tissue hypoperfusion, renal function impairment and myocardial ischemia and injury, adversely affect patients' clinical outcome. Classical inotropes, such as beta-agonists (dobutamine, dopamine) and phosphodiesterase inhibitors (milrinone), seem to improve clinical symptoms and hemodynamics of acutely decompensated chronic heat failure patients, but they have been associated with increased long-term mortality. Thus, on the basis of the available evidence, these agents can be used only as a temporary treatment of acute heart failure exacerbations with stringent criteria (ESC AHF guidelines), resistant to intravenous vasodilators and/or diuretics when systolic blood pressure (SBP) is >100 mmHg or as a first-line treatment in patients with worsening of chronic cardiac failure and low SBP (<100 mmHg). The calcium sensitizer levosimendan is a new cardiac enhancer that seems to be more effective than classical inotropes in improving cardiac mechanical efficiency and reducing congestion, without causing cardiomyocyte death or increasing myocardial oxygen uptake. Recent randomized trials showed that levosimendan is not superior to placebo or dobutamine in improving 1- and 6-month mortality, although it caused a greater reduction of neurohormonal response. More data are needed regarding patient selection and the optimum regimen and dosing of levosimendan before this treatment modality become the first line therapy of acutely decompensated chronic heart failure patients.

A prospective study of drug utilization pattern in cardiac intensive care unit at a tertiary care teaching hospital

“…11,12 In our study, Dopamine 12 (85.7%) was the most common inotropic drug administered, followed by dobutamine 2 (14.3%).…”

Istaroxime: Is the Remedy Better than the Disease?

“…In addition, an improvement of coronary flow reserve was also documented [19]. These two latter findings are of particular importance given the fact that two main drawbacks of classical inotropes are the detrimental effects of sympathetic activation, including tachycardia and arrhythmogenesis, as well as the myocardial ischemia resulting from the increase of myocardial oxygen demand [5]. Therefore, both drawbacks that may largely be responsible for the negative effects of inotropes on long-term outcome, seem to be adequately addressed by istaroxime at least in the experimental field.…”

“…The currently available inotropic agents, including betaadrenergic agonists, phosphodiesterase-III inhibitors and calcium sensitizers, although they lead to a short-term hemodynamic and symptomatic improvement, they are followed by a neutral or even adverse long-term outcome [5,6]. Beta-adrenergic agonists, such as dobutamine, enhance cardiac contractility at the expense of increased myocardial oxygen demand, and therefore may lead to exacerbation of underlying myocardial ischemia, while, at the same time, cause cardiomyocyte calcium overload and increases the risk of arrhythmogenesis, leading to increased mortality [5,7,8].…”

“…Beta-adrenergic agonists, such as dobutamine, enhance cardiac contractility at the expense of increased myocardial oxygen demand, and therefore may lead to exacerbation of underlying myocardial ischemia, while, at the same time, cause cardiomyocyte calcium overload and increases the risk of arrhythmogenesis, leading to increased mortality [5,7,8]. Phosphodiesterase-III inhibitors, on the other hand, may also induce arrhythmias as well as hypotensive episodes and thus adverse clinical outcomes [9,10].…”

Prognosis on Chronic Dobutamine or Milrinone Infusions for Stage D Heart Failure

“…2 Dobutamine and milrinone are the 2 most commonly used intravenous inotropes in the United States. These medications have significantly differing pharmacological properties, 3 cost, 2 and short-term clinical response, 4 though it is unknown if they have differing mortality outcomes. Therefore, we sought to examine the rate of all-cause mortality among patients with stage D HF who were discharged on intravenous dobutamine versus milrinone infusion, while adjusting for demographic, clinical, and laboratory measures.…”