title: Effects of transendocardial CD34+ cell transplantation in patients with ischemic cardiomyopathy.
abstract: BACKGROUND
  We investigated the effects of transendocardial CD34(+) cell transplantation in patients with ischemic cardiomyopathy.
  
  
  RESULTS
  In a prospective crossover study, we enrolled 33 patients with ischemic cardiomyopathy with New York Heart Association class III and left ventricular ejection fraction <40%. In phase 1, patients were treated with medical therapy for 6 months. Thereafter, all patients underwent transendocardial CD34(+) cell transplantation. Peripheral blood CD34(+) cells were mobilized by granulocyte colony stimulating factor, collected via apheresis, and injected transendocardially in the areas of hibernating myocardium. Patients were followed up for 6 months after the procedure (phase 2). Two patients died during phase 1 and none during phase 2. The remaining 31 patients were 85% men, aged 57±6 years. In phase 1, we found no change in left ventricular ejection fraction (from 25.2±6.2% to 27.1±6.6%; P=0.23), N-terminal pro B-type natriuretic peptide (from 3322±3411 to 3672±5165 pg/mL; P=0.75) or 6-minute walk distance (from 373±68 to 411±116 m; P=0.17). In contrast, in phase 2 there was an improvement in left ventricular ejection fraction (from 27.1±6.6% to 34.9±10.9%; P=0.001), increase in 6-minute walk distance (from 411±116 to 496±113 m; P=0.001), and a decrease in N-terminal pro B-type natriuretic peptide (from 3672±5165 to 1488±1847 pg/mL; P=0.04). The average number of injected CD34(+) cells was 90.6±7.5×10(6). Higher doses of CD34(+) cells and a more diffuse distribution of transendocardial cell injections were associated with better clinical response.
  
  
  CONCLUSIONS
  Transendocardial CD34(+) cell transplantation may be associated with improved left ventricular function, decreased N-terminal pro B-type natriuretic peptide levels, and better exercise capacity in patients with ischemic cardiomyopathy. These effects seem to be particularly pronounced in patients receiving diffusely distributed cell injections and high-dose cell therapy.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT01350310.
authors.affiliation: From the Department of Cardiology, Advanced Heart Failure and Transplantation Center (G.P., G.Z., B.V.), Department of Hematology (M.S., P.C.), and Department of Cardiovascular Surgery (I.K.), University Medical Center Ljubljana, Ljubljana, Slovenia; National Blood Transfusion Institute, Ljubljana, Slovenia (M.C.); and Stanford Cardiovascular Institute, Stanford University School of Medicine, Palo Alto, CA (F.H., J.C.W., B.V.).
authors.forename: Gregor
authors.initials: G
authors.lastname: Poglajen
authors.affiliation: From the Department of Cardiology, Advanced Heart Failure and Transplantation Center (G.P., G.Z., B.V.), Department of Hematology (M.S., P.C.), and Department of Cardiovascular Surgery (I.K.), University Medical Center Ljubljana, Ljubljana, Slovenia; National Blood Transfusion Institute, Ljubljana, Slovenia (M.C.); and Stanford Cardiovascular Institute, Stanford University School of Medicine, Palo Alto, CA (F.H., J.C.W., B.V.).
authors.forename: Matjaz
authors.initials: M
authors.lastname: Sever
authors.affiliation: From the Department of Cardiology, Advanced Heart Failure and Transplantation Center (G.P., G.Z., B.V.), Department of Hematology (M.S., P.C.), and Department of Cardiovascular Surgery (I.K.), University Medical Center Ljubljana, Ljubljana, Slovenia; National Blood Transfusion Institute, Ljubljana, Slovenia (M.C.); and Stanford Cardiovascular Institute, Stanford University School of Medicine, Palo Alto, CA (F.H., J.C.W., B.V.).
authors.forename: Marko
authors.initials: M
authors.lastname: Cukjati
authors.affiliation: From the Department of Cardiology, Advanced Heart Failure and Transplantation Center (G.P., G.Z., B.V.), Department of Hematology (M.S., P.C.), and Department of Cardiovascular Surgery (I.K.), University Medical Center Ljubljana, Ljubljana, Slovenia; National Blood Transfusion Institute, Ljubljana, Slovenia (M.C.); and Stanford Cardiovascular Institute, Stanford University School of Medicine, Palo Alto, CA (F.H., J.C.W., B.V.).
authors.forename: Peter
authors.initials: P
authors.lastname: Cernelc
authors.affiliation: From the Department of Cardiology, Advanced Heart Failure and Transplantation Center (G.P., G.Z., B.V.), Department of Hematology (M.S., P.C.), and Department of Cardiovascular Surgery (I.K.), University Medical Center Ljubljana, Ljubljana, Slovenia; National Blood Transfusion Institute, Ljubljana, Slovenia (M.C.); and Stanford Cardiovascular Institute, Stanford University School of Medicine, Palo Alto, CA (F.H., J.C.W., B.V.).
authors.forename: Ivan
authors.initials: I
authors.lastname: Knezevic
authors.affiliation: From the Department of Cardiology, Advanced Heart Failure and Transplantation Center (G.P., G.Z., B.V.), Department of Hematology (M.S., P.C.), and Department of Cardiovascular Surgery (I.K.), University Medical Center Ljubljana, Ljubljana, Slovenia; National Blood Transfusion Institute, Ljubljana, Slovenia (M.C.); and Stanford Cardiovascular Institute, Stanford University School of Medicine, Palo Alto, CA (F.H., J.C.W., B.V.).
authors.forename: Gregor
authors.initials: G
authors.lastname: Zemljic
authors.affiliation: From the Department of Cardiology, Advanced Heart Failure and Transplantation Center (G.P., G.Z., B.V.), Department of Hematology (M.S., P.C.), and Department of Cardiovascular Surgery (I.K.), University Medical Center Ljubljana, Ljubljana, Slovenia; National Blood Transfusion Institute, Ljubljana, Slovenia (M.C.); and Stanford Cardiovascular Institute, Stanford University School of Medicine, Palo Alto, CA (F.H., J.C.W., B.V.).
authors.forename: François
authors.initials: F
authors.lastname: Haddad
authors.affiliation: From the Department of Cardiology, Advanced Heart Failure and Transplantation Center (G.P., G.Z., B.V.), Department of Hematology (M.S., P.C.), and Department of Cardiovascular Surgery (I.K.), University Medical Center Ljubljana, Ljubljana, Slovenia; National Blood Transfusion Institute, Ljubljana, Slovenia (M.C.); and Stanford Cardiovascular Institute, Stanford University School of Medicine, Palo Alto, CA (F.H., J.C.W., B.V.).
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wu
authors.affiliation: From the Department of Cardiology, Advanced Heart Failure and Transplantation Center (G.P., G.Z., B.V.), Department of Hematology (M.S., P.C.), and Department of Cardiovascular Surgery (I.K.), University Medical Center Ljubljana, Ljubljana, Slovenia; National Blood Transfusion Institute, Ljubljana, Slovenia (M.C.); and Stanford Cardiovascular Institute, Stanford University School of Medicine, Palo Alto, CA (F.H., J.C.W., B.V.). bvrtovec@stanford.edu.
authors.forename: Bojan
authors.initials: B
authors.lastname: Vrtovec
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018952:Antigens, CD34 / Q000378:metabolism; D001773:Blood Cells / Q000473:pathology / Q000637:transplantation; D009202:Cardiomyopathies / Q000628:therapy; D018592:Cross-Over Studies; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D019650:Hematopoietic Stem Cell Mobilization; D007511:Ischemia / Q000628:therapy; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011446:Prospective Studies; D020127:Recovery of Function; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34; D016179:Granulocyte Colony-Stimulating Factor; D020097:Natriuretic Peptide, Brain; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76)
keywords: heart failure; ischemic heart disease; stem cells