2006•Recent Advances in Cardiovascular Drug Discovery (Formerly Recent Patents on Cardiovascular Drug Discovery)Requires access

Levosimendan: A Novel Agent in Heart Failure

Nikolas Koumallos, Charalambos A. Antoniades, Dimitris Tousoulis, Cheerag C. Shirodaria, Christodoulos Stefanadis

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Abstract

Heart failure is characterised by decreased cardiac output, which results in the development of both peripheral hypoperfusion and pulmonary congestion and can lead to the development of acute pulmonary edema. The primary objective in treating a patient with decompensated heart failure is hemodynamic stabilization, which is usually achieved by inotropic support. Classic inotropic agents provide short-term hemodynamic improvement, but their use has been correlated with poor prognosis. Levosimendan, a new calcium sensitizer, offers hemodynamic and symptomatic improvement without increasing cAMP and intracellular calcium concentrations. This agent improves contractility without increasing the risk of cardiac events such as arrhythmias. By combining a positive inotropic action mediated via calcium sensitization and a vasodilatory effect via ATP-dependent potassium channels, it appears to be superior than classic positive inotropic agents. Furthermore, it seems to have prolonged benefit in heart failure patients, and it also has anti-inflammatory and antiapoptotic properties. In conclusion, levosimendan seems to be a particularly promising agent for the treatment of decompensated heart failure, as in addition to improving cardiac output, it has a more favorable side-effect profile than classic inotropic agents, and it affects multiple pathways with key role in the pathophysiology of heart failure.

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What this paper is about

Heart failure is characterised by decreased cardiac output, which results in the development of both peripheral hypoperfusion and pulmonary congestion and can lead to the development of acute pulmonary edema. The primary objective in treating a patient with decompensated heart failure is hemodynamic stabilization, which is usually achieved by inotropic support. Classic inotropic agents provide short-term hemodynamic improvement, but their use has been correlated with poor prognosis. Levosimendan, a new calcium sensitizer, offers hemodynamic and symptomatic improvement without increasing cAMP and intracellular calcium concentrations. This agent improves contractility without increasing the risk of cardiac events such as arrhythmias. By combining a positive inotropic action mediated via calcium sensitization and a vasodilatory effect via ATP-dependent potassium channels, it appears to be superior than classic positive inotropic agents. Furthermore, it seems to have prolonged benefit in heart failure patients, and it also has anti-inflammatory and antiapoptotic properties. In conclusion, levosimendan seems to be a particularly promising agent for the treatment of decompensated heart failure, as in addition to improving cardiac output, it has a more favorable side-effect profile than classic inotropic agents, and it affects multiple pathways with key role in the pathophysiology of heart failure.

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Available abstract

Heart failure is characterised by decreased cardiac output, which results in the development of both peripheral hypoperfusion and pulmonary congestion and can lead to the development of acute pulmonary edema. The primary objective in treating a patient with decompensated heart failure is hemodynamic stabilization, which is usually achieved by inotropic support. Classic inotropic agents provide short-term hemodynamic improvement, but their use has been correlated with poor prognosis. Levosimendan, a new calcium sensitizer, offers hemodynamic and symptomatic improvement without increasing cAMP and intracellular calcium concentrations. This agent improves contractility without increasing the risk of cardiac events such as arrhythmias. By combining a positive inotropic action mediated via calcium sensitization and a vasodilatory effect via ATP-dependent potassium channels, it appears to be superior than classic positive inotropic agents. Furthermore, it seems to have prolonged benefit in heart failure patients, and it also has anti-inflammatory and antiapoptotic properties. In conclusion, levosimendan seems to be a particularly promising agent for the treatment of decompensated heart failure, as in addition to improving cardiac output, it has a more favorable side-effect profile than classic inotropic agents, and it affects multiple pathways with key role in the pathophysiology of heart failure.

Key concepts: Levosimendan, Medicine, Heart failure, Cardiology, Internal medicine

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