title: Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial.
abstract: OBJECTIVE
  Whether culture-expanded mesenchymal stem cells or whole bone marrow mononuclear cells are safe and effective in chronic ischemic cardiomyopathy is controversial.
  
  
  OBJECTIVE
  To demonstrate the safety of transendocardial stem cell injection with autologous mesenchymal stem cells (MSCs) and bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy.
  
  
  METHODS
  A phase 1 and 2 randomized, blinded, placebo-controlled study involving 65 patients with ischemic cardiomyopathy and left ventricular (LV) ejection fraction less than 50% (September 1, 2009-July 12, 2013). The study compared injection of MSCs (n=19) with placebo (n = 11) and BMCs (n = 19) with placebo (n = 10), with 1 year of follow-up.
  
  
  METHODS
  Injections in 10 LV sites with an infusion catheter.
  
  
  METHODS
  Treatment-emergent 30-day serious adverse event rate defined as a composite of death, myocardial infarction, stroke, hospitalization for worsening heart failure, perforation, tamponade, or sustained ventricular arrhythmias.
  
  
  RESULTS
  No patient had a treatment-emergent serious adverse events at day 30. The 1-year incidence of serious adverse events was 31.6% (95% CI, 12.6% to 56.6%) for MSCs, 31.6% (95% CI, 12.6%-56.6%) for BMCs, and 38.1% (95% CI, 18.1%-61.6%) for placebo. Over 1 year, the Minnesota Living With Heart Failure score improved with MSCs (-6.3; 95% CI, -15.0 to 2.4; repeated measures of variance, P=.02) and with BMCs (-8.2; 95% CI, -17.4 to 0.97; P=.005) but not with placebo (0.4; 95% CI, -9.45 to 10.25; P=.38). The 6-minute walk distance increased with MSCs only (repeated measures model, P = .03). Infarct size as a percentage of LV mass was reduced by MSCs (-18.9%; 95% CI, -30.4 to -7.4; within-group, P = .004) but not by BMCs (-7.0%; 95% CI, -15.7% to 1.7%; within-group, P = .11) or placebo (-5.2%; 95% CI, -16.8% to 6.5%; within-group, P = .36). Regional myocardial function as peak Eulerian circumferential strain at the site of injection improved with MSCs (-4.9; 95% CI, -13.3 to 3.5; within-group repeated measures, P = .03) but not BMCs (-2.1; 95% CI, -5.5 to 1.3; P = .21) or placebo (-0.03; 95% CI, -1.9 to 1.9; P = .14). Left ventricular chamber volume and ejection fraction did not change.
  
  
  CONCLUSIONS
  Transendocardial stem cell injection with MSCs or BMCs appeared to be safe for patients with chronic ischemic cardiomyopathy and LV dysfunction. Although the sample size and multiple comparisons preclude a definitive statement about safety and clinical effect, these results provide the basis for larger studies to provide definitive evidence about safety and to assess efficacy of this new therapeutic approach.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00768066.
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine2Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Heldman
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine.
authors.forename: Darcy L
authors.initials: DL
authors.lastname: DiFede
authors.affiliation: Department of Radiology, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Joel E
authors.initials: JE
authors.lastname: Fishman
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine2Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Zambrano
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine2Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Barry H
authors.initials: BH
authors.lastname: Trachtenberg
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine.
authors.forename: Vasileios
authors.initials: V
authors.lastname: Karantalis
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine2Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Muzammil
authors.initials: M
authors.lastname: Mushtaq
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine4Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Williams
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine.
authors.forename: Viky Y
authors.initials: VY
authors.lastname: Suncion
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine2Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida8MD Anderson Cancer Center, Houston, Texas.
authors.forename: Ian K
authors.initials: IK
authors.lastname: McNiece
authors.affiliation: Department of Radiology, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Eduard
authors.initials: E
authors.lastname: Ghersin
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine2Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Victor
authors.initials: V
authors.lastname: Soto
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine2Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida5Miami Veterans Affairs Healthcare System, Miami, Florida.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Lopera
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Roberto
authors.initials: R
authors.lastname: Miki
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Howard
authors.initials: H
authors.lastname: Willens
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Robert
authors.initials: R
authors.lastname: Hendel
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Raul
authors.initials: R
authors.lastname: Mitrani
authors.forename: Pradip
authors.initials: P
authors.lastname: Pattany
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine2Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Gary
authors.initials: G
authors.lastname: Feigenbaum
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine2Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Behzad
authors.initials: B
authors.lastname: Oskouei
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine2Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: John
authors.initials: J
authors.lastname: Byrnes
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Maureen H
authors.initials: MH
authors.lastname: Lowery
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine.
authors.forename: Julio
authors.initials: J
authors.lastname: Sierra
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine.
authors.forename: Mariesty V
authors.initials: MV
authors.lastname: Pujol
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine.
authors.forename: Cindy
authors.initials: C
authors.lastname: Delgado
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine.
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Gonzalez
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine.
authors.forename: Jose E
authors.initials: JE
authors.lastname: Rodriguez
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine.
authors.forename: Luiza Lima
authors.initials: LL
authors.lastname: Bagno
authors.affiliation: Biocardia Corporation, San Carlos, California.
authors.forename: Didier
authors.initials: D
authors.lastname: Rouy
authors.affiliation: Biocardia Corporation, San Carlos, California.
authors.forename: Peter
authors.initials: P
authors.lastname: Altman
authors.affiliation: Biocardia Corporation, San Carlos, California.
authors.forename: Cheryl Wong Po
authors.initials: CW
authors.lastname: Foo
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine.
authors.forename: Jose
authors.initials: J
authors.lastname: da Silva
authors.affiliation: EMMES Corporation, Rockville, Maryland.
authors.forename: Erica
authors.initials: E
authors.lastname: Anderson
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine.
authors.forename: Richard
authors.initials: R
authors.lastname: Schwarz
authors.affiliation: EMMES Corporation, Rockville, Maryland.
authors.forename: Adam
authors.initials: A
authors.lastname: Mendizabal
authors.affiliation: The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine2Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Hare
mesh_terms: D000368:Aged; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods*; D009202:Cardiomyopathies; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D008875:Middle Aged; D009203:Myocardial Infarction; D017202:Myocardial Ischemia / Q000628:therapy*; D020521:Stroke; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000628:therapy