Please select the eligibility criteria that correspond to the clinical trial below.
Title: Cell Therapy for Coronary Heart Disease: Infusion of Autologous Ex Vivo Cultivated Endothelial Progenitor Cells (EPCs)" and Autologous Bone Marrow Progenitor Cells in Crossover Design for Improvement of Vascularization and Cardiac Function
Brief Summary: Impaired contractile function after a heart attack and due to coronary heart disease is a major cause of "heart failure" limiting quality of life and prognosis, which cannot be prevented even with optimal standard therapy.

The aim of the current trial is to investigate whether infusion of progenitor cells into the coronary artery supplying the most dyskinetic left ventricular area may improve left ventricular contractile function, compared to no cell infusion in the control group, in patients with old (\>= 3 months) myocardial infarction.


Options:
A: Inclusion Criteria:

* Subjects with functional class (CCS) III or IV angina.
* Subjects who have attempted "best" medical therapy without control of symptoms.
* All subjects must have a recent coronary angiogram (within the last 3 months).
* Clinical signs and symptoms of clinically significant ischemia on nuclear perfusion imaging.
* Subjects must be able to complete a minimum of 1 minute but no more than 6 minutes of the Standard Bruce Protocol.
* Subject experiences angina during the baseline exercise tolerance test.
* Subjects must either be no longer capable of reproduction or taking acceptable measures to prevent reproduction during the study.
* Normal renal function.
* Normal liver function.
* Normal blood count.

Angiographic Inclusions:

* Total occlusion of an epicardial coronary artery.
* Candidates at high risk for percutaneous coronary angioplasty of treatment zone(s) based upon clinical or anatomic considerations including but not limited to the following: diabetes, congestive heart failure (severe right heart failure, NYHA class III or IV), left main disease, pulmonary hypertension, severe proximal vessel tortuosity, severe bendpoint obstructions, diffuse disease (\>2 cm in length), small vessel (\<2 mm reference diameter), stenosis which are either diffuse (\>2 cm in length) or distal, incessant restenosis lesions, unfavorable bifurcation stenosis, and degenerated or thrombosed saphenous vein grafts.

Exclusion Criteria:

* Predominant congestive heart failure symptoms.
* Patients who have been hospitalized with a primary diagnosis of CHF in the prior 6 months.
* Patients who have had diuretics added to their medical regimen or an increase in diuretic dosage for signs or symptoms of CHF in the past 6 months.
* Patients with a left ventricular ejection fraction of less than 25% as determined by transthoracic echocardiography.
* Patients with physical findings consistent with ongoing uncontrolled CHF.
* Myocardial infarction within 30 days of treatment.
* Successful coronary revascularization procedures within 3 months of study enrollment.
* Documented stroke or transient ischemic attack (TIA) within 60 days of study enrollment.
* History of severe aortic stenosis or insufficiency; severe mitral stenosis; or severe mitral insufficiency.
* Severe co-morbidity associated with a reduction in life expectancy of less than 1 year.
* Subjects with PT, PTT or platelet counts greater than the upper limit of normal and those with a hematocrit \<35%.
* Subjects with uncontrolled hypertension.
* Currently enrolled in another investigational device or drug trial (IDE or IND) that has not completed the required follow-up period.
* History of alcohol or drug abuse within 3 months of screening.
* Joint or peripheral vascular disease that severely limits treadmill walking.
* Chronic obstructive pulmonary disease that severely limits walking or FEV1.0\<30% predicted.
* Subjects who are pregnant or lactating.
* Males and females who are capable of reproduction and will not take acceptable measures to prevent reproduction during the study.
* Subjects who test positive for HIV, hepatitis B or hepatitis C, have a chronic inflammatory disease, autoimmune disease or are on chronic immunosuppressive medications.
* Subjects with a known hypersensitivity to E. coli-derived proteins.
* Subjects with evidence (clinical, laboratory, or imaging) of cancer recurrence within the past 5 years (other than non-melanoma skin cancer or in situ cervical carcinoma).
B: 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
C: Inclusion Criteria:

* Patients aged 18 to 80
* Patients post-myocardial infarction (\> 3 months old) or with diffuse ischemic CHD
* Signed informed consent

Exclusion Criteria:

- Existing neoplastic disease or signs of tumor recurrence within the last 5 years

* Active infection
* Active internal bleeding
* Stroke within the past 2 years
* Surgery or trauma within the past two months
* Uncontrolled hypertension over 160/100
* Arteriovenous malformations or aneurysms
* HIV infection
* Signs of significant kidney or liver failure (creatinine \> 2.0 mg/dL, GOT \> 2 x upper standard value)
* Thrombopenia (\< 100,000)
* Anemia (hemoglobin \< 8.5 g/dL)
* Mental retardation
* Participation in another clinical study
* Women of childbearing age
* Chronic inflammatory disease
D: Main Inclusion Criteria:

* Male or female participants who are 21 to 80 years of age at the time of signing the informed consent.
* Participants with Canadian Cardiovascular Society (CCS) class III or IV chronic refractory angina.
* Participants without control of their angina symptoms in spite of maximal tolerated doses of anti-angina drugs. Participants must be on optimal therapy for their angina and must have been on a stable anti-anginal medication regimen for at least 4 weeks before signing the informed consent form.
* Participants with obstructive coronary disease unsuitable for conventional revascularization due to unsuitable anatomy or comorbidity as determined at the site and confirmed by an independent adjudication committee.
* Participants must have evidence of inducible myocardial ischemia.
* Participants must experience angina episodes.
* Participants must be able to complete 2 exercise tolerance tests on the treadmill within 3 weeks of randomization.
* If female of childbearing potential, subject must not be pregnant and agree to employ adequate birth control measures for the duration of the study.

Main Exclusion Criteria:

* Cardiovascular hospitalization within 60 days prior to potential study enrollment. Participant has had a successful or partially successful coronary artery bypass graft (CABG) within 6 months or PCTA within 60 days of potential study enrollment.
* Participant has had a placement of a bi-ventricular pacemaker for cardiac resynchronization therapy (CRT) for heart failure within 180 days of potential study enrollment.
* Participant has documented stroke or transient ischemic attacks (TIAs) within 60 days of potential study enrollment.
* Participant has a history of moderate to severe aortic stenosis; or severe aortic insufficiency; or severe mitral stenosis; or severe mitral insufficiency.
* Participant has a prosthetic aortic valve or a mechanical mitral valve replacement.
* Participant has severe co-morbidity associated with a reduction in life expectancy to less than 3 years as a result of chronic medical illnesses.
* Participants with cancer are excluded with the following exceptions:

  * Subjects with in-situ non-melanoma skin cancer or in-situ cervical cancer are not excluded.
  * Participants that have been cancer free for \>= 5 years as determined by their oncologist are not excluded. Subjects with a prior history of stem cell transplant for cancer are excluded no matter how long they have been cancer-free.
* Participants with a history of leukemia or other bone marrow disease.
* Participant has sickle cell disease or sickle cell trait.
* Participants with proliferative retinopathy.
* Participants with Hb A1c \> 9%.
* Participant has platelet counts \>10% above the upper limit of normal (ULN) or platelet counts \< 70,000.
* Participant has a hematocrit \< 30% prior to potential study enrollment.
* Participant has a serum creatinine \> 2.5 mg/dL prior to potential study enrollment.
* Participant tests positive for HIV, hepatitis B, or hepatitis C, or is on chronic immunosuppressive medications, or has had a previous stem cell transplant.
* Participant has a known contraindication to Neupogen (filgrastim) or G-CSF.
* Participant was previously enrolled in an active treatment group of cell therapy trials for cardiovascular disease including any phase of CD34+ stem cell trials.
* Left ventricular (LV) thickness of \< 7 mm in the target areas of injection as measured by during a 2-D echocardiogram (ECHO).
* Atrial fibrillation, atrial flutter, or other uncontrolled arrhythmias that would prohibit accurate electromechanical mapping and NOGA-guided intramyocardial injection.
* Bleeding diathesis with an INR \> 1.8 when not receiving anti-thrombotic therapy.
* Hepatic dysfunction as evidenced by elevated AST or ALT levels \> 2.5 x ULN.
* Any previous transplant requiring immunosuppression.
* Disease state requiring chronic immunosuppression.

Answer: C