Plaques and Plaques and Vulnerable Vulnerable Patients Patients The 1 The 1 st st Guideline of Guideline of Association Association for Eradication of Heart Attack for Eradication of Heart Attack AEHA AEHA for Definition of Vulnerable for Definition of Vulnerable Plaque and Vulnerable Patient Plaque and Vulnerable Patient (VP.org) (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 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
Dangerous PlaqueDangerous Plaque Non-Calcified Non-Calcified Plaque Plaque AHA Type IV AHA Type IV PlaquePlaqueNon-Stenotic Non-Stenotic PlaquePlaque
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
Proposed Histopathological Proposed Histopathological and Clinical Criteria for and Clinical Criteria for Definition of Vulnerable Definition of Vulnerable
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)
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
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
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
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
Different Types of Vulnerable Plaque As underlying Cause of Acute Coronary Events
NormalRupture-prone
Fissured ErodedCritical Stenosis Hemorrhage
Rupture-Prone Inflamed Plaque
Vulnerable Plaque Type 1
Eroded Plaque with Exposed Proteoglycans Prone to Thrombosis
Vulnerable Plaque Type 2
Fissured Plaque with Old and Fresh Overlaying Thrombi
Vulnerable Plaque Type 3
Intra-Plaque Hemorrhage Prone to Thrombosis
Vulnerable Plaque Type 4
Vulnerable Plaque Type 5
Asymptomatic Significantly Stenotic Plaque Prone to Occlusion