Myoblast Autologous Grafting in Ischemic Cardiomyopathy - MAGIC


Preclinical studies have suggested that the implantation of contractile cells in the post-infarct myocardium could improve left ventricular (LV) function. This was the first clinical trial to address this issue, with the objective being to address the safety and efficacy of autologous skeletal myoblasts compared with a placebo injection in patients undergoing coronary artery bypass grafting (CABG) for multivessel coronary artery disease and severe LV dysfunction.


Patients with severe multivessel disease and ischemic cardiomyopathy would have a significant improvement in their LV function at 6 months with local delivery of autologous skeletal myoblasts into the myocardium during CABG.

Study Design

Patients Screened: 189
Patients Enrolled: 120
Mean Follow Up: 6 months
Mean Patient Age: 60.4 years
Female: 3.1
Mean Ejection Fraction: 27.6%

Patient Populations:

• Age 18-80 years
• Indication for CABG
• LVEF between 15% and 35%, as determined by echocardiography
• History of myocardial infarction at least 4 weeks prior to screening, with a residual akinesia affecting >2 of 16 accessible contiguous LV segments on echocardiography, with no viability after stimulation with low-dose dobutamine
• Stable NYHA functional class I-III with optimal medical management


• Need for emergent surgery
• Need for additional surgical procedure, such as mitral valve repair or LV aneurysmectomy
• Left or biventricular pacing
• Insufficient acoustic windows for accurate echocardiographic recording
• Contraindication to low-dose dobutamine
• Positive serological test results for human immunodeficiency virus and hepatitis

Primary Endpoints:

• Change from baseline to month 6 in LVEF
• Proportion of patients with recovery of contraction in previously akinetic myocardial segments at month 6

• MACE, defined as composite of death, myocardial infarction, congestive heart failure, resuscitated sudden death, and stroke
• Arrhythmias, defined as sustained ventricular fibrillation or polymorphic ventricular tachycardia (VT), sustained MVT at a rate >120 bpm, wide complex tachycardia for unclear type, sustained atrial fibrillation or flutter, bradyarrhythmia and shock delivered by ICD, bradyarrhythmia pacing, or antitachycardia pacing

Secondary Endpoints:

Change from baseline to month 6 in:
• Echocardiographic LV volumes
• Functional status, as assessed by NYHA classification
• Quality of life, as assessed by SF-36 health survey questionnaire

Drug/Procedures Used:

All patients underwent a muscle biopsy from the thigh under local anesthesia. For patients allocated to the treatment group, the biopsy was then expanded to a target of 400 or 800 million cells, after which they were duly processed as per study protocol. Criteria for product release included a percentage of myoblasts/CD56-positive cells ≥50%, a cellular viability ≥80%, and other quality control test results.

After placement of the bypass grafts, cells or the placebo solution were transferred into 1 ml vials and injected into an average of 30 sites in and around the echocardiography-identified myocardial akinetic segments for a total injection volume of 6 ml, which was accomplished with the use of a 27-gauge customized needle to make injections parallel to the epicardium and avoid inadvertent delivery of cells into the ventricular cavity. The transplanted/injected segments were marked on a 16-segment map, reproducing the echocardiographic division of the LV.

Concomitant Medications:

A significant proportion of patients were on angiotensin-converting enzyme inhibitors (73.1%) and beta-blockers (66.0%). All patients also received 3 doses of 240 mg of prednisolone on induction, at the time of aortic unclamping, and during the first 24 postoperative hours.

An implantable cardioverter defibrillator (ICD) was placed in all patients at the time of muscle biopsy or before postbypass hospital discharge. Amiodarone therapy starting at the time of biopsy and continued for 3 months postoperatively was strongly recommended to all investigators (started in 69.1% of all patients).

Principal Findings:

Of the 120 patients randomized, only 97 actually underwent CABG with myoblast injections. This was due to the recommendations of the safety committee, who advised premature termination of the trial based on futility. The baseline characteristics of the three groups (control, low-dose, and high-dose cell groups) were fairly similar. Only 3.1% of the enrolled patients were female.

Efficacy: Baseline LV ejection fraction (EF) had increased to a similar extent in all three groups at 6 months (35.1% for placebo, 32.3% for low-dose cell group, and 32.5% for high-dose cell group, p = 0.66). Similarly, the absolute decrease in global wall motion score index did not significantly differ between the three groups (p = 0.24). There was a significant difference in the reduction in LV end-diastolic volume (LVEDV) (-12.8 ml/m2, 95% confidence interval [CI] -25.2 to -3.6, p < 0.05), and LV end-systolic volume (LVESV) (-8.1 ml/m2, 95% CI -16.8 to -2.6, p < 0.05), between the high-dose cell and control groups, respectively. The percentage of patients who improved by 1 New York Heart Association (NYHA) class at 6 months, and quality of life, as assessed by the short form (SF)-36 quality-of-life questionnaire, were not different between the three groups.

Safety: The time to first major adverse cardiovascular events (MACE) was not significantly different between the three groups (p = 0.32). Similarly, the incidence of MACE was not significantly different between the three groups either (21% vs. 39% vs. 20%, p = 0.29). The time to first arrhythmia did not significantly differ between the three groups (p = 0.44). The incidence of arrhythmias was nonsignificantly elevated in the myoblast groups (6% vs. 12% vs. 17%, p = 0.17). No death occurred that was thought to be secondary to an arrhythmia.


The results of this small, but first-of-its-kind clinical trial indicate that there was no additional benefit of autologous skeletal myoblasts in improving regional or global LV function in patients with severe ischemic cardiomyopathy, compared with CABG alone. This was despite the fact that the highest dose of myoblasts was associated with a significant antiremodeling effect at 6 months, as evidenced by a reduction in both LVEDV and LVESV, when compared with placebo. There was no increase in the incidence of MACE or arrhythmias with myoblast injections, although there was a nonsignificant doubling of arrhythmias in the myoblast groups.

Although this was a negative study, cardiac cell therapy is a fascinating, and rapidly evolving field. It is left to be seen if future clinical trials, with optimization of the best cells, their method of harvesting and delivery, and their functional integration in the myocardium, will be able to demonstrate improved patient outcomes in the days ahead.


Menasché P, Alfieri O, Janssens S, et al. The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) Trial: First Randomized Placebo-Controlled Study of Myoblast Transplantation. Circulation 2008;117:1189-200.

Presented by Dr. Philippe Menasche at the American Heart Association Annual Scientific Sessions, Chicago, IL, November.

Clinical Topics: Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Atherosclerotic Disease (CAD/PAD), Cardiac Surgery and Heart Failure, Acute Heart Failure, Interventions and Coronary Artery Disease, Interventions and Imaging, Echocardiography/Ultrasound

Keywords: Coronary Artery Disease, Myocardial Infarction, Quality Control, Ventricular Function, Left, Biopsy, Myocardium, Cell- and Tissue-Based Therapy, Thigh, Dobutamine, Quality of Life, Myoblasts, Skeletal, Cardiomyopathies, Heart Failure, Medical Futility, Confidence Intervals, Questionnaires, Coronary Artery Bypass, Echocardiography

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