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Vulnerable patient slides without movies
Dear Member of AEHA
Thank you for participating in the First Vulnerable
Patient Symposium. This educational CD contains
multiple PowerPoint slide presentations along with
animated movies. Also included the Part I and II of
the Vulnerable Patient Manuscript.
AEHA would like to thank the generous support
of :
Amersham Health, CV Therapeutics, diaDexus, and
American Heart Technologies.
Introducing
The Vulnerable Patient Consensus Statement
Published in
Circulation Journal Vol108, No14; October 7, 2003
Abstract
Circulation Journal Vol108, No14; October 7, 2003
Naghavi et al. Circulation. 2003;108:1664
Naghavi et al. Circulation. 2003;108:1664
Vulnerable patient slides without movies
Underlying Pathologies of "Culprit" Coronary Lesions
Naghavi et al. 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
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
Naghavi et al. Circulation. 2003;108:1664
Plaque ruptureFriedman 1966
Plaque rupture illustrated in 1966
The Challenge of Terminology
• Culprit Plaque; A Retrospective Term
Naghavi et al. Circulation. 2003;108:1664
Vulnerable Plaque = Future Culprit Plaque
• Vulnerable Plaque; A Prospective Term
• 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
Naghavi et al. Circulation. 2003;108:1664
• 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
Naghavi et al. Circulation. 2003;108:1664
• 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
Naghavi et al. Circulation. 2003;108:1664
• 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
Naghavi et al. Circulation. 2003;108:1664
Naghavi et al. Circulation. 2003;108:1664
The most common type
Naghavi et al. Circulation. 2003;108:1664
The Most Common Type of Vulnerable Plaque
Naghavi et al. Circulation. 2003;108:1664
Non-Stenotic Vulnerable Plaques overall are More Dangerous
Since they are far More Frequent than Stenotic Ones
Naghavi et al. Circulation. 2003;108:1664
Both Morphology and Activity Assessments are Needed
Vulnerable patient slides without movies
Naghavi et al. 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)
• 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)
Naghavi et al. Circulation. 2003;108:1664
Vulnerable patient slides without movies
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
Naghavi et al. Circulation. 2003;108:1664
Conditions and Markers Associated with Myocardial Vulnerability
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
Naghavi et al. Circulation. 2003;108:1664
Conditions and Markers Associated with Myocardial Vulnerability
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
Naghavi et al. Circulation. 2003;108:1664
Naghavi et al. Circulation. 2003;108:1664
The VP Pyramid
Screening >> Diagnosis Treatment>>
Outlines for Annual
CVD Genotyping?
Naghavi et al. Circulation. 2003;108:1664
Out-of- hospital
screening (EF,
serum tests,
physician visit)
Non-Invasive Imaging
Diagnostic Cath
Drug-Eluting Stent
Statin and other
Drugs
Annual Cost of
Heart Attacks
in the USA
Stay Tuned for the Guidelines
Screening >> Diagnosis Treatment>>
in Part III and IV
HELP AEHA SAVE VULNERABLE PATIENTS
Vulnerable patient slides without movies

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Vulnerable patient slides without movies

  • 2. Dear Member of AEHA Thank you for participating in the First Vulnerable Patient Symposium. This educational CD contains multiple PowerPoint slide presentations along with animated movies. Also included the Part I and II of the Vulnerable Patient Manuscript. AEHA would like to thank the generous support of : Amersham Health, CV Therapeutics, diaDexus, and American Heart Technologies.
  • 3. Introducing The Vulnerable Patient Consensus Statement Published in
  • 4. Circulation Journal Vol108, No14; October 7, 2003
  • 5. Abstract Circulation Journal Vol108, No14; October 7, 2003
  • 6. Naghavi et al. Circulation. 2003;108:1664
  • 7. Naghavi et al. Circulation. 2003;108:1664
  • 9. Underlying Pathologies of "Culprit" Coronary Lesions Naghavi et al. 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
  • 10. 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 Naghavi et al. Circulation. 2003;108:1664 Plaque ruptureFriedman 1966
  • 12. The Challenge of Terminology • Culprit Plaque; A Retrospective Term Naghavi et al. Circulation. 2003;108:1664 Vulnerable Plaque = Future Culprit Plaque • Vulnerable Plaque; A Prospective Term
  • 13. • 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 Naghavi et al. Circulation. 2003;108:1664
  • 14. • 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 Naghavi et al. Circulation. 2003;108:1664
  • 15. • 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 Naghavi et al. Circulation. 2003;108:1664
  • 16. • 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 Naghavi et al. Circulation. 2003;108:1664
  • 17. Naghavi et al. Circulation. 2003;108:1664 The most common type
  • 18. Naghavi et al. Circulation. 2003;108:1664 The Most Common Type of Vulnerable Plaque
  • 19. Naghavi et al. Circulation. 2003;108:1664 Non-Stenotic Vulnerable Plaques overall are More Dangerous Since they are far More Frequent than Stenotic Ones
  • 20. Naghavi et al. Circulation. 2003;108:1664 Both Morphology and Activity Assessments are Needed
  • 22. Naghavi et al. 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)
  • 23. • 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) Naghavi et al. Circulation. 2003;108:1664
  • 25. 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 Naghavi et al. Circulation. 2003;108:1664 Conditions and Markers Associated with Myocardial Vulnerability
  • 26. 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 Naghavi et al. Circulation. 2003;108:1664 Conditions and Markers Associated with Myocardial Vulnerability
  • 27. 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 Naghavi et al. Circulation. 2003;108:1664
  • 28. Naghavi et al. Circulation. 2003;108:1664
  • 29. The VP Pyramid Screening >> Diagnosis Treatment>> Outlines for Annual
  • 30. CVD Genotyping? Naghavi et al. Circulation. 2003;108:1664
  • 31. Out-of- hospital screening (EF, serum tests, physician visit) Non-Invasive Imaging Diagnostic Cath Drug-Eluting Stent Statin and other Drugs
  • 32. Annual Cost of Heart Attacks in the USA
  • 33. Stay Tuned for the Guidelines Screening >> Diagnosis Treatment>> in Part III and IV
  • 34. HELP AEHA SAVE VULNERABLE PATIENTS