Autologous BMCs for Patients with Chronic Ischemic Heart Failure

A randomized study of patients with chronic ischemic heart failure revealed that patients who received transendocardial injections of autologous bone marrow mononuclear cells (BMCs) did not demonstrate improved left ventricular end-systolic volume (LVESV) or maximal oxygen consumption when compared with patients who received placebo. The findings were recently reported online in the Journal of the American Medical Association [doi:10.1001/jama.2012.418].

Cell therapy may be a possible treatment for patients who suffer from advanced ischemic heart disease, and previous research has shown that the treatment is safe. Studies have also suggested the treatment is efficacious; however, according to the authors of this latest study, the previous research was not powered to evaluate specific measures of efficacy.

In the FOCUS-CCTRN (First Mononuclear Cells Injected in the United States-Cardiovascular Cell Therapy Research Network) trial, researchers used transendocardial injections of BMCs to assess whether these injections had an effect on LVESV, myocardial perfusion, or maximal oxygen consumption in 92 randomized patients who had chronic ischemic heart disease and left ventricular dysfunction but had no other revascularization options.

Patients who were ≥18 years of age with clinically stable coronary artery disease, LV ejection fraction of ≤45%, and limiting angina and/or congestive heart failure were randomized in a 2:1 ratio to receive BMCs or a placebo preparation.  

As part of the phase 2 study, researchers administered a targeted dose of 100 x 10⁶ BMCs to those in the treatment group and compared LV performance and perfusion at the 6-month mark with baseline data for both the treatment and placebo groups.

All participants initially underwent bone marrow harvesting, automated cell processing, and baseline testing as part of the study. Participants then received either cell-containing or cell-free preparations that were delivered to viable myocardial regions using electromechanical mapping of the LV endocardial surface.

The study was conducted at 5 National Heart, Lung, and Blood Institute-sponsored CCTRN sites between April 2009 and April 2011.

The primary end points of the study were changes in LVESV, maximal oxygen consumption, and reversibility on single-photon emission tomography (SPECT) after 6 months.

The researchers found that at 6 months, there was no significant difference in the change in the LVESV index between the 2 groups (-0.9 mL/m²; 95% confidence interval [CI], -6.1 to 4.3; P=.73). Based on the data, at baseline, the mean (SD) LVESV index was 57.9 (26.1) mL/m² in the BMC group and 65.0 (19.8) mL/m² in the placebo group. After 6 months, the mean (SD) LVESV index for the BMC group was 57.0 (25.5) mL/m², whereas the mean index for the placebo group was 65.0 (23.3) mL/m².

In addition, there was no statistically significant difference between the BMC group and the placebo group in terms of change in maximal oxygen consumption (1.0; 95% CI, -0.42 to 2.34; P=.17).

After assessing data from paired SPECT evaluations at baseline and 6 months for both study groups, the researchers were also unable to find a statistically significant difference in the change in percent reversible defect between the BMC group and the placebo group (-1.2; 95% CI, -12.50 to 10.12; P=.84).

There were also no significant differences between the groups in percent myocardial defect, total defect size, or fixed defect size.

The authors of the study acknowledged that the sample size was relatively small, which prevented any determination about the effect of therapy on the occurrence of community-wide accepted clinical outcomes such as total mortality.

They concluded by saying that further research is needed to further investigate the role of cardiac cell therapy in the treatment of chronic ischemic heart failure.