Featured Publications

Access each publication by clicking your chosen title. These publications have been selected for their relevance in the field of acute and advanced heart failure. These links will take you out of the Acute and Advanced Heart Failure Knowledge Centre into the main epgonline.org site.

Recently updated in September 2018 with a number of publications including: 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy

Previous publications

Click the links below to view previous publications that have been featured here.

2016 2017 2018

Recent publications

Listed here are the most recent studies to be published.

2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy

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.

Intravenous Levosimendan and Vasopressin in New-Onset Acute Pulmonary Hypertension After Weaning from Cardiopulmonary Bypass

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.

Differential Effects of Levosimendan and Dobutamine on Glomerular Filtration Rate in Patients With Heart Failure and Renal Impairment:A Randomized Double‐Blind Controlled Trial

Lannemyr et al. (Sahlgrenska University Hospital, Gothenburg, Sweden) for the ELDOR study.

The study enrolled 32 patients with heart failure and renal impairment comparing the acute renal and systemic effects of low doses of levosimendan (loading dose + continuous infusion of 0.1 µg/kg/min for 65 min) and dobutamine (7.5µg/kg/min). Both agents induced renal vasodilation and increased renal blood flow to a similar extent. However, only levosimendan treated patients experienced an increase in glomerular filtration rate (22%, P=0.012). In contrast, dobutamine treated patients experienced no improvement in glomerular filtration rate. The present study provides evidence of a mechanistic explanation for direct renal protective effects that is based on the K-ATP channel mechanism of levosimendan. The results indicate that levosimendan offers unique renal protective benefits to patients who have heart failure and coexisting impairment of their kidney function, and should therefore be the preferred drug for heart failure patients with impaired renal function. Limitation is the short duration of the study. 

Scheduled intermittent inotropes for Ambulatory Advanced Heart Failure. The RELEVANT-HF multicentre collaboration

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. 

Levosimendan use in patients with preoperative low ejection fraction undergoing cardiac surgery: A systematic review with meta-analysis and trial sequential analysis

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. 

The CardioMEMS system in the clinical management of end-stage heart failure patients: three case reports.

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.

Levosimendan in pulmonary hypertension and right heart failure

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. 

Ambulatory Intravenous Inotropic Support and or Levosimendan in Pediatric and Congenital Heart Failure: Safety, Survival, Improvement, or Transplantation

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.

Advanced heart failure: a position statement of the Heart Failure Association of the European Society of Cardiology

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.

Prevention of Heart Failure patients with decreased ejection fraction in Non-Cardiac surgery: Levosimendan or Anesthetic Cardioprotection?

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.

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