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  1. 1. Editorial Slides VP Watch –August 14, 2002 - Volume 2, Issue 32 Positive Arterial Remodeling and CoronaryPositive Arterial Remodeling and Coronary Plaque VulnerabilityPlaque Vulnerability Paul Schoenhagen M.D., FAHA The Cleveland Clinic Foundation, Cleveland, Ohio, USA
  2. 2.  As reported in VP Watch of this week, Rioufol et al. (Circulation 2002;106: 804 - 808), describe the presence of multiple ruptured atherosclerotic coronary plaques in patients presenting with an acute coronary syndrome (ACS). • Using intravascular ultrasound (IVUS), the authors systematically examined proximal portions of the entire coronary tree in 24 patients. Ruptured plaques were found in 9 patients (37.5%) at the “culprit lesion” but, more importantly, distant from the culprit lesion in 19 patients (79%).
  3. 3. • These additional, ruptured plaques were frequently multiple, located in a vessel different from the culprit vessel in 70% of patients and in 2 vessels not related to the acute event in 12% of patients. • Both culprit lesion and additional ruptured plaques were characterized by positive remodeling.
  4. 4. • Arterial Remodeling describes changes of vessel size at the site of atherosclerotic lesions. • Vessel expansion, as shown in the upper part of the following slide, is called positive remodeling and vessel constriction, as shown in the lower part, is called negative remodeling.
  5. 5. Positive Remodelin g Culprit Lesion EEM Contour Proximal Reference Proximal Reference Direction of Arterial RemodelingDirection of Arterial Remodeling Schoenhagen et al. Circulation 2000; 101:598-603 Negative Remodeli ng Culprit Lesion EEM Contour CCFIVUS
  6. 6. • Dr. Glagov and his colleagues at the University of Chicago described positive remodeling as a compensatory mechanism preventing lumen loss despite plaque growth in early atherosclerosis. • This is shown in the following slide showing tomographic sections through a vessel at different times. • Initially the plaque grows by expanding vessel size. With further plaque growth in more severe stages of the disease, the artery is unable to expand further and the lumen begins to narrow.
  7. 7. Adapted from Glagov et al.Adapted from Glagov et al. N Engl J MedN Engl J Med. 1987;316:1371-1375.. 1987;316:1371-1375. Glagov’s Coronary Remodeling Hypothesis NormalNormal vesselvessel MinimalMinimal CADCAD ProgressionProgression Compensatory expansionCompensatory expansion maintains constant lumenmaintains constant lumen Expansion overcome:Expansion overcome: lumen narrowslumen narrows SevereSevere CADCAD ModerateModerate CADCAD CCFIVUS
  8. 8. • The effect of this phenomenon is exemplified in the following slide. It shows a relative normal appearing angiogram on the left and IVUS images at point A and B on the right. – At point B the IVUS catheter is surrounded by the lumen. The vessel wall is seen as a narrow rim of tissue bound by the adventitia. – In panel A the lumen has similar size but a large plaque has expanded the vessel wall. In other words, positive remodeling allows plaque progression concealed to angiographic detection.
  10. 10. AA BB AA BB Lumen vs. Vessel WallLumen vs. Vessel Wall Lumen Plaque CCFIVUS
  11. 11. • Several recent studies have examined the relation between arterial remodeling and clinical presentation in different patient populations. • These studies consistently show that positive remodeling is associated with unstable coronary syndromes.
  12. 12. • We have compared the remodeling response in 85 patients presenting with unstable and 46 patients presenting with stable clinical presentation. • We found positive remodeling to be significantly more common in the unstable group. It was found in 52% of patients in the unstable but only 20% of the stable group. • Negative remodeling was significantly more common in the stable group. It was found in 56% of patients in the stable but only 32% of the stable group.
  13. 13. Direction of Remodeling and Clinical Presentation 00 2020 4040 6060 Percentof Cohort Positive Remodeling Absence of Remodeling Negative Remodeling Unstable Stable *p=0.000 3 *p=0.3 *p=0.006 Schoenhagen et al. Circulation 2000;101:598-603CCFIVUS
  14. 14. Unstable Presentation: Positive Remodeling Echolucent Plaque with Plaque Rupture and Remodeling Index of 1.42 Proximal Reference EEM = 14.3 mm2 EEM = 20.3 mm2 Culprit Lesion Schoenhagen et al. Circulation 2000; 101:598-603 CCFIVUS
  15. 15. • Both, positive remodeling and plaque vulnerability are characterized by an inflammatory response: – Femoral artery cross-sections with larger vessel and plaque area showed: (Pasterkamp et al. JACC 1998;32:655) • More CD68, CD 45 positive cells • Less collagen • Less alpha-actin staining MMP – Increased presence of MMP in abdominal aortic aneurysms.
  16. 16. • We examined pre-interventional intravascular ultrasound images of 35 patients for extent and direction of remodeling • Histologic samples were obtained with directional atherectomy (DCA) • Immuno-Staining for: MMP 1,2,3,9 • We found a significant relation between MMP3 presence and direction of remodeling. Intense MMP 3 presence was associated with positive remodeling and mild MMP 3 presence with negative remodeling.
  17. 17. MMP3 Presence and Direction of Remodeling 58 42 17 83 0 10 20 30 40 50 60 70 80 90 Percent of Cohort Positive Remodeling Negative/Intermediate Remodeling Direction of Remodeling Intense Mild Schoenhagen et al. Am J Cardiol. 2002;89:1354-9
  18. 18. Positive Remodeling and Heavy MMP3 Presence Remodeling Index = 1.40 LesionProximal Reference EEM = 10.5 mm2 Lesion EEM = 7.5 mm2 Schoenhagen et al. Am J Cardiol. 2002;89:1354-9 CCFIVUS
  19. 19. Negative Remodeling and Mild MMP3 Presence Remodeling Index = 0.71 LesionProximal Reference EEM = 10.5 mm2 Lesion EEM = 7.5 mm2 Schoenhagen et al. Am J Cardiol. 2002;89:1354-9 CCFIVUS
  20. 20. • Arterial remodeling could therefore be a characteristic of vulnerable lesions, at risk to rupture. • The association between positive remodeling and plaque vulnerability has been explored in a recent prospective study: • Dr. Yamagichi et al. at the National Cardiovascular Center in Osaka, Japan have examined mildly stenotic plaques prospectively with intravascular ultrasound. • Plaques causing acute coronary syndromes during follow up more frequently exhibited positive remodeling at baseline.
  21. 21. • 114 sites <50% diameter stenoses • Follow-up after 21.8 months • 12 acute coronary syndromes • Ruptured plaques at baseline showed: – Greater percent plaque area (67% vs. 57%) – Similar lumen area (6.7mm2 vs. 7.5mm2 ) – Frequent echolucent zones Yamagichi et al. JACC 2000; 35:106-11
  22. 22. • It is an attractive hypothesis to describe positive and negative remodeling as temporary stages of plaque development. • Positively remodeled lesions may represent early active lesions with increased inflammatory response. Matrix degradation may lead to vessel expansion but also to increased plaque vulnerability and plaque rupture. • Negative remodeling may be associated with advanced lesions characterized by fibrosis and decreased inflammation. These changes may lead to vessel shrinkage but also plaque stabilization.
  23. 23. Conclusion: • The findings of Rioufol et al. support the growing body of evidence that coronary artery disease is a systemic disease of the entire coronary tree. Further research is needed to illuminate the complex relation between focal manifestation and overall disease burden.
  24. 24. • Rioufol G, Finet G, Andre-Fouet X, et al. Multiple atherosclerotic plaque rupture in acute coronary syndrome: A three-vessel intravascular ultrasound study. Circulation 2002;106:804-808 • Goldstein JA, Demetriou D, Grines CL, et al. Multiple complex coronary plaques in patients with acute myocardial infarction. N Engl J Med 2000;343:915-22 3. Burke AP, Farb A, Malcom GT, et al. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med 1997;336:1276- 82 • Asakura M, Ueda Y, Yamaguchi O, et al. Extensive development of vulnerable plaques as a pan-coronary process in patients with myocardial infarction: An angioscopic study. J Am Coll Cardiol 2001;37:1284-8 • Burke AP, Kolodgie FD, Farb A, et al. Healed plaque ruptures and sudden coronary death: evidence that subclinical rupture has a role in plaque progression. Circulation 2001;103:934-40 • Varnava AM, Mills PG, Davies MJ. Relationship between coronary artery remodeling and plaque vulnerability. Circulation 2002;105:939-943 • Libby P. Current concepts of the pathogenesis of the acute coronary syndromes. Circulation 2001;104:365-372 • Casscells W, Hathorn B, David M, et al. Thermal detection of cellular infiltrates in living atherosclerotic plaques: possible implications for plaque rupture and thrombosis. Lancet 1996;347:1447-51 • Glagov S, Weisenberg E, Zarins CK, et al. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 1987;316:1371-53 • Schoenhagen P, Ziada KM, Kapadia SR, et al. Extent and direction of arterial remodeling in stable and unstable coronary syndromes. Circulation 2000;101:598-603 • Schroeder S, Kopp AF, Baumbach A, et al. Non-invasive characterization of coronary lesion morphology by multi-slice computed tomography: a promising new technology for risk stratification of patients with coronary artery disease. Heart 2001;85:576-577 • Fayad ZA, Fuster V. Clinical imaging of the high-risk or vulnerable atherosclerotic plaque. Circ Res 2001;89:305-16 References