Please select the eligibility criteria that correspond to the clinical trial below.
Title: Autologous Stem Cell Transplantation in Acute Myocardial Infarction
Brief Summary: Objectives

Intracoronary transplantation of different cell populations have been used in acute myocardial infarction (AMI) with promising results. The primary objective of the ASTAMI study is to test whether intracoronary transplantation of autologous mononuclear bone marrow cells (mBMC) improve left ventricular ejection fraction (LVEF) after anterior wall AMI.

Design

The ASTAMI study is a randomized, controlled, prospective study. One hundred patients with acute anterior wall ST-elevation myocardial infarction (STEMI) treated with acute PCI are randomized in a 1:1 way to either intracoronary transplantation of autologous mBMC 5-8 days after PCI or to control. Left ventricular function, exercise capacity, biochemical status, functional class, quality of life and complications are validated at baseline and during a 12-month 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:

* 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:

* Visual LVEF at angiogram or echocardiography ≤45%
* Treatment by primary PCI within 24 hours of the onset of chest pain or initial treatment with thrombolysis within the 12 hours followed by PCI within the 24 hours of the onset of chest pain
* Significant regional LV wall motion dysfunction in the infarct related territory
* Age \>18 years

Exclusion Criteria:

* Abnormal regional wall motion outside the infarct region
* Known previous myocardial infarction in the same target vessel
* Known pre-existing left ventricular dysfunction (EF\<45% prior to admission)
* Need for revascularization in the non infarct-related coronary within 4 months
* Pre-existing symptoms of heart failure or known cardiomyopathy
* Known active infection or chronic infection with HIV, HBV or HCV
* Chronic inflammatory disease
* Serious concomitant disease with a life expectancy of less than one year
* Follow up impossible (no fixed abode, etc)
* Contraindication for cardiac MRI (i.e. pace maker, neurostimulator, claustrophobia)
* Severe renal failure (creatinine \>250 mmol/l)
* Relevant liver disease (GOT \> 2x norm or spontaneous INR \> 1,5)
* Anemia (Hb \< 8.5 mg/dl), Thrombocytopenia (\<100.000/µl)
* Pregnancy
* Participation at a clinical trial in the last 30 days
D: 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.

Answer: B