Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Open-label, Multicenter Trial for the Safety and Efficacy of Intracoronary Adult Human Mesenchymal Stem Cells After Acute Myocardial Infarction
Brief Summary: Early reperfusion strategies in tandem with remarkable advances in drugs and devices for treating myocardial infarction (MI) have contributed to a reduction in early mortality, but cardiovascular disease remains the leading cause of death worldwide. Current management strategies cannot solve the problem of cardiomyocyte loss and consequent progression of heart failure. In this respect, stem-cell therapy has shown potential benefits for repairing the damaged myocardium. Mesenchymal stem cells (MSCs) have been considered to be attractive therapeutic candidates because of their high capacity for replication: paracrine effect: ability to preserve potency: and because they do not cause adverse reactions to allogeneic versus autologous transplants. Intracoronary injection of stem cells seems to be safe, but only one clinical trial using MSCs via the intracoronary route in the setting of acute myocardial infarction (AMI) has been carried out. The investigators therefore assessed the safety and efficacy of intracoronary autologous bone marrow (BM)-derived human MSCs in patients with AMI.


Options:
A: Inclusion Criteria:

* acute myocardial infarction with time to revascularization \>6 hours from symptom start
* clear target vessel
* large myocardial infarction defined as: proximal vessel occlusion, CK \> 1000 U/L, myocardial scar in magnetic resonance imaging \> 10% of left ventricular muscle mass
* potential prior thrombolysis
* written informed consent

Exclusion Criteria:

* acute myocardial infarction with revascularization within 6 hours after symptom start
* prior myocardial infarction
* no clear target vessel
* contraindication for magnetic resonance imaging (e.g. pacemaker, ICD)
* severely depressed left ventricular ejection fraction (less than 20% in magnetic resonance imaging)
* prior hematologic disease
* prior chemo therapy
* prior stem cell transplantation
* prior treatment with G-CSF
* known alteration of the bone marrow by alcohol or drugs, e.g. agranulocytosis
* local infection of puncture sites
B: Inclusion criteria:

* age 40-75 years
* anterior wall AMI with 120-720 minutes from onset of symptoms to PCI
* ST elevation on ECG according to WHO criteria
* angiographically significant stenosis on LAD proximal to the second diagonal branch
* successful PCI with stenting of culprit lesion
* hypokinetic, akinetic or dyskinetic segments assessed by echocardiography in a standard 16 segment model and
* CK-MB above 3 times upper reference value.

Exclusion criteria:

* previous MI with established significant Q-waves on ECG
* cardiogenic shock
* permanent pacemaker or other contraindication to MRI
* stroke with significant sequela
* short life expectancy due to extra cardiac reason
* uncontrolled endocrinological disturbance
* HIV and/or HBV/HCV positive serology
* mental disorder or other condition which interferes with patient possibility to comply with the protocol.
C: Inclusion Criteria:

* Patients will be eligible if presenting all characteristics described below:

  * ST segment elevation myocardial infarction in two or more contiguous leads, and according to the WHO definition, at least one of the following two:

    i) Presence of chest pain. ii) Elevation of the myonecrosis markers.
  * Age between 30 and 80 years old.
  * Ejection fraction ≤50% on Echocardiogram (Simpson) and segmentary dysfunction of the infarction area, measured between the 3rd and 5th day post AMI.

Among patients submitted to thrombolytic therapy, the angioplasty of the related artery should be preferably done up to 24h after thrombolysis, with a maximum deadline of 72h after thrombolysis.

Exclusion Criteria:

* Patients will be ineligible if presenting any of the characteristics described below:

  * AMI related artery presenting TIMI \< 3 at the moment f cell injection.
  * Left Main Coronary Artery Lesion of \>50% or multivessel coronariopathy (\>70% lesion in vessels with \>2,0mm diameter in left anterior descending, circumflex and right coronary territory) indicating the need for CABG or angioplasty with three or more stents implant.
  * Coronary anatomy, after thrombolytic reperfusion, presenting no need for angioplasty with stent implant.
  * Final Diastolic Pression of the LV higher than 30 mmHg during ventriculography for evaluating EF inclusion criteria for the research protocol (item "c" of inclusion criteria).
  * Cardiac arrest or Killip IV AMI at admission with need of ventilatory support.
  * Cardiogenic shock persisting up to the third day after AMI (with need of Intra-aortic balloon pump or vasopressors).
  * AMI mechanical complications (ventricular septal defect, papillary muscle rupture, and left ventricular free wall rupture).
  * Significant valve disease, defined as aortic stenosis (mean systolic pressure gradient across the aortic valve \>50mmHg), mitral stenosis with a valvar area less than 1,5 cm,2 moderate to severe aortic and/or mitral regurgitation.
  * Chronic use of immunosuppressive agents.
  * \> 2,0 mg/dl creatinine or previous dialysis treatment.
  * Presence of fever on the past 48h before injection glaring active systemic infection according to ACCP/SCCM (American College of Chest Physicians/Society of Critical Care Medicine) sepsis definition.
  * Sustained ventricular tachycardia 48h after AMI.
  * Illicit drugs abuse or alcohol abuse (based on DSM IV).
  * Any co morbidity, with survival impact in two years.
  * Myocarditis
  * Active liver disease
  * COPD in continuous steroids use.
  * Hematological disease, neoplasm, bone disease or hemostatic disturbances.
  * Inflammatory disease or chronicle infectious disease.
  * Presence of definitive implantation of a cardiac pace maker or cardiac defibrillator.
  * Impossibility to reach a cells suspension of 100 million mononuclear cells due to cells paucity in the bone marrow aspirate.
D: Inclusion Criteria:

* aged 18-70 years
* ischemic chest pain for \>30 min
* admitted to hospital \<24 h after the onset of chest pain
* electrocardiography showed ST segment elevation \>1 mm in two consecutive leads in the limb leads or \>2 mm in the precordial leads
* they could be enrolled in the study \<72 h after successful revascularization

Exclusion Criteria:

* cardiogenic shock (defined as systolic blood pressure \<90 mmHg requiring intravenous pressors or intra-aortic balloon counterpulsation)
* life-threatening arrhythmia
* impossible conditions for cardiac catheterization
* advanced renal or hepatic dysfunction
* history of previous coronary artery bypass graft
* history of hematologic disease
* history of malignancy
* major bleeding requiring blood transfusion
* stroke or transient ischemic attack in the previous 6 months
* structural abnormalities of the central nervous system (brain tumor, aneurysm, history of surgery)
* traumatic injury after myocardial infarction
* use of corticosteroids or antibiotics during the previous month
* major surgical procedure in the previous 3 months
* cardiopulmonary resuscitation for \>10 min within the previous 2 weeks
* positive skin test for penicillin
* positive result for viral markers (human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and Venereal Disease Research Laboratory (VDRL) test)
* pregnancy, possible candidate for pregnancy or breastfeeding females
* drug abusers
* inappropriate patients to participate in the study according to the chief investigator

Answer: D