(Circulation. 1999;99:44-52.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Pathology of Acute and Chronic Coronary Stenting in Humans
From the Department of Cardiovascular Pathology (A.F., A.J.C., R.V.), Armed Forces Institute of Pathology, Washington, DC; the Mayo Clinic (G.S., W.D.E., R.S.S.), Rochester, Minn; and The University of Ottawa Heart Institute and Ottawa Civic Hospital (V.M.W.), Ottawa, Ontario, Canada.
Correspondence to Renu Virmani, MD, Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000.
Background—Despite the increasing use of stents, few reports have described human coronary artery morphology early and late after stenting.
Methods and Results—Histology was performed on 55 stents in 35
coronary vessels (32 native arteries and 3 vein grafts) from 32
patients. The mean duration of stent placement was 39±82 days. Fibrin,
platelets, and neutrophils were associated with stent struts 
11
days after deployment. In stents implanted for 3 days, only 3% of
struts in contact with fibrous plaque had >20 associated inflammatory
cells compared with 44% of struts embedded in a lipid core and 36% of
struts in contact with damaged media (P<0.001).
Neointimal growth determined late
histological success, and increased
neointimal growth correlated with increased stent size
relative to the proximal reference lumen area. Neointimal
thickness was greater for struts associated with medial damage than
struts in contact with plaque (P<0.0001) or intact
media (P<0.0001). When matched for time since
treatment, neointimal cell density in stented arteries was
similar to that in unstented arteries that had undergone balloon
angioplasty and showed similar proteoglycan deposition.
Conclusions—Morphology after coronary stenting demonstrates early thrombus formation and acute inflammation followed by neointimal growth. Medial injury and lipid core penetration by struts result in increased inflammation. Neointima increases as the ratio of stent area to reference lumen area increases. Deployment strategies that reduce medial damage and avoid stent oversizing may lower the frequency of in-stent restenosis.
Key Words: stents • coronary disease • restenosis • angioplasty • pathology
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|
|
|
|
|
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|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 J. F. LaDisa Jr., L. E. Olson, I. Guler, D. A. Hettrick, S. H. Audi, J. R. Kersten, D. C. Warltier, and P. S. Pagel Stent design properties and deployment ratio influence indexes of wall shear stress: a three-dimensional computational fluid dynamics investigation within a normal artery J Appl Physiol, July 1, 2004; 97(1): 424 - 430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Tollefsen Does Heparin Cofactor II Modulate Atherosclerosis and Restenosis? Circulation, June 8, 2004; 109(22): 2682 - 2684. [Full Text] [PDF]
|
|
|
|
 |
|
 X. Ma and E. R. O'Brien Antagonism of the {alpha}4 integrin subunit attenuates the acute inflammatory response to stent implantation yet is insufficient to prevent late intimal formation J. Leukoc. Biol., June 1, 2004; 75(6): 1016 - 1021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 P. H Chong and J. W. Cheng Early Experiences and Clinical Implications of Drug-Eluting Stents: Part 1 Ann. Pharmacother., April 1, 2004; 38(4): 661 - 669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
 H. Kamiya, T. Ushijima, K. Mukai, C. Ikeda, K. Ueyama, and G. Watanabe Late patency of the left internal thoracic artery graft in patients with and without previous successful percutaneous transluminal coronary angioplasty Interactive CardioVascular and Thoracic Surgery, March 1, 2004; 3(1): 110 - 113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Delafontaine, Y.-H. Song, and Y. Li Expression, Regulation, and Function of IGF-1, IGF-1R, and IGF-1 Binding Proteins in Blood Vessels Arterioscler. Thromb. Vasc. Biol., March 1, 2004; 24(3): 435 - 444. [Abstract] [Full Text]
|
|
|
|
|
|
D. R. Holmes Jr, B. G. Firth, and D. L. Wood Paradigm shifts in cardiovascular medicine J. Am. Coll. Cardiol., February 18, 2004; 43(4): 507 - 512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Takamori, H. Azuma, M. Kato, S. Hashizume, K.-i. Aihara, M. Akaike, K. Tamura, and T. Matsumoto High Plasma Heparin Cofactor II Activity Is Associated With Reduced Incidence of In-Stent Restenosis After Percutaneous Coronary Intervention Circulation, February 3, 2004; 109(4): 481 - 486. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. L. Johnson, L. M. Schofield, D. K. Weber, F. Kolodgie, R. Virmani, and B. A. Khaw Uptake of 111In-Z2D3 on SPECT Imaging in a Swine Model of Coronary Stent Restenosis Correlated with Cell Proliferation J. Nucl. Med., February 1, 2004; 45(2): 294 - 299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Jaster, V Fuster, P Rosenthal, M Pauschinger, Q-V Tran, D Janssen, W Hinkelbein, P Schwimmbeck, H-P Schultheiss, and U Rauch Catheter based intracoronary brachytherapy leads to increased platelet activation Heart, February 1, 2004; 90(2): 160 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
G. W. Stone, S. G. Ellis, D. A. Cox, J. Hermiller, C. O'Shaughnessy, J. T. Mann, M. Turco, R. Caputo, P. Bergin, J. Greenberg, et al. A Polymer-Based, Paclitaxel-Eluting Stent in Patients with Coronary Artery Disease N. Engl. J. Med., January 15, 2004; 350(3): 221 - 231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
S. Sakai, K. Mizuno, S. Yokoyama, J. Tanabe, T. Shinada, K. Seimiya, M. Takano, T. Ohba, M. Tomimura, R. Uemura, et al. Morphologic changes in infarct-related plaque after coronary stent placement: A serial angioscopy study J. Am. Coll. Cardiol., November 5, 2003; 42(9): 1558 - 1565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
|