Neointimal Volume Research Articles

Effects of Low Dose Pioglitazone on Restenosis and Coronary Atherosclerosis in Diabetic Patients Undergoing Drug Eluting Stent Implantation

PurposeThiazolidinediones are insulin-sensitizing agents that reduce neointimal proliferation and the adverse clinical outcomes associated with percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM). There is little data on whether or not low dose pioglitazone reduces adverse clinical outcomes.Materials and MethodsThe study population included 121 DM patients with coronary artery disease and they were randomly assigned to 60 patients taking 15 mg of pioglitazone daily in addition to their diabetic medications and 61 patients with placebo after the index procedure with drug-eluting stents (DESs). The primary end points were rate of in-stent restenosis (ISR) and change in atheroma volume and in-stent neointimal volume. The secondary end points were all-cause death, myocardial infarction (MI), stent thrombosis and re-PCI.ResultsThere were no statistical differences in the clinical outcomes and the rate of ISR between the two groups [all-cause death; n=0 (0%) in the pioglitazone group vs. n=1 (1.6%) in the control group, p=0.504, MI; n=2 (3.3%) vs. n=1 (1.6%), p=0.465, re-PCI; n=6 (10.0%) vs. n=6 (9.8%), p=0.652, ISR; n=4 (9.3%) vs. n=4 (7.5%), p=1.000, respectively]. There were no differences in changes in neointimal volume, percent neointimal volume, total plaque volume and percent plaque volume between the two groups on intravascular ultrasonography (IVUS) study.ConclusionOur study demonstrated that low dose pioglitazone does not reduce rate of ISR, neointimal volume nor atheroma volume in DM patients who have undergone PCI with DESs, despite the limitations of the study.

Bortezomib Reduces Neointimal Hyperplasia in a Rat Carotid Artery Injury Model

Background and ObjectivesThe ubiquitin-proteasome system is the major intracellular protein degradation pathway in the eukaryotic cells. Bortezomib inhibits 26S proteasome-induced I-κBα degradation and suppresses nuclear factor-kappa B (NF-κB) activation. We examined the effect of bortezomib on neointima formation after of a rat carotid artery balloon injury.Materials and MethodsAfter carotid artery balloon denudation, bortezomib was immediately administered by tail vein injection (systemic treatment) and by using an F-127 pluronic gel (perivascular treatment). Two weeks after the injury, we compared the degree of neointima formation in the carotid artery and the tissue expression patterns of NF-κB and I-κBα.ResultsThe systemic treatment group exhibited a 29% reduction in neointima volume at two weeks after the balloon injury. On the western blot analysis, the bortezomib group exhibited an increased I-κBα expression, which suggested the inhibition of I-κBα degradation. On immunofluorescence analysis, the nuclear import of NF-κB was clearly decreased in the systemic bortezomib group. The perivascular bortezomib treatment group exhibited a significant reduction in the neointimal area (0.21±0.06 mm2 vs. 0.06±0.01 mm2, p<0.05), the neointima/media area ratio (1.43±0.72 vs. 0.47±0.16, p<0.05) and the % area stenosis (45.5±0.72% vs. 14.5±0.05%, p<0.05) compared with the control group. In situ vascular smooth muscle cell proliferation at 2 days after the injury was significantly inhibited (24.7±10.9% vs. 10.7±4.7%, p<0.05).ConclusionBortezomib suppressed NF-κB activation through the inhibition of I-κBα degradation, and significantly reduced neointima formation in a rat carotid artery injury model. These data suggested that bortezomib represented a new potent therapeutic agent for the prevention of restenosis.

Comparison of vascular response to the everolimus-eluting stent versus the paclitaxel-eluting stent: intravascular ultrasound results from the SPIRIT III trial

The purpose of this study was to investigate the vascular response of the everolimus-eluting stent (EES) compared with the paclitaxel-eluting stent (PES) using serial intravascular ultrasound (IVUS). Data were obtained from the SPIRIT III trial, a multicentre, 2:1 randomised, controlled study comparing EES and PES in de novo native coronary artery lesions. IVUS images were eligible for volumetric analysis at eight-month follow-up in 158 lesions (EES: 113, PES: 45). At eight months, EES had a smaller neointimal volume index (VI: mm3/mm) (EES: 0.4±0.4 vs. PES: 0.8±0.8 mm3/mm, p=0.002) and also a smaller % neointimal obstruction (EES: 7.1±6.7% vs. PES: 11.1±10.5%, p=0.005) compared with PES. While there was no significant change in vessel VI with EES, there was a significant increase in vessel VI in PES during eight-month follow-up (EES: 0.1±1.2 vs. PES: 1.2±0.8 mm3/mm, p=0.001). There were no statistical differences in the frequency of edge dissection or incomplete stent apposition between the two groups. Detailed IVUS analysis confirmed significantly less neointimal hyperplasia with EES compared with PES. While there was no increase in vessel volume with EES during the eight-month follow-up period, vessel enlargement was seen at the stented segment in PES.

Evaluation of Efficacy and Dose Response of Different Paclitaxel-Coated Balloon Formulations in a Novel Swine Model of Iliofemoral In-Stent Restenosis

The authors aimed to validate a novel iliofemoral in-stent restenosis (ISR) model for the efficacy evaluation of paclitaxel-coated balloons (PCB) using the familial hypercholesterolemic swine (FHS). Most of the validation work regarding PCB technologies has been performed in the coronary territory of juvenile domestic swine. Although invaluable for safety evaluation, this model is not suited for the evaluation of the efficacy of peripheral PCB technologies. Twenty-four iliofemoral segments in 12 FHS underwent balloon injury and self-expanding stent placement. After 21 days, the resulting ISR lesions were treated with either 1 μg/mm(2) dose (n = 8), or 3 μg/mm(2) dose (n = 8) PCB (Cotavance, Bayer Pharma AG/MEDRAD, Indianola, Pennsylvania), or with an identical uncoated control balloon (n = 8). At termination (28 days after treatment), the percent diameter stenosis by quantitative vascular analysis in the control group was higher (31.2 ± 13.7%) compared with the 1 μg/mm(2) (19.3 ± 14.0%, 38% reduction) and 3 μg/mm(2) (8.6 ± 10.7%, 72% reduction) PCB groups. Intravascular ultrasound analysis showed 36% (1 μg/mm(2) dose, p = 0.04) and 55% (3 μg/mm(2) dose, p < 0.01) reductions in neointimal volume stenosis. In the histological analysis, the control group showed the highest degree of percent area stenosis (65 ± 14.3%). The reductions in percent area stenosis was 13.2% (p = 0.5) and 26% (p = 0.04) in the 1 μg/mm(2) and 3 μg/mm(2) dose groups, respectively. The FHS model of iliofemoral ISR demonstrated a dose-dependent effect on the inhibition of neointimal proliferation of a clinically validated PCB technology. This model represents a positive step toward the efficacy evaluation of PCB in the peripheral vascular territory.

Local delivery of sirolimus nanoparticles for the treatment of in‐stent restenosis

To test the local delivery of sirolimus nanoparticles following percutaneous transluminal coronary angioplasty (PTCA) to treat in-stent restenosis (ISR) in a swine model. Coronary bare-metal stent (BMS) implantation reduces major adverse cardiac events when compared with PTCA; however, ISR rates remain high. Eighteen swine underwent BMS deployment guided by intravascular ultrasound (IVUS). Of these, 16 developed ISR (1 stent/swine) and underwent angioplasty with a noncompliant balloon (PTCA-NC). The animals were then randomized into four groups for local infusion of sirolimus nanoparticles through a porous balloon catheter, as follows: (1) PTCA-NC alone (control); (2) PTCA-NC + (polylactic acid)-based nanoparticle formulation (anionic 1); (3) PTCA-NC + (polylactic-co-glycolic acid)-based nanoparticle formulation (anionic 2); and (4) PTCA-NC + Eudragit RS nanoparticle formulation (cationic). Coronary angiography and IVUS follow-up were performed 28 days after ISR treatment. There was one episode of acute coronary occlusion with the cationic formulation. Late area loss was similar in all groups at 28 days according to IVUS. However, luminal volume loss (control = 20.7%, anionic 1 = 4.0%, anionic 2 = 6.7%, cationic = 9.6%; P = 0.01) and neointimal volume gain (control = 68.7%, anionic 1 = 17.4%, anionic 2 = 29.5%, cationic = 31.2%; P = 0.019) were significantly reduced in all treatment groups, especially in anionic 1. PTCA-NC followed by local infusion of sirolimus nanoparticles was safe and efficacious to reduce neointima in this model, and this strategy may be a promising treatment for BMS ISR. Further studies are required to validate this method in humans.

Randomized trial of insulin versus usual care in reducing restenosis after coronary intervention in patients with diabetes. the STent Restenosis And Metabolism (STREAM) study

Diabetes status is an independent marker of restenosis after percutaneous coronary intervention (PCI). Previous studies suggest that metabolic abnormalities associated with diabetes increase stent restenosis by promoting intimal hyperplasia. Preclinical studies have indicated that insulin therapy reduces intimal hyperplasia. The objective of this study was to determine whether insulin-mediated glucose lowering reduces in-stent restenosis in patients with diabetes undergoing PCIs. We conducted a prospective, randomized, multicenter, open-labeled study with blinded outcomes. Patients were randomized 1:1 to daily bedtime subcutaneous NPH insulin (Novo Nordisk) versus usual therapy with oral hypoglycemic agents. The main outcomes were change in volume of intimal hyperplasia within the stent measured by intravascular ultrasound and late lumen loss by quantitative coronary angiography at 6 months post-PCI. Seventy-eight patients (36 insulin, 42 usual care) were randomized. Eight patients in each group received drug-eluting stents. The insulin group achieved greater reductions in both glycosylated hemoglobin A1c (mean±S.D.) (insulin: 8.0%±1.2% to 6.7%±0.7% vs. control: 7.5%±1.2% to 7.1%±1.0 %, P=.0038) and fasting glucose (insulin: 9.3±3.8 to 5.8±1.7 vs. usual care: 8.4±2.4 to 7.7±2.0 mmol/l, P<.0001). There were no hypoglycemic events. At 6 months, there were no significant differences in either intravascular-ultrasound-determined neointimal volume (insulin: 41.2±38.9 vs. usual care: 48.4±40.2 mm(3), P=.33) or late lumen loss by angiography (insulin: 1.29±0.74 mm vs. usual care: 1.02±0.71 mm, P=.17). Addition of a single bedtime dose of insulin in patients with diabetes does not influence in-stent restenosis.

Porównanie bezpieczeństwa i skuteczności stentów uwalniających paklitaksel z polimeru trwałego i biodegradowalnego w zmianach zlokalizowanych w żylnych pomostach aortalno-wieńcowych. Ocena angiograficzna i metodą ultrasonografii wewnątrznaczyniowej po dziewięciu miesiącach od implantacji stentu

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Pregowski J, Witkowski A, Chmielak Z, et al. Original paperComparison of safety and efficacy of paclitaxel-eluting stents with durable versus biodegradable polymer implanted in saphenous vein graft lesions. Nine-month angiographic and intravascular ultrasound follow-up. Advances in Interventional Cardiology/Postępy w Kardiologii Interwencyjnej. 2012;8(4):269-274. doi:10.5114/pwki.2012.31906. APA Pregowski, J., Witkowski, A., Chmielak, Z., Kalińczuk, Ł., Ciszewski, A., & Karcz, M. et al. (2012). Original paperComparison of safety and efficacy of paclitaxel-eluting stents with durable versus biodegradable polymer implanted in saphenous vein graft lesions. Nine-month angiographic and intravascular ultrasound follow-up. Advances in Interventional Cardiology/Postępy w Kardiologii Interwencyjnej, 8(4), 269-274. https://doi.org/10.5114/pwki.2012.31906 Chicago Pregowski, Jerzy, Adam Witkowski, Zbigniew Chmielak, Łukasz Kalińczuk, Andrzej Ciszewski, Maciej Karcz, and Jakub Przyłuski et al. 2012. "Original paperComparison of safety and efficacy of paclitaxel-eluting stents with durable versus biodegradable polymer implanted in saphenous vein graft lesions. Nine-month angiographic and intravascular ultrasound follow-up". Advances in Interventional Cardiology/Postępy w Kardiologii Interwencyjnej 8 (4): 269-274. doi:10.5114/pwki.2012.31906. Harvard Pregowski, J., Witkowski, A., Chmielak, Z., Kalińczuk, Ł., Ciszewski, A., Karcz, M., Przyłuski, J., Jastrzebski, J., Wolny, R., and Dziarmaga, M. (2012). Original paperComparison of safety and efficacy of paclitaxel-eluting stents with durable versus biodegradable polymer implanted in saphenous vein graft lesions. Nine-month angiographic and intravascular ultrasound follow-up. Advances in Interventional Cardiology/Postępy w Kardiologii Interwencyjnej, 8(4), pp.269-274. https://doi.org/10.5114/pwki.2012.31906 MLA Pregowski, Jerzy et al. "Original paperComparison of safety and efficacy of paclitaxel-eluting stents with durable versus biodegradable polymer implanted in saphenous vein graft lesions. Nine-month angiographic and intravascular ultrasound follow-up." Advances in Interventional Cardiology/Postępy w Kardiologii Interwencyjnej, vol. 8, no. 4, 2012, pp. 269-274. doi:10.5114/pwki.2012.31906. Vancouver Pregowski J, Witkowski A, Chmielak Z, Kalińczuk Ł, Ciszewski A, Karcz M et al. Original paperComparison of safety and efficacy of paclitaxel-eluting stents with durable versus biodegradable polymer implanted in saphenous vein graft lesions. Nine-month angiographic and intravascular ultrasound follow-up. Advances in Interventional Cardiology/Postępy w Kardiologii Interwencyjnej. 2012;8(4):269-274. doi:10.5114/pwki.2012.31906.

First-in-Man Study of Simvastatin-Eluting Stent in De Novo Coronary Lesions

Statins have anti-inflammatory and antiproliferative properties irrespective of their cholesterol-lowering effects. The aim of the present study was to evaluate a simvastatin-eluting stent (SimvES) in the treatment of de novo coronary lesions. Forty-two patients with de novo coronary artery lesions were assigned to SimvES, bare-metal stent (BMS) or everolimus-eluting stent (EES) implantation followed by intravascular ultrasound (IVUS) for neointimal quantitative analysis. Six months later, quantitative coronary angiography (QCA) and IVUS were repeated. QCA showed no binary restenosis, a mean in-stent late loss of 1.05 ± 0.25 mm (BMS, 1.12 ± 0.48 mm; EES, 0.20 ± 0.16 mm) and a diameter stenosis of 33.5 ± 7.1% (BMS, 35.5 ± 15.30%; EES, 7.2 ± 3.12%). Control IVUS showed a mean in-stent obstruction of 18.3 ± 9.4% (BMS, 32.8 ± 19.1%; EES, 9.8 ± 2.4%) and a neointimal volume index of 1.58 ± 0.75 mm(3)/mm (BMS, 2.93 ± 1.76 mm(3)/mm; EES, 0.80 ± 0.16 mm(3)/mm). Thrombus, late incomplete apposition and major adverse cardiac events were not observed. In this sample of patients with de novo coronary lesions, the use of a SimvES was not related to major adverse cardiac events, but it was associated with a higher level of neointimal proliferation than expected.

Comparison of Vascular Remodeling in Patients Treated With Sirolimus‐Versus Zotarolimus‐Eluting Stent Following Acute Myocardial Infarction

The differences in the vascular response to stent implantation or in the incidence of late acquired stent malapposition among different types of drug-eluting stents are not well known in patients with acute myocardial infarction (MI). The pattern of vascular remodeling and degree of neointimal proliferation were different depending on the different types of drug-eluting stents. This study used intravascular ultrasound (IVUS) to investigate vascular remodeling in patients treated with implantation of sirolimus-eluting stents (SESs) vs zotarolimus-eluting stents (ZESs) following acute MI. The study population consisted of 100 patients with acute MI who were treated either with SES (n = 41) or ZES (n = 59) and underwent both poststenting and 9-month follow-up IVUS examination. Serial vascular changes surrounding stented segments were compared between SES- and ZES-treated lesions. Percentage of neointimal volume obstruction at follow-up was significantly smaller in SES-treated compared to ZES-treated lesions (2.8 ± 7.1% vs 18.1 ± 15.7%, respectively; P < 0.001). However, positive vascular remodeling, which was defined as greater than 10% increase in external elastic membrane volume index (31.7% vs 10.2%, respectively, P = 0.007), and late acquired stent malapposition (12.0% vs 0%, respectively, P = 0.006 ) occurred more frequently in SES-treated than in ZES-treated lesions. The pattern of vascular remodeling, including positive remodeling, late acquired stent malapposition, and degree of neointimal proliferation might be different depending on the different types of drug-eluting stents in patients with acute MI.

Effects of Combination Therapy with Celecoxib and Doxycycline on Neointimal Hyperplasia and Inflammatory Biomarkers in Coronary Artery Disease Patients Treated with Bare Metal Stents

PurposeCyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 play a key role in the pathogenesis of in-stent restenosis. We investigated the effect of a short-term therapy of celecoxib, a COX-2 inhibitor, with or without doxycycline, an MMP inhibitor, after coronary stenting on inflammatory biomarkers and neointimal hyperplasia.Materials and MethodsA total of 75 patients (86 lesions) treated with bare metal stents were randomized into three groups: 1) combination therapy (200 mg celecoxib and 20 mg doxycycline, both twice daily), 2) celecoxib (200 mg twice daily) only, and 3) non-therapy control. Celecoxib and doxycycline were administered for 3 weeks after coronary stenting. The primary endpoint was neointimal volume obstruction by intravascular ultrasound (IVUS) at 6 months. The secondary endpoints included clinical outcomes, angiographic data, and changes in blood levels of inflammatory biomarkers.ResultsFollow-up IVUS revealed no significant difference in the neointimal volume obstruction among the three treatment groups. There was no difference in cardiac deaths, myocardial infarctions, target lesion revascularization or stent thrombosis among the groups. Blood levels of high-sensitivity C-reactive protein, soluble CD40 ligand, and MMP-9 varied widely 48 hours and 3 weeks after coronary stenting, however, they did not show any significant difference among the groups.ConclusionOur study failed to demonstrate any beneficial effects of the short-term therapy with celecoxib and doxycycline or with celecoxib alone in the suppression of inflammatory biomarkers or in the inhibition of neointimal hyperplasia. Large scale randomized trials are necessary to define the role of anti-inflammatory therapy in the inhibition of neointimal hyperplasia.

Abstract 17782: New Generation Drug Eluting Stent Has Increased Vascular Healing by Resolved Postprocedural Incomplete Stent Apposition

Background: While there are controversies regarding the late clinical impact of post-procedural incomplete stent apposition (PISA) and late incomplete stent apposition (LISA), there has been limited data in the newer generation of drug eluting stent. The aim of this study was to investigate the morphologic change of PISA and incidence of LISA during 1 year follow up. Methods: We prospectively enrolled 128 patients who underwent percutaneous coronary intervention (PCI); stable angina (n=30), unstable angina (n=82), and non-ST segment elevation myocardial infarction (n=16) (61.2±10.4 years, 78 male, 194 lesions - 106 left anterior descending artery, 25 left circumflex artery, 63 right coronary artery). The implanted stent was randomly assigned (the proportion of 2:1), zotarolimus eluting stent (group I, n=130, Endeavor Resolute TM , Medtronic) or everolimus eluting stent (group II, n=64, Xience TM V, Abbott Vascular). Post-PCI and 1 year follow up intravascular ultrasound (IVUS) analysis were performed in all patients. Results: There were no baseline clinical, angiographic, and procedural differences between the two groups. The Post-PCI external elastic membrane (EEM) volume (group I vs group II, 377.2±111.8 vs 436.1±219.6 mm 3 , p =0.155), Post-PCI lumen volume (208.3±66.1 vs 233.8±112.3 mm 3 , p =0.283), 1 year EEM volume (387.4±106.8 vs 436.6±218.3 mm 3 , p =0.240), 1 year lumen volume (212.5±64.9 vs 231.9±112.5 mm 3 , p =0.395), and 1 year intra-stent neointimal hyperplasia volume (4.8±7.3 vs 5.2±17.6 mm 3 , p =0.914) by IVUS analysis were not different between the two groups. There were three LISA (1.5%, two Endeavor, one Xience), and ten PISA (5.2%, five Endeavor, five Xience) that were resolved (40%, three Endeavor, one Xience) or persistent (60%, two Endeavor, four Xience). However, both LISA and PISA did not associated with MACE during 1 year follow up. Conclusions: In conclusion, the incidence of both LISA and PISA was very low in new generation drug eluting stent. The morphologic healing or persistence of PISA during 1 year IVUS follow up was observed. Future larger long-term follow up study to clarify the clinical course of LISA and PISA would be needed.

Are Paclitaxel-Eluting Stents Better in Unprotected Left Main Coronary Artery Disease? Three-Year Clinical and Intravascular Imaging Results From a Randomized Study

Recent publications have demonstrated superior outcomes in unprotected left main patients after paclitaxel-eluting stent (PES) implantation. Long-term data in these patients are limited. The aim of this study was to evaluate if intravascular ultrasound (IVUS)-guided PES implantation is superior to bare metal stent (BMS) implantation in unprotected left main disease after lesion pretreatment with cutting balloon during long-term follow-up. Unprotected left main patients were randomized to BMS (n=50) or PES implantation (n=53). All interventions were IVUS-guided and cutting balloon pretreatment before stenting was performed in all patients. All patients were scheduled for 6-month and 3-year follow-up. Subgroups of patients who underwend IVUS and OCT imaging at 3-year follow-up were analyzed. The primary endpoint was the major adverse cardiac events (MACEs) defined as death, Q-wave myocardial infarction, or target lesion revascularization. Baseline characteristics were similar in both the groups with a mean SYNTAX score of 31.4±14.5 in BMS and 32.6±11.7 in PES patients (P=0.718). At 3 years, MACEs occurred in 18 patients (36.0%) in the BMS and 7 patients (13.2%) in the PES group (P=0.011). By IVUS, percent neointimal volume obstruction at 3 years was reduced from 18.1%±8.7% with BMSs to 10.0%±5.4% with PESs (P<0.001). The total number of uncovered stent struts per OCT image and IVUS image was 0.4±0.8 and 1.2±1.5, respectively (P<0.001). The current study demonstrated that IVUS-guided PES implantation was superior to BMS implantation after cutting balloon pretreatment in unprotected left main disease at 3 years. If compared with IVUS, OCT was more precise in the assessment of stent endothelization.

Paclitaxel-coated balloon in combination with bare metal stent for treatment of de novo coronary lesions: an optical coherence tomography first-in-human randomised trial, balloon first vs. stent first

To test the efficacy of sequential application of drug-coated balloon (DCB) and bare metal stent (BMS) for treatment of de novo coronary lesions, comparing the sequence of application (DCB first vs. BMS first). In a multicentre pilot trial, 26 patients with de novo coronary lesions were randomised to receive a paclitaxel-coated balloon application followed by BMS implantation (DCB first) or vice versa (BMS first). Quantitative coronary angiography (QCA) and optical coherence tomography (OCT) were performed post-procedure and at six months, with OCT % neointimal volume obstruction as primary endpoint. Longitudinal geographical miss was only observed in DCB first (23.1 vs. 0.0%, p=0.220). Implantation of BMS first resulted in fewer malapposed struts (p=0.013) but similar coverage at six months. No significant difference was found regarding the primary endpoint (25.5 vs. 24.9%, p=0.922), mean thickness of coverage (261 vs. 225 µm, p=0.763), late loss (0.53 vs. 0.45 mm, p=0.833), binary restenosis (27.3 vs. 16.7% in-segment, p=0.640) or clinical endpoints. Sequential application of DCB and not pre-mounted BMS for treatment of de novo coronary lesions results in efficient inhibition of neointimal hyperplasia. The sequence of application (DCB first vs. BMS first) does not seem to influence the outcome, except for better apposition in BMS first.

YIA 3 Effect of intracellular glucocorticoid metabolism on neointimal proliferation in a mouse model of wire angioplasty

RationaleGlucocorticoid administration increases cardiovascular risk but inhibits neointimal proliferation in animal models. Glucocorticoid activity in target tissues is regulated by the isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD); type-1 regenerates active glucocorticoids...

Should stent selection in diabetic patients be considered as a special case?

■Interventional cardiologists are very aware of the additional challenges of treating patients with diabetes. They recognise the likelihood of increased procedural complexity due to more diffuse vascular disease and the reduced certainty of long-term clinical outcomes due to accelerated rates of atheroma progression combined with increased rates of bare metal stent restenosis 1 and stent thrombosis 2 . However despite this solid knowledge base, diabetic patients entering the catheterisation laboratory are commonly treated with remarkably little additional consideration. Many operators decide revascularisation strategies based predominantly on anatomical characteristics and the choice of which type of stent to implant can appear to be arbitrary. In this edition of EuroIntervention, colleagues present comparative IVUS analysis following DES implantation in diabetics 3 and a cost-efficiency analysis of data from comparative randomised DES trials enrolling diabetic patients 4 . When we consider these new data, should we conclude that the outcomes associated with use of alternative DES in diabetic patients are sufficiently diverse to mandate a particular stent for this “special” group of patients? It is easy to forget that DES technology entered our clinical practice less than ten years ago. Initial trial data from randomised trials of focal lesions in larger vessels demonstrated the additional benefits of drug elution compared with bare metal stents 5 . Intravascular ultrasound was an important part of these early DES trials. Measurement of neointimal volume allowed ready comparison of drug efficacy and insights into the moderated healing process. However, there was considerable debate concerning the clinical relevance of differing neointimal volume, the “optimal amount” of neointima and the desirability of stent strut coverage to minimise the risk of stent thrombosis. In their paper Jensen and colleagues show substantial differences in the median volume obstruction in diabetic patients after implantation of either the sirolimus-eluting Cypher stent or the first generation zotarolimus-eluting Endeavour stent (median volume obstruction 0% vs. 13%, respectively) 3 . They also make comparison with their previous similar investigations in diabetic patients undergoing implantation of either the Cypher or the paclitaxel eluting Taxus Express stent (median volume obstruction 0% vs. 7.5%, respectively) 6 . Interest

Telmisartan reduces neointima volume and pulse wave velocity 8 months after zotarolimus-eluting stent implantation in hypertensive type 2 diabetic patients

ObjectiveTelmisartan is a peroxisome proliferator-activated receptor-γ activator with potent anti-inflammatory and antiatherogenic effects. The authors compared the effects of telmisartan and valsartan on neointima volume, atherosclerosis progression and brachial-ankle pulse...

Tissue coverage of a hydrophilic polymer-coated zotarolimus-eluting stent vs. a fluoropolymer-coated everolimus-eluting stent at 13-month follow-up: an optical coherence tomography substudy from the RESOLUTE All Comers trial

AimsTo compare the tissue coverage of a hydrophilic polymer-coated zotarolimus-eluting stent (ZES) vs. a fluoropolymer-coated everolimus-eluting stent (EES) at 13 months, using optical coherence tomography (OCT) in an ‘all-comers' population of patients, in order to clarify the mechanism of eventual differences in the biocompatibility and thrombogenicity of the devices.Methods and resultsPatients randomized to angiographic follow-up in the RESOLUTE All Comers trial (NCT00617084) at pre-specified OCT sites underwent OCT follow-up at 13 months. Tissue coverage and apposition were assessed strut by strut, and the results in both treatment groups were compared using multilevel logistic or linear regression, as appropriate, with clustering at three different levels: patient, lesion, and stent. Fifty-eight patients (30 ZES and 28 EES), 72 lesions, 107 stents, and 23 197 struts were analysed. Eight hundred and eighty-seven and 654 uncovered struts (7.4 and 5.8%, P= 0.378), and 216 and 161 malapposed struts (1.8 and 1.4%, P= 0.569) were found in the ZES and EES groups, respectively. The mean thickness of coverage was 116 ± 99 µm in ZES and 142 ± 113 µm in EES (P= 0.466). No differences in per cent neointimal volume obstruction (12.5 ± 7.9 vs. 15.0 ± 10.7%) or other areas–volumetric parameters were found between ZES and EES, respectively.ConclusionNo significant differences in tissue coverage, malapposition, or lumen/stent areas and volumes were detected by OCT between the hydrophilic polymer-coated ZES and the fluoropolymer-coated EES at 13-month follow-up.

Comparison of neointimal morphology of in-stent restenosis with sirolimus-eluting stents versus bare metal stents: virtual histology-intravascular ultrasound analysis

Sirolimus-eluting stents (SES) have reduced the incidence of restenosis and target lesion revascularization compared to bare metal stents (BMS). However, inhibition of endothelialization and neointimal formation after SES implantation may produce vulnerable plaques. The present study compared the neointimal morphology of in-stent restenosis (ISR) between SES and BMS using virtual histology-intravascular ultrasound (VH-IVUS). Thirty ISR lesions (SES n=15, BMS n=15) demonstrated by coronary angiography in 30 patients with stable angina pectoris were analyzed with VH-IVUS between 6months to 3years after stent implantation. Tissue maps were reconstructed from radiofrequency data using VH-IVUS software. ISR lesions after SES implantation consisted of a significantly increased necrotic core (NC) compared to BMS (12.9 vs. 5.6% of neointimal volume, p<0.01). However, the NC in ISR lesions after SES implantation was covered with a thick fibrous cap. An increase in the size of NC covered with a thick fibrous cap is a characteristic morphological feature of ISR after SES implantation. Further studies are needed to clarify whether such a morphological change is related to the attenuation of stent thrombosis after SES implantation.

Angiographic and intravascular ultrasound follow up of paclitaxel‐ and sirolimus‐eluting stent after poststent high‐pressure balloon dilation: From the poststent optimal stent expansion trial

The aims of this study were to identify the efficacy of optimal stent expansion (OSE) according to the Multicenter Ultrasound Stenting in Coronaries Study (MUSIC Study) criteria in drug-eluting stent (DES) and compare paclitaxel-eluting stent (PES) to sirolimus-eluting stent (SES). Although poststent high-pressure balloon dilatation is proposed after bare metal stent implantation according to OSE, defined by the criteria of the MUSIC Study, very little data are available in DES. Two hundred fifty patients (M:F = 149:101; age, 61.5 ± 9.2 years) who underwent 9-month follow-up angiography in the Poststent Optimal Stent Expansion Trial (POET) were included in this study. We assessed angiographic in-stent restenosis (ISR) and neointima volume (NV) using IVUS at 9 months. At 9-month follow up, there were no significant differences in ISR and NV index (NV/stent length, mm(2) ) between patients with and without OSE. However, the rate of ISR and NV index were higher in PES [ISR: 18 (13.7%) and 4 (3.4%), P = 0.004; NV index: 1.02 ± 0.99 mm(2) and 0.21 ± 0.37, P < 0.001 in PES and SES]. OSE according to the MUSIC Study criteria was not related to ISR and NV in the DES era but PES had a significantly higher ISR rate and NV than SES after poststent high-pressure balloon dilatation.

Coronary bare metal stent implantation in homozygous LDL receptor deficient swine induces a neointimal formation pattern similar to humans

Introduction To date, most of all new developments in stent technologies are tested in normal animals. Although invaluable in the evaluation of device safety, the juvenile domestic swine (DS) do not follow the biological healing response occurring in humans following coronary stent implantation. By using a novel swine breed afflicted with familial hypercholesterolemia (FHS), we aimed to analyse the vascular response occurring following bare metal stent (BMS) implantation by comparing in vivo endovascular imaging and histological data. Methods A total of 26 swine were included in this study (12 FHS and 14 DS). Sixty eight BMS (FHS = 28 versus DS = 40) were implanted using a 10% overstretch ratio. Imaging evaluation (IVUS and OCT) was conducted in all animals at 30 ( n = 14) or 90 ( n = 12) days following stent implantation. After imaging, the stented coronary segments were harvested for histological evaluation. Results At 30 days, the degree of neointimal formation analysed by OCT (%AS = DS 21.9 ± 10% versus FHS 25.4 ± 12%; p = 0.18) and histology (DS 24.6 ± 10% versus FHS 23.58 ± 10%; p = 0.8) was similar between both animal groups. At 90 days, the degree of neointimal formation in the DS group decreased in all analysed variables (−40% in IVUS neointimal volume, −57% in OCT %AS, and −30% in %AS by histology) compared to the progression of neointimal formation observed in the FHS group (+29% in IVUS neointimal volume, +27% in OCT %AS and +43% in %AS by histology). Conclusion The pattern of neointimal formation following BMS implantation in the FHS follows a progressive course that does not occur in the DS. Therefore, by providing a progressive neointimal biological response to BMS implantation, the FHS could serve as an ideal efficacy model for the validation of drug eluting stent technologies.