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Progression, Regression, and Remodeling of Atherosclerosis ( 동맥경화증의 진행 , 퇴축 , 그리고 재성형 )

Progression, Regression, and Remodeling of Atherosclerosis ( 동맥경화증의 진행 , 퇴축 , 그리고 재성형 ) Hyo-Soo Kim, MD, PhD Cardiovascular Center, Seoul National University Hospital, Seoul, Korea 김 효 수 서울대학교병원 심혈관센터 서울대학교 의과대학 내과학교실. The Spectrum of Vascular Remodeling.

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Progression, Regression, and Remodeling of Atherosclerosis ( 동맥경화증의 진행 , 퇴축 , 그리고 재성형 )

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  1. Progression, Regression, and Remodeling of Atherosclerosis (동맥경화증의 진행, 퇴축, 그리고 재성형) Hyo-Soo Kim, MD, PhD Cardiovascular Center, Seoul National University Hospital, Seoul, Korea 김 효 수 서울대학교병원 심혈관센터 서울대학교 의과대학 내과학교실

  2. The Spectrum of Vascular Remodeling Gibbons G & Dzau VJ NEJM 1994;330;1431-8

  3. Clinical Conditions involving Vascular Remodeling Gibbons G & Dzau VJ NEJM 1994;330;1431-8

  4. Longitudinal & Cross Sectional Images (Positive Remodeling) Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;297-306.

  5. Extremes of Vascular Remodeling RR = EEM area lesion / EEM area prox reference Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;297-306.

  6. Tomographic Sections of Human Coronary Artery (IVUS image) Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;297-306.

  7. Tomographic Sections of Human Coronary Artery (IVUS image) Birnbaum Y,, Siegel RJ. JACC 1997;30;1149-64.

  8. Positive Remodeling (RR = 18.9/14.9 = 1.32) Negative Remodeling (RR = 11.5/16.0 = 0.71)

  9. Various Types of Vascular Remodeling Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;297-306.

  10. Positive Remodeling at Early Stage of Atherosclerosis Results in False Negative on CAG • Positive Remodeling • at Early Lesion • Distal Reference Nissen SE & Yock P. Circulation 2001;103;604-616.

  11. Negative Remodeling in addition to Neointimal Formation Results in Significant Stenosis on CAG • Distal Reference • Stenotic Lesion Nissen SE & Yock P. Circulation 2001;103;604-616.

  12. The Possible Sequential Changes of Atherosclerotic Artery ( based on the postmortem analysis of 136 LMCA ) Early Phase : Overcompensation Vss Enlargement > Plaque Accumulation Late Phase : Decompensation Vss Enlargement < Plaque Accumulation Glagov S, et al. NEJM 1987;316;1371-53.

  13. LAD in worst quartile LAD in best quartile Segmental Comparison between Normal and Atherosclerotic Human Coronary Artery Pts = 125 LAD = 481 segs LAD with Atherosclerosis : Plaq Area correlates with Vss Area : compensatory enlargement : esp, at distal segment Zarins CK,, Glagov S. J Vasc Surg 1988;7;386.

  14. Two Extremes of Vascular Remodeling Birnbaum Y,, Siegel RJ. JACC 1997;30;1149-64.

  15. Proportions of Positive or Negative Remodeling (IVUS Data of Human Coronary Primary Atherosclerosis) (+) (-) Nishioka T,, Siegel RJ. JACC 1996;27;1571-6.

  16. Proportions of Positive or Negative Remodeling (IVUS Data of Human Coronary Primary Atherosclerosis) 25% 55% 20% 15% or 22% in other studies# Nishioka T,, Siegel RJ. JACC 1996;27;1571-6. # Mintz GS, et al. Circulation 1997;95;1791 Lim TT, et al. Circulation 1997;95;855-9.

  17. Saphenous Vein Graft Atherosclerosis at the Site of Venous Valves Siegel RJ, et al. [letter] Circulation 1996;94;3005-6.

  18. Absence of Positive Remodeling in Saphenous Vein Bypass Graft ( IVUS Data ) Nishioka T,, Siegel RJ. Circulation 1996;93;683-90.

  19. Direction of Remodeling & Plaque Stability Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;297-306.

  20. Direction of Remodeling & Plaque Stability • Early Phase of Atherosclerosis • Compensatory Enlargement • Positive Remodeling • Unstable Plaque • Late Phase of Atherosclerosis • Shrinkage of Vessel • Negative Remodeling • Stable Plaque Nissen SE & Yock P. Circulation 2001;103;604-616.

  21. Ruptured Plaque with Positive Remodeling • Prox Reference • Ruptured Plaque Nissen SE & Yock P. Circulation 2001;103;604-616.

  22. Summary of Vascular Remodeling in Native Coronary Atherosclerosis • 1. Sequential Change of Remodeling (in Histologic study) • Compensatory enlargement at early phase • No lumen loss until plaque area reaches 40% of EEM area • 2. Proportion of Remodeling (in IVUS study) • 50% of lesions show compensatory enlargement • 15 ~ 25 % of lesions show vascular shrinkage • Shrinkage is highly associated with lesion calcification • 3. Special Issues on Compensatory Enlargement • impaired in DM & smokers & saphenous vein graft • greater in eccentric lesion or concentric lesion ?

  23. Mechanism of Positive Remodeling in Early Atherosclerosis • Medial change • Atherosclerosis • Atrophy & thinning of media • weakening of the arterial wall • dilatation • Shear stress change • Expanding atheroma • lumen narrowing • increased shear stress •  dilatation with normalization of shear stress

  24. Mechanism of Negative Remodeling • Early event ? (failure of the adaptive compensatory dilation) • Calcified lesion is highly associated with negative remodeling • Fibrocalcific element limits adaptive positive remodeling ? • Late event ? (active arterial shrinkage) • Mature plaque • with increased fibrous and calcific deposits & apoptosis • as well as decreased lipid content • results in retraction • Contributing factor ? (Venturi effect) • Vascular narrowing  rapid flow & low pressure  shrinkage

  25. Serial Observation of Arterial Remodeling Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;297-306.

  26. Association of Remodeling & Restenosis after Coronary Balloon Angioplasty Restenotic Patent Luo H,, Siegel RJ. ATVB 1996;16;1393-8.

  27. Summary of Vascular Remodeling during Restenosis after PTCA or DCA • Vascular shrinkage is important determinant for restenosis • 75% of luminal loss d/t decrease of EEM area • 25% of luminal loss d/t increase of Plaque area • 2. Shrinkage is more important • for restenosis after balloon or DCA with shallow injury • 3. Intimal hyperplasia is more important • for restenosis after DCA with deep injury or stenting • DM pts

  28. Mechanism of Negative Remodeling after PTCA or DCA • Adventitial role • Overstretch & deep tear • Inflammation & proliferation & differentiation of Fb to myofibroblast • Contraction of adventitial scar • Late lumen narrowing Determinant of Remodeling Direction ? • Severity and depth of the wall injury • Extent of inflammatory reaction • Pressure, wall stress, & flow through lesion

  29. The Agents of Vascular Remodeling Gibbons G & Dzau VJ NEJM 1994;330;1431-8

  30. The Factors that modulate the Growth of VSMC Gibbons G & Dzau VJ NEJM 1994;330;1431-8

  31. Mediators of Vascular Remodeling in ECM Gibbons G & Dzau VJ NEJM 1994;330;1431-8

  32. Progression, Regression, and Remodeling Glagov S, et al. NEJM 1987;316;1371-53.

  33. Atherosclerosis Regression Trial with IVUS F/U by Lipid-Lowering Agent REVERSAL (Reversal of Atherosclerosis with Lipitor) Nissen SE. AJC 2000;86(suppl 1);12-17H.

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