The primary problems in the setting of post-myocardial infarction heart failure is the loss of myocardium and replacement of with fibrous scar tissue. Recent advances in biotechnology have allowed investigators to consider restoring missing contractile elements within the left ventricle. They hope to improve contractile function in patients with post-myocardial infarction heart failure.

Investigators have considered several types of cells for possible use to improve contractile dysfunction. These include stem cells, cardiomyocytes and fibroblasts. Dr. Siminiak and colleagues have studied the possibility of using autologous skeletal myoblasts for replacing missing myocardium.

There are several advantages to using autologous cells for this application. Patients will not need immunosuppression. Supply of cells is not a problem. Furｔhermore, the use of autologous cells does not raise the ethical issues that have surrounded the potential use of embryonic or fetal cells.

Preclinical data show that transplanted skeletal myoblasts in the post-infarction scar form myocyte-like elements that possibly restore function. Investigators have replicated these findings in a number of species. Hagège et al. showed the effects of transplanting autologous skeletal myoblasts in sheep.

Dr. Siminiak and colleagues launched an independent phase I clinical trial to evaluate the safety and feasibility of transplanting skeletal myoblasts during coronary artery bypass graft surgery. This investigation included 10 patients about to undergo surgery. All patients had akinesia or dyskinesia involving 1 to 3 segments of the left ventricle.

For each patient, researchers obtained a cell sample from the vastus lateralus approximately 1 cubic centimeter in size. They isolated the myoblasts and put them in cell culture for 3 weeks. They injected the resulting myoblasts into the akinetic or dyskinetic area during the bypass procedure.

One patient died 7 days after the procedure. However, the autopsy revealed a recent myocardial infarction in an area that was previously normokinetic. They assumed this new infarction was not related to the transplantation of cells and continued the trial.

Previously, investigators reported an increase in ejection fraction for all 9 surviving participants. Here at ACC, Dr. Siminiak showed that this increase in ejection fraction persisted throughout the 12 month follow-up period.

Investigators also observed changes in segmental contractility at 5 months. Dr. Siminiak said 5 of 9 dyskinetic segments became akinetic, and 4 of 10 akinetic segments became hypokinetic.

After observing episodes of serious ventricular tachycardia in the first 2 patients, the researchers decided to use prophylactic amiodarone. In the following patients, they observed no sustained ventricular tachycardia episodes. Only 2 patient were on oral amiodarone at 2 months. No patient remained on amiodarone at 3 months.

These results suggest autologous skeletal myoblast transplantation is at least feasible. However, many questions remain. Investigators must conduct further studies to validate this method and establish its potential role in clinical practice. For example, a phase II study will provide data on left ventricular performance improvement after transplantation.