Please select the eligibility criteria that correspond to the clinical trial below.
Title: C-Cure - Safety, Feasibility and Efficacy of Guided Bone Marrow-derived Mesenchymal Cardiopoietic Cells for the Treatment of Heart Failure Secondary to Ischemic Cardiomyopathy
Brief Summary: The purpose of this clinical trial is to evaluate the feasibility, safety and efficacy of left ventricular endocardial injection of guided bone marrow-derived cardiopoietic cells (C-Cure) in the setting of chronic heart failure secondary to ischemic cardiomyopathy.


Options:
A: Inclusion Criteria:

* Diagnosis of dilated cardiomyopathy according to WHO criteria
* Syndromic heart failure in functional class III or IV of the NYHA
* Enrollment and continuous follow-up in cardiac out-patient clinic
* Adequate medical therapy after optimization therapy
* Echocardiogram with an ejection fraction equal to or less than 35% by Simpson's rule

Exclusion Criteria:

* Valvular diseases, except functional mitral or tricuspid reflow
* Coronariography showing a significant lesion (obstruction of at least 50% of the lumen in the troncus or the main arteries - LAD, CX, RC) in one or more arteries
* Serologic diagnosis for Chagas disease or at least two of the following criteria: epidemiology, right bundle branch block, anterior hemi-block, apical aneurism
* Sustained ventricular tachycardia
* Abusive use of alcohol or illicit drugs
* Pregnancy
* Use of cardio toxic drugs
* Any co-morbidity with impact in life expectancy in 2 years
* Renal function compromised (creatinine above 2 mg/dl)
B: Inclusion Criteria:

* Subject is ≥ 18 and \< 75 years old;
* Subject has Heart Failure, New York Heart Association (NYHA) class II or class III with LVEF \> 15% and ≤ 40% as assessed by transthoracic echocardiography;
* Subject has ischemic heart disease;
* Subject has an identifiable (by transthoracic echocardiography) area of transmural scar within the left ventricle;
* Subject is on optimal and stable medical therapy for more than 2 months;
* Subject is willing and able to undergo an ICD implantation, prior to receiving C-Cure™ or already has an ICD implanted;
* Subject agrees to comply with all follow-up evaluations;
* Subject has been informed of the nature of the clinical trial and agrees to its provision and has provided written informed consent.

Exclusion Criteria:

* Subject has been treated with cell-based therapy;
* Subject has myocardial revascularization by PCI or CABG within 2 months prior to enrolment;
* Subject has had an MI within 2 months prior to enrolment;
* Subject is planned for PCI, CABG or any cardiac surgery;
* Subject has received a biventricular pacemaker within 6 month prior to enrolment;
* Subject has moderate to severe aortic valve heart disease, aortic or mitral prosthetic valve;
* Subject has a significant mitral valve insufficiency (Effective Regurgitant Orifice (ERO) \> 0.2 cm²) with possibility of mitral valve surgery;
* Subject has left ventricular thrombus;
* Subject has LV aneurysma or is a candidate for surgical aneurysmectomy;
* Subject LV ventricular wall thickness is \< 5 mm in the target territory;
* Subject has proven high grade atrioventricular block or sustained ventricular tachyarrhythmias;
* Subject has an hemodynamically significant congenital heart disorder;
* Subject has clinical evidence for infection or active malignancy;
* Subject has known stable chronic kidney dysfunction with serum creatinine \> 2.5 mg/dL at two occasions during the screening period;
* Subject has experienced severe adverse reaction/allergies to contrast agents;
* Subject has 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, in the judgment of the investigator;
* Subject is on chronic immunosuppressive transplant therapy;
* Subject had an autologous or allogenic bone marrow or peripheral stem cell transplant or prior solid organ transplantation;
* Subject has a multisystem disease;
* Subject has been tested positive for Human Immunodeficiency Virus (HIV 1 or HIV 2), Hepatitis B Virus (HBV), Hepatitis C (HCV) and/or syphilis;
* Women of child bearing potential;
* Subject has life expectancy \< 1 year from non heart failure related causes;
* Subject suffers from morbid obesity (Body Mass Index (BMI) \> 40);
* Subject has a recent history of alcohol or drug abuse;
* Subject has any other surgical or medical condition that, in the judgment of the investigator might warrant exclusion or be contraindicated for safety reasons;
* Subject is currently participating in another trial.
C: Inclusion Criteria:

* Diagnosis of ischemic or nonischemic DCM according to World Health Organization criteria; OR ischemic DCM (DCM in a patient with a history of myocardial infarction or evidence of clinically significant (\>/= 70% narrowing of a major epicardial artery) coronary artery disease)
* No other cardiac surgery or percutaneous cardiac interventions likely to produce clinical improvement, in the opinion of the investigator and the referring interventional cardiologist
* Left ventricular ejection fraction \</= 30% by echocardiogram
* Symptomatic heart failure in NYHA functional class III or IV
* Able to comply with scheduled visits in cardiac out-patient clinic
* Able to tolerate study procedures, including bone marrow aspiration, left lateral thoracotomy or thoracoscopy with single lung ventilation, MRI or cardiac CT, spirometry and 6 minute walk test
* Males and females, 18-86 years of age
* Life expectancy of 6 months or more in the opinion of investigator
* Able to give informed consent
* Normal organ and marrow function (Leukocytes \>/= 3,000/microgram, Absolute neutrophil count \>/= 1,500/microgram, Platelets \>/= 140,000/microgram, AST (SGOT)/ALT (SGPT) \</= 2.5 x institutional standards range) and Creatinine \</= 2.5 mg/dL)
* Adequate pulmonary function (forced expiratory volume in one second \[FEV1\] \> 50% predicted)
* Controlled blood pressure (systolic blood pressure \</= 140; diastolic blood pressure \</= 90 mmHg) and established anti-hypertensive therapy as necessary prior to entry into the study
* Adequate medical management of DCM and other pre-existing conditions. Drug treatment regimen must have been established for at least a month prior to randomization in eligible patients.
* Fertile patients must agree to use an appropriate form of contraception while participating in the study

Exclusion Criteria:

* Severe primary valvular insufficiency(ies)
* Known history of Chronic Obtrusive Pulmonary Disease (Gold stages IIB or more severe only) or restrictive pulmonary disease
* Known history of primary pulmonary hypertension
* Ventricular Assist Device implantation
* Myocardial infarction within 4 weeks of randomization
* Life-threatening ventricular arrhythmia, except if implantable cardioverter defibrillator is implanted
* Unstable angina, characterized by increasingly frequent episodes with modest exertion or at rest, worsening severity, and prolonged duration
* Patients receiving treatment with hematopoietic growth factors
* Patients who require uninterruptible anticoagulation or anti-platelet therapy \[i.e. anticoagulation therapy (e.g. warfarin) that cannot be stopped for 72 hours prior to bone marrow aspiration and intramyocardial injections\]
* Patients receiving anti-platelet therapy (e.g. clopidogrel) that cannot be stopped for 7 days prior to bone marrow aspiration and intramyocardial injections
* Known cancer and undergoing treatment including chemotherapy and radiotherapy
* Patients who will require continuous, systemic, high dose corticosteroid therapy (more than 7.5 mg/day) within 6 months after surgery
* End stage renal disease requiring dialysis
* Patients pregnant or lactating; positive for hCG
* History of alcohol consumption regularly exceeding the equivalent of 2 drinks/day (1 drink = 5 oz of wine or 12 oz \[360mL\] of beer or 1.5 oz \[45mL\] of hard liquor) or history of illicit drug use within 6 months of screening
* Known allergies to protein products (horse or bovine serum, or porcine trypsin)
* Body Mass Index of 40 Kg/m2 or greater
* Patients receiving experimental medications or participating in another clinical study within 30 days of screening
* HIV or syphilis, positive at time of screening
* Active Hepatitis B, or Hepatitis C infection at time of screening
* In the opinion of the investigator, patient is unsuitable for cellular therapy
* Patients receiving anti-angiogenic drugs
D: Inclusion Criteria:

* Diagnosis of ischemic or non-ischemic dilated cardiomyopathy according to WHO criteria. Ischemic: DCM in a patient with a history of myocardial infarction or evidence of clinically significant (\>/= 70% narrowing of a major epicardial artery) coronary artery disease. Non-ischemic: Dilation and impaired contraction of left ventricle or both ventricles of idiopathic, familial/genetic, viral and/or immune, toxic origin, or associated with recognized cardiovascular disease in which the degree of myocardial dysfunction is not explained by normal loading conditions or the extent of ischemic damage.
* No other cardiac surgery or percutaneous cardiac interventions likely to produce clinical improvement, as determined by an interventional cardiologist (for PTCA) and a cardiothoracic surgeon (for CABG). This condition is satisfied in patients w/chronic ischemic disease who have previously been successfully revascularized but have failed to show clinical improvement. All patients who are candidates for revascularization are ineligible for participation.
* LVEF \</= 30% by echocardiogram within 30 days prior to randomization.
* Symptomatic heart failure in NYHA class III or IV.
* Able to comply with scheduled visits in cardiac out-patient clinic.
* Able to tolerate study procedures, including bone marrow aspiration, cardiac CT, metabolic stress test,6 minute walk test.
* Males and females, 18-86 years of age.
* Life expectancy of 6 months or more in the opinion of the investigator.
* Able to give informed consent.
* Normal organ and marrow function (Leukocytes \>/= 3,000/microgram, Absolute neutrophil count \>/= 1,500/microgram, Platelets \>/= 140,000/microgram, AST(SGOT)/ALT (SGPT) \</= 2.5 X institutional standards range and Creatinine \</= 2.5 mg/dL).
* Controlled blood pressure (systolic blood pressure \</= 140; diastolic blood pressure \</= 90 mmHg) and established anti-hypertensive therapy as necessary prior to entry into the study.
* Stable, standard medical therapy for DCM for at least 1 month with NO new medications to treat the disease introduced in the last 3 months. Standard medical therapy includes: Placement of AICD unless contraindicated (refusal of AICD not considered valid contraindication), use of ACE inhibitors and/or AT-1 receptor blockers as well as loop diuretics unless contraindicated and, depending on the type of heart failure associated with the disease, standard therapy may also include use of vasodilators, beta blockers, digoxin, and aldosterone or other medications.
* Pre-existing conditions are adequately controlled in the opinion of the investigator.
* Fertile patients must agree to use an appropriate form of contraception while participating in the study.

Exclusion Criteria:

* Severe primary valvular heart disease including, but not limited to, aortic valve stenosis and insufficiency.
* Known history of COPD defined as Gold stage IIB (FEV1/FVC\<70% with 30%\</=FEV1\<50% predicted, with or without chronic symptoms of cough, sputum production, dyspnea) or more severe or restrictive pulmonary disease.
* Known history of primary pulmonary hypertension.
* VAD implantation.
* Myocardial infarction within 4 weeks prior to randomization.
* History of life-threatening ventricular arrhythmia, except if an AICD is implanted.
* Unstable angina, characterized by increasingly frequent episodes with modest exertion or at rest, worsening severity, and prolonged duration.
* Patients at high risk for complications due to injection procedure (e.g. patients who have severe peripheral atherosclerotic disease that does not allow advancement of the catheter; patients who have a prosthetic aortic or mitral valve; patients who have a LV thrombus or aneurysm; patients who have an aortic dissection or aneurysm, etc.).
* Patients w/poorly controlled diabetes mellitus (HbAlc\>9.0%).
* Patients receiving treatment with hematopoietic growth factors (e.g. EPO, G-CSF).
* Patients who require uninterruptible anticoagulation therapy (e.g. warfarin)that cannot be stopped for 72 hours prior to bone marrow aspiration and intramyocardial injections; OR patients receiving anti-platelet therapy (e.g. clopidogrel) that cannot be stopped for 7 days prior to bone marrow aspiration and transendocardial injections, unless contraindicated.
* Known cancer and undergoing treatment including chemotherapy and radiation.
* Patients requiring continuous, systemic, high dose corticosteroid therapy (more than 7.5 mg/day) within 1 month before aspiration or 6 months after injection procedure.
* End stage renal disease requiring dialysis.
* Patients pregnant or lactating; positive for hCG
* History of alcohol consumption regularly exceeding the equivalent of 2 drinks/day (1 drink = 5 oz of wine or 12 oz \[360mL\] of beer or 1.5 oz \[45mL\]) of hard liquor or history of illicit drug use w/in 6 months of screening.
* Known allergies to protein products (horse or bovine serum, or porcine trypsin) used in the ex-vivo cell production process.
* BMI of 40 Kg/m2 or greater.
* Patients receiving experimental medications or participating in another clinical study within 30 days of screening.
* HIV or syphilis, positive at time of screening.
* Active Hepatitis B or Hepatitis C infection at the time of screening.
* Patient determined unsuitable for cellular therapy, in the opinion of the investigator or sponsor.
* Patients receiving anti-angiogenic drugs (e.g. anti-VEGF).
* Known allergy or sensitivity to contrast agents used in imaging procedures.
* Minimum LV wall thickness of less than 6mm as determined by ECHO.

Answer: B