title: Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: the LateTIME randomized trial.
abstract: BACKGROUND
  Clinical trial results suggest that intracoronary delivery of autologous bone marrow mononuclear cells (BMCs) may improve left ventricular (LV) function when administered within the first week following myocardial infarction (MI). However, because a substantial number of patients may not present for early cell delivery, the efficacy of autologous BMC delivery 2 to 3 weeks post-MI warrants investigation.
  
  
  OBJECTIVE
  To determine if intracoronary delivery of autologous BMCs improves global and regional LV function when delivered 2 to 3 weeks following first MI.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled trial (LateTIME) of the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network of 87 patients with significant LV dysfunction (LV ejection fraction [LVEF] ≤45%) following successful primary percutaneous coronary intervention (PCI) between July 8, 2008, and February 28, 2011.
  
  
  METHODS
  Intracoronary infusion of 150 × 10(6) autologous BMCs (total nucleated cells) or placebo (BMC:placebo, 2:1) was performed within 12 hours of bone marrow aspiration after local automated cell processing.
  
  
  METHODS
  Changes in global (LVEF) and regional (wall motion) LV function in the infarct and border zone between baseline and 6 months, measured by cardiac magnetic resonance imaging. Secondary end points included changes in LV volumes and infarct size.
  
  
  RESULTS
  A total of 87 patients were randomized (mean [SD] age, 57 [11] years; 83% men). Harvesting, processing, and intracoronary delivery of BMCs in this setting was feasible. Change between baseline and 6 months in the BMC group vs placebo for mean LVEF (48.7% to 49.2% vs 45.3% to 48.8%; between-group mean difference, -3.00; 95% CI, -7.05 to 0.95), wall motion in the infarct zone (6.2 to 6.5 mm vs 4.9 to 5.9 mm; between-group mean difference, -0.70; 95% CI, -2.78 to 1.34), and wall motion in the border zone (16.0 to 16.6 mm vs 16.1 to 19.3 mm; between-group mean difference, -2.60; 95% CI, -6.03 to 0.77) were not statistically significant. No significant change in LV volumes and infarct volumes was observed; both groups decreased by a similar amount at 6 months vs baseline.
  
  
  CONCLUSIONS
  Among patients with MI and LV dysfunction following reperfusion with PCI, intracoronary infusion of autologous BMCs vs intracoronary placebo infusion, 2 to 3 weeks after PCI, did not improve global or regional function at 6 months.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00684060.
authors.affiliation: Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, Minnesota, USA.
authors.forename: Jay H
authors.initials: JH
authors.lastname: Traverse
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Henry
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Ellis
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Pepine
authors.forename: James T
authors.initials: JT
authors.lastname: Willerson
authors.forename: David X M
authors.initials: DX
authors.lastname: Zhao
authors.forename: John R
authors.initials: JR
authors.lastname: Forder
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Byrne
authors.forename: Antonis K
authors.initials: AK
authors.lastname: Hatzopoulos
authors.forename: Marc S
authors.initials: MS
authors.lastname: Penn
authors.forename: Emerson C
authors.initials: EC
authors.lastname: Perin
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Baran
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Chambers
authors.forename: Charles
authors.initials: C
authors.lastname: Lambert
authors.forename: Ganesh
authors.initials: G
authors.lastname: Raveendran
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Simon
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Vaughan
authors.forename: Lara M
authors.initials: LM
authors.lastname: Simpson
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Gee
authors.forename: Doris A
authors.initials: DA
authors.lastname: Taylor
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Cogle
authors.forename: James D
authors.initials: JD
authors.lastname: Thomas
authors.forename: Guilherme V
authors.initials: GV
authors.lastname: Silva
authors.forename: Beth C
authors.initials: BC
authors.lastname: Jorgenson
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Olson
authors.forename: Sherry
authors.initials: S
authors.lastname: Bowman
authors.forename: Judy
authors.initials: J
authors.lastname: Francescon
authors.forename: Carrie
authors.initials: C
authors.lastname: Geither
authors.forename: Eileen
authors.initials: E
authors.lastname: Handberg
authors.forename: Deirdre X
authors.initials: DX
authors.lastname: Smith
authors.forename: Sarah
authors.initials: S
authors.lastname: Baraniuk
authors.forename: Linda B
authors.initials: LB
authors.lastname: Piller
authors.forename: Catalin
authors.initials: C
authors.lastname: Loghin
authors.forename: David
authors.initials: D
authors.lastname: Aguilar
authors.forename: Sara
authors.initials: S
authors.lastname: Richman
authors.forename: Claudia
authors.initials: C
authors.lastname: Zierold
authors.forename: Judy
authors.initials: J
authors.lastname: Bettencourt
authors.forename: Shelly L
authors.initials: SL
authors.lastname: Sayre
authors.forename: Rachel W
authors.initials: RW
authors.lastname: Vojvodic
authors.forename: Sonia I
authors.initials: SI
authors.lastname: Skarlatos
authors.forename: David J
authors.initials: DJ
authors.lastname: Gordon
authors.forename: Ray F
authors.initials: RF
authors.lastname: Ebert
authors.forename: Minjung
authors.initials: M
authors.lastname: Kwak
authors.forename: Lemuel A
authors.initials: LA
authors.lastname: Moyé
authors.forename: Robert D
authors.initials: RD
authors.lastname: Simari
mesh_terms: D000328:Adult; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D016026:Bone Marrow Transplantation / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000628:therapy*; D013318:Stroke Volume; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000628:therapy*; D016277:Ventricular Function, Left
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