Biomedical Engineering Reference
In-Depth Information
further follow-up will show whether this treatment is effective in preventing nega-
tive remodeling of the left ventricle and reveal potential late adverse events (arrhyth-
mogenicity and propensity for re-stenosis) [
2
]. On the other hand, in another pilot
study (
n
= 5), Kuethe et al. reported that intracoronary transplantation of autologous,
mononuclear bone marrow stem cells did not lead to any significant improvement
in myocardial function and physical performance of patients with chronic ischemic
heart disease at 12-month follow-up [
83
] . Two German studies [
28,
77
] using
sophisticated cardiac magnetic resonance imaging and F-18-Fluorodeoxyglucose-
positron emission tomography (FDG-PET) showed significant decreasing of infarc-
tion area and increasing of myocardial viability in the infarction zone. In all these
clinical trials, which have together 83 patients, there were no reported major adverse
cardiac events, including death, reinfarction and symptomatic heart failure. However,
MAGIC trial [
21
], the only trial that had control coronarography in study protocol
after 6 months, showed very high incidence of in stent restenosis (5 of 7 patients) in
the group of patients received cell therapy. But, in this trial G-CSF was used for the
mobilization of bone marrow progenitors to peripheral blood, and this fact might be
the reason for the high incidence of in-stent restenosis [
84
] .
Zohlnhöfer et al. from the Technische Universität, Munich, Germany, conducted
a randomized, double-blind, placebo-controlled study (REVIVAL-2) to assess the
value of G-CSF treatment in a large group of patients following a heart attack. The
114 patients, diagnosed with ST-segment elevation AMI (a certain pattern on an
electrocardiogram indicating a heart attack), had successful reperfusion (restoration
of blood flow) to the heart by PCI (procedures such as angioplasty in which a cath-
eter-guided balloon is used to open a narrowed coronary artery) within 12 h after
onset of symptoms. Patients were randomly assigned to receive by injection either
a daily dose of 10 mg/kg of G-CSF or placebo (an inactive substance) for 5 days.
The patients were treated between February 2004 and February 2005. Treatment
with G-CSF produced a significant mobilization of bone marrow stem cells.
However, the researchers found that this did not alter infarct size (area of damage)
or left ventricular function after a heart attack. “Moreover, in contrast to other stud-
ies, no increase in the risk of restenosis (narrowing again of an artery after treat-
ment) or major adverse cardiac events was observed with G-CSF treatment,” the
authors write [
86
]. “The REVIVAL-2 trial had a cohort that was larger than all 3
previous trials taken together and had a relatively long follow-up period based on
sensitive assessment methods of left ventricular function and infarct size. In conclu-
sion, use of G-CSF therapy to mobilize bone marrow-derived stem cell did not
improve left ventricular recovery in patients with AMI after successful mechanical
reperfusion, in this study [
87
]. In humans, the biological limitations to cardiac
regenerative growth create both a clinical imperative—to offset cell death in acute
ischemic injury and chronic heart failure—and a clinical opportunity; that is, for
using cells, genes, and proteins to rescue cardiac muscle cell number or in other
ways promote more efficacious cardiac repair. Yet, recent experimental studies and
early-phase clinical trials lend credence to the visionary goal of enhancing cardiac
repair as an achievable therapeutic target. The most of the clinical trials and their
outcomes are presented in Tables
11.2
and
15.1
.
