Please select the eligibility criteria that correspond to the clinical trial below.
Title: Intracoronary Injection of Autologous Bone Marrow Mononuclear Cells for Severe Myocardial Infarction
Brief Summary: Emerging evidence suggests that stem cells and progenitor cells derived from bone marrow can be used to improve cardiac function in patients after acute myocardial infarction. In this randomised trial, we aim to assess whether intracoronary transfer of autologous bone-marrow cells could improve myocardial viability at 3 and 12 months' follow-up.


Options:
A: 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.
B: Inclusion Criteria:

* Men or women between 18-75 years.
* Acute myocardial infarction
* Absence of viability in the infarcted zone and LVEF \<45%.

Exclusion Criteria:

* History of prior myocardial infarction
* Significant stenosis in another coronary territory than the acutely treated vessel
C: Inclusion Criteria

* Myocardial infarction due to coronary artery atherosclerotic disease. Myocardial infarction will be defined by a rise in serum troponin I to greater than the 99th percentile of the upper limits of normal with at least one of the following:

  * symptoms of ischemia
  * ECG changes indicative of new ischemia (new ST-T changes or new left bundle branch block)
  * development of pathological Q waves on the ECG
  * imaging evidence of new loss of viable myocardium, OR
  * new regional wall motion abnormality.
* An area of regional dysfunction, i.e., hypokinetic, akinetic, or dyskinetic, as assessed by echocardiography, left ventriculography, or MRI.
* History of successful angioplasty and stent placement, with resultant TIMI grade flow ≥ 2, in the artery supplying the infarcted, dysfunctional territory and through which the cells will be infused.
* Left ventricular ejection fraction of ≥ .25 and ≤ .45 as determined by clinically-indicated assessment of cardiac function (echocardiogram, gated blood pool scan, x-ray contrast ventriculography, CT and/or MRI one day or more following successful reperfusion).
* No further revascularization clinically indicated at the time the patient is assessed for participation in the clinical trial. This will be determined by a cardiologist who is not an investigator in the clinical trial. No further revascularization may be indicated by no arteries with significant stenosis, the location, and extent of any stenosis may not be suitable for angioplasty, the distal vessels may not be suitable for placement of bypass grafts, and/or the patient declines angioplasty or bypass surgery.
* Ability to provide informed consent and follow-up with protocol procedures.
* Age \> 18 years.

Exclusion Criteria:

* Non-cardiovascular disease with expected life expectancy of \< 3 years.
* Contraindications to MRI, including:

  * prior ICD placement
  * estimated glomerular filtration rate \< 50 ml/min
  * known reaction to gadolinium
  * claustrophobia
  * pacemaker
  * ear implant, and cochlear implant.
* History of possible presence of ferromagnetic material including programmable shunt, shrapnel, penile prosthesis, intra-uterine device, bullets, tattoos, artificial limb, blood vessel coil, and tissue expander may require special screening.
* Septal infarction involving the right ventricular endocardium as demonstrated by screening MRI (because its presence might increase the potential risk of septal biopsy and decrease treatment benefit due to decreased viability of injured septal-based stem cells).
* History of cardiac tumor, or cardiac tumor demonstrated on MRI.
* Requirement for chronic immunosuppressive therapy.
* Participation in an on-going protocol studying an experimental drug or device.
* Diagnosis of right ventricular arrhythmogenic dysplasia.
* Patients with occlusion of the infarct-related artery before administration of the study agent.
* Current alcohol abuse.
* Current drug abuse.
* Pregnancy.
* Child-bearing potential without use of effective contraception. Men intending to "father" children are also excluded.
* Human Immunodeficiency virus infection.
* Viral hepatitis.
* Uncontrolled diabetes and/or hemoglobin A1C \> 8.5%.
* Abnormal liver function (SGPT \> 3 times the upper reference range) and hematology (hematocrit \< 25%, WBC \< 3000, platelets \< 100,000) studies without a reversible, identifiable cause.
* Ventricular tachycardia or fibrillation not associated with an acute ischemic episode.
* New York Heart Association Class 4 congestive heart failure.
* Canadian Cardiovascular Society Angina Class 3 or 4.
* Evidence of tumor on screening chest/abdominal/pelvic (body) CT scan.
* Symptomatic ventricular tachyarrhythmia complicating the index myocardial infarction.
* Individuals who are not fluent in English.
D: Inclusion Criteria:

* ST elevation acute myocardial infarction
* \< 80years
* successful revascularization of culprit vessel

Exclusion Criteria:

* uncontrolled congestive heart failure
* uncontrolled myocardial ischemia
* uncontrolled ventricular arrhythmia
* malignancy
* serious hematologic disease
* chronic renal failure

Answer: B