title: Levosimendan improves exercise performance in patients with advanced chronic heart failure.
abstract: OBJECTIVE
  Cardiopulmonary exercise test (CPET) provides parameters such as peak VO2and ventilation/CO2production (VE/VCO2) slope, which are strong prognostic predictors in patients with stable advanced chronic heart failure (ADHF). The study aim was to evaluate the effects of the inodilator levosimendan on CPET in patients with ADHF under stable clinical conditions.
  
  
  RESULTS
  We enrolled patients with ADHF (peak VO2< 12 mL/min/kg) in a double-blind, placebo-controlled protocol. Patients were randomly assigned to i.v. infusion of placebo (500 mL 5% glucose;n= 19) or levosimendan (in 500 mL 5% glucose;n= 23). Before and 24 h after the end of the infusion, patients underwent determination of New York Heart Association class, B-type natriuretic peptide (BNP), haemoglobin, serum creatinine, and blood urea nitrogen levels, as well as CPET, standard spirometry, and alveolar capillary gas diffusion. BNP showed no change with placebo (1042 ± 811 to 1043 ± 867 pg/mL), but it was decreased with levosimendan (1163 ± 897 to 509 ± 543 pg/mL,P< 0.001). No changes were observed for haemoglobin, creatinine, and blood urea nitrogen in either group. With levosimendan, a minor improvement was observed in spirometry measurements, but not in alveolar capillary gas diffusion. Peak VO2showed a small, non-significant increase with placebo (9.5 ± 1.7 to 10.0 ± 2.1 mL/kg/min,P= 0.12), and a greater increase with levosimendan (9.8 ± 1.7 to 11.0 ± 1.9 mL/kg/min,P< 0.005). The VE/VCO2slope showed no change (44.0 ± 11 vs. 43.4 ± 10.3,P= 0.44), and a decrease (41.9 ± 10 vs. 36.6 ± 6.4,P< 0.001) in the placebo and in the levosimendan group, respectively.
  
  
  CONCLUSIONS
  Levosimendan treatment significantly improves peak VO2and reduces VE/VCO2slope and BNP in patients with ADHF.
authors.affiliation: Centro Cardiologico Monzino Scientific Institute for Research, Hospitalisation and Health Care (IRCCS) Milan Italy.
authors.forename: Saima
authors.initials: S
authors.lastname: Mushtaq
authors.affiliation: Centro Cardiologico MonzinoScientific Institute for Research, Hospitalisation and Health Care (IRCCS)MilanItaly; Cardiovascular Section, Department of Clinical Sciences and Community HealthUniversity of MilanMilanItaly.
authors.forename: Daniele
authors.initials: D
authors.lastname: Andreini
authors.affiliation: Centro Cardiologico Monzino Scientific Institute for Research, Hospitalisation and Health Care (IRCCS) Milan Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Farina
authors.affiliation: Centro Cardiologico Monzino Scientific Institute for Research, Hospitalisation and Health Care (IRCCS) Milan Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Salvioni
authors.affiliation: Centro Cardiologico Monzino Scientific Institute for Research, Hospitalisation and Health Care (IRCCS) Milan Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Pontone
authors.affiliation: Department of Cardiovascular, Respiratory, Nephrological, Anaesthesiological and Geriatric Sciences 'La Sapienza' University of Rome Rome Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Sciomer
authors.affiliation: Centro Cardiologico Monzino Scientific Institute for Research, Hospitalisation and Health Care (IRCCS) Milan Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Volpato
authors.affiliation: Centro Cardiologico MonzinoScientific Institute for Research, Hospitalisation and Health Care (IRCCS)MilanItaly; Cardiovascular Section, Department of Clinical Sciences and Community HealthUniversity of MilanMilanItaly.
authors.forename: Piergiuseppe
authors.initials: P
authors.lastname: Agostoni
keywords: Advanced chronic heart failure; Cardiopulmonary exercise test; Levosimendan