Objectives
The study is designed to determine the relation between various clinical and laboratory variables and the occurrence of no reflow phenomenon or in hospital MACE (Cardiac death, myocardial infarction, stent thrombosis, or target vessel revascularization) in patients with STEMI undergoing primary PCI.
Background
The investigation of no-reflow phenomenon after primary percutaneous coronary intervention (PPCI) in patients with acute ST-segment–elevation myocardial infarction (STEMI) has therapeutic implications. Patients with no-reflow have more congestive heart failure early after myocardial infarction and demonstrate progressive left ventricular cavity dilatation in the convalescent stage of the infarction.
Methods
We studied prospectively 120 patients with STEMI presenting to Alexandria Main University Hospital (under umbrella of Stent for Life program) and International Cardiac Center (ICC) from April 2013 to October 2013, and eligible for PPCI according to European Society of Cardiology (ESC) guidelines.
Results
The incidence of no reflow was 13.2%, and in hospital MACE was 5%, with cardiac death as the predominant form of in hospital MACE. The group with no reflow and/or in hospital MACE showed significantly older age (62.29 ± 7.90 vs. 56.30 ± 10.34, p=0.014), longer pain to balloon time (15.90 ± 7.87 vs. 6.08 ± 3.82, p˂ 0.001), higher levels of admission random plasma glucose (RPG), neutrophils / lymphocytes (N/L) ratio (8.19 ± 3.05 vs. 5.44 ± 3.53, p˂0.001), and MPV (11.90 ± 2.09 vs. 8.58 ± 1.84, p˂0.001).
Conclusion
Older patient age, longer pain to balloon time, admission hyperglycemia, higher admission N/L ratio and MPV are useful predictive factors for the occurrence of no reflow post PPCI, and/or in hospital MACE. Therefore strong attention should be paid to patients with one or more of these predictive factors, to protect them from the deleterious effects of no reflow, and avoid any of the in hospital MACE.
mortality, myocardial infarction, no reflow, percutaneous coronary intervention, reperfusion.
The phenomenon of no-reflow is defined as inadequate myocardial perfusion through a given segment of the coronary circulation without angiographic evidence of mechanical vessel obstruction [1]. No-reflow has been documented in 30% of patients after thrombolysis or mechanical intervention for acute myocardial infarction [2]. No reflow implies abnormal tissue perfusion and persistent no-reflow is associated with higher incidence of congestive heart failure early after myocardial infarction and demonstrate progressive left ventricular cavity dilatation in the convalescent stage of the infarction [3].
Several key patho-physiological processes, usually in combination, are believed to be responsible for this phenomenon, including distal embolization of atherothrombotic debris, thrombus formation, and endothelial dysfunction of the distal arteriolar and capillary bed, including endothelial desquamation and microcirculatory vasospasm.
The study is designed to determine the relation between various clinical and laboratory variables and the occurrence of no reflow phenomenon or in hospital MACE (Cardiac death, myocardial infarction, stent thrombosis, or target vessel revascularization) in patients with STEMI undergoing primary PCI.
The study was conducted on 120 patients with STEMI presenting to Alexandria Main University Hospital (under umbrella of Stent For Life program) and International Cardiac Center (ICC) from April 2013 to October 2013, and eligible for PPCI according to European Society of Cardiology (ESC) guidelines. Informed consent taken from patients. Thorough history taking with special emphasis on risk factors (Age, gender, diabetes, hypertension, smoking, dyslipidemia, family history), history of acute coronary syndromes (ACS) and revascularization, Pain to balloon time, and the presence of pre-infarction angina. Complete clinical examination was done. Admission laboratory investigation included: Complete blood count (CBC) (including mean platelet volume [MPV] and neutrophils/lymphocytes ratio), and random plasma glucose level. All patients had 12 lead electrocardiogram (ECG). The results of the coronary angiography indicating the infarct related artery (IRA), initial TIMI flow in the IRA, and the type of stent used in the PPCI were recorded. The patients were studied according to the presence of various clinical and laboratory variables (age, gender, absence of pre-infarction angina, pain to balloon time, location of the infarction, admission random plasma glucose level and CBC including neutrophils/lymphocytes ratio and MPV, and initial TIMI flow in the IRA), the final TIMI flow after the primary PCI, and the incidence of in hospital MACE [4].
The patients are divided into two groups according to the final TIMI flow after the primary PCI, and the incidence of in hospital MACE as follows: Group A: had a normal flow after the 1ry PCI and did not have In hospital MACE. Group B: had either no reflow after the 1ry PCI or experienced In hospital MACE.
The distribution of the studied groups is shown in Table 1.
Table 1. Distribution of the studied groups
|
No
|
%
|
Normal (group A)
|
99
|
82.5
|
No reflow or hospital MACE (group B)
|
21
|
17.5
|
No reflow only
|
15
|
71.4
|
In hospital MACE only ( all in the form of cardiac death)
|
5
|
23.8
|
Both
|
1
|
4.8
|
The demographic data of the two studied groups are shown in table 2.
Table 2. Comparison between the two studied groups according to demographic data
|
Group A (n = 99)
|
Group B (n = 21)
|
Test of sig.
|
p
|
No
|
%
|
No
|
%
|
Sex
|
|
|
|
|
|
|
Male
|
75
|
75.8
|
13
|
61.9
|
χ2=1.700
|
0.192
|
Female
|
24
|
24.2
|
8
|
38.1
|
Age
|
|
|
|
|
Min. – Max.
|
29.0 – 81.0
|
44.0 – 78.0
|
t=2.498
|
0.014
|
Mean ± SD
|
56.30 ± 10.34
|
62.29 ± 7.90
|
Median
|
58.0
|
62.0
|
The distribution of the studied groups with respect to pre PPCI variable is shown in tables 3-6.
Table 3. Comparison between the two studied groups according to diabetes, hypertension and smoking
|
Group A (n = 99)
|
Group B (n = 21)
|
χ2
|
p
|
No
|
%
|
No
|
%
|
Diabetes
|
|
|
|
|
|
|
Non diabetic
|
62
|
62.6
|
9
|
42.9
|
2.803
|
MCp=0.094
|
Diabetic
|
37
|
37.4
|
12
|
57.1
|
Insulin
|
9
|
9.1
|
2
|
9.5
|
-
|
-
|
OHD
|
28
|
28.3
|
10
|
47.6
|
Hypertension
|
48
|
48.5
|
7
|
33.3
|
1.602
|
0.206
|
Smoking
|
|
|
|
|
|
|
Non smoker
|
43
|
43.4
|
11
|
52.4
|
0.560
|
0.454
|
Smoker
|
52
|
52.5
|
9
|
42.9
|
0.648
|
0.421
|
Ex-smoker
|
4
|
4.0
|
1
|
4.8
|
0.023
|
FEp =1.000
|
Dyslipidemia
|
54
|
54.5
|
15
|
71.4
|
2.021
|
0.155
|
Family History
|
17
|
17.2
|
2
|
9.5
|
0.760
|
FEp=0.521
|
Previous ACS
|
19
|
19.2
|
3
|
14.3
|
0.279
|
FEp=0.762
|
Absence of preinfarction angina
|
56
|
56.6
|
15
|
71.4
|
1.584
|
0.208
|
Table 4. Comparison between the two studied groups according to SBP, DBP and pulse
|
Group A (n = 99)
|
Group B (n = 21)
|
t
|
p
|
SBP
|
|
|
|
|
Min. – Max.
|
50.0 – 200.0
|
70.0 – 160.0
|
1.971
|
0.051
|
Mean ± SD
|
129.29 ± 27.93
|
116.67 ± 19.32
|
Median
|
130.0
|
120.0
|
DBP
|
|
|
|
|
Min. – Max.
|
30.0 – 120.0
|
40.0 – 90.0
|
1.870
|
0.064
|
Mean ± SD
|
81.06 ± 15.62
|
74.29 ± 12.07
|
Median
|
80.0
|
70.0
|
Pulse
|
|
|
|
|
Min. – Max.
|
41.0 – 120.0
|
60.0 – 130.0
|
0.069
|
0.945
|
Mean ± SD
|
84.56 ± 16.33
|
84.29 ± 15.69
|
Median
|
80.0
|
88.0
|
Table 5. Comparison between the two studied groups according to ECG.
|
Group A (n = 99)
|
Group B
(n = 21)
|
χ2
|
p
|
No
|
%
|
No
|
%
|
ECG
|
|
|
|
|
|
|
Anterior MI
|
72
|
72.7
|
14
|
66.7
|
0.313
|
0.576
|
Lateral MI
|
6
|
6.1
|
2
|
9.5
|
0.334
|
FEp=0.628
|
Inferior MI
|
21
|
21.2
|
6
|
28.6
|
0.538
|
FEp=0.565
|
Right MI
|
8
|
8.1
|
1
|
4.8
|
0.275
|
FEp=1.000
|
Posterior MI
|
7
|
7.1
|
2
|
9.5
|
0.150
|
FEp=0.656
|
Table 6. Comparison between the two studied groups according to pain to balloon time.
|
Group A (n = 99)
|
Group B
(n = 21)
|
Z
|
p
|
Pain to balloon time
|
|
|
|
|
Min. – Max.
|
1.0 – 19.0
|
1.0 – 30.0
|
4.999*
|
<0.001*
|
Mean ± SD
|
6.08 ± 3.82
|
15.90 ± 7.87
|
Median
|
5.0
|
17.0
|
The distribution of the studied groups with respect to laboratory results, angiographic findings and procedural aspects is shown in tables 7-9.
Table 7. Comparison between the two studied groups according to laboratory results (on admission)
|
Group A (n = 99)
|
Group B
(n = 21)
|
Test of sig.
|
p
|
Plasma glucose
|
|
|
|
|
Min. – Max.
|
84.0 – 442.0
|
104.0 – 440.0
|
Z = 3.377*
|
0.001*
|
Mean ± SD
|
186.38 ± 84.65
|
275.29 ± 104.11
|
Median
|
150.0
|
280.0
|
N/L ratio
|
|
|
|
|
Min. – Max.
|
1.20 – 24.0
|
2.80 – 13.0
|
Z = 3.665
|
<0.001*
|
Mean ± SD
|
5.44 ± 3.53
|
8.19 ± 3.05
|
Median
|
4.50
|
8.0
|
MPV
|
|
|
|
|
Min. – Max.
|
5.0 – 13.0
|
5.90 – 15.0
|
t = 7.320*
|
<0.001*
|
Mean ± SD
|
8.58 ± 1.84
|
11.90 ± 2.09
|
Median
|
8.20
|
12.20
|
Table 8. Comparison between the two studied groups according to infarct related artery
|
Group A (n = 99)
|
Group B
(n = 21)
|
χ2
|
p
|
No
|
%
|
No
|
%
|
Infarct related artery
|
|
|
|
|
|
|
LAD
|
70
|
70.7
|
14
|
66.7
|
0.135
|
0.714
|
D1
|
5
|
5.1
|
0
|
0.0
|
-
|
-
|
CX
|
2
|
2.0
|
2
|
9.5
|
3.027
|
FEp =0.141
|
OM
|
1
|
1.0
|
0
|
0.0
|
-
|
-
|
RCA
|
20
|
20.2
|
5
|
23.8
|
0.137
|
FEp =0.769
|
PDA
|
1
|
1.0
|
0
|
0.0
|
0.214
|
FEp = 1.000
|
Table 9. Comparison between the two studied groups according to initial TIMI flow and Type of stent used
|
Group A (n = 99)
|
Group B
(n = 21)
|
Test of sig.
|
p
|
No
|
%
|
No
|
%
|
Initial TIMI flow
|
|
|
|
|
|
|
0
|
87
|
87.6
|
19
|
90.4
|
Z = 1.844
|
0.065
|
1
|
25
|
25.3
|
1
|
4.8
|
2
|
5
|
5.1
|
1
|
4.8
|
Type of stent used
|
|
|
|
|
|
|
No stent
|
0
|
0.0
|
2
|
9.5
|
χ2 = 9.588*
|
FEp =0.029*
|
BMS
|
51
|
51.5
|
12
|
57.1
|
χ2 = 0.220
|
0.810
|
DES
|
48
|
48.5
|
7
|
33.3
|
χ2 = 1.602
|
0.236
|
2021 Copyright OAT. All rights reserv
A lot of researchers tried to study variables predicting the incidence of no reflow and/or in hospital MACE in STEMI patients undergoing PPCI. Ndrepepa G et al. [5], found that initial TIMI 0 flow in the infarct-related artery (P˂0.001), initial perfusion defect (P˂0.03), and previous myocardial infarction (P˂0.013) as independent predictors of no reflow. Akpek M et al. [6], reported that N/L ratio > 3.3 predicted no reflow with 74% sensitivity, and 83% specificity, and that high N/L ratio is independent predictor of no reflow, and in hospital MACE. Iwakura K et al. [7], found that admission hyperglycemia ( >160 mg/dl) was an independent prognostic factor for no reflow, along with older age, male gender, absence of pre-infarction angina, complete occlusion of the culprit lesion, and anterior STEMI. Huczek Z et al. [8], found that high mean platelet volume (>10.3 fl) is a strong, independent predictor of no reflow in STEMI patients undergoing PPCI. In our study, we found that the groups with no reflow or in hospital MACE showed significantly older age, longer pain to balloon time, and higher levels of admission random plasma glucose (RPG), N/L ratio, and MPV.
Older patient age, longer pain to balloon time, admission hyperglycemia, higher admission N/L ratio and MPV are useful predictive factors for the occurrence of no reflow post PPCI, and/or in hospital MACE. Therefore strong attention should be paid to patients with one or more of these predictive factors, to protect them from the deleterious effects of no reflow, and avoid any of the in hospital MACE.
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- Abbo KM, Dooris M, Glazier S, O'Neill WW, Byrd D, et al. (1995) Features and outcome of no-reflow after percutaneous coronary intervention. Am J Cardiol 75: 778-782. [Crossref]
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- Rezkella SH, Kloner RA (2002) No-reflow phenomenon. Circulation 105: 656-662. [Crossref]
- Ndrepepa G, Tiroch K, Keta D, Fusaro M, Seyfarth M, et al. (2010) Predictive Factors and Impact of No Reflow After Primary Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction. Circ Cardiovasc Interv 3: 27-33. [Crossref]
- Akpek M, Sahin O, Elick D, Kaya MG (2013) The association of neutrophils/lymphocytes ratio with coronary flow and in hospital MACE in patients with STEMI undergoing primary PCI. Eur Heart J 27: 534 –539.
- Iwakura K, Ito H, Ikushima M, Kawano S, Okamura A, et al. (2003) Association between hyperglycemia and the no-reflow phenomenon in patients with acute myocardial infarction. J Am Coll Cardiol 41: 1–7. [Crossref]
- Huczek Z, Kochman J, Filipiak KJ, Horszczaruk GJ, Grabowski M, et al. (2005) Mean platelet volume on admission predicts impaired reperfusion and long-term mortality in acute myocardial infarction treated with primary percutaneous coronary intervention. J Am Coll Cardiol 46: 284 –290. [Crossref]