An unusual case of acute coronary syndrome late after stent implantation

Summary

We report a case of a 66-year-old Caucasian male who presented to our department with unstable angina in July 2011. He had a medical history of trivessel coronary artery disease and underwent several percutaneous coronary interventions (2003, 2004, and 2006). The latest coronary angiography, performed in January 2011, showed mild intimal hyperplasia within the proximal left anterior descending segment, treated with a sirolimus-eluting stent in 2003. On admission, electrocardiogram was positive for a recent acute coronary syndrome, so the patient underwent coronary angiography, which showed proximal left anterior descending stent thrombosis, occurred eight years after drug-eluting stent implantation. Intravascular ultrasound revealed a soft plaque rupture within the stented segment, which was the cause of stent thrombosis.

So the lack of endothelialization over stent struts is not the only mechanism determining acute coronary syndromes late after stent implantation. In-stent neoatherosclerosis, frequently disregarded, is another possible actor especially of very late thrombotic events. However, the pathogenesis of this phenomenon has not been clearly established.

Introduction

Drug-eluting stents (DES) are thought to be superior to bare-metal stents (BMS) in reducing restenosis rates. However, due to the use of this technology, stent thrombosis, the most dangerous complication of DES, has been reported more frequently in recent times 1, 2.

The main mechanism is known to be the lack of complete endothelialization over stent struts and is considered to be responsible for most acute coronary syndromes late after percutaneous coronary intervention (PCI). However, in-stent neoatherosclerosis, frequently disregarded, could be another possible actor of some late and very late thrombotic events. The present case report describes a very late stent thrombosis caused by a soft plaque rupture within the stented segment eight years after DES implantation.

Case report

A 66-year-old Caucasian male with hypertension, a family history of coronary artery disease, and former smoker was referred to our department for a clinical evaluation for unstable angina in July 2011. He had a medical history of trivessel coronary artery disease and underwent several PCIs with DES implantation of proximal left anterior descending artery (2003), proximal circumflex artery (2004), and medium-distal right coronary artery (2006). The latest coronary angiography was performed in January 2011 and showed mild intimal hyperplasia within the proximal left anterior descending stented segment (Fig. 1), which had been treated with a sirolimus-eluting stent in 2003.

Figure 1.

Coronary angiography showing mild intimal hyperplasia (arrow) within the proximal left anterior descending stented segment.

On admission to our department, the patient related that he had been suffering from unstable angina for two weeks, with an episode at rest. The electrocardiogram was positive for a recent acute coronary syndrome. The following day, the patient underwent coronary angiography which showed an intrastent proximal left anterior descending subocclusion (Fig. 2); intravascular ultrasound showed a soft plaque rupture with a thrombus localized only at the rupture site; the previous implanted stent did not appear to be not well expanded (Fig. 3A and B). We preferred to treat the patient with two everolimus-eluting stents (Promus Element 3.5 mm × 20 mm and 3 mm × 20 mm; Boston Scientific, Natick, MA, USA) because of the high prognostic value of the left anterior descending proximal tract, in order to reduce the risk of restenosis as much as possible. After 3 months, the patient was asymptomatic and underwent an exercise stress echocardiogram that resulted negative for inducible ischemia.

Figure 2.

Coronary angiography showing an intrastent proximal left anterior descending subocclusion (arrow).

Figure 3.

(A and B) Intravascular ultrasound revealing a soft plaque rupture (arrows) within the stented segment, which determined stent thrombosis.

Discussion

Late and very late stent thrombosis are important but rare complications of DES, occurring up to eight years after stent implantation. In fact, while these stents have reduced rates of restenosis and late lumen loss compared to BMS, late and very late stent thrombosis, a life-threatening complication of this technology, has emerged as a major concern 1, 2. The etiology is likely to be multifactorial and it is still not completely understood.

However several risk factors have been investigated. Some of them are procedure-related factors such as stent under expansion, late malapposition, incomplete apposition, strut penetration into a necrotic core lesion, and arterial dissection. On the other hand, patient-related factors include diabetes, chronic renal failure, low left ventricular ejection fraction, and in-stent restenosis [3].

Moreover aspirin and clopidogrel resistance are emerging as major risk factors, which could be responsible for some thrombotic events. Bouman et al. have observed that early stent thrombosis was frequently associated with clopidogrel resistance while, especially in some cases of late stent thrombosis, aspirin or dual antiplatelet therapy resistance were more prevalent [4].

The pathophysiology of late and very late stent thrombosis is unclear, as well.

The most recognized mechanism, as clinical imaging and autopsy studies confirmed, is the lack of complete endothelialization over stent struts, which in patients receiving DES is approximately 20% at 2 years [5].

Other well known mechanisms include local hypersensitivity reactions due to the polymers used in the manufacture of earlier generations of DES and extensive fibrin deposition, especially for first-generation DES [6].

However, in some cases, the real mechanism underlying late and very late stent thrombosis could be plaque rupture, determined by in-stent neoatherosclerosis. The incidence and type of this phenomenon have been only recently investigated with histologic studies by Nakazawa et al. [7]. These authors found a different underlying plaque morphology after implantation of DES and BMS: unstable lesions, such as thin-cap fibroatheromas and ruptured plaques were more frequent in DES, whereas fibrocalcific and pathological intimal thickening were more common in BMS.

Moreover, the incidence of this phenomenon was different between DES and BMS, according to time after implantation. In fact, in less than 2 years span, DES had a greater incidence of any neoatherosclerosis (peri-strut foamy macrophage clusters and fibroatheromas) than BMS; between 2 and 6 years, DES still had a higher incidence of neoatherosclerosis, while after 6 years no significant differences were observed between the two devices. Unstable neoatherosclerotic lesions were identified in BMS > 5 years and in DES < 2 years and this could possibly explain some cases of late stent thrombotic events 5, 7, 8.

However, the underlying process responsible for the development of neoatherosclerosis after stent implantation is still unknown.

Joner et al. hypothesized that it may involve the inability to maintain a fully functional endothelialized luminal surface within the stented segment. A possible reason of why neoatherosclerosis develops faster in DES than BMS could be related to drug effects, which damage the endothelial stem cells and create a proinflammatory environment, leading to monocyte adherence, subendothelial migration, and plaque formation [9].

Farb et al. suggest that neoatherosclerosis within stented segment is associated either with delayed arterial healing and lethal injury to smooth muscle cells and endothelial cells [10].

Conclusions

The lack of endothelialization over stent struts is not the only mechanism determining acute coronary syndromes late after stent implantation. In-stent neoatherosclerosis is thought to be responsible especially for very late thrombotic events and its role has been demonstrated by histologic studies. Unfortunately, there is not a specific therapy for very late stent thrombosis prevention except for antiplatelet therapy continuation, which could be one of the leading causes of very late stent thrombosis [11].

This reminds us once again the importance of lifestyle changes and optimal medical therapy for the treatment of our patients and prevention of atherothrombotic disease progression.