Vulnerable patient slides without movies

Dear Member of AEHAThank 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.

IntroducingThe Vulnerable Patient Consensus Statement

Published in

Circulation Journal Vol108, No14; October 7, 2003

http://circ.ahajournals.org/cgi/content/abstract/108/14/1664

Abstract

Circulation Journal Vol108, No14; October 7, 2003

http://circ.ahajournals.org/cgi/content/abstract/108/14/1664

Naghavi et al. Circulation. 2003;108:1664


Underlying Pathologies of "Culprit" Coronary Lesions


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


Plaque ruptureFriedman 1966

Plaque rupture illustrated in 1966

The Challenge of Terminology

• Culprit Plaque; A Retrospective Term


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


• 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


• 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



• 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




The most common type


The Most Common Type of Vulnerable Plaque


Non-Stenotic Vulnerable Plaques overall are More Dangerous Since they are far More Frequent than Stenotic Ones


Both Morphology and Activity Assessments are Needed


• 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)


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


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


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



The VP PyramidScreening >> Diagnosis Treatment>>

Outlines for Annual

CVD Genotyping?


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

Health & Medicine

Vulnerable patient slides without movies