From the Guidelines
Levosimendan is a calcium sensitizer that improves cardiac function in heart failure by enhancing myocardial contractility without increasing oxygen demand, and its use is recommended in acute decompensated heart failure, particularly in patients with low cardiac output syndrome or cardiogenic shock, based on the most recent evidence from 2025 1.
Mechanism of Action
Levosimendan's primary mechanism of action involves binding to cardiac troponin C and stabilizing the calcium-bound conformation, which increases the sensitivity of cardiac myofilaments to calcium. This allows the heart to contract more forcefully without requiring higher intracellular calcium concentrations, unlike traditional inotropes.
- It also opens ATP-sensitive potassium channels in vascular smooth muscle, causing vasodilation in both systemic and pulmonary circulation, which reduces preload and afterload.
- Additionally, it has phosphodiesterase-3 inhibitory effects at higher doses.
Clinical Use
In clinical practice, levosimendan is typically administered as an intravenous infusion, usually starting with a loading dose of 6-12 μg/kg over 10 minutes, followed by a continuous infusion of 0.05-0.2 μg/kg/min for 24 hours.
- It's primarily used for acute decompensated heart failure, particularly in patients with low cardiac output syndrome or cardiogenic shock, and in those who have not responded adequately to conventional therapies.
- The drug's unique advantage is its ability to improve cardiac performance without significantly increasing myocardial oxygen consumption or arrhythmia risk, and its effects persist for days after discontinuation due to active metabolites, as supported by recent studies 1.
Key Benefits
- Improves cardiac performance without increasing myocardial oxygen consumption
- Reduces preload and afterload through vasodilation
- Has phosphodiesterase-3 inhibitory effects at higher doses
- Effects persist for days after discontinuation due to active metabolites
- Recommended for use in acute decompensated heart failure, particularly in patients with low cardiac output syndrome or cardiogenic shock, based on recent guidelines and studies 1.
From the Research
Mechanism of Action (MOA) of Levosimendan
- Levosimendan is a calcium sensitizer that increases myocardial contractility by binding to cardiac troponin C in a calcium-dependent manner 2, 3, 4.
- It also acts as an opener of ATP-dependent potassium channels in vascular smooth muscle, inducing vasodilation 2, 3, 4.
- The positive inotropic effect of levosimendan is based on calcium-dependent binding of the drug to cardiac troponin C, without increasing myocardial oxygen consumption 2, 5, 4.
Role of Levosimendan in Treating Heart Failure
- Levosimendan is used for the treatment of decompensated heart failure, producing significant, dose-dependent increases in cardiac output, stroke volume, and heart rate, and decreases in PCWP, mean blood pressure, mean pulmonary artery pressure, mean right atrial pressure, and total peripheral resistance 2, 3.
- It has been shown to have favorable effects on symptoms of heart failure, superior to placebo and at least comparable to dobutamine 2, 3, 4.
- Mortality and morbidity in levosimendan-treated patients have been shown to be significantly lower when compared to dobutamine or placebo-treated patients 2, 3, 4.
- Levosimendan can be a valuable resource in the treatment of acute cardiac dysfunction, especially in the presence of beta-blockers or ischemic cardiomyopathy 5.
Key Benefits of Levosimendan
- Levosimendan offers a new effective option for the treatment of acutely decompensated heart failure, with a favorable safety profile compared to traditional inotropes 2, 5, 4.
- It does not exhibit clinically relevant phosphodiesterase inhibition at therapeutic concentrations, and is not associated with significant increases in myocardial oxygen consumption, proarrhythmia, or neurohormonal activation 2, 3, 4.
- The active metabolite of levosimendan (OR-1896) significantly prolongs the duration of the hemodynamic effects of the therapeutic 24-hour levosimendan infusion 2, 6, 3.