Transcript The Detrimental Impact of Chronic Renal Insufficiency

The pathogenesis and treatment of
no-reflow in patient with ACS
Jian Liu, MD
Chief Physician, Associate Professor of Medicine
Cardiology Department, Peking University People’s
Hospital, Beijing
Contents
1
Case report
2
Epidemiology of no reflow
3
Definition and classification
4
Pathophysiology of no reflow
5
Influencing factors and diagnostic methods
6
Prevention and treatment of no reflow
 Female, 55 yr.
 “ Chest pain 5 months，aggravated for 1 week” .
 Risk factors: Hypertension 6 years；Hyperlipidaemia
10 years.
 CTA: LAD, RCA severe stenosis and soft plaque.
 Diagnosis: Acute coronary syndrome.
ECG at rest, pre PCI
Left Coronary Artery Angiogram
Right Coronary Artery Angiogram
After balloon predilation
After DES deployed
No-reflow
 Severe chest pain
 Blood pressure dropped
 Heart rate dropped
Blood flow recover
 Nitroglycerin ( IC)
 Atropine ( IV )
 Dopamine ( IV )
Final result
ECG 2 days later
 Myocardial injury biomarker：TNI 4.62ng/ml
Contents
1
Case report
2
Epidemiology of no reflow
3
Definition and classification
4
Pathophysiology of no reflow
5
Influencing factors and diagnostic methods
6
Prevention and treatment of no reflow
Epidemiology
 Incidence
Overall incidence was 2%;
10%-15% in patients undergoing PCI of SVGs;
 30% in AMI undergoing direct PCI;
 Influence
 The hospital mortality and recurrent MI increased 5-10 times;
 Associated with increased malignant arrhythmias,cardiac failure and poor
long-term prognosis;
 A large area of microvascular injury might impair the healing of the infarct
area and could prevent the delivery of pharmacologic agents into that area;
Contents
1
Case report
2
Epidemiology of no reflow
3
Definition and classification
4
Pathophysiology of no reflow
5
Influencing factors and diagnostic methods
6
Prevention and treatment of no reflow
Definition
 No-reflow (NR) was known as "primary percutaneous coronary
intervention (PPCI) achieves epicardial coronary artery
reperfusion but not myocardial reperfusion";
 The term “no-reflow” has been increasingly used in published
medical reports to describe microvascular obstruction and
reduced myocardial flow after opening an occluded artery;
 Manifested as stagnant contrast and myocardial ischemia
symptoms.
Classification according to the different situation
Experimental no-reflow
Definition
No-reflow induced under experimental conditions
Mechanisms
• Myocardial necrosis—stunning
• Reperfusion injury—oxygen free radical production
• α-adrenergic macro- and microvascular constriction
• Local increase in angiotension II receptor density
• Neutrophil activation—interaction with endothelium
Myocardial infarction reperfusion no-reflow
Definition
Mechanisms
No-reflow in the setting of pharmacological and/or mechanical
revascularization for acute myocardial infarction
As for experimental no-reflow
Angiographic no-reflow
Definition
No-reflow during percutaneous coronary interventions
Mechanisms
• Distal embolization of plaque and/or thrombus
• Local release of vasoconstrictor substances
Classification according to morphological
and functional studies
 Structural no-reflow
- microvessels confined within necrotic myocardium exhibit irreversible
damage of the cellular components of their wall.
 Functional no-reflow
- patency of anatomically intact microvessels is compromised because of
spasm and/or microembolisation.
Classification according to the duration of
the preceding myocardial ischemia
Reperfusion NR
Interventional NR
 Distal coronary embolization
- Microvascular obstruction
- Inflammatory response
- Secondary
seconds-minutes
 Ischemia-reperfusion injury
 Myocardial edema
 Endothelial swelling
 Capillary obstruction
 Vasospasm
 Inflammatory response
 Distal coronary embclization
Duration
of Preceding
ischemia
Circulation. 2008;117:3152-3156
hours
Contents
1
Case report
2
Epidemiology of no reflow
3
Definition and classification
4
Pathophysiology of no reflow
5
Influencing factors and diagnostic methods
6
Prevention and treatment of no reflow
Pathophysiology
 Mechanical obstruction from embolization
 Vascular autoregulation
 Extrinsic coagulation pathway
 Leukocyte adherence, platelet thrombi, and free radicals
 Microvascular ischemia and edema
 Vasoconstrictor mediators
 Individual susceptibility
Coronary microembolization
Debris +
Plaque rupture/fissure
Thrombotic material
+ Soluble factors
Microembolization
Acute ischemia
Infarctlets
Protection
TNFα
Inflammatory reaction
Adhesin
NO, TNF, ROS
Arrhythmia
Myocardial dysfunction
Serotonin
TXA2
Coronary reserve
Summarizing different mechanisms
Heart 2002; 87: 162–8
Contents
1
Case report
2
Epidemiology of no reflow
3
Definition and classification
4
Pathophysiology of no reflow
5
Influencing factors and diagnostic methods
6
Prevention and treatment of no reflow
Influencing factors of NR
 The course of ACS and reperfusion time
 Acute phase of ACS (<2w)
 Reperfusion time<6h
 Characteristics of coronary artery lesions
 Plaque rupture
 Ulcerative lesions
 Rich lipid,etc
 Pathological vessels and interventions
 SVG
 Rotational atherectomy
Evaluation methods
Diagnostic technique
Parameter evaluated
Definition of no-reflow
TIMI flow grade
TIMI flow grade <3
MBG
MBG <2
TIMI and MBG
TIMI flow grade ≤3 with MBG <2
ECG
STR
STR <50%
Myocardial contrast
Intramyocardial contrast
Segmental lack of
echocardiography
opacification
contrast opacification
Myocardial enhancement
Lack of gadolinium enhancement
during first pass or within a
Coronary angiography
Cardiac magnetic resonance
by gadolinium
Single-photon emission
Myocardial perfusion
tomography and PET
tracer captation
ecrotic region identified by
gadolinium hyperenhancement
Lack of perfusion tracer captation
Coronary angiography
Reflow
No-reflow
 The sensitivity of TIMI flow grade is rather low as no-reflow occurs even in patients
showing TIMI flow grade 3.
 MBG provides a semi-quantitative evaluation of tissue perfusion after injection of
contrast media in the epicardial vessel,represents a newer and more sensitive method.
ECG
Reflow
No-reflow
 Electrocardiographic STR is assessed 1 h
after PCI,represents the most widely used
technique, both in experimental studies
and in clinical practice.
 Sustained elevation of the ST segment
after successful PCI is also associated with
unfavorable functional and clinical
outcomes.
 Almost 30% of patients with TIMI flow
grade 3 and MBG 2 or 3 do not exibit STR.
Myocardial contrast echocardiography
Reflow
No-reflow
 MCE uses ultrasound to detect the presence of microbubbles in myocardial microvessels;
 Microvascular obstruction is detectable as a perfusion defect during myocardial contrast
echocardiography and represents the extent of no-reflow;
 AMICI study indicated the extent of no-reflow was the best predictor of adverse left
ventricular remodeling after STEMI, being superior to STR and MBG among patients with a
TIMI flow grade 3.
Cardiac magnetic resonance
Reflow
No-reflow
 No-reflow can be diagnosed as a lack of
gadolinium enhancement during first pass
or a lack of gadolinium enhancement
within a necrotic region, identified by late
gadolinium hyperenhancement;
 CMR evaluation of microvascular perfusion
has been shown to strictly correlate with
MBG;
 The detection of hypoenhancement zones
on first-pass perfusion CMR,is associated
with permanent dysfunction at follow-up
Contents
1
Case report
2
Epidemiology of no reflow
3
Definition and classification
4
Pathophysiology of no reflow
5
Influencing factors and diagnostic methods
6
Prevention and treatment of no reflow
Prevention and treatment of no reflow
 Medical therapy
 Anti-platelet therapy: Abciximab
 Vasodilators: Nitroglycerine, Adenosine, Calcium channel
blockers, Nicorandil,Sodium nitroprusside
 Intracoronary thrombolytics: Streptokinase
 New drugs: Cyclosporine,Statins,Endothelin-1 and
Thromboxane-A2 receptor antagonists
Evidence Concerning Medical Prevention and Treatment of No-Reflow
Drug
Evaluated
Abciximab
Study
Thiele
et al
Marzilli
et al
Timing of
Patients
(n)
Intervention
154
54
Primary End Points
Results
Periprocedural
Infarct size and extent of
microvascular obstruction
Significant reduction in infarct size and microvascular
obstruction with intracoronary abciximab
Pre-PCI
Feasibility, safety, and TIMI flow
Pre- and
Inhospital heart failure,
rehospitalization for heart
failure, or 6-month death.
Safe and feasible in MI, reduction in
incidence of no-reflow, and improvement of LVEF
Adenosine
Ross
et al
Nitroprusside
Nicorandil
Amit
et al
Ishii
et al
2118
98
360
post-PCI
During PCI
Pre-PCI
Corrected TIMI frame count and
ST resolution >70%
No effect on clinical outcomes and infarct size
reduction with adenosine 70 mg/kg per min
No effect on coronary flow and myocardial
tissue reperfusion, improvement in
clinical outcomes at 6 months
Cardiovascular death or
Improved myocardial reperfusion, fewer
rehospedalization for
deaths, and less cardiac failure after 2.4-
congestive heart failure.
year follow-up
Improvement in TIMI flow grade, reduction
Verapamil
Piana
et al
39
During PCI
Corrected TIMI frame count,
TIMI flow grade, and ST
resolution.
in cineframes to opacify a distal vascular
landmark, and relief of chest pain and
ischemic ST-segment shifts
Cyclosporine
Statins
Piot
et al
Iwakura
et al
58
Pre-PCI
Infarct size
293
Pre-PCI
Incidence of no-reflow and EF
Smaller infarct size but no effect on final
TIMI flow
Lower incidence of no-reflow, better wall motion,
smaller LV dimension, and better EF
Prevention and treatment of no reflow
 Mechanical therapies
 Embolic protection devices
1. Distal or proximal protection
2. Thrombectomy devices
 PCI techniques :
1. Minimization of balloon inflations
2. Stent deployment without predilation
3. Pre- and postconditioning methods
Thrombectomy devices
 Manual thrombectomy devices
1. Export [Medtronic Corporation, Minneapolis,MN, USA]
2. Driver CE [Invatec, Brescia, Italy]
3. Pronto [Vascular solutions, Minneapolis, MN, USA]
 Mechanical thrombectomy devices
1. Angiojet [MEDRAD Interventional/Possis Medical Inc., Minneapolis,MN, USA]
2. X-Sizer [eV3, White Bear Lake, MN,USA]
Manual thrombectomy devices
a. The Diver CE device.b. The Pronto catheter. c. The Export catheter. d. The Hunter
catheter. e. The VMax catheter.
Mechanical thrombectomy devices
The Angiojet System
The Rinspirator system
The X-sizer system
Effect of Thrombectomy Devices on Surrogate End Points of Myocardial Reperfusion
Study
Noel et al
EXPORT
EXPIRA
Thrombectomy
Angiographic
Exclusion
Primary
Device
Patients
(n)
Export
50
TIMI flow > 2
N/A
STR > 70%
50% vs 12%
Export
249
RVD < 2.5 mm TIMI
flow 2-3
67.8
STR > 50% þ MBG 3
85% vs 71.9%
Export
175
100
MBG 3 STR > 70%
70.3% vs 28.7%
Criteria
RVD < 2.5 mm TIMI
flow 2-3
GP IIb/IIIa
Use (%)
End Points
Results
TTG < 3
TAPAS
Export
1071
None
93.4
MBG 0 or 1
17.1% vs 26.3%
Export
44
None
55
Infarct size
30.6% vs 28.5%
Export
111
None
100
STR > 70%
71% vs 39%
Export
74
None
26
△DTIMI flow △MBG
2.2 vs 1.5 2.3 vs 1.0
Angiojet
100
RVD < 2.5 mm
98
Early STR 50%
90% vs 72%
AiMI
Angiojet
480
RVD < 2.0 mm
94.5
Infarct size
12.5% vs 9.8%
JETSTENT
Angiojet
501
TTG < 3 RVD < 2.5 mm
97.5
Early STR 50%
85.8% vs 78.8% 11.8% vs
Infarct size
12.7%
Lipiecki
et al
Liistro
et al
Chao
et al
Antoniuc
ci
et al
Both manual and mechanical were associated with better
STR, albeit manual thrombectomy demonstrated a clear
superiority.Manual thrombectomy device suggest that it is
associated with a benefit in terms of death, stroke, and MI
compared to standard PCI.Mechanical thrombectomy, on
the other hand, does not seem to improve outcome over
standard PCI.
Therefore, current evidence suggests the routine use of
manual thrombectomy in primary PCI
Costopoulos C, Gorog DA, Di Mario C, Kukreja N. Use of thrombectomy devices in primary percutaneous coronary
intervention: a systematic review and meta-analysis [published online December 11, 2011]. Int J Cardiol. 2011.
Prevention and treatment of no reflow
 Mechanical therapies
 Embolic protection devices
1. Distal or proximal protection
2. Thrombectomy devices
 PCI techniques :
1. Minimization of balloon inflations
2. Stent deployment without predilation
3. Pre- and postconditioning methods
Prevention and treatment of no reflow
 Others
 Oxygen intracoronary administration
 Therapeutic hypothermia
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