definition of vulnerable plaque naghavi- thi
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Vulnerable Vulnerable Plaques and Plaques and Vulnerable Vulnerable
PatientsPatientsThe 1The 1stst Guideline of Guideline of Association for Association for Eradication of Heart Attack AEHA Eradication of Heart Attack AEHA for Definition of Vulnerable Plaque and for Definition of Vulnerable Plaque and
Vulnerable PatientVulnerable Patient(VP.org)(VP.org)
Morteza Naghavi, Erling Falk, Mohammad Madjid, Silvio Litovsky, James E. Muller, Ward Casscells,
Renu Virmani, Valentin Fuster, James T. Willerson
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Vulnerable plaques, vulnerable Vulnerable plaques, vulnerable myocardium, and hypercoagulable state of myocardium, and hypercoagulable state of
the blood lead to the blood lead to sudden cardiac death and acute myocardial sudden cardiac death and acute myocardial
infarction.infarction.
Vulnerable Blood
Vulnerable Myocardium
Vulnerable Plaque
Vulnerable Patient
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Potential Underlying Cause of All (fatal and non-fatal) Heart Attacks(Sudden Cardiac Death + Acute Coronary Syndrome)
With Occlusive Thrombi
With Rupture
>70% Stenosis
With Significant Atherosclerosis or Ischemic Heart
<70% Stenosis
Without Significant Atherosclerosis or Atherosclerosis-Derived Myocardial Damage
Without Occlusive Thrombi
Without Rupture With Old Myocardial Damage
WithoutOld Myocardial Damage
Only Myocardial-Derived Factors(conductive disorders, …)
Erosion Calcified Nodule Others
With Critical Stenosis Without Critical Stenosis
With Expansive Remodeling
Without Expansive Remodeling
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Terminology:Terminology:
Culprit Plaque:Culprit Plaque: a a RetrospectiveRetrospective Terminology Terminology
Vulnerable PlaqueVulnerable Plaque: : a a ProspectiveProspective Terminology Terminology
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Underlying Underlying pathologies of pathologies of
“culprit” coronary “culprit” coronary lesionslesions1.1. Ruptured Plaques (~70%) Ruptured Plaques (~70%)
Stenotic (~20%)Stenotic (~20%) Non-stenotic (~50%) Non-stenotic (~50%)
2.2. Non-Ruptured Plaques (~ Non-Ruptured Plaques (~ 30%)30%)
ErosionErosion Calcified NoduleCalcified Nodule Others / UnknownOthers / Unknown MJ Davies, Circ. 1990; Falk et al. Circ. 1995; Virmani et al. ATVB 2000
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Interchangeable TerminologiesInterchangeable Terminologies YESYES NONO
Vulnerable Plaque =Vulnerable Plaque = Vulnerable Vulnerable Plaque=Plaque=
High-Risk PlaqueHigh-Risk Plaque Soft-PlaqueSoft-Plaque
Dangerous PlaqueDangerous Plaque Non-Calcified Non-Calcified Plaque Plaque AHA Type IV AHA Type IV PlaquePlaqueNon-Stenotic Non-Stenotic PlaquePlaque
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Proposed Histopathological Proposed Histopathological and Clinical Criteria for and Clinical Criteria for Definition of Vulnerable Definition of Vulnerable
PlaquePlaque MajorMajor Criteria: Criteria:1.1. Active Inflammation (monocyte/ Active Inflammation (monocyte/
macrophage infiltration) macrophage infiltration) 2.2. Thin Cap with Large Lipid Core Thin Cap with Large Lipid Core 3.3. Endothelial Denudation with Endothelial Denudation with
Superficial Platelet Aggregation Superficial Platelet Aggregation 4.4. Fissured / Wounded PlaqueFissured / Wounded Plaque
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Proposed Histopathological Proposed Histopathological and Clinical Criteria for and Clinical Criteria for Definition of Vulnerable Definition of Vulnerable
PlaquePlaque MinorMinor Criteria: Criteria:1.1. Superficial Calcified nodule Superficial Calcified nodule 2.2. Glistening Yellow Glistening Yellow 3.3. Intraplaque Hemorrhage Intraplaque Hemorrhage 4.4. Critical StenosisCritical Stenosis5.5. Positive Remodeling? Positive Remodeling?
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Ideal method for Ideal method for screening vulnerable screening vulnerable
plaque/patientplaque/patient Non-invasiveNon-invasive InexpensiveInexpensive AccurateAccurate Widely Reproducible Widely Reproducible
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Diagnosis and Screening- Diagnosis and Screening- Plaque LevelPlaque Level
Plaque inflammation (macrophage density or rate of monocyte Plaque inflammation (macrophage density or rate of monocyte infiltration) infiltration)
Matrix digesting enzyme activity in the cap (MMP 2, 3,9, etc) Matrix digesting enzyme activity in the cap (MMP 2, 3,9, etc)
Endothelial denudation or dysfunction (local NO production, Endothelial denudation or dysfunction (local NO production, anti/pro-coagulation properties of the endothelium) anti/pro-coagulation properties of the endothelium)
Superficial platelet aggregation and fibrin deposition (residual Superficial platelet aggregation and fibrin deposition (residual mural thrombus)mural thrombus)
Plaque cap thickness with a resolution of <100 micron Plaque cap thickness with a resolution of <100 micron
Collagen content, lipid core size, mechanical stability (stiffness and Collagen content, lipid core size, mechanical stability (stiffness and elasticity) elasticity)
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Diagnosis and Screening- Diagnosis and Screening- Plaque LevelPlaque Level
Calcification burden and pattern (nodule, scattered, Calcification burden and pattern (nodule, scattered, intimal, deep) intimal, deep)
Angiogenesis, leaking vasa vaserum, and intraplaque Angiogenesis, leaking vasa vaserum, and intraplaque hemorrhagehemorrhage
Presence of certain microbial antigensPresence of certain microbial antigens
Rate of apoptosis (apoptosis protein markers, coronary Rate of apoptosis (apoptosis protein markers, coronary microsatellite, etc) microsatellite, etc)
Shear stress imaging (flow pattern throughout coronary Shear stress imaging (flow pattern throughout coronary arteryartery
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Diagnosis and Screening- Diagnosis and Screening- Systemic LevelSystemic Level
CRP, CD40L, ICAM-1, VCAM, and other CRP, CD40L, ICAM-1, VCAM, and other serological markers of inflammationserological markers of inflammation
MMPs and acidic digesting proteinases MMPs and acidic digesting proteinases and their inhibitors such as TIMMPs and and their inhibitors such as TIMMPs and cystatin cystatin
Circulating apoptosis marker(s)Circulating apoptosis marker(s)
Markers of blood hypercoagulabilityMarkers of blood hypercoagulability
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Diagnosis and Screening- Diagnosis and Screening- Systemic LevelSystemic Level
Markers of blood fibrinolysisMarkers of blood fibrinolysis
Markers of lipid-peroxidation Markers of lipid-peroxidation
PAPP-A, pregnancy associated plasma PAPP-A, pregnancy associated plasma protein –Aprotein –A
Plaque specific markers of immune Plaque specific markers of immune activation activation (anti-LDL Ab)(anti-LDL Ab)
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A composite risk score
Plaque vulnerability index
Patient vulnerability index (e.g. VP Score)
Screening
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Diagnosis- Active Diagnosis- Active InflammationInflammation
Intravascular: Intravascular: Thermography, Thermography, CE-MRICE-MRI FDG-PETFDG-PET ImmunoscintigraphyImmunoscintigraphy
Non-invasive: Non-invasive: CE-MRI (SPIO)CE-MRI (SPIO) Targeted CE-MRI, (macrophage specific Targeted CE-MRI, (macrophage specific
Gd-labeled Ab)Gd-labeled Ab)
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Dx- Thin cap and large Dx- Thin cap and large lipid corelipid core
Intravascular: Intravascular: OCTOCT IVUSIVUS High-resolution IVUSHigh-resolution IVUS AngioscopyAngioscopy NIR SpectroscopyNIR Spectroscopy ElastographyElastography MRIMRI IVUS-RF analysisIVUS-RF analysis
Non-invasiveNon-invasive MRIMRI
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DX-Endothelial denudation DX-Endothelial denudation with superficial platelet with superficial platelet
aggregation aggregation Intravascular: Intravascular:
OCTOCT Angioscopy with dyeAngioscopy with dye Matrix-targeted / fibrin-targeted immune-Matrix-targeted / fibrin-targeted immune-
scintigraphy scintigraphy
Non-invasive:Non-invasive: Fibrin/Matrix-targeted CE MRIFibrin/Matrix-targeted CE MRI Platelet/fibrin-targeted SPECTPlatelet/fibrin-targeted SPECT
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Fissured/Wounded Fissured/Wounded PlaquesPlaques
Intravascular:Intravascular: OCTOCT IVUSIVUS High-resolution IVUSHigh-resolution IVUS MRI MRI
Non-invasive: Non-invasive:
Fibrin-targeted CE-MRI Fibrin-targeted CE-MRI
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Dx-Superficial Calcified Dx-Superficial Calcified Nodule Nodule
Intravascular: Intravascular: OCTOCT High-resolution IVUSHigh-resolution IVUS IVUSIVUS
Non-invasive: Non-invasive: EBCTEBCT MSCTMSCT MRIMRI
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Yellow Color (in Yellow Color (in Angioscopy)Angioscopy)
Intravascular: Intravascular: AngioscopyAngioscopy Transcatheter colorimetryTranscatheter colorimetry
Non-invasive: Non-invasive: Presently impossiblePresently impossible
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Dx- Intraplaque Dx- Intraplaque HemorrhageHemorrhage
Intravascular: Intravascular: NIR SpectroscopyNIR Spectroscopy Tissue DopplerTissue Doppler
Non-invasive: Non-invasive: MRIMRI
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Dx-Stenotic PlaquesDx-Stenotic Plaques Intravascular: Intravascular:
Invasive X-ray AngiographyInvasive X-ray Angiography
Non-invasive: Non-invasive: Non-invasive MS-CECTNon-invasive MS-CECT MRA w/wo contrastMRA w/wo contrast EBT AngiographyEBT Angiography
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Blood FactorBlood Factor Antithrombin III deficiencyAntithrombin III deficiency Protein C or S deficiencyProtein C or S deficiency Resistance to activated protein C Resistance to activated protein C
(factor V Leiden) (factor V Leiden) Antiphospholipid syndromeAntiphospholipid syndrome Nephrotic syndrome Nephrotic syndrome Platelet polymorphisms Platelet polymorphisms
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MyocardialMyocardial FactorFactor Different cardiomyopathies Different cardiomyopathies Valvular diseaseValvular disease Primary electric disturbances Primary electric disturbances Chest trauma Chest trauma Anomalous origin of coronary arteriesAnomalous origin of coronary arteries Myocarditis Myocarditis Myocardial bridging Myocardial bridging
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Different Types of Vulnerable Plaque As underlying Cause of Acute Coronary Events
NormalRupture-prone
Fissured ErodedCritical Stenosis Hemorrhage
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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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Vulnerable Plaque Type 5
Asymptomatic Significantly Stenotic Plaque Prone to Occlusion