Previous studies using autologous bone marrow mononuclear cells (BMCs) in patients
with ischemic cardiomyopathy have demonstrated safety and suggested efficacy.
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.
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.
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).
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.
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.
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.
clinicaltrials.gov Identifier: NCT00824005.