Reduced Histologic Neo In-stent Restenosis After Use of a Paclitaxel-coated Cutting Balloon in Porcine Coronary Arteries

Overview

Journal Histol Histopathol

Specialties Anatomy & Histology
Pathology

Date 2019 Oct 25

PMID 31646547

Authors

Denise Traxler

Rayyan Hemetsberger

Andreas Spannbauer

Katrin Zlabinger

Alfred Gugerell

Dominika Lukovic

Ljubica Mandic

Noemi Pavo

Johannes Winkler

Mariann Gyongyosi

Affiliations

Soon will be listed here.

Abstract

The incidence of in-stent restenosis (ISR) has declined dramatically, but once it develops, no current treatment option, such as drug-eluting stents, drug-coated balloons, or cutting balloons (CBs), prevents re-narrowing of the stented atherosclerotic artery. In this preclinical study, we aimed to improve the efficacy of ISR treatment by coating CBs with paclitaxel (paclitaxel-eluting cutting balloon; PECB) and to characterize the histological features of neo-ISRs that arise after ISR treatment. ISR was induced by bare metal stent (BMS) implantation in coronary arteries in pigs. After one month of follow-up, the BMS-induced ISR was treated with either CB or PECB. After another month, we performed quantitative coronary angiography, explanted the treated arteries and assessed histopathological and histomorphometric parameters. In addition, we compared the histological features of neo-ISRs with pre-treatment ISRs. Injury, inflammation, fibrin deposition, and endothelialization scores were similar between the CB and PECB groups at one month after ISR treatment. Neointimal area (0.87±0.61 vs. 1.95±1.14 mm², p=0.02), mean neointimal thickness (0.40±0.39 vs. 0.99±0.56 mm, p=0.01), and percent area stenosis (27.3±20.4 vs. 48.3±22.9%, p=0.04) were decreased in PECB-treated coronary arteries compared to CB-treated arteries, respectively. Density of cells (predominantly smooth muscle cells; SMCs) was increased in neo-ISRs (3.51±3.05×10³ vs. 6.35±2.57×10³ cells/mm², p<0.01), but significantly more CD68⁺ and CD20⁺ cells were found in the pre-treatment ISRs. In conclusion, PECB treatment of ISRs led to better results in terms of smaller neointimal area and %area stenosis of the neo-ISR. SMC density was increased in neo-ISRs in contrast with higher percentage of CD68⁺ and CD20⁺ cells in pre-treatment ISRs.

References

Adamian M, Colombo A, Briguori C, Nishida T, Marsico F, Di Mario C . Cutting balloon angioplasty for the treatment of in-stent restenosis: a matched comparison with rotational atherectomy, additional stent implantation and balloon angioplasty. J Am Coll Cardiol. 2001; 38(3):672-9. DOI: 10.1016/s0735-1097(01)01458-9. View

Albiero R, Silber S, Di Mario C, Cernigliaro C, Battaglia S, Reimers B . Cutting balloon versus conventional balloon angioplasty for the treatment of in-stent restenosis: results of the restenosis cutting balloon evaluation trial (RESCUT). J Am Coll Cardiol. 2004; 43(6):943-9. DOI: 10.1016/j.jacc.2003.09.054. View

Ansel G, Sample N, Botti III Jr C, Tracy A, Silver M, Marshall B . Cutting balloon angioplasty of the popliteal and infrapopliteal vessels for symptomatic limb ischemia. Catheter Cardiovasc Interv. 2003; 61(1):1-4. DOI: 10.1002/ccd.10731. View

Axel D, Kunert W, Goggelmann C, Oberhoff M, Herdeg C, Kuttner A . Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery. Circulation. 1997; 96(2):636-45. DOI: 10.1161/01.cir.96.2.636. View

Barath P, Fishbein M, Vari S, Forrester J . Cutting balloon: a novel approach to percutaneous angioplasty. Am J Cardiol. 1991; 68(11):1249-52. DOI: 10.1016/0002-9149(91)90207-2. View

Byrne R, Joner M, Kastrati A . Polymer coatings and delayed arterial healing following drug-eluting stent implantation. Minerva Cardioangiol. 2009; 57(5):567-84. View

Carter A, Laird J, Farb A, Kufs W, Wortham D, Virmani R . Morphologic characteristics of lesion formation and time course of smooth muscle cell proliferation in a porcine proliferative restenosis model. J Am Coll Cardiol. 1994; 24(5):1398-405. DOI: 10.1016/0735-1097(94)90126-0. View

Cassese S, Byrne R, Tada T, Pinieck S, Joner M, Ibrahim T . Incidence and predictors of restenosis after coronary stenting in 10 004 patients with surveillance angiography. Heart. 2013; 100(2):153-9. DOI: 10.1136/heartjnl-2013-304933. View

Costa M, Simon D . Molecular basis of restenosis and drug-eluting stents. Circulation. 2005; 111(17):2257-73. DOI: 10.1161/01.CIR.0000163587.36485.A7. View

10.

Cremers B, Schmitmeier S, Clever Y, Gershony G, Speck U, Scheller B . Inhibition of neo-intimal hyperplasia in porcine coronary arteries utilizing a novel paclitaxel-coated scoring balloon catheter. Catheter Cardiovasc Interv. 2013; 84(7):1089-98. DOI: 10.1002/ccd.25296. View

11.

Dangas G, Claessen B, Caixeta A, Sanidas E, Mintz G, Mehran R . In-stent restenosis in the drug-eluting stent era. J Am Coll Cardiol. 2010; 56(23):1897-907. DOI: 10.1016/j.jacc.2010.07.028. View

12.

Glover C, Ma X, Chen Y, Miller H, Veinot J, Labinaz M . Human in-stent restenosis tissue obtained by means of coronary atherectomy consists of an abundant proteoglycan matrix with a paucity of cell proliferation. Am Heart J. 2002; 144(4):702-9. DOI: 10.1067/mhj.2002.123577. View

13.

Grube E, Silber S, Hauptmann K, Mueller R, Buellesfeld L, Gerckens U . TAXUS I: six- and twelve-month results from a randomized, double-blind trial on a slow-release paclitaxel-eluting stent for de novo coronary lesions. Circulation. 2003; 107(1):38-42. DOI: 10.1161/01.cir.0000047700.58683.a1. View

14.

Jinnouchi H, Kuramitsu S, Shinozaki T, Tomoi Y, Hiromasa T, Kobayashi Y . Difference of Tissue Characteristics Between Early and Late Restenosis After Second-Generation Drug-Eluting Stents Implantation　- An Optical Coherence Tomography Study. Circ J. 2017; 81(4):450-457. DOI: 10.1253/circj.CJ-16-1069. View

15.

Mitra A, Agrawal D . In stent restenosis: bane of the stent era. J Clin Pathol. 2006; 59(3):232-9. PMC: 1860348. DOI: 10.1136/jcp.2005.025742. View

16.

Mohan S, Dhall A . A comparative study of restenosis rates in bare metal and drug-eluting stents. Int J Angiol. 2012; 19(2):e66-72. PMC: 3005409. DOI: 10.1055/s-0031-1278368. View

17.

Moses J, Leon M, Popma J, Fitzgerald P, Holmes D, OShaughnessy C . Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med. 2003; 349(14):1315-23. DOI: 10.1056/NEJMoa035071. View

18.

Nakazawa G, Otsuka F, Nakano M, Vorpahl M, Yazdani S, Ladich E . The pathology of neoatherosclerosis in human coronary implants bare-metal and drug-eluting stents. J Am Coll Cardiol. 2011; 57(11):1314-22. PMC: 3093310. DOI: 10.1016/j.jacc.2011.01.011. View

19.

de Prado A, Perez-Martinez C, Cuellas Ramon C, Regueiro Purrinos M, Nieto A, Gonzalo-Orden J . Safety and efficacy of different paclitaxel-eluting balloons in a porcine model. Rev Esp Cardiol (Engl Ed). 2014; 67(6):456-62. DOI: 10.1016/j.rec.2013.09.030. View

20.

Posa A, Hemetsberger R, Petnehazy O, Petrasi Z, Testor M, Glogar D . Attainment of local drug delivery with paclitaxel-eluting balloon in porcine coronary arteries. Coron Artery Dis. 2008; 19(4):243-7. DOI: 10.1097/MCA.0b013e3283030b26. View