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

Study Questions:

What is the effect of bone marrow mononuclear cell (BMC) administration through transendocardial injections on myocardial perfusion, left ventricular end-systolic volume (LVESV), and maximal oxygen consumption in patients with coronary artery disease or LV dysfunction, and limiting heart failure or angina?


FOCUS-CCTRN was a phase 2 randomized, double-blind, placebo-controlled trial of symptomatic patients (New York Heart Association class II-III or Canadian Cardiovascular Society class II-IV) with an LV 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 five 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) was performed. The main outcome measures included co-primary endpoints 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 the BMC group and n = 31 in the placebo group). Changes in LVESV index (−0.9 ml/m2; 95% confidence interval [CI], −6.1 to 4.3; p = 0.73), maximal oxygen consumption (1.0; 95% CI, −0.42 to 2.34; p = 0.17), and reversible defect (−1.2; 95% CI, −12.50 to 10.12; p = 0.84) 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.


The authors concluded that 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.


This large, adequately powered study of cell therapy in patients with chronic ischemic heart disease and LV dysfunction (LV ejection fraction ≤45%) found no significant differences in a priori selected primary endpoints between patients treated with BMCs and placebo in this first-in-man study that administered 100 million cells via transendocardial injection. While further studies to determine the relationship between the composition and function of bone marrow product and clinical endpoints are indicated, the future for cell therapy using current methodology does not look promising.

Clinical Topics: Heart Failure and Cardiomyopathies, Noninvasive Imaging, Atherosclerotic Disease (CAD/PAD), Novel Agents, Acute Heart Failure, Computed Tomography, Echocardiography/Ultrasound, Nuclear Imaging

Keywords: Carbamates, Outcome Assessment (Health Care), Coronary Artery Disease, Myocardial Ischemia, National Heart, Lung, and Blood Institute (U.S.), Ventricular Function, Left, Tomography, Emission-Computed, Single-Photon, Canada, Coronary Circulation, New York, Cell- and Tissue-Based Therapy, Bone Marrow, Oxygen Consumption, Benzimidazoles, Heart Failure, Stroke Volume, Confidence Intervals, United States, Echocardiography

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