Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 1 Randomized, Double-blind, Placebo-controlled, Dose Escalation, Multicenter Study to Determine the Safety of Intravenous Ex-vivo Cultured Adult Human Mesenchymal Stem Cells (Provacel) Following Acute Myocardial Infarction
Brief Summary: The purpose of the study is to determine whether adult stem cells \[Provacel™(PUMP1)\] are safe and possibly effective in the treatment of acute myocardial infarction (heart attack).


Options:
A: Inclusion Criteria:

* Subject is ≥ 18 and \< 75 years old;
* Subject has Heart Failure, New York Heart Association (NYHA) class II or class III with LVEF \> 15% and ≤ 40% as assessed by transthoracic echocardiography;
* Subject has ischemic heart disease;
* Subject has an identifiable (by transthoracic echocardiography) area of transmural scar within the left ventricle;
* Subject is on optimal and stable medical therapy for more than 2 months;
* Subject is willing and able to undergo an ICD implantation, prior to receiving C-Cure™ or already has an ICD implanted;
* Subject agrees to comply with all follow-up evaluations;
* Subject has been informed of the nature of the clinical trial and agrees to its provision and has provided written informed consent.

Exclusion Criteria:

* Subject has been treated with cell-based therapy;
* Subject has myocardial revascularization by PCI or CABG within 2 months prior to enrolment;
* Subject has had an MI within 2 months prior to enrolment;
* Subject is planned for PCI, CABG or any cardiac surgery;
* Subject has received a biventricular pacemaker within 6 month prior to enrolment;
* Subject has moderate to severe aortic valve heart disease, aortic or mitral prosthetic valve;
* Subject has a significant mitral valve insufficiency (Effective Regurgitant Orifice (ERO) \> 0.2 cm²) with possibility of mitral valve surgery;
* Subject has left ventricular thrombus;
* Subject has LV aneurysma or is a candidate for surgical aneurysmectomy;
* Subject LV ventricular wall thickness is \< 5 mm in the target territory;
* Subject has proven high grade atrioventricular block or sustained ventricular tachyarrhythmias;
* Subject has an hemodynamically significant congenital heart disorder;
* Subject has clinical evidence for infection or active malignancy;
* Subject has known stable chronic kidney dysfunction with serum creatinine \> 2.5 mg/dL at two occasions during the screening period;
* Subject has experienced severe adverse reaction/allergies to contrast agents;
* Subject has atherosclerosis and/or tortuosity of the aorta, iliac or femoral arteries of a degree, that could impede or preclude the safe retrograde passage of the delivery catheter, in the judgment of the investigator;
* Subject is on chronic immunosuppressive transplant therapy;
* Subject had an autologous or allogenic bone marrow or peripheral stem cell transplant or prior solid organ transplantation;
* Subject has a multisystem disease;
* Subject has been tested positive for Human Immunodeficiency Virus (HIV 1 or HIV 2), Hepatitis B Virus (HBV), Hepatitis C (HCV) and/or syphilis;
* Women of child bearing potential;
* Subject has life expectancy \< 1 year from non heart failure related causes;
* Subject suffers from morbid obesity (Body Mass Index (BMI) \> 40);
* Subject has a recent history of alcohol or drug abuse;
* Subject has any other surgical or medical condition that, in the judgment of the investigator might warrant exclusion or be contraindicated for safety reasons;
* Subject is currently participating in another trial.
B: Inclusion Criteria:

* Male or female between 21 and 85 years old
* First heart attack within 1 to 10 days

Exclusion Criteria:

* Positive for HIV 1 and 2
* Previous heart attack
* Pacemaker or other device
* Pregnant or breastfeeding
* Allergic to cow or pig derived products
* Previous bone marrow transplant
* Involved in another clinical trial within the past 30 days
* Alcohol or recreational drug abuse within the past 6 months
* Hepatitis Positive
* Major surgical procedure or major trauma within the past 14 days
* Body weight greater than 300 pounds
* Autoimmune disease ( e.g. Lupus, Multiple Sclerosis)
C: Inclusion Criteria:

* Diagnosis of chronic ischemic left ventricular dysfunction secondary to MI.
* Be a candidate for cardiac catheterization.
* Been treated with appropriate maximal medical therapy for heart failure or post-infarction left ventricular dysfunction.
* Ejection fraction between 20% and 50%.
* Able to perform a metabolic stress test.

Exclusion Criteria:

* Baseline glomerular filtration rate \<50 ml/min/1.73m2.
* Presence of a mechanical aortic valve or heart constrictive device.
* Documented presence of aortic stenosis (aortic stenosis graded as ≥+2 equivalent to an orifice area of 1.5cm2 or less).
* Documented presence of moderate to severe aortic insufficiency (echocardio- graphic assessment of aortic insufficiency graded as ≥+2).
* Evidence of a life-threatening arrhythmia (nonsustained ventricular tachycardia ≥20 consecutive beats or complete heart block) or QTc interval \>550 ms on screening ECG. In addition; patients with sustained or a short run of ventricular tachycardia on ECG or 48 hour Ambulatory ECG during the screening period will be removed from the protocol.
* Documented unstable angina.
* AICD firing in the past 60 days prior to the procedure.
* Be eligible for or require coronary artery revascularization.
* 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.
* 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 hepatitis C.
* Female patient who is pregnant, nursing, or of child-bearing potential and not using effective birth control.
D: Inclusion Criteria:

* Diagnosis of ischemic or non-ischemic dilated cardiomyopathy according to WHO criteria. Ischemic: DCM in a patient with a history of myocardial infarction or evidence of clinically significant (\>/= 70% narrowing of a major epicardial artery) coronary artery disease. Non-ischemic: Dilation and impaired contraction of left ventricle or both ventricles of idiopathic, familial/genetic, viral and/or immune, toxic origin, or associated with recognized cardiovascular disease in which the degree of myocardial dysfunction is not explained by normal loading conditions or the extent of ischemic damage.
* No other cardiac surgery or percutaneous cardiac interventions likely to produce clinical improvement, as determined by an interventional cardiologist (for PTCA) and a cardiothoracic surgeon (for CABG). This condition is satisfied in patients w/chronic ischemic disease who have previously been successfully revascularized but have failed to show clinical improvement. All patients who are candidates for revascularization are ineligible for participation.
* LVEF \</= 30% by echocardiogram within 30 days prior to randomization.
* Symptomatic heart failure in NYHA class III or IV.
* Able to comply with scheduled visits in cardiac out-patient clinic.
* Able to tolerate study procedures, including bone marrow aspiration, cardiac CT, metabolic stress test,6 minute walk test.
* Males and females, 18-86 years of age.
* Life expectancy of 6 months or more in the opinion of the investigator.
* Able to give informed consent.
* Normal organ and marrow function (Leukocytes \>/= 3,000/microgram, Absolute neutrophil count \>/= 1,500/microgram, Platelets \>/= 140,000/microgram, AST(SGOT)/ALT (SGPT) \</= 2.5 X institutional standards range and Creatinine \</= 2.5 mg/dL).
* Controlled blood pressure (systolic blood pressure \</= 140; diastolic blood pressure \</= 90 mmHg) and established anti-hypertensive therapy as necessary prior to entry into the study.
* Stable, standard medical therapy for DCM for at least 1 month with NO new medications to treat the disease introduced in the last 3 months. Standard medical therapy includes: Placement of AICD unless contraindicated (refusal of AICD not considered valid contraindication), use of ACE inhibitors and/or AT-1 receptor blockers as well as loop diuretics unless contraindicated and, depending on the type of heart failure associated with the disease, standard therapy may also include use of vasodilators, beta blockers, digoxin, and aldosterone or other medications.
* Pre-existing conditions are adequately controlled in the opinion of the investigator.
* Fertile patients must agree to use an appropriate form of contraception while participating in the study.

Exclusion Criteria:

* Severe primary valvular heart disease including, but not limited to, aortic valve stenosis and insufficiency.
* Known history of COPD defined as Gold stage IIB (FEV1/FVC\<70% with 30%\</=FEV1\<50% predicted, with or without chronic symptoms of cough, sputum production, dyspnea) or more severe or restrictive pulmonary disease.
* Known history of primary pulmonary hypertension.
* VAD implantation.
* Myocardial infarction within 4 weeks prior to randomization.
* History of life-threatening ventricular arrhythmia, except if an AICD is implanted.
* Unstable angina, characterized by increasingly frequent episodes with modest exertion or at rest, worsening severity, and prolonged duration.
* Patients at high risk for complications due to injection procedure (e.g. patients who have severe peripheral atherosclerotic disease that does not allow advancement of the catheter; patients who have a prosthetic aortic or mitral valve; patients who have a LV thrombus or aneurysm; patients who have an aortic dissection or aneurysm, etc.).
* Patients w/poorly controlled diabetes mellitus (HbAlc\>9.0%).
* Patients receiving treatment with hematopoietic growth factors (e.g. EPO, G-CSF).
* Patients who require uninterruptible anticoagulation therapy (e.g. warfarin)that cannot be stopped for 72 hours prior to bone marrow aspiration and intramyocardial injections; OR patients receiving anti-platelet therapy (e.g. clopidogrel) that cannot be stopped for 7 days prior to bone marrow aspiration and transendocardial injections, unless contraindicated.
* Known cancer and undergoing treatment including chemotherapy and radiation.
* Patients requiring continuous, systemic, high dose corticosteroid therapy (more than 7.5 mg/day) within 1 month before aspiration or 6 months after injection procedure.
* End stage renal disease requiring dialysis.
* Patients pregnant or lactating; positive for hCG
* History of alcohol consumption regularly exceeding the equivalent of 2 drinks/day (1 drink = 5 oz of wine or 12 oz \[360mL\] of beer or 1.5 oz \[45mL\]) of hard liquor or history of illicit drug use w/in 6 months of screening.
* Known allergies to protein products (horse or bovine serum, or porcine trypsin) used in the ex-vivo cell production process.
* BMI of 40 Kg/m2 or greater.
* Patients receiving experimental medications or participating in another clinical study within 30 days of screening.
* HIV or syphilis, positive at time of screening.
* Active Hepatitis B or Hepatitis C infection at the time of screening.
* Patient determined unsuitable for cellular therapy, in the opinion of the investigator or sponsor.
* Patients receiving anti-angiogenic drugs (e.g. anti-VEGF).
* Known allergy or sensitivity to contrast agents used in imaging procedures.
* Minimum LV wall thickness of less than 6mm as determined by ECHO.

Answer: B