Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase IIa Randomized Study to Assess the Safety, Tolerability, and Preliminary Efficacy of a Single Intravenous Dose of Ischemia-tolerant Allogeneic Mesenchymal Bone Marrow Cells to Subjects With Non-ischemic Heart Failure
Brief Summary: A phase IIa study to assess the safety and preliminary efficacy of intravenous dose of ischemia-tolerant Allogeneic Mesenchymal Bone Marrow Cells in subjects with non-ischemic heart failure.


Options:
A: 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.
B: 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 less than or equal to 50%.
* Able to perform a metabolic stress test.

Exclusion Criteria:

* Baseline glomerular filtration rate \< 45 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 (echocardiographic 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.
* Contra-indication to performance of a magnetic resonance imaging scan.
* 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 non-viremic hepatitis C.
* Female patient who is pregnant, nursing, or of child-bearing potential and not using effective birth control.
C: Inclusion Criteria:

Eligible patients must meet all of the following inclusion criteria:

1. Age ≥ 18 and \< 80 years.
2. Systolic dysfunction with left ventricular ejection fraction (LVEF) ≤ 35% as assessed by echocardiography.
3. Ischemic heart failure without known need for revascularization.
4. Total MLHFQ score \> 30.
5. Ability to perform a 6 minute walk test \> 100 m and ≤ 400 m.
6. History of hospitalization for heart failure (HF) within 12 months prior to screening or treatment in an outpatient clinic with intravenous vasoactive therapy (including vasodilators, positive inotropic agents and vasopressors) or diuretics for worsening Heart Failure within 12 months prior to screening.
7. Be or must have been within the previous 12 months in New York Heart Association (NYHA) Class III or IV or Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) class 4, 5, 6 or 7, and at the time of inclusion, must be at least in NYHA Class II or greater.
8. Use of ACE inhibitor and/or angiotensin receptor blocker (ARB); and beta blocker, for at least 3 months prior to screening visit, unless intolerant or contraindicated.
9. Stable dosing of ACE inhibitor, angiotensin receptor blocker , beta blocker, aldosterone blocker,and diuretics for at least one month prior to screening visit, defined as ≤50% change in total dose of each agent.
10. Willing and able to give written informed consent.

Exclusion Criteria (summarized):

Eligible patients must meet none of the following exclusion criteria:

1. Women who are pregnant, confirmed by a positive urine or serum human chorionic gonadotropin laboratory test at screening.
2. Women of child-bearing potential without a negative serum or urine pregnancy test at screening. Women who are postmenopausal (12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH level \> 40 mIU/mL or 6 weeks post surgical bilateral oophorectomy) or surgically sterile are not considered to be of child-bearing potential. Reliable contraception includes surgical sterilization, hormonal contraception, or doublebarrier methods.
3. Men refusing to exercise a reliable form of contraception.
4. Myocardial infarction, unstable angina or percutaneous coronary intervention (PCI) within 90 days prior to screening, or coronary artery bypass graft surgery within 180 days prior to screening.
5. Patient on a cardiac transplant list or previously received any solid organ transplant.
6. Previously underwent cardiac surgery with remodeling procedure, left ventricular assist device placement or cardiomyoplasty. This exclusion does not apply to patients who underwent ventricularplasty without placement device more than one year ago.
7. Patient has undergone cardiac resynchronization therapy within 6 months prior to screening.
8. Severe uncontrolled HF requiring need for intensive intravenous diuretics or inotropic support within 1 month prior to screening.
9. Inability to perform a 6 minute walk test due to physical limitations other than HF including:

   1. Severe peripheral vascular disease
   2. Severe pulmonary disease or chronic obstructive pulmonary disease limiting exercise
   3. Orthopedic limitations, severe muscular diseases, any other joint or muscular disease or neurological disorder (such as an old stroke or neuropathy) limiting the ability to walk for 6 minutes.
10. Dependence on chronic oral steroid therapy.
11. Stroke or transient ischemic attack leading to limitations in lower extremities or occurring within 180 days prior to screening.
12. Active myocarditis, constrictive pericarditis, restrictive, hypertrophic or congenital cardiomyopathy.
13. BMI \< 19 or \> 45.
14. Left ventricular thrombus.
15. Left ventricular (LV) wall thickness \< 8mm visualized in more than 50% of LV, and defined as a "LV no-go zone".
16. LV aneurysm or candidate for surgical aneurysmectomy.
17. Sustained ventricular tachycardia or ventricular fibrillation which led to automatic implantable cardioverter/defibrillator (AICD) therapy (shock) within 3 months prior to screening.
18. Primary significant organic valvular heart disease.
19. Moderate to severe aortic valve disease precluding catheter entry into the LV.
20. Mechanical prosthetic valve in aortic or mitral position.
21. Chronic infection or active malignancy.
22. Patient has compromised renal function as reflected by a serum creatinine level \>3.0 mg/dL (\>0.265 mmol/L) or is currently on dialysis.
23. Hematocrit \< 28%.
24. 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.
25. Chronic immunosuppressive therapy due to inflammatory or systemic disease.
26. Patient tested positive for HIV 1 or 2, Hepatitis B or C, human T-cell lymphotrophic virus (HTLV) 1 or 2 (if required by regulations) or syphilis.
27. Exposure to any previous experimental cell or angiogenic therapy and/or myocardial laser therapy and/or therapy with another investigational drug within 60 days prior to screening or enrollment in any concurrent study that may confound the results of this study.
28. Known drug or alcohol dependence or any other factors which will interfere with the study conduct or interpretation of the results or in the opinion of the investigator are not suitable to participate.
29. Any illness other than congestive heart failure which might reduce life expectancy to less than 2 years from screening.
30. Known and relevant allergies and/or hypersensitivities to Dextran or other plasma volume expanders to include Gentran, Hyskon and Macrodex.
D: 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)

Answer: D