141were significantly reduced by −2.60 ml/m^2 and −3.17 ml/m^2 , respectively, following
cell therapy. Improvement in LVEF and LVESVI was superior in patients under the
age of 55 and in those with baseline LVEF <40%. Patients younger than 55 also
showed a significant improvement in LVEDVI compared with older patients.
Kandala et al. performed a meta-analysis of ten RCTs that included 519 patients, in
the setting of chronic ischemic cardiomyopathy [ 86 ]. BMC therapy improved LVEF
by 4.48%, reduced LVESV by 20.64 ml and LVEDV by 16.71 ml at 6 months com-
pared with controls. However, the ACCRUE study, a meta-analysis based on indi-
vidual patient data from 12 trials for cell therapy in patients with AMI, failed to
identify any significant improvement in cardiac parameters with cell therapy [ 34 ].
9.4 Impact of Imaging Modalities on Outcomes of BMC
Therapy
Although differences in other aspects of trial design may account for the observed
variances in outcomes, the choice of imaging modalities has been implicated as one
of the underlying reasons. A notion has been advanced that some of the benefits of
BMC injection stem from the use of rather inaccurate imaging techniques that are
inferior to MRI, the current gold standard. Irrespective of the superiority of one
method over another, RCTs of BMC therapy have indeed utilized diverse imaging
modalities to assess parameters of cardiac structure and function. Echocardiography,
LVG, SPECT and MRI are the most commonly used techniques for the assessment
of LVEF, infarct size, LVESV, and LVEDV, as shown in Table 9.1. These modalities
vary considerably with regard to fundamental principles of imaging, and some are
more appropriate in certain scenarios than others. For instance, functional and volu-
metric assessment by MRI is more reliable than by echocardiography [ 87 ].
Myocardial scar size measured by MRI closely agrees with PET data [ 88 ]. However,
MRI also tends to overestimate infarct size soon after an MI due to the presence of
tissue edema. Therefore, the assessment of infarct size by MRI was delayed until
2–3 weeks after the MI in select trials [ 25 ]. Table 9.2 summarizes the relative advan-
tages and disadvantages of these cardiac imaging modalities. MRI is generally con-
sidered the gold standard for assessment of cardiac structure and function.
The various imaging methods utilized in BMC clinical trials are provided in
Table 9.1. In these trials, echocardiography was almost always used due to its wide-
spread availability and relative lack of contraindications. It is a fast and fairly accu-
rate tool to assess cardiac structure and function. However, several trials chose more
than one imaging modality so that LV structure and function could be assessed
using the optimal techniques for respective parameters. For example, the FOCUS-
CCTRN trial used echocardiography for LVEF and LVESVI assessment, but used
SPECT to assess perfusion defect [ 30 ]. Confirmation of results with the use of
another imaging technique reduces the possibility of assessments being affected by
the type of imaging technique chosen. The ASTAMI trial used both echocardiogra-
phy and MRI to assess LVEF, LVESV, and LVEDV [ 26 ], while the FINCELL trial
9 Bone Marrow Cell Therapy for Ischemic Heart Disease...