Neointimal Response Research Articles

Insights into the biocompatibility of biodegradable metallic molybdenum for cardiovascular applications-a critical review.

Atherosclerotic cardiovascular disease (ACD) is the leading cause of death worldwide. The gold standard of treatment is the implantation of a permanent stent implant that is often associated with complications such as thrombus formation, vascular neointimal response, and stent fracture, which altogether decrease the long-term safety and efficacy of the stent. Biodegradable metallic materials have become an attractive alternative because of the ability to facilitate a more physiological healing response while the metal degrades. Recently, Molybdenum (Mo) has been considered as a potential candidate due to its excellent mechanical and medical imaging properties. Moreover, the biomedical research studies performed to date have shown minimal adverse effects in vitro and in vivo. However, there are still concerns of toxicity at high doses, and the impact of the biochemical mechanisms of Mo on material performance especially in pathophysiological environments are yet to be explored. Mo is an essential co factor for enzymes such as xanthine oxidoreductase (XOR) that plays a critical role in vascular homeostasis and ACD progression. Herein, this review will focus on the biochemistry of Mo, its physiological and pathological effects with an emphasis on cardiovascular disease as well as the recent studies on Mo for cardiovascular applications and its advantages over other biodegradable metals. The limitations of Mo research studies will also be discussed and concluded with an outlook to move this revolutionary metallic biomaterial from the bench to the bedside.

Estudio comparativo de la cobertura neointimal entre los stents con recubrimiento de titanio-óxido nítrico y los liberadores de everolimus en el sindrome coronario agudo

Introduction and objectivesTo evaluate by optical coherence tomography neointimal healing response after implantation of cobalt-chromium-based titanium-nitride-oxide-coated (TiNO) stents and platinum-chromium-based biodegradable-polymer-coated everolimus-eluting stents (EES) in patients with acute coronary syndrome. MethodsPatients were randomized (1:1) to receive either a TiNO-stent or EES. Optical coherence tomography images were obtained at 30-day (cohort A, n = 52) and 6-month (cohort B, n = 30) follow-up. The primary endpoint was the percentage of uncovered struts per patient. ResultsIn cohort A, the percentage of uncovered struts was lower with TiNO-stents vs EES (3.2% vs 19.6%, P <.001). The percentage of malapposed struts was 0.4% in the TiNO-group and 2.1% in the EES group (P <.001). In cohort B, the percentage of uncovered struts was also lower with TiNO-stents (0.0% vs 8.7% (P <.001). The percentage of malapposed struts was 0% in the TiNO-stent group and 0.3% in the EES group (P=.008). None of the patients had repeat revascularization during the 6 months of follow-up. ConclusionsFollowing percutaneous intervention for acute coronary syndrome, TiNO stent implantation was associated with a lower percentage of uncovered and malapposed struts per patient, compared with EES, at early and mid-term follow-up.This study is registered under ClinicalTrials.gov, with number NCT02464397.

Comparative study of neointimal coverage between titanium-nitric oxide-coated and everolimus-eluting stents in acute coronary syndromes

Introduction and objectivesTo evaluate by optical coherence tomography neointimal healing response after implantation of cobalt-chromium-based titanium-nitride-oxide-coated (TiNO) stents and platinum-chromium-based biodegradable-polymer-coated everolimus-eluting stents (EES) in patients with acute coronary syndrome. MethodsPatients were randomized (1:1) to receive either a TiNO-stent or EES. Optical coherence tomography images were obtained at 30-day (cohort A, n = 52) and 6-month (cohort B, n = 30) follow-up. The primary endpoint was the percentage of uncovered struts per patient. ResultsIn cohort A, the percentage of uncovered struts was lower with TiNO-stents vs EES (3.2% vs 19.6%, P <.001). The percentage of malapposed struts was 0.4% in the TiNO-group and 2.1% in the EES group (P <.001). In cohort B, the percentage of uncovered struts was also lower with TiNO-stents (0.0% vs 8.7%, (P <.001). The percentage of malapposed struts was 0% in the TiNO-stent group and 0.3% in the EES group, (P=.008). None of the patients had repeat revascularization during the 6 months of follow-up. ConclusionsFollowing percutaneous intervention for acute coronary syndrome, TiNO stent implantation was associated with a lower percentage of uncovered and malapposed struts per patient, compared with EES, at early and mid-term follow-up.This study is registered under ClinicalTrials.gov, with number NCT02464397.

Relation between pre-existing plaque size and neointimal healing in an adult porcine model of familial hypercholesterolemia

Abstract Background Despite the efficacy of novel drug eluting stents (DES) in preventing restenosis, this complication still occurs, as do neo-atherosclerosis development and poor stent strut coverage that are associated with stent thrombosis. Safety and efficacy of novel coronary stents are preclinically being tested using an established porcine coronary model. However, the use of young healthy animal only allow limited conclusions to be drawn on the long-term effects, as the artieries do not reflect human pathology of advanced atherosclerosis. A key unresolved question is whether and how the presence, size and composition of pre-existing atherosclerotic plaque affect neointimal healing. Purpose The objective of this study is to understand the role of atherosclerotic plaque in neointimal response following DES placement in a large animal model of coronary artery disease by using optical coherence tomography (OCT) analysis. Methods The study was approved by the animal ethics committee. Familial hypercholesterolemia (FH) swine (n=6 Bretoncelles-Meishan) were given a high fat diet for 12 months to develop atherosclerosis. Stents (n=14) were implanted in n=14 coronary arteries under guidance of OCT with a stent-artery ratio of 1.1:1 at sites of atherosclerotic plaque, and animals were sacrificed after 28 days. Two types of Sirolimus eluting stents with different release profiles were implanted. Serial OCT pullbacks were taken before and after stent placement and after 28 days (follow-up), quantitatively analyzed and compared using dedicated software. The lumen area, stent area, plaque size (calculated as external elastic lamina (EEL) area - lumen area) and neointima (calculated as stent area – lumen area) were evaluated for each frame and averaged per stent. The plaque burden before stent implantation was evaluated at the same site of stent placement using coronary side branches as reference. Results The graph shows the association between the pre-existing plaque size before stenting and neointima formation after 28 days. Surprisingly, more pre-existing plaque size resulted in less neointima (P&amp;lt;0.01). There was one outlier, a stent with long dissection and extensive malapposition at baseline which showed an excessive tissue response at follow-up. The response in this animal model shows similarity to human vessel response as both regions with thin neointima formation as well as poor strut coverage were observed for both stent types. Conclusion The novel model of adult FH swine shows long-term vessel response to DES, that is similar to human response. This work shows that pre-existing atherosclerotic plaque affects the neointima after DES implantation. This insight highlights the necessity to use relevant disease models for safety and efficacy testing. Plaque size and neointima relation Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Netherlands Organisation for Health Research and Development (ZonMw)

Vein Source Influences Neointimal Response in Rat Vein-to-Artery Grafts

BackgroundVein graft stenosis is a major complication of coronary artery bypass surgery and peripheral arterial bypass procedures. Experimental models of this clinical complication have used in vivo grafting procedures, relying on the relatively modest neointimal thickening in these models as a surrogate for clinical graft stenosis without regard to the donor site origin of the vein graft. Materials and methodsIn a standard rat model of vein grafting, three different donor sites were used to supply veins used as interpositional grafts to the femoral artery: the superficial inferior epigastric vein, the common femoral vein, and the posterior facial vein (distal branch of the jugular vein). Grafts were harvested as 4 wk and histomorphometrically evaluated for the extent of neointimal formation and lumen narrowing. ResultsThe posterior facial vein showed significantly thicker neointima and a greater extent of lumen narrowing than the other two graft sources, despite having a similar diameter to the femoral vein and nearly twice the initial diameter of the epigastric vein. ConclusionsThe source of donor graft material can greatly influence the extent of neointimal response after interpositional vein grafting to arterial flow. These findings support use of the posterior facial vein graft over other more standard donor vein grafts in research directed at understanding the causes and prevention of vein graft stenosis.

Empagliflozin attenuates neointimal hyperplasia after drug-eluting-stent implantation in patients with type 2 diabetes.

The effects of empagliflozin, a sodium-glucose co-transporter 2 inhibitor, on neointimal response after drug-eluting-stent (DES) implantation remains unknown. Insufficiently controlled diabetes patients with coronary artery disease planned for DES stenting were consecutively enrolled. The patients were assigned to receive empagliflozin in addition to standard therapy or intensive therapy using other glucose-lowering drugs (oGLD). The primary endpoint was thickness of neointimal hyperplasia (NIH) 12months after stenting assessed by optical coherence tomography (OCT). A total of 28 patients were analyzed (n = 15 in the empagliflozin group, n = 13 in the oGLD group). The levels of glucose profile were not significantly different between both groups at follow-up [HbA1c; 7.2 ± 0.8 vs 7.3 ± 0.9%, p = 0.46]. In OCT analysis, neointima was significantly less in the empagliflozin group than the oGLD group [mean NIH thickness: 137 ± 32 vs 168 ± 39μm, p = 0.02]. Changes of systolic and diastolic blood pressure (BP), changes of body mass index, and changes of hematocrit after additional treatment were significantly associated with NIH attenuation, whereas no correlation was observed in changes in blood glucose parameters. Multivariate logistic regression analysis revealed that changes in systolic BP was the strongest predictor for NIH attenuation, followed by changes in diastolic BP. In patients with type 2 diabetes, standard plus empagliflozin attenuated neointimal progression as compared with intensive standard therapy after DES implantation. Our data possibly support a beneficial effect of empagliflozin in type 2 diabetes required for coronary revascularization therapy.

Peri-strut low intensity areas and in-scaffold neointima growth after bioresorbable scaffold implantation in STEMI. A serial optical coherence tomography study

BackgroundPeri-strut low intensity areas (PLIA) visualized by optical coherence tomography (OCT) have been related to neointimal proliferation and increased incidence of target lesion revascularization in stable coronary artery disease. The aim of this study was to determine the association between PLIA by OCT and the long-term vascular healing response after bioresorbable scaffold (BRS) implantation in the setting of ST-segment elevation myocardial infarction (STEMI). MethodsThis is a single-centre, longitudinal, cohort study with a serial: baseline, 1, 2 and 5 years OCT evaluation of neointimal response (lumen area and neoatherosclerosis) after percutaneous coronary intervention (PCI) with BRS Absorb™ 1.0 implantation in patients presenting with STEMI. PLIA was analyzed in every cross section and scored: 0–no PLIA; 1-PLIA < 1 quadrant; 2-PLIA ≥ 1 and <2 quadrants; 3-PLIA ≥ 2 and <3 quadrants; 4-PLIA in ≥3 quadrants. ResultsOf the 23 patients implanted BRS, 18 completed 2-year follow-up, whereas complete OCT data up to 5 years were available in 12 patients. Presence of PLIA was identified in 100% patients at 1 and 2 years, whereas at 5 years neither PLIA nor scaffold struts were visualized by OCT. Neoatherosclerosis was identified in 73,68% patients after 1 year and in all patients at 2 and 5 years. The mean PLIA score > 1 at 2 years was associated with greater percentage of minimum lumen area decrease after 2 years from index procedure. ConclusionsThe extent of PLIA by OCT at 2 years after primary PCI with BRS was associated with lumen area decrease. Neoatherosclerosis formation was detected in all patients at 2 and 5 years. PLIA assessment could serve as an additive means to predict neointimal healing pattern after next generation BRS implantation.

Effects of local hemodynamics and plaque characteristics on neointimal response following bioresorbable scaffolds implantation in coronary bifurcations.

Heterogeneous neointimal response has been observed after implantation of all generations of coronary stents. Our aim was assessing local factors of shear stress (SS) and plaque characteristics in neointimal response after implantation of bioresorbable scaffolds (BRS) in bifurcations. Ten patients from the BIFSORB pilot study were analysed. Follow-up optical frequency domain imaging (OFDI) was performed at 1 month and 2 years. Coronary lumen and BRS structure were reconstructed by fusion of OFDI and angiography and were used for subsequent flow simulation. Plaque arc degree and SS were quantified using post-procedural OFDI data and were matched with follow-up OFDI using anatomical landmarks. Strut-level and segment-level analysis were performed for 1-month and 2-year follow-up respectively. A total of 444 struts (54 jailing struts) were included at 1-month follow-up. Time-average SS (TASS) was significantly lower for covered struts than for uncovered struts in non-bifurcation segments (TASS: 1.81 ± 1.87 vs. 3.88 ± 3.72Pa, p < 0.001). The trend remained the same for jailing struts, although statistically insignificant (TASS: 10.85 ± 13.12 vs. 13.64 ± 14.48Pa, p = 0.328). For 2-year follow-up, a total of 66 sub-regions were analysed. Neointimal hyperplasia area (NTA) was negatively correlated with TASS in core-segments (ρ = - 0.389, p = 0.037) and positively correlated with plaque arc degree in non-core segments (ρ = 0.387, p = 0.018). Slightly stronger correlations with NTA were observed when combining TASS and plaque arc degree in both core segments (ρ = - 0.412, p = 0.026) and non-core segments (ρ = - 0.395, p = 0.015). Hemodynamic microenvironment and baseline plaque characteristics may regulate neointimal response after BRS implantation in bifurcation. These findings underline the combined role of plaque characteristics and local hemodynamics in vessel healing after stent implantation.

TCT-59 Atherosclerotic Swine Model for Anatomically Correct Investigation of Below-the-Knee Interventional Therapies: Preliminary Characterization

Owing to robust inflammatory and neointimal response and exceedingly high cholesterol levels, the familial hypercholesterolemic swine (FHS) model has been very successful in predicting efficacy of peripheral antirestenotic therapies. It clearly differentiates the antiproliferative effects of drug-

TCT-182 Peristrut Low-Intensity Areas and Neointimal Response Evaluation by Serial Optical Coherence Tomography at Baseline and 1, 2, and 5 Years After Bioresorbable Scaffold Implantation in STEMI

Peristrut low-intensity areas (PLIA) surrounding metallic stent struts, visualized by optical coherence tomography (OCT), have been recently linked to inflammation, neointimal proliferation, and increased incidence of target lesion revascularization. In-scaffold neoatherosclerosis with luminal

Abstract 492: Adipolin/C1q/Tnf-related Protein 12 reduces Neointimal Formation And Atherosclerotic Lesion Development By Modulation Of Macrophage Inflammatory Response And Endothelial Cell Function

Objectives: Obesity is causally linked to the progression of vascular disorders including atherosclerosis and post-angioplasty restenosis. Recently, we identified adipolin/C1q/Tnf-related protein 12 as an insulin sensitizing adipokine,which is downregulated in rodent models of obesity. Here, we investigated whether adipolin modulates the development of vascular diseases using loss-of-function genetic manipulations. Methods and Results: Under basal conditions, no significant differences were observed in body weight, organ weights, blood pressure and fasting plasma glucose levels between wild-type (WT) and adipolin-knockout (APL-KO) mice. APL-KO mice exhibited enhanced neointimal thickening after femoral artery injury compared with WT mice, which was accompanied by increased expression levels of pro-inflammatory mediators including tumor necrosis factor (TNF)-α and interleukin (IL)6 in injured vessels. Conversely, systemic administration of adipolin to WT mice using adenoviral vector expression systems ameliorated injury-induced neointimal thickening and inflammatory response. APL-KO mice also showed impaired re-reendothelialization after vascular injury compared with WT mice. Furthermore, adipolin deficiency increased atherosclerotic lesion area in an apolipoprotein E-knockout mouse model, which was accompanied by enhanced inflammatory response in the arterial vessel walls. Treatment of cultured macrophages with recombinant adipolin protein attenuated lipopolysaccharide-stimulated expression of inflammatory mediators, such as TNF-α and IL6. The anti-inflammatory actions of adipolin in macrophages were reversed by inhibition of transforming growth factor-β receptor II (TGF-βRII)/Smad2 signaling. In addition, treatment of human umbilical vein endothelial cells with adipolin protein promoted migratory activity and reduced serum starvation-induced apoptosis. Conclusion: These data suggest that adipolin suppresses injury-induced neointimal formation and atherosclerosis development through its abilities to modulate macrophage inflammatory responses and endothelial cell functions in vascular walls.

Association between inflammatory biomarkers and neointimal response following elective implantation of the ABSORB bioresorbable vascular scaffold.

The ABSORB bioresorbable vascular scaffold (BVS) is associated with greater neointimal proliferation and thrombotic rate than metal stent. The role of inflammatory biomarkers on neointimal proliferation has not been studied in the setting of BVS implantation. Thirty patients had arterial blood sampling before elective percutaneous coronary intervention with the ABSORB BVS and at 9-months follow-up. Plasma levels of interleukin-6, soluble CD40 ligand, monocyte chemotactic protein-1 and C-reactive protein were measured using enzyme-linked immunosorbent assay. Baseline and follow-up levels were compared for each biomarker. Optical frequency domain imaging was performed at follow-up and the neointimal burden was calculated as the ratio of neointimal area to scaffold area. The levels of inflammatory mediators were correlated with the neointimal burden. There was no significant increase in the levels of biomarkers from baseline to follow-up. Median C-reactive protein levels changed from 1.1 [interquartile range (IQR): 0.5-2.5] to 2.2 (IQR: 0.5-3.5) μg/ml, interleukin-6 from 1.0 (IQR: 0.6-1.4) to 1.0 (IQR: 0.6-1.4) pg/ml, monocyte chemotactic protein-1 from 120.4 (IQR: 86.0-153.4) to 102.0 (IQR: 70.3-148.1) pg/ml and soluble CD40 ligand from 108.3 (IQR: 74.1-173.7) to 112.0 (IQR: 71.0-225.9) pg/ml. The average neointimal burden in the cohort was 18±6%. Baseline, follow-up and change in plasma levels of inflammatory markers between these two time points did not correlate with the neointimal burden. Elective percutaneous coronary intervention with the ABSORB BVS does not provoke a chronic inflammatory response. The degree of neointimal proliferation after elective implantation of the ABSORB BVS is independent of the pre-existing inflammatory environment.

Re-endothelialisation after Synergy stent and Absorb bioresorbable vascular scaffold implantation in acute myocardial infarction: COVER-AMI study

Background/aimsDrug eluting stent (DES) decrease the risk of restenosis by reducing the neointimal response. However, DES may impair strut coverage, and this has been associated with late stent/scaffold thrombosis. Bioresorbable vascular scaffold (BVS) may overcome the risk of stent/scaffold thrombosis when completely resorbed. The purpose of this randomised trial was to compare the arterial healing response in the short term, as a surrogate for safety and efficacy, between the metallic everolimus-eluting stent (Synergy; Boston Scientific, Marlborough, MA, USA) and the everolimus BVS (Absorb; Abbott Vascular, Santa Clara, CA, USA) in the particular setting of acute myocardial infarction (AMI). This pilot study sought to compare the neointimal response of metallic everolimus DES (Synergy) with polymeric everolimus BVS (Absorb) by optical coherence tomography (OCT) 3 months after an AMI.MethodsCOVER-AMI was a single-centre, single-blind, non-inferiority, randomised controlled trial. Patients with ST segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention were randomly allocated (1:1) to treatment with the Synergy DES or Absorb BVS. The primary endpoint was the 3-month neointimal response assessed as the percentage of uncovered struts, neointimal thickness, in-stent/scaffold area obstruction, and pattern of neointima. The main secondary endpoint included the device-oriented composite endpoint according to the Academic Research Consortium definition.ResultsTwenty patients without clinical and/or angiographic complications (Synergy (n = 10) or BVS (n = 10); mean age 59.0 years; 20% female) were enrolled in our centre. The stent diameter was higher in the Synergy group (3.7 ± 0.4 mm vs 3.4 ± 0.4 mm in the BVS group, p = 0.01). At 3 months, no significant differences in angiographic lumen loss were observed between the everolimus DES and everolimus BVS (0.04 mm (IQR 0.00–0.07) vs 0.11 mm (IQR 0.04–0.31), p = 0.165). OCT analysis of 420 cross-sections showed that the total neointimal area and in-stent obstruction were lower in the Synergy group, while OCT analysis at the strut level (n = 3942 struts) showed that the rate of uncovered struts was lower in the BVS group.ConclusionsStenting of culprit lesions in the setting of STEMI resulted in a nearly complete arterial healing for both the Synergy and the BVS devices. Lower neointimal thickness and in-stent obstruction but a higher rate of uncovered struts were observed in the Synergy group. These findings provide the basis for further exploration in clinically oriented outcome trials.

Calcification and Thrombosis as Mediators of Bioprosthetic Valve Deterioration

Calcific aortic valve disease is the most common indication for surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) of diseased valves worldwide. 1 For years,...

Impact of Combination Therapy with Ezetimibe/Simvastatin Treatment on the Neointimal Response to Biodegradable Polymer Biolimus-Eluting Stent Implantation in Patients with Acute Myocardial Infarction: Serial Assessment with Optical Coherence Tomography

The aim of this study was to compare the neointimal response at 12-month follow-up between ezetimibe/simvastatin (Vytorin, manufactured by Merck) 10/10 mg and Vytorin 10/40 mg after biodegradable polymer Biolimus-eluting stent (BP-BES) implantation in patients with acute myocardial infarction (AMI). A total of 20 patients requiring revascularization were randomly assigned to receive either Vytorin 10/10 mg (n = 9) or Vytorin 10/40 mg (n = 11). Baseline optical coherence tomography (OCT) was performed after stent implantation, and follow-up OCT was scheduled at 12 months. We performed follow-up OCT in 18 patients (Vytorin 10/10 mg (n = 9) or Vytorin 10/40 mg (n = 9)). A total of 842 frames and 8552 struts were analyzed at initial and follow-up OCT. At follow-up, the percentage of uncovered struts was not significantly different between both groups (6.61 ± 10.29% vs. 7.57 ± 6.45%, p = 0.815). The percentage of malapposed struts was also similar between both groups (0.69 ± 1.58% vs. 1.55 ± 2.72%, respectively, p = 0.422). Mean percent neointimal hyperplasia area was not significantly different between both groups (6.53 ± 3.26% vs. 6.37 ± 8.96%, p = 0.961). This OCT study showed that both high- and moderate-intensity dosing of Vytorin was associated with relatively lower percentages of uncovered struts and malapposed struts after Biolimus A9-eluting stent implantation in patients with AMI.

TCT-267 Serial stent healing analysis of bioresorbable stent implanted in coronary bifurcations with optical coherence tomography: correlation with baseline shear stress

Heterogeneous neointimal response has been observed after implantation of all generations of stents. Our aim was to assess the correlation between baseline shear stress (SS) and neointimal response after implantation of bioresorbable stents (BRS). Ten patients with BRS implanted at coronary

A serial 3- and 9-year optical coherence tomography assessment of vascular healing response to sirolimus- and paclitaxel-eluting stents

Early-generation drug-eluting stents (DES) have been demonstrated to delay vascular healing. Limited optical coherence tomography (OCT) data on the very long-term neointimal response after DES implantation are available. The aim of this study was a serial OCT assessment of neointimal thickness, stent strut coverage, malapposition, and protrusion as markers of neointimal response at 3 and 9 years after implantation of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). In this single-centre, longitudinal study consecutive patients undergoing elective PCI with SES or PES were included. OCT analysis was performed after 3 and 9 years by the independent core laboratory. A total of 22 subjects (8 SES and 14 PES) underwent an OCT assessment at 3 and 9 years post index procedure. The lumen, neointimal and malapposition area and the neointimal thickness (SES ∆50 µm, p = 0.195, PES ∆10 µm, p = 0.951) did not change significantly over the 6 year follow-up. No differences in the incidence of uncovered, malapposed or protruding struts were found in each type of stent. At 3 and 9 years after PCI, implantation of early-generation SES and PES may be associated with similar neointimal thickness, strut coverage, malapposition and protrusion, as assessed by serial OCT examination among patients with uneventful follow-up at 3 years post procedure. The small size of the study warrants judicious interpretation of our results and confirmation in larger multimodality imaging studies, including patients treated with contemporary stent platforms.

In-stent neoatherosclerosis and tissue characteristics of restenotic lesions following implantation of second generation drug-eluting stents in unrestricted coronary lesions: Optical frequency domain imaging study.

Differences in stent platform, polymer coatings, and antirestenotic drugs among the current in use second-generation drug-eluting stents (G2-DESs) may induce significant variations in neointimal response and vascular healing, which may impact the prevalence of neoatherosclerosis (NA) and morphological appearance of the restenotic tissue. Utilizing Optical frequency domain imaging, two independent reviewers, retrospectively compared the prevalence of neoatherosclerosis (NA), and the morphological differences, and tissue characteristics of 50 G2-DESs in-stent restenosis (ISR) lesions (35 everolimus-eluting stent [22 cobalt-chromium (CoCr), 13 platinum-chromium (PtCr)], and 15 biolimus-eluting stent [BES]) implanted liberally in unrestricted coronary lesions. More than half of the stents were implanted in type C lesions, while 40% of the stents were implanted primarily in lesions with recanalized chronic total occlusion. NA, defined as a neointima formation with the presence of lipids or calcification, was observed in fewer than half (24/50) of all ISR lesions with no significant in-between group differences (41%, 69%, and 40% in CoCr, PtCr, and BES respectively, P = 0.22), nor were there any significant differences in the morphological appearance or tissue characteristics between all G2-DESs subtypes. Acknowledging some limitations, our results may suggest that the prevalence of NA and the morphological appearance of restenotic lesions might not differ when G2-DESs are implanted in unrestricted, rather complex, coronary lesions.

Comparison of two different sampling intervals for optical coherence tomography evaluation of neointimal healing response after coronary stent implantation

Background/objectivesOptical coherence tomography (OCT) is widely used for evaluation of healing response to stent implantation. We sought to test the agreement between the 1-mm and 0.6-mm sampling intervals for assessment of the percentage of uncovered and malapposed struts by OCT. MethodsThirty­eight patients presenting with acute coronary syndrome were randomized to receive either a titanium­nitride­oxide­coated stent (n=19) or an everolimus­eluting stent (n=19). Neointimal strut coverage and strut apposition were evaluated by OCT at 2­month follow­up. Two independent investigators performed offline OCT image analysis at 1­mm intervals. One investigator repeated the measurements at 0.6­mm intervals and measurements were compared between the two sampling intervals. ResultsAt a median follow­up of 60 [8] days, 694 cross­sections (7603 struts) and 1138 cross­sections (12,331 struts) were analysed at 1­mm and at 0.6­mm intervals, respectively. The median [IQR] percentage of uncovered struts was 3.27% [11.1] versus 3.38% [9.76] (p=0.001), and the mean (±SD) percentage was 7.69±9.99% versus 6.27±8.14% (p=0.004), for the 1­mm sampling interval versus the 0.6­mm sampling interval analysis, respectively; the median percentage of malapposed struts was 0.42% [2.04] versus 0.12% [1.63], respectively, (p=0.003). The intraclass correlation coefficient between the two observers for the percentage of uncovered struts was 0.95. ConclusionsThe OCT-evaluated strut-level measurements of neointimal healing after stent implantation differ significantly between the 1-mm and the 0.6-mm sampling intervals.

TCT-596 In-Stent Neoatherosclerosis and Tissue Characteristics of Restenotic Lesions Following Implantation of Second Generation Drug-Eluting Stents in Unrestricted Coronary Lesions: Optical Frequency Domain Imaging study

Differences in stent platform, polymer coatings, and antirestenotic drugs among the current in use second-generation drug-eluting stents (G2-DESs) may induce significant variations in neointimal response and vascular healing, which may impact the prevalence of neoatherosclerosis (NA) and