title: A randomized study of transendocardial injection of autologous bone marrow mononuclear cells and cell function analysis in ischemic heart failure (FOCUS-HF).
abstract: BACKGROUND
  Autologous bone marrow mononuclear cell (ABMMNC) therapy has shown promise in patients with heart failure (HF). Cell function analysis may be important in interpreting trial results.
  
  
  METHODS
  In this prospective study, we evaluated the safety and efficacy of the transendocardial delivery of ABMMNCs in no-option patients with chronic HF. Efficacy was assessed by maximal myocardial oxygen consumption, single photon emission computed tomography, 2-dimensional echocardiography, and quality-of-life assessment (Minnesota Living with Heart Failure and Short Form 36). We also characterized patients' bone marrow cells by flow cytometry, colony-forming unit, and proliferative assays.
  
  
  RESULTS
  Cell-treated (n = 20) and control patients (n = 10) were similar at baseline. The procedure was safe; adverse events were similar in both groups. Canadian Cardiovascular Society angina score improved significantly (P = .001) in cell-treated patients, but function was not affected. Quality-of-life scores improved significantly at 6 months (P = .009 Minnesota Living with Heart Failure and P = .002 physical component of Short Form 36) over baseline in cell-treated but not control patients. Single photon emission computed tomography data suggested a trend toward improved perfusion in cell-treated patients. The proportion of fixed defects significantly increased in control (P = .02) but not in treated patients (P = .16). Function of patients' bone marrow mononuclear cells was severely impaired. Stratifying cell results by age showed that younger patients (≤60 years) had significantly more mesenchymal progenitor cells (colony-forming unit fibroblasts) than patients >60 years (20.16 ± 14.6 vs 10.92 ± 7.8, P = .04). Furthermore, cell-treated younger patients had significantly improved maximal myocardial oxygen consumption (15 ± 5.8, 18.6 ± 2.7, and 17 ± 3.7 mL/kg per minute at baseline, 3 months, and 6 months, respectively) compared with similarly aged control patients (14.3 ± 2.5, 13.7 ± 3.7, and 14.6 ± 4.7 mL/kg per minute, P = .04).
  
  
  CONCLUSIONS
  ABMMNC therapy is safe and improves symptoms, quality of life, and possibly perfusion in patients with chronic HF.
authors.affiliation: Stem Cell Center, Texas Heart Institute, St Luke's Episcopal Hospital, Houston, TX, USA. eperin@bluegate.com
authors.forename: Emerson C
authors.initials: EC
authors.lastname: Perin
authors.forename: Guilherme V
authors.initials: GV
authors.lastname: Silva
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Henry
authors.forename: Maria G
authors.initials: MG
authors.lastname: Cabreira-Hansen
authors.forename: Warren H
authors.initials: WH
authors.lastname: Moore
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Coulter
authors.forename: J Patrick
authors.initials: JP
authors.lastname: Herlihy
authors.forename: Marlos R
authors.initials: MR
authors.lastname: Fernandes
authors.forename: Benjamin Y C
authors.initials: BY
authors.lastname: Cheong
authors.forename: Scott D
authors.initials: SD
authors.lastname: Flamm
authors.forename: Jay H
authors.initials: JH
authors.lastname: Traverse
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Deirdre
authors.initials: D
authors.lastname: Smith
authors.forename: Sandi
authors.initials: S
authors.lastname: Shaw
authors.forename: Lynette
authors.initials: L
authors.lastname: Westbrook
authors.forename: Rachel
authors.initials: R
authors.lastname: Olson
authors.forename: Dipsu
authors.initials: D
authors.lastname: Patel
authors.forename: Amir
authors.initials: A
authors.lastname: Gahremanpour
authors.forename: John
authors.initials: J
authors.lastname: Canales
authors.forename: William K
authors.initials: WK
authors.lastname: Vaughn
authors.forename: James T
authors.initials: JT
authors.lastname: Willerson
mesh_terms: D000368:Aged; D016026:Bone Marrow Transplantation / Q000379:methods*; D055426:Cardiac-Gated Single-Photon Emission Computer-Assisted Tomography; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D005260:Female; D005434:Flow Cytometry; D006333:Heart Failure / Q000209:etiology / Q000628:therapy*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications; D011446:Prospective Studies; D011788:Quality of Life; D016037:Single-Blind Method