Autologous stem/progenitor cells have been investigated for several years as a novel therapy for patients with advanced ischaemic heart disease, particularly those with ongoing angina or heart failure.  In particular, for patients with ischaemic cardiomyopathy, autologous bone marrow mononuclear cells (BMCs) have been shown to be safe and possibly effective.  However, none of the trials performed to date have been sufficiently powered to investigate clinical outcome measures.

The FOCUS-CCTRN trial (First Mononuclear Cells injected in the United States conducted by the  Cardiovascular Cell Therapy Research Network) was a phase II randomised double-blind, placebo-controlled trial.  All patients were symptomatic with either NYHA class II-III heart failure or CCS class III-IV angina and a left ventricular ejection fraction of 45% or less, a perfusion defect detected by single-photon emission tomography (SPECT), and coronary artery disease not amenable to revascularization but receiving maximal medical therapy.  The study took place at five large US research sites between 2009 and 2011.  Patients were randomised to receive either 100 million isolated BMCs injected transendocardially, or placebo.  The main outcome measures, assessed at six months, were: change in left ventricular end systolic volume (as assessed by ECHO), maximal oxygen consumption, and reversibility on SPECT.  Phenotypic and functional analyses of the cell product were performed by a biorepository core laboratory.

92 patients were randomised, 61 to BMCs and 31 to placebo.  However, there were no statistically significant changes seen in left ventricular end-systolic volume (p=.73), maximal oxygen consumption (p=.17), nor perfusion defects (p=.84).  Several secondary outcome measures, including regional wall motion, the percent myocardial defect, and clinical improvement, also showed no improvement.

Conclusions:

In this study of patients with chronic ischemic heart failure, transendocardial injection of autologous BMCs -compared with placebo – did not improve left ventricular function, maximal oxygen consumption, or reversibility of myocardial ischaemia.

• Perin C, Willerson JT, Pepine CJ et al.  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;307:1717-1726.