14 4
electronic cardiac devices. These conditions pose contraindications for MRI, and trial
investigators may have to either exclude these patients from the analysis or use other
imaging techniques to incorporate these patients in their trials. Together, these factors
weave a complex scenario wherein the ultimate choice of imaging technique for cell
therapy trials may be made for reasons other than reliability and reproducibility of
data, i.e. cost, availability, feasibility, and patient characteristics.
A review of the FOCUS-CCTRN trial highlights the practical implications of the
above points. In this study, 92 patients with ischemic cardiomyopathy were random-
ized in a 2:1 ratio with 62 patients scheduled to receive BMC therapy and 31 standard
therapy [ 30 ]. Of these patients, 54 and 28 patients, respectively, underwent echocar-
diography evaluations at baseline and at 6 months. SPECT for perfusion defects was
performed on 52 and 25 patients respectively. Surprisingly, only 17 of the 92 initially
randomized patients were without contraindications for MRI. The investigators were
unable to obtain meaningful data from MRI analysis due to the large number of
patients, who were excluded due to ineligibility for MRI evaluation.
9.5 Assessment of Clinical Outcomes
Although accurate measurement of cardiac structure and function is important
toward determining the efficacy of cell therapy, assessment of impact of such ther-
apy on clinical events is perhaps more important. Indeed, data generated over 15
years of clinical cardiac cell therapy have consistently proven that bone marrow
cells are safe for use in humans. As the injected cells are mostly autologous, they do
not generate an immune response. Mere transference of these cells from the bone
marrow to the heart has not been associated with any major adverse effects. Besides
safety, clinical outcomes also determine the long-term efficacy of this emerging
therapy. However, the incidence of adverse clinical events is often low, and given
the relatively small number of patients in individual trials, analysis of clinical out-
comes from pooled data in meta-analysis has been particularly helpful.
In the most recent meta-analysis, our data indicated that BMC therapy was asso-
ciated with significant reduction in all-cause mortality, recurrent MI, ventricular
tachycardia/ventricular fibrillation and CVA/transient ischemic attack compared
with standard therapy [ 19 ]. There were trends toward reduction in cardiac death,
heart failure and stent thrombosis, although these differences did not reach signifi-
cance (Table 9.4). The lack of increase in stent thrombosis and in-stent restenosis in
BMC-treated patients was particularly encouraging, since BMC injection in the
infarct-related artery has been shown to increase atheroma burden [ 90 ]. On the other
hand, the recently reported ACCRUE study failed to show any improvement in clin-
ical outcomes following cell transplantation [ 34 ]. In view of these differences, the
results of the currently ongoing phase III Effect of Intracoronary Reinfusion of
Bone Marrow-derived Mononuclear cells on All Cause Mortality in Acute
Myocardial Infarction (BAMI) trial are likely to provide a definitive answer regard-
ing the efficacy of BMC therapy on patient survival.
A. Samanta et al.