Vulnerable Plaques and Vulnerable Patients

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Vulnerable Plaques and Vulnerable Patients

• The 1st Guideline of Association for Eradication
  of Heart Attack AEHA for Definition of Vulnerable
  Plaque and Vulnerable Patient
• (VP.org)

Morteza Naghavi, Erling Falk, Mohammad Madjid,
Silvio Litovsky, James Muller, Ward Casscells,
Renu Virmani, P.K. Shah, MD, Robert S. Schwartz,
MD, Juan Jose Badimon, PhD, Valentin Fuster,
James T. Willerson
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Vulnerable plaques, vulnerable myocardium, and
hypercoagulable state of the blood lead to
sudden cardiac death and acute myocardial
infarction.
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•  Terminology
• Culprit Plaque
• a Retrospective Terminology
• Vulnerable Plaque
• a Prospective Terminology

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Underlying pathologies of culprit coronary
lesions

• Ruptured Plaques (70)
• Stenotic (20)
• Non-stenotic (50)
• Non-Ruptured Plaques ( 30)
• Erosion
• Calcified Nodule
• Others / Unknown

MJ Davies, Circ. 1990 Falk et al. Circ. 1995
Virmani et al. ATVB 2000
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Interchangeable Terminologies
YES NO
Vulnerable Plaque Vulnerable Plaque
High-Risk Plaque Soft-Plaque
Dangerous Plaque Non-Calcified Plaque
AHA Type IV Plaque
Non-Stenotic Plaque
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Proposed Histopathological and Clinical Criteria
for Definition of Vulnerable Plaque

•  Major Criteria
• Active Inflammation (monocyte/ macrophage
  infiltration)
• Thin Cap with Large Lipid Core
• Endothelial Denudation with Superficial Platelet
  Aggregation
• Fissured / Wounded Plaque

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Proposed Histopathological and Clinical Criteria
for Definition of Vulnerable Plaque

•  Minor Criteria
• Superficial Calcified nodule
• Glistening Yellow
• Intraplaque Hemorrhage
• Critical Stenosis
• Positive Remodeling?

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Ideal method for screening vulnerable
plaque/patient

• Non-invasive
• Inexpensive
• Accurate
• Widely Reproducible

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Diagnosis and Screening- Plaque Level

• Plaque inflammation (macrophage density or rate
  of monocyte infiltration)
• Matrix digesting enzyme activity in the cap (MMP
  2, 3,9, etc)
• Endothelial denudation or dysfunction (local NO
  production, anti/pro-coagulation properties of
  the endothelium)
• Superficial platelet aggregation and fibrin
  deposition (residual mural thrombus)
• Plaque cap thickness with a resolution of lt100
  micron
• Collagen content, lipid core size, mechanical
  stability (stiffness and elasticity)  

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Diagnosis and Screening- Plaque Level

• Calcification burden and pattern (nodule,
  scattered, intimal, deep)
• Angiogenesis, leaking vasa vaserum, and
  intraplaque hemorrhage
• Presence of certain microbial antigens
• Rate of apoptosis (apoptosis protein markers,
  coronary microsatellite, etc)
• Shear stress imaging (flow pattern throughout
  coronary artery

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Diagnosis and Screening- Systemic Level

• CRP, CD40L, ICAM-1, VCAM, and other serological
  markers of inflammation
• MMPs and acidic digesting proteinases and their
  inhibitors such as TIMMPs and cystatin
• Circulating apoptosis marker(s)
• Markers of blood hypercoagulability

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Diagnosis and Screening- Systemic Level

• Markers of blood fibrinolysis
• Markers of lipid-peroxidation
• PAPP-A, pregnancy associated plasma protein A
• Plaque specific markers of immune activation
  (anti-LDL Ab)

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Screening

• A composite risk score
• Plaque vulnerability index
• Patient vulnerability index
• (e.g. VP Score)

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Diagnosis- Active Inflammation

• Intravascular
• Thermography,
• CE-MRI
• FDG-PET
• Immunoscintigraphy
• Non-invasive
• CE-MRI (SPIO)
• Targeted CE-MRI, (macrophage specific Gd-labeled
  Ab)

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Dx- Thin cap and large lipid core

•  Intravascular
• OCT
• IVUS
• High-resolution IVUS
• Angioscopy
• NIR Spectroscopy
• Elastography
• MRI
• IVUS-RF analysis
•  
• Non-invasive
• MRI

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DX-Endothelial denudation with superficial
platelet aggregation

• Intravascular
• OCT
• Angioscopy with dye
• Matrix-targeted / fibrin-targeted
  immune-scintigraphy
• Non-invasive
• Fibrin/Matrix-targeted CE MRI
• Platelet/fibrin-targeted SPECT

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Fissured/Wounded Plaques

• Intravascular
• OCT
• IVUS
• High-resolution IVUS
• MRI
•  
• Non-invasive
• Fibrin-targeted CE-MRI

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Dx-Superficial Calcified Nodule

• Intravascular
• OCT
• High-resolution IVUS
• IVUS
• Non-invasive
• EBCT
• MSCT
• MRI

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Yellow Color (in Angioscopy)

• Intravascular
• Angioscopy
• Transcatheter colorimetry
• Non-invasive
• Presently impossible

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Dx- Intraplaque Hemorrhage

• Intravascular
• NIR Spectroscopy
• Tissue Doppler
• Non-invasive
• MRI

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Dx-Stenotic Plaques

• Intravascular
• Invasive X-ray Angiography
• Non-invasive
• Non-invasive MS-CECT
• MRA w/wo contrast
• EBT Angiography

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Blood Factor

• Antithrombin III deficiency
• Protein C or S deficiency
• Resistance to activated protein C (factor V
  Leiden)
• Antiphospholipid syndrome
• Nephrotic syndrome
• Platelet polymorphisms

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Myocardial Factor

• Different cardiomyopathies
• Valvular disease
• Primary electric disturbances
• Chest trauma
• Anomalous origin of coronary arteries
• Myocarditis
• Myocardial bridging

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Different Types of Vulnerable Plaque As
underlying Cause of Acute Coronary Events
Rupture-prone
Critical Stenosis
Hemorrhage
Normal
Fissured
Eroded
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Rupture-Prone Inflamed Plaque
Vulnerable Plaque Type 1
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Eroded Plaque with Exposed Proteoglycans Prone to
Thrombosis
Vulnerable Plaque Type 2
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Fissured Plaque with Old and Fresh Overlaying
Thrombi
Vulnerable Plaque Type 3
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Intra-Plaque Hemorrhage Prone to Thrombosis
Vulnerable Plaque Type 4
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Asymptomatic Significantly Stenotic Plaque Prone
to Occlusion
Vulnerable Plaque Type 5