What is Levosimendan?

From the Guidelines

Levosimendan is a calcium sensitizer medication that improves cardiac contractility by increasing the sensitivity of cardiac muscle to calcium, making it a valuable treatment option for acute decompensated heart failure. According to the most recent and highest quality study available, levosimendan works by binding to troponin-C in cardiomyocytes, exerting significant vasodilatation mediated through ATP-sensitive potassium channels, and having mild PDE inhibitory action 1.

Key Characteristics of Levosimendan

• Improves cardiac contractility without significantly increasing oxygen consumption
• Does not raise intracellular calcium levels, reducing the risk of arrhythmias
• Has vasodilatory effects through opening potassium channels in vascular smooth muscle
• Reduces both preload and afterload, improving cardiac output and decreasing pulmonary congestion
• Common side effects include headache, hypotension, and arrhythmias
• Has a long-acting active metabolite that provides hemodynamic effects for several days after discontinuation of the infusion

Administration and Dosage

• Typically administered as an intravenous infusion
• Usually starts with a loading dose of 6-12 mcg/kg over 10 minutes, followed by a continuous infusion of 0.05-0.2 mcg/kg/min for 24 hours
• May be particularly beneficial in patients with heart failure who are also on beta-blockers, as its mechanism of action doesn't rely on beta-adrenergic stimulation 1

Clinical Benefits

• Decreases the time to extubation compared to milrinone
• Decreases the incidence of postoperative atrial fibrillation and myocardial infarction, ICU length of stay, acute renal dysfunction, ventricular arrhythmias, and mortality in the treatment of postoperative LV dysfunction 1
• Shows little change in MVO2 and improves early heart relaxation after aortic valve replacement 1

From the Research

What is Levosimendan

• Levosimendan is a calcium sensitizer developed for the treatment of congestive heart failure 2, 3, 4, 5, 6.
• It increases myocardial contractility and dilates both the peripheral and coronary vessels 2.
• The positive inotropic effect of levosimendan is based on calcium-dependent binding of the drug to cardiac troponin C 2, 6.
• Levosimendan also acts as an opener of ATP-dependent potassium channels in vascular smooth muscle, thus inducing vasodilation 2, 3, 6.

Mechanism of Action

• Levosimendan has a unique mechanism of action that includes calcium sensitization of contractile proteins and the opening of adenosine triphosphate-dependent K channels 3.
• It increases the heart's sensitivity to calcium, thereby increasing cardiac contractility 6.
• The combination of positive inotropy with anti-ischemic effects of K-channel opening offers potential benefits in comparison with currently available intravenous inotropes 3.

Clinical Applications

• Levosimendan has been shown to be effective in the treatment of acute decompensated heart failure 2, 3, 5.
• It has also been used as rescue therapy for septic shock, weaning patients from assisted devices, and weaning patients from inotropic therapy 6.
• Levosimendan may be preferable to milrinone for patients in cardiogenic shock after cardiac surgery or for weaning from extracorporeal life support 5.
• It may be superior to dobutamine in terms of short-term survival, especially in patients on beta-blockers 2, 5.

Safety and Tolerability

• Levosimendan has been shown to be well tolerated and safe in patients with heart failure 2, 4.
• The most common adverse events associated with levosimendan treatment are headache and hypotension, as a likely consequence of the vasodilating properties of the compound 2.
• Levosimendan can be a valuable resource in the treatment of acute cardiac dysfunction, especially in the presence of beta-blockers or ischemic cardiomyopathy 5.