Autologous Skeletal Myoblast Transplantation in Patients Undergoing Coronary Artery Bypass Graft Surgery - Autologous Skeletal Myoblast Transplantation in Patients Undergoing CABG

May 07, 2004
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Date Presented:
01/01/2004
Date Updated:
05/07/2004
Original Posted Date:
05/07/2004
References

Description:

The goal of the study was to evaluate safety and feasibility of autologous skeletal myoblast transplantation (AMT) in patients scheduled to undergo elective coronary artery bypass grafting (CABG).

Hypothesis:

AMT will be feasible and safe in patients scheduled to undergo elective CABG.

Study Design

Study Design:

Patients Enrolled: 24
Mean Follow Up: Follow-up 11-45 months
Mean Patient Age: Mean age 55 years
Female: 4
Mean Ejection Fraction: Mean baseline EF 28%

Patient Populations:

Previous myocardial infarction and an LVEF <40%

Drug/Procedures Used:

Patients who met the inclusion criteria and were scheduled for CABG underwent a skeletal muscle biopsy to excise approximately 2 g from each patient to isolate and expand myoblasts over 2-6 weeks. Between three and 30 direct injections of myoblasts were delivered into the area of infarction using one of four escalating doses (10, 30, 100, or 300 million cells) following completion of the CABG procedure. Pre- and post-injection ECG, echocardiogram, Holter monitoring, positron emission tomography (PET), and magnetic resonance imaging were performed.

Principal Findings:

Delivery success of the AMT was 100%. Purity of the cells ranged from 47% to 98% CD 56+, and myoblast viability was 85% to 98%.

Among the seven patients who had PET scans after myoblast transplantation demonstrated, improvements in scar area to viable muscle tissue were observed in four patients. New York Heart Association (NYHA) class heart failure improved from 2.1 at baseline to 1.4 at three months (p=0.001) and to 1.7 at two years (p=0.18).

Left ventricular ejection fraction (LVEF) significantly increased from 28.2% at baseline to 34.7% at one year (p=0.02) and in the subset of patients with two-year data, from 26.8% at baseline to 36.2% (p=0.01). Four patients had serious adverse events possibly related to transplantation: two patients had nonsustained ventricular tachycardia (NSVT) during the two weeks following cell transplantation, one had increased frequency of asymptomatic NSVT on Holter at day 10, and one had symptomatic episodes one week post-injection.

In addition, there was one mortality and there were seven cases of arrhythmia. Other serious adverse events were reported that were determined to not be related to the transplantation, including two strokes, one case of pneumothorax, and one patient requiring coronary intervention.

Interpretation:

Among patients with prior myocardial infarction scheduled for elective CABG, AMT was feasible and safe in this phase I study. Much larger randomized phase 2 and 3 clinical trials will be needed to assess efficacy and a broader safety evaluation.

Additionally, a randomized trial would help determine if the improvements in EF and NYHA class were related to the transplantation or to the CABG procedure. Data from this study support the initiation of future trials, which could have widespread implications if myocardial regeneration of damaged tissue succeeds.

References:

Presented by Dr. Nabil Dib at the March 2005 ACC Annual Scientific Session, Orlando, FL.

Also presented by Dr. Nabil Dib at the March 2004 ACC Annual Scientific Session, New Orleans, LA.

Keywords: Stroke, Myocardial Infarction, Biopsy, Pneumothorax, Magnetic Resonance Imaging, Positron-Emission Tomography, Cell Transplantation, Tachycardia, Ventricular, Cicatrix, Myoblasts, Skeletal, Heart Failure, Stroke Volume, Electrocardiography, Ambulatory, Coronary Artery Bypass, Echocardiography


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