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Impact of myocardial blush on left ventricular remodeling after first anterior
myocardial infarction treated successfully with emergency percutaneous coronary
intervention
Mohamed Salem, MD, PhD, Karem El Tagoury,Msc, Hamza Kabil, MD, and
Hesham Abou-Elainen, MD
Department of Cardiology, Benha University Hospital, Benha, Egypt
Corresponding author:
Mohamed Salem
Department of Cardiology, Benha Faculty of Medicine, Benha University, Benha,
Egypt
Tel. 0020133106725, Mobile . 01092773227
E.mail. [email protected]
Abstract
Background. Myocardial blush grade (MBG) is routinely used to assess the
effectiveness of myocardial reperfusion in patients with acute myocardial
infarction. Impaired MBG has been found to be an independent predictor of
outcome after reperfusion therapy. Objectives. To assess the impact of myocardial
blush grade on left ventricular remodeling in patients undergoing successful
emergency percutaneous coronary intervention (PCI). Methods. The study
included 30 consecutive patients with first time acute ST segment elevation
myocardial infarction (STEMI). All patients underwent successful emergency
percutaneous coronary intervention (PCI). Patients with TIMI flow-III were further
submitted to MBG grading. Echocardiography was done at 24hours and 3 months
post intervention to assess the impact of MBG on left ventricular remodeling.
Results. Eight patients (26.7%) had MBG 0; 7 patients (23.3%) had MBG I; 12
patients (40%) had MBG II, and 3 patients (10%) had MBG III. There was no
significant difference between MB grades in baseline characteristics. Chest pain
was the main presenting symptom (100%). Time from symptom onset was
inversely correlated with MB grades. Remodeling was presented in 11 patients
(37%). 75% of patients with grade 0 MBG, 57% of grade I, 8.3% of grade II, and
0% of grade III had ventricular remodeling at 3 months respectively.(p=0.007).
Conclusion. Impaired MBG after emergency PCI is associated with increased
risk of LV remodeling. It has the advantage of being simple method to assess
myocardial microcirculation.
Key words. Acute myocardial infarction, reperfusion, myocardial blush
Introduction
Restoration of epicardial blood flow in the infarct-related artery does not always
correlate with the presence of adequate myocardial perfusion
(1)
. In fact, the
success of STEMI treatment is not warranted solely by the re-establishment of
patency of the infarct-related artery, but full reperfusion at the level of the
myocardium is equally or even more important. Despite TIMI III flow, the infarct
core may undergo limited reperfusion at the tissue level because of injury to the
microvasculature and its subsequent obstruction by erythrocytes, neutrophils and
debris, a phenomenon also known as the “no-reflow” phenomenon, which is a
negative independent predictor of myocardial function recovery and long-term
survival (2). Several techniques can be used to assess reperfusion at the tissue level,
such as myocardial contrast echocardiography, scintigraphy, positron emission
tomography and magnetic resonance imaging
(3)
. However, its application during
the acute phase of STEMI is difficult and time consuming. By contrast, the
angiographic myocardial blush score, based on the contrast dye density and
washout in the infarcted myocardium, is a simple tool that correlates significantly
with tissue-level perfusion shortly after recanalization of the infarct-related artery
(4)
. We hypothesized that after successful PCI (restoration of TIMI III flow) in
patients with STEMI, analysis of MB grade may be used to predict LV remodeling.
To test this hypothesis, we assessed myocardial reperfusion, immediately after
PCI, using MB grade and then evaluated baseline and 3 month LV volumes using
echocardiography.
Patients and methods
Study design
This prospective study included 30 patients with first time acute anterior STEMI
who were admitted to the coronary care unit (CCU) of cardiology department,
Damietta cardiology &gastroenterology center, Egypt, during the period from
February 2011 to August 2012. The study aimed to assess the impact of
myocardial blush grade on left ventricular remodeling in patients undergoing
successful emergency PCI (primary or rescue) in patients with first time acute
anterior STEMI. All patients signed an informed consent and the study was
approved by local ethics committee. Key inclusion criteria were: 1. confirmed
acute anterior STEMI defined as > 30 minutes of continuous typical chest pain and
ST-segment elevation (≥1mm in V4-6, I-AVL or ≥2 mm in V2-3). 2. Successful
reperfusion of the infarct-related artery, defined as TIMI III flow, and visually
assessed residual stenosis < 20%. While key Exclusion criteria were: known
coronary artery disease, valvular heart disease, technically poor acoustic window
for two-dimensional echocardiography, severe renal impairment (S. creatinine>3.0
mg/dl), any contraindication to anti platelet therapy.
Methods
A. Baseline evaluation
Baseline evaluation included: review of medical history, presence of risk factors of
coronary artery disease, associated co morbidities, clinical examination, 12 leads
ECG, and routine laboratory investigations
B. Coronary angiography and emergency PCI
All patients received aspirin (300 mg loading then 150 mg daily), clopidogrel (600
mg loading, then 150 mg /day maintenance dose). Un-fractionated heparin (UFH)
(10000 units) bolus dose was injected after sheath insertion. The procedure was
performed according to the standard technique of PCI. Femoral approach was the
standard in all patients using 6-7 Fr sheath. Diagnostic coronary angiography was
done to detect the culprit vessel. XB or JL guide catheters were used during PCI.
Aspiration devices and glycoprotein inhibitors were used in lesions with heavy
thrombus burden. The operator determined the size and length of the stent during
PCI. Sheaths were removed 6 hours post PCI and compression was done manually.
C. Study protocol
After the procedure myocardial blush was graded for patients with TIMI III flow
only and patients were classified according to their MBG into 4 groups:
o Grade 0 (8 patients): no opacification of the myocardium in the distribution
of the culprit artery.
o Grade 1 (7 patients): Minimal opacification of the myocardium in the
distribution of the culprit artery.
o Grade 2 (12 patients): Moderate myocardial blush, less than that obtained
during angiography of the contralateral or ipsilateral non–infarct-related
artery.
o Grade 3 (3 patients): Normal myocardial blush, comparable with that
obtained during angiography of the contra lateral or ipsilateral non-infarctrelated artery.
D. Echocardiography
Two-dimensional echocardiography was performed with the patient in the left
lateral decubitus position. The following parameters of the left ventricle were
determined from apical two- and four-chamber views: end-diastolic volume
(EDV), end-systolic volume (ESV), and ejection fraction was calculated using
modified Simpson’s rule. In this method the endocardium of LV cavity was traced
manually & the length of the long axis of LV cavity was also measured from the
apex to the base then the echo machine automatically divide LV into number of
discs or cylinders of equal heights, the height of each cylinder is determined by the
number of cylinders & length of the long axis of LV cavity, the volume of cylinder
is calculated from the two diameters of the cylinder
(5)
.In all cases, end systolic
&end diastolic volumes were measured in the same cardiac cycle.
LV remodeling was defined as an increase in EDV by ≥ 20%, 3 months after PCI
compared to baseline value.
E. Study definitions
1. Primary PCI
Coronary angioplasty/stenting without prior administration of fibrinolytic agents.
2. Rescue PCI
PCI performed within 12 hours of failed fibrinolysis (primary failure) defined as
persistent or recurrent chest pain, partial or no ST segment resolution on ECG (
less than 50% resolution of initial ST segment elevation on follow up ECG 60-90
minutes after fibrinolytic therapy), TIMI grade 0/1 in infarct related artery by
angiography.
3. TIMI flow grade.
TIMI 0: no perfusion; no antegrade flow beyond the point of occlusion.
TIMI I: penetration without perfusion; contrast material passes beyond the area of
obstruction but fails to opacify the entire coronary bed distal to the obstruction.
TIMI II: partial perfusion; contrast material passes across the obstruction and
opacifies the coronary artery distal to the obstruction, but the rate of entry into the
vessel distal to the obstruction or the rate of clearance from the distal bed (or both)
is slower than into areas perfused by non-culprit arteries.
TIMI III: complete perfusion; antegrade flow into the bed distal to the obstruction
and clearance of contrast material from the involved bed occur as promptly as in an
uninvolved bed (6).
Statistical analysis
The collected data were organized, tabulated and statistically analyzed using SPSS
version 20. For qualitative data, frequency and percent distribution were calculated
and for comparison between groups, Chi square test was used. For quantitative
data, mean and standard deviation (SD) were calculated and for comparison
between two means, independent samples student (t) test was used. For comparison
between more than 2 means, the one way analysis of variance (ANOVA) test was
used. To compare between the same groups (means) at two different points of time,
the paired samples (t) test was used. For interpretation of results, p value ≤ 0.05
was considered significant.
Results
Study population
The mean age was 57±6 years, 90% were males. Hypertension was reported in
67% of all patients, diabetes in 50%, dyslipidemia in 73%, and smoking in 77% ,
63% of patients had positive family history of coronary artery disease (CAD).
There was no significant difference in baseline characteristics between different
groups. Table 1.
Table 1. Baseline characteristics of study population
All patients
n=30
Grade 0
n=8
Grade I
n=7
Grade II
n=12
Grade III
n=3
P value
57±6
59±7
56.5±4
55.5±6
59.7±8.7
0.59
n(%)
27(90%)
6(75%)
6(86%)
12(100%)
3(100%)
0.28
Hypertension
20(67%)
7(87.5%)
3(43%)
7(58%)
3 (100%)
0.15
Diabetes M.
15(50%)
3(37.5%)
3 (43%)
7(58%)
2(66.6%)
0.72
Dyslipidemia
22(73%)
7(87.5%)
3(43%)
10(83.3%)
2(66.6%)
0.18
Smoking
23(77%)
4(50%)
6(86%)
10(83.3%)
3(100%)
0.19
19(63%)
6(75%)
4(57%)
7(58%)
2(66.6%)
0.37
Age, years
mean± SD
Male Sex
Family history
of CAD
CAD= Coronary Artery Disease
Clinical presentation on admission
Chest pain was the main presenting symptom in all patients. Three patients (10%)
had non sustained ventricular tachycardia on admission. The mean systolic blood
pressure was 139±20 mmHg (155±15 mmHg, 136±23 mmHg, 130±15 mmHg,
132±19 mmHg in grade 0, I, II,III respectively, p=0.027). The mean diastolic
blood pressure was 86±12 mmHg (96±8 mmHg, 84±12 mmHg, 82±11 mmHg,
82±13 mmHg in grade 0, I, II, III respectively, p=0.032). The mean heart rate was
89±13 beats/min (93±20, 84±2, 90±11, 85±4 beats/min in grade 0, I, II,III
respectively, p=0.49).
Time from symptom onset
The mean time was 182±60 minutes in all patients (range from 90 to 300 minutes).
Between groups analysis showed shorter time from symptom onset in patients who
had MBG II (145±46 minutes) and grade III (170±114) compared to those with
MBG 0(206±25 minutes) and MBG I (223±54 minutes), P=0.017. Figure 1.
Time from symptom onset (minutes)
250
Grade I
Grade 0
200
all patients
Grade III
150
Grade II
100
50
0
Figure 1. Time from symptom onset.
Cardiac biomarkers and MBG
The mean total CK was 916±318 u/l( range:402 to 1720 u/l). There was significant
inverse correlation between peak CK values and MBG. The higher the MBG, the
lower peak CK (p=0.008). The mean peak CK-MB was 225±87u/l( range:108 to
436 u/l). We reported a significant inverse relation between peak CK-MB and
MBG (p=0.001).
ECG on admission
According to ECG on admission, 6 patients (20 %) presented with anterolateral
MI, 16 patients (53%) presented with anteroseptal MI and 8 patients (27 %)
presented with extensive anterior MI. Patients with anterolateral MI were (1, 2, 2
& 1patients in grade 0, I, II,III respectively, p=0.88), patients with anteroseptal MI
were (5, 3, 6, 2 in grade 0, I, II, III respectively, p=0.47) while patients with
extensive anterior MI were (2, 2, 4, 0 in grade 0, I, II ,III respectively, p=0.61).
Emergency PCI data
Primary PCI was done in 11 patients (36.7%). While rescue PCI in 19 patients
(63.3%). Glycoprotein IIb/IIIa inhibitors were used in 9 patients (26.7%). Stents
were implanted in 29 patients (96.6%). The mean number of stents per patient was
2±1. The mean stent diameter was 2.95±0.18 mm, the mean stent length was
23.3±4.24 mm. There were no procedure related complications except no reflow in
one patient. We did not report significant difference in the above mentioned data
between different MBG groups.
Cardiac medications post PCI
All patients received dual anti platelet drugs and statins, 27 patients received ACE
inhibitors, 21 patients received beta blockers. Between groups analysis did not
reveal significant difference in cardiac medications.
Echocardiographic data
 End diastolic volume (EDV)
At 24 hours post PCI, the mean EDV was 98±27ml (106±32ml, 101±14ml,
89±31ml, 109±17ml in grade 0, I, II & III respectively, P=0.49). After 3 months,
the mean EDV significantly increased in all patients compared to baseline
(112±37.5 vs. 98±27ml, p=0.03). Between groups analysis showed significant
increase in EDV in grade 0 MBG (119.5±32ml) and grade I (139.5±36ml)
compared to that in grade II (91±35.3ml) and grade III (112±27.5ml),p=0.029.
Within groups analysis showed significant increase in EDV from baseline to 3
months
in
grade
0
(106±32
vs
119.5±32ml,
p=0.03)
and
grade
I(101±14vs139.5±36ml, p=0.044) with 25% increase from baseline. However
there were no significant changes in EDV in grade II, III (89±31vs91±35.3ml,
p=0.2) and grade III( 109±17vs112±27.5ml, p=0.53). Table 2.
Table 2. Echocardiographic data
EDV(baseline), (ml)
All patients
n=30
98±27
Grade 0
n=8
106±32
Grade I
n=7
101±14
Grade II
n=12
89±31
Grade III
n=3
109±17
P
value
0.49
EDV(3months), (ml)
112±37.5*
119.5±32*
139.5±36*
91±35.3
112±27.5
0.029
ESV( baseline), (ml)
52±22
50.7±17.8
68.5±24
42±18
56±28
0.08
ESV( 3months), (ml)
60±33.5*
72.5±29.5*
86±25*
40±30.5
48.7±22
0.01
LVEF % (baseline)
50±11.7
51.9±7
43.6±15.3
53±10
49.3±19
0.38
LVEF % ( 3 months)
48±16
39.8±9.2*
34±9.5*
59.6±14
57±14
<0.001
11(37%)
6(75%)
4(57%)
1(8.3%)
0(0%)
0.007
Remodeling
* = significant difference between values at 24 hours and 3 months (within groups)
EDV= End diastolic volume, ESV= End systolic volume, LVEF= Left ventricular ejection
fraction
 End systolic volume (ESV)
In baseline analysis, the mean ESV was 52±22ml (50.7±17.8ml, 68.5±24ml,
42±18ml, 56±28ml in grade 0, I, II, III respectively, p=0.08). Three months
measurements showed that the mean ESV significantly increased in all patients
compared to baseline (60±33.5ml vs 52±22ml respectively, p=0.027). Between
groups analysis showed significant increase in ESV in group 0 MBG
(72.5±29.5ml) and grade I (86±25ml) compared to grade II (40±30.5ml) and grade
III (48.7±22ml), p=0.01. Within groups analysis showed significant increase in
ESV from baseline to 3 months in grade 0, I (50.7±17.8vs72.5±29.5ml, p=0.037
& 68.5±24 vs 86±25ml, p=0.012 respectively, 35 % higher). However there were
no significant changes in grade II, III (42±18 vs 40±30.5ml, p=0.28
&56±28vs48.7±22ml, p=0.72 respectively), Table 2.
 Left ventricular Ejection fraction (LVEF)
LVEF at baseline was 50±11.7% (51.9±7%, 43.6±15.3%, 53±10% , 49.3±19% in
grade 0, I, II and III respectively, p=0.38). After 3 months, the mean LVEF
decreased in all patients compared to baseline (48±16% vs. 50±11.7%, p=0.83).
Between groups analysis showed significant decrease in LVEF in group 0 MBG
(39.8±9.2%) and grade I (34±9.5%) compared to grade II (59.6±14%) and grade
III (57±14%), p<0.001. Within groups analysis showed significant decrease in
LVEF from 24 hours to 3 months in grade 0, I (51.9±7% vs. 39.8±9.2%, p=0.041
&43.6±15.3% vs 34±9.5%, p=0.034 respectively, 23% lower). However there
were no significant changes in grade II, III (53±10%vs.59.6±14%, p=0.84
&49.3±19% vs. 57±14%, p=0.92 respectively), Table 2.
 Remodeling
Defined as > 20% increase in EDV from baseline value, 11 patients had
remodeling at 3 months (37%).75% of patients with grade 0 MBG versus 57% of
grade I versus 8.3% of grade II versus 0% of grade III MBG had ventricular
remodeling at 3 months,(p=0.007), Table 2.
Discussion
Myocardial blush grade (MBG) is routinely used to assess the effectiveness of
myocardial reperfusion, and impaired MBG has been found to be an independent
predictor of long-term outcome
(7)
. The present study was designed to assess the
impact of myocardial blush grade on left ventricular remodeling in patients
undergoing successful emergency PCI. We reported that the
presence of
myocardial reperfusion (MBG 2-3) after emergency PCI was associated with a
significantly lower rate of remodeling than the absence of myocardial reperfusion
(MBG 0-1) .
Our data showed that there was no significant difference between different MBG
in the prevalence of risk factors of CAD. Similar results were reported in prior
studies
(8-10)
which reported that, there was non significant difference between
different grades of MBG regarding the profile of CAD risk factors.
In the present work, time from symptom onset ranged from 90 to 300 minutes with
a mean of 182 minutes. In addition we reported a significant inverse correlation
between time and myocardial blush grade. Porto et al.
relationship between total ischemic time and MBG.
(9)
reported an inverse
In this study, there was a significant increase in EDV at 3 months compared to
baseline value in patients with MB grade 0 (119 vs. 106respectively) and in those
with MBG grade I (139 vs. 101 respectively). However, no significant changes in
EDV were reported in patients with MB grades II and III. In addition, changes in
ESV and LVEF were in correlation with that of EDV. These results reflects an
inverse relationship between MBG grades and cardiac remodeling (with increased
grade, remodeling decreased). These results are in agreement with that reported by
Hamdan et al.
(10)
who reported that, at 6 months, patients with MBG 2-3 had
significantly smaller LV end-diastolic (94±21.5 ml vs. 115.2± 26 ml, P = 0.04) and
end systolic volume (38.6± 16.5 ml vs. 55.8±17.5 ml, P = 0.03), and significantly
higher LV ejection fraction (60.8±9.9% vs. 50.3±11.6%, p=0.03) compared to
patients with MBG 0-1. Porto et al.(11) reported that, micro vascular impairment is a
dynamic process, and improved blush at angiographic follow-up may be due to
disappearance of cellular edema compressing the vascular lumen and to dissolution
of intravascular microthrombi.
Consistent with results of the present study, Dibra et al. (12) also demonstrated that
a TMPG of 2/3 measured at 1-2 weeks after either PPCI or thrombolysis was
strongly and independently related to larger myocardial salvage. Furthermore,
Korosoglou et al.
(8)
reported that, patients with MBG 0/1 had significantly lower
follow-up ejection fraction compared with patients who had MBG 2/3. In another
large cohort study, higher MBG values were associated with smaller left
ventricular volumes, more systolic wall thickening, and higher left ventricular
ejection fraction measured by CMRI 6 months post PCI
(13)
. In the present work,
remodeling was evident in 37% of the study population with higher prevalence in
those with MBG 0(75%) and MBG I(57%) versus those with MBG II(8%) and
MBG III(0%). The results are in accordance with Hamdan et al.
(10)
who reported
that, LV remodeling had occurred in 34.6% at 6 months. The LV remodeling rate
was significantly lower in patients with MB 2-3 as compared to those with MB 01(17.6% vs. 66.6%; P = 0.012). In addition, Bolognese et al.
(14)
strongly linked
between lack of myocardial reperfusion, as assessed by myocardial contrast
echocardiography, and progressive LV dilation, whereas Wu et al
(15)
found that
microvascular obstruction evaluated by magnetic resonance imaging 10 days after
myocardial infarction predicted LV remodeling and poor patient prognosis.
In our work, MBG analysis has been shown to be a simple method to assess
myocardial micro- circulation after successful reperfusion. Porto et al.
(11)
concluded that, angiographic assessment of myocardial perfusion is a useful,
widely available, and under-utilized clinical tool for the assessment of reperfusion
at the time of PPCI. It comes at no additional cost, is immediately feasible at the
time of catheterization, and provides prognostic information that may help guide
treatment decisions. The angiographic methods to assess perfusion (MBG and
TPMG) are simple and well validated (12).
Conclusion
Impaired MBG after emergency PCI is associated with increased risk of LV
remodeling. It has the advantage of being simple method to assess
myocardial microcirculation.
Study limitations
Small sample size, short follow up period, heterogeneity of emergency PCI
(primary & rescue).
Recommendations
MBG should be measured after successful reperfusion to predict recovery of left
ventricular function. Further studies with larger sample size are required.
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