Effects of intracoronary CD34+ stem cell transplantation in nonischemic dilated cardiomyopathy patients: 5-year follow-up

Circ Res. 2013 Jan 4;112(1):165-73. doi: 10.1161/CIRCRESAHA.112.276519. Epub 2012 Oct 12.

Abstract

Rationale: CD34+ transplantation in dilated cardiomyopathy was associated with short-term improvement in left ventricular ejection fraction and exercise tolerance.

Objective: We investigated long-term effects of intracoronary CD34+ cell transplantation in dilated cardiomyopathy and the relationship between intramyocardial cell homing and clinical response.

Methods and results: Of 110 dilated cardiomyopathy patients, 55 were randomized to receive CD34+ stem cell transplantation (SC group) and 55 received no cell therapy (controls). In the SC group, CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and cells were injected in the artery supplying segments with the greatest perfusion defect. At baseline, 2 groups did not differ in age, sex, left ventricular ejection fraction, or N-terminal B-type natriuretic peptide levels. At 5 years, stem cell therapy was associated with increased left ventricular ejection fraction (from 24.3 ± 6.5% to 30.0 ± 5.1%; P=0.02), increased 6-minute walk distance (from 344 ± 90 m to 477 ± 130 m; P<0.001), and decreased N-terminal B-type natriuretic peptide (from 2322 ± 1234 pg/mL to 1011 ± 893 pg/mL; P<0.01). Left ventricular ejection fraction improvement was more significant in patients with higher myocardial homing of injected cells. During follow-up, 27 (25%) patients died and 9 (8%) underwent heart transplantation. Of the 27 deaths, 13 were attributed to pump failure and 14 were attributed to sudden cardiac death. Total mortality was lower in the SC group (14%) than in controls (35%; P=0.01). The same was true of pump failure (5% vs. 18%; P=0.03), but not of sudden cardiac death (9% vs. 16%; P=0.39).

Conclusions: Intracoronary stem cell transplantation may be associated with improved ventricular function, exercise tolerance, and long-term survival in patients with dilated cardiomyopathy. Higher intramyocardial homing is associated with better stem cell therapy response.

Trial registration: ClinicalTrials.gov NCT01350310.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD34 / metabolism*
  • Biomarkers / metabolism
  • California
  • Cardiomyopathy, Dilated / blood
  • Cardiomyopathy, Dilated / diagnosis
  • Cardiomyopathy, Dilated / immunology
  • Cardiomyopathy, Dilated / mortality
  • Cardiomyopathy, Dilated / pathology
  • Cardiomyopathy, Dilated / physiopathology
  • Cardiomyopathy, Dilated / surgery*
  • Cause of Death
  • Cell Movement
  • Cell Tracking
  • Chi-Square Distribution
  • Coronary Circulation
  • Echocardiography
  • Exercise Test
  • Exercise Tolerance
  • Female
  • Follow-Up Studies
  • Humans
  • Injections, Intra-Arterial
  • Interleukin-6 / blood
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myocardial Perfusion Imaging
  • Myocardium / immunology
  • Myocardium / pathology*
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Proportional Hazards Models
  • Recovery of Function
  • Slovenia
  • Stem Cell Transplantation* / adverse effects
  • Stem Cell Transplantation* / mortality
  • Stem Cells / immunology*
  • Stroke Volume
  • Texas
  • Time Factors
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / blood
  • Ventricular Function, Left*

Substances

  • Antigens, CD34
  • Biomarkers
  • IL6 protein, human
  • Interleukin-6
  • Peptide Fragments
  • Tumor Necrosis Factor-alpha
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain

Associated data

  • ClinicalTrials.gov/NCT01350310