Published Online
on February 19, 2008

A more recent version of this article appeared on March 4, 2008

This Article Full Text (PDF) CME: Take the course for this article: Circulation: March 4, 2008, Volume 117, Number 9 All Versions of this Article: 117/9/1189    most recent CIRCULATIONAHA.107.734103v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Google Scholar Articles by Menasché, P. Articles by Hagège, A. A. PubMed PubMed Citation Articles by Menasché, P. Articles by Hagège, A. A. Pubmed/NCBI databases Medline Plus Health Information Cardiomyopathy Related Collections Chronic ischemic heart disease Congestive CV surgery: transplantation, ventricular assistance, cardiomyopathy Related Article

Submitted on August 16, 2007
Accepted on December 27, 2007

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, and 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 Gefächirurgie, 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.).

^* To whom correspondence should be addressed. E-mail: philippe.menasche{at}egp.aphp.fr.

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.

Key words: heart failure • myoblasts • myocardial infarction • stem cells • transplantation

Related Article:

Clinical Summaries
Circulation 2008 117: 1121-1123. [Full Text]

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