Clinical study
Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction

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Abstract

Objectives

This phase I trial was designed to assess the feasibility and safety of autologous skeletal myoblast transplantation in patients with severe ischemic cardiomyopathy.

Background

Experimentally, myoblast grafting into postinfarction myocardial scars improves left ventricular function.

Methods

Ten patients were included on the basis of the following criteria: 1) severe left ventricular dysfunction (ejection fraction ≤35%); 2) the presence of a postinfarction akinetic and nonviable scar, as assessed by dobutamine echocardiography and 18-fluorodeoxyglucose positron emission tomography; and 3) an indication of coronary bypass in remote areas. Skeletal myoblasts were grown from a biopsy taken at the thigh.

Results

An average of 871 × 106cells (86% of myoblasts) were obtained after a mean period of 16 days and implanted uneventfully across the scar at the time of bypass. Except for one patient whose early death was unrelated to the cell transplantation, all patients had an uncomplicated postoperative course. Four patients showed delayed episodes of sustained ventricular tachycardia and were implanted with an internal defibrillator. At an average follow-up of 10.9 months, the mean New York Heart Association functional class improved from 2.7 ± 0.2 preoperatively to 1.6 ± 0.1 postoperatively (p < 0.0001), and the ejection fraction increased from 24 ± 1% to 32 ± 1% (p < 0.02). A blinded echocardiographic analysis showed that 63% of the cell-implanted scars (14 of 22) demonstrated improved systolic thickening. One noncardiac death occurred 17.5 months after transplantation.

Conclusions

These preliminary data suggest the feasibility and safety of autologous skeletal myoblast transplantation in severe ischemic cardiomyopathy, with the caveat of an arrhythmogenic potential. New-onset contraction of akinetic and nonviable segments suggests a functional efficacy that requires confirmation by randomized studies.

Abbreviations

AICD
automatic internal cardioverter-defibrillator
CABG
coronary artery bypass graft
18FDG
fluorine-18–labeled fluorodeoxyglucose
LV
left ventricle/ventricular
LVEDV
left ventricular end-diastolic volume
LVEF
left ventricular ejection fraction
LVESV
left ventricular end-systolic volume
NYHA
New York Heart Association
PET
positron emission tomography
VT
ventricular tachycardia

Cited by (0)

This work was supported by the Délégation à la Recherche Clinique de l’Assistance Publique-Hôpitaux de Paris, as well as by grants from the Association Française contre les Myopathies and the Institut National de la Santé et de la Recherche Médicale (35 4CS15F and 35 7783). The authors acknowledge the support of the Commissariat à l’Energie Atomique (Prof. A. Syrota, Orsay, France).