Late peri-stent contrast staining appearance due to rupture of atherogenic neointima following drug-eluting stent

Abstract

The development of peri-stent contrast staining (PSS) after coronary intervention with implantation of a stent is observed in approximately 1–3% of patients treated with drug-eluting stent. Although the cumulative incidences of late in-stent restenosis and stent thrombosis are significantly higher in lesions with PSS than in those without the finding, the mechanisms for the development of PSS have not yet been fully elucidated. In this report, we describe a case of rapid development of PSS with ulcer formation caused by rupture of atherogenic neointima, which was observed by serial optical coherence tomography examinations over 6 months. Protrusion of the stent-jailed underlying necrotic core toward the lumen by the contracting force might have resulted in formation of atherogenic neointima within the stent. Subsequently, rupture of this necrotic core induced by iatrogenic neointimal injury due to balloon dilation and dissolution of the accumulated necrotic core may have resulted in PSS formation 6 months after the procedure. These findings may be helpful for consideration of etiology and therapeutic strategy for lesions with PSS.

<Learning objective: The mechanisms of peri-stent contrast staining (PSS) formation late after drug-eluting stent (DES) implantation are diverse. Rupture of atherogenic neointima with subsequent dissolution of the stent-jailed underlying plaque debris could be one of the mechanisms of rapid PSS formation after implantation of DES. An accurate assessment of lesion morphology within the stent and patient-tailored management can reduce morbidity and mortality in patients who have undergone DES implantation.>

Introduction

Previous studies have reported that angiographically detected contrast staining outside the struts at the site of stent implantation, known as peri-stent contrast staining (PSS), was observed in approximately 1–3% of patients treated with drug-eluting stents (DES) [1], and was associated with increased risk of late in-stent restenosis and stent thrombosis [1]. Although the underlying mechanisms of PSS formation are diverse and include various patient-, lesion-, stent-, and procedure-related factors, the mechanisms have not yet been fully elucidated. Herein, we report a rare case showing rapid development of PSS at the site of DES implantation and confirm its etiology by serial optical coherent tomography (OCT) examinations.

Case report

An 80-year-old man was admitted to our hospital due to complaints of atypical chest pain at rest. History of diabetes mellitus was noted as a risk factor for coronary disease. His-low-density lipoprotein cholesterol was 86 mg/dl without lipid-lowering therapy at the admission. He had a history of acute anterior wall myocardial infarction 8 years before admission. At the time of acute myocardial infarction, a 3.5 × 18 mm everolimus-eluting stent was deployed from the proximal left ascending artery (LAD) into the middle left main followed by kissing balloon inflation with a 4.0 mm balloon in the LAD and a 3.0 mm balloon in the left circumflex artery (LCX). At this time, he was diagnosed with stable angina and coronary angiography (CAG) revealed moderate stenosis within the stented segment in the ostial LAD and a diffuse 90% stenosis in the mid LAD, distal to the everolimus-eluting stent (Fig. 1A, B). OCT was performed to evaluate the morphological features of the stenotic lesions. The OCT image showed a heterogeneous diffusely bordered signal-poor region with marked signal attenuation and invisible stent strut behind a low signal intensity region (Fig. 1G) along with a disrupted neointima (Fig. 1H) in the stented segments. At the segment distal to the stent, the OCT image revealed a coronary plaque with heterogeneous low signal intensity with a diffuse border that may represent lipid-rich plaque in the native coronary artery (Fig. 1I). Subsequently, new 2.5 × 28 mm and 3.0 × 24 mm everolimus-eluting stents were deployed overlapping the old stent from the mid to the distal LAD. Balloon dilation was performed in the ostial LAD with good results on CAG (Fig. 1C, D), even though the post-procedural OCT showed minor tears in the low signal intensity neointima at the ostial LAD (Fig. 1G’). After the procedure, dual antiplatelet therapy with 100 mg aspirin and 3.75 mg prasugrel was maintained until the day of follow-up CAG. A routine follow-up CAG, performed 6 months after the procedure, revealed a focal significant in-stent restenosis in the ostial LAD and PSS at the distal part of the old everolimus-eluting stent in the proximal LAD (Fig. 2A, C, D). OCT images revealed significant lumen narrowing and ulcer-like appearance around the struts (Fig. 2E, F) in the middle part of the old everolimus-eluting stent and 5 mm proximal from the proximal edge of the new everolimus-eluting stent. The OCT images showed large incomplete stent apposition at the distal part of the old everolimus-eluting stent in the proximal LAD (Fig. 2G, H). At this segment, OCT showed an intramural protruding mobile mass, which was detached from the intima (Fig. 2H). After the OCT examination, a 3.0 × 15 mm drug-coated balloon was inflated in the lesion following pre-dilation with a 3.5 × 13 mm non-slip element balloon. Finally, kissing balloon inflation with a 4.0 mm balloon in the LAD and a 3.0 mm balloon in the LCX was performed with an excellent final angiographic result (Fig. 2B).

Fig. 1.

Straight caudal and right cranial oblique projections show moderate stenosis in the ostial LAD, and diffuse 90% stenosis in the mid LAD distal to the old everolimus-eluting stent (A, B). Post-procedural CAG shows good expansion of severe stenosis in the mid to distal LAD, and persistence of moderate stenosis in the ostial LAD (C, D). OCT examination shows a heterogeneous diffusely bordered signal-poor region with marked signal attenuation and invisible stent strut behind a low signal intensity region within the old stent in the ostial LAD (arrowheads in E, F, G), and the neointima contained a cavity that communicated with the lumen with an overlying residual fibrous cap fragment (arrows in H). OCT image of the native coronary artery distal to the old stent shows a coronary plaque with heterogeneous low signal intensity with diffuse border (I). Post-procedural OCT shows minor tears (open arrows) in the low signal intensity neointima at the same cross-section of G (G’).

CAG, coronary angiography; LAD, left anterior descending artery; OCT, optical coherence tomography.

Fig. 2.

A routine follow-up CAG taken after 6 months shows in-stent restenosis with peri-stent contrast staining in the ostial LAD (A, C, D). White dotted line in C shows stent strut of 3.5 × 18 mm everolimus-eluting stent 8 years previously. The OCT images (E, F) reveal significant lumen narrowing and large cavity formation involving the stent struts at the same site where the atherogenic neointima was observed on OCT performed before 6 months (Fig. 1 E, F). Large incomplete stent apposition in the stented segment in the proximal LAD (G), which was the same site as Fig. 1 G. Intramural protruding mass detached from the intimal wall identified at the distal part of the stented segment (arrows) (H, the different site of Fig. 1 H). After the OCT examination, drug-coated balloon was inflated in the lesion following pre-dilation with non-slip element balloon. Finally, kissing balloon inflation in the LAD and left circumflex artery was performed with an excellent final angiographic result (B).

CAG, coronary angiography; LAD, left anterior descending artery; OCT, optical coherence tomography.

Discussion

In this report, we described a case of rapid development of PSS with ulcer formation caused by rupture of atherogenic neointima, which was observed by serial OCT examinations over 6 months.

Although the development of PSS after coronary intervention with implantation of a DES is generally considered a rare complication, previous studies have demonstrated that the cumulative incidences of late in-stent restenosis and stent thrombosis are significantly higher in lesions with PSS than in those without the finding [1]. Several hypotheses have been suggested regarding the mechanisms of development of PSS. A previous study described that the number of eosinophils in the aspirated thrombus at the time of very-late stent thrombosis was associated with the extent of stent malapposition [2]. Localized vascular hypersensitivity in response to the DES polymer may cause intimal damage leading to vascular surface defects with PSS [3], which may further lead to medial disruption with aneurysmal dilatation. This was confirmed by Yamaji et al. [4] who noted that the eosinophil fraction in the aspirated thrombus of patients presenting with very-late stent thrombosis was significantly higher in the presence of PSS than in patients without the finding. Other potential mechanisms for the development of PSS include medial injury at the site of stent implantation with subsequent vessel enlargement and dissolution of the jailed thrombus [5]. The precise mechanism of the unique appearance of PSS at the stented site in our case was unclear; however, the postulated mechanism was rupture of atherogenic intima due to the procedure with the subsequent necrotic core being transported downstream. Rupture of the atherosclerotic neointima inside the DES may be associated with late in-stent restenosis after implantation [6]. Our previous ex-vivo validation study comparing OCT and histopathological images showed that the atherosclerotic neointima appeared as a heterogeneous pattern with invisible stent strut behind a low signal intensity region [7]. In the present case, a large cavity formation with malapposed struts was observed at the same site where the heterogeneous neointima with invisible stent strut behind a low signal intensity region was identified on pre-procedural OCT performed before 6 months. One of the mechanisms of formation of atherogenic neointima after DES implantation is late-acquired protrusion of the atherogenic plaque. The underlying atherogenic plaque between the stent strut and internal elastic membrane could be pushed into the lumen by the contracting force of the vessel wall, because the neointimal tissue within the struts is thin and fragile in DES. Recently, a case report confirmed this finding that delayed protrusion of the underlying necrotic core between the struts could occur after implantation of DES [8]. Therefore, in our case, it could be speculated that a stent-jailed underlying plaque debris in the ostial LAD may have grown continuously even after the onset of myocardial infarction. Furthermore, protrusion of the native necrotic core toward the lumen by the contracting force might have resulted in formation of atherogenic neointima within the stent. Subsequently, rupture of the atherogenic neointima induced by iatrogenic neointimal injury due to balloon dilation and dissolution of the accumulated plaque debris could have resulted in PSS formation 6 months after the procedure. The precise mechanism underlying delayed rupture of atherogenic neointima is unclear. However, a previous study reported that some new silent plaque rupture cavities were identified within untreated segments of infarct-related arteries in patients with acute myocardial infarction [9]. Diffuse and multiple destabilization of atherosclerotic plaques and subsequent fissure formation within the plaque in patients with acute myocardial infarction, which is known as the concept of “pan-coronaritis”, may support this delayed plaque rupture appearance [10]. Therefore, as reported here, it is reasonable to assume that minor neointimal injury by balloon dilatation could result in rupture of atherogenic neointima after a while, but not immediately after percutaneous coronary intervention.

The present case report is the first to demonstrate that rupture of atherogenic neointima with subsequent dissolution of the necrotic core was the mechanism of rapid PSS formation after implantation of DES. It is important to evaluate lesions with in-stent restenosis after implantation of DES by OCT in order to collect evidence of the natural history of neoatherosclerosis against these devices, given the high number of such stents implanted in patients.

Declaration of Competing Interest

The authors declare that there is no conflict of interest.

Appendix. Supplementary materials

Movie 1

Pre-procedural optical coherence tomography video image from the distal left ascending artery to left main at the time of initial procedure.

Movie 2

Pre-procedural optical coherence tomography video image taken 6 months after the initial procedure.