The Spatial Distribution of Plaque Vulnerabilities in Patients with Acute Myocardial Infarction

Objective

Although the plaque characteristics have been recognized in patients with acute myocardial infarction (AMI), the plaque spatial distribution is not well clarified. Using color-mapping intravascular ultrasound (iMAP-IVUS), we examined culprit lesions to clarify plaque morphology, composition and spatial distribution of the sites of potential vulnerability.

Methods

Sixty-eight culprit lesions in 64 consecutive AMI patients who underwent angiography and IVUS examinations before intervention were analyzed. Plaque morphology and composition were quantified with iMAP-IVUS. The spatial distribution of the sites of potential vulnerability was assessed with longitudinal reconstruction of the consecutive IVUS images. The plaque characteristics were also compared between ruptured and non-ruptured lesions, and between totally occlusive (TO) and non-TO lesions.

Results

The sites with maximum necrotic area (maxNA), maximum plaque burden (maxPB) and most severely narrowed (minimal luminal area, MLA) were recognized vulnerability. In the majority of cases, maxNA sites were proximal to the maxPB sites, and MLA sites were distal to the maxNA and maxPB sites. Ruptures usually occurred close to maxNA sites and proximal to maxPB and MLA sites. The average distance from the site of rupture to the maxNA site was 0.33 ± 4.04 mm. Ruptured lesions showed significant vessel remodeling, greater plaque volume, and greater lipidic volume compared to those of non-ruptured lesions. Both the length and plaque burden (PB) of TO lesions were greater than those of non-TO lesions.

Conclusions

Instead of overlapping on maxPB sites, most maxNA sites are proximal to the maxPB sites and are the sites most likely to rupture. Plaque morphology and composition play critical roles in plaque rupture and coronary occlusion.     

Stents Eluting 6-Mercaptopurine Reduce Neointima Formation and Inflammation while Enhancing Strut Coverage in Rabbits

Background

The introduction of drug-eluting stents (DES) has dramatically reduced restenosis rates compared with bare metal stents, but in-stent thrombosis remains a safety concern, necessitating prolonged dual anti-platelet therapy. The drug 6-Mercaptopurine (6-MP) has been shown to have beneficial effects in a cell-specific fashion on smooth muscle cells (SMC), endothelial cells and macrophages. We generated and analyzed a novel bioresorbable polymer coated DES, releasing 6-MP into the vessel wall, to reduce restenosis by inhibiting SMC proliferation and decreasing inflammation, without negatively affecting endothelialization of the stent surface.

Methods

Stents spray-coated with a bioresorbable polymer containing 0, 30 or 300 μg 6-MP were implanted in the iliac arteries of 17 male New Zealand White rabbits. Animals were euthanized for stent harvest 1 week after implantation for evaluation of cellular stent coverage and after 4 weeks for morphometric analyses of the lesions.

Results

Four weeks after implantation, the high dose of 6-MP attenuated restenosis with 16% compared to controls. Reduced neointima formation could at least partly be explained by an almost 2-fold induction of the cell cycle inhibiting kinase p27^Kip1. Additionally, inflammation score, the quantification of RAM11-positive cells in the vessel wall, was significantly reduced in the high dose group with 23% compared to the control group. Evaluation with scanning electron microscopy showed 6-MP did not inhibit strut coverage 1 week after implantation.

Conclusion

We demonstrate that novel stents coated with a bioresorbable polymer coating eluting 6-MP inhibit restenosis and attenuate inflammation, while stimulating endothelial coverage. The 6-MP-eluting stents demonstrate that inhibition of restenosis without leaving uncovered metal is feasible, bringing stents without risk of late thrombosis one step closer to the patient.     

The Influence of a Metal Stent on the Distribution of Thermal Energy during Irreversible Electroporation

Purpose

Irreversible electroporation (IRE) uses short duration, high-voltage electrical pulses to induce cell death via nanoscale defects resulting from altered transmembrane potential. The technique is gaining interest for ablations in unresectable pancreatic and hepatobiliary cancer. Metal stents are often used for palliative biliary drainage in these patients, but are currently seen as an absolute contraindication for IRE due to the perceived risk of direct heating of the metal and its surroundings. This study investigates the thermal and tissue viability changes due to a metal stent during IRE.

Methods

IRE was performed in a homogeneous tissue model (polyacrylamide gel), without and with a metal stent placed perpendicular and parallel to the electrodes, delivering 90 and 270 pulses (15–35 A, 90 μsec, 1.5 cm active tip exposure, 1.5 cm interelectrode distance, 1000–1500 V/cm, 90 pulses/min), and in-vivo in a porcine liver (4 ablations). Temperature changes were measured with an infrared thermal camera and with fiber-optic probes. Tissue viability after in-vivo IRE was investigated macroscopically using 5-triphenyltetrazolium chloride (TTC) vitality staining.

Results

In the gel, direct stent-heating was not observed. Contrarily, the presence of a stent between the electrodes caused a higher increase in median temperature near the electrodes (23.2 vs 13.3°C [90 pulses]; p = 0.021, and 33.1 vs 24.8°C [270 pulses]; p = 0.242). In-vivo, no temperature difference was observed for ablations with and without a stent. Tissue examination showed white coagulation 1mm around the electrodes only. A rim of vital tissue remained around the stent, whereas ablation without stent resulted in complete tissue avitality.

Conclusion

IRE in the vicinity of a metal stent does not cause notable direct heating of the metal, but results in higher temperatures around the electrodes and remnant viable tissue. Future studies should determine for which clinical indications IRE in the presence of metal stents is safe and effective.     

The Use of Solitaire AB Stents in Coil Embolization of Wide-Necked Cerebral Aneurysms

Background

The Solitaire AB stent is one of many assistant stents used for treating wide-necked cerebral aneurysm, and has been used since 2003. However, large sample studies on its safety and effectiveness are lacking. The objective of this study was to evaluate the effectiveness and safety of the Solitaire AB stent in the coil embolization of wide-necked cerebral aneurysms.

Methods

Retrospective review of the clinical and image data of 116 patients with wide-necked cerebral aneurysms who had been enrolled at six interventional neuroradiology centers from February 2010 to February 2014 and had been treated by coil embolization; in total, 120 Solitaire AB stents were used. The degree of aneurysm occlusion was examined using digital subtraction angiography (DSA) immediately after the procedure and during follow-up, and was graded using the modified Raymond classification. We also observed complications to evaluate the safety and effectiveness of this therapy.

Results

The 120 Solitaire AB stents (4 mm × 15 mm, four stents; 4 mm × 20 mm, 16 stents; 6 mm × 20 mm, 36 stents; 6 mm × 30 mm, 64 stents) were inserted to treat 120 wide-necked cerebral aneurysms. All stents were inserted successfully. DSA immediately post-surgery revealed 55 cases of complete occlusion, 59 cases of neck remnant, and six cases of aneurysm remnant. Perioperatively, there were four cases of hemorrhage and four cases of stent thrombosis. The follow-up spanned 3–37 months; of 92 patients examined by DSA at the 6-month follow up, 12 had disease recurrence.

Conclusions

The Solitaire AB stent is effective with a good technical success rate and short-term effect for assisting coil embolization of wide-necked cerebral aneurysms.     

Can Platforms Affect the Safety and Efficacy of Drug-Eluting Stents in the Era of Biodegradable Polymers?: A Meta-Analysis of 34,850 Randomized Individuals

Objective

In the era of bare metal stents (BMSs), alloys have been considered to be better materials for stent design than stainless steel. In the era of biodegradable polymer drug-eluting stents (BP-DESs), the safety and efficacy of BP-DESs with different metal platforms (stainless steel or alloys) have not yet been reported, although their polymers are eventually absorbed, and only the metal platforms remain in the body. This study sought to determine the clinical safety and efficacy of BP-DESs with different platforms compared with other stents (other DESs and BMSs).

Methods

PubMed, Embase and Clinical Trials.gov were searched for randomized controlled trials (RCTs) that compared BP-DESs with other stents. After performing pooled analysis of BP-DESs and other stents, we performed a subgroup analysis using two classification methods: stent platform and follow-up time. The study characteristics, patient characteristics and clinical outcomes were abstracted.

Results

Forty RCTs (49 studies) comprising 34,850 patients were included. Biodegradable polymer stainless drug-eluting stents (BP-stainless DESs) were superior to the other stents [mainly stainless drug-eluting stents (DESs)] in terms of pooled definite/probable stent thrombosis (ST) (OR [95% CI] = 0.76[0.61–0.95], p = 0.02), long-term definite/probable ST (OR [95% CI] = 0.73[0.57–0.94], p = 0.01), very late definite/probable ST (OR [95% CI] = 0.56[0.33–0.93], p = 0.03) and long-term definite ST. BP-stainless DESs had lower rates of pooled, mid-term and long-term target vessel revascularization (TVR) and target lesion revascularization (TLR) than the other stainless DESs and BMSs. Furthermore, BP-stainless DESs were associated with lower rates of long-term death than other stainless DESs and lower rates of mid-term myocardial infarction than BMSs. However, only the mid-term and long-term TVR rates were superior in BP-alloy DESs compared with the other stents.

Conclusion

Our results indirectly suggest that BP-stainless DESs may offer more benefits than BP-alloy DESs in the era of BP-DESs. Further well-designed RCTs comparing BP-stainless with BP-alloy DESs are needed to confirm which platform is better.     

Spectral Imaging for Intracranial Stents and Stent Lumen

Introduction

Application of computed tomography for monitoring intracranial stents is limited because of stent-related artifacts. Our purpose was to evaluate the effect of gemstone spectral imaging on the intracranial stent and stent lumen.

Materials and Methods

In vitro, we scanned Enterprise stent phantom and a stent–cheese complex using the gemstone spectral imaging protocol. Follow-up gemstone spectral images of 15 consecutive patients with placement of Enterprise from January 2013 to September 2014 were also retrospectively reviewed. We used 70-keV, 140-keV, iodine (water), iodine (calcium), and iodine (hydroxyapatite) images to evaluate their effect on the intracranial stent and stent lumen. Two regions of interest were individually placed in stent lumen and adjacent brain tissue. Contrast-to-noise ratio was measured to determine image quality. The maximal diameter of stent markers was also measured to evaluate stent-related artifact. Two radiologists independently graded the visibility of the lumen at the maker location by using a 4-point scale. The mean of grading score, contrast/noise ratio and maximal diameter of stent markers were compared among all modes. All results were analyzed by SPSS version 20.

Results

In vitro, iodine (water) images decreased metallic artifact of stent makers to the greatest degree. The most areas of cheese were observed on iodine (water) images. In vivo, iodine (water) images had the smallest average diameter of stent markers (0.33 ± 0.17mm; P < .05) and showed the highest mean grading score (2.94 ± 0.94; P < .05) and contrast/noise ratio of in-stent lumen (160.03 ±37.79; P < .05) among all the modes.

Conclusion

Iodine (water) images can help reduce stent-related artifacts of Enterprise and enhance contrast of in-stent lumen. Spectral imaging may be considered a noninvasive modality for following-up patients with in-stent stenosis.     

Intraductal Radiofrequency Ablation Followed by Locoregional Tumor Treatments for Treating Occluded Biliary Stents in Non-Resectable Malignant Biliary Obstruction: A Single-Institution Experience

Objectives

To determine the safety and feasibility of intraductal radiofrequency ablation (RFA) followed by locoregional tumor treatments in patients with non-resectable malignant biliary obstruction and stent re-occlusion.

Methods

Fourteen patients with malignant biliary obstruction and blocked metal stents were studied retrospectively. All had intraductal RFA followed by locoregional tumor treatments and were monitored clinically and radiologically. The practicality, safety, postoperative complications, jaundice remission, stent patency and survival time were analyzed.

Results

Combination treatment was successful for all patients. There were no severe complications during RFA or local treatments. All patients had stent patency restored, with a decline in serum bilirubin. Three patients had recurrent jaundice by 195, 237 and 357 days; two patients underwent repeat intraductal RFA; and one required an internal-external biliary drain. The average stent patency time was 234 days (range 187-544 days). With a median follow-up of 384 days (range 187-544 days), six patients were alive, while eight had died. There was no mortality at 30 days. The 3, 6, 12 and 18 month survival rates were 100%, 100%, 64.3% and 42.9%, respectively.

Conclusion

Intraductal RFA followed by locoregional tumor treatments for occluded metal stents is safe and practically feasible and potential increase stent patency and survival times.     

Effects of Clopidogrel and Proton Pump Inhibitors on Cardiovascular Events in Patients with Type 2 Diabetes Mellitus after Drug-Eluting Stent Implantation: A Nationwide Cohort Study

Objective

To investigate whether there is an increased risk of cardiac events in diabetic patients with a combined therapy of clopidogrel (CLO) and proton pump inhibitors (PPIs) after drug-eluting stent (DES) deployment.

Methods

By using National Health Insurance Research Database, all patients who received CLO with or without PPI therapy within 90 days after undergoing DES (limus-eluting or paclitaxel-eluting stents) deployment were enrolled. Endpoints were acute coronary syndrome (ACS) and readmission for revascularization (percutaneous coronary intervention or coronary artery bypass graft surgery) after 3, 6, and 12 months.

Results

A total of 6,603 diabetic patients received LESs (5,933 in the CLO subgroup and 670 in the CLO plus PPIs subgroup), and 3,202 patients received PESs (2,923 in the CLO subgroup and 279 in the CLO plus PPIs subgroup). The patients who received CLO plus PPIs were at higher risk of ACS than those receiving CLO within 1 year after DES deployment (LESs: 6-month hazard ratio [HR] = 1.63, and 1-year HR = 1.37; PESs: 3-month HR = 1.72). Patients with a history of ACS who received CLO plus PPIs were at higher risk of ACS after LES implantation (HR = 1.55) than those in the CLO group.

Conclusion

In “real-world” diabetic patients with LES deployment, the combination of PPIs and CLO is associated with higher rates of ACS after 6 months and 1 year. Even after correction for confounding factors, concomitant PPI use remained an independent predictor of cardiac events, emphasizing the clinical importance of this drug—drug interaction.     

Stent Thrombosis is the Primary Cause of ST-Segment Elevation Myocardial Infarction following Coronary Stent Implantation: A Five Year Follow-Up of the SORT OUT II Study

Background

The widespread use of coronary stents has exposed a growing population to the risk of stent thrombosis, but the importance in terms of risk of ST-segment elevation myocardial infarctions (STEMIs) remains unclear.

Methods

We studied five years follow-up data for 2,098 all-comer patients treated with coronary stents in the randomized SORT OUT II trial (mean age 63.6 yrs. 74.8% men). Patients who following stent implantation were readmitted with STEMI were included and each patient was categorized ranging from definite- to ruled-out stent thrombosis according to the Academic Research Consortium definitions. Multivariate logistic regression was performed on selected covariates to assess odds ratios (ORs) for definite stent thrombosis.

Results

85 patients (4.1%), mean age 62.7 years, 77.1% men, were admitted with a total of 96 STEMIs, of whom 60 (62.5%) had definite stent thrombosis. Notably, definite stent thrombosis was more frequent in female than male STEMI patients (81.8% vs. 56.8%, p = 0.09), and in very late STEMIs (p = 0.06). Female sex (OR 3.53 [1.01–12.59]) and clopidogrel (OR 4.43 [1.03–19.01]) was associated with increased for definite stent thrombosis, whereas age, time since stent implantation, use of statins, initial PCI urgency (STEMI [primary PCI], NSTEMI/unstable angina [subacute PCI] or stable angina [elective PCI]), and glucose-lowering agents did not seem to influence risk of stent thrombosis.

Conclusion

In a contemporary cohort of coronary stented patients, stent thrombosis was evident in more than 60% of subsequent STEMIs.     

Malignant Ureteral Obstruction: Functional Duration of Metallic versus Polymeric Ureteral Stents

Background

Ureteral obstruction caused by extrinsic compression is often associated with intra-abdominal cancers. Internal drainage with ureteral stents is typically the first-line therapy to relieve such obstructions. Novel designs of ureteral stents made of different materials have been invented to achieve better drainage. In this study, we described the functional outcomes of a Resonance metallic ureteral stent (Cook Medical, Bloomington, Indiana, USA) in patients with malignant ureteral obstruction and compare the functional duration of Resonance stents with regular polymeric stents in the same cohort.

Methods

Cancer patients who received polymeric stents and subsequent Resonance stents for ureteral obstruction between July 2009 and November 2012 were included in a chart review. Stent failure was detected by clinical symptoms, imaging studies, and renal function tests. The functional durations of each stent were calculated, and possible factors affecting stent patency were investigated.

Results

A total of 50 stents were successfully inserted into 50 ureteral units in 42 patients with malignant ureteral obstruction. There were 7 antegrade stents and 43 retrograde stents. There were no major complications. Stent-related symptoms were similar in both kinds of stents. After polymeric stents were replaced with Resonance metallic stents, hydronephrosis subsided or remained stable in 90% (45/50) of the ureteral units. Serum creatinine decreased or remained stable in 90% (38/42) of these patients. The Resonance stent exhibited a mean increase in functional duration of 4 months compared with the polymeric stents (p<0.0001), and 50% (25/50) of the Resonance stents exhibited a significant increase in functional duration (more than 3 months). Pre-operative serum creatinine < 2 was associated with a substantial increase in stent duration.

Conclusions

Resonance stents are effective and safe in relieving malignant ureteral obstructions after polymeric stents failure. Resonance stents can provide a longer functional duration than polymeric stents and should be offered as an option for internal drainage.     

Efficacy of Gastric Balloon Dilatation and/or Retrievable Stent Insertion for Pyloric Spasms after Pylorus-Preserving Gastrectomy: Retrospective Analysis

Purpose

We retrospectively investigated the feasibility and clinical efficacy of balloon dilatation and subsequent retrievable stent insertion, when necessitated, for pyloric spasms after pylorus-preserving gastrectomy (PPG).

Materials and Methods

Forty-five patients experiencing pyloric spasms after PPG underwent fluoroscopic balloon dilations to alleviate obstructive symptoms due to delayed gastric emptying. Patients showing poor response to balloon dilation underwent subsequent retrievable stent insertion. Safety of the procedures was analyzed, and subjective symptoms and objective signs of pyloric spasms were analyzed and compared before and after treatment.

Results

Thirty-three patients (73.3%, 33/45) showed good response to balloon dilatation requiring no further treatment (balloon group). Conversely, 12 patients (26.7%, 12/45) showed poor or no response after balloon dilation requiring subsequent stent insertion (stent group). Balloon dilations and/or stent insertions were safely performed in all patients except one patient who suffered a transmural tear after balloon dilatation. In both groups, mean subjective symptom score was significantly improved and mean pyloric canal-to-height of the adjacent vertebral body ratio was significantly increased after the procedures (P <.05).

Conclusion

Balloon dilation is a safe and effective treatment for patients with pyloric spasms after PPG. In patients refractory to balloon dilations, retrievable stent placement can be a safe alternative tool.     

Release of Intracoronary Microparticles during Stent Implantation into Stable Atherosclerotic Lesions under Protection with an Aspiration Device

Objective

Stent implantation into atherosclerotic coronary vessels impacts on downstream microvascular function and induces the release of particulate debris and soluble substances, which differs qualitatively and quantitatively between native right coronary arteries (RCAs) and saphenous vein grafts on right coronary arteries (SVG-RCAs). We have now quantified the release of microparticles (MPs) during stent implantation into stable atherosclerotic lesions and compared the release between RCAs and SVG-RCAs.

Methods

In symptomatic, male patients with stable angina and a stenosis in their RCA or SVG-RCA, respectively (n = 14/14), plaque volume and composition were analyzed using intravascular ultrasound before stent implantation. Coronary aspirate was retrieved during stent implantation with a distal occlusion/aspiration device and divided into particulate debris and plasma. Particulate debris was weighed. Platelet-derived MPs (PMPs) were distinguished by flow cytometry as CD41⁺, endothelium-derived MPs (EMPs) as CD144⁺, CD62E⁺ and CD31⁺/CD41^-, leukocyte-derived MPs as CD45⁺, and erythrocyte-derived MPs as CD235⁺.

Results

In patients with comparable plaque volume and composition in RCAs and SVG-RCAs, intracoronary PMPs and EMPs were increased after stent implantation into their RCAs and SVG-RCAs (CD41⁺: 2729.6±645.6 vs. 4208.7±679.4 and 2355.9±503.9 vs. 3285.8±733.2 nr/µL; CD144⁺: 451.5±87.9 vs. 861.7±147.0 and 444.6±74.8 vs. 726.5±136.4 nr/µL; CD62E⁺: 1404.1±247.7 vs. 1844.3±378.6 and 1084.6±211.0 vs. 1783.8±384.3 nr/µL, P<0.05), but not different between RCAs and SVG-RCAs.

Conclusion

Stenting in stable atherosclerotic lesions is associated with a substantial release not only of PMPs, but also of EMPs in RCAs and SVG-RCAs. Their release does not differ between RCAs and SVG-RCAs.

Trial Registration

ClinicalTrials.gov NCT01430884     

Nanoporous CREG-Eluting Stent Attenuates In-Stent Neointimal Formation in Porcine Coronary Arteries

Background

The goal of this study was to evaluate the efficacy of a nanoporous CREG-eluting stent (CREGES) in inhibiting neointimal formation in a porcine coronary model.

Methods

In vitro proliferation assays were performed using isolated human endothelial and smooth muscle cells to investigate the cell-specific pharmacokinetic effects of CREG and sirolimus. We implanted CREGES, control sirolimus-eluting stents (SES) or bare metal stents (BMS) into pig coronary arteries. Histology and immunohistochemistry were performed to assess the efficacy of CREGES in inhibiting neointimal formation.

Results

CREG and sirolimus inhibited in vitro vascular smooth muscle cell proliferation to a similar degree. Interestingly, human endothelial cell proliferation was only significantly inhibited by sirolimus and was increased by CREG. CREGES attenuated neointimal formation after 4 weeks in porcine coronary model compared with BMS. No differences were found in the injury and inflammation scores among the groups. Scanning electron microscopy and CD31 staining by immunohistochemistry demonstrated an accelerated reendothelialization in the CREGES group compared with the SES or BMS control groups.

Conclusions

The current study suggests that CREGES reduces neointimal formation, promotes reendothelialization in porcine coronary stent model.     

Combining short stent implantation and drug-eluting stenting for routine use yields a low restenosis rate

Background

Stent length serves as a predictor of restenosis in use of bare metal stents (BMS). This has been demonstrated in a feasibility study that used a single short BMS implant (<9 mm) in a high proportion of lesions; the study observed a low rate of restenosis.

Methods

We performed a pilot prospective study to investigate in a series of consecutive patients the immediate and long-term effects of implantation of either 1) a single short BMS for all lesions with low probability of restenosis or 2) a drug-eluting stent (DES) for all other lesions.

Results

The 200 patients studied had 236 coronary artery lesions that were treated with short BMS in 168/236 patients (71.2%) and with DES in 68/236 patients (28.8%). Angiographic success was achieved in 230/236 lesions (97.5%) and procedural success in 194/200 patients (97.0%). Restenosis occurred in 15/153 lesions (9.8%) after short BMS, in 3/62 lesions (4.8%) after DES, and in 18/215 of all lesions (8.4%) angiographically controlled after six to eight months. Target vessel revascularization was performed in 16/218 lesion (7.4%).

Conclusion

Most of the coronary artery lesions in this small group of consecutive patients were treated sufficiently with a single BMS implant. This differential approach of treating suitable lesions in medium- to large-sized vessels with a single short BMS device and treating all other lesions with a DES implant resulted in a low incidence of restenosis.     

Long-term outcomes of patients receiving drug-eluting stents

Background

We sought to establish the long-term safety of drug-eluting stents compared with bare-metal stents in a usual care setting.

Methods

Using data from a prospective multicentre registry, we compared rates of death and of death or repeat revascularization during 3 years of follow-up of 6440 consecutive patients who underwent angioplasty with either drug-eluting or bare-metal stents between Apr. 1, 2003, and Mar. 31, 2006.

Results

Drug-eluting stents were inserted in 1120 patients and bare-metal stents in 5320. The drug-eluting stents were selected for patients who had a greater burden of comorbid illness, including diabetes mellitus (32.8% v. 20.8% in the bare-metal group, p < 0.001) and renal disease (7.4% v. 5.0%, p = 0.001). At 1-year follow-up, the drug-eluting stents were associated with a mortality of 3.0%, as compared with 3.7% with the bare-metal stents (adjusted odds ratio [OR] 0.62, 95% confidence interval [CI] 0.46–0.83). The rate of the composite outcome of death or repeat revascularization was 12.0% for the drug-eluting stents and 15.8% for the bare-metal stents (adjusted OR 0.40, 95% CI 0.33–0.49). In the subgroup of patients who had acute coronary syndromes, the adjusted OR for this composite outcome was 0.46 (95% CI 0.35–0.61). During the 3 years of observation, the relative risks for death and repeat revascularization varied over time. In year 1, there was an initial period of lower risk in the group with drug-eluting stents than in the group with bare-metal stents; this was followed by a shift toward outcome rates favouring bare-metal stents in years 2 and 3. The adjusted relative risk of the composite outcome of death or repeat revascularization associated with drug-eluting stents relative to bare-metal stents was 0.73 early in the first year of follow-up; it then rose gradually over time, to a peak of 2.24 at 3 years.

Interpretation

Drug-eluting stents are safe and effective in the first year following insertion. Thereafter, the possibility of longer term adverse events cannot be ruled out.Drug-eluting stents now comprise at least 85% of stents used in the United States and up to 40% or more of stents elsewhere. The overwhelming worldwide use of drug-eluting stents has, however, been tempered by the cost differential to bare-metal stents, the lack of data on long-term outcomes in large patient populations and, more recently, emerging concerns about safety because of reports of late thrombosis.^1–8The use of stents has been shown to reduce the rates of repeat revascularization and restenosis after angioplasty compared with angioplasty alone.⁹ Despite this, the long-term efficacy of stent use has been limited by the need for repeat revascularization owing to restenosis.¹⁰ Drug-eluting stents were developed to address this problem. Both clinical trials^11–20 and registry data^21–25 have shown reduced rates of restenosis with drug-eluting stents up to 4 years after implantation. This advantage appears to extend to patients with acute coronary syndromes: a recent 2-year follow-up study involving 7217 patients with acute coronary syndromes suggested that rates of death were lower among patients with drug-eluting stents than among those with bare-metal stents.²⁶The possibility of late thrombosis associated with drug-eluting stents is, however, a concern. Rates of late thrombosis have been reported to be 3.6–5.9 events per 1000 patients receiving drug-eluting stents.²⁷ This adverse event has been the subject of a review by the US Food and Drug Administration and has captured the attention of authoritative bodies around the world.Because of concerns about the long-term safety of drug-eluting stents, we compared the rates of death and of death or repeat revascularization over 3 years among patients who received either bare-metal or drug-eluting stents during angioplasty.     

The Impact of Blood Rheology on Drug Transport in Stented Arteries: Steady Simulations

Background and Methods

It is important to ensure that blood flow is modelled accurately in numerical studies of arteries featuring drug-eluting stents due to the significant proportion of drug transport from the stent into the arterial wall which is flow-mediated. Modelling blood is complicated, however, by variations in blood rheological behaviour between individuals, blood’s complex near-wall behaviour, and the large number of rheological models which have been proposed. In this study, a series of steady-state computational fluid dynamics analyses were performed in which the traditional Newtonian model was compared against a range of non-Newtonian models. The impact of these rheological models was elucidated through comparisons of haemodynamic flow details and drug transport behaviour at various blood flow rates.

Results

Recirculation lengths were found to reduce by as much as 24% with the inclusion of a non-Newtonian rheological model. Another model possessing the viscosity and density of blood plasma was also implemented to account for near-wall red blood cell losses and yielded recirculation length increases of up to 59%. However, the deviation from the average drug concentration in the tissue obtained with the Newtonian model was observed to be less than 5% in all cases except one. Despite the small sensitivity to the effects of viscosity variations, the spatial distribution of drug matter in the tissue was found to be significantly affected by rheological model selection.

Conclusions/Significance

These results may be used to guide blood rheological model selection in future numerical studies. The clinical significance of these results is that they convey that the magnitude of drug uptake in stent-based drug delivery is relatively insensitive to individual variations in blood rheology. Furthermore, the finding that flow separation regions formed downstream of the stent struts diminish drug uptake may be of interest to device designers.     

Prognostic Impact of 9-Month High-Sensitivity C-Reactive Protein Levels on Long-Term Clinical Outcomes and In-Stent Restenosis in Patients at 9 Months after Drug-Eluting Stent Implantation

Introduction

The level of 9-month high-sensitivity C-reactive protein (hsCRP) in predicting cardiovascular outcomes is scanty in patients at 9 months after receiving drug-eluting stent (DES) implantations. This study aims to evaluate the relationship between 9-month follow-up hsCRP levels and long-term clinical outcomes in patients at 9 months after receiving DES.

Methods

A total of 1,763 patients who received 9-month follow-up angiography were enrolled and grouped according to hsCRP level 9 months after the DES implantation: group I (718 patients, hsCRP<1.0 mg/L), group II (639 patients, 1.0≦hsCRP≦3.0 mg/L), and group III (406 patients, hsCRP>3.0 mg/L).

Results

Group III patients had a lower cardiovascular event-free survival rate than group I or II patients during a follow-up of 64±45 months (64.5% vs. 71.6% vs. 72.8%, respectively, p = 0.012). Multivariate analysis showed that a follow-up hsCRP level <3.0 mg/L was an independent predictor of a major adverse cardiovascular event (cardiac death, reinfarction, target lesion revascularization, stenting in a new lesion, or coronary bypass surgery). Group III patients had a higher restenosis rate (11.3% vs. 5.8% vs. 6.6%, respectively, p = 0.002) and loss index (0.21±0.32 vs. 0.16±0.24 vs. 0.18±0.28, respectively, p = 0.001) than group I or II patients in 9-month follow-up angiography.

Conclusions

A high 9-month follow-up hsCRP level is an independent predictor of long-term clinical cardiovascular outcomes in patients at 9 months after DES implantation. It is also associated with a higher restenosis rate, larger late loss and loss index at 9 months after DES implantation.     

Impact of Temporary Opening Using a Stent Retriever on Clinical Outcome in Acute Ischemic Stroke

Background

Stent retriever has a distinct ability to restore blood flow temporarily before achieving final reperfusion. There has been a limited report regarding the clinical impact of it. We investigated if temporary opening of occluded vessels using a stent retriever before final reperfusion might improve clinical outcome in acute ischemic stroke patients who received the endovascular reperfusion treatment.

Methods

We enrolled consecutive ischemic stroke patients who had an initial occlusive lesion in the anterior circulation and achieved final reperfusion (Thrombolysis In Cerebral Infarction [TICI] ≥2) by endovascular treatment. Temporary opening was defined as the presence of ante grade flow (TICI≥2) during deployment of a stent retriever. Favorable outcome was defined as a modified Rankin scale score≤2 at 90 day.

Results

A total of 98 patients were included in the study and temporary opening was achieved in 49 (50%). Temporary opening was associated with favorable outcome (odds ratio, 7.825; 95% confidence interval, 1.592–38.461; p = 0.011) in the multivariate analysis. The probability of having a favorable outcome tended to decrease as time from onset to final reperfusion increased in patients without temporary opening. However, this trend was not evident in the patient with temporary opening. The beneficial effect of temporary opening on clinical outcome seemed to be present in patients with good collaterals but not in patients with poor collaterals.

Conclusions

Temporary opening of occluded vessel using a stent retriever may be beneficial for improving clinical outcome in acute ischemic stroke patients.     

Myeloid-Specific Deletion of Diacylglycerol Lipase α Inhibits Atherogenesis in ApoE-Deficient Mice

Background

The endocannabinoid 2-arachidonoylglycerol (2-AG) is a known modulator of inflammation. Despite its high concentration in vascular tissue, the role of 2-AG in atherogenesis has not yet been examined.

Methods

ApoE-deficient mice were sublethally irradiated and reconstituted with bone marrow from mice with a myeloid-specific knockout of the 2-AG synthesising enzyme diacylglycerol lipase α (Dagla) or control bone marrow with an intact 2-AG biosynthesis. After a cholesterol-rich diet for 8 weeks, plaque size and plaque morphology were examined in chimeric mice. Circulating inflammatory cells were assessed by flow cytometry. Aortic tissue and plasma levels of endocannabinoids were measured using liquid chromatography-multiple reaction monitoring.

Results

Mice with Dagla-deficient bone marrow and circulating myeloid cells showed a significantly reduced plaque burden compared to controls. The reduction in plaque size was accompanied by a significantly diminished accumulation of both neutrophil granulocytes and macrophages in atherosclerotic lesions of Dagla-deficient mice. Moreover, CB2 expression and the amount of oxidised LDL within atherosclerotic lesions was significantly reduced. FACS analyses revealed that levels of circulating inflammatory cells were unaltered in Dagla-deficient mice.

Conclusions

Myeloid synthesis of the endocannabinoid 2-AG appears to promote vascular inflammation and atherogenesis. Thus, myeloid-specific disruption of 2-AG synthesis may represent a potential novel therapeutic strategy against atherosclerosis.     

Short-Term Consequences of Angiographically-Confirmed Coronary Stent Thrombosis

Objectives

To conduct a meta-analysis to quantify the real-world incidence of in-hospital or 30-day death or myocardial infarction (MI), and angiographically-confirmed ST-related treatment costs.

Background

The short-term clinical and economic consequences of coronary stent thrombosis (ST) are thought to be significant.

Methods

We searched MEDLINE, Embase and Scopus from January 2000-July 2012 to identify observational/registry studies that evaluated a cohort of ≥25 patients experiencing angiographically-confirmed thrombosis of a drug-eluting or bare-metal stent, required the use of dual-antiplatelet therapy for guideline-recommended durations, and reported incidences of in-hospital or 30-day death or MI and/or ST-related treatment costs. Incidences and costs from each study were pooled using random-effects meta-analysis.

Results

Twenty-three studies were included. Of the 13 studies reporting in-hospital outcomes, 12 (N=8,832 STs) reported mortality data, with the pooled incidence rate estimated to be 7.9%, 95%CI=5.4%-11.3%, I²=86%. Ten studies (N=1,294 STs) reported 30-day death, with a pooled incidence of 11.6%, 95%CI=8.8%-15.1%, I²=55%. Patients experiencing early ST (within 30-days of implant) had higher in-hospital and 30-day mortality than those experiencing very-late ST (interaction p<0.04 for both). Stent type had no significant effect on in-hospital or 30-day mortality. In the 5 studies (N=542 STs) and 3 studies (N=180 STs) reporting in-hospital and 30-day MI, respectively, the pooled incidence rates were 6.1%, 95%CI=2.1%-16.2%, I²=88% and 9.5%, 95%CI=3.8%-22.0%, I²=65%. One study reported costs associated with ST, estimating the median/patient cost of hospitalization to treat early ST at $11,134 (in 2000US$).

Conclusions

Regardless of stent type used, the short-term consequences of coronary ST appear significant.