Efficacy and safety of a calcium sensitizer, levosimendan, in patients with right heart failure due to pulmonary hypertension

Jiang, Rong; Zhao, Qin‐Hua; Wu, Wenhui; Zhang, Rui; Yuan, Ping; Gong, Shan Shan; He, Jing; Luo, Ci‐Jun; Qiu, Hong‐Ling; Wang, Lan

doi:10.1111/crj.12699

Cited by 23 publications

(17 citation statements)

References 28 publications

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“…31 In a prospective non-randomized open-label study of 45 PH patients with severe acute right heart failure, levosimendan improved WHO functional class, Borg dyspnea score, 6-min walk test, biochemical markers and echocardiographic parameters of RV function. 32 On the contrary, a paradoxical rise in pulmonary arterial pressure were described in two idiopathic PAH patients with RV failure and a negative vasoreactivity test. 33 The authors discussed whether this could be due to improved RV function in the setting of a relatively fixed pulmonary arterial resistance, but no cardiac output or pulmonary vascular resistance values were reported.…”

Section: Levosimendan In Phmentioning

confidence: 99%

Levosimendan in pulmonary hypertension and right heart failure

Hansen¹,

Andersen²,

Nielsen‐Kudsk³

2018

Pulm. circ.

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Pulmonary hypertension is a multifactorial disease with a high morbidity and mortality. Right ventricular function is the most important predictor of morbidity and mortality in patients suffering from pulmonary hypertension, but currently there are no approved treatments directly supporting the failing right ventricle. Levosimendan is a calcium sensitizing agent with inotropic, pulmonary vasodilatory, and cardioprotective properties. Given its pharmacodynamic profile, levosimendan could be a potential novel agent for the treatment of right ventricular failure caused by pulmonary hypertension. The aim of this review is to provide an overview of the current knowledge on the effects of levosimendan in pulmonary hypertension and right heart failure.

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Section: Levosimendan In Phmentioning

confidence: 99%

Levosimendan in pulmonary hypertension and right heart failure

Hansen¹,

Andersen²,

Nielsen‐Kudsk³

2018

Pulm. circ.

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“…Decisive randomized trials of levosimendan are lacking in right ventricular failure with or without pulmonary hypertension (PH) but two proof-of-concept trials by Jiang et al 43 . and of Kleber et al 44 suggest some benefits.…”

Section: Right Heart Failure and Pulmonary Hypertensionmentioning

confidence: 99%

Use of levosimendan in acute heart failure

Harjola

Giannakoulas

Lewinski

et al. 2018

European Heart Journal Supplements

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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.

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“…Moreover, echocardiography showed improved RV function after levosimendan infusion, and the drug was well tolerated. 57 The use of levosimendan may be justified in selected cases of PAH with right HF, especially in patients requiring inotropic drugs, after cardiac output syndrome and, as a result, circulatory centralization. However, this clinical outcome may be achieved only in patients with normal blood volume.…”

Section: Levosimendan In Pulmonary Hypertensionmentioning

confidence: 99%

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

Tycińska¹,

Gierlotka²,

Bugajski³

et al. 2020

Kardiol Pol

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Levosimendan is a new inodilator which involves 3 main mechanisms: increases the calcium sensitivity of cardiomyocytes, acts as a vasodilator due to the opening of potassium channels, and has a cardioprotective effect. Levosimendan is mainly used in the treatment of acute decompensated heart failure (class IIb recommendation according to the European Society of Cardiology guidelines). However, numerous clinical trials indicate the validity of repeated infusions of levosimendan in patients with stable heart failure as a bridge therapy to heart transplantation, and in patients with accompanying right ventricular heart failure and pulmonary hypertension. Due to the complex mechanism of action, including the cardioprotective and anti aggregating effect, the use of levosimendan may be particularly beneficial in acute coronary syndromes, preventing the occurrence of acute heart failure. There are data indicating that levosimendan administered prior to cardiac surgery may improve outcomes in patients with severely impaired left ventricular function. The multidirectional mechanism of action also affects other organs and systems. The positive effect of levosimendan in the treatment of cardio renal and cardio hepatic syndromes has been shown. It has a safe and predictable profile of action, does not induce tolerance, and shows no adverse effects affecting patients survival or prognosis. However, with inconclusive results of previous studies, there is a need for a welldesigned multicenter randomized placebo controlled study, including an adequately large group of outpatients with chronic advanced systolic heart failure.

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Efficacy and safety of a calcium sensitizer, levosimendan, in patients with right heart failure due to pulmonary hypertension

Abstract: Intravenous levosimendan can effectively improve severe RHF of PH patients in hospital and well tolerated.

Cited by 23 publications

References 28 publications

Levosimendan in pulmonary hypertension and right heart failure

Levosimendan in pulmonary hypertension and right heart failure

Use of levosimendan in acute heart failure

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

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