What is the role of Levosimendan (levosimendan) in treating acutely decompensated heart failure?

From the Guidelines

Levosimendan is a recommended treatment option for acutely decompensated heart failure, particularly in patients with reduced ejection fraction who are not responding adequately to standard therapies, due to its unique mechanism of action and potential benefits in improving cardiac output and reducing morbidity and mortality. The use of levosimendan in this context is supported by studies such as those published in the European Journal of Heart Failure 1 and the European Heart Journal 1, which highlight its efficacy and safety profile. Some key points to consider when using levosimendan include:

• It is typically administered as an intravenous infusion, starting with a loading dose of 3-12 mcg/kg over 10 minutes, followed by a continuous infusion of 0.05-0.2 mcg/kg/min for 24 hours 1.
• Levosimendan increases myocardial contractility without significantly increasing oxygen consumption or arrhythmia risk, making it a valuable alternative to traditional inotropes such as dobutamine or milrinone 1.
• The drug has a long-acting active metabolite providing hemodynamic effects for up to 7-9 days after a 24-hour infusion, which can be beneficial in patients with prolonged periods of decompensation 1.
• Levosimendan should be used cautiously in patients with hypotension (systolic BP <90 mmHg) or severe renal impairment, and is not recommended for patients with severe aortic or mitral stenosis 1. Overall, the available evidence suggests that levosimendan can be a useful addition to the treatment arsenal for acutely decompensated heart failure, particularly in patients who are not responding to standard therapies.

From the Research

Role of Levosimendan in Treating Acutely Decompensated Heart Failure

• Levosimendan is a calcium-sensitising drug that stabilises the troponin molecule in cardiac muscle, thus prolonging its effects on contractile proteins, with concomitant vasodilating properties 2.
• It is approved for the short-term treatment of acute severe decompensated heart failure, with a recommended dosage of 12-24 microg/kg loading dose followed by 0.1-0.2 microg/kg/min for 24 hours, adjusted for response and tolerability 2.
• Studies have shown that levosimendan is effective in increasing cardiac output and decreasing pulmonary capillary wedge pressure and systemic vascular resistance in patients with decompensated heart failure 2, 3.
• Compared to dobutamine, levosimendan has been shown to have similar or superior efficacy in terms of haemodynamic response, mortality, and morbidity 2, 3, 4, 5.

Haemodynamic Effects of Levosimendan

• Levosimendan increases myocardial contractility and dilates both the peripheral and coronary vessels 3.
• It acts as an opener of ATP-dependent potassium channels in vascular smooth muscle, thus inducing vasodilation 3.
• The drug has a positive inotropic effect based on calcium-dependent binding of the drug to cardiac troponin C 3.

Clinical Applications and Recommendations

• Levosimendan can be a valuable resource in the treatment of acute cardiac dysfunction, especially in the presence of beta-blockers or ischemic cardiomyopathy 6.
• The drug may be preferable to milrinone for patients in cardiogenic shock after cardiac surgery or for weaning from extracorporeal life support 6.
• Early use of levosimendan in the treatment algorithm is preferred, with attention given to avoiding or correcting hypovolemia and hypokalemia 6.

Comparison with Other Inotropes

• Levosimendan has been shown to have favourable effects on symptoms of heart failure superior to placebo and at least comparable to dobutamine 2, 3.
• The drug may be associated with reduced mortality compared with both placebo and dobutamine 2, 3, 5.
• Levosimendan has been shown to improve renal function in patients with acute decompensated heart failure, compared to dobutamine 4.