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.

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use

“…85 Due to the large therapeutic field they encompass, the European guidelines on acute and chronic HF are not as detailed as they could be and, in recommending therapeutic agents, ignore some of the different aetiologies and manifestations of AHF. Supplementary information and recommendations can be found in more than 20 expert consensus papers co-authored by more than 180 clinicians from 30 countries who have discussed when and how to use levosimendan in different therapeutic settings, including AHF and cardiogenic shock, 74,81,[86][87][88] AdHF, [89][90][91][92] perioperative use, [93][94][95] and use in the intensive care unit (ICU), 96 and who have described its cardiorenal effects, 88,97 its effects on quality of life, 98,99 exercise performance, 100 lung function, 101 and pharmaco-economic considerations. 102 In the context of a 20-year retrospective it is worth noting at this point that its complex mode of action might have had the potential to disadvantage levosimendan both in fact and in perception.…”

“…Therefore, the use of an initial bolus of levosimendan is now generally not recommended, and it has often been avoided in clinical practice and used only if an instant effect is sought and the systolic blood pressure (SBP) is adequate. [ 73 , 74 ]…”

Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use

“…Therefore, use of an initial bolus of levosimendan is now generally not recommended, and it has often been avoided in clinical practice and used only if an instant effect is sought and the systolic blood pressure is adequate. 73 , 74 …”

“…Due to the large therapeutic field they encompass, the European guidelines on acute and chronic HF are not as detailed as they could be and, in recommending therapeutic agents, ignore some of the different etiologies and manifestations of AHF. Supplemental Digital Content 1 (see Supplementary Information , http://links.lww.com/JCVP/A472 ) and recommendations can be found in more than 20 expert consensus papers coauthored by more than 180 clinicians from 30 countries who have discussed when and how to use levosimendan in different therapeutic settings, including AHF and cardiogenic shock, 74 , 81 , 86 – 88 AdHF, 89 – 92 perioperative use, 93 – 95 and use in the intensive care unit (ICU), 96 and who have described its cardiorenal effects, 88 , 97 its effects on quality of life, 98 , 99 exercise performance, 100 lung function, 101 and pharmacoeconomic considerations. 102 …”

Levosimendan in the treatment of patients with acute cardiac conditions: an expert opinion of the Association of Intensive Cardiac Care of the Polish Cardiac Society

“…By improving renal blood flow parameters, levosimendan was also shown to improve kidney function. 39 There have been no clinical trials assessing the effect of levosimendan on isolated right HF. Available data supporting its beneficial action come from a few case reports.…”