Annales de Cardiologie et d’Angéiologie 70 (2021) 136–142

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Original article

Predictors of no-reflow phenomenon following percutaneous

coronary intervention for ST-segment elevation myocardial infarction
Prédicteurs du phénomène de non-refusion après une intervention coronaire
percutanée pour l’infarctus du myocarde avec élévation du segment ST
P. Aggarwal a,∗ , L. Rekwal b , S.K. Sinha b , R.K. Nath a , D. Khanra c , A.P. Singh a
a
ABVIMS and Dr RML Hospital, New Delhi, India
b
LPS Institute of Cardiology, Kanpur, India
c
AIIMS, Rishikesh, India

a r t i c l e i n f o a b s t r a c t

Article history: Objectives. – No reflow during percutaneous coronary intervention (PCI) is a complex issue with serious
Received 1st November 2020 outcomes. Multiple studies have studied predictors of no-reflow during primary PCI, but data on patients
Accepted 3 April 2021 with the late presentation is sparse, which constitutes the majority of patients in peripheral centers.
Available online 4 May 2021
This study aimed to determine predictors of no-reflow during PCI in patients with ST-segment elevation
myocardial infarction (STEMI) in 7 days.
Keywords: Methods. – It was a single-center prospective case-control study performed at a tertiary care center
No-reflow phenomenon
and included 958 patients with STEMI who underwent PCI within 7 days of symptom onset. Baseline
ST-elevation Myocardial Infarction
Angiography
and angiographic data of patients undergoing PCI were recorded and patients divided into reflow and
Percutaneous coronary intervention no-reflow group.
Results. – Of 958 who underwent PCI, 182 (18.9%) showed no-reflow by myocardial blush grade (MBG) < 2.
No-reflow group had a higher mean age (66.46 ± 10.71 vs. 61.36 ± 9.94 years), lower systolic blood pres-
sure (SBP) on admission (100.61 ± 26.66 vs. 112.23 ± 24.35, P < 0.0001), a higher level of peak Troponin I
level (9.37 ± 2.81 vs. 7.66 ± 3.11 ng/dL, P < 0.0001), low left ventricular ejection fraction (36.71 ± 3.89 vs.
39.58 ± 4.28% respectively P < 0.0001). Among angiographic data and procedural features, multivariable
logistic regression analysis identified that advanced age, reperfusion time > 6 hours, SBP < 100 mmHg on
admission, functional status of Killip class for heart failure ≥ 3, lower EF (≤ 35%), low initial myocardial
blush grade (≤ 1) before PCI, long target lesion length, larger reference diameter of vessel (> 3.5 mm) and
high thrombus burden on angiography were found to be independent predictors of no-reflow (P < 0.05).
Conclusion. – No-reflow phenomenon after PCI for STEMI is complex and multifactorial and can be identi-
fied by simple clinical, angiographic, and procedural features. Preprocedural characters of the lesion and
early perfusion decides the fate of the outcome.
© 2021 Elsevier Masson SAS. All rights reserved.

r é s u m é

Mots clés : Objectifs. – L’absence de reflux lors d’une intervention coronarienne percutanée (ICP) est un problème
Phénomène de non-refusion complexe avec des conséquences graves. Plusieurs études ont étudié les prédicteurs de non-reflux
Infarctus du myocarde avec élévation du ST pendant l’ICP primaire, mais les données sur les patients présentant une présentation tardive sont rares,
Angiographie ce qui constitue la majorité des patients dans les centres périphériques. Cette étude visait à déterminer les
Intervention coronarienne percutanée
prédicteurs de nonreflux pendant l’ICP chez les patients atteints d’infarctus du myocarde avec élévation
du segment ST (STEMI) en 7 jours.

∗ Corresponding author. 10, Ajay Park, Naya Bazaar, Najafgarh, New Delhi, India.
E-mail addresses: puneetaggarwal4u@gmail.com (P. Aggarwal), lokendra5rekwal@gmail.com (L. Rekwal), fionasan@rediffmail.com (S.K. Sinha), rajitknath@yahoo.com
(R.K. Nath), ddk3987@gmail.com (D. Khanra), ajayaps04@gmail.com (A.P. Singh).

https://doi.org/10.1016/j.ancard.2021.04.004
0003-3928/© 2021 Elsevier Masson SAS. All rights reserved.
P. Aggarwal et al. Annales de Cardiologie et d’Angéiologie 70 (2021) 136–142

Méthodes. – Il s’agissait d’une étude cas-témoins prospective monocentrique réalisée dans un centre de
soins tertiaires et incluant 958 patients atteints de STEMI qui ont subi une ICP dans les 7 jours suivant
l’apparition des symptômes. Les données de base et angiographiques des patients subissant une ICP ont
été enregistrées et les patients ont été divisés en groupes de refusion et de non-refusion.
Résultats. – Sur 958 qui ont subi une ICP, 182 (18,9 %) ont montré une absence de reflux par le grade de
blush myocardique (MBG) < 2. Le groupe sans refusion avait un âge moyen plus élevé (66,46 ± 10,71 vs
61,36 ± 9,94 ans), une pression artérielle systolique (PAS) inférieure à l’admission (100,61 ± 26,66 vs
112,23 ± 24,35, p < 0,0001), un niveau de pic plus élevé Taux de troponine I (9,37 ± 2,81 vs 7,66 ± 3,11 ng/dl,
p < 0,0001), faible fraction d’éjection ventriculaire gauche (36,71 ± 3,89 vs 39,58 ± 4,28 % respective-
ment p < 0,0001). Parmi les données angiographiques et les caractéristiques procédurales, une analyse
de régression logistique multivariée a identifié un âge avancé, un temps de reperfusion > 6 heures, une
PAS < 100 mmHg à l’admission, un état fonctionnel de la classe Killip pour une insuffisance cardiaque ≥ 3,
une FE inférieure (≤ 35 %), une faible Le grade de blush myocardique (≤ 1) avant ICP, la longueur de la
lésion cible longue, le diamètre de référence plus grand du vaisseau (> 3,5 mm) et la charge de thrombus
élevée sur l’angiographie se sont avérés être des prédicteurs indépendants de la non-refusion (p < 0,05).
Conclusion. – Le phénomène de non-refusion après PCI pour STEMI est complexe et multifactoriel et peut
être identifié par de simples caractéristiques cliniques, angiographiques et procédurales. Les caractères
pré-procéduraux de la lésion et la perfusion précoce déterminent le sort du résultat.
© 2021 Elsevier Masson SAS. Tous droits réservés.

1. Introduction
Early and adequate revascularization of the infarct-related
artery (IRA) plays an important role in the management of
ST-segment Elevation Myocardial Infarction (STEMI). Late pre-
sentation or non-availability of cath labs in acute settings leads
to pharmaco-invasive approach or rescue percutaneous coronary
intervention (PCI). No reflow during PCI is a complex issue with
serious outcomes. As no effective treatment are available for no-
reflow, it is important to predict and prevent no-reflow from
occurring. Multiple studies have studied predictors of no-reflow
during primary PCI but little data is available on patients with
the late presentation which constitutes the majority of patients in
peripheral centers. This study was designed to identify the predic-
tors of no-reflow during Percutaneous Coronary Intervention (PCI)
in patients with Acute STEMI in the first 7 days of symptom onset.
2. Methods
It was a single centered, hospital-based, prospective, case-
control study conducted at a tertiary care center from 1st October
2016 to 30th September 2019. Patients with STEMI undergoing PCI
within 7 days of symptom onset as per guideline-directed treat-
ment [1] and age > 18 years were included in the study. However,
patients who were managed conservatively for coronary artery
spasm or had a < 50% diameter stenosis of the culprit lesion with
normal coronary blood flow or patients who had undergone Coro-
nary Artery Bypass Graft (CABG) or require CABG were excluded
from the study. Patients who did not achieve coronary artery
patency or with chronic kidney disease were also excluded from
the study.
The design of the work was approved by the Institutional Ethics
Committee and confirmed to the principle of good clinical practice
and declaration of Helsinki. Informed written consent was taken
from all the patients in their understanding language.
2.1. Parameters studied
Detailed history and physical examination along with elec-
trocardiographic (ECG), echocardiographic and laboratory exam-
ination was performed and relevant catheterization data were
collected prospectively. The patients were studied based on the
following parameters.
Baseline characteristics like age in years, sex, and risk fac-
tors like smoking or chewing tobacco, Diabetes Mellitus (DM) [2],
Hypertension (HTN) [3], family history of a premature heart attack,
dyslipidemia [4], and reperfusion time were assessed. Reperfusion
time was defined as the time from onset of chest pain to first balloon
inflation.
Routine clinical examinations were conducted including Car-
diovascular System examinations, Blood Pressure, Pulse, Juglar
venous pressure and chest examinations and patients were man-
aged accordingly. Patients were categorized to Killip class for heart
failure at the time of admission [5].
ECG, quantitative Troponin I after 6 hours of chest pain (at base-
line) and repeated measurement was taken at 2 hours following
PCI. The upper limit of the assay was considered as 0.02 ng/mL.
2D Echocardiogram were conducted along with clinical assess-
ment. Routine laboratory tests (including Complete Blood Count,
Fasting Blood Sugar, Post Prandial Blood Sugar, urea, creatinine,
sodium/potassium, Lipid profiles) were sent and patients were
managed according to the abnormalities of the report if any.
Troponin I was measured at the time of admission in all patients
as per institutional protocol.
2.2. Coronary angiography and PCI
All patients received oral aspirin (300 mg) and ticagrelor
(180 mg). Those patients in whom ticagrelor was contraindicated
were prescribed either prasugrel (60 mg) or clopidogrel (300 mg),
80 mg atorvastatin as well as intravenous 7500–10,000 U unfrac-
tionated heparin as per the weight of the patient.
They received PCI through either femoral or radial artery access.
Standard left and right coronary angiograms with at least 2 ortho-
gonal projections were obtained for each patient before the PCI.
Each angiogram was assessed by two experienced interventional
cardiologists and consensus on findings was made. For each case,
specific angiographic features of the lesion responsible for the
infarction were recorded as per the ABC stenosis morphology clas-
sification of the American College of Cardiology/American Heart
Association (ACC/AHA) task force [6,7].
These parameters included: morphology of the Infarct Related
Artery (IRA), Rentrop collateral flow [8], angiographic features of
the target lesion, myocardial blush grade (MBG) before and after
PCI [9], degree of culprit lesion stenosis, target lesion length, and
luminal diameter. On angiography, a thrombus was identified and

137
P. Aggarwal et al.
graded as per Gibson scoring [10] prior to PCI. Quantitative angi-
ographic analysis were also carried out to determine reference
luminal diameter (RLD), target lesion length and post-procedural
minimal luminal diameter (MLD), using a digital edge detection
algorithm, and the end-diastolic frames that demonstrated the
stenosis in its most severe form in a non-foreshortened projec-
tion were analyzed. The contrast-filled guiding catheter was used
as a standard for calibration. PCI was performed using standard
technique.
The reperfusion therapy (balloon angioplasty or stent place-
ment) was determined by the physician’s discretion during PCI.
Stent placement with drug eluting stents was strongly encouraged
unless the IRA was heavily calcified or RLD was < 2.25 mm. Routine
use of nitroglycerin and verapamil was done wherever necessary, to
prevent no-reflow. Thrombosuction and GpIIbIIIa inhibitors were
used as per the interventionist’s discretion.
No-reflow phenomenon was defined as MBG < 2 was in the tar-
get vessel despite successful dilatation and absence of mechanical
complications such as dissection, spasm, or angiographically evi-
dent distal embolization after completion of the procedure. On the
basis of post-procedural MBG in the IRA all patients were divided
into two groups based: MBG < 2 (no-reflow) and MBG ≥ 2 (reflow).
2.3. Statistical analysis
Microsoft Access was used for data collection and Microsoft
Excel was used as the spreadsheet for export and data conver-
sion. The data were analyzed with SPSS version 16. Chi-square test
was used to compare categorical variables and Student’s t-test was
used for comparisons between means (continuous variables). Sig-
nificance was assumed at P < 0.05. Multivariate logistic regression
analyses were performed for significant variables and odds ratio for
different predictors was calculated. The confidence intervals were
stated and their statistical significance was calculated.
3. Results
The present study was conducted under the auspices of the
department of cardiology at a tertiary care center. The study was
conducted on 958 patients admitted with the diagnosis of acute
STEMI in past 7 days who underwent PCI. The patients were divided
into 2 groups, those with reflow (MBG ≥ 2) and those with no-
reflow (MBG < 2).
3.1. Baseline clinical characteristics
Of the 958 enrolled patients, 182 patients had no-reflow phe-
nomenon after PCI, with an incidence of 18.9%. The baseline
characteristics of the patients were as shown in Table 1. The base-
line characteristics of the patients were as shown in Table 1. The
baseline characterstics like sex distribution, hypertension, diabetes
mellitus, dyslipidemia, current smoking, family history of coro-
nary artery disease, previous Myocardial Infarction (MI) and infarct
localization were not significantly different between the reflow
group and the no-reflow group (P > 0.05).
As compared to the reflow group, the no-reflow group had a
higher mean age (66.46 ± 10.71 vs. 61.36 ± 9.94 years for no-reflow
and reflow, respectively), a lower SBP at the time of admission
(100.61 ± 26.66 vs. 112.23 ± 24.35, respectively), a higher level of
Troponin I (9.37 ± 2.81 vs. 7.66 ± 3.11 ng/dl, respectively) and lower
left ventricle ejection fraction (LVEF) before PCI (36.71 ± 3.89 vs.
39.58 ± 4.28% respectively) (p < 0.05). Moreover, patients in the no-
reflow group had higher Killip class before PCI as compared to the
reflow group (p < 0.05).
A subgroup analysis was done according to reperfusion time.
In patients undergoing PCI within 24 hrs after the appearance of
138
Annales de Cardiologie et d’Angéiologie 70 (2021) 136–142
symptoms, the mean reperfusion time was significantly longer in
the no-reflow group as compared to reflow group [12.35 ± 4.83 (n-
20) vs. 8.2 ± 4.55 (n-140) respectively] but in comparison to this,
patients undergoing PCI between 24 hrs and 7 days with recur-
rent angina (whether thrombolysed or not) the difference between
mean reperfusion time was not statistically significant between
the no-reflow group and reflow group.[52.89 ± 17.66 (n-162) vs.
50.26 ± 17.17 (n-636)].
3.2. Angiographic findings and PCI characteristics
The angiographic data and procedural features of patients were
as shown in Table 2. In all, 182 patients out of 958 had no-reflow
(18.9%). Of the total cohort of the STEMI population, PCI was per-
formed via femoral arterial access in 90.4% of patients and via radial
access in 9.6% of patients and there was no significant difference
between the two groups. Anterior Wall MI (AWMI) was most com-
mon in both groups. Left Anterior Descending (LAD) as a target
vessel was more common in both of the groups. The incidence of
multivessel disease between the two groups was similar in two
groups. Drug eluting stents (DESs) were used in all the patients.
No-reflow was more common in patients who had a low ini-
tial MBG (< 2) compared to the reflow group (90.1% vs. 73.96%,
t2 – 21.71, P < 0.0001). A total cut-off occlusion was more common
in the no-reflow group (31.86% vs. 21.39%) which was signifi-
cantly different when compared with (P = 0.003) the reflow group.
The mean reference vessel diameter and target lesion length were
higher in the no-reflow group (no-reflow 3.15 ± 0.28 vs. 3.07 ± 0.29,
P = 0.0008 and 26.73 ± 10.93 vs. 23.08 ± 8.67, P < 0.0001 respec-
tively) as compared to the reflow group, which was statistically
significant.
Moreover, the no-reflow incidence was significantly higher in
patients with delayed reperfusion and a high thrombus burden
(p < 0.05). The method of reperfusion also determined whether the
no-reflow phenomenon occurs in two groups (p < 0.05). However,
IRA, the presence of multivessel diseases, locations of target lesions,
types of lesions in subtotal occlusions, number of implanted stents,
post-dilation after stenting, repeated balloon dilatations, throm-
bosuction and GpIIbIIIa inhibitor use did not significantly affect the
incidence of no-reflow (p > 0.05).
3.3. Independent predictors of no-reflow phenomenon
Multivariate regression analyses as shown in Table 3, identified
that age > 60 years (OR = 3.364, 95%CI 1.919–5.896, P < 0.0001),
reperfusion time > 6 hours (OR = 2.835, 95%CI 1.038–7.740,
P = 0.042), systolic blood pressure (SBP) on admission < 100 mmHg
(OR = 10.27, 95%CI 2.760–38.24, P = 0.001), cardiac function killip
class ≥ 3 before PCI (OR = 2.940, 95%CI 1.159–7.456, P = 0.023), a
low LVEF (≤ 35%) (OR = 3.413, 95%CI 1.745–6.678, P < 0.0001), a
low initial MBG (< 2) (OR = 6.051, 95%CI 1.029–35.58, P = 0.046), a
high thrombus burden (OR = 0.300, 95%CI 0.174–0.517, P < 0.0001),
a long target lesion (> 24 mm) (OR = 1.033, 95%CI 1.013–1.053,
P = 0.001) and larger reference diameter (> 3.5 mm) (OR = 4.686,
95%CI 2.475–8.872, P < 0.0001) were the independent predictors of
the no-flow phenomenon.
4. Discussion
In our study, the incidence of the no-reflow phenomenon after
PCI in STEMI was 18.9%, which was similar to that (5%–25%),
reported previously [11]. In our study, certain factors, like advanced
age, delayed reperfusion, low SBP on admission, higher Killip class,
low LVEF, long target lesion, large vessel diameter, low MBG before
PCI, and high grade of thrombus burden were found to be indepen-
dent predictors of no reflow during PCI. Del Turco and Colleagues
P. Aggarwal et al. Annales de Cardiologie et d’Angéiologie 70 (2021) 136–142

Table 1
Baseline clinical data in the reflow group and the no-reflow group (n, %).

Variables Reflow (776) No-reflow (182) t/x2 P-value

Age (years) 61.36 ± 9.94 66.46 ± 10.71 6.13 < 0.0001

Male 488 (62.8%) 126 (69.23%) 2.578 0.1083
Hypertension 232 (29.8%) 62 (34.06%) 1.205 0.2724
Diabetes mellitus 140 (18.04%) 40 (21.9%) 1.497 0.2211
Dyslipidemia 350 (45.1%) 90 (49.4%) 1.122 0.2895
Current smoker 357 (46%) 76 (41.7%) 1.073 0.3002
Family history 230 (29.6%) 59 (32.4%) 0.540 0.4623
Previous MI 50 (6.4%) 16 (8.79%) 1.267 0.2603
Infarction location 4.998 0.0822
Anterior 450 (57.9%) 109 (59.89%)
Inferior 264 (34.02%) 67 (36.81%)
Other Location 62 (7.98%) 6 (3.29%)
SBP on admission (mmHg) 112.23 ± 24.35 100.61 ± 26.66 5.6881 < 0.0001
DBP on admission (mmHg) 72.02 ± 12.69 70 ± 13.82 1.8996 0.0578
Peak Troponin I 7.66 ± 3.11 9.37 ± 2.81 6.7952 < 0.0001
Reperfusion time
< 24 hours 8.2 ± 4.55 (140) 12.35 ± 4.83 (20) 3.7868 0.0002
≥ 24 hours 50.26 ± 17.17 (636) 52.89 ± 17.66 (162) 1.7304 0.0839
Killip class 27.78 < 0.0001
1 481 (61.9%) 87 (47.8%)
2 225 (28.99%) 61 (33.51%)
3 47 (6.05%) 14 (7.69%)
4 23 (2.96%) 20 (10.98%)
LVEF % 39.58 ± 4.28 36.71 ± 3.89 8.2793 < 0.0001

DBP: diastolic blood pressure; LVEF: left ventricle ejection fraction; MI: myocardial infarction; SBP: systolic blood pressure.

Table 2
Angiographic and procedural data in the reflow group and the no-reflow group (n, %).

Variables Reflow (776) No-reflow (182) t/x2 P-value

Radial access 78 (10.05%) 14 (7.69%) 0.9452 0.3309

Multivessel disease 380 (48.96%) 102 (56.04%) 2.9518 0.0857
Infarct related artery 1.044 0.593
LAD 490 (64.1%) 126 (69.2%)
LCX 62 (7.98%) 12 (6.59%)
RCA 224 (28.86%) 44 (24.17%)
Initial MBG 21.71 <0.0001
0/1 574 (73.96%) 164 (90.1%)
2/3 202 (26.03%) 18 (9.89%)
Target lesion location 2.616 0.270
Proximal 342 (44.1%) 88 (48.4%)
Mid 408 (52.6%) 85 (46.7%)
Distal 26 (3.4%) 9 (4.9%)
Type of occlusion 11.6543 0.003
Sub-total 458 (59.02%) 84 (46.15%)
Tapered (Total) 152 (19.58%) 40 (21.97%)
Cut-off (Total) 166 (21.39%) 58 (31.86%)
Target lesion length (mm) 23.08 ± 8.67 26.73 ± 10.93 4.8483 <0.0001
Reference diameter (mm) 3.07 ± 0.29 3.15 ± 0.28 3.3712 0.0008
Thrombus burden 18.515 <0.0001
Low 256 (32.98%) 36 (19.78%)
Medium 272 (35.05%) 60 (32.96%)
High 248 (31.95%) 86 (47.25%)
Method of reperfusion 14.116 0.001
Balloon angioplasty 8 (1.0%) 2 (1.1%)
Stenting after pre-dilation 484 (62.4%) 140 (76.9%)
Direct stenting 284 (36.6%) 40 (22.0%)
Repeated balloon dilatations (≥ 2) 186 (23.96%) 56 (30.77%) 3.61 0.057
Multiple stents (≥ 2) 90 (11.59%) 30 (16.48%) 3.2115 0.073
Postdilation 274 (35.3%) 78 (48.85%) 3.6135 0.057
Thrombosuction and GpIIbIIIa inhibitor use 175 (22.55%) 52 (28.57%) 2.9548 0.0856

LAD: left anterior descending artery; LCX: left circumflex artery; MBG: myocardial blush grade; RCA: right coronary artery.

[12] demonstrated that elderly patients (> 65 years) suffer from
higher rates of no-reflow and attributable it to a more pronounced
pro-inflammatory state.
Patients with low MBG (<2) in the IRA before PCI showed a 6 fold
higher rate of the no-reflow phenomenon than patients with MBG
(≥ 2) on baseline angiography similar to study by Zwolle Myocardial
Infarction Study Group [13].
In our study, patients with low SBP on admission (< 100 mmHg)
had an increase in no-reflow rates than patients with
SBP ≥ 100 mmHg on admission (P = 0.001). Presentation with
Killip class ≥ 3 at the time of admission had 2.9 fold of the risk for
no-reflow. The correlation between heart failure and no-reflow
is a complex involving neurohumoral activation that leads to
endothelial dysfunction by decreasing bioavailability of nitric

139
P. Aggarwal et al. Annales de Cardiologie et d’Angéiologie 70 (2021) 136–142

Table 3
Multivariate analysis (binary logistic regression) of various parameters for independent prediction of no-reflow.

Variables B Wald df P-value aOR 95% confidence interval for aOR

Lower bound Upper bound

Age > 60 years 1.213 17.954 1 < 0.0001 3.364 1.919 5.896
Pre-infarction angina −0.302 2.255 1 0.133 0.739 0.498 1.097
SBP on admission <100 mmhg 2.330 12.065 1 0.001 10.273 2.760 38.246
Troponin I ≥ 10 ng/dL 0.579 3.416 1 0.065 1.784 0.966 3.296
LVEF ≤ 35% 1.228 12.854 1 < 0.0001 3.413 1.745 6.678
Killip class 3/4 1.078 5.156 1 0.023 2.940 1.159 7.456
Reperfusion time 4.861 2 0.088
Reperfusion time < 6hr 0.627 1.679 1 0.195 1.871 0.725 4.827
Reperfusion time ≥ 6hr 1.042 4.136 1 0.042 2.835 1.038 7.740
Long lesion length 0.033 11.000 1 0.001 1.033 1.013 1.053
Reference luminal diameter > 3.5 mm 1.545 22.494 1 < 0.0001 4.686 2.475 8.872
Thrombus burden 18.784 2 < 0.0001
Thrombus burden-high −1.204 18.784 1 < 0.0001 0.300 0.174 0.517
Thrombus burden-moderate 37.542 0.000 1 0.993 2.01E + 16 0.000 –
MBG 0/1 1.800 3.966 1 0.046 6.051 1.029 35.589
Type of oclusion cut-off 0.397 1.426 1 0.232 1.487 0.775 2.854
Reperfusion method 2.207 2 0.332
Reperfusion method (predilation) −17.561 0.000 1 0.996 0.000 0.000 –
Reperfusion method(balloon angioplasty) −0.412 2.207 1 0.137 0.662 0.384 1.141

LVEF: left ventricle ejection fraction; MBG: myocardial blush grade; SBP: Systolic blood pressure.

Table 4
Predictors of No-Reflow in various study among patients with STEMI.

No Authors Number of patients Predictors of no-reflow

Total No-reflow Normal

STEMI flow

1. Sani et al. [24] 141 35 105 WBC, MPV, Cr, blood glucose, HDL
2. Abdi et al. [25] 438 49 389 WBC, thrombus grade, lesion (Bifurcation and eccentric)
3. Wang et al. [26] 1776 367 1409 Age > 55 years, neutrophil count > 8800 mm3 , thrombus
score > 2, blood glucose > 12 mmol/l, High Killip Class 4,
Chest pain to PCI duration > 24 hrs, Collateral circulation < 1
4. Mazhar et al. 781 189 592 Age ≥ 60 years, Thrombus score > 4, duration of chest pain
[27] to PCI duration 6 ≥ hrs
5. Soeda et al. [28] 145 72 73 OCT and IVUS performed within 12 hours of symptom
1. OCT: Lipid index of plaque rupture ≥ 3500
IVUS: plaque burden ≥ 81.5%
OCT and IVUS revealed the best morphological
discriminating predictors for no-reflow
6. Current 998 182 716 A. Clinical:
study 1. Advanced age (≥ 60 years)
2. Reperfusion time >6 hours,
3. SBP < 100 mmHg on admission, 4. Killip class for ≥ 3,
5. Lower EF (≤ 35%),
B. Angiographic parameters-
1. Initial myocardial blush grade (≤ 1) before PCI,
2. long target lesion length (20 mm),
3. larger reference diameter of vessel (> 3.5 mm)
4. High thrombus burden

STEMI: ST elevation myocardial infarction; WBC: white blood cell; MPV: mean platelet volume; Cr: Creatinine; HDL: high density lipoprotein; PCI: percutaneous coronary
intervention; OCT: optical coherence tomography; IVUS: intravascular ultrasound; SBP: systolic blood pressure; EF: ejection fraction.

oxide and increased reactive oxygen species in the vessel wall
[14,15].
Patients with LVEF ≤ 35% had a 3.4 fold increase in no-reflow
rates than patients with LVEF > 35% before PCI. This can be
explained by the severity of coronary lesion and occlusion, and
subsequently, more damage to the myocardium in the no-reflow
group. Peak troponin level was also significantly higher in patients
with no-reflow as compared to patients with reflow (P < 0.0001).
Matetzky et al. [16] reported lower myocardial flow in patients
with higher admission Troponin I level. Elevated Troponin I level
on admission appears to be an independent marker of an early and
extensive myocardial and microvascular damage.
Thrombus grade was another predictive factor of the no-reflow
phenomenon, which was higher within the no-reflow group. An
increased clot volume causes higher thrombus grade and subse-
quently increases the likelihood of the no-reflow phenomenon
[17]. Logistic regression in this study shows that thrombus grade
is an independent predictive factor of developing no-reflow phe-
nomenon.
One of the foremost important issues associated with the
no-reflow phenomenon is the reperfusion time. Our study demon-
strates that patients with a long delay in reperfusion (> 6 hours)
had a significantly greater thrombus burden and a 1.8 fold increase
in no-reflow rate than patients with early reperfusion. Myocar-
dial necrosis occurs in about 6 hours after coronary occlusion
[18,19]. Although Yip et al. [20] did not detect a direct relationship
between thrombus burden and reperfusion time, they demon-
strated that among patients with high thrombus burden, the rate of
the no-reflow phenomenon was lower in patients with reperfusion
time < 4 h. Prolonged ischemia in patients with delayed reperfusion
leads to greater destruction of the microvasculature, causing an
increased rate of no-reflow [21].

140
P. Aggarwal et al.
Our study demonstrates that large luminal size, especially those
with the IRA diameter above 3.5 mm, increased the occurrence of
no-reflow by 4.6 fold. Large vessels can contain large amounts of
plaque lipid or thrombus and have slower flow velocity increas-
ing no-reflow [22]. We found that patients with long target lesion
length were more likely to develop the no-reflow phenomenon
than those with a discrete or tubular target lesion length. Longer
target lesion signifies a larger amount of thrombus, more plaque
burden, and longer stent length [23]. In our study, we achieved
an MBG >2 in the IRA after pre-dilatation, yet the same patients
developed no-reflow after stent implantation.
Comparision of different parameters of no reflow in STEMI in dif-
ferent studies is as shown in Table 4 [24–28]. As there is no effective
treatment for no-reflow once it has occurred, it is important to pre-
dict and prevent no-reflow from occurring. Better prediction of the
no-reflow phenomenon would help us to conduct measures to pre-
vent this phenomenon and reduce the subsequent complications.
4.1. Limitations of study
Microvascular no-reflow was not evaluated using myocardial
contrast echocardiography or nuclear scintigraphy. Intravascular
ultrasonography (IVUS) was not used to quantitatively evaluate
the thrombus burden and plaque content. The effect of drugs that
the patient received during the pre infarction period and use of
vasodilators during PCI was not studied.
5. Conclusion
In light of our study, the no-reflow phenomenon after PCI in
STEMI can be predicted by simple clinical and angiographic fea-
tures. In particular, advanced age, delayed reperfusion, low SBP at
the time of admission, higher Killip class, low LVEF, low MBG, high
thrombus burden on baseline angiography and patients who have a
long target lesion and larger reference luminal diameter increased
risk for no-reflow development. Early reperfusion and lesser win-
dow period can prove to be an important strategy to decrease the
incidence of no-reflow.
Disclosure of funding
No funding.
Disclosure of interest
The authors declare that they have no competing interest.
Acknowledgement
None.
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