Please select the eligibility criteria that correspond to the clinical trial below.
Title: Transplantation in Myocardial Infarction Evaluation (TIME) Protocol: A Phase II, Randomized, Controlled, Double-Blind Trial Evaluating the Effect of Timing on the Administration of Bone Marrow Mononuclear Cells (BMMNCs) Versus Placebo in Patients With Acute Myocardial Infarction
Brief Summary: Heart attacks are a leading cause of death for both men and women in the United States. A heart attack occurs when blood flow to the heart is restricted, commonly due to a blood clot that has formed in one of the coronary arteries. If the clot becomes large enough, blood flow to the heart can be blocked almost completely and the heart muscle in that area can suffer permanent injury or death. Although a percutaneous coronary intervention (PCI) can be used to open up the blocked artery and restore blood flow to the heart muscle, there may be a significant amount of heart tissue that has been irreversibly damaged. Recent studies have shown that adult stem cells from bone marrow may be able to improve heart function after a heart attack. This study will evaluate the safety and effectiveness of using adult stem cells for improving heart function in people who have had a recent heart attack and a PCI.


Options:
A: Inclusion Criteria:

* Informed consent;
* age: 18-65 years;
* large acute myocardial infarction (due to proximal occlusion of the left anterior descending or the right coronary artery) after successful primary PTCA carried out between the IV and the XXIV hour from the onset of AMI symptoms;
* signs of microvascular dysfunction in the infarcted area: absence of STeR and angiographic MB, graded according to the dye density score (see van't Hof et al., Circulation, 1998); life expectancy more than 6 months.

Exclusion Criteria:

* Pregnancy;
* indication to aorto-coronaric by-pass;
* neoplasia (previous or in progress);
* primary diseases of the BM;
* diabetes;
* immunosuppressive therapy;
* laboratory alterations of protein S, protein C, ATIII or Fibrinogen;
* severe co-morbidity.
B: Inclusion Criteria:

* Patients with acute myocardial infarction (ST elevation in at least 2 leads \>= 0.2 mV in V1,V2 or V3 or \>= 0.1 mV in other leads), treated by one of the following procedures

  * Either acute PCI with stent implantation within 24 hours after symptom onset or
  * treatment with thrombolysis within 12 hours of symptom onset followed by PCI with stent implantation within 24 hours after thrombolysis.
* Acute PCI / stent implantation has been successful (residual stenosis visually \< 30% and TIMI flow \>= 2).
* At the time of inclusion patient does no longer require i.v. catecholamines or mechanical hemodynamic support (aortic balloon pump)
* Significant regional wall motion abnormality in LV angiogram at the time of acute PCI (ejection fraction \<= 45% on visual estimation).
* Maximal CK elevation \>= 400 U/l (measured at 37° C) with significant MB fraction \> 6%
* Age 18 - 80 Years
* Written informed consent

Exclusion Criteria:

* Regional wall motion abnormality outside the area involved in the index acute myocardial infarction.
* Need to revascularize additional vessels, outside the infarct artery.
* Arteriovenous malformations or aneurysms
* Active infection (CRP \> 10 mg/dl) now, or fever or diarrhea within last 4 weeks.
* Chronic inflammatory disease
* HIV infection or active hepatitis
* Neoplastic disease without documented remission within the past 5 years.
* Cerebrovascular insult within 3 months
* Impaired renal function (creatinine \> 2 mg/dl) at the time of cell therapy
* Significant liver disease (GOT \> 2x upper limit) or spontaneous INR \> 1,5)
* Anemia (hemoglobin \< 8.5 mg/dl)
* Platelet count \< 100.000/µl
* Hypersplenism
* Known allergy or intolerance to clopidogrel, heparin or abciximab.
* History of bleeding disorder
* Gastrointestinal bleeding within 3 months
* Major surgical procedure or traumata within 2 months
* Uncontrolled hypertension
* Pregnancy
* Mental retardation
* Previously performed stem / progenitor cell therapy
* Participation in another clinical trial within the last 30 days.
C: Inclusion Criteria:

* patient included in one of the registered cell-based cardiac therapy of the participating center

Exclusion Criteria:

* none
D: Inclusion criteria

1. Patients at least 21 years of age
2. Patients with first acute MI with successful primary percutaneous coronary intervention (PCI) in an artery at least 2.5 mm in diameter within 24 hours of onset of symptoms.
3. No contraindications to undergoing cell therapy procedure within three to seven days following AMI and PCI.
4. Hemodynamic stability as defined as no requirement for IABP, inotropic or blood pressure supporting medications.
5. Ejection fraction following reperfusion with PCI \<=45% as assessed by echocardiography.
6. Consent to protocol and agree to comply with all follow-up visits and studies.
7. Women of child bearing potential willing to use an active form of birth control.

Exclusion criteria

Patients will be excluded from the study if they meet any of the following conditions:

1. History of sustained ventricular arrhythmias not related to their AMI (evidenced by previous holter monitoring and/or medication history for sustained ventricular arrhythmias in patient's medical chart).
2. Require CABG or PCI due to the presence of residual coronary stenosis \>70% luminal obstruction in the non-infarct related vessel (Additional PCI of non-culprit vessels may be performed prior to enrollment).
3. History of any malignancy within the past five years excluding non-melanoma skin cancer or cervical cancer in-situ.
4. History of chronic anemia (hemoglobin (Hb) \<9.0 mg/dl).
5. History of thrombocytosis (platelets \>500k).
6. History of thrombocytopenia in the absence of recent evidence that platelet counts are normal
7. Known history of elevated INR (PT) or PTT.
8. Life expectancy less than one year.
9. History of untreated alcohol or drug abuse.
10. Currently enrolled in another investigational drug or device trial
11. Previous CABG.
12. Previous MI resulting in LV dysfunction (LVEF \<55%)
13. History of stroke or transient ischemic attack (TIA) within the past six months.
14. History of severe valvular heart disease (aortic valve area \<1.0 cm2 or \>3+ mitral regurgitation).
15. Pregnancy or breast feeding
16. Subjects with a known history of HIV, or has active hepatitis B,active hepatitis C, or active TB
17. Patients with active inflammatory or autoimmune disease on chronic immuno-suppressive therapy.
18. Contraindications to cMRI.
19. Previous radiation to the pelvis with white blood cell count (WBC) and platelet counts below hospital specific normal values.
20. Women child bearing potential not willing to practice an active form of birth control.
21. Chronic liver disease that might interfere with survival or treatment with cell therapy.
22. Chronic renal insufficiency as defined by a creatinine ≥ 2.0 mg/dL or requires chronic dialysis.

Answer: D