Circ J 2008; 72: 716 – 721

Clinical and Procedural Predictors of No-Reflow

Phenomenon After Primary Percutaneous
Coronary Interventions
Experience at a Single Center

Cevat Kirma, MD; Akin Izgi, MD; Cihan Dundar, MD; Ali Cevat Tanalp, MD;
Vecih Oduncu, MD; Soe Moe Aung, MD; Kenan Sonmez, MD;
Bulent Mutlu, MD; Nihal Ozdemir, MD; Vedat Erentug, MD*

Background The aim of the study was to identify clinical factors, angiographic findings, and procedural features
that predict no-reflow phenomenon (Thrombolysis In Myocardial Infarction (TIMI) flow grade ≤2) in patients
with acute myocardial infarction (AMI) who undergo primary percutaneous coronary intervention (PCI).
Methods and Results A series of 382 consecutive patients with AMI underwent primary PCI within 12 h of
symptom onset. Patients with ischemic symptoms continuing for more than 12 h were also included. Clinical,
angiographic and procedural data were collected for each subject. Ninety-three (24.3%) of the patients developed
no-reflow phenomenon, and their findings were compared with those of the reflow group. Univariate analysis
showed that advanced age (>60 years), delayed reperfusion (≥4 h), low (≤1) TIMI flow prior to PCI, cut-off type
total occlusion, high thrombus burden on baseline angiography, long target lesion (>13.5 mm) and large vessel
diameter all correlated with no-reflow (p<0.05 for all). Multiple logistic regression analysis identified that
advanced age (odds ratio (OR) 1.04, p=0.001), delayed reperfusion (OR 1.4, p=0.0004), low TIMI flow before
primary PCI (OR 1.1, p=0.0002), target lesion length (OR 5.1, p=0.0003) and high thrombus burden (OR 1.6,
p=0.03) on angiography as independent predictors of no-reflow phenomenon.
Conclusion The occurrence of no-reflow phenomenon after primary PCI can be predicted using simple clini-
cal, angiographic and procedural features. In this selected group of patients, adjunctive pharmacotherapy and/or
distal protection device may be of value. (Circ J 2008; 72: 716 – 721)
Key Words: Acute myocardial infarction; No-reflow phenomenon; Primary percutaneous coronary interven-
tion; Thrombus

niques,7 myocardial contrast echocardiography,8 Doppler

T
he aim of treatment for acute myocardial infarction
(AMI) is to restore full antegrade blood flow in the
infarct-related artery (IRA) and minimize ischemic
damage to the myocardium. Thrombolytic therapy is an op-
tion, but primary percutaneous coronary intervention (PCI)
is the treatment of choice, based on lower rates of recurrent
ischemia or infarction and good success rates in restoring
antegrade blood flow in the IRA.1,2 However, primary PCI is
associated with a serious problem known as the no-reflow
phenomenon (Thrombolysis In Myocardial Infarction (TIMI)
flow ≤2), which occurs in 5–25% of cases.3,4
Although PCI achieves full patency of epicardial arteries,
patients who develop this phenomenon are at increased risk
for left ventricular dysfunction, more progressive myocar-
dial damage, and have higher rates of morbidity and mortali-
ty.5,6 A number of studies have focused on the risk factors,
but most of those investigators used nuclear imaging tech-
(Received May 15, 2007; revised manuscript received December 7,
2007; accepted December 25, 2007)
Cardiology, *Cardiovascular Surgery Clinics, Kartal Kosuyolu Yuksek
Ihtisas Education and Research Hospital, Istanbul, Turkey
Mailing address: Cevat Kirma, MD, Cardiology, Kartal Kosuyolu
Yuksek Ihtisas Egitim ve Arastirma H., Kardiyoloji Klinigi, 34846,
Kartal, Istanbul, Turkey. E-mail: ckirma@hotmail.com
All rights are reserved to the Japanese Circulation Society. For per-
missions, please e-mail: cj@j-circ.or.jp
flow measurements,9 TIMI frame count method10 or myo-
cardial blush grade11 to assess no-reflow phenomenon.
Although these techniques have greater accuracy for de-
tecting post-PCI suboptimal reperfusion, TIMI flow grade
is the easiest and most commonly used method of evaluat-
ing primary PCI success.12 The aim of this study was to
identify simple clinical factors, angiographic findings and
procedural features that predict no-reflow phenomenon in
patients with AMI who undergo primary PCI.
Methods
Study Population
This prospective observational study was conducted in
the Cardiology Department of Kartal Kosuyolu Yuksek
Ihtisas Education and Research Hospital between January
2003 and February 2006. During this period, emergency
cardiac catheterization was performed in 612 patients who
(1) presented with AMI of ≤12 h duration or (2) were ad-
mitted between 12 and 24 h after onset with signs and symp-
toms of continuing ischemia. Exclusions were: patients
treated conservatively for coronary artery spasm or ≤50%
diameter stenosis of the culprit lesion with normal coronary
blood flow; patients who required emergency surgical
revascularization for severe left main coronary artery or

Circulation Journal Vol.72, May 2008

Primary PCI and No-Reflow 717

Table 1 Baseline Characteristics and Demographic Data of Patients

Reflow (n=289) No-reflow (n=93) p value

Age (years) 51.6±10.8 56.0±11.2 0.001
>60, n (%) 56 (19) 33 (36) 0.001
Gender (M/F) 253/36 77/16 0.323
Hypertension, n (%) 105 (36.3) 41 (44.1) 0.224
Diabetes mellitus, n (%) 56 (19.4) 21 (22.6) 0.602
Hypercholesterolemia†, n (%) 87 (30.1) 32 (34.4) 0.436
Current smoker, n (%) 227 (78.5) 62 (66.7) 0.020
Family history of CAD, n (%) 99 (34.3) 33 (35.5) 0.829
Previous MI, n (%) 115 (39.8) 45 (48.4) 0.144
Pre-infarction angina, n (%) 88 (30.4) 21 (22.6) 0.184
Infarct location, n (%) 0.494
Anterior 176 (60.9) 63 (67.7)
Inferior 91 (31.5) 24 (25.8)
Other locations 22 (7.6) 6 (6.5)
Mean reperfusion time (min) 179±99 225±106 0.0001
<2 h 75 (26) 11 (11.8)
2-4 h 138 (47.8) 37 (39.8)
≥4 h 76 (26.2) 45 (48.4)
ST segment resolution, n (%) 0.0002
≥70% 142 (77.2) 14 (23.7)
<70% 42 (22.8) 45 (76.3)
Peak CK values (u/L) 2,637±2,458 3,557±2,765 0.014

Data are mean ± SD or number (%) of patients.

†Plasma cholesterol level >220 mg/dl.

CAD, coronary artery disease; MI, myocardial infarction; CK, creatine kinase.

multivessel disease; patients with saphenous vein grafts or
left internal mammary artery lesions; patients treated with
thrombolytic therapy or platelet glycoprotein IIb/IIIa recep-
tor antagonists prior to procedure, and cases where the pro-
cedure did not achieve coronary artery patency. In total 382
patients (330 men, aged 19–85 years; mean age, 52.6±11.0
years) constituted the study population and of them 4
(0.9%) were admitted to hospital more than 12 h after onset
of AMI and were still exhibiting symptoms at the time of
admission.
The patients were divided into 2 groups based on post-
procedural TIMI flow in the IRA: TIMI flow ≤2 (no-reflow)
and TIMI flow 3 (reflow).
Angiographic Analysis and Primary PCI Procedure
Upon admission, all patients were treated with 300 mg
aspirin PO, intravenous nitroglycerin, and at least 10,000 U
unfractionated heparin. In all cases, the femoral artery was
cannulated with an 8F sheath and coronary artery cannu-
lation was performed using an 8F guiding catheter. Before
the primary PCI procedure, standard left and right coronary
angiograms with at least 2 best projections were obtained
for each individual. Two experienced interventional cardiol-
ogists (CK and KS) who were unaware of patients’ clinical
data carefully assessed a set of parameters for each angio-
gram and reached consensus on the findings. These param-
eters were: morphology of the IRA, Rentrop collateral
flow,13 angiographic features of the target lesion, and TIMI
flow grades before and after primary PCI. Quantitative
angiographic analyses 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,14 and the frames analyzed
were end-diastolic frames that demonstrated the stenosis in
its most severe form in a non-foreshortened projection. The
contrast-filled guiding catheter was used as a calibration
standard. Primary PCI was performed using standard tech-
nique. Decisions to perform balloon angioplasty or stent
implantation were made at the surgeon’s discretion during
primary PCI. Stent implantation was strongly encouraged
unless the IRA was heavily calcified or RLD was <2.5 mm.
Bare metal stents were used for all stenting procedures.
For each case, specific angiographic features of the lesion
responsible for the infarction were recorded: (1) thrombus
burden (mild, moderate or high), (2) type of total occlusion
if present (tapered or cut-off lesion), (3) type of lesion if
subtotal occlusion is present (eccentric or concentric
lesion), (4) length of target lesion (≤13.5 mm or >13.5 mm)
and (5) lesion location (proximal, mid or distal lesion).
Thrombus burden was evaluated according to the TIMI
thrombus classification.15 It was also classified as mild if
consistent with TIMI thrombus class 0 and 1, moderate if
consistent with TIMI thrombus class 2 and 3, and high if
the greatest linear dimension of the thrombus is more than
TIMI thrombus class 3.
Each patient was treated with clopidogrel for at least 2
months after PCI. Infarct size was estimated based on the
measurement of peak serum creatine kinase (CK) activity,
and peak enzyme release was assessed using 5–6 serial mea-
surements taken within the first 96 h after symptom onset.
Evaluation of ST-segment resolution was done before and
1 h after primary PCI, as described previously.16 Only 243
electrocardiograms (ECGs; 63.6% of the 382 total cases)
were completely interpreted. In the remaining cases, ECGs
were not assessed because of missing data, inadequate
strips, presence of idioventricular rhythm, functioning ven-
tricular pacemaker or new onset left bundle-branch block.
Definitions
AMI was defined as typical chest pain of >30 min dura-
tion and either ST segment elevation of >1 mm in 2 con-
secutive leads or new onset left bundle-branch block with
2-fold elevation of CK and CK-MB fraction. Pre-infarction
angina was defined as typical anginal chest pain in the 48-h
period preceding the infarction. Reperfusion time was
defined as the time from onset of chest pain to first balloon

Circulation Journal Vol.72, May 2008

718 KIRMA C et al.

Table 2 Angiographic and Procedural Findings

Reflow (n=289) No-reflow (n=93) p value

Multivessel disease, n (%) 154 (53.3) 55 (59.1) 0.324
IRA, n (%) 0.534
LAD 172 (59.5) 61 (65.5)
LCx 26 (9) 6 (6.5)
RCA 91 (31.5) 26 (28)
Initial TIMI flow, n (%) 0.0007
0/1 202 (69.9) 87 (93.5)
2/3 87 (30.1) 6 (6.5)
Target lesion location, n (%) 0.411
Proximal 94 (32.5) 37 (39.8)
Mid 178 (61.6) 52 (55.9)
Distal 17 (5.9) 4 (4.3)
Type of occlusion, n (%) 0.014
Subtotal 116 (40.1) 19 (20.4)
Tapered 91 (31.5) 34 (36.6)
Cut-off 82 (28.4) 40 (43.0)
Lesion types in subtotal occlusion, n (%) 0.339
Eccentric 25 (21.6) 6 (31.6)
Concentric 91 (78.4) 13 (68.4)
Lesion length (mm) 0.0009
≤13.5 mm 194 (67.1) 38 (40.9)
>13.5 mm 95 (32.9) 55 (59.1)
Reference luminal diameter (mm) 3.1±0.3 3.3±0.4 0.029
Thrombus burden, n (%) 0.010
Low 79 (27.4) 17 (18.2)
Moderate 84 (29) 22 (23.7)
High 126 (43.6) 54 (58.1)
Good collateral flow 18 (6.2) 6 (6.5) 0.938
Final MLD (mm) 2.81±0.3 2.75±0.2 0.034
Final TIMI flow 0.0005
0 0 (0.0) 3 (3.2)
1 0 (0.0) 12 (12.9)
2 0 (0.0) 78 (83.9)
3 289 (100) 0 (0.0)
Method of reperfusion, n (%) 0.0003
Balloon angioplasty 10 (3.5) 7 (7.5)
Stenting with predilation 183 (63.3) 77 (82.8)
Direct stenting 96 (33.2) 9 (9.7)
Mean stent length (mm) 19.2±6.2 22.6±7.2 0.0003
Max. inflation pressure (atm) 12.8±2.5 13.1±2.1 0.057
Multiple stents (≥2), n (%) 47 (16.8) 24 (27.9) 0.051
Repeated balloon dilatations (≥2) 50 (25.4) 36 (42.4) 0.054

Data are mean ± SD or number (%) of patients.

IRA, infarct-related artery; LAD, left anterior descending artery; LCx, left circumflex artery; RCA, right coronary artery; TIMI,
Thrombolysis In Myocardial Infarction; MLD, minimal luminal diameter.

inflation. Multivessel disease was defined as >50% diame-
ter stenosis of 2 or more major epicardial coronary arteries.
Good collateral flow was defined as Rentrop collateral flow
2–3. Occlusion was defined as tapered type if the lesion
morphology featured a tapered end and as cut-off type if
the lesion morphology featured an abrupt end (no tapering).
In cases of subtotal obstruction, a lesion was defined as
eccentric if its most protruding margin was located in the
outer quarter of an apparently normal vessel lumen. On
angiography before primary PCI, a thrombus was identified
as any intraluminal filling defect near the target lesion that
was not associated with calcification. A patient was consid-
ered to exhibit no-reflow phenomenon if blood flow in the
target vessel was TIMI ≤2 flow despite successful dilatation
and absence of mechanical complications such as dissec-
tion, spasm or angiographically evident distal embolization
after completion of the procedure.
Statistical Analysis
Data are expressed as mean ± SD. Continuous variables
were compared using the unpaired Student’s t-test. Chi-
square analysis was used to test differences between propor-
tions. Fisher’s exact test was used when the expected value
for a cell was <5. Receiver-operating characteristic (ROC)
curve analysis was done to determine the best cut-off value
for target lesion length that predicted no-reflow phenome-
non. For 13.5-mm lesion length, 78% sensitivity and 62%
specificity was found on ROC curve analysis. Multiple
stepwise logistic regression analysis was used to identify
independent predictors of no-reflow phenomenon. Patients
age (>60 years), reperfusion times, thrombus burden, target
lesion length (>13.5 mm), RLD and reperfusion method
were included in the analysis. All statistical analysis were
done using SPSS version 11.0 (SPSS Inc, Chicago, IL,
USA). Statistical significance was defined as p<0.05.
Results
Patient Characteristics
Of the 382 patients who underwent primary PCI on an
IRA, 93 (24.3%) developed no-reflow phenomenon after
the procedure. Table 1 shows a comparison of the baseline

Circulation Journal Vol.72, May 2008

 Primary PCI and No-Reflow 719

A B
70 70

60 60
frequency

frequency
50 50

40 40

30 30

20 20 Fig 1. When compared with the reflow group

10 10 (A), the reperfusion time and thrombus burden
0
2
0
2
relationship demonstrated that the no-reflow
≥4 h 1 rde
n ≥4 h 1 rde
n group (B) mainly consisted of patients with de-
2-4 < h u 2-4 < h u
reperf sb reperf sb layed reperfusion (≥4 h) and a high thrombus
usion <2h 0 bu usion <2h 0 bu
om om
time thr time thr burden.

characteristics of the patients. There were no significant Table 3 Independent Predictors of No-Reflow Phenomenon
differences between the reflow and no-reflow groups with in Multivariate Analysis
respect to sex distribution, frequencies of major coronary p value OR (95%CI)
risk factors (ie, diabetes mellitus, hypertension, hyper-
cholesterolemia, family history of coronary artery disease), Age (>60 years) 0.001 1.04 (1.01–1.06)
incidence of previous AMI, infarct localization or occur- Reperfusion time (≥4 h) 0.0004 1.4 (1.19–1.69)
Initial TIMI flow (0-1) 0.0002 1.1 (1.08–1.25)
rence of pre-infarction angina (p<0.05 for all). Compared Reference luminal diameter 0.7 2.3 (1.15–4.70)
with the reflow group, the no-reflow group had significant- Lesion length (>13.5 mm) 0.0003 5.1 (2.09–12.63)
ly higher mean age (56.0±11.2 vs 51.6±10.8 years for no- High thrombus burden 0.03 1.6 (1.02–2.82)
reflow and reflow, respectively), significantly longer mean Method of reperfusion (DS) 0.09 0.3 (0.01–0.06)
reperfusion time (225±106 vs 179±99 min, respectively), OR, odds ratio; CI, confidence interval; DS, direct stenting. Other abbrevia-
and significantly higher peak CK level (3,557±2,765 vs tion see in Table 2.
2,637±2,458 u/L, respectively) (p<0.05 for all). Moreover,
the no-reflow group had a significantly smaller proportion
of active smokers (66.7% vs 78.5% for no-reflow vs reflow, 2.09–12.6; p<0.001) and high thrombus burden (OR 1.6,
respectively; p=0.02) and a significantly lower frequency 95% CI 1.02–2.82; p=0.03) were independent predictors of
of ST-segment resolution (≥70%, 23.7% vs 77.2%, respec- no-reflow phenomenon (Table 3).
tively; p<0.001).

Angiographic Findings and Primary PCI Procedure

Discussion
Analysis of the angiographic data revealed that no- In our study, the rate of no-reflow phenomenon after pri-
reflow was significantly more frequent in patients who had mary PCI was 24.3%, which was consistent with previous-
low (≤1) initial TIMI flow (93.3% vs 69.9%, respectively), ly published no-reflow rates of 5–25% of.3,4 Certain factors,
cut-off type total occlusion (43% vs 28.4%, respectively), such as advanced age, delayed reperfusion, low TIMI flow
long target lesion (>13.5 mm, 59.1% vs 32.9%, respective- prior to PCI, long target lesion and high thrombus burden,
ly) and large vessel diameter (3.3±0.4 vs 3.1±0.3, respec- were found to be independent predictors of this peculiar
tively) (Table 2). It was also observed that the no-reflow phenomenon.
group mainly consisted of patients with delayed reperfu- Large-scale prospective studies performed on elderly
sion (≥4 h) and high thrombus burden (58.1% vs 43.6%, patients with AMI indicate that in-hospital and long-term
respectively) (Fig 1). However, the presence of multivessel mortality rates are higher and the success rate of primary
disease, IRA, target lesion locations, lesion types in sub- PCI is lower than for younger patients,17,18 mainly because
total occlusions and collateral flow grades showed no dif- of delayed hospital admission of the elderly and their in-
ference between the 2 groups (p>0.05 for all). creased number of co-morbidities. Certain conditions, such
Among the procedural features, the incidence of no- as diffuse coronary atherosclerosis, severe vascular calci-
reflow was significantly lower in the direct stenting group fication, predisposition to distal microembolization and
than in the group with stenting with predilation or with disrupted microcirculation, are more common in elderly
balloon angioplasty (9/96 (8.6%), 77/183 (29.6%), 7/10 patients. These pathologic changes are related to advanced
(41.2%) respectively, p<0.001). The number of implanted age and probably cause a tendency to distal embolization
stents, maximal inflation pressures and repeated balloon during primary PCI, consequently resulting in the no-reflow
dilatations did not affect the incidence of no-reflow (p>0.05 phenomenon.
for all). However, the mean implanted stent length was sig- In our study, patients who had low (≤1) TIMI flow in the
nificantly greater in the no-reflow group (22.6±7.2 vs 19.2± IRA prior to PCI showed a 1.1-fold higher rate of no-reflow
6.2 mm for no-reflow and reflow, respectively; p<0.01). phenomenon than patients with good (≥2) TIMI flow on
baseline angiography. In a large cohort of patients with AMI,
Independent Predictors of No-Reflow Phenomenon Brodie et al indicated that procedural success was better in
Multiple stepwise logistic regression analysis identified patients with initial TIMI 2–3 flow (97.4% for TIMI 2 vs
that advanced age (>60 years, odds ratio (OR) 1.04, 95% 93.8% for TIMI 3 flow, respectively; p=0.02), and catheteri-
confidence interval (CI) 1.01–1.06; p=0.001), delayed re- zation laboratory events were less frequent.19 More recent-
perfusion (≥4 h, OR 1.4, 95% CI 1.19–1.69; p<0.001), low ly, De Luca et al showed that pre-procedural good TIMI
(≤1) TIMI flow prior to PCI (OR 1.1, 95% CI 1.08–1.25; flow was strongly related to post-procedural TIMI 3 flow,
p<0.001), target lesion length (>13.5 mm, OR 5.1, 95% CI myocardial blush grade 2–3 and lower enzymatic infarct

Circulation Journal Vol.72, May 2008

720
size.20 Good patency of the IRA prior to PCI suggests lower
thrombus burden, spontaneous endogenous lysis of the
thrombus, resolution of vasospasm and smaller infarct size.
Thus, treatment of AMI should focus on achieving sustained
antegrade blood flow as soon as possible. Although pri-
mary PCI is superior to thrombolytic therapy in achieving
TIMI 3 flow, its main limitation is the time delay while
transferring patients to tertiary PCI centers. Administration
of platelet glycoprotein IIb/IIIa receptor antagonists or low-
dose thrombolytic drugs in the early phase of AMI, when a
delay to primary PCI is expected, can help restore early IRA
patency and increase the chances of achieving post-proce-
dural TIMI 3 flow.21,22
One of the most important issues related to no-reflow
phenomenon is the reperfusion time. In our study, patients
with long reperfusion time (≥4 h) had a significantly greater
thrombus burden and a 1.4-fold increase in no-reflow rates
than patients with short reperfusion times. It is well estab-
lished that prolonged ischemia leads to edema of distal
capillary beds, swelling of myocardial cells, neutrophil
plugging and alterations of capillary integrity.23,24 Further-
more, delayed reperfusion can result in an older, more
organized intracoronary thrombus,25 which may increase the
risk of distal embolization during primary PCI and reduce
the likelihood of achieving TIMI 3 flow after the proce-
dure. Although Yip et al 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 no-reflow phenomenon was lower in the subgroup
with reperfusion time <4 h.26 In the early stages of AMI, the
thrombus is rich in thrombocytes and relatively easier to lyse
with adjunctive pharmacotherapy. With a longer time to
reperfusion, the thrombus takes on more and more erythro-
cytes and becomes more firm. Such thrombi tend to fragment
with balloon dilatation, which can lead to distal emboliza-
tion and could explain why the no-reflow phenomenon
occurs less frequently in cases of early reperfusion. As
shown previously, in cases of long reperfusion time and
high thrombus burden, the use of a distal protection device
may improve myocardial reperfusion by alleviating the
adverse effects of the organized thrombus.27
However, the no-reflow phenomenon can occur even in
patients with AMI who have a low thrombus burden and
long reperfusion time. Even if the material potential to em-
bolize is small, prolonged ischemia can disrupt the micro-
vascular bed28 and the degree of this disruption is known to
be a key factor in the pathogenesis of no-reflow. Delayed
reperfusion leads to greater destruction of the microvascu-
lature, which is why an increased rate of no-reflow is seen
in cases of prolonged reperfusion.
It is well known that acute coronary syndromes almost
always result from plaque rupture or fissuring with super-
imposed thrombus formation. Microvascular embolization
of plaque material and thrombus content can occur sponta-
neously or iatrogenically during the PCI procedure.29
Watanabe et al investigated pre-interventional intravascu-
lar ultrasound (IVUS) findings and their results suggest a
possible relationship between lipid-rich plaque and the no-
reflow phenomenon.30 Also, Tanaka et al used IVUS to
examine plaque burden and identified higher lipid content in
the plaque inner core and width of the external elastic mem-
brane as independent markers for no-reflow phenomenon.31
Those studies indicate that not only thrombus burden but
also plaque material determines the development of no-
reflow phenomenon. It is reasonable to equate lesion length
KIRMA C et al.
with plaque burden. In our study, we found that patients
with a target lesion length >13.5 mm were 5.4-fold more
likely to develop the no-reflow phenomenon than those with
a target lesion length ≤13.5 mm. As suggested by Isaaz et
al,32 we advise treatment with low-dose thrombolytic drugs
or glycoprotein receptor antagonists and postponing of PCI
if adequate antegrade flow is achieved by initial predilata-
tion in patients with high thrombus burden or a long target
lesion.
In order to reduce the risk of no-reflow developing dur-
ing primary PCI, we make every effort to avoid or minimize
trauma to the vessel wall. Specifically, it is important to
avoid repetitive balloon dilatations and use the shortest
stent at 1 tray if possible. In our experience, we have often
achieved TIMI 3 flow in the IRA after predilation, yet the
same patient developed no-reflow phenomenon following
stent implantation. In recent years, it has been shown that
coronary stent implantation without predilation is feasible
and can be performed safely in selected patients with AMI.33
Nevertheless, for direct stenting, a certain level of basal
antegrade TIMI flow and suitable lesion features (ie, sub-
total occlusion without angulation or severe calcification)
are required. Several mechanisms may explain the reduced
no-reflow rates in direct stenting. The lack of predilation
before stenting may decrease the likelihood of thrombus
and/or plaque content dislodgement and subsequent distal
embolization. The complete and direct scaffolding of a
mural thrombus at 1 tray may be another explanation of the
preventive effect of direct stenting. However, the presence
of basal TIMI flow and/or easily accessible lesion features
in the IRA before the procedure is itself an independent
predictor of increased success rate. Thus the fact that direct
stenting can decrease no-reflow remains a questionable
issue.
Study Limitations
First, we did not use IVUS to quantitatively evaluate
thrombus burden and plaque content. However, IVUS can
prolong a PCI procedure and is more expensive than con-
ventional primary PCI. Second, we excluded patients who
received pre-procedural glycoprotein IIb/IIIa receptor
antagonists, the use of which would have reduced the in-
cidence of no-reflow. Third, we did not perform in-depth
analysis of factors that may prevent no-reflow phenomenon,
such as cigarette smoking or direct stenting. Moreover, we
did not evaluate microvascular no-reflow using myocardial
contrast echocardiography or nuclear scintigraphy.
In conclusion, the pathogenesis of no-reflow phenome-
non is complex and multifactorial. In the light of our recent
study, patients who are likely to develop the no-reflow phe-
nomenon after primary PCI can be predicted by simple
clinical and angiographic features. In particular, patients
with advanced age, delayed reperfusion, low TIMI flow
and/or high thrombus burden on baseline angiography and
patients who have a long target lesion are at increased risk
for no-reflow development. In this selected group of patients,
the use of a distal protection device or administration of
pharmacologic agents that have favorable effects on micro-
vasculature (ie, platelet glycoprotein IIb/IIIa antagonists,
low-dose thrombolytics) may be of value. Because most
patients with AMI have a combination of these factors,
combined treatment strategies are preferred.
Circulation Journal Vol.72, May 2008
Primary PCI and No-Reflow
Acknowledgment
The authors thank Omer U. Erzengin for his great contribution to the
statistical analysis.
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