Vulnerable Plaque

분당서울대학교병원 심장센터연 태 진

Causes / mediators of atherothrombosis

Endothelialdysfunction

Fattystreak

Fibrousplaque

UnstableFibrous plaque

Plaquerupture/fissure &

thrombosis

Acute coronary syndrome Cardiovasculardeath

Ross R. NEJM 1999; 340: 115-126

Inflammation

Vascular risk factorsGenes, BP, Smoking, Chol., Diabetes

Upregulationof adhesion molecules

permeability topl. lipoproteins(NO, A II, PDGF)

Leucocytesmigrate intoartery wall(ox. LDL, PDGF)

Lipid-laden macrophages(foam cells)

T lymphocyteactivation

Smooth muscle cellsmigrate & lipid laden

Fibrous cap

Necrotic core(apoptosis oflipid & WBC)

Expansion atshoulders asleucocytesadhere & enter(ox. LDL, PDGF)

Thinning/fissuring of fibrous cap

Large, lipid core

Influx &activation ofmacrophages -releasemetalloproteinases

Haemorrhage from- vasa vasorum- lumen of artery

……………………....

AtherogenesisAtherogenesis AtherothrombosAtherothrombosii

Angina

Stable and Rupture-prone plaqueStable and Rupture-prone plaque

Rupture of a coronary plaque

The fibrous cap ruptures and the lipid core is exposed to the blood stream

Platelets aggregate around the exposed lipid coreand initiate thrombus formation

Rupture of a coronary plaque- Thrombosis

Thrombosis propagation

v

v

v

v

v

v

vv

Underlying pathology of acute coronary syndrome (unstable angina, acute MI) and

sudden cardiac death

Ruptured plaques (~ 70%)• Stenotic (~ 20%)• Nonstenotic (~ 50%)

Nonruptured plaques (~ 30%)• Erosion• Calcified nodule• Others/Unknown

*Adapted from Falk and associates,6 Davies,7 and Virmani and colleagues.7

Underlying Pathologies of "Culprit" Coronary Lesions

Naghavi et al. Circulation. 2003;108:1664

Different Types of Vulnerable Plaques

Major Underlying Cause of Acute Coronary Events

Normal

Rupture-prone Fissured Eroded

Critical Stenosis

Hemorrhage

Rupture-prone plaque

Eroded plaque with thrombosis

Calcified nodule

The Challenge of Terminology

Culprit Plaque; A Retrospective Term Vulnerable Plaque; A Prospective Term

Vulnerable Plaque (high-risk plaque)= Future Culprit

Plaque

좁은 의미 : Rupture-prone plaque 넓은 의미 : Plaque that is at increased risk of

thrombosis and rapid stenosis progression

Naghavi et al. Circulation. 2003;108:1664

Criteria for Defining Vulnerable Plaque Based on the Study of Culprit

Plaques Major criteria. Active inflammation (monocyte/macrophage and

sometimes T-cell

infiltration)

. Thin cap with large lipid core

. Endothelial denudation with superficial platelet aggregation

. Fissured plaque

. Stenosis 90%

Minor criteria. Superficial calcified nodule

. Glistening yellow

. Intraplaque hemorrhage

. Endothelial dysfunction

. Outward (positive) remodeling

Markers of Vulnerability at the Plaque/Artery Level

PlaqueMorphology/Structure

. Plaque cap thickness

. Plaque lipid core size

. Plaque stenosis (luminal narrowing)

. Remodeling (expansive vs constrictive remodeling)

. Color (yellow, glistening yellow, red, etc)

. Collagen content versus lipid content, mechanical stability (stiffness

and elasticity)

. Calcification burden and pattern (nodule vs scattered, superficial vs

deep, etc)

. Shear stress (flow pattern throughout the coronary artery)

Activity/Function. Plaque inflammation (macrophage density, rate of monocyte

infiltration and density of activated T cell)

. Endothelial denudation or dysfunction (local NO production,

anti-/procoagulation properties of the endothelium)

. Plaque oxidative stress

. Superficial platelet aggregation and fibrin deposition (residual mural

thrombus)

. Rate of apoptosis (apoptosis protein markers, coronary

microsatellite, etc)

. Angiogenesis, leaking vasa vasorum, and intraplaque hemorrhage

. Matrix-digesting enzyme activity in the cap (MMPs 2, 3, 9, etc)

. Certain microbial antigens (eg, HSP60, C. pneumoniae)

Markers of Vulnerability at the Plaque/Artery Level

Pan-Arterial

. Transcoronary gradient of serum markers of vulnerability

. Total coronary calcium burden

. Total coronary vasoreactivity (endothelial function)

. Total arterial burden of plaque including peripheral (eg, carotid IMT)

Markers of Vulnerability at the Plaque/Artery Level

Diagnostic technique

Intravascular Ultrasound (IVUS)

Advantage:

Reveals the morphology of the plaque

Disadvantages:

Low spatial resolution (~ 200 m)

Limited information about the plaque

composition

IVUS

IVUS-radiofrequency data

Virtual histology

Elastography

Morphological

Lesion size

Lesion shape

% Stenosis

Cap thickness

Chemical Lipid, Protein, Water Calcium

Collagen

Physiological Flow disturbances

CFR, FFR

Spectroscopy

Polarization

Grey Scale

(2-D, L-Mode)

Doppler

infrared light wave reflection

Optical Coherence Tomography (OCT)

lp

lp

Homogeneous,Signal-rich

Fibrous Lipid

Echolucent, Diffuse Borders

Echolucent, Sharp Borders

Calcific

500 µm

OCT characteristics

Histology OCT

High lipidcontent

Fibro-fattyplaque

Thin Cap

OCT

Advantage:

High resolution

improved visualization of fibrous caps and

plaque components

Possibility to detect inflammation

Disadvantages:

Limited penetration

OCT

Angioscopy

Advantages:

Direct visualization of the plaque surface

Disadvantages:

Visualizes only the surface of the plaque

Requires a proximal occluding balloon

Subjective interpretation

Angioscopy

Intravascular Thermography

Intravascular Thermography

Advantages:

Gives information about plaque inflammation

Disadvantages:

Overlap in temperature heterogeneity b/w stable and

unstable presentations

Plaque temperature may be affected by the

blood flow

Spectroscopy

Advantage:

Chemical compounds detection

Disadvantage:

lack of structural definition

may needs combination with imaging

techniques

Analyze the light scattered from the tissue

Others

Intravascular MRI

Intravascular nuclear imaging

MRI

Electron Beam Computed Tomography (EBCT)

Therapeutic options

Focal

Regional

Systemic: medical tx. (aspirin, statins, beta-blocker,

ACE inhibitor…..)

• PCI in selected case

• Under investigationscryoplasty

sonotherapy photodynamic

therapy…..