Listed here are all the publications that featured in 2018.
Regitz-Zagrosek V et al. (Charite Universitätsmedizin Berlin, Berlin, Germany) for ESC guidelines.
Eur Heart J 2018; 39: 3165-3241. ESC GUIDELINES.
The guidelines state that if a patient is in cardiogenic shock or dependent on inotropes or vasopressors, levosimendan may be the preferred inotrope.
Poidinger B et al. (Klinikum Wels, Wels, Austria).
J Cardiothorac Vasc Anesth 2018 (ePub Aug 16). RETROSPECTIVE CLINICAL TRIAL.
This case series included 19 cardiac surgery patients who experienced new-onset pulmonary hypertension with acute right ventricular dysfunction after weaning. All patients received a combination of levosimendan, vasopressin and norepinephrine. Mean pulmonary artery pressure decreased and cardiac output increased after intervention.
Oliva F et al. (ASST-Great Metropolitan Hospital Niguarda, Milan, Italy) for the RELEVANT registry.
Int J Cardiol 2018 (ePub Aug 21). RETROSPECTIVE REGISTRY STUDY.
The primary aim of the study was to compare days spent in hospital during 6 months before treatment start versus during 6 months after treatment start in patients with ambulatory advanced refractory heart failure. 185 patients who received intermittent levosimendan at a dose range from 0.05 to 0.2 mcg/kg/min for a duration of 12 to 48 hours with intervals from 3 to 4 weeks were included. Days spent in hospital decreased from 9.4 to 2.8 days (p<0.0001) after treatment start. Repetitive levosimendan dosing was well tolerated, the adverse event rate being fairly low (12%). The authors conclude that levosimendan represents a treatment option for these patients before resorting to more costly and demanding mechanical support.
Ng KT et al. (Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia).
J Clin Anesth 2018; 52: 37-47. META-ANALYSIS.
For this meta-analysis 12 trials were selected (CHEETAH, LEVO-CTS and LICORN included) with in total 1867 patients, all with a preoperative ejection fraction of ≤50%. Levosimendan was associated with a significant reduction in overall mortality rate compared to placebo (Odds Ratio 0.56; 95% CI 0.39 - 0.80). However, the quality of evidence in many studies was considered low, and trial sequential analysis was inconclusive. The authors conclude that the available low bias data neither supports nor opposes the utility of levosimendan as a prophylactic to reduce mortality rate in adult cardiac patients with preoperative low ejection fraction of ≤50%. Still, it is important to note that the greatest reductions in mortality was observed in the subgroups of patients with a low ejection fraction of ≤30%, in those who received levosimendan preoperatively, and in those receiving an initial loading dose. The levosimendan group also showed a lower incidence of low-cardiac-output-syndrome and lesser need for mechanical cardiac assist devices.
Tschöpe C et al. (Berlin-Brandenburg Center for Regeneration Therapies, Charite, Berlin, Germany).
BMC Cardiovasc Disord 2018; 18: 155. CASE REPORT SERIES.
CardioMEMS is an implantable device positioned in the pulmonary artery able to detect high cardiac filling pressures. Of the three cases presented, two received 24-hour levosimendan. It improved hemodynamics and pressure profiles in these patients. The authors state that the new concept to combine CardioMEMS in the setting of an outpatient levosimendan programme looks promising.
Hansen MS et al. (Aarhus University Hospital, Aarhus, Denmark).
Pulm Circ 2018 (ePub Jan 1). REVIEW.
The authors suggest that levosimendan is potentially favorable in treating pulmonary hypertension and associated right ventricular failure resulting from different etiologies as pulmonary arterial hypertension, left heart disease, and congenital heart disease. Larger, well-designed and adequately powered studies are required to confirm the potentially favorable effects of levosimendan in this important clinical setting.
Apostolopoulou SC et al. (Onassis Cardiac Surgery Center, Athens, Greece).
Pediatr Cardiol 2018 (ePub May 18). RETROSPECTIVE CLINICAL TRIAL.
The present observational, retrospective study included 27 patients (aged 0.1 to 26 years) over a period of 21 years. Periodic levosimendan infusions were given to 6 patients, 7 patients received only ambulatory inotropes (dobutamine, milrinone), while 14 patients received both levosimendan and ambulatory inotropes for a follow-up period of 0.3 to 21 years. The authors conclude that prolonged ambulatory inotropes and/or periodic levosimendan infusions are feasible and relatively safe therapies for end-stage heart failure in the pediatric population, without discussing the specific role of levosimendan. However, the lack of control, the very wide age span and long study period, as well as the small number of patients makes it difficult to draw firm conclusions from the study.
Crespo-Leiro MG et al. (Complexo Hospitalario Universitario A Coruna, La Coruna, Spain).
Eur J Heart Fail 2018 (ePub May 21). ESC-ENDORSED POSITION PAPER.
This article updates the classification of advanced heart failure and describes new diagnostic and treatment options for these patients. Levosimendan is mentioned, referring mainly to the LION-HEART study, and the authors conclude that intermittent levosimendan may be useful in the advanced heart failure settings. In this position paper, endorsed by the European Society of cardiology, advanced heart failure is presented more as a permanently decompensated state than as a series of acute events.
Likhvantsev VV et al. M.F. (Vladimirsky Moscow Regional Research Clinical Institute, Moscow, Russia).
Anesteziologiya i Reanimatologiya 2016;61:411-417. RANDOMISED CLINICAL TRIAL (in Russian; short summary in English).
The study comprised 92 patients operated on the descending aorta. The patients were divided into 3 groups: a control group, a group with anesthetic cardioprotection, and one receiving preoperative levosimendan. The incidence of heart failure (estimated by need of inotropic drugs) was significantly lower in the levosimendan group compared to the other groups, while there were no significant differences in 30-day mortality between the groups. It is not clear from the summary whether the study was blinded. Neither was the levosimendan dose specified.
Altenberger J & Pölzl G. (Teaching Hospital of Paracelsus Medical Private University, Salzburg, Austria). Eur J Heart Fail 2018 (ePub May 3). EDITORIAL COMMENT.
In this article the authors comment the recently published LION-HEART study about intermittent administration of levosimendan in advanced heart failure. Both primary and secondary endpoints were positive in this trial. The authours point out that both in the LION-HEART and LevoRep studies safety and tolerability were favourable for levosimendan. In the text it is highlighted that the current study LEODOR, a prospective trial with firm clinical endpoints, is meant to confirm the encouraging results.
Desai PM et al. Seth GS (Medical College and KEM Hospital, Mumbai, India). Ann Card Anaesth 2018; 21:123-128. RANDOMISED CLINICAL TRIAL.
The present, open study included 60 patients. The levosimendan group received 0.1 mcg/kg/min of the drug beginning at the night before surgery (without a loading dose) and continued for 24 h including the intraoperative period. Levosimendan significantly increased cardiac index, decreased PCWP and serum lactate, as well as reduced the incidence of atrial fibrillation, low cardiac output syndrome and acute kidney injury compared to the control group. Pre- and intraoperative infusion of levosimendan, without a loading dose, aids in successful conduct of off-pump surgery in this clinical setting.
Qiang H et al. (First Affiliated Hospital of Xian Jiaotong University, Xian, Shaanxi, China). J Cardiovasc Pharmacol 2018 (ePub Apr 3). META-ANALYSIS.
In the present meta-analysis, all three recent large clinical trials were included (CHEETAH, LEVO-CTS, LICORN). The total number of patients was 3,247 from 25 studies, the meta-analysis thus being the largest in cardiac surgery. In the mortality analysis, only 19 studies were included. The results show that levosimendan reduced 30-day mortality significantly compared to the control group (OR 0.63; 95% CI 0.47-0.84), but this reduction remained evident only in the subgroup of patients with a low ejection fraction of < 50% (OR 0.49; 95% CI 0.35-0.70). Levosimendan also significantly reduced the incidence of acute kidney injury, renal replacement therapy use, and duration of ICU stay. These results are in close agreement with the meta-analysis of Tena et al (2018), which is commented in this issue of Simdax BKU.
Zhou S et al. (Second Affiliated Hospital to Nanchang University, Nanchang of Jiangxi, China). Herz 2018 (ePub Apr 10). META-ANALYSIS.
The present meta-analysis assessed some relevant hemodynamic and neurohumoral variables. The patient material included 257 patients from 7 studies, of which about half of the patients received levosimendan and the other half served as controls (dobutamine, furosemide, or no comparator). The number of patients analysed for each variable does not seem to match the reported total number of patients. Levosimendan significantly reduced BNP levels and increased left ventricular ejection fraction. The results, at least in the way they are presented in this paper, seem a little confusing. Further studies on the subject are warranted.
Rainer-Hartley E. et al. (St. Paul’s Hospital, University of British Columbia, Vancouver, Canada). Curr Opin Cardiol 2018;33:225–231. REVIEW.
The authors conclude that despite multiple treatment modalities, no consistent mortality benefit has been observed in AHF. The paragraph about levosimendan is short, and only the LIDO, REVIVE and SURVIVE studies are mentioned. However, the authors recommend considering the use of levosimendan in hypotensive heart failure. However, a bolus dose should be given only in patients with a systolic blood pressure above 100 mmHg.
Najjar E. et al. (Karolinska University Hospital, Stockholm, Sweden). ESC Heart Fail 2018 (ePub Feb 22). OPEN CLINICAL TRIAL.
By this open uncontrolled trial the authors found that a single 24-hour infusion of levosimendan improved haemodynamics also in stable chronic heart failure. Cardiac output (measured with a non-invasive rebreathing method) increased, and peripheral resistance decreased. The small sample size of 23 patients and the absence of a control group limit the interpretation of the results.
Schuman J et al. (Martin-Luther-University Halle-Wittenberg, Halle, Germany). Cochrane Database Syst Rev 2018 (ePub Jan 29). SYSTEMATIC REVIEW.
The effect of inotropic or vasodilator drugs on mortality was analysed in totally 2001 patients with cardiogenic shock or low cardiac output syndrome from 13 studies. Many of the studies had serious limitations. The review presents low-quality evidence that levosimendan reduces short-term mortality significantly compared to dobutamine. However, this survival benefit is not confirmed in long-term follow-up. At present there are no robust data to support any distinct inotropic or vasodilator drug to reduce mortality in this clinical setting.
Wang B et al. (The second affiliated hospital and Yuying children's hospital on Wenzhou Medical University, Zhejiang, China). Oncotarget 2017; 8: 100524-100532. META-ANALYSIS.
A total of 816 patients from 10 trials with very different study designs were included in this meta-analysis. There was no significant difference in mortality between the levosimendan group and the group receiving standard inotropic therapy. The trial sequential analysis indicated that the evidence was inconclusive. Further randomised, controlled clinical trials are needed to assess the effect of levosimendan in septic shock.
Guarracino F et al. Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. J Cardiovasc Pharmacol 2018;71(1):1-9 EXPERT OPINION.
Levosimendan is safe and well tolerated in patients undergoing cardiac surgery with cardiopulmonary bypass who have low LVEF and are at risk of the development of postoperative low cardiac output syndrome. The lack of any deterioration in survival is particularly noteworthy. Levosimendan safety and efficacy confirmed also after the latest three clinical trials.