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Vulnerable Plaque 분당서울대학교병원 심장센터 연태진 Causes / mediators of atherothrombosis Atherogenesis Atherothrombosi Vascular risk factors Genes, BP, Smoking, Chol., Diabetes Endothelial dysfunction Fatty streak Fibrous plaque Inflammation Unstable Fibrous plaque Plaque rupture/ fissure & thrombosis …… …….. Upregulation of adhesion molecules Lipid-laden macrophages (foam cells) permeability to pl. lipoproteins (NO, A II, PDGF) T lymphocyte activation Leucocytes migrate into artery wall (ox. LDL, PDGF) Smooth muscle cells migrate & lipid laden Fibrous cap Thinning/fissuring of fibrous cap Necrotic core (apoptosis of lipid & WBC) Large, lipid core Expansion at shoulders as leucocytes adhere & enter (ox. LDL, PDGF) Angina Influx & activation of macrophages release metalloproteinases Acute coronary syndrome Cardiovascular death Haemorrhage from - vasa vasorum Ross R. NEJM 1999; 340: 115-126 - lumen of artery Stable and Rupture-prone plaque Rupture of a coronary plaque The fibrous cap ruptures and the lipid core is exposed to the blood stream Rupture of a coronary plaque- Thrombosis Platelets aggregate around the exposed lipid core and initiate thrombus formation Thrombosis propagation Underlying pathology of acute coronary syndrome (unstable angina, acute MI) and sudden cardiac death 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 Naghavi et al. Circulation. 2003;108:1664 Different Types of Vulnerable Plaques Major Underlying Cause of Acute Coronary Events Rupture-prone Normal Fissured Critical Stenosis Hemorrhage Eroded Rupture-prone plaque Eroded plaque with thrombosis Calcified nodule The Challenge of Terminology Culprit Plaque; A Retrospective Term Vulnerable Plaque; A Prospective Term Vulnerable Plaque (high-risk plaque) = Future Culprit Plaque 좁은 의미: Rupture-prone plaque 넓은 의미: Plaque that is at increased risk of thrombosis and rapid stenosis progression Naghavi et al. Circulation. 2003;108:1664 Criteria for Defining Vulnerable Plaque Based on the Study of Culprit Plaques Major criteria . Active inflammation (monocyte/macrophage and sometimes Tcell infiltration) . Thin cap with large lipid core . Endothelial denudation with superficial platelet aggregation . Fissured plaque . Stenosis 90% Minor criteria . Superficial calcified nodule . Glistening yellow . Intraplaque hemorrhage . Endothelial dysfunction . Outward (positive) remodeling Markers of Vulnerability at the Plaque/Artery Level Plaque Morphology/Structure . Plaque cap thickness . Plaque lipid core size . Plaque stenosis (luminal narrowing) . Remodeling (expansive vs constrictive remodeling) . Color (yellow, glistening yellow, red, etc) . Collagen content versus lipid content, mechanical stability (stiffness and elasticity) . Calcification burden and pattern (nodule vs scattered, superficial vs deep, etc) . Shear stress (flow pattern throughout the coronary artery) Markers of Vulnerability at the Plaque/Artery Level Activity/Function . Plaque inflammation (macrophage density, rate of monocyte infiltration and density of activated T cell) . Endothelial denudation or dysfunction (local NO production, anti-/procoagulation properties of the endothelium) . Plaque oxidative stress . Superficial platelet aggregation and fibrin deposition (residual mural thrombus) . Rate of apoptosis (apoptosis protein markers, coronary microsatellite, etc) . Angiogenesis, leaking vasa vasorum, and intraplaque hemorrhage . Matrix-digesting enzyme activity in the cap (MMPs 2, 3, 9, etc) . Certain microbial antigens (eg, HSP60, C. pneumoniae) Markers of Vulnerability at the Plaque/Artery Level Pan-Arterial . Transcoronary gradient of serum markers of vulnerability . Total coronary calcium burden . Total coronary vasoreactivity (endothelial function) . Total arterial burden of plaque including peripheral (eg, carotid IMT) Diagnostic technique Intravascular Ultrasound (IVUS) Advantage: Reveals the morphology of the plaque Disadvantages: Low spatial resolution (~ 200 m) Limited information about the plaque composition IVUS IVUS-radiofrequency data Virtual histology Elastography Optical Coherence Tomography (OCT) infrared light wave reflection Morphological Chemical Physiological Lesion size Lesion shape % Stenosis Cap thickness Lipid, Protein, Water Calcium Collagen Flow disturbances CFR, FFR Grey Scale (2-D, L-Mode) Spectroscopy Polarization Doppler OCT characteristics Fibrous Lipid Calcific 500 µm lp lp Homogeneous, Signal-rich Echolucent, Diffuse Borders Echolucent, Sharp Borders OCT Fibro-fatty plaque Histology Thin Cap High lipid content OCT OCT Advantage: High resolution improved visualization of fibrous caps and plaque components Possibility to detect inflammation Disadvantages: Limited penetration Angioscopy Angioscopy Advantages: Direct visualization of the plaque surface Disadvantages: Visualizes only the surface of the plaque Requires a proximal occluding balloon Subjective interpretation Intravascular Thermography Intravascular Thermography Advantages: Gives information about plaque inflammation Disadvantages: Overlap in temperature heterogeneity b/w stable and unstable presentations Plaque temperature may be affected by the blood flow Spectroscopy Analyze the light scattered from the tissue Advantage: Chemical compounds detection Disadvantage: lack of structural definition may needs combination with imaging techniques Others Intravascular MRI Intravascular nuclear imaging MRI Electron Beam Computed Tomography (EBCT) Therapeutic options Focal • PCI in selected case • Under investigations cryoplasty sonotherapy photodynamic therapy….. Regional Systemic: medical tx. (aspirin, statins, beta-blocker, ACE inhibitor…..)
