An update on levosimendan in acute cardiac care: applications and recommendations for optimal efficacy and safety

ABSTRACT

Introduction: In the 20 years since its introduction to the palette of intravenous hemodynamic therapies, the inodilator levosimendan has established itself as a valuable asset for the management of acute decompensated heart failure. Its pharmacology is notable for delivering inotropy via calcium sensitization without an increase in myocardial oxygen consumption.

Areas covered: Experience with levosimendan has led to its applications expanding into perioperative hemodynamic support and various critical care settings, as well as an array of situations associated with acutely decompensated heart failure, such as right ventricular failure, cardiogenic shock with multi-organ dysfunction, and cardio-renal syndrome. Evidence suggests that levosimendan may be preferable to milrinone for patients in cardiogenic shock after cardiac surgery or for weaning from extracorporeal life support and may be superior to dobutamine in terms of short-term survival, especially in patients on beta-blockers. Positive effects on kidney function have been noted, further differentiating levosimendan from catecholamines and phosphodiesterase inhibitors.

Expert opinion:Levosimendan can be a valuable resource in the treatment of acute cardiac dysfunction, especially in the presence of beta-blockers or ischemic cardiomyopathy. When attention is given to avoiding or correcting hypovolemia and hypokalemia, an early use of the drug in the treatment algorithm is preferred.

KEYWORDS:

• Critical care
• calcium sensitization
• adenosine triphosphate-sensitive potassium (K_ATP) channels
• mitochondria
• levosimendan
• cardiogenic shock
• acute heart failure
• low cardiac output syndrome

Article highlights

• The inodilator levosimendan is established in the repertoire of hemodynamic therapies for severe heart failure with various etiologies, and in various clinical settings.

• The unique mechanism of action and pharmacology of levosimendan make it a safe choice for restoring hemodynamic and neurohormonal balance, alleviating symptoms and protecting cardiac tissue.

• In acute cardiac care, the evidence-base for using levosimendan in patients with acutely decompensated chronic heart failure treated with beta-blockers is much stronger than for any other inotrope or inodilator.

• Levosimendan evokes specific vasodilation of the renal afferent (preglomerular) arterioles, allowing the restoration of renal function and reducing the need for renal replacement therapy after cardiac surgery.

• The efficacy of levosimendan has been investigated but is still to be definitely proven in other clinical settings, such as right heart failure, perioperative low cardiac output syndrome, cardiogenic and septic shock, etc. To date, non-regulatory studies have mostly been performed in these areas; properly powered randomized controlled trials are warranted.

Declaration of interest

PP is a full-time employee of Orion Pharma. Over the past 5 years, all other authors have received honoraria for educational lectures and/or unrestricted grants for investigator-initiated studies from Orion Pharma, where levosimendan was discovered and developed. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed they have received Grants from Orion Pharma for research in the past. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Acknowledgments

We thank Hughes associates, Oxford, UK, for editorial assistance.