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IntroducingThe 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
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
Writer and Director: Morteza Naghavi, MDDesign and Animation: Mark JohnsonMusic: Eric Jarvis
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Click to view the Natural History of Atherosclerosis and Vulnerable Plaques
Naghavi et al. Circulation. 2003;108:1664
Both Morphology and Activity Assessments are Needed
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
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
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Click to view the Vulnerable Plaque-Blood-Myocardium Movie
The VP PyramidScreening >> 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 CathDrug-Eluting Stent
Statin and other Drugs
Annual Cost of Heart Attacks
in the USA
Stay Tuned for the GuidelinesScreening >> Diagnosis Treatment>>
in Part III and IV
HELP AEHA SAVE VULNERABLE PATIENTS
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