Please select the eligibility criteria that correspond to the clinical trial below.
Title: Safety & Efficacy of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Recipients
Brief Summary: The main purpose of this research is to determine whether injecting mesenchymal precursor cells (MPC) into the heart during surgery to implant a left ventricular assist device (LVAD) is safe. MPCs are normally present in human bone marrow and have been shown to increase the development of blood vessels and new heart muscle cells in the heart. In addition, this research is being done to test whether injecting the MPCs into the heart is effective in improving heart function.


Options:
A: Inclusion Criteria:

1. Males and females ≥18 years of age
2. LVEF ≤35% on echocardiogram within 12 months of randomization to undergo MRI
3. Screening cardiac MRI at baseline with:

   Ejection fraction ≤40% No significant hyper enhancement on MRI scan in the opinion of the central imaging lab reviewer
4. Patients with non-ischemic heart failure etiology, as documented by absent or non-obstructive coronary artery disease on x-ray angiography or coronary computed tomography
5. Patients with history of heart failure and treated for at least three months with GDMT
6. NYHA class II-III symptoms
7. Ability to understand and provide signed informed consent
8. Reasonable expectation that patient will receive standard post-treatment care and attend all scheduled safety follow-up visits

Exclusion Criteria:

1. Pregnant or nursing women or those of childbearing age and not using an effective method of contraception
2. History of stroke within 3 months
3. Cardiac surgery within 3 months prior to randomization or the likelihood of a requirement for such procedures during the study period
4. Current ICD or CRT or implantation planned within 6 months of infusion
5. Presence of clinically significant, uncorrected valvular heart disease, hypertrophic or restrictive cardiomyopathy, active myocarditis, or uncontrolled hypertension
6. History of cardiac arrest or life-threatening arrhythmias within 3 months
7. Treatment with parenteral inotropic agents within 1 month of randomization
8. Anticipated cardiac transplantation within 1 year
9. Illness other than heart failure with life expectancy less than 1 year
10. Received an experimental drug or device within 30 days of randomization
11. Left ventricular assist device or implantation planned in the next 6 months
12. Patients with complex congenital heart disease
13. Uncontrolled seizure disorder
14. Presence of immune deficiency
15. Clinically significant hematologic, hepatic, or renal impairment as determined by screening clinical laboratory tests:

    * Liver disease = ALT or AST \> 3x normal, alkaline phosphatase or bilirubin \>2x normal)
    * Renal disease = estimated glomerular filtration rate as assessed by the MDRD formula \<30 ml/min
    * Hematologic = Unexplained leukocytosis \>10 or hemoglobin \< 9gm/dl
16. Presence of any other clinically-significant medical condition, psychiatric condition, or laboratory abnormality, that in the judgment of the investigator or sponsor for which participation in the study would pose a safety risk to the subject
17. Inability to comply with the conditions of the protocol
18. Malignancy within the previous five years, except adequately treated basal cell carcinoma, provided that it is neither infiltrating nor sclerosing, and carcinoma in situ of the cervix
19. Active myocarditis or early postpartum cardiomyopathy (within six months).
20. Systemic corticosteroids, cytostatics, immunosuppressive drug therapy (cyclophosphamide, methotrexate, cyclosporine, azathioprine, etc.), and DNA depleting or cytotoxic drugs taken within four weeks prior to study treatment
21. Porphyria
22. Allergy to sodium citrate or any "caine" type of local anesthetic
23. Any contraindication for gadolinium use for MRI
24. Patient scheduled for hospice care
25. Clinically relevant abnormal findings in the clinical history, physical examination, ECG, or laboratory tests at the screening assessment that would interfere with the objectives of the study or would preclude safe completion of the study. Abnormal findings could include: known HIV infection or other immunodeficiency state, chronic active viral infection (such as hepatitis B or C), acute systemic infections (defined as patients undergoing treatment with antibiotics), gastrointestinal tract bleeding, or any severe or acute concomitant illness or injury
26. Any other medical, social, or geographical factor that would make it unlikely that the patient could comply with study procedures (e.g., alcohol abuse, lack of permanent residence, severe depression, disorientation, distant location, or noncompliance)
B: Inclusion Criteria:

* Normal coronary angiogram
* Left ventricular ejection fraction \< 40%
* NYHA III or IV heart failure symptoms
* Bone marrow reactivity (G-CSF test)
* Presence of viable myocardium

Exclusion Criteria:

* Hematologic malignancy
* Multiorgan failure
C: Inclusion Criteria:

* Signed informed consent, inclusive of release of medical information, and Health Insurance Portability and Accountability Act (HIPAA) documentation
* Age 18 years or older
* If the subject or partner is of childbearing potential, he or she must be willing to use adequate contraception (hormonal or barrier method or abstinence) from the time of screening and for a period of at least 16 weeks after procedure
* Female subjects of childbearing potential must have a negative serum pregnancy test at screening
* Admitted to the clinical center at the time of randomization
* Clinical indication and accepted candidate for implantation of an FDA-approved (US sites only) or Health Canada-approved (Canadian sites only) implantable, non-pulsatile LVAD as a bridge to transplantation or for destination therapy.

Exclusion Criteria:

* Planned percutaneous LVAD implantation
* Anticipated requirement for biventricular mechanical support
* Concomitant arrhythmia ablation at time of LVAD implantation

  -- Planned aortic valve intervention for aortic insufficiency at the time of LVAD implantation
* Cardiothoracic surgery within 30 days prior to randomization
* Spontaneous myocardial infarction related to ischemia due to a primary coronary event such as unstable plaque rupture, erosion or dissection within 30 days prior to randomization
* Prior cardiac transplantation, LV reduction surgery, or cardiomyoplasty
* Acute reversible cause of heart failure (e.g. myocarditis, profound hypothyroidism)
* Stroke within 30 days prior to randomization
* Platelet count \< 100,000/ul within 24 hours prior to randomization
* Acute infectious process: acute bacterial, fungal, or viral disease OR acute exacerbation of chronic infectious disease such as hepatitis
* Presence of \>10% anti-HLA antibody titers with known specificity to MPC donor HLA antigens
* A known hypersensitivity to dimethyl sulfoxide (DMSO), murine, and/or bovine products
* History of a known active malignancy within the past 3 years except for localized prostate cancer, cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that has been definitively treated
* Presence of human immunodeficiency virus (HIV)
* Received investigational intervention within 30 days prior to randomization
* Treatment and/or an incomplete follow-up treatment of any investigational cell based therapy within 6 months prior to randomization
* Active participation in other research therapy for cardiovascular repair/regeneration
* Prior recipient of stem precursor cell therapy for cardiac repair
* Pregnant or breastfeeding at time of randomization.
* History of known or suspected hypercoagulable state in the opinion of the investigator
D: 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.

Answer: C