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Pandemic of cvd atlanta

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Pandemic of cvd atlanta

  1. 1. Vulnerable Plaques andVulnerable Plaques and Vulnerable PatientsVulnerable Patients The 1The 1stst   Guideline ofGuideline of Association for EradicationAssociation for Eradication of Heart Attack AEHAof Heart Attack AEHA for Definition offor Definition of Vulnerable Plaque and Vulnerable PatientVulnerable Plaque and Vulnerable 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
  2. 2. How the World Dies Today? 
  3. 3. Atherosclerotic Diseases Are Not Diseases of Affluence!  Only 2.7 millions of 6.3 million of whoOnly 2.7 millions of 6.3 million of who died by IHD were in the developeddied by IHD were in the developed country.country.  Cerebrovascular disease (stroke) killed 4.4 million people, of whom only 1.4 million were in the developed world.
  4. 4. Vulnerable plaques, vulnerable myocardium, andVulnerable plaques, vulnerable myocardium, and hypercoagulable state of the blood lead tohypercoagulable state of the blood lead to sudden cardiac death and acute myocardial infarction.sudden cardiac death and acute myocardial infarction. Vulnerable Blood Vulnerable Myocardium Vulnerable Plaque Vulnerable Patient
  5. 5. 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 Without Old Myocardial Damage Only Myocardial-Derived Factors (conductive disorders, …) Erosion Calcified Nodule Others With Critical Stenosis Without Critical Stenosis With Expansive Remodeling Without Expansive Remodeling
  6. 6.   Terminology:Terminology:  Culprit Plaque:Culprit Plaque: aa RetrospectiveRetrospective TerminologyTerminology  Vulnerable PlaqueVulnerable Plaque:: aa ProspectiveProspective TerminologyTerminology
  7. 7. Underlying pathologies ofUnderlying pathologies of “culprit” coronary lesions“culprit” coronary lesions 1.1. Ruptured Plaques (~70%)Ruptured Plaques (~70%)  Stenotic (~20%)Stenotic (~20%)  Non-stenotic (~50%)Non-stenotic (~50%) 2.2. Non-Ruptured Plaques (~ 30%)Non-Ruptured Plaques (~ 30%)  ErosionErosion  Calcified NoduleCalcified Nodule  Others / UnknownOthers / Unknown MJ Davies, Circ. 1990; Falk et al. Circ. 1995; Virmani et al. ATVB 2000
  8. 8. InterchangeableInterchangeable TerminologiesTerminologies YESYES NONO Vulnerable Plaque =Vulnerable Plaque = Vulnerable Plaque=Vulnerable Plaque= High-Risk PlaqueHigh-Risk Plaque Soft-PlaqueSoft-Plaque Dangerous PlaqueDangerous Plaque Non-Calcified PlaqueNon-Calcified Plaque AHA Type IV PlaqueAHA Type IV Plaque Non-Stenotic PlaqueNon-Stenotic Plaque
  9. 9. Proposed Histopathological and ClinicalProposed Histopathological and Clinical Criteria for Definition of VulnerableCriteria for 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 CoreThin Cap with Large Lipid Core 3.3. Endothelial Denudation with SuperficialEndothelial Denudation with Superficial Platelet AggregationPlatelet Aggregation 4.4. Fissured / Wounded PlaqueFissured / Wounded Plaque
  10. 10. Proposed Histopathological and ClinicalProposed Histopathological and Clinical Criteria for Definition of VulnerableCriteria for Definition of Vulnerable PlaquePlaque ••  MinorMinor Criteria:Criteria: 1.1. Superficial Calcified noduleSuperficial Calcified nodule 2.2. Glistening YellowGlistening Yellow 3.3. Intraplaque HemorrhageIntraplaque Hemorrhage 4.4. Critical StenosisCritical Stenosis 5.5. Positive Remodeling?Positive Remodeling?
  11. 11. Ideal method for screeningIdeal method for screening vulnerable plaque/patientvulnerable plaque/patient  Non-invasiveNon-invasive  InexpensiveInexpensive  AccurateAccurate  Widely ReproducibleWidely Reproducible
  12. 12. Diagnosis and Screening- PlaqueDiagnosis and Screening- Plaque LevelLevel  Plaque inflammation (macrophage density or rate of monocyte infiltration)Plaque inflammation (macrophage density or rate of monocyte 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, anti/pro-Endothelial denudation or dysfunction (local NO production, anti/pro- coagulation properties of the endothelium)coagulation properties of the endothelium)  Superficial platelet aggregation and fibrin deposition (residual muralSuperficial platelet aggregation and fibrin deposition (residual mural thrombus)thrombus)  Plaque cap thickness with a resolution of <100 micronPlaque cap thickness with a resolution of <100 micron  Collagen content, lipid core size, mechanical stability (stiffness andCollagen content, lipid core size, mechanical stability (stiffness and elasticity)  elasticity)  
  13. 13. Diagnosis and Screening- PlaqueDiagnosis and Screening- Plaque LevelLevel  Calcification burden and pattern (nodule, scattered, intimal,Calcification burden and pattern (nodule, scattered, intimal, deep)deep)  Angiogenesis, leaking vasa vaserum, and intraplaqueAngiogenesis, leaking vasa vaserum, and intraplaque hemorrhagehemorrhage  Presence of certain microbial antigensPresence of certain microbial antigens  Rate of apoptosis (apoptosis protein markers, coronaryRate of apoptosis (apoptosis protein markers, coronary microsatellite, etc)microsatellite, etc)  Shear stress imaging (flow pattern throughout coronary arteryShear stress imaging (flow pattern throughout coronary artery
  14. 14. Diagnosis and Screening-Diagnosis and Screening- Systemic LevelSystemic Level  CRP, CD40L, ICAM-1, VCAM, and otherCRP, CD40L, ICAM-1, VCAM, and other serological markers of inflammationserological markers of inflammation  MMPs and acidic digesting proteinases and theirMMPs and acidic digesting proteinases and their inhibitors such as TIMMPs and cystatininhibitors such as TIMMPs and cystatin  Circulating apoptosis marker(s)Circulating apoptosis marker(s)  Markers of blood hypercoagulabilityMarkers of blood hypercoagulability
  15. 15. Diagnosis and Screening-Diagnosis and Screening- Systemic LevelSystemic Level  Markers of blood fibrinolysisMarkers of blood fibrinolysis  Markers of lipid-peroxidationMarkers of lipid-peroxidation  PAPP-A, pregnancy associated plasma protein –PAPP-A, pregnancy associated plasma protein – AA  Plaque specific markers of immune activationPlaque specific markers of immune activation (anti-LDL Ab)(anti-LDL Ab)
  16. 16. A composite risk score Plaque vulnerability index Patient vulnerability index (e.g. VP Score) Screening
  17. 17. Diagnosis- Active InflammationDiagnosis- Active Inflammation  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 Gd-labeledTargeted CE-MRI, (macrophage specific Gd-labeled Ab)Ab)
  18. 18. Dx- Thin cap and large lipid coreDx- Thin cap and large lipid 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
  19. 19. DX-Endothelial denudation withDX-Endothelial denudation with superficial platelet aggregationsuperficial platelet aggregation  Intravascular:Intravascular:  OCTOCT  Angioscopy with dyeAngioscopy with dye  Matrix-targeted / fibrin-targeted immune-scintigraphyMatrix-targeted / fibrin-targeted immune-scintigraphy  Non-invasive:Non-invasive:  Fibrin/Matrix-targeted CE MRIFibrin/Matrix-targeted CE MRI  Platelet/fibrin-targeted SPECTPlatelet/fibrin-targeted SPECT
  20. 20. Fissured/Wounded PlaquesFissured/Wounded Plaques  Intravascular:Intravascular:  OCTOCT  IVUSIVUS  High-resolution IVUSHigh-resolution IVUS  MRIMRI     Non-invasive:Non-invasive:  Fibrin-targeted CE-MRIFibrin-targeted CE-MRI
  21. 21. Dx-Superficial Calcified NoduleDx-Superficial Calcified Nodule  Intravascular:Intravascular:  OCTOCT  High-resolution IVUSHigh-resolution IVUS  IVUSIVUS  Non-invasive:Non-invasive:  EBCTEBCT  MSCTMSCT  MRIMRI
  22. 22. Yellow Color (in Angioscopy)Yellow Color (in Angioscopy)  Intravascular:Intravascular:  AngioscopyAngioscopy  Transcatheter colorimetryTranscatheter colorimetry  Non-invasive:Non-invasive:  Presently impossiblePresently impossible
  23. 23. Dx- Intraplaque HemorrhageDx- Intraplaque Hemorrhage  Intravascular:Intravascular:  NIR SpectroscopyNIR Spectroscopy  Tissue DopplerTissue Doppler  Non-invasive:Non-invasive:  MRIMRI
  24. 24. 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
  25. 25. Blood FactorBlood Factor  Antithrombin III deficiencyAntithrombin III deficiency  Protein C or S deficiencyProtein C or S deficiency  Resistance to activated protein C (factor VResistance to activated protein C (factor V Leiden)Leiden)  Antiphospholipid syndromeAntiphospholipid syndrome  Nephrotic syndromeNephrotic syndrome  Platelet polymorphismsPlatelet polymorphisms
  26. 26. MyocardialMyocardial FactorFactor  Different cardiomyopathiesDifferent cardiomyopathies  Valvular diseaseValvular disease  Primary electric disturbancesPrimary electric disturbances  Chest traumaChest trauma  Anomalous origin of coronary arteriesAnomalous origin of coronary arteries  MyocarditisMyocarditis  Myocardial bridgingMyocardial bridging
  27. 27. Different Types of Vulnerable Plaque As underlying Cause of Acute Coronary Events Normal Rupture-prone Fissured Eroded Critical Stenosis Hemorrhage
  28. 28. Rupture-Prone Inflamed Plaque Vulnerable Plaque Type 1
  29. 29. Eroded Plaque with Exposed Proteoglycans Prone to Thrombosis Vulnerable Plaque Type 2
  30. 30. Fissured Plaque with Old and Fresh Overlaying Thrombi Vulnerable Plaque Type 3
  31. 31. Intra-Plaque Hemorrhage Prone to Thrombosis Vulnerable Plaque Type 4
  32. 32. Vulnerable Plaque Type 5 Asymptomatic Significantly Stenotic Plaque Prone to Occlusion

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