Use of levosimendan in acute heart failure

Abstract

As a calcium sensitizer and inodilator that augments cardiac contractility without increasing myocardial oxygen demand or exacerbating ischaemia, levosimendan may be well configured to deliver inotropic support in cases of acute heart failure (AHF). Other factors favouring levosimendan in this setting include its extended duration of action due to the formation of an active metabolite and the lack of any attenuation of effect in patients treated with beta-blockers. Effects of levosimendan on systemic haemodynamics include its significant, dose-dependent increases in cardiac output, stroke volume and heart rate, and decreases in right and left ventricular filling and total peripheral resistance. Rapid and sustained reduction in levels of natriuretic peptides is a consistent effect of levosimendan use and potentially favourable effects on other neurohormonal indicators of cardiac distress are also observed. Levosimendan has repeatedly been shown to be effective in relief of symptoms of AHF, notably dyspnoea and fatigue, while mortality data from clinical trials and registries suggest that levosimendan is markedly less likely than catecholaminergic inotropes to worsen prognosis. The vasodilator pharmacology of levosimendan is also pertinent to the drug's use in AHF, in which setting organ under-perfusion is often a key pathology. These considerations suggest that levosimendan may have a more favourable impact on the circumstances of the majority of AHF patients than adrenergic agents that act only or primarily as cardiac stimulants. They also suggest that levosimendan may advantageously be integrated into a comprehensive strategy of early intervention designed and intended to prevent cardiac destabilization worsening to the point where hospitalization is necessary. Levosimendan should be used with caution and with tightened haemodynamic monitoring in patients who have low baseline blood pressure (systolic blood pressure <100 mmHg; diastolic blood pressure <60 mmHg), or who are at risk of a hypotensive episode.

Keywords: Cardioactive; Efficacy; Inodilator; Inotrope; Safety; Treatment; Vasoactive.

Figure 1

European Society of Cardiology-advised criteria for classifying acute heart failure based on the presence/absence of congestion and/or hypoperfusion. From Ponikowski et al.

Figure 2

Levosimendan infusion in the REVIVE II study was associated with a marked and sustained reduction in circulating brain natriuretic peptide levels. From Packer et al.

Figure 3

Levosimendan, a calcium-sensitizing inotrope and vasodilator, was associated with a substantially lower mortality rate in the population of the ALARM-HF registry than was seen with traditional adrenergic, calcium-mobilizing inotropes such as dobutamine. From Mebazaa et al.

Figure 4

Analysis of deaths in the REVIVE II study according to patients’ baseline blood pressure revealed an association between higher blood pressures and improved outcomes with levosimendan use. From Packer et al.