Single or Repeated Intravenous Administration of umbiliCAl Cord Mesenchymal sTrOmal Cells in Ischemic Cardiomyopathy

Eligibility Criteria

• 1. Be ≥ 21 and ≤ 85 years of age.
• 2. Have documented CAD (\> 70% lesion in at least 1 epicardial vessel) with evidence of myocardial injury, LV dysfunction, and clinical evidence of HF.
• 3. Have a "detectable" area of myocardial injury defined as ≥ 5% LV involvement (infarct volume) and any subendocardial involvement by MRI.
• 4. Have an EF ≤ 40% by MRI.
• 5. Be receiving guideline driven medical therapy for HF (beta blockers, diuretics, ACE inhibitors or ARBs, or ARNIs, aldosterone antagonists, hydralazine isosorbide, sodium-glucose transporter 2 inhibitors) ) at stable, maximally tolerated doses for ≥ 1 month prior to consent. "Stable" is defined as stable dose with no changes for 30 days after last dose adjustment. For beta blockade "stable" is defined as no greater than a 50% reduction in dose or no more than a 100% increase in dose.
• 6. Have NYHA class I, II or III symptoms of HF (see Appendix A)
• 7. If a female of childbearing potential, be willing to use one form of birth control for the duration of the study and undergo a serum pregnancy test at baseline and within 36 hours prior to infusion
• 1. Indication for standard of care surgery (including valve surgery, placement of left ventricular assist device, or imminent heart transplantation), coronary artery bypass grafting (CABG) procedure, and/or percutaneous coronary intervention (PCI) for the treatment of ischemic and/or valvular heart disease. Subjects who require or undergo PCI should undergo these procedures a minimum of 3 months in advance of randomization. Subjects who require or undergo CABG should undergo these procedures a minimum of 3 months in advance of randomization. In addition, subjects who develop a need for revascularization following enrollment should undergo revascularization without delay. Indication for imminent heart transplantation is defined as a high likelihood of transplant prior to collection of the 12 month study endpoint. Candidates cannot be UNOS 1A or 1B, and they must have documented a low probability of being transplanted.
• 2. Severe valvular (any valve) insufficiency and/or regurgitation within 12 months of consent
• 3. History of ischemic or hemorrhagic stroke within 90 days of consent
• 4. Presence of a pacemaker and/or implantable cardiac device (ICD) generator with any of the following limitations/conditions:
• * manufactured before the year 2000
• * leads implanted \< 6 weeks prior to consent
• * non transvenous epicardial or abandoned leads
• * subcutaneous ICDs (if not MRI compatible)
• * leadless pacemakers
• * any other condition that, in the judgment of device trained staff, would deem an MRI contraindicated
• 5. Pacemaker dependence with an ICD (Note: pacemaker dependent candidates without an ICD are not excluded)
• 6. A cardiac resynchronization therapy (CRT) device implanted less than 3 months prior to consent.
• 7. Other MRI contraindications (e.g. patient body habitus incompatible with MRI)
• 8. An appropriate ICD firing or anti tachycardia pacing (ATP) for ventricular fibrillation or ventricular tachycardia within 30 days of consent
• 9. Ventricular tachycardia ≥ 20 consecutive beats without an ICD within 3 months of consent, or symptomatic Mobitz II or higher degree atrioventricular block without a functioning pacemaker within 3 months of consent
• 10. Evidence of active myocarditis
• 11. Baseline glomerular filtration rate (eGFR) \< 35 ml/min/1.73m2
• 12. Blood glucose levels (HbA1c) \>10%
• 13. Hematologic abnormality evidenced by hematocrit \< 25%, white blood cell \< 2,500/ul or platelet count \< 100,000/ul
• 14. Liver dysfunction evidenced by enzymes (AST and ALT) ˃ 3 times the ULN.
• 15. HIV and/or active HBV or HCV
• 16. Known history of anaphylactic reaction to penicillin or streptomycin
• 17. Received gene or cell based therapy from any source within the previous 12 months.
• 18. History of malignancy within 2 years (i.e., subjects with prior malignancy must be disease free for 2 years), excluding basal cell carcinoma and cervical carcinoma in situ which have been definitively treated.
• 19. Condition that limits lifespan to \< 1 year
• 20. History of drug abuse (illegal "street" drugs except marijuana, or prescription medications not being used appropriately for a pre-existing medical condition) or alcohol abuse (≥ 5 drinks/day for ˃ 3 months), or documented medical, occupational, or legal problems arising from the use of alcohol or drugs within the past 12 months.
• 21. Participation in an investigational therapeutic or device trial within 30 days of consent
• 22. Cognitive or language barriers that prohibit obtaining informed consent or any study elements
• 23. Pregnancy or lactation or plans to become pregnant in the next 12 months.
• 24. Any other condition that, in the judgment of the Investigator or Sponsor, would impair enrollment, study product administration, or follow up.