title: Autologous bone marrow mononuclear cell transplantation in ischemic heart failure: a prospective, controlled, randomized, double-blind study of cell transplantation combined with coronary bypass.
abstract: BACKGROUND
  Bone marrow mononuclear cell (BMMC) transplantation for heart failure has shown inconsistent therapeutic efficacy.
  
  
  METHODS
  We enrolled 104 ischemic heart failure patients scheduled for coronary artery bypass surgery (CABG). After 4- to 12-week pharmacotherapy optimization, 39 patients with left ventricular ejection fraction (LVEF) of ≤45% received injections of BMMC or vehicle intra-operatively into the myocardial infarction border area in a randomized, double-blind manner.
  
  
  RESULTS
  The median number of cells injected was 8.4 × 10(8) (interquartile range [IQR]: 5.2 × 10(8) to 13.5 × 10(8)). We measured LV function and myocardial scar size by magnetic resonance imaging (MRI), and viability by positron emission tomography (PET) and single-photon emission computed tomography (SPECT), pre-operatively and after 1-year follow-up. LVEF, the pre-defined primary end-point measure, improved by a median of 5.6% in the control group (IQR 0.2 to 10.1) and by 4.8% in the BMMC group (IQR -0.5 to 8.2) (p = 0.59). Wall thickening in injected segments rose by a median of 4.5% among controls (IQR -18.1 to 23.9) and by 5.5% in the BMMC group (IQR -6.6 to 26.5) (p = 0.68). Changes in viability by PET and SPECT did not differ between groups. Myocardial scar size by MRI in injected segments rose by a median of 5.1% among controls (IQR -3.3 to 10.8), but fell by 13.1% in the BMMC group (IQR -21.4 to -6.5) (p = 0.0002).
  
  
  CONCLUSIONS
  BMMC therapy combined with CABG failed to improve LV systolic function, or viability, despite reducing myocardial scar size.
authors.affiliation: Department of Cardiothoracic Surgery.
authors.forename: Tommi
authors.initials: T
authors.lastname: Pätilä
authors.affiliation: Department of Cardiothoracic Surgery.
authors.forename: Miia
authors.initials: M
authors.lastname: Lehtinen
authors.affiliation: Department of Cardiothoracic Surgery.
authors.forename: Antti
authors.initials: A
authors.lastname: Vento
authors.affiliation: Division of Nuclear Medicine, Department of Clinical Physiology.
authors.forename: Jukka
authors.initials: J
authors.lastname: Schildt
authors.affiliation: Division of Cardiology, Department of Medicine.
authors.forename: Juha
authors.initials: J
authors.lastname: Sinisalo
authors.affiliation: Division of Cardiology, Department of Medicine.
authors.forename: Mika
authors.initials: M
authors.lastname: Laine
authors.affiliation: Department of Cardiothoracic Surgery.
authors.forename: Pekka
authors.initials: P
authors.lastname: Hämmäinen
authors.affiliation: Department of Hematology.
authors.forename: Anne
authors.initials: A
authors.lastname: Nihtinen
authors.affiliation: Stem Cell Laboratory, Department of Clinical Chemistry and Hematology, HUSLAB.
authors.forename: Riitta
authors.initials: R
authors.lastname: Alitalo
authors.affiliation: Division of Nuclear Medicine, Department of Clinical Physiology.
authors.forename: Päivi
authors.initials: P
authors.lastname: Nikkinen
authors.affiliation: Division of Nuclear Medicine, Department of Clinical Physiology.
authors.forename: Aapo
authors.initials: A
authors.lastname: Ahonen
authors.affiliation: Department of Radiology.
authors.forename: Miia
authors.initials: M
authors.lastname: Holmström
authors.affiliation: Department of Radiology.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Lauerma
authors.affiliation: Department of Anesthesiology and Intensive Care, Helsinki University Central Hospital, Helsinki.
authors.forename: Reino
authors.initials: R
authors.lastname: Pöyhiä
authors.affiliation: Division of Cardiology, Department of Medicine.
authors.forename: Markku
authors.initials: M
authors.lastname: Kupari
authors.affiliation: Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland.
authors.forename: Esko
authors.initials: E
authors.lastname: Kankuri
authors.affiliation: Department of Cardiothoracic Surgery; Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland. Electronic address: ari.harjula@hus.fi.
authors.forename: Ari
authors.initials: A
authors.lastname: Harjula
mesh_terms: D000368:Aged; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000175:diagnosis / Q000209:etiology / Q000628:therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000637:transplantation*; D009203:Myocardial Infarction / Q000150:complications / Q000473:pathology / Q000628:therapy*; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D013318:Stroke Volume; D015899:Tomography, Emission-Computed, Single-Photon; D014182:Transplantation, Autologous; D016896:Treatment Outcome
keywords: bone marrow mononuclear cells; bypass surgery; cell therapy; clinical trial; heart failure; myocardial infarction