Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy of Intramyocardial Injection of Autologous Bone-Marrow Cells in Patients With Severe, Chronic Ischemic Heart Disease Undergoing Coronary Bypass Surgery
Brief Summary: This study was designed to test the hypothesis that direct injection of bone-marrow cells in the heart may increase the number of blood vessels, ameliorating the heart's performance, and relieving patients from symptoms like angina and/or shortness of breath.


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: Major Inclusion Criteria:

* Be ≥ 18 and \< 95 years of age.
* Provide written informed consent.
* Diagnosis of nonischemic dilated cardiomyopathy.
* Be a candidate for cardiac catheterization within 5 to 10 weeks of screening.
* Been treated with appropriate maximal medical therapy for heart failure.
* Ejection fraction below 40% and either a left ventricular end diastolic diameter (LVEDD) \> 5.9cm in male subjects, an LVEDD of \> 5.6cm in female subjects or left ventricular end diastolic volume index \> 125 mL/m2
* Be able to undergo an MRI or CT.

Major Exclusion Criteria:

* Baseline glomerular filtration rate equal or \< 45 ml/min/1.73m2.
* Be eligible for or require standard-of-care surgical or percutaneous intervention for the treatment of nonischemic dilated cardiomyopathy.
* Presence of a prosthetic aortic valve or heart constrictive device.
* Presence of a prosthetic mitral valve.
* Previous myocardial infarction (MI) as documented by a clinical history that will include an elevation of cardiac enzymes and/or ECG changes consistent with MI.
* Diagnosis of nonischemic dilated cardiomyopathy due to valvular dysfunction, mitral regurgitation, tachycardia, or myocarditis.
* Previous treatment for post-infarction left ventricular dysfunction including PCI and thrombolytic therapy.
* Documented presence of a known LV thrombus, aortic dissection, or aortic aneurysm.
* Documented presence of epicardial stenosis of 70% or greater in one or more major epicardial coronary arteries.
* Documented presence of aortic stenosis (aortic stenosis graded as 1.5cm2 or less).
* Documented presence of moderate to severe aortic insufficiency (echocardiographic assessment of aortic insufficiency graded as ≥+2).
* Evidence of a life-threatening arrhythmia in the absence of a defibrillator (nonsustained ventricular tachycardia ≥ 20 consecutive beats or complete second or third degree heart block in the absence of a functioning pacemaker) or QTc interval \> 550 ms on screening ECG.
* AICD firing in the past 30 days prior to the procedure
* Be eligible for or require coronary artery revascularization.
* Diabetic with poorly controlled blood glucose levels and/or evidence of proliferative retinopathy.
* Have a hematologic abnormality as evidenced by hematocrit \< 25%, white blood cell \< 2,500/ul or platelet values \< 100,000/ul without another explanation.
* Have liver dysfunction, as evidenced by enzymes (ALT and AST) greater than three times the ULN.
* Have a coagulopathy condition = (INR \> 1.3) not due to a reversible cause.
* Known, serious radiographic contrast allergy.
* Known allergies to penicillin or streptomycin.
* Organ transplant recipient.
* Have a history of organ or cell transplant rejection
* Clinical history of malignancy within 5 years (i.e., patients with prior malignancy must be disease free for 5 years), except curatively-treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma.
* Non-cardiac condition that limits lifespan to \< 1 year.
* On chronic therapy with immunosuppressant medication.
* Serum positive for HIV, hepatitis BsAg, or viremic hepatitis C.
* Female patient who is pregnant, nursing, or of child-bearing potential and not using effective birth control.
* Have a history of drug or alcohol abuse within the past 24 months.
* Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial.
C: Inclusion Criteria:

* Age 18-70 years old
* Diagnosis of DCM according to European Society of Cardiology position statement
* Left ventricular ejection fraction (LVEF) by echocardiography 20-40%,
* New York Heart Association (NYHA) functional class heart failure II or III for at least 3 months before referral.

Exclusion Criteria:

* Acute multi-organ failure
* History of any malignant disease within 5 years
* Diminished functional capacity due to non-cardiac co-morbidities (COPD, PAOD, morbid obesity)
* Pregnancy
D: Inclusion Criteria:

* Diagnosis of chronic, severe, diffuse, multivessel atherosclerotic coronary artery disease (CAD) referred for CABG.
* Echocardiogram-assessed LVEF between 25 and 55% (Simpson's rule).
* Angina (or equivalent) functional class II to IV (Canadian Cardiovascular Society) despite maximally tolerated medical therapy.
* Abnormal myocardial perfusion tests:

  i. Cardiac scintigraphy ii. Magnetic resonance imaging iii. Dobutamine-atropine stress-echocardiogram
* Non-candidates for a percutaneous coronary intervention (PCI) due to ANY of the following:

  i. High risk lesion ii. Extensive lesion iii. Diffuse, small vessel disease
* Non-candidates for a complete CABG, or candidates for a complete CABG in whom, according to an expert panel, there is a high probability of failure of the grafts due to the extension and severity of the disease, with diffuse, small vessel involvement.
* To provide a signed, written informed consent, according to the National Guidelines for Clinical Trials.

Exclusion Criteria:

* Severe valve heart disease requiring surgical repair.
* Serologic diagnostic of Chagas' disease.
* Symptoms of heart failure, even from an ischemic etiology, in the absence of objectively documented myocardial ischemia.
* Malignant ventricular arrhythmias (like VT), unless an ICD have been placed.
* Any acute coronary syndrome in the past 3 months.
* End-stage renal disease requiring maintenance dialysis.
* History of neoplasia.
* Drug or alcohol abuse.
* Life expectancy below 2 years.
* Enrollment in any cell therapy trial in the past 2 years.

Answer: D