Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Double-Blind, Randomized, Placebo-Controlled Study of Levosimendan in Patients With Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass
Brief Summary: A study to evaluate levosimendan compared with placebo in reducing the composite event rate of all-cause death, perioperative MI, need for new dialysis, or use of mechanical assist (IABP, LVAD or ECMO) in subjects with reduced ejection fraction undergoing cardiac surgery on cardiopulmonary bypass (CPB).


Options:
A: Inclusion Criteria:

* Written, signed and dated informed consent
* Male and female patients over 18 years of age. Females of childbearing potential must have a negative pregnancy test and must refrain from breastfeeding. Women who are postmenopausal \[two years since last menstrual cycle\], surgically sterilised or who have undergone a hysterectomy are considered not to be of childbearing potential
* Hospitalised patients with acutely decompensated heart failure
* Left ventricular ejection fraction less than or equal to 30 % as assessed using echocardiography, radionuclide ventriculography or contrast angiography within 12 months
* Clinical need for intravenous inotropic support as evidenced by insufficient response to intravenous diuretics and/or vasodilators (nitroglycerin, nitroprusside) and at least one of the following at screening:

  * oliguria (mean urine output \< 30 ml/h for at least 6 hours) and not a result of hypovolemia
  * dyspnoea at rest or mechanical ventilation for heart failure
  * haemodynamic impairment in those patients with Swan-Ganz catheter inserted (PCWP ≥ 18 mmHg and/or Cardiac Index ≤ 2.2 l/min/m2)

Exclusion Criteria:

* Severe obstruction of ventricular outflow tracts such as haemodynamically significant uncorrected primary valve disease or hypertrophic cardiomyopathy or impaired ventricular filling such as restrictive cardiomyopathy
* Weight ≥ 160 kg
* Cardiac surgery within 30 days before screening
* Stroke within 3 months before screening
* Systolic blood pressure persistently less than 85 mmHg at screening or at baseline
* Heart rate persistently 130 bpm or greater at screening or at baseline
* Serum potassium less than 3.5 mmol/l at screening
* Administration of any inotropic agent (e.g. dobutamine, milrinone, amrinone, enoximone, epinephrine, norepinephrine) except digitalis or dopamine (with dose of less than or equal than 2 mg/kg/min) during the current hospitalisation
* Hypersensitivity to levosimendan or dobutamine or any of their excipients
* A history of Torsades de Pointes
* Severe renal insufficiency (serum creatinine \> 450 mmol/l \[5.0 mg/dl\]) or on dialysis
* Significant hepatic impairment at discretion of the investigator
* Acute bleeding
* Severe anemia (haemoglobin \< 8 g/dl) at screening
* Septicaemia or septic shock
* Other serious diseases limiting life expectancy considerably (e.g. end-stage cancer)
* Participation in a clinical trial with any experimental treatment within 30 days prior to screening or previous participation in the present study
* Administration of levosimendan within 30 days prior to screening
B: Inclusion Criteria:

* Confirmed myocardial infarction (heart attack)
* Confirmed persistent cardiogenic shock
* Confirmed patency of the infarct related artery (heart attack artery has been opened through the use of a blood clot dissolving drug or a balloon or angioplasty heart procedure)
* Less than 24 hour duration of cardiogenic shock (the time since the heart attack occurred and the artery was opened must be less than 24 hours)

Exclusion Criteria:

* Infection
* Other cause of shock (not heart attack)
* Shock due to heart valve disease
* Severe heart valve disease
* Right sided heart failure
* Shock due to arrhythmia (irregular heart rhythm)
* Severe kidney disease
* Aortic dissection (tear in aorta)
* Adult respiratory distress syndrome (ARDS) (severe lung inflammation)
* Severe brain damage
* Severe irreversible multi-system failure (failure of multiple body organs)
* Major chest or abdominal surgical procedure within 30 days except if prior CABG and reocclusion occurs
* Primary pulmonary hypertension (high blood pressure in the arteries of the lungs)
* Age younger than 18 years
* Requirement for emergency coronary artery bypass grafting (CABG) or infarct-related artery occlusion (heart attack artery completely blocked)
* Ongoing or recent participation in another clinical trial of an investigational drug
* Prior enrollment in this study or rapid resolution of cardiogenic shock before treatment (shock gets better before study starts)
* Positive pregnancy test in women who are of childbearing potential
C: Inclusion Criteria:

* A written informed consent must be obtained for hospitalized male or female patients over 18 years old of age.
* The eligible patients must be diagnosed with worsening heart failure as evidenced by dyspnea at rest, poor ejection fraction and have been treated with IV diuretics.
* It is allowable for the patients to be treated with IV inotropes and vasodilators.

Exclusion Criteria:

The following criteria would exclude the patient from study:

* invasive cardiac procedure (e.g. cardiac surgery, LVAD, cardioversion, cardiac re-synchronization),
* rhythm disorders (e.g. earlier Torsades de Pointes, increased heart rate),
* severe ventricular outflow obstruction,
* angina,
* hypotension,
* uncorrected hypokalemia,
* CNS (e.g. stroke, TIA),
* respiratory (e.g. COPD, intubated patients, oral,
* intravenous or intramuscular steroids),
* renal insufficiency (e.g. increased serum creatinine, dialysis),
* hepatic impairment (e.g. significant increase in liver enzymes),
* decompensation from active infection and acute bleeding (e.g. severe anemia).
* Female patients of child bearing potential must have a negative pregnancy test and use adequate contraceptive precautions.
* Also excluded is the use of amrinone and milrinone prior to randomization, a history of hypersensitivity to levosimendan or any of the excipients and previous participation in a clinical trial with any experimental treatment within the last 30 days.
D: Inclusion Criteria:

* Documented LVEF ≤35% measured by ventriculogram, echocardiogram (ECHO), nuclear scan, or MRI within 60 days before surgery.
* Scheduled or urgent 1) CABG surgery, 2)CABG with aortic valve surgery, 3) CABG with mitral valve surgery, or 4) mitral valve surgery with or without other valves
* Surgery will employ CPB pump
* Signed (by the subjects or their legally acceptable representatives) informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

Exclusion Criteria:

* Restrictive or obstructive cardiomyopathy, constrictive pericarditis, restrictive pericarditis, pericardial tamponade, or other conditions in which cardiac output is dependent on venous return.
* Evidence of systemic bacterial, systemic fungal, or viral infection within 72 hours before surgery.
* Dialysis at randomization (either hemodialysis, peritoneal dialysis, continuous venovenous hemofiltration, or ultrafiltration).
* Estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73m2.
* Weight ≥ 170 kg.
* Patients whose SBP cannot be managed to ensure SBP \> 90 mmHg at initiation of study drug.
* Heart rate ≥ 120 bpm, persistent for at least 10 minutes screening and unresponsive to treatment.
* Hemoglobin \< 80 g/L.
* Serum potassium \< 3.5 mmol/L and \> 5.5 mmol/L at baseline.
* A history of Torsades de Pointes.
* Mechanical assist device (IABP, LVAD, ECMO) in the patient at the start of surgery or pre-planned to be inserted during surgery before coming off CPB.
* Patients with aortal femoral occlusive disease that would prohibit use of IABP unless VAD or ECMO not available.
* Liver dysfunction Child Pugh Class B or C
* Patients having severely compromised immune function
* Pregnant, suspected to be pregnant, or breast-feeding.
* Received an experimental drug or used an experimental medical device in previous 30 days.
* Known allergic reaction or sensitivity to Levosimendan or excipients.
* Received commercial Levosimendan within 30 days before the planned start of study drug.
* Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator.

Answer: D