Effect of Impaired Myocardial Reperfusion on Left Ventricular Remodeling in

Patients With Anterior Wall Acute Myocardial Infarction Treated

With Primary Coronary Intervention
Aleksander Araszkiewicz, MD*, Stefan Grajek, MD, PhD, Maciej Lesiak, MD, Marek Prech, MD,
Małgorzata Pyda, MD, Magdalena Janus, MD, and Andrzej Cieslinski, MD, PhD
We assessed the effect of impaired myocardial blush after primary coronary intervention
(PCI) on left ventricular remodeling in patients with ST-segment elevation myocardial
infarction (STEMI). The study population consisted of 145 patients with first anterior
STEMI that was treated successfully (Thrombolysis In Myocardial Infarction grade 3 flow)
with PCI. Left ventricular remodeling was defined as an increase of >20% in end-diastolic
volume based on repeated echocardiographic measurements in patients. The study popu-
lation was divided into 2 groups according to the presence (myocardial blush grade [MBG]
2 to 3, n ⴝ 86) or absence (MBG 0 to 1, n ⴝ 59) of myocardial reperfusion. Left ventricular
remodeling appeared in 21% of the entire study group. Poor myocardial blush after PCI
was associated with an increased rate of remodeling compared with good myocardial
reperfusion (32% vs 14%, hazard ratio 2.308, 95% confidence interval [CI] 1.21 to 4.39,
p ⴝ 0.014). Symptoms of heart failure were observed significantly more often in patients
with MBG 0 to 1 (35.6% vs 18.6%, p ⴝ 0.032) than in patients with MBG 2 to 3. In
multivariate analysis, only age (odds ratio 0.96, 95% CI 0.92 to 0.99, p ⴝ 0.02) and MBG
0 to 1 (odds ratio 3.15, 95% CI 1.35 to 7.31, p ⴝ 0.008) were associated with left ventricular
dilation. In conclusion, impaired microvascular reperfusion is associated with left ventric-
ular remodeling and development of congestive heart failure in patients with anterior
STEMI that is treated with primary coronary angioplasty. © 2006 Elsevier Inc. All rights
reserved. (Am J Cardiol 2006;98:725–728)

Left ventricular remodeling after myocardial infarction is an
important predictor of long-term prognosis and precedes the
development of overt symptoms of congestive heart fail-
ure.1 The benefits of primary percutaneous coronary inter-
ventions (PCIs) in patients with ST-segment elevation myo-
cardial infarction (STEMI) have been ascribed to early
restoration of Thrombolysis In Myocardial Infarction grade 3
flow in the infarct-related artery that results in a limitation of
infarct size and increased survival compared with thrombolytic
treatment.2 However, some recent reports have shown quite a
high prevalence of left ventricular dilation that occurs in pa-
tients with STEMI that is treated successfully with primary
PCI.3 In addition, restoration of infarct-related artery patency
does not always correlate with the presence of adequate myo-
cardial perfusion.4 An ischemic episode may cause serious
damage to coronary microvasculature so that the flow to the
infarcted myocardium is decreased or absent (“no-reflow” phe-
nomenon). We hypothesized that, despite early restoration of
optimal flow in the infarct-related artery in patients with
STEMI treated with primary PCI, impaired myocardial reper-
fusion may be associated with the development of left ventric-
ular remodeling. To test this hypothesis, we assessed myocar-
The 1st Department of Cardiology, Poznan University of Medical
Sciences, Poznan, Poland. Manuscript received January 29, 2006; revised
manuscript received and accepted April 14, 2006.
* Corresponding author: Tel: 48-61-854-9146; fax: 48-61-854-9094.
E-mail address: aaraszkiewicz@interia.pl (A. Araszkiewicz).
dial reperfusion after primary PCI using a simple angiographic
marker of tissue reperfusion, myocardial blush grade (MBG),
and then evaluated baseline and 6-month echocardiographic
data.
Methods and Results
The study population consisted of 172 consecutive patients
with first anterior wall STEMI who were admitted to our
institution within 12 hours of symptom onset between October
2001 and January 2004. They were prospectively enrolled in
the study if they underwent successful primary PCI, which was
defined as residual infarct-related artery stenosis ⬍30% and
Thrombolysis In Myocardial Infarction grade 3 flow after the
procedure. Of 172 patients who were initially selected for the
study, 6 (3.5%) were excluded for inadequate echocardio-
graphic image quality, 5 (2.9%) for bad quality of angiograms,
and 16 (9.3%) died within 6 months. Thus, 145 patients con-
stituted the final study group. All patients gave their written
informed consent to participate in this trial. The study protocol
was approved by the local ethics committee.
Coronary angiography was performed with Judkins’
technique and digitally recorded by a HICOR system (Sie-
mens, Munich, Germany). Thrombolysis In Myocardial In-
farction flow grade was evaluated from the baseline angio-
gram and after completion of coronary angioplasty. MBG
was assessed by 2 reviewers who were blinded to each other
and to the clinical data. Intraobserver variability in the

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doi:10.1016/j.amjcard.2006.04.009
726 The American Journal of Cardiology (www.AJConline.org)

Table 1 Table 2
Baseline characteristics of studied groups Echocardiographic data
Variable MBG 0–1 MBG 2–3 p Value Variable MBG 0–1 MBG 2–3 p Value
(n ⫽ 59) (n ⫽ 86) (n ⫽ 59) (n ⫽ 86)

Age (yrs) 61 ⫾ 11 59 ⫾ 13 0.26 Ejection fraction at baseline (%) 46 ⫾ 10 48 ⫾ 9 0.19

Men 41 (70%) 65 (76%) 0.71 Ejection fraction at 6 mo (%) 51 ⫾ 15 56 ⫾ 14 0.02
Diabetes mellitus 16 (27%) 12 (14%) 0.06 End-diastolic volume at baseline (ml) 114 ⫾ 38 111 ⫾ 37 0.61
Systemic hypertension 38 (64%) 42 (49%) 0.09 End-diastolic volume at 6 mo (ml) 127 ⫾ 49 112 ⫾ 50 0.02
Current smoker 26 (44%) 46 (54%) 0.31 End-systolic volume at baseline (ml) 63 ⫾ 27 57 ⫾ 26 0.24
Time to therapy (min) 300 ⫾ 190 223 ⫾ 122 0.004 End-systolic volume at 6 mo 66 ⫾ 36 53 ⫾ 36 0.02
Glycoprotein IIb/IIIa inhibitors 25 (42%) 32 (37%) 0.6 Wall motion score index at baseline 1.7 ⫾ 0.4 1.6 ⫾ 0.4 0.06
Stents 57 (97%) 79 (92%) 0.31 Wall motion score index at 6 mo 1.6 ⫾ 0.4 1.4 ⫾ 0.4 0.002
Peak creatine kinase (U/L) 3154 ⫾ 2421 3191 ⫾ 2824 0.94
Multivessel disease 34 (58%) 27 (3%) 0.002
TIMI grade 3 flow before PCI 4 (5%) 11 (13%) 0.28
Angiotensin-converting 52 (88%) 71 (83%) 0.48
enzyme inhibitors
Statins 50 (85%) 68 (79%) 0.52
␤ Blockers 52 (88%) 69 (88%) 0.51

TIMI ⫽ Thrombolysis In Myocardial Infarction.

assessment of MBG when using a random sample of 40

films showed a ␬ value of 0.94. Angiographic follow-up
was performed at 6 months in 113 patients (78%). Blush
was graded according to a dye density score (0 ⫽ no
myocardial blush or persistent blush, 1 ⫽ minimal blush, 2
⫽ moderate blush but less than obtained during angiogra-
phy of the contralateral or ipsilateral noninfarct-related ar-
tery, 3 ⫽ normal myocardial blush).5 A 2-dimnesional echo-
cardiogram was obtained within 36 hours of admission
(baseline) and at 6 months after STEMI with a SONOS
model 5500 (Hewlett-Packard, Andover, Massachusetts)
and 3.5-MHz transducers. Analysis was performed by 2
observers who were blinded to the clinical and angiographic
data. End-diastolic volume, end-systolic volume, and left
ventricular ejection fraction were computed with a modified
Simpson’s technique. Left ventricular wall motion score
index was calculated with a model proposed by the Amer-
ican Society of Echocardiography. Left ventricular remod-
eling was defined as significant left ventricular dilation
(increase of ⱖ20% in end-diastolic volume) based on re-
peated measurements in patients and on the upper 95%
confidence interval [CI] of intraobserver variability.3 The
study population was divided into 2 groups according to the
presence (MBG 2 to 3) or absence (MBG 0 to 1) of myo-
cardial blush. The diagnosis of heart failure was based on
hospitalization for heart failure or the presence of ⱖ2 of the
following criteria at 6-month follow-up: dyspnea, bibasilar
pulmonary rales, third heart sound, or radiographic evidence
of pulmonary congestion.
Data are expressed as means ⫾ SDs for continuous
variables and as absolute and relative frequencies for cate-
gorical variables. Continuous variables were compared us-
ing nonparametric tests (Mann-Whitney U statistic test).
Fisher’s exact test was used to compare categorical vari-
ables. Multiple logistic regression analysis was performed
to evaluate variables that were significant in univariate anal-
ysis. A p value ⬍0.05 was considered statistically signifi-
Figure 1. Presence (percentage) of left ventricular remodeling at 6 months
in groups with adequate (MBG 2 to 3) and impaired (MBG 0 to 1)
myocardial reperfusion.
cant. Statistical analysis was performed with Statistica 6.0
(StatSoft, Inc., Tulsa, Oklahoma).
Baseline clinical characteristics of the 2 study groups are
presented in Table 1. There were no significant differences
between groups in terms of prevalence of risk factors, co-
morbidities, or administration and dosage of angiotensin-con-
verting enzyme inhibitors, ␤ blockers, statins, and other drugs.
Multivessel disease was significantly more frequent in patients
with MBG 0 to 1, and time between onset of symptoms and
balloon angioplasty was longer in these patients.
Echocardiographic data are presented in Table 2. Mean
ejection fraction estimated at 6-month follow-up was sig-
nificantly lower in the group with MBG 0 to 1 (51 ⫾ 15%
vs 56 ⫾ 14%, p ⫽ 0.02), whereas end-diastolic volume
increased significantly in these patients (127 ⫾ 49 vs 112 ⫾
50 ml, p ⫽ 0.02). Wall motion score index was lower in the
group with MBG 2 to 3 at 6-month follow-up (1.4 ⫾ 0.4 vs
1.6 ⫾ 0.4, p ⫽ 0.002).
Coronary angiography performed 6 months after STEMI
showed no significant differences between groups in rate of
restenosis in the infarct-related artery (19.4% vs 22%,
p ⫽ 0.8).
Overall, significant left ventricular dilation occurred in
31 patients (21%) at 6 months. Left ventricular dilation was
observed in 19 patients (32.2%) with MBG 0 to 1 and in 12
 Coronary Artery Disease/Myocardial Reperfusion and Left Ventricular Remodeling
(14%) with MBG 2 to 3 (RR 2.3, 95% CI 1.2 to 4.4, p ⫽
0.012; Figure 1). Symptoms of heart failure were observed
significantly more often in patients with impaired myocar-
dial reperfusion (35.6% vs 18.6%, p ⫽ 0.032).
Apart from impaired myocardial reperfusion, univariate
analysis showed a significant relation across age (p ⫽
0.0135), peak creatine kinase concentration (p ⫽ 0.05), and
left ventricular dilation. Of these, only MBG 0 to 1 (odds
ratio 3.15, 95% CI 1.35 to 7.31, p ⫽ 0.008) and age (odds
ratio 0.96, 95% CI 0.92 to 0.99, p ⫽ 0.02) were confirmed
in multivariate analysis to be significant factors predispos-
ing to the development of left ventricular remodeling.
Discussion
The major finding of this study is that in almost 33% of
patients with anterior wall STEMI, impaired myocardial
reperfusion (MBG 0 to 1) results in progressive left ven-
tricular dilation despite rapid restoration of Thrombolysis In
Myocardial Infarction grade 3 flow. Moreover, poor MBG
was significantly more often associated with development
of heart failure symptoms.
Early reperfusion of the occluded infarct-related artery
results in myocardial salvage and subsequent increases in
left ventricular function and patient survival.6 Since the
introduction of primary PCI in acute settings of STEMI, its
major advantages over intravenous thrombolysis have been
more effective restoration of coronary patency, less recur-
rent myocardial ischemia, increased residual left ventricular
function, and better clinical outcome.2 However, Bolognese
et al3 found that, 6 months after successful treatment of
STEMI with primary PCI, left ventricular remodeling oc-
curred in about 30% of patients, a rate close to the 34%
observed in patients who underwent thrombolysis.7
Restoration of blood flow to a previously ischemic zone
leads to serious physiologic changes, including neutrophil
infiltration, endothelial and tissue edema, macro- and micro-
embolization, and, as a consequence, impairment of microcir-
culatory flow.4,8 Quite recently, results of some studies inves-
tigating the effect of impaired myocardial reperfusion on left
ventricular remodeling have been reported. Bolognese et al9
strongly associated lack of myocardial reperfusion (as assessed
by myocardial contrast echocardiography) with progressive
left ventricular dilation, whereas Wu et al10 found that micro-
vascular obstruction, evaluated by magnetic resonance imag-
ing, performed 10 days after an infarct predicted left ventric-
ular remodeling and poor patient prognosis.
The present study focused on the relations between dif-
ferent clinical and angiographic factors and left ventricular
remodeling after STEMI. Of several factors that were as-
sessed, age and impaired myocardial reperfusion (MBG 0 to
1) were confirmed in univariate and multivariate analyses to
play a crucial role in the development of left ventricular
remodeling. The deleterious effect of advanced age, a non-
modifiable factor, on left ventricular structure and perfor-
mance has been previously demonstrated.11 Moreover,
727
De Luca et al12 associated aging with worse myocardial
reperfusion after myocardial infarction.12 Results of that
study confirmed that myocardial reperfusion (a potentially
modifiable factor) was more predictive of the development
of left ventricular remodeling than restoration of Thrombol-
ysis In Myocardial Infarction grade 3 flow. To the best of
our knowledge, this is the first study to evaluate the effec-
tiveness of MBG, which is a simple angiographic marker of
microvascular reperfusion, in predicting left ventricular re-
modeling after STEMI. Echocardiographic measurements
performed at 6-month follow-up showed that overall signif-
icant left ventricular dilation appeared in 21% of patients, a
rate not as low as in some previous studies.3 However, when
the results of MBG assessment were taken into consider-
ation, progressive left ventricular dilation was observed in
32% of patients with impaired myocardial reperfusion.
More importantly, such a high rate of left ventricular re-
modeling was associated with the development of heart
failure symptoms. In contrast, the rate of left ventricular
remodeling in patients with Thrombolysis In Myocardial
Infarction grade 3 flow and adequate myocardial reperfu-
sion was 14%, 1 of the lowest reported in the literature.
The major limitation of the study was that angiographic
follow-up was available in only 78% of patients. Restenosis
has been identified as an important factor that increases the
process of left ventricular remodeling.13,14 Due to method-
ologic reasons, it is difficult to perform angiographic fol-
low-up in all patients. However, the reported numbers are
quite high compared with those in other studies and, more
importantly, there were no significant differences in the rate
of restenosis between groups (19.4% vs 22%, respectively,
p ⫽ 0.8).
The number of patients (172) included in the study was
not large, but the study group consisted only of patients with
first STEMI of the anterior wall. Thus, despite the relatively
small number of patients, its homogeneity allowed us to
compare echocardiographic parameters with greater objec-
tivity.
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