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J Am Coll Cardiol, 2003; 41:1078-1083, doi:10.1016/S0735-1097(03)00092-5 © 2003 by the American College of Cardiology Foundation |






* Assistance Publique-Hôpitaux de Paris, Department of Cardiovascular Surgery B, Hôpital Bichat, Paris, France
Department of Cardiology, Hôpital Européen Georges Pompidou and INSERM EMI 00-16, Faculté de Médecine Necker Enfants-Malades, Paris V University, Paris, France
INSERM U 582, Groupe Hospitalier Pitié Salpêtrière, Paris, France
Department of Pathology, Hôpital Européen Georges Pompidou, Paris, France
|| Laboratory of Cell Therapy, Hôpital Saint Louis, Paris, France
¶ Department of Cardiology, Hôpital Cochin, Paris V University, Paris, and Department of Nuclear Medicine Frédéric Joliot, Commissariat à lEnergie Atomique, Orsay, France
Manuscript received June 11, 2002; revised manuscript received October 2, 2002, accepted October 17, 2002.
* Reprint requests and correspondence: Dr. Philippe Menasché, Département de Chirurgie Cardiovasculaire, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015 Paris, France.
philippe.menasche{at}hop.egp.ap-hop-paris.fr
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 x 106 cells (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.
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