Phase I Trial of Endocavitary Injection of Bone Marrow Derived CD133+ Cells in Ischemic Refractory Cardiomyopathy (RECARDIO Trial)

This will be a Phase I study investigating the safety and preliminary efficacy of endocavitary injection of bone-marrow-derived CD133+ cells in 15 patients with ischemic heart failure (IHF) not eligible for conventional revascularization. Patients eligible will undergo bone-marrow aspiration. On the day following bone-marrow aspiration patients will undergo fluoroscopy-based endocavitary intramyocardial injections of the target areas previously identified by gated-SPECT/CMR. CD133+ cells suspended in physiological saline supplemented with 5% human albumin solution will be injected into the myocardium via the endocardial route.

After discharge, efficacy follow-up will last 6-months safety follow-up (FU) will be extended up to 1 year.

Inclusion criteria

• Ischemic heart failure not amenable to any type of revascularization procedure (percutaneous or surgical) as determined by one interventional cardiologist and one cardiovascular surgeon,
• Canadian Cardiovascular Society Angina functional class III to IV angina and/or symptoms of heart failure (NYHA score IIb to IV) under state-of-the-art maximal medical therapy,
• Left Ventricular Ejection Fraction between 20% and 45%,
• Peak V02 ≤ 21 mL/Kg/min,
• Presence of a reversible perfusion defect ≥ 10% of the left ventricular myocardium (at least 2 segments over 20) as determined by gated-SPECT, 6.18 years ≤ Age ≤ 75 years,

7.Hemodynamic stability, 8.Ability to accomplish a cardiopulmonary exercise testing, 9.Are not pregnant and do not plan to become pregnant during the study. Females with childbearing potential must provide a negative pregnancy test within 1-7 days before intervention and must be using oral or injectable contraception (non-childbearing potential is defined as post-menopausal for at least 1 year or surgical sterilization or hysterectomy at least 3 months before study start), 10.A signed consent form that has been approved by the institutional review board.

Exclusion criteria

• A high-risk acute coronary syndrome (ACS) or a myocardial infarction in the past 3 months,
• Presence of a documented unstable angina,
• Left ventricular thrombus, as documented by echocardiography,
• Evidence of a life-threatening arrhythmia,
• Presence of any severe mitral valve disease requiring valve replacement or reconstruction,
• Presence of a mechanical aortic valve,
• Presence of stenosis of the aortic valve, graded as ≥+2 equivalent to an orifice area of 1,5 cm2 or less,
• Presence of moderate to severe insufficiency of the aortic valve,
• A left ventricular wall thickness of <8 mm at the target site for cell injection, as assessed by 2-D echocardiography and/or cardiac MRI,
• Have a known, serious radiographic contrast allergy,
• Contraindications to bone-marrow aspiration,
• Be an organ transplant recipient,
• Have liver dysfunction, as evidenced by enzymes (AST,ALT) >3x the upper limits of normals,
• Severe renal failure (creatinine plasma levels > 2.5 mg/dl),
• A bleeding diathesis (defined as an INR greater than 1,5 not because of a reversible cause, i.e. warfarin),
• Have an hematologic abnormality without other explanation,
• Apparent infection (c-reactive protein (CPR)>30 mg/L, fever > 37 °C),
• An infectious-disease test result positive for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C, treponema pallidum (VDRL), HTLV 1 and 2,
• Previous or current documented history of leukemia, myeloproliferative or myeloplastic disorders,
• Have a cardiac condition that limits lifespan to <1 y,
• A history of malignancy in the past 5 years,
• Have a history of drug or alcoholic abuse within the past 24 months,
• Be on chronic therapy with immunosuppressants,
• Pregnant or lactating status,
• Any condition that, in the judgment of the investigator, would place the patient at undue risk.