Elsevier

Life Sciences

Volume 184, 1 September 2017, Pages 30-36
Life Sciences

Efficacy and safety of levosimendan in patients with acute right heart failure: A meta-analysis

https://doi.org/10.1016/j.lfs.2017.07.001Get rights and content

Abstract

Aims

Right heart failure (RHF), which is caused by a variety of heart and lung diseases, has a high morbidity and mortality rate. Levosimendan is a cardiac inotropic drug and vasodilator. The effect of levosimendan on RHF remains unclear. We sought to evaluate the efficacy and safety of levosimendan in patients with acute RHF.

Materials and methods

We systematically searched PubMed, Cochrane Library, EMBASE, and ClinicalTrials.gov to identify studies reporting the efficacy and safety of levosimendan for the treatment of RHF.

Key findings

Ten trials, including 359 participants from 6 RCTs and 4 self-controlled trials, were evaluated. In the 6 RCTs, we found that patients treated with levosimendan for 24 h showed a significant increase in tricuspid annular plane systolic excursion [1.53; 95% CI (0.54, 2.53); P = 0.002] and ejection fraction [3.59; 95% CI (1.21, 5.98); P = 0.003] as well as a significant reduction in systolic pulmonary artery pressure [− 6.15; 95% CI (− 9.29, − 3.02); P = 0.0001] and pulmonary vascular resistance [− 39.48; 95% CI (− 65.59, − 13.38); P = 0.003], whereas changes in mean pulmonary pressure were nonsignificant. Adverse events did not significantly differ between the two groups.

Significance

Our study shows that levosimendan exhibits short-term efficacy for treating RHF in patients with a variety of heart and lung diseases. Additional strict multicentre RCTs with long follow-up times and large sample sizes are required to further validate the efficacy and safety of this treatment.

Introduction

Right heart failure (RHF), a clinical syndrome with multiple possible causes that results in right ventricular systolic and/or diastolic dysfunction, can eventually result in circulatory failure and death [1]. A variety of heart and lung diseases, including pulmonary hypertension (PH), left heart failure (LHF), myocardial infarction, congenital heart disease, pulmonary embolism, perioperative and chronic obstructive pulmonary disease, can lead to right ventricular pressure and/or volume overload or myocardial disease [2]. According to the US Health Center, the estimated prevalence of RHF is 5%, fairly to LHF. In addition, RHF induced by PH has a mortality rate of up to 48% in intensive care units (ICUs), which is higher than that of LHF [3]. Poor right ventricular function is an independent prognostic marker for mortality in patients with heart failure or PH [1], [4], [5]. Although the management of RHF has improved, the associated morbidity and mortality remain high. Additionally, published guidelines describe only a limited number of efficient treatments for RHF.

Intracellular Ca2 + controls numerous cellular processes via excitation-contraction coupling, and Ca2 +-release channels (CRCs) play important roles in the heart, skeletal muscle, and brain as well as in the processes of metabolism and aging [6]. Levosimendan, a cardiac inotropic drug and vasodilator, inhibits phosphodiesterases and promotes Ca2 + binding with troponin-C to improve ventricular function without increasing oxygen demand. Moreover, levosimendan activates ATP-sensitive K+-channels in smooth muscle to cause vasodilation [7]. In addition, after a 24-h infusion of levosimendan, its active metabolite OR-1896, which has a long half-life (approximately 80 h), can be detected and persists for many days in human blood [8].

Evidence-based medicine has confirmed that levosimendan treatment is beneficial for patients with LHF, but its effect on patients with RHF remains unclear [9], [10], [11]. Several trials have examined this relationship, but the sample sizes were small, and the results were inconclusive and even conflicting. Moreover, the molecular mechanisms of RHF are not well known [12]. Therefore, traditional therapies may be ineffective at improving RV function or survival in patients with RHF.

In this meta-analysis, we sought to evaluate the efficacy and safety of levosimendan for treating patients with RHF using Doppler echocardiography and right heart catheterization.

Section snippets

Literature search

We systematically searched PubMed (from 1950 to February 2017), EMBASE (from 1966 to February 2017), the Cochrane Library database and ClinicalTrials.gov for primary literature as well as reviews of relevant articles using the keyword “levosimendan” paired with the following: “right heart or right ventricular (failure)”, “pulmonary hypertension”, “pulmonary embolism”, “acute respiratory distress syndrome”, “perioperative”, “chronic obstructive pulmonary disease” or “congenital heart defect”.

Results of the literature search

A total of 1399 studies were identified through the database search. However, most studies were excluded because they were not relevant to the purpose of this meta-analysis or they were non-human studies, cross-sectional studies, reviews, commentaries, letters or case reports.

Ultimately, 10 observational articles (10 trials; 359 patients) satisfied our inclusion criteria [16], [17], [18], [19], [20], [21], [22], [23], [24], [25]. Of these, 5 trials evaluated right ventricular function using

Discussion

We performed a meta-analysis to assess the effects of levosimendan on right ventricular function. Our results showed that levosimendan was effective for treating acute RHF and provided preliminary evidence supporting its use as a clinical intervention for RHF.

Over the past decade, the importance of pathologies affecting the right ventricle (RV) has become an increasing focus of research. In 2006, right ventricular physiology was identified as a priority of cardiovascular research by the

Conclusion

Our study shows that levosimendan is effective for the short-term improvement of RHF in patients with a variety of heart and lung diseases. Additional strict, multicentre randomized controlled trials with long follow-up times and large sample sizes are required to further validate the efficacy and safety of this drug.

Conflict of interest

None.

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