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INTRODUCTION
IMPORTANCE
DEFINITION
HISTORICAL BACKGROUND
INCIDENCE
TYPES OF NO REFLOW
ASSESSMENT AND PREDICTION OF CORONARY NO-REFLOW
PHENOMENON
CLINICAL PREDICTORS OF NO-REFLOW PHENOMENON
ANGIOGRAPHIC PREDICTORS OF NOREFLOW PHENOMENON
BIOCHEMICAL MARKERS PREDICTING NOREFLOW PHENOMENON
IMAGING MODALITIES TO ASSESS AND PREDICT NOREFLOW
PHENOMENON
SCORING SYSTEMS
PROPHYLAXSIS
INITIAL EVALUATION ON CATHETER LABORATORY
DIFFERENTIAL DIAGNOSIS OF CORONARY SLOW FLOW
PHENOMENA
TREATMENT
REFRACTORY NO-REFLOW
PROGNOSIS
AIM OF STUDY
STUDY DESIGN
INCIDENCE OF NOREFLOW IN OUR STUDY
CONCLUSIONS
RECOMMENDATION
STUDY LIMITATIONS
NO-REFLOW CASE PRESENTATION
• The key of acute STEMI treatment is to quickly restore the IRA
perfusion, resulting in the slogan ‘Time is the Myocardium, Time is
Life’. As the body has a complex regulatory mechanism, where, on the
one hand, the necrotic myocardium cannot be restored, and on the
other hand, it is accompanied with reperfusion injuries and even the
no-reflow phenomenon, the occurrence and development of the no-
reflow phenomenon contain reperfusion injuries
• No-reflow phenomenon is a common and severe complication of
patients with acute myocardial infarction AMI after direct PCI. As
its occurrence hinders the effective myocardial reperfusion, it has
become an independent predicative indicator for short-term
prognosis as well as long-term heart failure, arrhythmia, sudden
cardiac death and other cardiac events
• No-reflow phenomenon is characterized by the failure of
myocardial reperfusion despite the absence of mechanical coronary
obstruction (Rossington, Sol et al. 2020). (Ito, Tomooka et al. 1992)
first described the phenomenon of ‘no reflow’ in humans with acute
myocardial infarction, whereby perfusion is not re-established
despite patency of the epicardial coronary artery.
Prediction of patients at risk for no-reflow before PCI may be
beneficial from the perspective of prevention. Risk awareness will lead to
the use of certain techniques that may ameliorate the degree of no-reflow
No reflow (NR) defined as final thrombolysis in myocardial
infarction (TIMI) flow <III or TIMI III flow with TIMI myocardial
blush grade (TMBG) 0 or 1 in absence of mechanical obstruction. TIMI
flow grade is the easiest and most commonly used method of
evaluating success of PCI in the setting of STEMI
• The TIMI grade flow is classified as follows: TIMI-0 indicates there
is no antegrade flow beyond the point of occlusion, TIMI-1 indicates
there is a faint antegrade coronary flow beyond the occlusion with an
incomplete filling of the distal coronary bed, TIMI-2 indicates there
is delayed or sluggish antegrade flow with complete filling of the
distal territory, and TIMI-3 indicates normal flow with complete
filling of the distal territory (Avci, Yildirim et al. 2018).
TIMI Blood Flow Grades
• In primary angioplasty, myocardial blush grade independently predicts
long-term mortality, TIMI flow, and LV function. TIMI frame counts
and myocardial blush are more reproducible and more accurate than
TIMI flow grades. A combination of TIMI flow and TIMI myocardial
perfusion grade before and after PCI has been described (Angiographic
Perfusion Score) as a single myocardial perfusion grade
Myocardial Blush
Angiographic assessment of myocardial perfusion: TIMI myocardial perfusion (TMP) grading
system.
Permission reproduced from (Appleby, ANGEJA et al. 2001), BMJ Publishing Group Ltd.
• The first clinical observation of coronary no-reflow was reported by
Schofer et al.in 1985.
• In 1989, Wilson et al. observed persistent angina with ST elevation in
association with a slow angiographic antegrade flow despite a widely
patent angioplasty site in five patients immediately after PTCA of a
thrombus containing lesion.
• In 1991,Pomerantz et al. reported five more cases of noreflow
successfully treated by intracoronary verapamil.
• the first clinical case of no-reflow during PTCA for acute myocardial
infarction was reported by Feld et al. in 1992
Reflow is an under-reported complication. A low incidence of 1–3%
has been recorded in large registries based on TIMI flow grade,
myocardial blush grade and ST resolution. Modern more sensitive
methods of assessing no reflow and microcirculatory dysfunction include
myocardial contrast echocardiography (MCE) and cardiac magnetic
resonance imaging (CMRI), which have recorded a higher incidence (10–
30%) (Gupta and Gupta 2016).
NR has a multifactorial aetiology and broadly can be defined by four
distinct groups:
I. Distal atherothrombotic embolisation
II. Ischaemic injury
III. Reperfusion injury
IV. Susceptibility of coronary micro-circulation to injury. Distal
embolization is a result of debris (thrombi, endothelial cells and
lipid matrix) migrating downstream from the primary lesion, leading
to microvascular obstruction and further injury
Sustained
Result of anatomical irreversible changes of coronary microcirculation
Undergo unfavorable LV remodeling
Reversible
Result of functional & thus reversible changes of microcirculation
Maintain their left ventricle volumes unchanged over time
 TIMI Blood Flow Grades
 The Corrected TIMI Frame Count (CTFC)
 Myocardial Blush
Clinical predictors
 Age
 Family history of CAD
 Pre infarction angina
 Heart rate
 Killip class
 Delayed reperfusion
 Low preoperative systolic blood
pressure
 Smoking
 Atrial fibrillation
 Shock index
 CHA2DS2–VASc score
 Psychological distress
 Sex hormones
Angiographic Predictors
 TIMI blood flow grades
 The corrected TIMI frame count
(CTFC)
 Myocardial blush
 Lesion length and reference lumen
diameter
 Thrombus burden
 Coronary artery ectasia
 Culprit artery
 Syntax score
 Stent overexpansion
 Saphenous vein coronary bypass grafts
 Collateral Flow Grade
 Chronic Total Occlusion
 Bifurcation lesions
Angiographic predictors
 Air embolism
 Contrast agent
 Iatrogenic Dissection of the Left Main
Coronary Artery
 Treatment of coronary in-stent
restenosis with a paclitaxel-coated
balloon catheter
 Plaque prolapse
 Lesion Morphology
 OCT
 Rotational atherectomy
 orbital atherectomy
 Intravascular lithotripsy.
Biomarkers
 Cardiac biomarkers
 The blood glucose level
 Serum uric acid
 CBC Parameters
a) hemoglobin level
b) RDW levels
c) Polycythemia vera
d) Platelet Indices
e) Leukocyte Indices
f) The neutrophil lymphocyte
ratio
 Hs-CRP
 LDH
 D-dimer
Biomarkers
 Dyslipidemia
 Serum B-type natriuretic peptide
 Renal impairment
 Serum bilirubin levels
 Fibrinogen
 Cystatin C
 Plasma myeloperoxidase levels
 Microalbuminuria
 Serum endocan levels
 Clot permeability
 Soluble CD40b ligand level
 Angiopoietin-Like 4 Serum Levels
 MicroRNAs
Imaging Modalities Predictors
 Myocardial contrast echocardiography
 Left Ventricular Ejection Fraction
 EAS index
 Speckle-tracking echocardiography
 Magnetic resonance imaging
 Cardiac computed tomography (CCT)
 Nuclear magnetic imaging
Electrocardiographic predictors
 higher Q/R in admission ECG
Scoring Systems
(Bakr, Roshdy et al. 2017) suggested a weighted scoring system , to predict the
development of no reflow phenomenon during primary percutaneous coronary
intervention in patients with acute myocardial infarction. An 8 variable scoring
system was constructed as follows age above 60 years old 1 point, delayed
reperfusion time more than 4hrs 2 points, large luminal diameter ≥2.8 mm 2
points, long target lesion ≥20 mm 4 points, high thrombus burden 1 point, initial
TIMI flow ≤ 1 is 3 points, positive Ck-Mb on admission 2 points and elevated D-
dimer ≥ 500 ng/ml 1 point, with final total score 16 points. scoring 10 points or
more are most likely to have no reflow phenomenon, test sensitivity was 86% and
specificity was 73%.
Strategies For Prevention How To Apply
 Aggressive lifestyle modification
 Cessation of smoking
 Exercise regularly
 Avoid stress
 Control blood pressure
 BB ,ACEI ,CCB
 Strict control of blood sugar
 Oral hypoglycemic or insulin
 Treatment of dyslipidemia  Intensive statin therapy
 Preoperative loading of antiplatelet
 Ticagrelor loading
 Anti-ischemic
 Chronic Pre-treatment With Beta
Blockers on no-reflow phenomenon
 IV metoprolol
 Coronary vasodilator  Intracoronary nicorandil
 Revascularization
 Shortened door-to-balloon times
 Primary stenting
 Avoidance of high pressure stent
deployment
 Avoid long stents
 Mechanical and Device Therapies
 Embolic Protection Devices
 Thrombectomy before the
intervention
 'MAP strategy'
 Maximum aspiration of athero-
thrombus
 Adjuvant utilization of GP IIb/IIIa
inhibitor
 Prolonged inflation of the
balloon/stent
 Deferred Stenting
 delaying a stent implantation after
mechanical flow restoration,
vasodilators, antithrombotic drugs
(GP IIb/IIIa inhibitors) and statins.
 Ischemic preconditioning
 4 × 5 min inflations/deflations of
cuff on upper arm before
thrombolysis
Coronary slow flow
phenomena
What to do
 In situ thrombus
 Manual catheter aspiration.
 Additional angioplasty and stenting might be necessary.
 Dissection  additional stenting
 Severe spasm
 Intracoronary nitroglycerin (100 mcg/cc) can be given until the vasospasm
is relieved
 Plaque rupture
 Manual catheter aspiration
 Additional angioplasty and stenting might be necessary.
 Distal athero-
thrombo-
embolization.
 Additional anticoagulation with more heparin and/or gp receptor IIB/IIIA
inhibitors should be started.
 Rechecking activated clotting time (act) levels is prudent.
Exclude dissection, thrombus, spasm at lesion site (IVUS, distal contrast
injections, and/or translesion pressure gradient may be useful).
UFH (weight-adjusted i.v. bolus during PCI of 70-100 IU/kg, or 50-70
IU/kg in combination with a GP IIb/IIIa inhibitor; activated clotting time target
range of 250-350 s, or 200-250 s if a GP IIb/IIIa inhibitor is given) is recommended
in patients undergoing PCI ,class I level of evidence A in 2020 ESC Guidelines for
the management of acute coronary syndromes in patients presenting without
persistent ST-segment elevation: (Collet, Thiele et al. 2020).
(Hashemifard 2009) demonstrated when no reflow occurs in the right
coronary artery or inferior distribution, atropine therapy may be necessary to treat
the reflex hypotension and bradycardia that may occur.
Maintain adequate perfusion pressure with intravenous fluids,
vasopressors, inotropes, and IABP if necessary as routine use of IABP in patients
with CS and no mechanical complications due to ACS is not recommended class
III level of evidence B in 2020 ESC Guidelines for the management of acute
coronary syndromes in patients presenting without persistent ST-segment
elevation (Collet, Thiele et al. 2020) . Administer intracoronary nitroglycerin
(100–200 µg up to four doses) to exclude epicardial spasm. Consider
administering a glycoprotein IIb/IIIa receptor inhibitor .
Algorithm for management of no-reflow (Berg and Buhari 2012).
 Medical Therapies
 Adenosine
 Calcium Channel Blockers
 Nitroprusside
 Epinephrine
 Glycoprotein IIB-IIIA Receptor
Antagonists
 Nicorandil
 Ranolazine
 Thrombolytic Therapy
 Intracoronary Propanolol,
Nicorandil, and Diltiazem
 Anisodamine
 Intravenous Dexamethasone
 Non Pharmacological Interventions
 Induced Hypothermia
 Ischemic Post-conditioning
 Intracoronary Transfusion Of Autologus
Blood
 Intracoronary Delivery Of Mitochondria
 Embryonic Haemangioblasts
 Alternative Therapies For Treating No-reflow
 Diagnostic Ultrasound And Microbubbles
Treatment Improves Outcomes Of Coronary No-
reflow In Canine Models By Sonothrombolysis
 Intra-aortic Balloon Pump
 Coronary Artery Bypass Graft Surgery
 Newer Drugs And Prospectives Under Investigation
 Cyclosporine-A
 Glucagon-like Peptide (GLP)-1 Analog
 Bendavia
 Atrial Natriuretic Peptide
 Fx 06
 Pexelizumab
 Eniporide
 Cp-4715
 Imatinib
 Pyrrolidine Dithiocarbamate
 Miscellaneous Drugs
 Monoclonal Antibodies Against Leukocytes
 Complement Receptor Inhibitors
 Adhesion Molecule Antibodies
 Erythropoietin
 Antioxidants
 Endothelin-a Selective Antagonist
 Thromboxane A2 Receptor Antagonist
 Chinese Medicine.
 Danhong Injection
It was defined as persistent TIMI flow grade (TFG) ≤2 despite intracoronary
administration of at least one other pharmacologic intervention. Intracoronary
epinephrine may become an effective alternative in patients suffering refractory no-
reflow following primary PCI, at a dose of at least 100 μg (range, 100–400 μg) given
through the central lumen of an over-the-wire balloon catheter (Aksu, Guler et al. 2015).
Epinephrine causes potent coronary vasodilator effect via β2 receptor activation, in
addition to its chronotropic and inotropic effects on the heart. Thus, it should not be
confusing that intracoronary epinephrine may reveal a beneficial effect on the
prevention of the no-reflow in the patients with STEMI.
(Khuyag, Chimed et al. 2017) demonstrated that in patients with
STEMI who underwent primary PCI for reperfusion, a coronary no-
reflow phenomenon is a strong and independent predictor of 30-day
mortality.
This study is conducted to identify simple clinical factors,
laboratory, angiographic findings and procedural features that
predict no-reflow phenomenon in patients with STEMI who
undergo PCI in cardiovascular medicine department at Mansoura
Specialized Medical Hospital.
We compared the predictor data in subjects with normal reflow
and no reflow after PCI. No reflow phenomenon is diagnosed based
on angiographical evidence of reopening of the occluded coronary
artery with no evidence of flow-limiting residual stenosis (<50%),
dissection, vessel spasm or thrombus burden. Angiographical
documentation of thrombolysis in myocardial infarction (TIMI) flow
grade ≤II. A TIMI flow grade III with a myocardial blush grade 0 or I,
at least 10 min after the end of the PPCI procedure
Enrollment
Assessed for eligibility
(n=444)
Excluded (n=26)
Not meeting inclusion criteria (n= 26)
Studied groups
(n=418)
TIMI flow
No reflow
n=61(14.6%)
(TIMI ≤2)
Reflow
n=357(85.4%)
(TIMI =3)
Mortality
n=18(5%)
Mortality
n=6(9.8%)
total number
n=418
No reflow
)N=61
Reflow
)N=357)
test of
significance
p-value
Age/years
mean±SD
55.88±8.33 54.88±11.61 56.05±7.65 t=1.04 p=0.317
Age/years
<60
≥60
264
154
N (%)
37(60.7)
24(39.3)
N (%)
227(63.6)
130(36.4)
χ2=0.192 p=0.661
Sex
Male
Female
339
79
52(85.2)
9(14.8)
287(80.4)
70(19.6)
χ2=0.801 p=0.371
Total number
=418
No reflow
N=61(%)
Reflow
N=357(%)
test of significance p-value
Hypertension
-VE
+VE
218
200
29(47.5)
32(52.5)
189(52.9)
168(47.1)
χ2=0.609 p=0.489
DM
-ve
+ve
225
193
33(54.1)
28(45.9)
192(53.8)
165(46.2)
χ2=0.002
p=0.963
Smoking
-ve
+ve
291
127
40(65.6)
21(34.4)
251(70.3)
106(29.7)
χ2=0.552 p=0.457
Family history of
IHD
-ve
+ve
346
72
46(75.4)
15(24.6)
300(84.0)
57(16.0)
χ2=2.72 p=0.09
Association Between Medical History And No Reflow Among Studied Cases
Association Between Demographic Characteristics And No Reflow Among Studied Cases.
Total number
No reflow
)N=61
Reflow
)N=357)
Test of
significance
p value
DBP 76.12±8.28 75.90±8.44 76.15±8.26 t=0.152 P=0.828
SBP 123.99±10.39 123.77±10.03 124.03±10.46 t=0.193 P=0.857
Pre-operative HR 76.38±9.91 77.09±11.95 76.26±9.53 t=0.254 P=0.542
Pre-infarction angina 278 29(47.5) 249(69.7) χ2=11.53 p=0.001*
Pre-operative KILLIP
class
1
2
3
4
396
18
3
1
59(96.7)
2(3.3)
0(0.0)
0(0.0)
337(94.4)
16(4.5)
3(0.80)
1(0.30)
MC P=0.828
CHA2DS2-VASc Risk
Criteria
1.56±1.12 2.33±1.01 1.42±1.08 t=6.09 p<0.001*
Association Between No Reflow And Clinical Characteristics Among Studied Cases.
2.33
1.56
0
0.5
1
1.5
2
2.5
3
3.5
4
No reflow Reflow
CHA2DS2-VASc Risk Criteria
Total
number
No reflow
N=61(%)
Reflow
N=357(%)
Test of
significance
P-value
Ticagrelor or Clopidogrel
loading
Ticagrelor
Clopidogrel
23
395
5(8.2)
56(91.8)
18(5.0)
339(95.0) χ2=0.997 P=0.318
Prior statin therapy
-ve
+ve
260
158
35(57.4)
26(42.6)
225(63.0)
132(37.0)
χ2=0.707
p=0.400
Dose & type of prior statin
therapy
Rosuvastatin
Simvastatin
Atorvastatin
N=158
6
27
125
N=26
1(3.8)
3(11.5)
22(84.6)
N=123
5(3.8)
24(18.2)
103(78.0)
MC p=0.712
Drug Use Among Studied Groups
Total number
=418
No reflow
N=61(%)
Reflow
N=357(%)
test of significance p-value
Infarction location
Anterior 290 46(75.4) 244(68.3)
MC P=0.316
Inferior 89 12(19.7) 77(21.6)
Lateral 21 3(4.9) 18(5.0)
other locations 18 0(0.0) 18(5.0)
Presence of pathologic Q
waves in admission ECG
207 44(72.1) 163(45.7) χ2=14.61 p<0.001*
Absence of STR≥50
–VE
+VE
234
184
15(24.6)
46(75.4)
219(61.3)
138(38.7)
χ2=28.56 P<0.001*
Association Between ECG Changes And No Reflow Among Studied Cases.
Total Number
=418
No Reflow
N=61(%)
Reflow
N=357(%)
Test Of
Significance
P-value
EF %
Mean ± Sd
47.29±5.53 45.67±5.02 47.57±5.57 T=2.49 P=0.013*
Association Between Echocardiographic Changes And No Reflow Among Studied Cases
Association Between No Reflow And Initial TIMI Flow, TFC, Myocardial Blush And Collateral Flow Grade Among
Studied Cases
Total
number
=418
No reflow
N=61(%)
Reflow
N=357(%)
test of
significance
p-value
Initial TIMI
flow
0/1
2/3
88
330
30(49.2)
31(50.8)
58(16.2)
299(83.8)
χ2=33.99 P<0.001*
TFC 21.64±8.20 36.41±9.95 19.11±4.27 t=14.58 p<0.001*
Myocardial
blush grade
<2
≥2
61
357
60(98.4)
1(1.6)
1(0.3)
356(99.7)
FET p<0.001*
Collateral
flow grade
<2
≥2
53
365
38(62.3)
23(37.7)
15(4.2)
342(95.8)
χ2=158.803 p<0.001*
Total number
=418
No reflow
)N=61)
Reflow
)N=357)
test of
significance
p-value
Infarction related artery
LAD
RCA
LCX
282
106
30
43(70.5)
12(19.7)
6(9.8)
239(66.9)
94(26.3)
24(6.7)
χ2=1.71 p=0.425
Culprit lesion length 21.40±6.75 27.75±8.49 20.33±5.77 t=18.97 p<0.001*
Vessel diameter 3.13±0.23 3.32±0.26 3.10±0.21 t=12.56 p<0.001*
Thrombus grade
0
1
2
3
4
5
3
9
22
249
108
27
0(0.0)
0(0.0)
1(1.6)
22(36.1)
23(37.7)
15(24.6)
3(0.8)
9(2.5)
21(5.9)
227(63.6)
85(23.8)
12(3.4)
MC p<0.001*
Thrombus grade
Grade 0(Nil)
Low (grade 1/2)
Moderate (grade 3)
High (grade 4/5)
3
31
249
135
0(0.0)
1(1.6)
22(36.1)
38(62.3)
3(0.8)
30(8.4)
227(63.6)
97(27.2)
MC P<0.001*
<4
≥4
283
135
23(37.7)
38(62.3)
260(72.8)
97(27.2)
χ2=29.39 p<0.001*
Syntax score
mean±SD
23.48±3.89 27.46±3.52 22.80±3.54
t=9.51 P<0.001*
Multivessel disease 132 35(57.4) 97(27.2) χ2=22.0 p<0.001*
Lesion type
Eccentric
Concentric
221
197
28(45.9)
33(54.1)
193(54.1)
164(45.9)
χ2=1.39 p=0.238
Type of occlusion
Total
Tappered
Subtotal
Cut off
27
77
174
140
25(40.9)
9(14.8)
5(8.2)
22(36.1)
2(0.6)
68(19.0)
169(47.3)
118(33.1)
MC P<0.001*
Lesion location
Proximal
Ostial
Mid
Distal
199
16
134
69
34(55.7)
2(3.3)
22(36.1)
3(4.9)
165(46.2)
14(3.9)
112(31.4)
66(18.5)
MC p=0.06
Association
Between
No
Reflow
And
Lesion
Characteristics
Among
Studied
Cases.
Total
number
N=418
No reflow
N=61
Reflow
)N=357)
test of
significance
P Value
Direct stenting
no
Yes
137
281
26(42.6)
35(57.4)
111(31.1)
246(68.9)
χ2=3.14 P=0.076
Pre-balloon
dilatation with
stenting
74 18(29.5) 56(15.7) χ2=6.83 p=0.009*
Post-balloon
dilatation
25 12(19.7) 13(3.6) χ2=23.81 p<0.001*
Maximal inflation
pressure of stent
14.93±1.64 16.42±1.99 14.68±1.43 t=2.5 p<0.001*
DES
BMS
414
4
60(98.4)
1(1.6)
354(99.16)
3(0.84)
FET p=0.427
Number of stents
1
2
3
4
350
60
7
1
44(72.1)
12(19.7)
4(6.6)
1(1.6)
306(85.7)
48(13.4)
3(0.8)
0(0.0)
MC p<0.001*
Aspiration
thrombectomy
36 15(24.6) 21(5.9) χ2=23.17 p<0.001*
Use of GP 2b3a
inhibitor
39 37(60.7) 2(0.6) χ2=222.41 p<0.001*
Contrast volume 126.48±50.97 178.03±68.55 117.68±41.45 t=17.81 p<0.001*
Technique Of Reperfusion Among Studied Groups.
Total number
No reflow
)N=61)
Reflow
)N=357)
Test of
significa
nce
p-value
Total ischemic
time (min) from
symptom onset to
ballon crossing in
PPCI
97.29±70.30 135±114.3 88.96±53.32 t=3.46 p=0.001*
Total ischemic
time (min) from
symptom onset to
successfull
reperfusion by
thrombolysis
141.05±103.45 177.86±140.94 129.07±86.73 t=1.55 p=0.126
Total ischemic
time (min) in
rescure PCI
344.38±147.74 368±115.34
333.64±160.8
1
t=0.743 p=0.461
Association Between No Reflow And Total Ischemic Time Results Among Studied Cases
Total
number
n=418
No reflow
N=61(%)
Reflow
N=357(%)
Test of
significance
p value
Primary PCI 178 32(52.5) 146(40.9) χ2=2.85 P=0.09
Pharmacoinvasive with successful
SK
113 9(14.8) 104(29.1) χ2=5.46 p=0.019*
Rescue PCI 48 15(24.6) 33(9.2) χ2=12.07 p=0.001*
Failed SK then early elective PCI 12 1(1.6) 11(3.1) χ2=0.388 P=0.533
Successful SK then early elective
PCI
47 3(4.9) 44(12.3) χ2=0.187 p=0.09
Missed STEMI then early elective
PCI
20 1(1.6) 19(5.3) χ2=0.356 P=0.213
Association Between No Reflow And Methods Of Reperfusion Among Studied
Cases.
Total number
No reflow
N=61
Reflow
N=357
Test of
significan
ce
P-value
Blood glucose level per
PCI(mg/dl)
215.65±90.56 288.72±115.38 160.25±80.85 z=3.68 p<0.001*
Serum urea (mg/dl) 32.79±10.69 32.26±10.92 32.88±10.66 z=0.426 p=0.670
Peak CPK(IU/L) 1077.41±1303.05 1542.86±1537.28 997.89±1243.83 z=2.75 p=0.006*
CKMB(IU/L) 262.18±378.0 439.21±537.22 231.94±335.32 z=3.26 p=0.001*
LDH(U/L) 573.38±686.39 489.43±666.46 587.73±689.62 z=1.67 p=0.095
Serum creatinine (mg/dl) 1.02±0.22 1.02±0.24 1.01±0.24 t=0.41 p=0.681
AST( u/l) 84.05±106.78 98.09±133.27 81.65±101.59 z=0.549 p=0.583
ALT( u/l) 43.41±50.23 50.40±78.14 42.23±43.89 z=0.466 p=0.641
RDW % 13.77±0.54 13.74±0.58 13.79±0.54 t=0.54 p=0.587
HB(gm/dl) 11.94±1.22 12.18±1.28 11.90±1.21 t=1.31 p=0.191
TLC/mm3 8227.7±4077.66 8670.17±3336.32 8153.35±4188.84 z=0.709 p=0.478
MPV(fl) 7.78±0.44 7.80±0.48 7.77±0.43 t=0.564 p=0.573
PDW(fl) 13.71±0.55 13.86±0.58 13.69±0.54 t=2.37 p=0.018*
PLT*1000 494.78±5086.02 205.57±46.52 543.39±5496.41 z=0.757 p=0.449
Serum uric acid(mg/dl) 5.88±1.55 6.05±1.78 5.86±1.52 t=0.748 p=0.455
Cholesterol(mg/dl) 189.68±55.199 194.80±56.89 188.82±54.94 t=0.815 p=0.416
TGS (mg/dl) 170.46±97.79 194.07±147.85 166.49±85.87 z=0.138 p=0.890
LDL (mg/dl) 104.33±51.49 115.0±85.53 102.54±43.17 z=0.453 p=0.650
HDL(mg/dl) 93.63±38.64 96.65±33.61 93.13±39.44 z=0.972 p=0.331
Serum bilirubin levels
prePCI(mg/dl)
1.09±0.18 1.146±0.21 1.092±0.175 t=2.16 p=0.03*
Laboratory Results Among Studied Groups.
MACE N=418
No reflow
)N=61)
Reflow
)N=357)
test of significance
recurrent chest pain 93 21(34.4) 72(20.2) P=0.013*
re-infarction 43 18(29.5) 25(7.0) P<0.001*
ventricular arrythmia 51 10(16.4) 41(11.5) p=0.236
heart failure 34 9(14.8) 25(7.0) p=0.04*
all cause mortality 25 8(13.1) 17(4.8) p=0.01*
MACE Distribution Within 180 Days Among Studied Groups.
ROC Curve of significant predictors of no-
reflow with cut off point less than, indicate
positive results.
ROC Curve of significant predictors of no-
reflow with cut off point greater than, indicate
positive results.
Test Result Variable(s) AUC P
Asymptotic 95% Confidence
Interval Cut off
point
Sensitivity
(%)
Specificity
(%)
Lower Bound Upper Bound
age/years
0.530 0.460 0.443 0.616 60.5 70.0 26.3
total ischemic time (min) from
symptom onset to ballon
crossing in PPCI. 0.609 0.054 0.495 0.723 150 91.0 39.1
CKMB (IU/L) 0.607 0.059 0.492 0.722 237.5 74.5 46.9
PDW(fl) 0.539 0.495 0.429 0.648 14.05 70.3 40.6
Syntax score 0.870 <.001* 0.792 0.948 27.50 85.5 81.2
Culprit lesion length 0.790 <0.001* 0.695 0.886 24.5 86.1 61.3
TFC 0.916 <0.001* 0.852 0.981 25.5 90.3 80.6
Contrast volume 0.812 <0.001* 0.717 0.907 205.0 95.8 51.6
EF% 0.601 <0.001* 0.524 0.679 46.5 63.3 51.5
Thrombus grade 0.741 <0.001* 0.635 0.846 4 72.4 69.4
Maximal inflation pressure of
stent
0.736 <0.001* 0.630 0.841 15.0 72.4 69.4
CHA2DS2-VASc Risk Criteria
0.761 <0.001* 0.672 0.850 2 86.2 51.2
Validity Of Significant Indices In Differentiating Cases With No Reflow
Predictors β p
Odds ratio
(95% CI)
EF % -0.071 0.013* 0.931(0.881-0.985)
Blood glucose level per PCI 0.001 0.147 1.00(1.00-1.002)
Initial time flow -2.70 0.116 0.067(0.002-1.95)
Myocardial blush grade -5.06 <0.001* 0.006(0.001-0.077)
Collateral flow grade -2.35 0.014* 0.05(0.014-0.625)
Culprit lesion length 0.095 0.007* 1.09(1.026-1.178)
Vessel diameter 1.64 0.118 5.13(0.659-39.96)
Contrast volume 0.01 0.02* 1.01(1.002-1.02)
TFC 0.245 <0.001* 1.278(1.189-1.374)
Aspiration thrombectomy 1.65 <0.001* 5.19(2.32-11.65)
Thrombus grade ≥ 4 1.19 <0.001* 3.29(2.18-4.98)
Number of stents 0.653 0.03* 1.92(1.07-3.45)
Type of occlusion 1.05 0.06 1.0(0.89-4.2)
Total ischemic time (min) from
symptom onset to ballon crossing in PCI
0.519 0.002* 1.68(1.21-2.33)
Pharmacoinvasive with successful SK -2.09 0.047* 0.25(0.03-0.98)
Rescue PCI 1.76 0.223 5.82(0.343-98.57)
Pre-infarction angina 0.902 0.06 2.46(0.99-4.29)
Maximal inflation pressure of stent 0.335 0.009* 1.39(1.09-1.79)
Use of GP 2b3a inhibitor 5.67 <0.001* 29.98(20-44.89)
Syntax score 0.357 <0.001* 1.43(1.24-1.65)
Multivessel disease 1.56 0.002* 4.78(1.78-12.79)
CHA2DS2-VASc Risk Criteria 0.722 <0.001* 2.05(1.51-2.81
Pre-ballon dilatation with stenting 0.835 0.037* 2.30(1.05-5.05)
Post-ballon dilatation 1.426 0.006* 4.16(1.49-11.56)
Overall percent predicted=88.0%
Predictors for no reflow among studied cases.
In the present study; clinical, angiographic and laboratory predictive factors have
been recognized and correlated with presence of no reflow phenomenon with overall
percent predicted=88.0%.
Currently there are many lines to manage no reflow. Such patients warrant urgent
supportive measures to save life. Many lines of treatment are available depending
upon the underlying mechanism/s and the choice of interventional cardiologist.
Unfortunately, no reflow may prove resistant to pharmacological therapy in 5–10%
cases with adverse short term and long-term outcomes. A personalized attention to
tide over the crisis in cath lab is required for patient to prevent and promptly treat the
no-reflow phenomenon.
• Based on the present study, there are clinical, angiographic and laboratory
predictive factors associated with presence of no reflow phenomenon with
overall percent predicted=88.0%.
• Prevention is always better than treatment and no-reflow phenomenon should
be predicted and successfully treated to improve myocardial salvage and
improve outcomes.
• Angiographic examinations were performed by different clinicians and it is likely
that studies were performed with different sized catheters and angiographic
projections.
• In our study, we didn’t use ivus to identify atherosclerotic changes of coronaries.
• We have not analysed the microvascular function and no-reflow using myocardial
contrast echocardiography ,CMR or nuclear scintigraphy.
• A relatively small sample size, additional analysis of clinical, laboratory,
angiographic predictors of no-reflow phenomenon may be considered by
examing more cases.
432
: 26-01-2020
: 56 years old
Smoker, HTN
Typical anginal pain (CCS III)
: Lateral STEMI
: Standard Right Radial approach using XB3.5.
(LCX): Atherosclerotic Vessel showing
proximal subtotal atheroma 80 % stenosis with good distal flow.
: XB 3.5
PT 2 LS wire
NC TREK (4.00*15mm)
Resolute Integrity (4.00*18mm)
352
: 20-7-2019
: 55 years old
HTN,DM
Dyspnea and retrosternal chest pain (stuttering
course) during the previous week, becoming persistent and of
increased intensity on the morning of july 20 2019.
: Anterior STEMI
: Standard Right femoral approach using XB4.
LAD: atherosclerotic, sub- totally occluded at
its mid segment.
: XB 4
ASAHI soft floppy wire
NC Sprinter (3.50x15mm), NC Sprinter (3.75x21mm)
PROMUS (3.00*28mm)
351
: 19-7-2019
: 60 years old
HTN,DM,smoker
Acute severe burning retrosternal chest pain
Patient sought medical advice.
: Standard Right femoral approach using XB4.
LAD: Atherosclerotic Vessel showing
proximal and distal stenosis
: XB 4
PT 2 MS wire
Promus (3*38mm), Promus (2.5*38mm)
407
: 01-11-2019
: 64 years old
HTN,DM,smoker and upon solicitation of a more detailed
history, it became apparent that his father had suffered from an acute
myocardial infarction at the age of 50.
He describes the pain as a substernal heavy pressure
that radiates to his left arm, associated with diaphoresis, nausea, and
tingling in his fingers. His pain was minimally relieved with sublingual
nitroglycerin tablets.
: Standard Right radial approach using JL,JR 3.5.
LAD: Atherosclerotic Vessel with proximal to
midsegment subtotal significant lesion .
: XB3.5
ASAHI soft .
Resolute 2.5*22- 3*38
: PTCA 2*15
438
: 02-17-2020
: 65 years old
HTN
Acute typical chest pain from 4hours
before admission. she felt dyspnea and diaphoretic
• Patient sought medical advice .
: Standard Right femoral approach using JR 3.5.
LAD
• : XB 3.5
PT 2 LS.
Resolute (2.75*30 mm) and others
: MiniTREK (2*12) and others
No-reflow phenomenon
No-reflow phenomenon
No-reflow phenomenon
No-reflow phenomenon

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No-reflow phenomenon

  • 1.
  • 2. INTRODUCTION IMPORTANCE DEFINITION HISTORICAL BACKGROUND INCIDENCE TYPES OF NO REFLOW ASSESSMENT AND PREDICTION OF CORONARY NO-REFLOW PHENOMENON CLINICAL PREDICTORS OF NO-REFLOW PHENOMENON ANGIOGRAPHIC PREDICTORS OF NOREFLOW PHENOMENON BIOCHEMICAL MARKERS PREDICTING NOREFLOW PHENOMENON IMAGING MODALITIES TO ASSESS AND PREDICT NOREFLOW PHENOMENON SCORING SYSTEMS PROPHYLAXSIS INITIAL EVALUATION ON CATHETER LABORATORY DIFFERENTIAL DIAGNOSIS OF CORONARY SLOW FLOW PHENOMENA TREATMENT REFRACTORY NO-REFLOW PROGNOSIS AIM OF STUDY STUDY DESIGN INCIDENCE OF NOREFLOW IN OUR STUDY CONCLUSIONS RECOMMENDATION STUDY LIMITATIONS NO-REFLOW CASE PRESENTATION
  • 3. • The key of acute STEMI treatment is to quickly restore the IRA perfusion, resulting in the slogan ‘Time is the Myocardium, Time is Life’. As the body has a complex regulatory mechanism, where, on the one hand, the necrotic myocardium cannot be restored, and on the other hand, it is accompanied with reperfusion injuries and even the no-reflow phenomenon, the occurrence and development of the no- reflow phenomenon contain reperfusion injuries
  • 4. • No-reflow phenomenon is a common and severe complication of patients with acute myocardial infarction AMI after direct PCI. As its occurrence hinders the effective myocardial reperfusion, it has become an independent predicative indicator for short-term prognosis as well as long-term heart failure, arrhythmia, sudden cardiac death and other cardiac events
  • 5. • No-reflow phenomenon is characterized by the failure of myocardial reperfusion despite the absence of mechanical coronary obstruction (Rossington, Sol et al. 2020). (Ito, Tomooka et al. 1992) first described the phenomenon of ‘no reflow’ in humans with acute myocardial infarction, whereby perfusion is not re-established despite patency of the epicardial coronary artery.
  • 6. Prediction of patients at risk for no-reflow before PCI may be beneficial from the perspective of prevention. Risk awareness will lead to the use of certain techniques that may ameliorate the degree of no-reflow No reflow (NR) defined as final thrombolysis in myocardial infarction (TIMI) flow <III or TIMI III flow with TIMI myocardial blush grade (TMBG) 0 or 1 in absence of mechanical obstruction. TIMI flow grade is the easiest and most commonly used method of evaluating success of PCI in the setting of STEMI
  • 7. • The TIMI grade flow is classified as follows: TIMI-0 indicates there is no antegrade flow beyond the point of occlusion, TIMI-1 indicates there is a faint antegrade coronary flow beyond the occlusion with an incomplete filling of the distal coronary bed, TIMI-2 indicates there is delayed or sluggish antegrade flow with complete filling of the distal territory, and TIMI-3 indicates normal flow with complete filling of the distal territory (Avci, Yildirim et al. 2018). TIMI Blood Flow Grades
  • 8. • In primary angioplasty, myocardial blush grade independently predicts long-term mortality, TIMI flow, and LV function. TIMI frame counts and myocardial blush are more reproducible and more accurate than TIMI flow grades. A combination of TIMI flow and TIMI myocardial perfusion grade before and after PCI has been described (Angiographic Perfusion Score) as a single myocardial perfusion grade Myocardial Blush
  • 9. Angiographic assessment of myocardial perfusion: TIMI myocardial perfusion (TMP) grading system. Permission reproduced from (Appleby, ANGEJA et al. 2001), BMJ Publishing Group Ltd.
  • 10.
  • 11. • The first clinical observation of coronary no-reflow was reported by Schofer et al.in 1985. • In 1989, Wilson et al. observed persistent angina with ST elevation in association with a slow angiographic antegrade flow despite a widely patent angioplasty site in five patients immediately after PTCA of a thrombus containing lesion. • In 1991,Pomerantz et al. reported five more cases of noreflow successfully treated by intracoronary verapamil. • the first clinical case of no-reflow during PTCA for acute myocardial infarction was reported by Feld et al. in 1992
  • 12. Reflow is an under-reported complication. A low incidence of 1–3% has been recorded in large registries based on TIMI flow grade, myocardial blush grade and ST resolution. Modern more sensitive methods of assessing no reflow and microcirculatory dysfunction include myocardial contrast echocardiography (MCE) and cardiac magnetic resonance imaging (CMRI), which have recorded a higher incidence (10– 30%) (Gupta and Gupta 2016).
  • 13. NR has a multifactorial aetiology and broadly can be defined by four distinct groups: I. Distal atherothrombotic embolisation II. Ischaemic injury III. Reperfusion injury IV. Susceptibility of coronary micro-circulation to injury. Distal embolization is a result of debris (thrombi, endothelial cells and lipid matrix) migrating downstream from the primary lesion, leading to microvascular obstruction and further injury
  • 14. Sustained Result of anatomical irreversible changes of coronary microcirculation Undergo unfavorable LV remodeling Reversible Result of functional & thus reversible changes of microcirculation Maintain their left ventricle volumes unchanged over time
  • 15.  TIMI Blood Flow Grades  The Corrected TIMI Frame Count (CTFC)  Myocardial Blush
  • 16. Clinical predictors  Age  Family history of CAD  Pre infarction angina  Heart rate  Killip class  Delayed reperfusion  Low preoperative systolic blood pressure  Smoking  Atrial fibrillation  Shock index  CHA2DS2–VASc score  Psychological distress  Sex hormones
  • 17. Angiographic Predictors  TIMI blood flow grades  The corrected TIMI frame count (CTFC)  Myocardial blush  Lesion length and reference lumen diameter  Thrombus burden  Coronary artery ectasia  Culprit artery  Syntax score  Stent overexpansion  Saphenous vein coronary bypass grafts  Collateral Flow Grade  Chronic Total Occlusion  Bifurcation lesions Angiographic predictors  Air embolism  Contrast agent  Iatrogenic Dissection of the Left Main Coronary Artery  Treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter  Plaque prolapse  Lesion Morphology  OCT  Rotational atherectomy  orbital atherectomy  Intravascular lithotripsy.
  • 18. Biomarkers  Cardiac biomarkers  The blood glucose level  Serum uric acid  CBC Parameters a) hemoglobin level b) RDW levels c) Polycythemia vera d) Platelet Indices e) Leukocyte Indices f) The neutrophil lymphocyte ratio  Hs-CRP  LDH  D-dimer Biomarkers  Dyslipidemia  Serum B-type natriuretic peptide  Renal impairment  Serum bilirubin levels  Fibrinogen  Cystatin C  Plasma myeloperoxidase levels  Microalbuminuria  Serum endocan levels  Clot permeability  Soluble CD40b ligand level  Angiopoietin-Like 4 Serum Levels  MicroRNAs
  • 19. Imaging Modalities Predictors  Myocardial contrast echocardiography  Left Ventricular Ejection Fraction  EAS index  Speckle-tracking echocardiography  Magnetic resonance imaging  Cardiac computed tomography (CCT)  Nuclear magnetic imaging Electrocardiographic predictors  higher Q/R in admission ECG
  • 20. Scoring Systems (Bakr, Roshdy et al. 2017) suggested a weighted scoring system , to predict the development of no reflow phenomenon during primary percutaneous coronary intervention in patients with acute myocardial infarction. An 8 variable scoring system was constructed as follows age above 60 years old 1 point, delayed reperfusion time more than 4hrs 2 points, large luminal diameter ≥2.8 mm 2 points, long target lesion ≥20 mm 4 points, high thrombus burden 1 point, initial TIMI flow ≤ 1 is 3 points, positive Ck-Mb on admission 2 points and elevated D- dimer ≥ 500 ng/ml 1 point, with final total score 16 points. scoring 10 points or more are most likely to have no reflow phenomenon, test sensitivity was 86% and specificity was 73%.
  • 21. Strategies For Prevention How To Apply  Aggressive lifestyle modification  Cessation of smoking  Exercise regularly  Avoid stress  Control blood pressure  BB ,ACEI ,CCB  Strict control of blood sugar  Oral hypoglycemic or insulin  Treatment of dyslipidemia  Intensive statin therapy  Preoperative loading of antiplatelet  Ticagrelor loading  Anti-ischemic  Chronic Pre-treatment With Beta Blockers on no-reflow phenomenon  IV metoprolol
  • 22.  Coronary vasodilator  Intracoronary nicorandil  Revascularization  Shortened door-to-balloon times  Primary stenting  Avoidance of high pressure stent deployment  Avoid long stents  Mechanical and Device Therapies  Embolic Protection Devices  Thrombectomy before the intervention  'MAP strategy'  Maximum aspiration of athero- thrombus  Adjuvant utilization of GP IIb/IIIa inhibitor  Prolonged inflation of the balloon/stent  Deferred Stenting  delaying a stent implantation after mechanical flow restoration, vasodilators, antithrombotic drugs (GP IIb/IIIa inhibitors) and statins.  Ischemic preconditioning  4 × 5 min inflations/deflations of cuff on upper arm before thrombolysis
  • 23. Coronary slow flow phenomena What to do  In situ thrombus  Manual catheter aspiration.  Additional angioplasty and stenting might be necessary.  Dissection  additional stenting  Severe spasm  Intracoronary nitroglycerin (100 mcg/cc) can be given until the vasospasm is relieved  Plaque rupture  Manual catheter aspiration  Additional angioplasty and stenting might be necessary.  Distal athero- thrombo- embolization.  Additional anticoagulation with more heparin and/or gp receptor IIB/IIIA inhibitors should be started.  Rechecking activated clotting time (act) levels is prudent.
  • 24.
  • 25. Exclude dissection, thrombus, spasm at lesion site (IVUS, distal contrast injections, and/or translesion pressure gradient may be useful). UFH (weight-adjusted i.v. bolus during PCI of 70-100 IU/kg, or 50-70 IU/kg in combination with a GP IIb/IIIa inhibitor; activated clotting time target range of 250-350 s, or 200-250 s if a GP IIb/IIIa inhibitor is given) is recommended in patients undergoing PCI ,class I level of evidence A in 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: (Collet, Thiele et al. 2020).
  • 26. (Hashemifard 2009) demonstrated when no reflow occurs in the right coronary artery or inferior distribution, atropine therapy may be necessary to treat the reflex hypotension and bradycardia that may occur. Maintain adequate perfusion pressure with intravenous fluids, vasopressors, inotropes, and IABP if necessary as routine use of IABP in patients with CS and no mechanical complications due to ACS is not recommended class III level of evidence B in 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation (Collet, Thiele et al. 2020) . Administer intracoronary nitroglycerin (100–200 µg up to four doses) to exclude epicardial spasm. Consider administering a glycoprotein IIb/IIIa receptor inhibitor .
  • 27. Algorithm for management of no-reflow (Berg and Buhari 2012).
  • 28.  Medical Therapies  Adenosine  Calcium Channel Blockers  Nitroprusside  Epinephrine  Glycoprotein IIB-IIIA Receptor Antagonists  Nicorandil  Ranolazine  Thrombolytic Therapy  Intracoronary Propanolol, Nicorandil, and Diltiazem  Anisodamine  Intravenous Dexamethasone
  • 29.  Non Pharmacological Interventions  Induced Hypothermia  Ischemic Post-conditioning  Intracoronary Transfusion Of Autologus Blood  Intracoronary Delivery Of Mitochondria  Embryonic Haemangioblasts
  • 30.  Alternative Therapies For Treating No-reflow  Diagnostic Ultrasound And Microbubbles Treatment Improves Outcomes Of Coronary No- reflow In Canine Models By Sonothrombolysis  Intra-aortic Balloon Pump  Coronary Artery Bypass Graft Surgery
  • 31.  Newer Drugs And Prospectives Under Investigation  Cyclosporine-A  Glucagon-like Peptide (GLP)-1 Analog  Bendavia  Atrial Natriuretic Peptide  Fx 06  Pexelizumab  Eniporide  Cp-4715  Imatinib  Pyrrolidine Dithiocarbamate
  • 32.  Miscellaneous Drugs  Monoclonal Antibodies Against Leukocytes  Complement Receptor Inhibitors  Adhesion Molecule Antibodies  Erythropoietin  Antioxidants  Endothelin-a Selective Antagonist  Thromboxane A2 Receptor Antagonist  Chinese Medicine.  Danhong Injection
  • 33. It was defined as persistent TIMI flow grade (TFG) ≤2 despite intracoronary administration of at least one other pharmacologic intervention. Intracoronary epinephrine may become an effective alternative in patients suffering refractory no- reflow following primary PCI, at a dose of at least 100 μg (range, 100–400 μg) given through the central lumen of an over-the-wire balloon catheter (Aksu, Guler et al. 2015). Epinephrine causes potent coronary vasodilator effect via β2 receptor activation, in addition to its chronotropic and inotropic effects on the heart. Thus, it should not be confusing that intracoronary epinephrine may reveal a beneficial effect on the prevention of the no-reflow in the patients with STEMI.
  • 34. (Khuyag, Chimed et al. 2017) demonstrated that in patients with STEMI who underwent primary PCI for reperfusion, a coronary no- reflow phenomenon is a strong and independent predictor of 30-day mortality.
  • 35. This study is conducted to identify simple clinical factors, laboratory, angiographic findings and procedural features that predict no-reflow phenomenon in patients with STEMI who undergo PCI in cardiovascular medicine department at Mansoura Specialized Medical Hospital.
  • 36. We compared the predictor data in subjects with normal reflow and no reflow after PCI. No reflow phenomenon is diagnosed based on angiographical evidence of reopening of the occluded coronary artery with no evidence of flow-limiting residual stenosis (<50%), dissection, vessel spasm or thrombus burden. Angiographical documentation of thrombolysis in myocardial infarction (TIMI) flow grade ≤II. A TIMI flow grade III with a myocardial blush grade 0 or I, at least 10 min after the end of the PPCI procedure
  • 37. Enrollment Assessed for eligibility (n=444) Excluded (n=26) Not meeting inclusion criteria (n= 26) Studied groups (n=418) TIMI flow No reflow n=61(14.6%) (TIMI ≤2) Reflow n=357(85.4%) (TIMI =3) Mortality n=18(5%) Mortality n=6(9.8%)
  • 38. total number n=418 No reflow )N=61 Reflow )N=357) test of significance p-value Age/years mean±SD 55.88±8.33 54.88±11.61 56.05±7.65 t=1.04 p=0.317 Age/years <60 ≥60 264 154 N (%) 37(60.7) 24(39.3) N (%) 227(63.6) 130(36.4) χ2=0.192 p=0.661 Sex Male Female 339 79 52(85.2) 9(14.8) 287(80.4) 70(19.6) χ2=0.801 p=0.371 Total number =418 No reflow N=61(%) Reflow N=357(%) test of significance p-value Hypertension -VE +VE 218 200 29(47.5) 32(52.5) 189(52.9) 168(47.1) χ2=0.609 p=0.489 DM -ve +ve 225 193 33(54.1) 28(45.9) 192(53.8) 165(46.2) χ2=0.002 p=0.963 Smoking -ve +ve 291 127 40(65.6) 21(34.4) 251(70.3) 106(29.7) χ2=0.552 p=0.457 Family history of IHD -ve +ve 346 72 46(75.4) 15(24.6) 300(84.0) 57(16.0) χ2=2.72 p=0.09 Association Between Medical History And No Reflow Among Studied Cases Association Between Demographic Characteristics And No Reflow Among Studied Cases.
  • 39. Total number No reflow )N=61 Reflow )N=357) Test of significance p value DBP 76.12±8.28 75.90±8.44 76.15±8.26 t=0.152 P=0.828 SBP 123.99±10.39 123.77±10.03 124.03±10.46 t=0.193 P=0.857 Pre-operative HR 76.38±9.91 77.09±11.95 76.26±9.53 t=0.254 P=0.542 Pre-infarction angina 278 29(47.5) 249(69.7) χ2=11.53 p=0.001* Pre-operative KILLIP class 1 2 3 4 396 18 3 1 59(96.7) 2(3.3) 0(0.0) 0(0.0) 337(94.4) 16(4.5) 3(0.80) 1(0.30) MC P=0.828 CHA2DS2-VASc Risk Criteria 1.56±1.12 2.33±1.01 1.42±1.08 t=6.09 p<0.001* Association Between No Reflow And Clinical Characteristics Among Studied Cases.
  • 41. Total number No reflow N=61(%) Reflow N=357(%) Test of significance P-value Ticagrelor or Clopidogrel loading Ticagrelor Clopidogrel 23 395 5(8.2) 56(91.8) 18(5.0) 339(95.0) χ2=0.997 P=0.318 Prior statin therapy -ve +ve 260 158 35(57.4) 26(42.6) 225(63.0) 132(37.0) χ2=0.707 p=0.400 Dose & type of prior statin therapy Rosuvastatin Simvastatin Atorvastatin N=158 6 27 125 N=26 1(3.8) 3(11.5) 22(84.6) N=123 5(3.8) 24(18.2) 103(78.0) MC p=0.712 Drug Use Among Studied Groups
  • 42. Total number =418 No reflow N=61(%) Reflow N=357(%) test of significance p-value Infarction location Anterior 290 46(75.4) 244(68.3) MC P=0.316 Inferior 89 12(19.7) 77(21.6) Lateral 21 3(4.9) 18(5.0) other locations 18 0(0.0) 18(5.0) Presence of pathologic Q waves in admission ECG 207 44(72.1) 163(45.7) χ2=14.61 p<0.001* Absence of STR≥50 –VE +VE 234 184 15(24.6) 46(75.4) 219(61.3) 138(38.7) χ2=28.56 P<0.001* Association Between ECG Changes And No Reflow Among Studied Cases.
  • 43. Total Number =418 No Reflow N=61(%) Reflow N=357(%) Test Of Significance P-value EF % Mean ± Sd 47.29±5.53 45.67±5.02 47.57±5.57 T=2.49 P=0.013* Association Between Echocardiographic Changes And No Reflow Among Studied Cases
  • 44. Association Between No Reflow And Initial TIMI Flow, TFC, Myocardial Blush And Collateral Flow Grade Among Studied Cases Total number =418 No reflow N=61(%) Reflow N=357(%) test of significance p-value Initial TIMI flow 0/1 2/3 88 330 30(49.2) 31(50.8) 58(16.2) 299(83.8) χ2=33.99 P<0.001* TFC 21.64±8.20 36.41±9.95 19.11±4.27 t=14.58 p<0.001* Myocardial blush grade <2 ≥2 61 357 60(98.4) 1(1.6) 1(0.3) 356(99.7) FET p<0.001* Collateral flow grade <2 ≥2 53 365 38(62.3) 23(37.7) 15(4.2) 342(95.8) χ2=158.803 p<0.001*
  • 45. Total number =418 No reflow )N=61) Reflow )N=357) test of significance p-value Infarction related artery LAD RCA LCX 282 106 30 43(70.5) 12(19.7) 6(9.8) 239(66.9) 94(26.3) 24(6.7) χ2=1.71 p=0.425 Culprit lesion length 21.40±6.75 27.75±8.49 20.33±5.77 t=18.97 p<0.001* Vessel diameter 3.13±0.23 3.32±0.26 3.10±0.21 t=12.56 p<0.001* Thrombus grade 0 1 2 3 4 5 3 9 22 249 108 27 0(0.0) 0(0.0) 1(1.6) 22(36.1) 23(37.7) 15(24.6) 3(0.8) 9(2.5) 21(5.9) 227(63.6) 85(23.8) 12(3.4) MC p<0.001* Thrombus grade Grade 0(Nil) Low (grade 1/2) Moderate (grade 3) High (grade 4/5) 3 31 249 135 0(0.0) 1(1.6) 22(36.1) 38(62.3) 3(0.8) 30(8.4) 227(63.6) 97(27.2) MC P<0.001* <4 ≥4 283 135 23(37.7) 38(62.3) 260(72.8) 97(27.2) χ2=29.39 p<0.001* Syntax score mean±SD 23.48±3.89 27.46±3.52 22.80±3.54 t=9.51 P<0.001* Multivessel disease 132 35(57.4) 97(27.2) χ2=22.0 p<0.001* Lesion type Eccentric Concentric 221 197 28(45.9) 33(54.1) 193(54.1) 164(45.9) χ2=1.39 p=0.238 Type of occlusion Total Tappered Subtotal Cut off 27 77 174 140 25(40.9) 9(14.8) 5(8.2) 22(36.1) 2(0.6) 68(19.0) 169(47.3) 118(33.1) MC P<0.001* Lesion location Proximal Ostial Mid Distal 199 16 134 69 34(55.7) 2(3.3) 22(36.1) 3(4.9) 165(46.2) 14(3.9) 112(31.4) 66(18.5) MC p=0.06 Association Between No Reflow And Lesion Characteristics Among Studied Cases.
  • 46.
  • 47. Total number N=418 No reflow N=61 Reflow )N=357) test of significance P Value Direct stenting no Yes 137 281 26(42.6) 35(57.4) 111(31.1) 246(68.9) χ2=3.14 P=0.076 Pre-balloon dilatation with stenting 74 18(29.5) 56(15.7) χ2=6.83 p=0.009* Post-balloon dilatation 25 12(19.7) 13(3.6) χ2=23.81 p<0.001* Maximal inflation pressure of stent 14.93±1.64 16.42±1.99 14.68±1.43 t=2.5 p<0.001* DES BMS 414 4 60(98.4) 1(1.6) 354(99.16) 3(0.84) FET p=0.427 Number of stents 1 2 3 4 350 60 7 1 44(72.1) 12(19.7) 4(6.6) 1(1.6) 306(85.7) 48(13.4) 3(0.8) 0(0.0) MC p<0.001* Aspiration thrombectomy 36 15(24.6) 21(5.9) χ2=23.17 p<0.001* Use of GP 2b3a inhibitor 39 37(60.7) 2(0.6) χ2=222.41 p<0.001* Contrast volume 126.48±50.97 178.03±68.55 117.68±41.45 t=17.81 p<0.001* Technique Of Reperfusion Among Studied Groups.
  • 48. Total number No reflow )N=61) Reflow )N=357) Test of significa nce p-value Total ischemic time (min) from symptom onset to ballon crossing in PPCI 97.29±70.30 135±114.3 88.96±53.32 t=3.46 p=0.001* Total ischemic time (min) from symptom onset to successfull reperfusion by thrombolysis 141.05±103.45 177.86±140.94 129.07±86.73 t=1.55 p=0.126 Total ischemic time (min) in rescure PCI 344.38±147.74 368±115.34 333.64±160.8 1 t=0.743 p=0.461 Association Between No Reflow And Total Ischemic Time Results Among Studied Cases
  • 49. Total number n=418 No reflow N=61(%) Reflow N=357(%) Test of significance p value Primary PCI 178 32(52.5) 146(40.9) χ2=2.85 P=0.09 Pharmacoinvasive with successful SK 113 9(14.8) 104(29.1) χ2=5.46 p=0.019* Rescue PCI 48 15(24.6) 33(9.2) χ2=12.07 p=0.001* Failed SK then early elective PCI 12 1(1.6) 11(3.1) χ2=0.388 P=0.533 Successful SK then early elective PCI 47 3(4.9) 44(12.3) χ2=0.187 p=0.09 Missed STEMI then early elective PCI 20 1(1.6) 19(5.3) χ2=0.356 P=0.213 Association Between No Reflow And Methods Of Reperfusion Among Studied Cases.
  • 50. Total number No reflow N=61 Reflow N=357 Test of significan ce P-value Blood glucose level per PCI(mg/dl) 215.65±90.56 288.72±115.38 160.25±80.85 z=3.68 p<0.001* Serum urea (mg/dl) 32.79±10.69 32.26±10.92 32.88±10.66 z=0.426 p=0.670 Peak CPK(IU/L) 1077.41±1303.05 1542.86±1537.28 997.89±1243.83 z=2.75 p=0.006* CKMB(IU/L) 262.18±378.0 439.21±537.22 231.94±335.32 z=3.26 p=0.001* LDH(U/L) 573.38±686.39 489.43±666.46 587.73±689.62 z=1.67 p=0.095 Serum creatinine (mg/dl) 1.02±0.22 1.02±0.24 1.01±0.24 t=0.41 p=0.681 AST( u/l) 84.05±106.78 98.09±133.27 81.65±101.59 z=0.549 p=0.583 ALT( u/l) 43.41±50.23 50.40±78.14 42.23±43.89 z=0.466 p=0.641 RDW % 13.77±0.54 13.74±0.58 13.79±0.54 t=0.54 p=0.587 HB(gm/dl) 11.94±1.22 12.18±1.28 11.90±1.21 t=1.31 p=0.191 TLC/mm3 8227.7±4077.66 8670.17±3336.32 8153.35±4188.84 z=0.709 p=0.478 MPV(fl) 7.78±0.44 7.80±0.48 7.77±0.43 t=0.564 p=0.573 PDW(fl) 13.71±0.55 13.86±0.58 13.69±0.54 t=2.37 p=0.018* PLT*1000 494.78±5086.02 205.57±46.52 543.39±5496.41 z=0.757 p=0.449 Serum uric acid(mg/dl) 5.88±1.55 6.05±1.78 5.86±1.52 t=0.748 p=0.455 Cholesterol(mg/dl) 189.68±55.199 194.80±56.89 188.82±54.94 t=0.815 p=0.416 TGS (mg/dl) 170.46±97.79 194.07±147.85 166.49±85.87 z=0.138 p=0.890 LDL (mg/dl) 104.33±51.49 115.0±85.53 102.54±43.17 z=0.453 p=0.650 HDL(mg/dl) 93.63±38.64 96.65±33.61 93.13±39.44 z=0.972 p=0.331 Serum bilirubin levels prePCI(mg/dl) 1.09±0.18 1.146±0.21 1.092±0.175 t=2.16 p=0.03* Laboratory Results Among Studied Groups.
  • 51.
  • 52. MACE N=418 No reflow )N=61) Reflow )N=357) test of significance recurrent chest pain 93 21(34.4) 72(20.2) P=0.013* re-infarction 43 18(29.5) 25(7.0) P<0.001* ventricular arrythmia 51 10(16.4) 41(11.5) p=0.236 heart failure 34 9(14.8) 25(7.0) p=0.04* all cause mortality 25 8(13.1) 17(4.8) p=0.01* MACE Distribution Within 180 Days Among Studied Groups.
  • 53. ROC Curve of significant predictors of no- reflow with cut off point less than, indicate positive results. ROC Curve of significant predictors of no- reflow with cut off point greater than, indicate positive results.
  • 54. Test Result Variable(s) AUC P Asymptotic 95% Confidence Interval Cut off point Sensitivity (%) Specificity (%) Lower Bound Upper Bound age/years 0.530 0.460 0.443 0.616 60.5 70.0 26.3 total ischemic time (min) from symptom onset to ballon crossing in PPCI. 0.609 0.054 0.495 0.723 150 91.0 39.1 CKMB (IU/L) 0.607 0.059 0.492 0.722 237.5 74.5 46.9 PDW(fl) 0.539 0.495 0.429 0.648 14.05 70.3 40.6 Syntax score 0.870 <.001* 0.792 0.948 27.50 85.5 81.2 Culprit lesion length 0.790 <0.001* 0.695 0.886 24.5 86.1 61.3 TFC 0.916 <0.001* 0.852 0.981 25.5 90.3 80.6 Contrast volume 0.812 <0.001* 0.717 0.907 205.0 95.8 51.6 EF% 0.601 <0.001* 0.524 0.679 46.5 63.3 51.5 Thrombus grade 0.741 <0.001* 0.635 0.846 4 72.4 69.4 Maximal inflation pressure of stent 0.736 <0.001* 0.630 0.841 15.0 72.4 69.4 CHA2DS2-VASc Risk Criteria 0.761 <0.001* 0.672 0.850 2 86.2 51.2 Validity Of Significant Indices In Differentiating Cases With No Reflow
  • 55. Predictors β p Odds ratio (95% CI) EF % -0.071 0.013* 0.931(0.881-0.985) Blood glucose level per PCI 0.001 0.147 1.00(1.00-1.002) Initial time flow -2.70 0.116 0.067(0.002-1.95) Myocardial blush grade -5.06 <0.001* 0.006(0.001-0.077) Collateral flow grade -2.35 0.014* 0.05(0.014-0.625) Culprit lesion length 0.095 0.007* 1.09(1.026-1.178) Vessel diameter 1.64 0.118 5.13(0.659-39.96) Contrast volume 0.01 0.02* 1.01(1.002-1.02) TFC 0.245 <0.001* 1.278(1.189-1.374) Aspiration thrombectomy 1.65 <0.001* 5.19(2.32-11.65) Thrombus grade ≥ 4 1.19 <0.001* 3.29(2.18-4.98) Number of stents 0.653 0.03* 1.92(1.07-3.45) Type of occlusion 1.05 0.06 1.0(0.89-4.2) Total ischemic time (min) from symptom onset to ballon crossing in PCI 0.519 0.002* 1.68(1.21-2.33) Pharmacoinvasive with successful SK -2.09 0.047* 0.25(0.03-0.98) Rescue PCI 1.76 0.223 5.82(0.343-98.57) Pre-infarction angina 0.902 0.06 2.46(0.99-4.29) Maximal inflation pressure of stent 0.335 0.009* 1.39(1.09-1.79) Use of GP 2b3a inhibitor 5.67 <0.001* 29.98(20-44.89) Syntax score 0.357 <0.001* 1.43(1.24-1.65) Multivessel disease 1.56 0.002* 4.78(1.78-12.79) CHA2DS2-VASc Risk Criteria 0.722 <0.001* 2.05(1.51-2.81 Pre-ballon dilatation with stenting 0.835 0.037* 2.30(1.05-5.05) Post-ballon dilatation 1.426 0.006* 4.16(1.49-11.56) Overall percent predicted=88.0% Predictors for no reflow among studied cases.
  • 56. In the present study; clinical, angiographic and laboratory predictive factors have been recognized and correlated with presence of no reflow phenomenon with overall percent predicted=88.0%. Currently there are many lines to manage no reflow. Such patients warrant urgent supportive measures to save life. Many lines of treatment are available depending upon the underlying mechanism/s and the choice of interventional cardiologist. Unfortunately, no reflow may prove resistant to pharmacological therapy in 5–10% cases with adverse short term and long-term outcomes. A personalized attention to tide over the crisis in cath lab is required for patient to prevent and promptly treat the no-reflow phenomenon.
  • 57. • Based on the present study, there are clinical, angiographic and laboratory predictive factors associated with presence of no reflow phenomenon with overall percent predicted=88.0%. • Prevention is always better than treatment and no-reflow phenomenon should be predicted and successfully treated to improve myocardial salvage and improve outcomes.
  • 58. • Angiographic examinations were performed by different clinicians and it is likely that studies were performed with different sized catheters and angiographic projections. • In our study, we didn’t use ivus to identify atherosclerotic changes of coronaries. • We have not analysed the microvascular function and no-reflow using myocardial contrast echocardiography ,CMR or nuclear scintigraphy. • A relatively small sample size, additional analysis of clinical, laboratory, angiographic predictors of no-reflow phenomenon may be considered by examing more cases.
  • 59.
  • 60. 432 : 26-01-2020 : 56 years old Smoker, HTN Typical anginal pain (CCS III) : Lateral STEMI
  • 61. : Standard Right Radial approach using XB3.5. (LCX): Atherosclerotic Vessel showing proximal subtotal atheroma 80 % stenosis with good distal flow. : XB 3.5 PT 2 LS wire NC TREK (4.00*15mm) Resolute Integrity (4.00*18mm)
  • 62.
  • 63. 352 : 20-7-2019 : 55 years old HTN,DM Dyspnea and retrosternal chest pain (stuttering course) during the previous week, becoming persistent and of increased intensity on the morning of july 20 2019. : Anterior STEMI
  • 64. : Standard Right femoral approach using XB4. LAD: atherosclerotic, sub- totally occluded at its mid segment. : XB 4 ASAHI soft floppy wire NC Sprinter (3.50x15mm), NC Sprinter (3.75x21mm) PROMUS (3.00*28mm)
  • 65.
  • 66. 351 : 19-7-2019 : 60 years old HTN,DM,smoker Acute severe burning retrosternal chest pain Patient sought medical advice.
  • 67. : Standard Right femoral approach using XB4. LAD: Atherosclerotic Vessel showing proximal and distal stenosis : XB 4 PT 2 MS wire Promus (3*38mm), Promus (2.5*38mm)
  • 68.
  • 69. 407 : 01-11-2019 : 64 years old HTN,DM,smoker and upon solicitation of a more detailed history, it became apparent that his father had suffered from an acute myocardial infarction at the age of 50. He describes the pain as a substernal heavy pressure that radiates to his left arm, associated with diaphoresis, nausea, and tingling in his fingers. His pain was minimally relieved with sublingual nitroglycerin tablets.
  • 70. : Standard Right radial approach using JL,JR 3.5. LAD: Atherosclerotic Vessel with proximal to midsegment subtotal significant lesion . : XB3.5 ASAHI soft . Resolute 2.5*22- 3*38 : PTCA 2*15
  • 71.
  • 72. 438 : 02-17-2020 : 65 years old HTN Acute typical chest pain from 4hours before admission. she felt dyspnea and diaphoretic • Patient sought medical advice .
  • 73. : Standard Right femoral approach using JR 3.5. LAD • : XB 3.5 PT 2 LS. Resolute (2.75*30 mm) and others : MiniTREK (2*12) and others

Editor's Notes

  1. Timely PPCI remain reperfusion strategy of choice for acute STEMI
  2. NR is a common complication affecting prognosis And no operator didn’t face NR , thus prediction help prevention and treatment
  3. Epicardial coronary artery opening with poor distal run off In absence of
  4. Myocardial contrast density
  5. Focusing on MBG as the core definition of NR
  6. We maily assess NR by..
  7. Are among the most important predictors
  8. IPC neurohoronal pathway