Wolak, Arik

Zahger, Doron

Elsevier - Publisher Connector 

Grade of Ischemia to Assess No Reflow After Reperfusion 

i
i
t
m
p
t
m
w
*
S
*
S
H
C
3
G
E
R
1
2
3
4
5
R
T
c
i
e
d
w
d
T
n
a
a
a
t
i
B
B
M
q
f
1
g
i
t
(
p
s
i
d
m
a
m
w
*
M
C
M
*
D
H
M
4
G
E
R
1
2
3
4
5
G
N
W
a
a
A
m
e
264 Correspondence JACC Vol. 55, No. 3, 2010
January 19, 2010:255–69nto an ischemic area results in modulation of the local tissue
mmune system and altered cytokine production (4). Indeed, BMC
ransplantation results in local inflammatory changes that activate
yofibroblasts, thus reducing infarct size (5). Thus, modulation of
ro- and anti-inflammatory intramyocardial cytokine levels by
ransplanted cells and their crosstalk with the local tissue environ-
ent likely affect survival and differentiation of progenitor cells, as
ell as overall cardiac outcome.
Thomas Thum, MD, PhD
tefan Anker, MD, PhD
Department of Molecular and Translational Therapeutic
trategies
annover Medical School
arl-Neuberg-Str. 1
0625 Hannover
ermany
-mail: Thum.Thomas@mh-hannover.de
doi:10.1016/j.jacc.2009.07.064
EFERENCES
. Yousef M, Schannwell CM, Köstering M, Zeus T, Brehm M, Strauer
BE. The BALANCE study: clinical benefit and long-term outcome
after intracoronary autologous bone marrow cell transplantation in
patients with acute myocardial infarction. J Am Coll Cardiol 2009;53:
2262–9.
. Forrester JS, Makkar RR, Marba´n E. Long-term outcome of stem cell
therapy for acute myocardial infarction: right results, wrong reasons.
J Am Coll Cardiol 2009;53:2270–2.
. Cao F, Sun D, Li C, et al. Long-term myocardial functional improve-
ment after autologous bone marrow mononuclear cells transplantation
in patients with ST-segment elevation myocardial infarction: 4 years
follow-up. Eur Heart J 2009;30:1986–94.
. Thum T, Bauersachs J, Poole-Wilson PA, Volk HD, Anker SD. The
dying stem cell hypothesis: immune modulation as a novel mechanism
for progenitor cell therapy in cardiac muscle. J Am Coll Cardiol
2005;46:1799–802.
. Sun J, Li SH, Liu SM, et al. Improvement in cardiac function after bone
marrow cell therapy is associated with an increase in myocardial
inflammation. Am J Physiol Heart Circ Physiol 2009;296:43–50.
eply
he letter by Drs. Thum and Anker touches various aspects of
ardiac stem cell therapy (e.g., mortality, paracrine effects, and
nflammation), all of which may be briefly addressed as follows.
Intracoronary stem cell therapy seems to represent a safe and
ffective regimen for treatment of heart failure after acute myocar-
ial infarction (1,2), in an old myocardial infarction (8 years)
ith ischemic cardiomyopathy (3), and in advanced dilated car-
iomyopathy (4). Our study (5) did not aim to speculate (Drs.
hum and Anker) on stem cell-induced inflammation (which has
ot yet been documented in the overwhelming majority of studies)
nd on possible paracrine effects by stem cells, but fortunately was
ble to analyze the different parameters of ventricular performance
nd potential effects on cardiac mortality in large patient groups,
reated and untreated, in long-term follow-up after myocardial
nfarction.
When carefully reading our paper (5), the BALANCE (Clinical
enefit and Long-Term Outcome After Intracoronary Autologous
one Marrow Cell Transplantation in Patients With Acute
yocardial Infarction) study showed that mortality, as a conse-
uence of stem cell therapy, is significantly reduced; in a median
ollow-up time of 4.6  2.1 years in the bone marrow cell group ppatient died, and in 4.8  2.2 years, 7 patients in the control
roup died (p  0.03).
Mortality is dependent on both the degree of ventricular
mpairment and the amount of arrhythmogenicity. Dependent on
he multifactorial mode of action of stem cells, systolic function
e.g., ejection fraction, stroke volume, contractility) and diastolic
erformance are improved; infarct size, end-systolic volume, and
ystolic wall stress decrease; and the arrhythmogenicity of the heart
s presumably reduced. Thus, several of the main myocardial
eterminants of cardiac mortality are influenced in favor of reduced
ortality by stem cell treatment in chronically ill cardiac patients.
Undoubtedly, further large studies are needed to analyze the
ction of stem cells on ventricular performance and cardiac
ortality in different stages of chronic cardiac failure, especially
ith regard to the distinct origin of this chronic disease.
Bodo-Eckehard Strauer, MD
ichael Brehm, MD
hristiana Mira Schannwell, MD
uhammad Yousef, MD
Department of Medicine
ivision of Cardiology, Pneumology, and Angiology
einrich-Heine-University of Düsseldorf
oorenstr. 5
0225 Düsseldorf
ermany
-mail: strauer@med.uni-duesseldorf.de
doi:10.1016/j.jacc.2009.11.005
EFERENCES
. Strauer BE, BrehmM, Zeus T, et al. [Intracoronary, human autologous
stem cell transplantation for myocardial regeneration following myocar-
dial infarction]. Dtsch Med Wochenschr 2001;126:932–8.
. Strauer BE, Brehm M, Zeus T, et al. Repair of infarcted myocardium
by autologous intracoronary mononuclear bone marrow cell transplan-
tation in humans. Circulation 2002;106:1913–8.
. Strauer BE, Brehm M, Zeus T, et al. Regeneration of human infarcted
heart muscle by intracoronary autologous bone marrow cell transplan-
tation in chronic coronary artery disease: the IACT study. J Am Coll
Cardiol 2005;46:1651–8.
. Strauer BE, Brehm M, Schannwell CM. The therapeutic potential of
stem cells in heart disease. Cell Prolif 2008;41 Suppl 1:126–45.
. Yousef M, Schannwell CM, Köstering M, Zeus T, Brehm M, Strauer
BE. The BALANCE study: clinical benefit and long-term outcome
after intracoronary autologous bone marrow cell transplantation in
patients with acute myocardial infarction. J Am Coll Cardiol
2009;53:2262–9.
rade of Ischemia to Assess
o Reflow After Reperfusion
e read with great interest the excellent review by Niccoli et al. (1)
bout the no-reflow phenomenon in humans. In their paper, the
uthors describe various techniques for the prediction of no-reflow.
s far as electrocardiography is concerned, the authors only
ention the QRS score as a predictor of ischemia-related injury.
The extent of terminal QRS distortion on the admission
lectrocardiogram, known as the grade of ischemia, is a strong
redictor of failure of ST-segment resolution as well as of
a
p
g
i
t
m
b
w
n
*
A
*
S
P
B
I
E
R
1
2
3
R
W
(
s
M
Q
d
u
m
i
p
i
t
p
w
m
W
s
s
r
S
t
i
d
o
p
*
F
L
F
*
U
L
R
I
E
R
1
2
3
4
V
W
M
W
r
s
p
o
v
m
M
h
i
q
v
p
a
M
(
d
2
(
e
p
t
t
265JACC Vol. 55, No. 3, 2010 Correspondence
January 19, 2010:255–69ngiographic no-reflow and infarct size. We have shown both in
atients receiving thrombolytic therapy (2) and in patients under-
oing primary percutaneous intervention (3) that grade 3 ischemia
s the strongest independent predictor available on admission for
he no-reflow phenomenon. Because electrocardiography is the
ost widely available and least expensive tool at our disposal, and
ecause this simple parameter is a robust predictor of no-reflow,
e believe that it should be widely used to predict the risk of
o-reflow and possibly to select patients for protective therapies.
Doron Zahger, MD
rik Wolak, MD
Department of Cardiology
oroka University Medical Center
. O. Box 151
eer Sheva 84101
srael
-mail: dzahger@bgu.ac.il
doi:10.1016/j.jacc.2009.08.055
EFERENCES
. Niccoli G, Burzotta F, Galiuto L, Crea F. Myocardial no-reflow in
humans. J Am Coll Cardiol 2009;54:281–92.
. Buber J, Gilutz H, Birnbaum Y, Friger M, Ilia R, Zahger D. Grade 3
ischemia on admission and absence of prior beta blockade predict failure
of ST resolution following thrombolysis for anterior myocardial infarc-
tion. Int J Cardiol 2005;104:131–7.
. Wolak A, Yaroslavtsev S, Amit G, et al. Grade 3 ischemia on the
admission electrocardiogram predicts failure of ST resolution following
primary angioplasty for acute myocardial infarction. Am Heart J
2007;153:410–7.
eply
e thank Drs. Zahger and Wolak for their interest in our paper
1) and for the observation about the role of grade of ischemia on
urface electrocardiography (ECG) in the prediction of no-reflow.
any ECG-derived indexes including the QRS score (number of
waves) (2) and the QRS duration (3) along with terminal
istortion of the QRS, known as grade of ischemia (4), have been
sed in the assessment of no-reflow risk. In our review (1), we
entioned the QRS score because it is the most widely used ECG
ndex in the triage of ST-segment elevation myocardial infarction
atients. We acknowledge that other indexes including grade of
schemia may be useful in risk stratification before primary percu-
aneous coronary intervention. Interestingly, in a previous study
erformed by Wolak et al. (4), grade of ischemia was associated
ith infarct size, thrombus burden, and admission glycemia, which
ay all contribute to the multifactorial pathogenesis of no-reflow.
e agree with Drs. Zahger and Wolak that, in an era of
uperspecialist and expensive tools that are not widely available,
uch as cardiac magnetic resonance imaging, inexpensive and
eadily available ECG still has a central role in the management of
T-segment elevation myocardial infarction patients with regard
o microvascular obstruction after primary percutaneous coronary
ntervention. Indeed, ECG is useful for risk prediction and
iagnosis of no-reflow, for monitoring the efficacy of mechanical
r pharmacological therapies against no-reflow, and finally, for
rognostic information. eGiampaolo Niccoli, MD, PhD
rancesco Burzotta, MD, PhD
eonarda Galiuto, MD, PhD
ilippo Crea, MD, PhD
Istituto di Cardiologia
niversità Cattolica del Sacro Cuore
.go A. Gemelli, 8
ome 00168
taly
-mail: gniccoli73@hotmail.it
doi:10.1016/j.jacc.2009.10.019
EFERENCES
. Niccoli G, Burzotta F, Galiuto L, Crea F. Myocardial no-reflow in
humans. J Am Coll Cardiol 2009;54:281–92.
. Iwakura K, Ito H, Kawano S, et al. Predictive factors for development
of the no-reflow phenomenon in patients with reperfused anterior wall
acute myocardial infarction. J Am Coll Cardiol 2001;38:472–7.
. Kacmaz F, Maden O, Aksuyek S, et al. Relationship of admission QRS
duration and changes in QRS duration with myocardial reperfusion in
patients with acute ST segment elevation myocardial infarction
(STEMI) treated with fibrinolytic therapy. Circ J 2008;72:873–9.
. Wolak A, Yaroslavtsev S, Amit G, et al. Grade 3 ischemia on the
admission electrocardiogram predicts failure of ST resolution following
primary angioplasty for acute myocardial infarction. Am Heart J
2007;153:410–7.
alue of a High Exercise
orkload to Rule Out
yocardial Ischemia
e read with great interest the paper by Bourque et al. (1)
egarding the value of a high exercise workload to rule out
ignificant myocardial ischemia. In that study, only 2 (0.4%) of 473
atients reaching 10 metabolic equivalents (METs) and 85%
f maximum age-predicted heart rate (MAPHR) had 10% left
entricular ischemia on myocardial perfusion imaging. Further-
ore, of the 430 patients reaching 10 METs and 85%
APHR without exercise-induced ST-segment depression, none
ad significant myocardial ischemia. These results suggest that the
nformation provided by cardiac imaging in these patients is
uestionable.
Our group previously assessed the prevalence and prognostic
alue of myocardial ischemia on exercise echocardiography in a
opulation of 1,433 patients with known or suspected coronary
rtery disease achieving a high exercise workload (defined as 10
ETs in men and 8 METs in women) (2). Of them, in 437
30%) patients, new or worsening wall motion abnormalities
eveloped during exercise. Over a follow-up of 2.3  1.5 years,
01 (14%) patients underwent coronary revascularization and 57
4%) patients had a hard cardiac event. Furthermore, exercise
chocardiography was shown to provide incremental value for
redicting hard cardiac events in these patients.
It might be argued that, in this study, 19% of the patients failed
o achieve 85% of MAPHR, and ST-segment changes during
he tests developed in 14% of the patients. Thus, we further
xplored whether the findings obtained by Bourque et al. (1) would


file:///data/remote/core/dit/data/elsevier/pdf/2da/aHR0cDovL2FwaS5lbHNldmllci5jb20vY29udGVudC9hcnRpY2xlL3BpaS9zMDczNTEwOTcwOTAzNTkyeA==.pdf

Grade of Ischemia to Assess No Reflow After Reperfusion

Abstract

Similar works

Full text

Available Versions

Elsevier - Publisher Connector

Elsevier - Publisher Connector