Toni Sarapohja

Levosimendan Facilitates Weaning From Cardiopulmonary Bypass in Patients Undergoing Coronary Artery Bypass Grafting With Impaired Left Ventricular Function

BACKGROUND Levosimendan is a compound with vasodilatory and inotropic properties. Experimental data suggest effective reversal of stunning and cardioprotective properties. METHODS This prospective, randomized, placebo-controlled, double-blind study included 60 patients with 3-vessel coronary disease and left ventricular ejection fraction (LVEF) of less than 0.50. Levosimendan administration (12 microg/kg bolus, followed by an infusion of 0.2 microg/kg/min) was started immediately after induction anesthesia. Predefined strict hemodynamic criteria were used to assess the success of weaning. If weaning was not successful, CPB was reinstituted and an epinephrine infusion was started. If the second weaning attempt failed, intraaortic balloon pumping (IABP) was instituted. RESULTS The groups had comparable demographics. The mean (standard deviation) preoperative LVEF was 0.36 (0.8) in both groups. The baseline cardiac index was 1.8 (0.3) L/min/m(2) in the levosimendan group and 1.9 (0.4) L/min/m(2) in the placebo group. The mean duration of CPB to primary weaning attempt was 104 (25) minutes in the levosimendan and 109 (22) minutes in the placebo group. Primary weaning was successful in 22 patients (73%) in the levosimendan group and in 10 (33%) in the placebo group (p = 0.002). The odds ratio for failure in primary weaning was 0.182 (95% confidence interval, 0.060 to 0.552). Four patients in the placebo group failed the second weaning and underwent IABP compared with none in the levosimendan group (p = 0.112). CONCLUSIONS Levosimendan significantly enhanced primary weaning from CPB compared with placebo in patients undergoing 3-vessel on-pump coronary artery bypass grafting. The need for additional inotropic or mechanical therapy was decreased.

Intravenous levosimendan vs. dobutamine in acute decompensated heart failure patients on beta-blockers

The aim of this study is to compare the effects of a 24 h intravenous infusion of levosimendan and a 48 h infusion of dobutamine on invasive haemodynamics in patients with acutely decompensated chronic NYHA class III–IV heart failure. All patients were receiving optimal oral therapy including a β‐blocker.

Oral levosimendan in patients with severe chronic heart failure—The PERSIST study

Intravenous levosimendan improves symptoms in acutely decompensated heart failure.

Repetitive use of levosimendan in advanced heart failure: need for stronger evidence in a field in dire need of a useful therapy

Patients in the latest stages of heart failure are severely compromised, with poor quality of life and frequent hospitalizations. Heart transplantation and left ventricular assist device implantation are viable options only for a minority, and intermittent or continuous infusions of positive inotropes may be needed as a bridge therapy or as a symptomatic approach. In these settings, levosimendan has potential advantages over conventional inotropes (catecholamines and phosphodiesterase inhibitors), such as sustained effects after initial infusion, synergy with beta-blockers, and no increase in oxygen consumption. Levosimendan has been suggested as a treatment that reduces re-hospitalization and improves quality of life. However, previous clinical studies of intermittent infusions of levosimendan were not powered to show statistical significance on key outcome parameters. A panel of 45 expert clinicians from 12 European countries met in Rome on November 24-25, 2016 to review the literature and envision an appropriately designed clinical trial addressing these needs. In the earlier FIGHT trial (daily subcutaneous injection of liraglutide in heart failure patients with reduced ejection fraction) a composite Global Rank Score was used as primary end-point where death, re-hospitalization, and change in N-terminal-prohormone-brain natriuretic peptide level were considered in a hierarchical order. In the present study, we tested the same end-point post hoc in the PERSIST and LEVOREP trials on oral and repeated i.v. levosimendan, respectively, and demonstrated superiority of levosimendan treatment vs placebo. The use of the same composite end-point in a properly powered study on repetitive levosimendan in advanced heart failure is strongly advocated.

Effect of baseline characteristics on mortality in the SURVIVE trial on the effect of levosimendan vs dobutamine in acute heart failure: Sub-analysis of the Finnish patients

BACKGROUND In the SURVIVE trial, including 1327 acute heart failure patients, no statistically significant difference between levosimendan and dobutamine in the 180-day all-cause mortality was seen. Country-specific differences in outcome were, however, present. In the Finnish sub-population in fact, mortality was significantly lower in levosimendan treated patients. We aim to understand the reasons for this disparity. METHODS The risk factors for all-cause mortality were identified in the whole study population using multivariate Cox proportional hazards regression analysis. Those factors were evaluated in the 95 patients of the Finnish sub-population. RESULTS The treatment by country interaction for mortality in Finland vs. other countries was significant, p=0.029. Levosimendan treated patients had a lower 180-day mortality compared to dobutamine treated (17% vs. 40%, p=0.023) in the Finnish sub-population. Baseline variables predicting survival in the whole SURVIVE trial population included age, systolic blood pressure, heart rate, myocardial infarction during admission, levels of NT-pro-BNP, glucose, creatinine, and alanine transferase, use of ACE inhibitors and β-blockers, oliguria, time from hospital admission to randomization, history of cardiac arrest, and left ventricular ejection fraction. Finnish patients were more frequently treated with β-blockers (88% vs. 52%, p<0.0001), their study treatment was started earlier (mean±SD 41±40h vs. 81±154; p<0.0001), and they had more often acute myocardial infarction at admission (39% vs. 16%, p<0.0001). CONCLUSION The lower mortality in the Finnish patients treated with levosimendan was associated with higher use of β-blockers, higher frequency of myocardial infarction at admission, and shorter delay between randomization and start of treatment.