title: Cell-based therapy for myocardial repair in patients with acute myocardial infarction: rationale and study design of the SWiss multicenter Intracoronary Stem cells Study in Acute Myocardial Infarction (SWISS-AMI).
abstract: BACKGROUND
  Recent studies report that intracoronary administration of autologous bone marrow mononucleated cells (BM-MNCs) may improve remodeling of the left ventricle after acute myocardial infarction (AMI). Subgroup analysis suggest that early treatment between days 4 and 7 after AMI is probably most effective; however, the optimal time point of intracoronary cell administration has never been addressed in clinical trials. Furthermore, reliable clinical predictors are lacking for identifying patients who are thought to have most benefit from cellular therapy.
  
  
  METHODS
  In a multicenter trial, 192 patients with AMI successfully treated by percutaneous coronary intervention (PCI) of the infarct-related artery will be randomized in a 1:1:1 pattern to 1 control and 2 BM-MNC treatment groups. The control group will be treated with state-of-the-art medical management. The treatment groups will receive intracoronary administration of autologous BM-MNC at 5 to 7 days or 3 to 4 weeks after the initial event, respectively. Left ventricular function as well as scar size, transmural extension, and regional wall motion score will be assessed by cardiac magnetic resonance (CMR) studies at baseline and after 4 and 12 months.
  
  
  METHODS
  Fifty milliliters of bone marrow will be harvested by aspiration from the iliac crest and then carried by courier to a centralized cell processing facility. The mononucleated cell fraction will be isolated by density gradient centrifugation, washed, and resuspended in 10 mL of injection medium. The cells will be characterized by fluorescence-activated cell sorting analysis and tested for sterility and potency both "in vitro" and "in vivo." Bone marrow MNC will then be reinfused directly in the infarct-related coronary artery.
  
  
  METHODS
  The primary end point is the change in global left ventricular (LV) ejection fraction by CMR at 4 months as compared to baseline. Comparisons will then be made between each of the prespecified therapy subgroups (early and late after AMI) and the control group. Secondary end points include change in infarct size, change in regional myocardial thickness, and wall motion at 4 and 12 months compared to baseline. Infarct extension (size and transmural extension), time delay to PCI, and coronary flow characteristics after PCI will be assessed as potential predictors of LV remodeling and change after cell therapy. Major adverse cardiac events (MACE) (death, myocardial infarction, coronary revascularization, rehospitalization for heart failure) will be assessed at 4, 12, and 24 months and time to MACE will be estimated.
  
  
  CONCLUSIONS
  With the present study, we aim to determine the optimal time point of intracoronary administration of autologous BM-MNC after AMI on LV remodeling.
authors.affiliation: Department of Cardiology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sürder
authors.forename: Jürg
authors.initials: J
authors.lastname: Schwitter
authors.forename: Tiziano
authors.initials: T
authors.lastname: Moccetti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Astori
authors.forename: Kaspar
authors.initials: K
authors.lastname: Rufibach
authors.forename: Sven
authors.initials: S
authors.lastname: Plein
authors.forename: Viviana
authors.initials: V
authors.lastname: Lo Cicero
authors.forename: Sabrina
authors.initials: S
authors.lastname: Soncin
authors.forename: Stephan
authors.initials: S
authors.lastname: Windecker
authors.forename: Aris
authors.initials: A
authors.lastname: Moschovitis
authors.forename: Andreas
authors.initials: A
authors.lastname: Wahl
authors.forename: Paul
authors.initials: P
authors.lastname: Erne
authors.forename: Peiman
authors.initials: P
authors.lastname: Jamshidi
authors.forename: Christoph
authors.initials: C
authors.lastname: Auf der Maur
authors.forename: Robert
authors.initials: R
authors.lastname: Manka
authors.forename: Gianni
authors.initials: G
authors.lastname: Soldati
authors.forename: Ines
authors.initials: I
authors.lastname: Bühler
authors.forename: Christophe
authors.initials: C
authors.lastname: Wyss
authors.forename: Ulf
authors.initials: U
authors.lastname: Landmesser
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: Roberto
authors.initials: R
authors.lastname: Corti
mesh_terms: D003331:Coronary Vessels; D005500:Follow-Up Studies; D006352:Heart Ventricles / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007261:Infusions, Intra-Arterial; D008279:Magnetic Resonance Imaging; D009203:Myocardial Infarction / Q000175:diagnosis / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000473:pathology*; D012720:Severity of Illness Index; D033581:Stem Cell Transplantation / Q000379:methods*; D013318:Stroke Volume; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000502:physiology*; D020257:Ventricular Remodeling / Q000502:physiology