Levosimendan in Acute Heart Failure Following Acute Myocardial Infarction.

• Efficacy: Changes in regional contractility, BNP and clinical symptoms. Safety:
• Hypotension: BP< 90 mmHg or a drop in MAP >10 mmHg in patients in cardiogenic shock.
• Ventricular arrhythmias.
• Atrial fibrillation.
• Tachycardia (heart rate above 120).
• Ischaemic episodes.

• Mace: Time to death, non-fatal myocardial infarction or revascularization during the first 6 weeks and 6 months. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
• Time to rehospitalisation for decompensated heart failure. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
• Days hospitalised/days in intensive/coronary care. [ Time Frame: At discharge ] [ Designated as safety issue: No ]
• Changes in inflammation markers. [ Time Frame: 1, 5 days, 6 weeks. ] [ Designated as safety issue: No ]
• Improvement in creatinine clearance. [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]
• Improvement of hemodynamic parameters. [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]
• Central venous oxygen saturation. [ Time Frame: 1 day ] [ Designated as safety issue: No ]
• Total mortality. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
• Arrhythmias, hypotension, ischaemic episodes. [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]
• Change in proBNP [ Time Frame: Baseline to day 5 ] [ Designated as safety issue: No ]
• Change in clinical symptom score [ Time Frame: Baseline to day 5 ] [ Designated as safety issue: No ]

• Mace: Time to death, non-fatal myocardial infarction or revascularization during the first 6 weeks and 6 months.
• Time to rehospitalisation for decompensated heart failure.
• Days hospitalised/days in intensive(coronary care.
• Changes in inflammation markers.
• Changes in hemostasis markers.
• Improvement creatinine clearance.
• In a subgroup of patients in cardiogenic shock:
• Improvement of hemodynamic parameters.
• Central venous oxygen saturation.
• Total mortality.
• Need for IV inotropes.

The purpose of this study is to determine the safety and efficacy of a 24 hour infusion with levosimendan in patients with acute myocardial infarction and heart failure after acute percutaneous coronary intervention (PCI) treatment.

Double blind placebo-controlled study with parallel groups in patients with acute PCI treated myocardial infarction complicated with decompensated heart failure. The study include a prospectively defined subgroup of patients in cardiogenic shock. Treating acute myocardial infarction with PCI restores blood flow, but decreased contractility remains for hours and days due to stunned myocardium. Levosimendan has both inotropic and vasodilatory effects which could support the failing heart after treating the acute myocardial infarction with PCI and may improve myocardial stunning and decrease pro-inflammatory cytokines. Levosimendan could improve myocardial contractility, symptoms and outcome without adverse effects. The aims of the study are to investigate whether a 24 hour infusion with levosimendan could improve regional contractility measured by echocardiography, improve BNP levels, reduce the levels of pro-inflammatory cytokines and improve symptoms in patients with acute decompensated heart failure during the first 24 hours after acute PCI.

• Myocardial Infarction
• Heart Failure
• Cardiogenic Shock

• Drug: levosimendan
  1 h infusion, 0.2 microgs/kg/min, 24 h infusion,0.1 microgs/kg/min
  Other Name: Simdax
• Drug: placebo,
  24 h, infusion
  Other Name: placebo

• Active Comparator: 1
  levosimendan
  Intervention: Drug: levosimendan
• Placebo Comparator: 2
  Placebo, 1 h infusion, 0.2 microgs/kg/min, 24 h infusion,0.1 microgs/kg/min
  Intervention: Drug: placebo,

Inclusion Criteria:

• Acute ST-elevation myocardial infarction subject to acute PCI or non-ST elevation myocardial infarction subject to PCI within 72 hours after start of chest pain and:
• Revascularization by PCI,
• Signs of decreased wall-motion in at least 3 of 16 segments of the left ventricle
• Dyspnoea at rest and one of the following:

pulmonary edema, pulmonary congestion,need for CPAP or ventilator, need for IC diuretics or oliguria.

Subgroup of patients in cardiogenic shock: Systolic BP below 90 after 1 hour of volume therapy.

Exclusion Criteria:

• Age below 20 years
• Heart rate above 120 bpm
• Septic shock
• ARDS
• Creatinine >450 micromol/l
• Hepatic impairment
• Significant mechanical outlet obstruction
• Allergy against study drug medication
• Anaemia (Hb <8 g/dl)
• Pregnancy