Please select the eligibility criteria that correspond to the clinical trial below.
Title: Injection of Autologous CD34-Positive Cells for Neovascularization and Symptom Relief in Patients With Myocardial Ischemia
Brief Summary: The purpose of this study is to determine if cell therapy with your own cells (autologous cells) delivered with a catheter to regions of the heart with poor blood flow will be safe and if it will relieve your chest pain and/or your ability to exercise.


Options:
A: 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.
B: Inclusion Criteria:

* patient included in one of the registered cell-based cardiac therapy of the participating center

Exclusion Criteria:

* none
C: Inclusion Criteria:

* Symptomatic patients with a diagnosis of heart failure secondary to ischaemic heart disease who are on optimal heart failure treatment and no further treatment options available
* Patient has been considered for an implantable defibrillator in keeping with NICE guidelines

Exclusion Criteria:

* Recent acute coronary syndrome as judged by a rise of Troponin above normal values in the last 6 months
* The presence of cardiogenic shock
* The presence of acute left and/or right-sided pump failure as judged by the presence of pulmonary oedema and/or new peripheral oedema
* Known severe pre-existent left ventricular dysfunction (ejection fraction \< 10% prior to randomisation)
* Congenital cardiac disease
* Cardiomyopathy secondary to a reversible cause e.g. thyroid disease, alcohol abuse, hypophosphataemia, hypocalcaemia, cocaine abuse, selenium toxicity \& chronic uncontrolled tachycardia
* Cardiomyopathy in association with a neuromuscular disorder e.g. Duchenne's progressive muscular dystrophy
* Contra-indication for bone marrow aspiration
* Known active infection
* Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) syphilis or HTLV
* Lifestyle with high risk for infection with HIV, HBV or HCV syphilis or HTLV
* Serum creatinine \>200 umol/L
* Chronic inflammatory disease
* Serious known concomitant disease with a life expectancy of less than one year
* Follow-up impossible (no fixed abode, etc)
* Previous participation in this study
* Female subjects of childbearing potential
* Atrial fibrillation
* Patients who have responded to the implantation of a biventricular pacemaker
* Weight \>140kg
D: 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).

Answer: D