the pathogenesis and treatment of no-reflow in patient with acs jian liu, md chief physician,...

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

Case report

Epidemiology of no reflow

Pathophysiology of no reflow

Contents

1

2

4

Influencing factors and diagnostic methods5

Prevention and treatment of no reflow6

Definition and classification3

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

Nitroglycerin ( IC)

Atropine ( IV )

Dopamine ( IV )

Blood flow recover

Final result

ECG 2 days later

Myocardial injury biomarker ： TNI 4.62ng/ml

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Epidemiology

Incidence

Influence

Overall incidence was 2%;10%-15% in patients undergoing PCI of SVGs; 30% in AMI undergoing direct PCI;

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;

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Definition

No-reflow (NR) was known as "primary percutaneous coronary i

ntervention (PPCI) achieves epicardial coronary artery reperfusio

n but not myocardial reperfusion";

The term “no-reflow” has been increasingly used in published m

edical reports to describe microvascular obstruction and reduced

myocardial flow after opening an occluded artery;

Manifested as stagnant contrast and myocardial ischemia sympt

oms.

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

DefinitionNo-reflow in the setting of pharmacological and/or mechanical

revascularization for acute myocardial infarction

Mechanisms 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

Interventional NR Distal coronary embolization - Microvascular obstruction - Inflammatory response - Secondary

Reperfusion NR Ischemia-reperfusion injury Myocardial edema Endothelial swelling Capillary obstruction Vasospasm Inflammatory response Distal coronary embclization

Durationof Preceding

ischemiaseconds-minutes hours

Circulation. 2008;117:3152-3156

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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

Plaque rupture/fissure Debris + Thrombotic material + Soluble factors

Microembolization

Acute ischemia

InfarctletsProtection

Inflammatory reaction

Arrhythmia Myocardial dysfunction Coronary reserve

Adhesin

TNFα

SerotoninTXA2

NO, TNF, ROS

Summarizing different mechanisms

Heart 2002; 87: 162–8

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Influencing factors of NR

The course of ACS and reperfusion time

Characteristics of coronary artery lesions

Pathological vessels and interventions

Acute phase of ACS (<2w) Reperfusion time<6h

Plaque rupture Ulcerative lesions Rich lipid,etc

SVG Rotational atherectomy

Evaluation methods

Diagnostic technique Parameter evaluated Definition of no-reflow

Coronary angiography

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

echocardiography

Intramyocardial contrast

opacification

Segmental lack of

contrast opacification

Cardiac magnetic resonanceMyocardial enhancement

by gadolinium

Lack of gadolinium enhancement during first pass or within a

ecrotic region identified by gadolinium hyperenhancement

Single-photon emission

tomography and PET

Myocardial perfusion

tracer captationLack of perfusion tracer captation

Coronary angiographyReflow No-reflow

The sensitivity of TIMI flow grade is rather low as no-reflow occurs even in patients s

howing TIMI flow grade 3.

MBG provides a semi-quantitative evaluation of tissue perfusion after injection of co

ntrast 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 an

d in clinical practice.

Sustained elevation of the ST segment a

fter successful PCI is also associated with

unfavorable functional and clinical outcom

es.

Almost 30% of patients with TIMI flow g

rade 3 and MBG 2 or 3 do not exibit STR.

Myocardial contrast echocardiographyReflow 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 ventricul

ar remodeling after STEMI, being superior to STR and MBG among patients with a TIMI flow gra

de 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

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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

EvaluatedStudy Patients

(n)Timing of

InterventionPrimary End Points Results

AbciximabThiele

et al154 Periprocedural Infarct size and extent of microv

ascular obstructionSignificant reduction in infarct size and microvascular

obstruction with intracoronary abciximab

Adenosine

Marzilli

et al54 Pre-PCI Feasibility, safety, and TIMI flow

Safe and feasible in MI, reduction in

incidence of no-reflow, and improvement of LVEF

Ross

et al2118

Pre- and

post-PCI

Inhospital heart failure, rehospitalization for heart failure, or 6-m

onth death.

No effect on clinical outcomes and infarct size reduction with adenosine 70 mg/kg per min

NitroprussideAmit

et al98 During PCI Corrected TIMI frame count and

ST resolution >70%

No effect on coronary flow and myocardial

tissue reperfusion, improvement in

clinical outcomes at 6 months

NicorandilIshii

et al360 Pre-PCI

Cardiovascular death or

rehospedalization for

congestive heart failure.

Improved myocardial reperfusion, fewer

deaths, and less cardiac failure after 2.4-

year follow-up

VerapamilPiana

et al39 During PCI Corrected TIMI frame count, TI

MI flow grade, and ST resolution.

Improvement in TIMI flow grade, reduction

in cineframes to opacify a distal vascular

landmark, and relief of chest pain and

ischemic ST-segment shifts

CyclosporinePiot

et al58 Pre-PCI Infarct size

Smaller infarct size but no effect on final

TIMI flow

StatinsIwakura

et al293 Pre-PCI Incidence of no-reflow and EF Lower incidence of no-reflow, better wall motion, sma

ller LV dimension, and better EF

Prevention and treatment of no reflowMechanical 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

StudyThrombectomy

DevicePatients

(n)

Angiographic Exclusion

Criteria

GP IIb/IIIa Use (%)

Primary

End PointsResults

Noel et al Export 50 TIMI flow > 2 N/A STR > 70% 50% vs 12%

EXPORTExport 249 RVD < 2.5 mm TIMI

flow 2-3 67.8 STR > 50% þ MBG 3 85% vs 71.9%

EXPIRAExport 175

RVD < 2.5 mm TIMI flow 2-3

TTG < 3100 MBG 3 STR > 70% 70.3% vs 28.7%

TAPAS Export 1071 None 93.4 MBG 0 or 1 17.1% vs 26.3%

Lipiecki

et alExport 44 None 55 Infarct size 30.6% vs 28.5%

Liistro

et alExport 111 None 100 STR > 70% 71% vs 39%

Chao

et alExport 74 None 26 △DTIMI flow MBG△ 2.2 vs 1.5 2.3 vs 1.0

Antoniucci

et alAngiojet 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 97.5Early STR 50%

Infarct size

85.8% vs 78.8% 11.8% vs

12.7%

Therefore, current evidence suggests the routine use of manual thrombectomy in primary PCI

Both manual and mechanical were associated with better

STR, albeit manual thrombectomy demonstrated a clear sup

eriority.Manual thrombectomy device suggest that it is asso

ciated with a benefit in terms of death, stroke, and MI comp

ared to standard PCI.Mechanical thrombectomy, on the othe

r hand, does not seem to improve outcome over standard PC

I.

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 reflowMechanical 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

Thank you for your attention ！

the pathogenesis and treatment of no-reflow in patient with acs jian liu, md chief physician,...

Documents

area slide

beijing slide

ngml slide

deployed slide

pre pci slide

final result slide

balloon predilation

myocardial reperfusion