Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure: the FOCUS-CCTRN trial

JAMA. 2012 Apr 25;307(16):1717-26. doi: 10.1001/jama.2012.418. Epub 2012 Mar 24.

Abstract

Context: Previous studies using autologous bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy have demonstrated safety and suggested efficacy.

Objective: To determine if administration of BMCs through transendocardial injections improves myocardial perfusion, reduces left ventricular end-systolic volume (LVESV), or enhances maximal oxygen consumption in patients with coronary artery disease or LV dysfunction, and limiting heart failure or angina.

Design, setting, and patients: A phase 2 randomized double-blind, placebo-controlled trial of symptomatic patients (New York Heart Association classification II-III or Canadian Cardiovascular Society classification II-IV) with a left ventricular ejection fraction of 45% or less, a perfusion defect by single-photon emission tomography (SPECT), and coronary artery disease not amenable to revascularization who were receiving maximal medical therapy at 5 National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network (CCTRN) sites between April 29, 2009, and April 18, 2011.

Intervention: Bone marrow aspiration (isolation of BMCs using a standardized automated system performed locally) and transendocardial injection of 100 million BMCs or placebo (ratio of 2 for BMC group to 1 for placebo group).

Main outcome measures: Co-primary end points assessed at 6 months: changes in LVESV assessed by echocardiography, maximal oxygen consumption, and reversibility on SPECT. Phenotypic and functional analyses of the cell product were performed by the CCTRN biorepository core laboratory.

Results: Of 153 patients who provided consent, a total of 92 (82 men; average age: 63 years) were randomized (n = 61 in BMC group and n = 31 in placebo group). Changes in LVESV index (-0.9 mL/m(2) [95% CI, -6.1 to 4.3]; P = .73), maximal oxygen consumption (1.0 [95% CI, -0.42 to 2.34]; P = .17), and reversible defect (-1.2 [95% CI, -12.50 to 10.12]; P = .84) were not statistically significant. There were no differences found in any of the secondary outcomes, including percent myocardial defect, total defect size, fixed defect size, regional wall motion, and clinical improvement.

Conclusion: Among patients with chronic ischemic heart failure, transendocardial injection of autologous BMCs compared with placebo did not improve LVESV, maximal oxygen consumption, or reversibility on SPECT.

Trial registration: clinicaltrials.gov Identifier: NCT00824005.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Angina Pectoris / etiology
  • Angina Pectoris / therapy
  • Bone Marrow Transplantation / methods*
  • Coronary Artery Disease / physiopathology
  • Coronary Artery Disease / therapy*
  • Coronary Circulation*
  • Double-Blind Method
  • Female
  • Heart Failure / complications
  • Heart Failure / diagnostic imaging
  • Heart Failure / physiopathology
  • Heart Failure / therapy*
  • Humans
  • Injections
  • Male
  • Middle Aged
  • Myocardial Ischemia
  • Oxygen Consumption
  • Tomography, Emission-Computed, Single-Photon
  • Transplantation, Autologous
  • Treatment Outcome
  • Ventricular Dysfunction, Left / etiology
  • Ventricular Dysfunction, Left / therapy*

Associated data

  • ClinicalTrials.gov/NCT00824005