This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sousa, J. E. Articles by Virmani, R. Search for Related Content PubMed PubMed Citation Articles by Sousa, J. E. Articles by Virmani, R. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Related Collections Catheter-based coronary interventions: stents Related Article

(Circulation. 2004;110:e5-e6.)
© 2004 American Heart Association, Inc.

Images in Cardiovascular Medicine

Vascular Healing 4 Years After the Implantation of Sirolimus-Eluting Stent in Humans

A Histopathological Examination

J. Eduardo Sousa, MD, PhD; Marco A. Costa, MD, PhD; Andrew Farb, MD; Alexandre Abizaid, MD, PhD; Amanda Sousa, MD, PhD; Ana C. Seixas, MD; Lilian M. da Silva, MD; Fausto Feres, MD, PhD; Ibraim Pinto, MD, PhD; Luiz A. Mattos, MD, PhD; Renu Virmani, MD

From the Institute Dante Pazzanese of Cardiology, São Paulo, Brazil (J.E.S., A.A., A.S., A.C.S., L.M.d.S., F.F., I.P., L.A.M.); University of Florida–Shands, Jacksonville, Fla (M.A.C.); and Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC (A.F., R.V.).

Correspondence to J. Eduardo Sousa, MD, PhD, Ave Dr Dante Pazzanese 500, Ibirapuera, São Paulo, SP, Brazil, CEP 04012-909. E-mail jesousa{at}uol.com.br

A 60-year-old male patient with coronary disease was included in the "First-in Man" study¹ and received a single sirolimus-eluting stent (SES, fast release) in December 1999 to treat a 90% diameter stenosis lesion located in the proximal right coronary artery (RCA). The patient had mild to moderate (<50% diameter stenosis) obstructions in the left anterior descending and left circumflex arteries. Coronary angiography and intravascular ultrasound (IVUS) revealed minimal neointimal growth in the midstent region at 4 months, 1 year, and 2 years after implantation. The patient underwent aortic and mitral valve replacement without complication 3 years after SES implantation. Left ventricle ejection fraction was 22%. He had a cardiac arrest out of the hospital in January 2004 (4-year follow-up). The patient was resuscitated but suffered severe cerebral damage. Postarrest angiography showed a widely patent SES in the RCA with a % obstruction volume of 19% by IVUS with minimal intimal hyperplasia by IVUS (Figure 1). The patient developed brain death and died. At necropsy, there was a 60% cross-sectional area of luminal narrowing of the RCA proximal to the stent. The stented segment was widely patent and well healed. Scanning electron microscopy of the proximal stent showed >95% of stent surface endothelialized (Figure 2). Light microscopic sections of the distal portion of the stent demonstrated a thin neointima consisting of smooth muscle cells and macrophages (predominately KP1-positive cells) in collagen-rich matrix. Approximately 75% of stent struts were covered by a thin type I collagen-rich neointima, and occasional calcific foci were present in neointima. The remaining 25% of struts were deeply embedded in the necrotic core of the plaque without associated inflammation. The RCA distal to stent was widely patent (<25% narrowing). The left anterior descending artery showed an acute plaque rupture and luminal thrombus in the proximal arterial segment. Atherosclerosis progression was noted in the left circumflex artery and posterior descending artery. The bioprosthetic aortic valve had a small fibrin thrombus deposition at the base of the right coronary cusp.

View larger version (98K): [in this window] [in a new window]   Figure 1. Sequential angiography performed before procedure, after procedure, and at 2- and 4-year follow-up after implantation of SES (arrows) in the RCA (upper panels). SES was patent with minimal late loss (late loss=0.21 mm). IVUS revealed minimal amount of neointimal hyperplasia at 2-year follow-up in the mid-stented segments (lower panels), which were unchanged at 4-year follow-up.

View larger version (120K): [in this window] [in a new window]   Figure 2. Morphological appearance of a 4-year fast-release SES implant. Radiograph in A shows a well-expanded stent; boxed area represents the proximal portion of the device, which was cut longitudinally for scanning electron microscopy (H and I). Remaining portion was embedded in resin and cut in cross section (D). B, The longitudinal sections on gross show a widely patent lumen with a thin neointima; the stent struts are well visualized. The cross section on gross reveals a thin neointima with the majority of stent struts positioned close to the lumen, while a few are seen penetrating deep within the plaque. D, Cross section of the segment in C showing the majority of struts in close proximity to the lumen with a few penetrating the necrotic core. E, Stent struts (*) covered by minimal neointima; note the absence of inflammation. Arrows outline a small area of calcified matrix. F, Higher magnification of the black box in D shows 2 adjacent struts localized to the necrotic core with numerous cholesterol clefts. G, Few -actin–positive smooth muscle cells are seen overlying stent struts (*). H and I, Scanning electron microscopy of the luminal surface of the proximal stent shows almost complete coverage by endothelial cells except for a lone strut near a branch point (arrow). I, Remaining surfaces show polygonal-shaped endothelial cells with mature tight junctions.

Footnotes

The editor of Images in Cardiovascular Medicine is Hugh A. McAllister, Jr, MD, Chief, Department of Pathology, St Luke’s Episcopal Hospital and Texas Heart Institute, and Clinical Professor of Pathology, University of Texas Medical School and Baylor College of Medicine.

Circulation encourages readers to submit cardiovascular images to the Circulation Editorial Office, St Luke’s Episcopal Hospital/Texas Heart Institute, 6720 Bertner Ave, MC1-267, Houston, TX 77030.

Reference

1. Sousa JE, Costa MA, Sousa AG, et al. Two-year angiographic and intravascular ultrasound follow-up after implantation of sirolimus-eluting stents in human coronary arteries. Circulation. 2003; 107: 381–383.[Abstract/Free Full Text]
   

Related Article:

Circulation 2004 110: 1. [Full Text]

This article has been cited by other articles:

				T. Cyrus, H. Zhang, J. S. Allen, T. A. Williams, G. Hu, S. D. Caruthers, S. A. Wickline, and G. M. Lanza Intramural Delivery of Rapamycin With {alpha}v{beta}3-Targeted Paramagnetic Nanoparticles Inhibits Stenosis After Balloon Injury Arterioscler. Thromb. Vasc. Biol., May 1, 2008; 28(5): 820 - 826. [Abstract] [Full Text] [PDF]

				J. Daemen and P. W. Serruys Drug-Eluting Stent Update 2007: Part I: A Survey of Current and Future Generation Drug-Eluting Stents: Meaningful Advances or More of the Same? Circulation, July 17, 2007; 116(3): 316 - 328. [Full Text] [PDF]

				A. V. Finn, M. Joner, G. Nakazawa, F. Kolodgie, J. Newell, M. C. John, H. K. Gold, and R. Virmani Pathological Correlates of Late Drug-Eluting Stent Thrombosis: Strut Coverage as a Marker of Endothelialization Circulation, May 8, 2007; 115(18): 2435 - 2441. [Abstract] [Full Text] [PDF]

				D. Matsumoto, J. Shite, T. Shinke, H. Otake, Y. Tanino, D. Ogasawara, T. Sawada, O. L. Paredes, K.-i. Hirata, and M. Yokoyama Neointimal coverage of sirolimus-eluting stents at 6-month follow-up: evaluated by optical coherence tomography Eur. Heart J., April 2, 2007; 28(8): 961 - 967. [Abstract] [Full Text] [PDF]

				E. Camenzind, P. G. Steg, and W. Wijns A Cause for Concern Circulation, March 20, 2007; 115(11): 1440 - 1455. [Full Text] [PDF]

				M. Joner, A. V. Finn, A. Farb, E. K. Mont, F. D. Kolodgie, E. Ladich, R. Kutys, K. Skorija, H. K. Gold, and R. Virmani Pathology of Drug-Eluting Stents in Humans: Delayed Healing and Late Thrombotic Risk J. Am. Coll. Cardiol., July 4, 2006; 48(1): 193 - 202. [Abstract] [Full Text] [PDF]

				I. Fishbein, I. S. Alferiev, O. Nyanguile, R. Gaster, J. M. Vohs, G. S. Wong, H. Felderman, I-W. Chen, H. Choi, R. L. Wilensky, et al. Bisphosphonate-mediated gene vector delivery from the metal surfaces of stents PNAS, January 3, 2006; 103(1): 159 - 164. [Abstract] [Full Text] [PDF]

				J. Aoki, A. C. Abizaid, P. W. Serruys, A. T.L. Ong, E. Boersma, J. E. Sousa, and N. Bruining Evaluation of Four-Year Coronary Artery Response After Sirolimus-Eluting Stent Implantation Using Serial Quantitative Intravascular Ultrasound and Computer-Assisted Grayscale Value Analysis for Plaque Composition in Event-Free Patients J. Am. Coll. Cardiol., November 1, 2005; 46(9): 1670 - 1676. [Abstract] [Full Text] [PDF]

				M. Togni, S. Windecker, R. Cocchia, P. Wenaweser, S. Cook, M. Billinger, B. Meier, and O. M. Hess Sirolimus-Eluting Stents Associated With Paradoxic Coronary Vasoconstriction J. Am. Coll. Cardiol., July 19, 2005; 46(2): 231 - 236. [Abstract] [Full Text] [PDF]

				A. V. Finn, F. D. Kolodgie, J. Harnek, L.J. Guerrero, E. Acampado, K. Tefera, K. Skorija, D. K. Weber, H. K. Gold, and R. Virmani Differential Response of Delayed Healing and Persistent Inflammation at Sites of Overlapping Sirolimus- or Paclitaxel-Eluting Stents Circulation, July 12, 2005; 112(2): 270 - 278. [Abstract] [Full Text] [PDF]

				J. E. Sousa, M. A. Costa, A. Abizaid, F. Feres, A. C. Seixas, L. F. Tanajura, L. A. Mattos, R. Falotico, J. Jaeger, J. J. Popma, et al. Four-Year Angiographic and Intravascular Ultrasound Follow-Up of Patients Treated With Sirolimus-Eluting Stents Circulation, May 10, 2005; 111(18): 2326 - 2329. [Abstract] [Full Text] [PDF]

				M. A. Costa and D. I. Simon Molecular Basis of Restenosis and Drug-Eluting Stents Circulation, May 3, 2005; 111(17): 2257 - 2273. [Full Text] [PDF]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sousa, J. E. Articles by Virmani, R. Search for Related Content PubMed PubMed Citation Articles by Sousa, J. E. Articles by Virmani, R. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Related Collections Catheter-based coronary interventions: stents Related Article