In-vivo assessment of vascular injury for the prediction of in-stent restenosis.

BACKGROUND: Despite optimizations of coronary stenting technology, a residual risk of in-stent restenosis (ISR) remains. Vessel wall injury has important impact on the development of ISR. While injury can be assessed in histology, there is no injury score available to be used in clinical practice. METHODS: Seven rats underwent abdominal aorta stent implantation. At 4 weeks after implantation, animals were euthanized, and strut indentation, defined as the impression of the strut into the vessel wall, as well as neointimal growth were assessed. Established histological injury scores were assessed to confirm associations between indentation and vessel wall injury. In addition, stent strut indentation was assessed by optical coherence tomography (OCT) in an exemplary clinical case. RESULTS: Stent strut indentation was associated with vessel wall injury in histology. Furthermore, indentation was positively correlated with neointimal thickness, both in the per-strut analysis (r = 0.5579) and in the per-section analysis (r = 0.8620; both p ≤ 0.001). In a clinical case, indentation quantification in OCT was feasible, enabling assessment of injury in vivo. CONCLUSION: Assessing stent strut indentation enables periprocedural assessment of stent-induced damage in vivo and therefore allows for optimization of stent implantation. The assessment of stent strut indentation might become a valuable tool in clinical practice.

Long-Term Intracoronary Structural and Vasomotor Assessment of the ABSORB Bioresorbable Vascular Scaffold.

We systematically categorized the longer-term (≥3 years) structural and functional characteristics of the ABSORB bioresorbable vascular scaffold (BVS) using optical coherence tomography imaging and coronary vasomotor reactivity testing and further compared the functional characteristics of BVS stented versus remote coronary segments. A total of 92 patients (mean age 56.4 ± 9.7 years, 22.8% women) who underwent percutaneous coronary intervention (76% with acute coronary syndrome) using the ABSORB BVS (112 lesions) were included. Optical coherence tomography analysis (38,790 visible struts) comprised in-segment quantitative lumen/plaque and semiquantitative plaque composition analysis of the neointimal pattern. Epicardial endothelium-dependent and-independent vasomotion was defined as any vasodilatation at low/intermediate intracoronary dose of acetylcholine (ACh) and nitroglycerine, assessed using quantitative coronary angiography. At a median time of 3.2 years follow-up, 79.8% of BVS segments still demonstrated visible struts with a predominant neointimal fibrotic healing pattern in 84% of BVS segments, with 99.5% of struts demonstrating coverage with apposition. Compared with remote segments, BVS segments demonstrated less endothelium-dependent vasodilatation at low (p = 0.06) and intermediate ACh doses (p = 0.04). Hypertension, longer time interval from index percutaneous coronary intervention, and the degree of in-BVS segment neointimal volume (p <0.03 for all) were each independently associated with abnormal BVS endothelium-dependent vasomotor function. Endothelium-independent function was more likely preserved in non-BVS (remote) segments compared with BVS segments (p = 0.06). In conclusion, at 3+ years post-ABSORB BVS insertion, the rate of complete scaffold resorption was low and residual strut presence was high, with a dominant fibrous healing response contributing toward neointimal hyperplasia and endothelium-dependent and-independent vasomotor dysfunction.

A novel endovenous scaffold for the treatment of chronic venous obstruction in a porcine model: Histological and ultrastructural assessment.

OBJECTIVE: To investigate the biological effects of a novel endovenous scaffold in a porcine model. METHODS: Petalo is a compliant venous scaffold implanted into the internal jugular veins of 12 healthy pigs. The pigs were sacrificed at one, two, three, and six months, respectively. Microscopic investigations were performed at two blinded laboratories. RESULTS: Neo-intima formation progressively covering up the stent metallic bars was observed. The inflammatory response of the venous wall showed a peak after three months by the implant, followed by marked reduction after six months. The device induced a significant ( p < 0.01) increase of the thickness respect to the control regions, but was comparable in sections obtained after three and six months. CONCLUSIONS: The implant of Petalo compliant venous scaffold in the venous wall of this porcine model is characterized by neointima formation and by an inflammatory reaction which tends to decrease after six months. Our data point against the induction of smooth muscle cells proliferation and migration as confirmed by electronic transmission microscopy analyses.

Abluminal Neointimal Healing by Optical Coherence Tomography Assessment After Drug-Eluting Stent Implantation on Organized Recanalized Thrombus.

Six-month PCI follow-up results of left anterior descending (LAD) and circumflex (CX) drug-eluting stent implantation are presented. Angiography showed patent LAD and CX stents. However, OCT revealed almost all abluminal cavities were completely filled, which the authors surmise was due to a neointimal healing process.

Optical Coherence Tomography Assessment of Glucose Fluctuation Impact on the Neointimal Proliferation After Stent Implantation in a Diabetic/Hypercholesterolemic Swine Model.

The aim of the present study was to investigate the effects of glucose fluctuation on neointimal proliferation after stent implantation by optical coherence tomography (OCT) in a diabetic/hypercholesterolemic (DM/HC) swine model.A total of 24 everolimus-eluting stents (EES) were implanted in the right coronary artery (RCA) of the animals using a 20% overstretch ratio. The 24 swines were divided into a DM-high glucose fluctuation (HGF) group (n = 8), DMlow glucose fluctuation (LGF) group (n = 8), and a control group (n = 8). Percent diameter stenosis (%DS), late loss (LL), percent area stenosis (%AS), and neointimal thickness (NIT) were analyzed. The differences in neointimal characteristics and circulating oxidative stress and inflammation biomarkers were assessed and measured.At 28 days, the highest values of %DS, LL, %AS, and NIT were achieved in the HGF group followed by the LGF group (P < 0.05) and the control group (P < 0.05). The highest frequency of the heterogeneous pattern was in the HGF group followed by the LGF group (P < 0.05) and the control group (P < 0.05). This was also the case for the oxidative stress and inflammation biomarkers.DM might have a deleterious impact on neointimal proliferation after EES implantation in this DM/HC swine model. The extent of glucose fluctuation may be related to the degree of neointimal proliferation and this needs to be further confirmed by long-term follow-up and histology.

Assessment of the hemodynamic characteristics of Absorb BVS in a porcine coronary artery model.

BACKGROUND AND AIM: Local hemodynamic changes are one of the main factors that determine the vessel wall biological response after stent/scaffold implantation. Computational fluid dynamic studies provide an opportunity to investigate the rheological effects of implanted stent/scaffold. The aim of this study was to assess the local hemodynamic microenvironment in scaffolded segments in porcine coronary models. METHODS: In six epicardial coronary arteries of healthy mini-pigs, six Absorb bioresorbable vascular scaffolds (Absorb BVS) were implanted. Optical coherence tomography(OCT) was performed after scaffold implantation and the images were fused with the angiographic data to reconstruct the three-dimensional coronary artery anatomy. Blood flow simulations were performed, and endothelial shear stress(ESS) distribution was estimated for each scaffolded segment. In a linear mixed-effect model, the contributing factors for low (<1.0Pa) ESS levels were assessed. At 30-day post-implantation, histopathological assessment was performed at 2 scaffolds. RESULTS: In scaffolded segments, the median ESS was 0.57 (IQR: 0.29-0.99) Pa. In linear mixed-effect analysis, cross-section area was associated with low shear stress levels. In scaffolded segments, the percentage of the recirculation zone per scaffolded luminal surface was 3.26±2.07%. At 30-day histopathological assessment of implanted vessel segments revealed minimal injury score, minimal neointimal inflammation and minimal adventitial inflammation scores with moderate endothelial coverage. Fibrin accumulation was seen at 95.69±2.47% of the struts. CONCLUSION: The thick rectangular strut design of the Absorb BVS incited flow disruptions with low shear stress inducing fibrin accumulation. CFD assessment can be used to guide improvements in the scaffold design for a more "hemo-compatible" geometry.

Ex vivo assessment of neointimal characteristics after drug-eluting stent implantation: Optical coherence tomography and histopathology validation study.

BACKGROUND: Optical coherence tomography (OCT) is one of the tools trying to distinguish neoatherosclerosis from other neointimal tissue but its role has to be still validated. This study evaluated the diagnostic accuracy of OCT for characterization of lipid-atherosclerotic neointima following drug-eluting stent (DES) implantation. METHODS: Twelve stented coronary arteries from the 7 autopsy hearts were imaged by OCT. These OCT images were compared with histology. By OCT, the morphological appearances of neointima were classified into three patterns: homogeneous pattern, heterogeneous pattern with visible strut, or heterogeneous pattern with invisible strut. RESULTS: Of 21 histological cross-sections, 6 were categorized as homogeneous patterns (29%), 11 as heterogeneous patterns with visible stent strut (52%), and 4 as heterogeneous patterns with invisible stent strut (19%). All homogeneous patterns were composed of smooth muscle cells with collagen fibers. The heterogeneous patterns with visible stent strut included proteoglycan-rich myxomatous matrix and calcium deposition. On the other hand, the heterogeneous patterns with invisible stent strut comprised atheromatous tissue, including a large amount of foam cell accumulation (25%) or large fibroatheroma/necrotic core (75%) inside the stent struts within neointima. The optical attenuation coefficient was highest in the heterogeneous pattern with invisible stent strut due to scattering of light by atheromatous tissue. CONCLUSION: The heterogeneous patterns with invisible stent strut on OCT imaging identify the presence of lipid-atherosclerotic tissue within neointima after DES. This may suggest the potential capability of OCT based on visualization of stent struts for discriminating atheromatous formation within neointima from other neointimal tissue.

Assessment of vascular response after drug-eluting stents implantation in patients with diabetes mellitus: an optical coherence tomography sub-study of the J-DESsERT.

Even in the drug-eluting stent era, diabetes mellitus (DM) patients have high incidences of restenosis and repeat revascularization after percutaneous coronary intervention. The aim of this study was to compare vascular response after stent implantation between sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) by using optical coherence tomography (OCT) in DM patients as well as in non-DM patients. In the Japan-Drug Eluting Stents Evaluation; a Randomized Trial (J-DESsERT), the OCT sub-study enrolled 75 patients who underwent 8 months follow-up imaging after SES or PES implantation. Mean neointimal hyperplasia (NIH) thickness was significantly thinner in SES than PES in the DM group (77 ± 47 vs. 201 ± 114 µm, p < 0.001) and in the non-DM group (84 ± 37 vs. 212 ± 128 µm, p < 0.001). Unevenness of NIH thickness in longitudinal axis was significantly smaller in SES than PES in the DM group (348 ± 191 vs. 726 ± 385 µm, p < 0.001) and in the non-DM group (344 ± 174 vs. 679 ± 314 µm, p < 0.001). The percentage of uncovered struts was significantly greater in SES than PES in the DM group (24 ± 4 vs. 9 ± 14 %, p < 0.001) and in the non-DM group (16 ± 16 vs. 3 ± 4 %, p = 0.002). Compared with PES, SES showed more potent NIH inhibition in DM patients as well as in non-DM patients.

STACCATO (Assessment of Stent sTrut Apposition and Coverage in Coronary ArTeries with Optical coherence tomography in patients with STEMI, NSTEMI and stable/unstable angina undergoing everolimus vs. biolimus A9-eluting stent implantation): a randomised controlled trial.

AIMS: To compare tissue coverage in coronary lesions stented with durable fluoropolymer-coated everolimus-eluting stents (EES) vs. biodegradable polymer-coated biolimus A9-eluting stents (BES). METHODS AND RESULTS: Sixty-four patients (64 lesions) with de novo coronary artery lesions were randomised to percutaneous treatment with XIENCE EES (Abbott Vascular, Santa Clara, CA, USA) vs. BioMatrix BES (Biosensors, Morges, Switzerland). The primary endpoint was the percentage of uncovered struts, as assessed with OCT, at nine months. The average percentage of uncovered struts was significantly lower with EES (4.3±4.8% vs. 8.7±7.8% with BES, p=0.019). There was no difference in the average percentage of malapposed struts at baseline (6.8±6.9% vs. 6.9±7.0%, respectively, p=0.974) and at follow-up (0.1±0.3% vs. 0.6±1.3%, p=0.143). Neointimal thickness at nine months was 109±43 µm in EES vs. 64±18 µm in BES (p<0.001), and angiographic LLL was 0.15 mm in EES vs. 0.10 mm in BES (p=0.581). We did not observe differences in the incidence of MACE and ST. CONCLUSIONS: A significantly higher percentage of uncovered struts was detected in the BioMatrix BES compared with the XIENCE EES at nine-month follow-up. Our findings do not support a preferential use of stents with biodegradable polymer-based biolimus elution to reduce the risk for ST.

Human recombinant activated protein C-coated stent for the prevention of restenosis in porcine coronary arteries.

Activated protein C (APC), an endogenous protein, inhibits inflammation and thrombosis and interrupts the coagulation cascade. Here, we investigated the effect of human recombinant APC on the development of neointimal hyperplasia in porcine coronary arteries. Yukon Choice bare metal stents were coated with 2.6 µg APC/mm(2). Under general anesthesia, APC-coated and bare stents were implanted in the left anterior descending and circumflex coronary arteries of 10 domestic pigs. During the 4-week follow-up, animals were treated with dual antiplatelet therapy and neointimal hyperplasia was evaluated via histology. Scanning electron microscopy indicated successful but unequal coating of stents with APC; nearly complete drug release occurred within 4 h. Enzyme-linked immunosorbent assay revealed that intracoronary stent implantation rapidly increased the levels of monocyte chemoattractant protein-1, an effect that was inhibited by APC release from the coated stent. Fibrin deposition and adventitial inflammation were significantly decreased 1 month after implanting APC-coated stents versus bare stents, paralleled by significantly smaller neointimal area (0.98 ± 0.92 vs. 1.44 ± 0.91 mm(2), P = 0.028), higher lumen area (3.47 ± 0.94 vs. 3.06 ± 0.91 mm(2), P = 0.046), and lower stenosis area (22.2 ± 21.2% vs. 32.1 ± 20.1%, P = 0.034). Endothelialization was complete with APC-coated but not bare (90%) stents. P-selectin immunostaining revealed significantly fewer activated endothelial cells in the neointima in the APC group (4.6 ± 1.9 vs. 11.6 ± 4.1%, P < 0.001). Thus, short exposure of coronary arteries to APC reduced inflammatory responses, neointimal proliferation, and in-stent restenosis, offering a promising therapy to improve clinical outcomes of coronary stenting. However, coating stents with APC for prolonged, controlled drug release remains technically challenging.

Two-year vessel healing after everolimus-eluting stent implantation: serial assessment by optical coherence tomography.

BACKGROUND: Previous reports have suggested the importance of delayed arterial healing and the development of neoatherosclerosis as major contributors to stent thrombosis and delayed restenosis. The difference of in vivo assessment of long-term vessel healing between first-generation drug-eluting stents and current generation everolimus-eluting stents (EESs) is limited. The aim of this study was to evaluate long-term arterial healing in EES in comparison with the first generation sirolimus-eluting stents (SES). METHODS: We evaluated 31 EES (23 patients) and 8 SES (7 patients) by serial optical coherence tomography at 12 months (mid-phase) and 24 months (late-phase) after stenting and evaluated the change in neointimal thickness (NIT), the percentages of uncovered struts, peri-strut low intensity area (PLIA; region around stent struts homogenously lower-intensity appearance than surrounding tissue), and thrombus. RESULTS: Although the average NIT showed no significant changes from the mid- to the late-phase follow-up in both EES and SES groups, the change in NIT and minimum lumen area was significantly larger in SES than EES (5.2±29.4 vs. 37.2±48.9; p=0.02, -0.06±0.36 vs. -0.45±0.74; p=0.04, respectively). The incidence of uncovered struts and struts with PLIA of EES was lower than those of SES, at both phases. Stents with in-stent thrombus of EES tended to be lower than that of SES at both phase follow-ups. CONCLUSION: Although both SES and EES showed progressive luminal narrowing from the mid- to the late-phase follow-up, the extent of delayed lumen narrowing and delayed neointimal proliferation was significantly less in the second generation EES than the first generation SES. EESs seem to offer sustained stability in efficacy, without sacrificing safety, up to 2 years after implantation.

Optical coherence tomography and histopathology assessment after implantation of first- and second-generation drug-eluting stents in a porcine coronary model.

BACKGROUND: This study directly compared optical coherence tomography (OCT) and histopathology for the assessment of vascular response to first- and second-generation drug-eluting stents. METHODS AND RESULTS: Sirolimus-, everolimus-, and biolimus-eluting stents (SES, EES, and BES, respectively) were randomly implanted into the coronary arteries of 12 porcine. OCT was conducted after implantation: at 1, 3, and 6 months; histopathology was assessed at 3 and 6 months. At 1-month OCT, EES had the highest neointimal area (NA) and lowest neointimal unevenness score (NUS). At 6 months, NA and NUS were equivalent among the stent types. ∆NA from 1 to 6 months was lowest for EES, and ∆NA correlated with the histopathological inflammation score at 6 months, which was highest for SES (P<0.001). The mean signal intensity (MSI) and the attenuation were different for the stent types at 3 months, and were associated with inflammation score. Moderate diagnostic efficiency for measuring MSI was found, with an optimal cut-off of 6.88 predicting a high (≥grade 3) inflammation score. CONCLUSIONS: EES had the greatest uniformity and the least neointimal proliferation and were associated with less persistent inflammation. OCT provides accurate morphometric data; furthermore, quantitative measurement of the optical properties may help assess histological inflammation, which was more predominantly associated with SES than with EES and BES.

Assessment of characteristics of neointimal hyperplasia after drug-eluting stent implantation in patients with diabetes mellitus: an optical coherence tomography analysis.

OBJECTIVE: This study aims to assess the characteristics of neointimal hyperplasia after drug-eluting stent (DES) implantation in patients with diabetes mellitus (DM) by optical coherence tomography (OCT). METHODS: OCT was performed in 109 patients (45 with DM and 64 without DM) 1 year after DES implantation. Neointimal coverage and thickness on the luminal side were measured. The characteristics of neointimal hyperplasia were classified into three patterns, namely, high signal pattern, low signal pattern and layered signal pattern, according to the neointimal signal intensity. The development of in-stent neoatherosclerosis was also examined. In the DM group, glycated hemoglobin (HbA1c) levels were analyzed in order to assess their contribution to neointimal characteristics. RESULTS: OCT results indicated that neointimal thickness was thicker in the DM group than in the non-DM group (177.19 ± 165.36 vs. 166.76 ± 132.38 µm, p < 0.001). Lower incidence of high signal pattern (58.33 vs. 75.34%, p = 0.037) and higher incidence of in-stent neoatherosclerosis (18.33 vs. 5.48%, p = 0.027) were observed in the DM group. In the DM subgroup with HbA1c >7%, significantly higher incidence of low signal pattern (37.50 vs. 21.43%, p = 0.001) and layered signal pattern (18.75 vs. 3.57%, p = 0.001) and lower incidence of high signal pattern were observed (43.75 vs. 75.0%, p < 0.001). In-stent neoatherosclerosis was also frequently detected in the high HbA1c group compared with the low HbA1c group (28.13 vs. 7.14%, p = 0.048). CONCLUSION: Neointimal characteristics differed between DM and non-DM patients. HbA1c levels in DM patients contributed to the development of neointimal hyperplasia and in-stent neoatherosclerosis.

Automatic assessment of stent neointimal coverage by intravascular optical coherence tomography.

AIMS: This study aimed to validate automatic intravascular optical coherence tomography (IVOCT) analysis for the evaluation of neointimal coverage in response to stent implantation. METHODS AND RESULTS: Fourteen stented segments in common iliac arteries, acquired from a total of seven adult male New Zealand White rabbits, were interrogated in vivo by IVOCT. Durable polymer everolimus-eluting stents (EES; Xience V, Abbott Vascular, Santa Clara, CA, USA) were used exclusively. Comparison with histology was made in a total of 63 pairs of images, where neointimal thickness over corresponding individual stent struts was assessed. A high correlation coefficient (R = 0.85, P < 0.001) was obtained by comparing automatic IVOCT analysis with histology. Moreover, Bland-Altman statistics showed good limits of agreement (LOAs) of ±45 µm, with an average difference of -10 µm. In addition, manual IVOCT assessment presented very similar results when compared with histology (R = 0.83, P < 0.001 and LOA = ±48 µm with an average difference of -8 µm). Therefore, a very high correlation value was found, comparing manual to automatic IVOCT measurements (R = 0.95, P < 0.001) together with good LOAs (±27 µm) and an average difference of -2 µm. CONCLUSION: The results of the study suggest that automatic IVOCT analysis is a reliable and accurate tool able to speed up current IVOCT analysis procedures. This would potentially allow for a better integration of IVOCT in clinical practice and clinical studies assessing vascular response to stent implantation in a large series of patients.

[SICI-GISE position paper on drug-coated balloon use in the coronary district]. / Documento di posizione SICI-GISE sul corretto utilizzo del pallone a rilascio di farmaco nel distretto coronarico.

Drug-coated balloons are a new tool for the treatment of patients with coronary artery disease. The main feature of this technology is a rapid and homogeneous transfer of an antiproliferative drug (paclitaxel) to the vessel wall just at the time of balloon inflation, when neointimal proliferation, in response to angioplasty, is the highest. Moreover, drug-coated balloons share adjunctive advantages over stents: the absence of permanent scaffold and polymer, the respect of the original coronary anatomy, and limited inflammatory stimuli, thereby allowing for short-term dual antiplatelet therapy. At present, a variety of devices are available in the market, with limited scientific data for the vast majority of them. Thus, the Italian Society of Interventional Cardiology (SICI-GISE) decided to coordinate the efforts of a group of renowned experts in this field, in order to produce a position paper on the correct use of drug-coated balloons in all settings of coronary artery disease, giving a class of indication to each one, based on clinical evidence. This position paper represents a quick reference for operators, investigators and manufacturers to promote the understanding and the correct use of the drug-coated balloon technology in everyday clinical practice.

Optical coherence tomography and histopathological assessment of delayed arterial healing after drug-eluting stent implant in a pig coronary model.

BACKGROUND: Delayed healing, such as persistent inflammation and fibrin deposition, and vascular dysfunction after drug-eluting stent has been reported. Histological validation of coronary optical coherence tomography (OCT) morphology has not yet been done. METHODS: Sirolimus eluting stents (SES, n=8) and bare metal stents (BMS n=8) were implanted in pig coronary arteries. One month after implantation, an acetylcholine challenge test and OCT were performed. The OCT texture pattern of the neointima was classified into one of the three categories; Layered type, Homo type, and Hetero type. Hearts were harvested for histopathological scoring of inflammation and intramural thrombus. RESULTS: Inflammation and intramural thrombus scores were higher in the Hetero type than in the Layered type and Homo type. OCT intensity of the Homo type was higher than that of the Layered type and Hetero type. Most SES were of the Hetero type. Conversely, most BMS were of the Homo type. SES exhibited higher inflammation and intramural thrombus than BMS (1.72 ± 0.89 vs 1.00 ± 0.00, P=0.0003, 2.39 ± 0.70 vs 0.92 ± 0.28, P<0.001 respectively). After acetylcholine injection, the diameter change was 4.31 ± 4.80% for SES versus -3.68 ± 6.81% for BMS (P=0.024). CONCLUSIONS: The Hetero type texture pattern in OCT images was associated with histological inflammation and intramural thrombus predominantly found in SES, and is related to endothelial dysfunction.

Tissue coverage and neointimal hyperplasia in overlap versus nonoverlap segments of drug-eluting stents 9 to 13 months after implantation: in vivo assessment with optical coherence tomography.

BACKGROUND: Histologic experimental studies have reported incomplete neointimal healing in overlapping with respect to nonoverlapping segments in drug-eluting stents (DESs), but these observations have not been confirmed in human coronary arteries hitherto. On the contrary, angiographic and optical coherence tomography studies suggest that DES overlap elicits rather an exaggerated than an incomplete neointimal reaction. METHODS: Optical coherence tomography studies from 2 randomized trials including sirolimus-eluting, biolimus-eluting, everolimus-eluting, and zotarolimus-eluting stents were analyzed at 9- to 13-month follow-up. Coverage in overlapping segments was compared versus the corresponding nonoverlapping segments of the same stents, using statistical pooled analysis. RESULTS: Forty-two overlaps were found in 31 patients: 11 in sirolimus-eluting stents, 3 in biolimus-eluting stents, 17 in everolimus-eluting stents, and 11 in zotarolimus-eluting stents. The risk ratio of incomplete coverage was 2.35 (95% CI 1.86-2.98) in overlapping versus nonoverlapping segments. Thickness of coverage in overlaps was only 85% (95% CI 81%-90%) of the thickness in nonoverlaps. Significant heterogeneity of the effect was observed, especially pronounced in the comparison of thickness of coverage (I(2) = 90.31). CONCLUSIONS: The effect of overlapping DES on neointimal inhibition is markedly heterogeneous: on average, DES overlap is associated with more incomplete and thinner coverage, but in some cases, the overlap elicits an exaggerated neointimal reaction, thicker than in the corresponding nonoverlapping segments. These results might help to understand why overlapping DES is associated with worse clinical outcomes, both in terms of thrombotic phenomena and in terms of restenosis and revascularization.

In stent restenosis and thrombosis assessment after EP224283 injection in a rat model.

OBJECTIVE: After stent implantation, platelet aggregation and thrombus formation are thought to play a key role in the early phase of in-stent restenosis (ISR). Drug-eluting stents have reduced ISR, but are associated with healing-related issues or hypersensitivity reactions, leading to an increased risk of late acute stent thrombosis. EP224283 is a new dual-action antithrombotic molecule combining a GPIIbIIIa antagonist and a factor Xa inhibitor. We investigated its efficacy on restenosis in a rat model of ISR and on platelet adhesion. METHODS AND RESULTS: Rat aortas were stented and the animals received either EP224283 or vehicle subcutaneously every 48 h. At day 7 and day 28 after surgery, the stented aortas were removed and processed for morphometric analysis or protein analysis. At day 28, EP224283 significantly reduced neointima growth (in the range of 20%). Protein analysis revealed that EP224283 reduced cell proliferation pathways: ERK1/2 and Akt were down-regulated and p38 up-regulated. Expression of Ki67 was also reduced. In vitro assessment depicted a reduction of platelet activation and platelet adhesion among treated rats. CONCLUSION: These results show a beneficial effect of EP224283 on in-stent restenosis and on stent thrombogenicity that may improve results after stent implantation. Further investigations are required to assess the efficacy of a local delivery of EP224283 on both acute thrombosis and ISR.

Qualitative and quantitative assessment of stent restenosis by optical coherence tomography: comparison between drug-eluting and bare-metal stents.

BACKGROUND: We hypothesized that the tissue components of in-stent restenosis (ISR) might differ between drug-eluting stents (DES) and bare-metal stents (BMS) and that these differences could be distinguished by qualitative and quantitative optical coherence tomography (OCT) analyses. METHODS AND RESULTS: One-hundred and twenty-two initial ISR lesions (sirolimus-eluting stents: n=28; paclitaxel-eluting stents: n=51; BMS: n=43) were evaluated with OCT. Based on their OCT appearance, the lesions were classified as homogeneous, layered or heterogeneous. The optical properties of backscatter, attenuation and signal intensity of the neointimal tissue (NIT) were quantified. To evaluate the vascular response after balloon angioplasty (BA), the rate of reduction of the NIT area (NITA) was calculated (NITA before - after BA/NITA before BA at the minimum lumen cross-sectional area). Among the morphologic OCT patterns, the layered type was predominant with DES, whereas lesions were homogeneous with BMS (P<0.001). Backscatter and signal intensity were significantly higher with BMS (P<0.05 and P<0.001 respectively). The NITA reduction rate was significantly greater in the layered and heterogeneous groups than in the homogeneous group (P<0.01). CONCLUSIONS: The morphologic OCT patterns of the NIT in ISR differed significantly between DES and BMS, probably reflecting pathologic differences. Layered and heterogeneous tissues might respond better than homogeneous tissue to simple balloon dilatation, suggesting a possible direction for OCT-based ISR treatment strategies.

Impact of stent platform of paclitaxel-eluting stents: assessment of neointimal distribution on optical coherence tomography.

BACKGROUND: The Taxus Express™ paclitaxel-eluting stent (Express-PES) and Taxus Liberté™ PES (Liberté-PES) have identical drugs, drug doses, and polymers, but different stent platforms. The Liberté-PES platform has thinner struts, specifically designed for more uniform drug elution. METHODS AND RESULTS: Fifty-four patients who underwent 6-month follow-up optical coherence tomography (OCT) after Express-PES (n=27) or Liberté-PES (n=27) implantation were enrolled. Longitudinal and circumferential uniformity of neointimal distribution was evaluated in 3-D by computing mean neointimal thickness (NIT) within 360 equally spaced radial sectors for every 1-mm cross-section. After stenting, intravascular ultrasound showed that Liberté-PES had a significantly smaller maximum angle between adjacent struts, with a tendency toward a lower incidence of % length of the segment with maximum angle >90° than Express-PES. Liberté-PES had a significantly thinner mean NIT than the Express-PES with comparable frequency of uncovered struts. Longitudinal and circumferential absolute variation of NIT expressed by standard deviation of NIT from each sector was significantly smaller for Liberté-PES than for Express-PES. Liberté-PES had a tendency toward a decreased incidence of thrombus and peri-strut low-intensity areas (findings suggestive of delayed arterial healing), compared to Express-PES. CONCLUSIONS: Stent design and thickness appeared to affect neointima suppression of PES. The stent platform of the Liberté-PES may offer greater and more homogeneous reduction of neointimal proliferation spatially across the full length of the PES.