Bioresorbable Vascular Scaffold Coronary Aneurysm and Thrombosis: Farewell to the Current Bioresorbable Vascular Scaffolds?

J INVASIVE CARDIOL 2017;29(11):E157-E158.

Key words: bioresorbable vascular scaffold, complications, coronary artery aneurysm

Several recent reports have shown that the development of coronary artery aneurysms following implantation of the newly approved bioresorbable scaffolds is increasingly occurring in cardiology practice.¹ These events come in parallel with the increasing incidence of bioresorbable scaffold thrombosis.² The exact mechanism of their formation is unknown, but several hypotheses have been proposed. They include increased intensity of predilation and postdilation during implantation, vascular remodeling, arterial wall injury, local microhemorrhage and/or ulceration, recovery of vessel pulsatility following polymer absorption, shear stress, guidewire injury to the adventitial layer, creation of a false lumen, rotational atherectomy, laser angioplasty, subintimal stenting, and local inflammation and hypersensitivity. A propensity to aneurysm formation due to special polymorphism in matrix metalloproteinase genes, which have been implicated in aneurysm formation and are known to have elastase activity, has been also incriminated.³ Recently, coronary aneurysm formation following bioresorbable scaffold implantation using cutting-balloon angioplasty for predilation has been observed more frequently than in conventional balloon predilation.⁴

In a very interesting report published in the Journal of Invasive Cardiology, Wainstein et al⁵ describe a 67-year-old male patient suffering from severe stenosis in the mid-segment of the left an-terior descending coronary artery that was treated with a 3.0 x 18 mm Absorb bioresorbable stent (Abbott Vascular); within months after implantation, an aneurysm developed at the site of scaffold deploy-ment. The authors of this report correctly emphasized that inflammation plays a central role in coronary aneurysm formation and speculated on re-sidual dissection, deep arterial wall injury, and hypersensitivity to the eluting drug (everolimus), polymer, or metal.

The implanted bioresorbable vascular scaffold consists of the following components:⁶ a bioresorbable poly(L-lactide) scaffold; a coating comprised of the active pharmaceutical ingredient everolimus and bioresorbable poly(D,L-lactide); four platinum marker beads, two embedded at both the proximal and distal ends of the scaffold for radiopacity; and a scaffold delivery system eluting the antiproliferative drug everolimus that leverages technology from the Xience family of products and incorporates design features from the Absorb BVS, Xience Xpedition, and Xience Alpine delivery systems.

The above components can all induce hypersensitivity and foreign-body reactions. The eluted everolimus substance from the Absorb stent has been already associated with the development of hypersensitivity pneumonitis, atopic dermatitis, exanthema, and generalized as well as lingual angioedema.^7-12 The rate of hypersensitivity reactions to platinum salts and taxanes is on the increase and the role of skin tests has been emphasized.¹³ Although infrequently, local and/or regional and/or systemic delayed and recurrent granulomatous reactions may complicate poly(L-lactide) gel injections.¹⁴ Systemic hypersensitivity reactions to poly(L-lactide) acid screws, used in orthopedics, have been proven by positive skin tests and have necessitated the removal of the screws.¹⁵ Therefore, the July 5, 2017 United States Food and Drug Administration (FDA) press release, which states that the subsequent approval letter and safety alert indicating that such devices are contraindicated for patients who have a known hypersensitivity or allergy to everolimus, materials used in the device, such as poly(L-lactide), poly(D,L-lactide), contrast media, aspirin, antiplatelet agents, or platinum, should be strictly applied.⁶

We suggest that in order to prevent and avoid such dangerous consequences,¹⁶ strict adherence to FDA recommendations, further improvements in technical procedures and current device technology, increasing efforts for inventing new inert materials, and long-term clinical data are warranted before bioresorbable vascular scaffold implantation.

References

1.    Kang J, Han JK, Yang HM, et al. Bioresorbable vascular scaffolds – are we facing a time of crisis or one of breakthrough? Circ J. 2017;81:1065-1074. 

2.    Patel A, Nazif T, Stone GW, Ali ZA. Intraluminal bioresorbable vascular scaffold dismantling with aneurysm formation leading to very late thrombosis. Catheter Cardiovasc Interv. 2017;89:876-879.

3.    Shimizu C, Matsubara T, Onouchi Y, et al. Matrix metalloproteinase haplotypes associated with coronary artery aneurysm formation in patients with Kawasaki disease. J Hum Genet. 2010;55:779-784.

4.    Rottländer D, Schneider T, Degen H, Haude M. Lesion preparation with cutting balloon angioplasty is associated with coronary aneurysm formation in polylactide bioresorbable vascular scaffold implantation. EuroIntervention. 2017 Aug 1 (Epub ahead of print).

5.    Wainstein RV, Araujo GN, Valle FH, Wainstein MV. Coronary artery aneurysm after bioresorbable scaffold implantation. J Invasive Cardiol. 2017;29:E79-E80.

6.    https://www.fda.gov/medicaldevices/productsandmedicalprocedures/deviceapprovalsandclearances/recently-approveddevices/ucm509951.htm. Accessed July 30, 2017.

7.    Kurtzman DJ, Oulton J, Erickson C, Curiel-Lewandrowski C. Everolimus-induced symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). Dermatitis. 2016;27:76-77.

8.    Andersen LK, Jensen JE, Bygum A. Second episode of near-fatal angioedema in a patient treated with everolimus. Ann Allergy Asthma Immunol. 2015;115:152-153.

9.    Fuchs U, Zittermann A, Berthold HK, et al. Immunosuppressive therapy with everolimus can be associated with potentially life-threatening lingual angioedema. Transplantation. 2005;79:981-983. 

10.    Mackenzie M, Wood LA. Lingual angioedema associated with everolimus. Acta Oncol. 2010;49:107-109.

11.    Sibertin-Blanc C, Norguet E, Duluc M, et al. Severe hypersensitivity pneumonitis associated with everolimus therapy for neuroendocrine tumour: a case report. BMC Res Notes. 2013;6:471. 

12.    Van Velsen SG, Haeck IM, Bruijnzeel-Koomen CA. Severe atopic dermatitis treated with everolimus. J Dermatolog Treat. 2009;20:365-367. 

13.    Brault F, Waton J, Poreaux C, Schmutz JL, Barbaud A. Hypersensitivity to platinum salts and taxanes: the value of skin tests and tolerance induction procedures. Ann Dermatol Venereol. 2017 Jul 28 (Epub ahead of print).

14.    Alijotas-Reig J, Garcia-Gimenez V, Vilardell-Tarres M. Late-onset immune-mediated adverse effects after poly-L-lactic acid injection in non-HIV patients: clinical findings and long-term follow-up. Dermatology. 2009;219:303-308.

15.    Mastrokalos DS, Paessler HH. Allergic reaction to biodegradable interference poly-L-lactic acid screws after anterior cruciate ligament reconstruction with bone-patellartendon-bone graft. Arthroscopy. 2008;24:732–733.

16.    Kounis NG, Koniari I, Roumeliotis A, et al. Thrombotic responses to coronary stents, bioresorbable scaffolds and the Kounis hypersensitivity-associated acute thrombotic syndrome. J Thorac Dis. 2017;9:1155-1164.

From the Department of Cardiology, University of Patras Medical School, Rion, Patras, Achaia, Greece. 

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein. 

Address for correspondence: Professor Nicholas G. Kounis, Queen Olgas Square, 7 Aratou Street, Patras 26221, Achaia, Greece. Email: ngkounis@otenet.gr