Effects of transendocardial CD34+ cell transplantation in patients with ischemic cardiomyopathy

Circ Cardiovasc Interv. 2014 Aug;7(4):552-9. doi: 10.1161/CIRCINTERVENTIONS.114.001436. Epub 2014 Aug 5.

Abstract

Background: We investigated the effects of transendocardial CD34(+) cell transplantation in patients with ischemic cardiomyopathy.

Methods and 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.

Clinical trial registration url: http://www.clinicaltrials.gov. Unique identifier: NCT01350310.

Keywords: heart failure; ischemic heart disease; stem cells.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD34 / metabolism
  • Blood Cells / pathology*
  • Blood Cells / transplantation
  • Cardiomyopathies / therapy*
  • Cross-Over Studies
  • Female
  • Follow-Up Studies
  • Granulocyte Colony-Stimulating Factor / metabolism
  • Hematopoietic Stem Cell Mobilization
  • Humans
  • Ischemia / therapy*
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / pathology*
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Prospective Studies
  • Recovery of Function
  • Treatment Outcome

Substances

  • Antigens, CD34
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Granulocyte Colony-Stimulating Factor

Associated data

  • ClinicalTrials.gov/NCT01350310