Mechanisms of Very Late Drug-Eluting Stent Thrombosis Assessed by Optical Coherence Tomography

Abstract

T he advent of coronary stents in conjunction with potent adjunctive medical treatment has resulted in substantial improvements in the efficacy and safety of percutaneous coronary interventions (PCIs).1 Although infrequent, stent thrombosis remains an important concern because of its sequelae, including myocardial infarction and death in up to 80%. 2,3 Early stent thrombosis is largely independent of stent type and mainly related to procedural variables, including major edge dissections and stent underexpansion. 4 Conversely, the mechanisms underlying very late stent thrombosis (VLST), occurring beyond 1 year after drug-eluting stent (DES) implantation, remain poorly defined, and the translation of mechanistic insights into therapeutic approaches is unsatisfactory. Despite an attenuation of the risk for VLST with the use of newer-generation DES, which is similar to that of bare metal stents, the accumulated long-term risk is still notable. Clinical Perspective on p 660Because of its high resolution (10-20 μm), optical coherence tomography (OCT) has become the imaging modality of choice for the in vivo assessment of stent failures, including VLST. 5 As a result of the infrequent encounter of this Background-The pathomechanisms underlying very late stent thrombosis (VLST) after implantation of drug-eluting stents (DES) are incompletely understood. Using optical coherence tomography, we investigated potential causes of this adverse event. Methods and Results-Between August 2010 and December 2014, 64 patients were investigated at the time point of VLST as part of an international optical coherence tomography registry. Optical coherence tomography pullbacks were performed after restoration of flow and analyzed at 0.4 mm. A total of 38 early-and 20 newer-generation drug-eluting stents were suitable for analysis. VLST occurred at a median of 4.7 years (interquartile range, 3.1-7.5 years). An underlying putative cause by optical coherence tomography was identified in 98% of cases. The most frequent findings were strut malapposition (34.5%), neoatherosclerosis (27.6%), uncovered struts (12.1%), and stent underexpansion (6.9%). Uncovered and malapposed struts were more frequent in thrombosed compared with nonthrombosed regions (ratio of percentages, 8.26; 95% confidence interval, 6.82-10.04; P<0.001 and 13.03; 95% confidence interval, 10. 13-16.93; P<0.001, respectively). The maximal length of malapposed or uncovered struts (3.40 mm; 95% confidence interval, 2.55-4.25; versus 1.29 mm; 95% confidence interval, 0.81-1.77; P<0.001), but not the maximal or average axial malapposition distance, was greater in thrombosed compared with nonthrombosed segments. The associations of both uncovered and malapposed struts with thrombus were consistent among early-and newer-generation drug-eluting stents. Conclusions-The leading associated findings in VLST patients in descending order were malapposition, neoatherosclerosis, uncovered struts, and stent underexpansion without differences between patients treated with early-and new...

Mechanisms of stent thrombosis: insights from optical coherence tomography

“…Thus, neoatherosclerotic lesion could be manifested with wide spectrum from stable coronary artery disease to acute myocardial infarction including late or very late ST (12). This feature was also confirmed in ST registries, in which ruptured neoatherosclerosis, as well as stent malapposition, was a frequent OCT finding in patients suffering from late or very late ST (3,6). Although the pathophysiology of neoatherosclerosis has remained unknown, several OCT studies suggested that specific factors such as stent type, stent age, patients' characteristics including current smoking, chronic kidney disease, usage of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockade, and the concentration of low-density lipoprotein cholesterol were associated with the presence of neoatherosclerosis at follow-up (13)(14)(15).…”

“…A similar finding was observed in an OCT study, in which adverse cardiac events did not occur in patients with late stent malapposition during follow-up of mean 28 months after DES implantation (5). Contrary to these studies, crosssectional OCT studies showed that the malapposition was a leading cause of early, late, or very late ST (3,6). These discrepancies were partly explained by the finding that stent malapposition could be spontaneously resolved over time (5,7).…”

Optical coherence tomography- vs. intravascular ultrasound-guided percutaneous coronary intervention

“…The findings of malapposed struts are clinically relevant: previous studies consistently reported that malapposition after PCI was the leading cause underlying early and very late stent thrombosis (21,22). In the ILUMIEN 3 trial, major malapposition was defined as ≥200 µm and associated with a stent underexpansion <90%.…”

Coronary stent thrombosis: what have we learned?

“…Guagliumi et al identified uncoverage struts as the most common OCT correlate of very late ST (12). Interestingly, Taniwaki et al comparing thrombus vs. control regions within the same stent observed a direct association between thrombus and uncovered struts or malapposition length (35). Additionally, strut coverage does not necessarily portend a functional endothelium, as OCT cannot differentiate material deposition (e.g., fibrin) over the struts from endothelial coverage (36).…”

“…Small areas of ISA might resolve spontaneously in nearly half of the patients, whereas larger ISA might persist over time. Late-acquired stent malapposition could results from thrombus dissolution (behind the struts) after primary PCI, positive vessel remodeling with detachment of the stent from the vessel wall and rarely from chronic stent recoil (31 (35,46). In the PESTO registry strut malapposition was the most frequent abnormality in patients with late and very late ST (13).…”