The purpose of this study is to determine whether the treatment strategy of long-term intermittent every 30 days, continuous intravenous infusion for 24 hours of Levosimendan, associated to optimal contemporary treatment for advanced heart failure reduce the incidence of admission for heart failure worsening at 12 months follow up, compared with the strategy based solely in the optimal contemporary treatment for advanced heart failure.

Aims: To evaluate the efficacy and safety of long-term, intermittent intravenous administration for 24 hours of Levosimendan for the treatment of advanced heart failure. Main end-point: incidence of admission due to decompensation, defined as first admission to emergency services or hospitalization more than 12 hours due to heart failure worsening.

Secondary end-points: major cardiac events, serious adverse events, change in NYHA scale at baseline, 30 days, 6 and 12 months; effects on inflammatory and neurohormonal activation in heart failure, identify factors associated with better survival of patients, quality of life, cost-effectiveness of treatment.

Study Design: Prospective, randomized, double-blind placebo controlled trial.

Scope of the study: patients with advanced heart failure.

Study Subjects: Patients over 18 years old with advanced HF of any etiology, with at least one admission for acute decompensation treated or treatable with Levosimendan within 6 months prior to randomization.

Interventions: a 24-hour infusion every 30 days of Levosimendan or placebo in addition to optimal pharmacological treatment for HF during 12 months.

Determinations: clinical monitoring, protocol-specified analytical determinations, echocardiographic assessment, invasive hemodynamic assessment, functional assessment by 6 min walk test in corridor, quality of life assessment at baseline, after 30 days, 6 months and 12 months.

Inclusion Criteria:

• Age over 18
• Severe symptoms of heart failure with dyspnea and/or fatigue at rest or minimal effort (functional class III and IV of NYHA)
• Episodes of fluid retention (pulmonary or systemic venous congestion, peripheral edema) and/or low cardiac output at rest (peripheral hypoperfusion)
• objective evidence of severe cardiac dysfunction determined by the presence of at least one of the following:
• Left ventricular ejection fraction </= 30%
• A severe impairment of cardiac function by echocardiography with Doppler transmitral flow pattern pseudonormal or restrictive.
• A left ventricular filling pressure elevated (PCP> 16 mmHg and / or DBP average> 12 mm Hg for pulmonary artery catheterization)
• Levels of BNP or NT-proBNP higher in the absence of noncardiac causes for this.
• Severe impairment of functional capacity as evidenced by one of the following:
• Inability to exercise
• A distance <300 m or less in women and / or patients >/= 75 years in the 6-minute walk test
• A test of myocardial oxygen consumption <12-14 ml / kg / min.
• >/= 1 prior history of HF hospitalization in the previous 6 months
• Presence of all the above criteria despite attempts to optimize therapy including diuretics, inhibitors of the renin-angiotensin-aldosterone system and beta-blockers, unless these drugs were not tolerated or were contraindicated, and cardiac resynchronization therapy when indicated.
• consent to participate in the study.

Exclusion Criteria:

• Levosimendan allergy or hypersensitivity.
• Severe renal impairment (creatinine clearance <30 ml / min).
• Severe liver impairment.
• History of autoimmune disease.
• Pregnancy.
• Women of childbearing age not using adequate contraception (hormonal, IUD, barrier + spermicide)
• Heart disease with significant obstructions to ventricular filling or emptying.
• Severe hypotension (Systolic < 90 mmHg).
• Tachycardia > 120 bpm or a history of torsion point type ventricular tachycardia.
• Severe concomitant disease with decreased short-term prognosis.
• Inability to give informed consent.
• Participation in another study.