Please select the eligibility criteria that correspond to the clinical trial below.
Title: Repetitive Intramyocardial CD34+ Cell Therapy in Dilated Cardiomyopathy
Brief Summary: The goal of REMEDIUM project is to develop personalized stem cell therapy for patients with chronic heart failure due to dilated cardiomyopathy (DCM). The main focus of the project is (1) on repetitive administration of cell therapy that would allow for long-lasting improvements in heart function and outcome in this patient population. In parallel, the investigators aim to (2) develop a standardized patient-specific stem cell product that could be cryopreserved and stored in a stem cell bank for prolonged time periods, and used for therapeutic application when clinically indicated. By using a unique multimodality imaging platform, the goal of this project is also to (3) define standardized clinical criteria that would serve as a guideline for evaluation of the effects of stem cell therapy in future clinical trials and everyday clinical settings. Finally, to improve the clinical implementation of cell therapy,the investigators aim to (4) develop a stem cell delivery technique that could be used to treat both left and right and ventricular failure and could be implemented in a standardized fashion designed for a widespread clinical use.


Options:
A: Inclusion Criteria:

* Age 18-70 years old
* Diagnosis of DCM according to European Society of Cardiology position statement
* Left ventricular ejection fraction (LVEF) by echocardiography 20-40%,
* New York Heart Association (NYHA) functional class heart failure II or III for at least 3 months before referral.

Exclusion Criteria:

* Acute multi-organ failure
* History of any malignant disease within 5 years
* Diminished functional capacity due to non-cardiac co-morbidities (COPD, PAOD, morbid obesity)
* Pregnancy
B: Inclusion Criteria:

* Normal coronary angiogram
* Left ventricular ejection fraction \< 40%
* NYHA III or IV heart failure symptoms
* Bone marrow reactivity (G-CSF test)
* Presence of viable myocardium

Exclusion Criteria:

* Hematologic malignancy
* Multiorgan failure
C: 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.
D: 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

Answer: A