Acta Biomed 2021; Vol. 92, N.

5: e2021297 DOI: 10.23750/abm.v92i5.10053 © Mattioli 1885

Original article

The No-reflow Phenomenon: Is it Predictable by Demo-

graphic factors and Routine Laboratory Data?
Mohammadhasan Namazi1, Elham Mahmoudi1, Morteza Safi1, Yaser Jenab2, Hossein Va-
kili1, Habibollah Saadat1, Saeed Alipour Parsa1, Isa Khaheshi1, Azita Hajhossein Talasaz2,
Seyed Hossein Hosseini2, Mohammadreza Tabary3, Hamidreza Poorhosseini2
Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Tehran Heart Center, Tehran
1

University of Medical Sciences, Tehran, Iran; 3School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Abstract. Background: The coronary no-reflow phenomenon is an adverse complication of percutaneous coro-
nary interventions (PCI) which significantly worsens the outcome and survival. In this study, we have evaluat-
ed the correlation of no-reflow phenomenon with demographic, biochemical and anatomical factors. Methods:
We included 306 patients (193 male) with acute ST-elevation myocardial infarction (STEMI) who under-
gone primary PCI in our center. Demographic factors, as well as biochemistry test results were obtained. Also,
the Thrombolysis in Myocardial Infarction (TIMI) grade and TIMI frame count (TFC) was measured. The
correlation of no-reflow phenomenon with demographic, biochemical and anatomical factors was analyzed.
Results: Patients with a mean age of 56.41 ± 11.8 years were divided into two groups depending on the TIMI
score (Group 1 or Normal flow and Group 2 or No-reflow). Symptom-to-procedure time, door-to-procedure
time, serum creatinine level, hs-CRP level, and Neutrophil to Lymphocyte Ratio (NLR) were significantly
higher among group 2. TFC had negative significant correlation with male gender, and positive significant
correlation with age, diabetes mellitus, hs-CRP level, WBC count, and NLR. Age of more than 62.5 years
and serum creatinine level of more than 0.89 mg/dL can optimally predict the no reflow phenomena. Conclu-
sions: According to our results, it seems that female gender, older ages, DM, multi-vessel involvement, delayed
reperfusion, and increased NLR can predict the risk of no-reflow after primary PCI in the setting of Acute
Myocardial Infarction. (www.actabiomedica.it)

Key words: Myocardial infarction; Percutaneous coronary intervention; No-reflow phenomenon

Introduction have also been used (6, 7). Due to discordant defini-
tions and diagnostic methods, there is no consensus on
The coronary no-reflow phenomenon is defined its incidence rate, yet. However, human studies have
as a lack of myocardial perfusion in the presence of reported an incidence of about 0.3 to 9.4 percent in
patent coronary artery, which mostly occurs during patients with Acute Myocardial Infarction undergoing
primary Percutaneous Coronary Intervention (PCI) primary PCI (1, 7, 8).
in the setting of acute myocardial infarction (1, 2) . A The development of No-reflow during a coro-
Thrombolysis in Myocardial Infarction (TIMI) score nary intervention, significantly worsens the long-term
lower than 3 has been widely used to objectively define outcome; it has been associated with lower ventricular
the no-reflow phenomenon in the previous studies (1- ejection fraction, higher rates of fatal and nonfatal myo-
5), though lower TIMI scores and perfusion defects cardial infarction, more hospitalization for heart failure,
2 Acta Biomed 2021; Vol. 92, N. 5: e2021297

and more cerebrovascular accidents (1, 9, 10). The patho-

physiology beyond the lack of optimal reflow after a suc- Lab data
cessful coronary intervention differs widely, depending
on the clinical setting; so is the appropriate therapeutic The lipid profile (total cholesterol, triglyceride,
strategy (2). Studies have suggested a combination of Low Density Lipoprotein (LDL), and High Density
the ischemia-reperfusion injury, inflammation, cellular Lipoprotein (HDL)), white blood cell (WBC), neu-
edema, vasospasm and distal micro-embolization as the trophil and platelet absolute count, high-sensitivity
responsible pathologies behind the impaired coronary C-Reactive Protein (hs-CRP), serum creatinine level,
flow (2, 11). Since the prevention of no-reflow phe- serum Uric Acid level and blood glucose level were as-
nomenon is the best strategy to minimize its adverse sessed on the first blood sample obtained just before
consequences (12), it would be helpful to determine the beginning of the coronary intervention. Blood cell
the modifiable factors associated with development of count was assessed by Sysmex cell counter, serum cre-
no-reflow. Multiple studies have been conducted to atinine was checked by Man kit, uric acid level was
clear the pathophysiology beyond no-reflow phenom- checked by bionic kit and hs-CRP and lipid profile
enon, but the results have been controversial. The aim was tested by Pars-azmoon kit.
of this study is to investigate the attributing factors of
no-reflow in a group of our STEMI patients and to TIMI and Corrected TIMI frame count (TFC)
compare it with the previous findings.
TFC was measured objectively by a single cardi-
ologist, using a protocol published by Gibson et al. in
Materials and methods 1996 (14). The starting frame was determined as the
frame in which the contrast touches both borders of
Patient selection the culprit artery (left main coronary artery when the
culprit lesion is on Left Anterior Descending artery
A total of 346 consecutive patients referred to our (LAD) or LCX arteries) and the leading point was de-
center with the diagnosis of STEMI (which was made termined as the frame in which the contrast reaches
by emergency medical services), as well as the patients the most distal branch of LAD, the branch with the
presented with angina pectoris or its equivalents to our longest total distance from the origin of LCX that
center (the diagnosis of STEMI was primarily stab- passes through the culprit lesion, and the first branch
lished in our emergency ward) were enrolled into our of posterolateral extension of the RCA. The estimated
study. The diagnosis of STEMI was based on Ameri- TFC had been adjusted for filming speed, to the stand-
can Heart Association protocols (13), though ECG ard speed of 30 frames per second. Then, the adjusted
finding of bundle branch blocks were not included TFC was corrected for the vessel length, by dividing
and all the participants received the same guideline the LAD TFC by 1.7.
directed oral adjuvant therapy before primary PCI, Also, the coronary anatomy including the culprit
including Aspirin 300mg, Atorvastatin 80mg, Clopi- coronary artery and number of total diseased vessels
dogrel 600mg and pantoprazole 40mg. Patients whose (narrowing>50% in each of the LAD/diagonal, LCX/
infarct-related lesion was located on a saphenous vein Obtuse Marginal (OM) and/or RCA/Posterior De-
graft, arterial graft or a previously stented coronary ar- scending artery (PDA)/Posterior Left Ventricular
tery were excluded due to relatively great risk for No- (PLV) branches) was obtained by the mentioned car-
reflow complication. diologist through angiography film review.
Demographic factors including age, gender, history
of Diabetes Mellitus, hypertension, current smoking, Data analysis
time of symptom onset, time of entrance to hospital and
time of stent implantation in culprit lesion were collect- Data was imported to Statistical Package for the
ed through bedside history taking and patients’ records. Social Sciences (SPSS) software version 25.0. The pa-
Acta Biomed 2021; Vol. 92, N. 5: e2021297 3

tients were classified as “No reflow” and “Normal re- 62.7%, 6% and 31.3% in group 2, P= 0.001) had sig-
flow” based on their TIMI score (Group 1: Normal nificantly different distribution between group 1 and
reflow, TIMI=3; Group 2: No-reflow, TIMI=0-2). group 2.
The mean value of quantitative variables was com- symptom-to-procedure time (234±39 minutes in
pared between the two groups by independent t-test group 1 and 246±42 in group 2, P= 0.028), door-to-
analysis and the frequency of qualitative variables procedure time (89±13 minutes in group 1 and 94±16
were compared between the two groups by chi-square in group 2, P= 0.031), serum creatinine level (0.90±0.25
test. Two-tailed P-value less than 0.05 was consid- mg/dL in group 1 and 97±19 mg/dL in group 2, P=
ered significant. Pearson correlation coefficient was 0.042), hs-CRP level (83.14±112.23 mg/dL in group
determined between TFC and binomial variables, as 1 and 127.12±133.45 mg/dL in group 2, P= 0.032) and
well as independent T-test and Analysis of Variences Neutrophil to Lymphocyte Ratio (NLR) (3.44±2.66
(ANOVA). Receiver Operating Characteristic (15) in group 1 and 4.66±3.99 in group 2, P= 0.011) was
curve analysis was done for correlated variables includ- significantly higher among group 2 compared to group
ing age, creatinine, hs-CRP, NLR and symptom-to- 1. The frequency and mean values of studied variables
balloon for the prediction of no-reflow phenomenon. are summarized in Table 1.

TFC analysis
Results
Older ages (r2= 0.138, P= 0.017) , hs-CRP lev-
From the total 346 patients who were enrolled to el (r =0.254, P=< 0.001), WBC count (r2=0.130, P=
2

the study, 28 cases excluded by the above-mentioned 0.023), and NLR (r2= 0.137, P= 0.018) had positive
exclusion criteria and another 12 cases were excluded correlation with TFC. The pearson correlation analysis
because of technical problems. between TFC and binomial variables are summarized
in Table 2.
TIMI grade analysis TFC was significantly lower in Male gen-
der (TFC=17.1±6.9 in male gender and 22.3±6.8
The study population included 193 male and 113 in female gender, P-value<0.001), SVD anatomy
female patients with a mean age of 56.41±11.8 years (TFC=17.1±6.4 in SVD, 21.4±7.5 for 2VD and
who were divided into two groups depending on the 22.3±7.7 for 3VD, P-value<0.001) and RCA occlu-
TIMI score. There were 223 patients in group 1 (Nor- sion (TFC=20.4±7.3 for LAD occlusion, 18.7±6.5for
mal reflow, TIMI=3) including 149 male and 74 fe- LCX occlusion and 18.3±6.2 for RCA occlusion, P-
males with a mean age of 55±10 years and 83 patients value=0.015). The independent T-test analysis and
in group 2 (No reflow, TIMI=0-2) including 44 male analysis of variances(ANOVA) between TFC and nor-
and 39 female patients with a mean age of 60±14 years. mally distributed variables are summarized in Table 3.
Gender (33.18% female in group 1 and 46.99%
female in group 2, P= 0.033), age (55±10 years old in ROC Analysis
group 1 and 60±14 in group 2, P= 0.001), DM (34.5%
diabetic in group 1 and 54.2 diabetic in group 2, P= The cut point of 62.5 years of age can optimally
0.002), coronary arteries involvement (the prevalence predict the no reflow phenomena with a sensitivity of
of single vessel disease(SVD), two vessel disease(2VD) 0.93 and specificity of 0.77 (positive Likelihood Ra-
and three vessel disease(3VD) was 57.4%, 22.9% and tio (LR+) = 4.04, negative Likelihood Ratio (LR-) =
19.7%, respectively in group 1 and 22.9%, 42.2% and 0.09, Diagnostic Odds Ratio (DOR) = 10.00, Area
34.9% in group 2, P< 0.001) and occlusion of coro- under the curve (AUC)= 0.636, P< 0.001). Symptom-
nary arteries (the occlusion of LAD, Left Circumflex to-Balloon longer than 221 minutes can predict the
(LCX) and Right Coronary Artery (RCA) was seen in no-reflow phenomenon with a sensitivity of 0.73 and
41.7%, 22.4% and 35.9%, respectively in group 1 and specificity of 0.49 (LR+ = 1.43, LR- = 0.55, DOR =
4 Acta Biomed 2021; Vol. 92, N. 5: e2021297

Table 1. Comparing patients’ characteristics between group 1 (normal flow) and group 2 (no-reflow)
Total Population Group 1 Group 2 P-Value
N=306 TIMI 3 TIMI 0-2
N=223(73%) N=83(27%)
Demographic
Age(years): mean±SD 56±12 55±10 60±14 0.001
Male: N(%) 193(63.1%) 149(66.8%) 44(53.0%) 0.033
Hypertension: N(%) 148(48.4%) 105(47.1%) 43(51.8%) 0.520
DM: N(%) 122(39.9%) 77(34.5%) 45(54.2%) 0.002
Current Smoking: N(%) 148(48.4%) 107(48.0%) 41(49.2%) 0.344
Admission
Symptom-to-procedure(minutes): mean±SD 237±40 234±39 246±42 0.028
Door-to-procedure (minutes): mean±SD 90±14 89±13 94±16 0.031
IRCA: N(%) 0.001
LAD/Diagonal 145(47.4%) 93(41.7%) 52(62.7%)
LCX/OM 55(17.9%) 50(22.4%) 5(6%)
RCA 106(34.6%) 80(35.9%) 26(31.3%)
Coronary arteries anatomy: N(%) <0.001
SVD 137(44.8%) 128(57.4%) 19(22.9%)
2VD 86(28.1%) 51(22.9%) 35(42.2%)
3VD 73(23.9%) 44(19.7%) 29(34.9%)
Serum creatinine(mg/dL): mean±SD 0.91±0.23 0.90±0.25 0.97±0.19 0.042
Blood glucose at admission(mg/dL): mean±SD 35029±37 118±34 105±48 0.712
Total Cholesterol(mg/dL): mean±SD 213±38 210±41 221±32 0.454
Triglyceride (mg/dL): mean±SD 138.66±71 143±75 127.8±61 0.245
LDL(mg/dL): mean±SD 95±46 95±44 97±51 0.533
HDL(mg/dL): mean±SD 33±14 34±12 31±18 0.527
Hs-CRP(mg/dL): mean±SD 95.07±117.99 83.14±112.23 127.12±133.45 0.032
Uric acid(mg/dL): mean±SD 8.47±1.72 8.45±1.25 8.51±2.97 0.820
Hemoglobin (g/dL): mean±SD 14.66±2.0 14.5±2.1 15.1±1.8 0.754
WBC(K/μL): mean±SD 11.79±3.63 11.42±3.52 12.80±3.94 0.212
NLR: mean±SD 3.77±3.02 3.44±2.66 4.66±3.99 0.011
Platelet (K/μL): mean±SD 226,673±75,574 229,589±75,546 218,842±75,652 0.271
DM: diabetes mellitus, IRCA: infarct-related coronary artery, SVD: single-vessel disease, 2VD: 2-vessel disease, 3VD: 3-vessel disease,
NLR: neutrophil-to-lymphocyte ratio

2.70, AUC=0.69, P=0.003). Door-to-Balloon longer no-reflow phenomenon with a sensitivity of 0.81 and
than 88 minutes can predict the no-reflow phenom- specificity of 0.67 (LR+ = 2.45, LR- = 0.28, DOR =
enon with a sensitivity of 0.58 and specificity of 0.60 2.04, AUC=0.633, P< 0.001). NLR higher than 3.02
(LR+ = 1.45, LR- = 0.70, DOR = 2.06, AUC=0.583, can predict the no-reflow phenomenon with a sensi-
P=0.025). Serum creatinine levels higher than 0.89 tivity of 0.60 and specificity of 0.59 (LR+ = 1.27, LR-
mg/dL can predict the no-reflow phenomenon with a = 0.71, DOR = 2.20, AUC=0.603, P= 0.006). The re-
sensitivity of 0.92 and specificity of 0.69 (LR+ = 2.79, sults of ROC curve analysis are summarized in Table
LR- = 0.12, DOR = 6.38, AUC=0.639, P< 0.001). Hs- 4 and Figure 1.
CRP levels higher than 13.45 mg/dL can predict the
Acta Biomed 2021; Vol. 92, N. 5: e2021297 5

Table 2. Correlation of quantitative characteristics of study Table 3. Mean TFC comparison between different study groups
population with TIMI frame count by independent T-test and analysis of variances (ANOVA)
Pearson P-value TFC P-value
coefficient Gender <0.001
Age(years) 0.138 0.017 Male 17.1±6.9
Symptom-to-procedure (minutes) 0.119 0.40 Female 22.3±6.8
Door-to-procedure (minutes) 0.131 0.024 Hypertension 0.341
Serum creatinine(mg/dL) 0.133 0.022 Yes 19.1±7.0
Blood glucose at admission(mg/dL) 0.066 0.517 No 18.9±6.6
Total Cholesterol(mg/dL) 0.109 0.092 DM 0.082
Triglyceride (mg/dL) 0.086 0.389 Yes 19.8±7.1
LDL(mg/dL) 0.081 0.345 No 18.2±6.6
HDL(mg/dL) 0.520 0.641 Current Smoking 0.144
Hs-CRP(mg/dL) 0.254 <0.001 Yes 19.2±7.0
Uric acid(mg/dL) 0.059 0.309 No 18.9±6.6
Hemoglobin (g/dL) 0.112 0.076 IRCA 0.015
WBC(K/ μL) 0.130 0.023 LAD/Diagonal 20.4±7.3
NLR 0.137 0.018 LCX/OM 18.7±6.5
Platelet (K/ μL) 0.094 0.107 RCA 18.3±6.2
Coronary arteries anatomy <0.001
NLR: neutrophil-to-lymphocyte ratio
SVD 17.1±6.4

Discussion 2VD 21.4±7.5

3VD 22.3±7.7
Although the pathophysiology of no-reflow has DM: diabetes mellitus, IRCA: infarct-related coronary artery, SVD:
single-vessel disease, 2VD: 2-vessel disease, 3VD: 3-vessel diseas
not been fully elucidated, its etiology appears to be
multi-factorial. Individual factors such as advanced Patient characteristics
age, hypertension, hyperglycemia and renal failure
have been studied as a predictor of no-reflow during Age is a well-known risk factor of coronary heart
primary PCI(3, 16, 17) and controlling the blood glu- disease, but its association with coronary flow has not
cose level, lowering blood pressure and statin therapy been well elucidated. Advanced age enhances various
have decreased the incidence of no-reflow phenom- degrees of endothelial dysfunction and arterial stiff-
enon in some studies(3, 18). Also, longer symptom-to- ness, which can be responsible for impaired coronary
procedure delays, more complicated angiographic le- flow in elderly patients(19). In our study population,
sions and more severe acute coronary syndromes seems older patients were more susceptible to develop the no
to increase the chance of developing no-reflow(16). reflow phenomenon, and years of age was positively

Table 4. ROC analysis of different variables for predicting No-reflow phenomenon

  Cut-off Sen. Spe. LR+ LR- DOR AUC 95% Confidence P-value
Interval
Age(Years) 62.5 0.93 0.77 4.04 0.09 10.00 0.636 0.621 0.650 <0.001
Symptom-to-Balloon(Minutes) 221 0.73 0.49 1.43 0.55 2.70 0.69 0.540 0.678 0.003
Door-to-Balloon(Minutes) 88 0.58 0.60 1.45 0.70 2.06 0.583 0.509 0.658 0.025
Serum Cr(mg/dL) 0.89 0.92 0.69 2.79 0.12 6.38 0.639 0.621 0.656 <0.001
Hs-CRP(mg/dL) 13.45 0.81 0.67 2.45 0.28 2.04 0.633 0.561 0.705 <0.001
NLR 3.02 0.60 0.59 1.27 0.71 2.20 0.603 0.529 0.677 0.006
6 Acta Biomed 2021; Vol. 92, N. 5: e2021297

Figure 1. ROC curve for different cut-offs of some variables in predicting the no-reflow phenomenon. NLR: Neutrophil-to-Lympho-
cyte Ratio

correlated with post-PCI TFC. The mentioned cor- ety of impacting factors may describe the controversial
relation was stronger in male subjects compared to results in different studies on the coronary reflow in
females. These findings suggest a common pathophys- populations enrolling both sexes (22-24) and larger
iology beyond the no-reflow incidence and the devel- study populations are strongly needed for subgroup
opment of endothelial dysfunction and atherosclerosis analysis in this field.
by the process of aging, which is important to consider We have also observed a higher risk of develop-
while planning the prevention strategies. The associa- ing no-reflow in patients with a past history of DM ,
tion between age and coronary reflow has been ana- which can be attributed to the hyper-coagulable and
lysed in cross-sectional studies on STEMI patients, pro-inflammatory state in diabetic patients, as well as
but the pathophysiology has not been discussed (20- the endothelial dysfunction which is mainly known to
24). be a result of Reactive Oxygen Species (ROS) produc-
Female patients in our study population, had a tion and imbalance of endothelium-derived vasodila-
greater chance of developing no-reflow. The gender tor and vasoconstrictor mediators in diabetes mellitus
differences in coronary anatomy and function are in- type 2(26, 27). Although the endothelial dysfunction
fluenced by multiple factors including hormonal dis- in setting of hypertension is well described and ac-
cordances between two sexes, social and habitual fac- cepted(28, 29), the hypertensive patients did not show
tors, common cardiovascular risk factors and genetic an increased risk of developing no reflow complication
variabilities based on sex chromosomes(25). This vari- in many of studies (22, 23, 30), as well as our patients.
Acta Biomed 2021; Vol. 92, N. 5: e2021297 7

The impaired renal function and the associated drug regimens which influence differently on plasma
hyperuricemia is another comorbidity of STEMI uric acid level in short and long term.
patients which is known to be associated with a hy- Another inflammatory marker that was studied in
percoagulable and inflammatory state and also cause our survey is NLR, a newly defined marker of inflam-
a retention of vasotoxic substances and ROS forma- mation, which has been described to be associated with
tion, which are believed to play an important role in adverse outcomes of coronary interventions by Akpek
creating an atherogenic milieu and endothelial dys- et al. in 2012 (22) and Balta et al. in 2016(23). We’ve
function(31). We have observed a higher occurrence of found that higher NLRs obtained at patient’s admission
no-reflow phenomenon in patients with higher levels time are associated with greater chances of developing
of serum creatinine; however, as the serum creatinine no-reflow after primary PCI, which supports the strong
is not a precise indicator of renal function and as the inflammatory background of the no-reflow phenom-
renal impairment is usually associated with multiple enon. We have previously reported this association in
comorbidities such as DM, the independent impact of another group of STEMI patients and discussed it more
renal function on endothelial dysfunction needs to be thoroughly in our previous studies in 2017(42, 43).
elucidated. Finally, we should note that although lipid profile
was not a predictor of coronary flow, neither in our
Inflammation study population nor in previous studies(20-24), high-
dose atorvastatin has decreased the risk of no-reflow,
With the growing understanding of the role of which probably is related to its anti-inflammatory
inflammation in developing coronary events, and also function and also its effect on lowering uric acid lev-
in the outcome of coronary interventions, studies have els(44).
focused on hs-CRP, a positive acute phase reactant, to
be an independent risk predictor of no-reflow(32). Hs- Coronary intervention
CRP is released into the circulation about 6 hours after
a coronary event(33) and its higher plasma levels were Delayed reperfusion is a risk predictor of devel-
correlated with more prolonged TFCs in our study oping adverse procedure outcomes (20-23), which is
population of STEMI patients. It is shown to also be described by the increased risk of micro-embolization,
correlated with the extent of coronary artery disease in distal capillary beds edema due to prolonged ischemia,
studies on STEMI patients (33-35). myocardial cells swelling, neutrophil plugging, altera-
We have also studied another inflammatory mark- tions of capillary integrity, and microvascular bed dis-
er, plasma uric acid, which its elevated levels has been ruption(45, 46). Consistent with these data, increased
a well-known predictor of coronary artery disease de- door-to- balloon time was positively correlated with
velopment and severity (36, 37). Uric acid is a product more prolonged TFC and higher risk of developing
of xanthine oxidase enzyme which also produce free no-reflow in our study population.
ROS and this may describe the association between Among all of our patients who underwent primary
hyperuricemia and endothelium-derived NO produc- PCI, those with occlusion of LAD branch of left main
tion and endothelial dysfunction(38, 39). Although coronary artery developed no-reflow more frequently
Xanthine-Oxidase inhibitor, Allopurinol, has shown compared to other cases. LAD has a longer course
some improvements in endothelial function(40), ac- compared to other coronary vessels, and its measure
cording to lack of large randomized clinical trials, uric TFC has to be corrected by dividing the LAD TFC by
acid lowering agents have not been yet recommended 1.7(14). Determining the correction bias in estimating
as a primary cardiovascular prevention in asympto- LAD TFC and the frequency of high-risk lesions in
matic hyperuricemia in clinical management guide- different coronary arteries can better clarify the asso-
lines(41). The plasma uric acid level was not signifi- ciation between LAD occlusions and prolonged TFC.
cantly correlated with no-reflow phenomenon in our Also, we have observed that multi-vessel coronary
study population, which can be due to cardiovascular involvement increases the risk of no-flow phenomena
8 Acta Biomed 2021; Vol. 92, N. 5: e2021297

after primary PCI, which can be described by more se- plasty. Am J Cardiovasc Drugs. 2009;9(2):81-9.
vere endothelial dysfunction and more diffuse complex 4. Li X, Li B, Gao J, Wang Y, Xue S, Jiang D, et al. Influence
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levels on coronary flow in patients with STEMI undergoing
reported controversial results (20-24). However, these
primary PCI. Atherosclerosis. 2011 Nov;219(1):334-41.
anatomical correlations have less clinical importance 6. Niccoli G, Burzotta F, Galiuto L, Crea F. Myocardial no-re-
compared to modifiable factors, but may help in better flow in humans. J Am Coll Cardiol. 2009 Jul 21;54(4):281-
risk estimation for more invasive risk factor modifica- 92.
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Z, et al. The no-reflow phenomenon in the young and in the
elderly. Int J Cardiol. 2016 Nov 1;222:1122-8.
8. Abbo KM, Dooris M, Glazier S, O’Neill WW, Byrd D,
Conclusion Grines CL, et al. Features and outcome of no-reflow after
percutaneous coronary intervention. Am J Cardiol. 1995
Apr 15;75(12):778-82.
Considering the available data on no-reflow phe-
9. Dong-bao L, Qi H, Zhi L, Shan W, Wei-ying J. Predictors
nomenon, it seems that female gender, advanced age, and long-term prognosis of angiographic slow/no-reflow
past medical history of diabetes, neutrophil to lym- phenomenon during emergency percutaneous coronary in-
phocyte ratio, greater symptom-to-procedure time and tervention for ST-elevated acute myocardial infarction. Clin
Cardiol. 2010 Dec;33(12):E7-12.
involvement of multiple coronary vessels are reliable
10. Resnic FS, Wainstein M, Lee MK, Behrendt D, Wain-
predictors of no-reflow phenomenon. We should note stein RV, Ohno-Machado L, et al. No-reflow is an inde-
that among all the multiple factors influencing the risk pendent predictor of death and myocardial infarction after
of no-reflow phenomenon, delayed reperfusion is the percutaneous coronary intervention. Am Heart J. 2003
only modifiable factor that can be reduced by improv- Jan;145(1):42-6.
11. Wong DT, Puri R, Richardson JD, Worthley MI, Worth-
ing healthcare policies. ley SG. Myocardial ‘no-reflow’--diagnosis, pathophysiology
and treatment. Int J Cardiol. 2013 Sep 1;167(5):1798-806.
Conflicts of interest: Each author declares that he or she has no 12. Rezkalla SH, Stankowski RV, Hanna J, Kloner RA.
commercial associations (e.g. consultancies, stock ownership, equity
Management of No-Reflow Phenomenon in the Cath-
interest, patent/licensing arrangement etc.) that might pose a con-
eterization Laboratory. JACC Cardiovasc Interv. 2017 Feb
flict of interest in connection with the submitted article.
13;10(3):215-23.
Ethical issues: This cross-sectional study has been approved by the 13. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ,
Ethics committee of Shahid Beheshti University of Medical Sci- Morrow DA, et al. Fourth Universal Definition of Myo-
ences and all the enrolled patients signed an informed consent after cardial Infarction (2018). J Am Coll Cardiol. 2018 Oct
receiving a description of the study protocol by their physician. 30;72(18):2231-64.
14. Gibson CM, Cannon CP, Daley WL, Dodge JT, Jr., Alexan-
der B, Jr., Marble SJ, et al. TIMI frame count: a quantitative
method of assessing coronary artery flow. Circulation. 1996
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N, Deanfield J. Angiotensin-converting enzyme genotype

is not associated with endothelial dysfunction in subjects Correspondence:
without other coronary risk factors. Atherosclerosis. 1994 Received: 16 June 2020 – Accepted: 2 July 2020
Nov;111(1):121-6. Hamidreza Poorhosseini
46. Hearse DJ, Bolli R. Reperfusion induced injury: manifesta- Tehran Heart Center, Tehran University of Medical Sciences,
tions, mechanisms, and clinical relevance. Cardiovasc Res. Tehran, Iran
1992 Feb;26(2):101-8. Address :Tehran Heart Center,North Kargar Avenue,Tehran,Iran
Post-code: 1411713138
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