CArdiosphere-Derived aUtologous Stem CElls to Reverse ventricUlar dySfunction (CADUCEUS)

Inclusion Criteria

• Myocardial infarction due to coronary artery atherosclerotic disease. Myocardial infarction will be defined by a rise in serum troponin I to greater than the 99th percentile of the upper limits of normal with at least one of the following:

  • symptoms of ischemia
  • ECG changes indicative of new ischemia (new ST-T changes or new left bundle branch block)
  • development of pathological Q waves on the ECG
  • imaging evidence of new loss of viable myocardium, OR
  • new regional wall motion abnormality.
• An area of regional dysfunction, i.e., hypokinetic, akinetic, or dyskinetic, as assessed by echocardiography, left ventriculography, or MRI.
• History of successful angioplasty and stent placement, with resultant TIMI grade flow ≥ 2, in the artery supplying the infarcted, dysfunctional territory and through which the cells will be infused.
• Left ventricular ejection fraction of ≥ .25 and ≤ .45 as determined by clinically-indicated assessment of cardiac function (echocardiogram, gated blood pool scan, x-ray contrast ventriculography, CT and/or MRI one day or more following successful reperfusion).
• No further revascularization clinically indicated at the time the patient is assessed for participation in the clinical trial. This will be determined by a cardiologist who is not an investigator in the clinical trial. No further revascularization may be indicated by no arteries with significant stenosis, the location, and extent of any stenosis may not be suitable for angioplasty, the distal vessels may not be suitable for placement of bypass grafts, and/or the patient declines angioplasty or bypass surgery.
• Ability to provide informed consent and follow-up with protocol procedures.
• Age > 18 years.

Exclusion Criteria:

• Non-cardiovascular disease with expected life expectancy of < 3 years.

• Contraindications to MRI, including:

  • prior ICD placement
  • estimated glomerular filtration rate < 50 ml/min
  • known reaction to gadolinium
  • claustrophobia
  • pacemaker
  • ear implant, and cochlear implant.
• History of possible presence of ferromagnetic material including programmable shunt, shrapnel, penile prosthesis, intra-uterine device, bullets, tattoos, artificial limb, blood vessel coil, and tissue expander may require special screening.
• Septal infarction involving the right ventricular endocardium as demonstrated by screening MRI (because its presence might increase the potential risk of septal biopsy and decrease treatment benefit due to decreased viability of injured septal-based stem cells).
• History of cardiac tumor, or cardiac tumor demonstrated on MRI.
• Requirement for chronic immunosuppressive therapy.
• Participation in an on-going protocol studying an experimental drug or device.
• Diagnosis of right ventricular arrhythmogenic dysplasia.
• Patients with occlusion of the infarct-related artery before administration of the study agent.
• Current alcohol abuse.
• Current drug abuse.
• Pregnancy.
• Child-bearing potential without use of effective contraception. Men intending to "father" children are also excluded.
• Human Immunodeficiency virus infection.
• Viral hepatitis.
• Uncontrolled diabetes and/or hemoglobin A1C > 8.5%.
• Abnormal liver function (SGPT > 3 times the upper reference range) and hematology (hematocrit < 25%, WBC < 3000, platelets < 100,000) studies without a reversible, identifiable cause.
• Ventricular tachycardia or fibrillation not associated with an acute ischemic episode.
• New York Heart Association Class 4 congestive heart failure.
• Canadian Cardiovascular Society Angina Class 3 or 4.
• Evidence of tumor on screening chest/abdominal/pelvic (body) CT scan.
• Symptomatic ventricular tachyarrhythmia complicating the index myocardial infarction.
• Individuals who are not fluent in English.