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065 association for eradication of heart attack

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065 association for eradication of heart attack

  1. 1. From The First Vulnerable Plaque Symposium 7-10pm Rosen Plaza Hotel March 27, 2001– Orlando, FL To The First Vulnerable Patient Symposium 7-10pm Rosen Plaza Hotel November 11, 2003 – Orlando, FL What Have We Learned?
  2. 2. Introducing The Vulnerable Patient Consensus Statement Published in
  3. 3. Circulation. 2003;108:1664
  4. 4. Abstract
  5. 5. Circulation. 2003;108:1664
  6. 6. Circulation. 2003;108:1664
  7. 7. Underlying Pathologies of "Culprit" Coronary Lesions Circulation. 2003;108:1664 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
  8. 8. Plaque rupture1966Constantinides Plaque rupture1966Chapman Thrombogenic gruel1964Byers Plaque ulceration1963Gore Plaque thrombosis1961Crawford Plaque erosion1957Helpern Plaque fissure1940Horn Rupture-induced occlusion1938Wartman Rupture of atheromatous abscess1934Leary Plaque rupture1931Olcott Description UsedYearAuthor Descriptions Used by Pioneers for Culprit Plaques Plaque ruptureFriedman 1966 Circulation. 2003;108:1664
  9. 9. Plaque rupture illustrated in 1966
  10. 10. The Challenge of Terminology • Culprit Plaque; A Retrospective Term Circulation. 2003;108:1664 Vulnerable Plaque = Future Culprit Plaque • Vulnerable Plaque; A Prospective Term
  11. 11. • Outward (positive) remodeling • Endothelial dysfunction • Intraplaque hemorrhage • Glistening yellow • Superficial calcified nodule Minor criteria • Critical Stenosis • Fissured plaque • Endothelial denudation with superficial platelet aggregation • Thin cap with large lipid core • Active inflammation (monocyte/macrophage and sometimes T-cell infiltration) Major criteria Criteria for Defining Vulnerable Plaque Based on the Study of Culprit Plaques Circulation. 2003;108:1664
  12. 12. • Shear stress (flow pattern throughout the coronary artery) • Calcification burden and pattern (nodule vs scattered, superficial vs deep, etc) • Collagen content versus lipid content, mechanical stability (stiffness and elasticity) • Color (yellow, glistening yellow, red, etc) • Remodeling (expansive vs constrictive remodeling) • Plaque stenosis (luminal narrowing) • Plaque lipid core size • Plaque cap thickness Plaque Morphology / Structure Markers of Vulnerability at the Plaque/Artery Level Circulation. 2003;108:1664
  13. 13. • Certain microbial antigens (eg, HSP60, C. pneumoniae) • Matrix-digesting enzyme activity in the cap (MMPs 2, 3, 9, etc) • Angiogenesis, leaking vasa vasorum, and intraplaque hemorrhage • Rate of apoptosis (apoptosis protein markers, coronary microsatellite, etc) Superficial platelet aggregation and fibrin deposition (residual mural • thrombus) • Plaque oxidative stress • Endothelial denudation or dysfunction (local NO production, anti- /procoagulation properties of the endothelium) • Plaque inflammation (macrophage density, rate of monocyte infiltration and density of activated T cell) Plaque Activity / Function Markers of Vulnerability at the Plaque/Artery Level Circulation. 2003;108:1664
  14. 14. • Total arterial burden of plaque including peripheral (eg, carotid IMT) • Total coronary vasoreactivity (endothelial function) • Total coronary calcium burden • Transcoronary gradient of serum markers of vulnerability Pan-Arterial Markers of Vulnerability at the Plaque/Artery Level Circulation. 2003;108:1664
  15. 15. Circulation. 2003;108:1664 The most common type
  16. 16. Circulation. 2003;108:1664 The Most Common Type of Vulnerable Plaque
  17. 17. Circulation. 2003;108:1664 Non-Stenotic Vulnerable Plaques overall are More Dangerous Since they are far More Frequent than Stenotic Ones
  18. 18. Writer and Director: Morteza Naghavi, MD Design and Animation: Mark Johnson Music: Eric Jarvis Click here to escape the movie Click to view the Natural History of Atherosclerosis and Vulnerable Plaques
  19. 19. Circulation. 2003;108:1664 Both Morphology and Activity Assessments are Needed
  20. 20. Circulation. 2003;108:1664 • Abnormal lipoprotein profile (e.g. high LDL, low HDL, abnormal LDL and HDL size density, lipoprotein (a), Lp-PLA2 …) • Serum markers of insulin resistance syndrome (e.g. diabetes, hyper triglyceridemia ) • Non-specific markers of inflammation (e.g. hsCRP, CD40L, ICAM-1, VCAM-1, P-selectin, leukocytosis, and other serologic markers related to the immune system. These markers may not be specific for atherosclerosis or plaque inflammation) • Specific markers of immune activation (e.g. anti-LDL antibody, anti-HSP antibody) • Markers of lipid-peroxidation (e.g. ox-LDL and ox-HDL) • Homocysteine • Pregnancy-associated plasma protein A (PAPP-A) • Circulating apoptosis marker(s) (e.g., Fas/Fas ligand, not specific to plaque) • Asymmetric dimethylarginine (ADMA) / dimethylarginine dimethylaminohydrolase (DDAH) • Circulating nonesterified fatty acids (e.g. NEFA) Serologic Markers of Vulnerability (Reflecting Metabolic and Immune Disorders)
  21. 21. • Markers of blood hypercoagulability (e.g. fibrinogen, D-dimer, and factor V Leiden) • Increased platelet activation and aggregation (e.g., gene polymorphisms of platelet glycoproteins IIb/IIIa, Ia/IIa, and Ib/IX) • Increased coagulation factors (e.g., clotting of factors V, VII, VIII, von Willebrand factor, XIII) • Decreased anticoagulation factors (e.g., proteins S, C, thrombomodulin, and antithrombin III) • Decreased endogenous fibrinolysis activity (e.g. reduced t-PA, increased PAI- 1, certain PAI-1 polymorphisms) • Prothrombin mutation (e.g. G20210A) • Other thrombogenic factors (e.g., anticardiolipin antibodies, thrombocytosis, sickle cell disease, polycythemia, diabetes mellitus, hypercholesterolemia, hyperhomocysteinemia) • Increased viscosity • Transient hypercoagulability (e.g. smoking, dehydration, infection, adrenergic surge, cocaine, estrogens, postprandial, etc.) Blood Markers of Vulnerability (Reflecting Hypercoagulability) Circulation. 2003;108:1664
  22. 22. With atherosclerosis-derived myocardial ischemia as shown by: ECG abnormalities: - During rest - During stress test - Silent ischemia (e.g. ST changes on Holter monitoring) Perfusion and viability disorder: - PET scan - SPECT Wall motion abnormalities: - Echocardiography - MR imaging - X-ray ventriculogram - MSCT Circulation. 2003;108:1664 Conditions and Markers Associated with Myocardial Vulnerability
  23. 23. Without atherosclerosis-derived myocardial ischemia: • Sympathetic hyperactivity • Impaired arterial baroreflex • Left ventricular hypertrophy • Cardiomyopathy (dilated, hypertrophic, restrictive, or right ventricular) • Valvular disease (aortic stenosis and mitral valve prolapse) • Electrophysiologic disorders: - Long QT syndrome, Brugada syndrome, Wolff-Parkinson-White syndrome, sinus and atrioventricular conduction disturbances, catecholaminergic polymorphic ventricular tachycardia, T-wave alternans, drug-induced torsades de pointes • Commotio cordis • Anomalous origination of a coronary artery • Myocarditis • Myocardial bridging Circulation. 2003;108:1664 Conditions and Markers Associated with Myocardial Vulnerability
  24. 24. Diagnostic Criteria: - Arrhythmia - QT dispersion - QT dynamics - T wave alternans - Ventricular late potentials - Heart rate variability Diagnostic Techniques: Non-Invasive: Resting ECG Stress ECG Ambulatory ECG Signal averaged electrocardiogram (SAECG) Surface high-resolution ECG Invasive: Programmed ventricular stimulation (PVS) Real-time 3D magnetic-navigated activation map Available Techniques for Electrophysiologic Risk Stratification of Vulnerable Myocardium Circulation. 2003;108:1664
  25. 25. Click here to escape the movie Click to view the Vulnerable Plaque-Blood-Myocardium Movie
  26. 26. The VP Pyramid Screening >> Diagnosis Treatment>> Outlines for Annual
  27. 27. CVD Genotyping? Naghavi et al. Circulation. 2003;108:1664
  28. 28. Out-of- hospital screening (EF, serum tests, physician visit) Non-Invasive Imaging Diagnostic Cath Drug-Eluting Stent Statin and other Drugs
  29. 29. Annual Cost of Heart Attacks in the USA