Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Controlled Single Blind Trial of Autologous Bone Marrow Mononuclear Cells Under Electromechanical Guidance for Therapeutic Angiogenesis
Brief Summary: This is a phase 1, single-blind trial to evaluate using autologous bone marrow mononuclear stem cells in ischemic cardiomyopathy patients. The patients must have a Left Ventricular Ejection Fraction (LVEF) of less than or equal to 45%. Once the patient meets all inclusion criteria, and no exclusion criteria are found, the subject is consented for the study, and extensive baseline testing is performed at St Luke's Hospital in Houston. Once all baseline testing criteria is met, the patient has their own bone marrow harvested and later that day the subject is taken to a cardiac catheterization lab where left ventricular electromechanical mapping using NOGA software (NOGA mapping) is performed and the processed stem cells are injected under electromechanical guidance into the affected areas of the left ventricle. The patient is usually discharged home the next day and returns for follow up visits at weeks 1, 2, 4, 6, 8, 12, months 6 and 12 and for phone call follow-up at months 4, 5, 7, 8, 9, 10, 11. Patients undergo extensive testing at most of these follow-up visits, including repeat cardiac catheterization with NOGA mapping at month 6 after stem cell injection.


Options:
A: Inclusion Criteria:

* Patients \>18 years of age with significant coronary heart disease not amenable to revascularization.
* Left ventricular dysfunction (LVEF) less than or equal to 45%, measured by echocardiogram; limiting angina (Class II to IV); and/or congestive heart failure (CHF), NYHA class II to III
* Receiving maximal medical therapy, defined as a medical regimen that includes the maximal tolerated dose of at least two antiangina medications, such as beta-blockers, nitrates, or calcium-channel blockers
* Presence of a defect, as identified by single photon emission computed tomography (SPECT) isotope protocol, or viability, as identified by NOGA electromechanical cardiac mapping system
* Coronary artery disease not well suited to any other type of revascularization procedure in the target region of the ventricle, as determined by a cardiovascular surgeon and interventional cardiologist who are not investigators in the trial
* Hemodynamic stability, as defined by systolic blood pressure of at least 80 mm Hg without intravenous pressors or support devices
* Females of childbearing potential must be willing to use two forms of birth control for the duration of the study

Exclusion Criteria:

* Atrial fibrillation or flutter without a pacemaker that guarantees a stable heart rate
* Unstable angina
* Left ventricular (LV) thrombus, as documented by echocardiography or LV angiography
* A vascular anatomy that precludes cardiac catheterization
* Severe valvular disease or mechanical aortic valve that precludes safe entry of the catheter into the left ventricle
* Pregnant or lactating
* Platelet count less than 100,000 per mm3
* White blood cell count less than 2,000 per mm3
* Revascularization within 30 days of consent
* Transient ischemic attack or stroke within 60 days of study consent
* Implantable cardioverter-defibrillator shock within 30 days of baseline consent, and within 30 days of randomization
* Presence of ventricular tachycardia lasting 30 seconds or more on 24-hour Holter monitor or electrocardiogram (ECG) performed during screening period
* Bleeding diathesis, defined as an international normalized ratio of at least 2.0 in the absence of warfarin therapy
* A history of malignancy in the last 5 years excluding basal cell carcinoma, that has been surgically removed, with proof of surgical clean margins
* Has a known history of HIV, has active hepatitis B or active hepatitis C
* Any condition requiring immunosuppressive medication
* High-risk acute coronary syndrome (ACS) or a myocardial infarction in the month prior to consent
* A left ventricular wall thickness of \<8 mm (by echocardiogram) of the infero-lateral wall at the target site for cell injection.
* Inability to walk on a treadmill, except for class IV angina patients, who will be evaluated separately
* Enrolled in an investigational device or drug study within the previous 30 days
* Hepatic dysfunction, as defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 1.5 times the upper limit of normal range prior to study entry
* Chronic renal insufficiency, defined as a serum creatinine level greater than 2.5 mg/dL or requiring dialysis
* Any other condition that in the judgment of the investigator would be a contraindication to enrollment or follow-up
B: Inclusion Criteria:

* LVEF less than 45%
* Functional class III or IV angina
* At least 7% reversibility by Single Photon Emission Computed Tomography (SPECT) nuclear study
* there are additional inc. criteria

Exclusion Criteria:

* AGe \<18 or \>70 years of age
* Constant atrial fibrillation
* Left ventricular (LV) thrombus
* History of malignancy in the last 5 years
* LV wall thickness of \< 8 mm at the target site
* there are additional exclusion criteria
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:

* EF \< 45 %
* NYHA 2 - 3

Exclusion Criteria:

* Acute coronary syndrome within last 6 weeks.
* Pregnancy
* FEV1 \<1.0
* Cancer
* Any severe disease which could interfere with the treatment or the outcome

Answer: B