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(Circulation. 2008;117:1189-1200.)
© 2008 American Heart Association, Inc.

Transplantation

The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) Trial

First Randomized Placebo-Controlled Study of Myoblast Transplantation

Philippe Menasché, MD, PhD; Ottavio Alfieri, MD; Stefan Janssens, MD, PhD; William McKenna, MD; Hermann Reichenspurner, MD; Ludovic Trinquart, MSc; Jean-Thomas Vilquin, PhD; Jean-Pierre Marolleau, MD; Barbara Seymour, BS; Jérôme Larghero, PharmD, PhD; Stephen Lake, ScD; Gilles Chatellier, MD, PhD; Scott Solomon, MD; Michel Desnos, MD; Albert A. Hagège, MD, PhD

From Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Département de Chirurgie Cardio-vasculaire; Université Paris Descartes, Faculté de Médecine; INSERM U633, Laboratoire de Recherches Biochirurgicales, Paris, France (P.M.); Ospedale San Raffaele, Dipartimento Cardiochirugia, Milano, Italy (O.A.); UZ Gasthuisberg, Cardiology Department, Leuven, Belgium (S.J.); The Heart Hospital, London, UK (W.M.); Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Herz- und Gefäβchirurgie, Hamburg, Germany (H.R.); Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Unité d’Epidémiologie et de Recherche Clinique; INSERM CIE4, Paris, France (L.T.); INSERM U582, Association Institut de Myologie, Université Paris-6, Groupe hospitalier Pitié-Salpêtrière, Paris, France (J.V.); Centre Hospitalo-Universitaire, Département d’Hématologie, Amiens, France (J.M.); Genzyme Corporation, Cambridge, Mass (B.S., S.L.); Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Laboratoire de Thérapie Cellulaire, Paris, France (J.L.); Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Unité d’Epidemiologie et de Recherche Clinique; INSERM CIE4; Université Paris Descartes, Faculté de Médecine, Paris, France (G.C.); Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (S.S.); and Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Départment de Cardiologie; Université Paris Descartes, Faculté de Médecine; INSERM U 633, Laboratoire de Recherches Biochirurgicales, Paris, France (M.D., A.A.H.).

Correspondence to Dr Philippe Menasché, Département de Chirurgie Cardio-vasculaire, Hôpital Européen Georges Pompidou, 20, rue Leblanc, 75015 Paris, France. E-mail philippe.menasche{at}egp.aphp.fr

Received August 16, 2007; accepted December 27, 2007.

Background— Phase I clinical studies have demonstrated the feasibility of implanting autologous skeletal myoblasts in postinfarction scars. However, they have failed to determine whether this procedure was functionally effective and arrhythmogenic.

Methods and Results— This multicenter, randomized, placebo-controlled, double-blind study included patients with left ventricular (LV) dysfunction (ejection fraction 35%), myocardial infarction, and indication for coronary surgery. Each patient received either cells grown from a skeletal muscle biopsy or a placebo solution injected in and around the scar. All patients received an implantable cardioverter-defibrillator. The primary efficacy end points were the 6-month changes in global and regional LV function assessed by echocardiography. The safety end points comprised a composite index of major cardiac adverse events and ventricular arrhythmias. Ninety-seven patients received myoblasts (400 or 800 million; n=33 and n=34, respectively) or the placebo (n=30). Myoblast transfer did not improve regional or global LV function beyond that seen in control patients. The absolute change in ejection fraction (median [interquartile range]) between 6 months and baseline was 4.4% (0.2; 7.3), 3.4% (–0.3; 12.4), and 5.2% (–4.4; 11.0) in the placebo, low-dose, and high-dose groups, respectively (P=0.95). However, the high-dose cell group demonstrated a significant decrease in LV volumes compared with the placebo group. Despite a higher number of arrhythmic events in the myoblast-treated patients, the 6-month rates of major cardiac adverse events and of ventricular arrhythmias did not differ significantly between the pooled treatment and placebo groups.

Conclusions— Myoblast injections combined with coronary surgery in patients with depressed LV function failed to improve echocardiographic heart function. The increased number of early postoperative arrhythmic events after myoblast transplantation, as well as the capability of high-dose injections to revert LV remodeling, warrants further investigation.

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CLINICAL PERSPECTIVE

Related Article:

Clinical Summaries
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