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Background: Symptomatic intracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke worldwide. In patients undergoing endovascular treatment for ICAS, in-stent restenosis (ISR) is associated with ischemic stroke recurrence. Objective: Intracranial drug-eluting self-expanding stent systems (COMETIU; Sinomed Neurovita Technology Inc., CHN) are new devices for treating ICAS. This study evaluated the perioperative experience and medium-term outcomes of COMETIU in 16 patients. Methods: We prospectively analyzed 16 patients with ICAS (≥ 70% stenosis) who underwent intravascular therapy between September 4, 2022, and February 1, 2023. The primary outcome was the incidence of ISR at 6 months postoperatively. The secondary efficacy outcomes were device and technical success rates. The secondary safety outcomes included stroke or death within 30 days after the procedure and the cumulative annual rate of recurrent ischemic stroke in the target-vessel territory from 31 days to 6 months and 1 year. Results: A total of 16 patients with 16 intracranial atherosclerotic lesions were treated with 16 COMETIUs. All procedures were performed under general anesthesia with 100% device and technical success rates, with no cases of periprocedural stroke or death. The mean radiographic follow-up duration was at least 6 months postoperatively, and all patients presented for radiographic and clinical follow-up. There were no reported ischemic or hemorrhagic strokes. Angiographic follow-up for all patients revealed no cases of ISR. Conclusion: COMETIU is safe and effective for treating ICAS, with minimal risk during the procedure and a low rate of ISR during medium-term follow-up. [ABSTRACT FROM AUTHOR]

Objectives: As a novel imaging marker, pericoronary fat attenuation index (FAI) reflects the local coronary inflammation which is one of the major mechanisms for in-stent restenosis (ISR). We aimed to validate the ability of pericoronary FAI to predict ISR in patients undergoing percutaneous coronary intervention (PCI). Materials and methods: Patients who underwent coronary CT angiography (CCTA) before PCI within 1 week between January 2017 and December 2019 at our hospital and had follow-up invasive coronary angiography (ICA) or CCTA were enrolled. Pericoronary FAI was measured at the site where stents would be placed. ISR was defined as ≥ 50% diameter stenosis at follow-up ICA or CCTA in the in-stent area. Multivariable analysis using mixed effects logistic regression models was performed to test the association between pericoronary FAI and ISR at lesion level. Results: A total of 126 patients with 180 target lesions were included in the study. During 22.5 months of mean interval time from index PCI to follow-up ICA or CCTA, ISR occurred in 40 (22.2%, 40/180) stents. Pericoronary FAI was associated with a higher risk of ISR (adjusted OR = 1.12, p = 0.028). The optimum cutoff was − 69.6 HU. Integrating the dichotomous pericoronary FAI into current state of the art prediction model for ISR improved the prediction ability of the model significantly (△area under the curve = + 0.064; p = 0.001). Conclusion: Pericoronary FAI around lesions with subsequent stent placement is independently associated with ISR and could improve the ability of current prediction model for ISR. Clinical relevance statement: Pericoronary fat attenuation index can be used to identify the lesions with high risk for in-stent restenosis. These lesions may benefit from extra anti-inflammation treatment to avoid in-stent restenosis. Key Points: • Pericoronary fat attenuation index reflects the local coronary inflammation. • Pericoronary fat attenuation index around lesions with subsequent stents placement can predict in-stent restenosis. • Pericoronary fat attenuation index can be used as a marker for future in-stent restenosis. [ABSTRACT FROM AUTHOR]

Coronary restenosis is the primary unsolved problem following open heart surgery or percutaneous transluminal coronary angioplasty, and yet, it remains unknown how a pharmaceutical strategy minimizes restenosis by scaffold-based administration of several medicines. In this study, 3D-printed hexagonal polymer scaffolds of sodium alginate/hyaluronic acid/gelatin (SA/HA/Gel) loaded with heparin drug were fabricated. The morphology, physicochemical, and surface properties of the scaffolds were investigated through SEM, FTIR, porosity, wettability, water absorption, mechanical properties, biodegradability, and heparin release studies. The cell-scaffold interactions were studied by the cell attachment assays and MTT assay on L929 cell lines. The investigation demonstrated that raising the print angle resulted in 3D-printed scaffolds having higher porosity percentages, mechanical qualities, and heparin release (P < 0.05), but had no discernible impact on the scaffolds' biological properties (P > 0.05). Heparin showed a regulated slow-release behavior that was consistent with the scaffolds' rate of degradation and may be continually efficient during tissue regeneration. According to the outcomes of the in vitro biological evaluation, the 3D-printed scaffolds showed suitable cell attachment and biocompatibility (> 90%), and they were not overtly hazardous. The findings support the use of the fabricated 3D-printed SA/HA/Gel heparin-loaded scaffolds for cardiovascular tissue applications. [ABSTRACT FROM AUTHOR]

Machine learning (ML) techniques have shown great potential in cardiovascular surgery, including real-time stenosis recognition, detection of stented coronary anomalies, and prediction of in-stent restenosis (ISR). However, estimating neointima evolution poses challenges for ML models due to limitations in manual measurements, variations in image quality, low data availability, and the difficulty of acquiring biological quantities. An effective in silico model is necessary to accurately capture the mechanisms leading to neointimal hyperplasia. Physics-informed neural networks (PINNs), a novel deep learning (DL) method, have emerged as a promising approach that integrates physical laws and measurements into modeling. PINNs have demonstrated success in solving partial differential equations (PDEs) and have been applied in various biological systems. This paper aims to develop a robust multiphysics surrogate model for ISR estimation using the physics-informed DL approach, incorporating biological constraints and drug elution effects. The model seeks to enhance prediction accuracy, provide insights into disease progression factors, and promote ISR diagnosis and treatment planning. A set of coupled advection-reaction-diffusion type PDEs is constructed to track the evolution of the influential factors associated with ISR, such as platelet-derived growth factor (PDGF), the transforming growth factor- β (TGF- β ), the extracellular matrix (ECM), the density of smooth muscle cells (SMC), and the drug concentration. The nature of PINNs allows for the integration of patient-specific data (procedure-related, clinical and genetic, etc.) into the model, improving prediction accuracy and assisting in the optimization of stent implantation parameters to mitigate risks. This research addresses the existing gap in predictive models for ISR using DL and holds the potential to enhance patient outcomes through predictive risk assessment. [ABSTRACT FROM AUTHOR]

Objectives: To explore the clinical relevance of stent-specific perivascular fat attenuation index (FAI) in patients with stent implantation. Methods: A total of 162 consecutive patients who underwent coronary computed tomography angiography (CCTA) following stent implantation were retrospectively included. The stent-specific FAI at 2 cm adjacent to the stent edge was calculated. The endpoints were defined as target vessel revascularization (TVR) on the stented vessel after CCTA and readmission times due to chest pain after stent implantation. Binary logistic regression analysis for TVR and ordinal regression models were conducted to identify readmission times (0, 1, and ≥ 2) with generalized estimating equations on a per-stent basis. Results: On a per-stent basis, 9 stents (4.5%) experienced TVR after PCI at a median 30 months' follow-up duration. Stent-specific FAI differed significantly among subgroups of patients with stent implantation and different readmission times (p = 0.002); patients with at least one readmission had higher stent-specific FAI than those without readmission (p < 0.001). Bifurcated stents (odds ratio [OR]: 11.192, p = 0.001) and stent-specific FAI (OR: 1.189, p = 0.04) were independently associated with TVR. With no readmission as a reference, stent-specific FAI (OR: 0.984, p = 0.007) was an independent predictor for hospital readmission times ≥ 2 (p = 0.003). Conclusion: Non-invasive stent-specific FAI derived from CCTA was found to be associated with TVR, which was a promising imaging marker for functional assessment in patients who underwent stent implantation. Clinical relevance statement: Noninvasive fat attenuation index adjacent to the stents edge derived from CCTA, an imaging marker reflecting the presence of inflammation acting on the neointimal tissue at the sites of coronary stenting, might be relevant clinically with target vessel revascularization. Key Points: • Non-invasive stent-specific FAI derived from CCTA was associated with TVR (OR: 1.189 [95% CI: 1.007–1.043], p = 0.04) in patients who underwent stent implantation. • Stent-specific FAI significantly differed among a subgroup of patients with chest pain after stent implantation and with different readmission times (p = 0.002); the patients with at least one readmission had higher stent-specific FAI than those without readmission (p < 0.001). • Non-invasive stent-specific FAI derived from CCTA could be used as an imaging maker for the functional assessment of patients following stent implantation. [ABSTRACT FROM AUTHOR]

Previous studies clarified that carotid endarterectomy has better outcomes in the elderly patients than carotid artery stenting. However, these studies did not evaluate the plaque characteristics of stenotic lesions. Therefore, we conducted a retrospective study to examine the safety and efficacy of carotid artery stenting with plaque evaluation in elderly patients. Overall, the data of 61 cases of 60 patients who underwent carotid artery stenting or carotid endarterectomy from October 2012 to December 2019 were included. The following data were compared between the carotid endarterectomy and carotid artery stenting cases: plaque characteristics on carotid magnetic resonance imaging (MRI), patient background characteristics, perioperative complications, prognosis, and presence of restenosis in patients aged > 70 years. Twenty-five patients aged > 70 years underwent carotid artery stenting, whereas 18 patients aged > 70 years underwent carotid endarterectomy. Carotid endarterectomy cases tended to have more unstable plaques characterized by high-intensity signals on carotid T1-weighted MRI images (carotid endarterectomy 12 cases (67%), carotid artery stenting 4 cases (16%); P: 0.0006). Perioperative complication occurred in two carotid artery stenting cases and one carotid endarterectomy case (carotid artery stenting 8%, CEA 5.6%; P: 0.75). The data of stroke, 30-day morbidity, modified Rankin Scale score after 90 days, and mortality showed no significant differences. Restenosis after intervention occurred in three carotid artery stenting cases and one carotid endarterectomy case. Carotid artery stenting can be safely performed even in elderly patients by selecting appropriate treatment based on plaque characteristics. [ABSTRACT FROM AUTHOR]

Background: Despite the recent progress made in drug-eluting stents (DESs), in-stent restenosis (ISR) is still a common complication of percutaneous coronary interventions. This retrospective study from a single center aimed to compare outcomes in 79 patients with ISR treated with paclitaxel-coated balloon (PCB) angioplasty or DES implantation. Results: From January 2017 to December 2021, 83 ISR lesions from 79 patients were included. Thirty-two were treated with PCB and 51 treated with available DES in the catheterization laboratory. Baseline characteristics were similar in both groups. Mean time between index angioplasty and restenosis was 27 months with a minimum of 4 months and a maximum of 70 months. Concerning Mehran ISR angiographic classification, classes II and III were more likely treated with DES. Stenosis diameter and minimal lumen diameter (MLD) were similar in both groups. PCB used was significantly shorter than DES: Mean length was 19.75 ± 5.7 versus 22.1 ± 16.5 (p < 0.001), respectively. Angiographic results immediately after intervention were similar in both groups: In-segment MLD after the procedure was 2.5 ± 0.4 in the DES group and 2.26 ± 0.55 in the PCB group. A median follow-up of 20 months was achieved for 68 patients, and 11 were lost to follow-up. There was also no difference in both groups regarding free from events survival. Conclusions: The findings from this study support recent international studies that have shown no significant differences between DES and PCB and in-stent restenosis. This suggests that PCB use is an option to consider in our local daily practice. [ABSTRACT FROM AUTHOR]

Purpose: To conduct a systematic review to identify studies that assessed the association between CYP2C19 polymorphisms and clinical outcomes in peripheral artery disease (PAD) patients who took clopidogrel. Methods: We systematically searched Ovid EMBASE, PubMed, and Web of Science from November 1997 (inception) to September 2020. We included observational studies evaluating how CYP2C19 polymorphism is associated with clopidogrel's effectiveness and safety among patients with PAD. We extracted relevant information details from eligible studies (e.g., study type, patient population, study outcomes). We used the Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) Tool to assess the risk of bias for included observational studies. Results: The outcomes of interest were the effectiveness and safety of clopidogrel. The effectiveness outcomes included clinical ineffectiveness (e.g., restenosis). The safety outcomes included bleeding and death related to the use of clopidogrel. We identified four observational studies with a sample size ranging from 50 to 278. Outcomes and comparison groups of the studies varied. Three studies (75%) had an overall low risk of bias. All included studies demonstrated that carrying CYP2C19 loss of function (LOF) alleles was significantly associated with reduced clinical effectiveness and safety of clopidogrel. Conclusions: Our systematic review showed an association between CYP2C19 LOF alleles and reduced functions of clopidogrel. The use of CYP2C19 testing in PAD patients prescribed clopidogrel may help improve the clinical outcomes. However, based on the limited evidence, there is a need for randomized clinical trials in PAD patients to test both the effectiveness and safety outcomes of clopidogrel. [ABSTRACT FROM AUTHOR]

Background: The incidence of in-stent restenosis (ISR) remains relatively common despite the use of drug-eluting stents. Outcomes and prognostic factors following ISR revascularization are still being investigated. We aimed to describe the outcomes following different ISR treatment strategies in order to identify prognostic factors associated with worse outcomes. Results: In a retrospective cohort study, we included patients who were admitted to our department and treated for ISR, from January 2017 to December 2018. All patients were followed up for a median period of 24 months. Major cardiac adverse event (MACE) was a composite outcome of the following events: myocardial infarction, target vessel revascularization, target lesion revascularization or cardiovascular death. MACEs were collected during follow-up. Our population consisted of 116 patients. Mean age was 60 years old with a sex ratio of 2.8. During follow-up, 44 patients (37.9%) had at least one MACE. Independent factors identified by multivariate logistic regression were ISR of the proximal left anterior descending artery [Odds ratio (OR) = 1.29; 95% confidence interval (95% CI) 1.16–1.81; p = 0.05], diffuse ISR [OR = 2.16; 95% CI 1.1–3.47; p = 0.022], double or triple vessel disease [OR = 2.97; 95% CI 1.2–6.8; p = 0.008], two or more stents per lesion [OR = 1.82; 95% CI 1.14–2.21, p = 0.031] and absence of post-dilatation in the initial angioplasty [OR = 1.32; 95% CI 1–1.35; p = 0.04]. Conclusions: Our study suggested that ISR is related to poor outcomes. Identifying prognostic factors would play a key role in the refinement of interventional techniques. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether contrast-enhanced ultrasound (CEUS) is an accurate, non-nephrotoxic diagnostic method and follow-up tool for use in patients with chronic kidney disease (CKD) and renal artery stenosis (RAS). Methods: In this prospective and monocentric study, we compared the sensitivity and specificity of CEUS for the diagnosis of RAS in CKD patients, using digital subtraction angiography (DSA) or computed tomographic angiography (CTA) as the gold standard methods. Further, the value of CEUS for distinguishing restenosis from other diseases was assessed. The ultrasound physicians conducted the examinations and served as the CEUS report readers who were blinded to the DSA or CTA results. Results: Patients with RAS (n = 60) were enrolled. Average patient age was 64.4 ± 18.0 years and median estimated glomerular filtration rate was 66.1 mL/min/1.73 m2. CEUS was used to image 94 stenotic renal arteries and DSA- or CTA-verified stenosis was present in 96 renal arteries. The kappa value for CEUS was 0.776 (P < 0.001), with an accuracy of 92.5%, a sensitivity of 94.7%, and a specificity of 84.0%. The accuracy of CEUS was the same for the diagnosis of the CKD3b–5 group as for the CKD1–3a group (100% vs. 87.5%, P = 0.148). There was no difference in CEUS accuracy for the diagnosis of Takayasu RAS compared with atherosclerotic RAS (95.8% vs. 91.7%, P = 0.795). Twenty-nine CEUS examinations were performed to follow in-stent restenosis or progression of RAS, with a median follow-up time of 5.0 months (range 1.0–20.0). Two cases of in-stent restenosis in patients suffering from deteriorating kidney function and recurrent hypertension were examined by CEUS. Conclusion: CEUS examination is a credible alternative for diagnosing moderate and severe RAS in patients with CKD, and is a reliable tool for follow-up surveillance after renal artery revascularization treatment. It shouldn't be thought as a color-coded duplex ultrasonography rescue in these patients. [ABSTRACT FROM AUTHOR]

Purpose: The purposes of this experimental study were to compare the quantitative and qualitative visibility of in-stent restenosis between conventional-resolution CT (CRCT) and ultra-high-resolution CT (U-HRCT) and to investigate the effects of the image reconstruction techniques on the visualization of in-stent restenosis. Materials and methods: A vessel tube with non-calcified plaque in a 3.0-mm stent was scanned by using CRCT and U-HRCT at 4 stent directions (0, 30, 60, and 90 degrees) to the through-plane direction. Hybrid iterative reconstruction (HIR); model-based iterative reconstruction (MBIR); deep-learning-based reconstruction (DLR) were used as reconstruction methods. The lumen size was assessed using the full width at half maximum method, and image quality was visually evaluated using 4-point scale. Results: U-HRCT had the significantly wider lumen sizes and narrower stent strut thickness than CRCT in three types of the reconstruction methods (P < 0.01). The lumen sizes for U-HRCT with 90 degrees were narrower than those with the other angle directions regardless of the reconstruction methods. Visual score was significantly higher for U-HRCT than CRCT (3.2 ± 0.7 vs 2.0 ± 0.4, P < 0.001). Conclusions: U-HRCT quantitatively and qualitatively provided better visualization of in-stent restenosis compared to CRCT. Image quality of U-HRCT may be affected by stent angle. [ABSTRACT FROM AUTHOR]

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Objectives: To investigate the feasibility and prognostic implications of coronary CT angiography (CCTA) derived fractional flow reserve (FFRCT) in patients who have undergone stents implantation. Methods: Firstly, the feasibility of FFRCT in stented vessels was validated. The diagnostic performance of FFRCT in identifying hemodynamically in-stent restenosis (ISR) in 33 patients with invasive FFR ≤ 0.88 as reference standard, intra-group correlation coefficient (ICC) between FFRCT and FFR was calculated. Secondly, prognostic value was assessed with 115 patients with serial CCTA scans after PCI. Stent characteristics (location, diameter, length, etc.), CCTA measurements (minimum lumen diameter [MLD], minimum lumen area [MLA], ISR), and FFRCT measurements (FFRCT, ΔFFRCT, ΔFFRCT/stent length) both at baseline and follow-up were recorded. Longitudinal analysis included changes of MLD, MLA, ISR, and FFRCT. The primary endpoint was major adverse cardiovascular events (MACE). Results: Per-patient accuracy of FFRCT was 0.85 in identifying hemodynamically ISR. FFRCT had a good correlation with FFR (ICC = 0.84). 15.7% (18/115) developed MACE during 25 months since follow-up CCTA. Lasso regression identified age and follow-up ΔFFRCT/length as candidate variables. In the Cox proportional hazards model, age (hazard ratio [HR], 1.102 [95% CI, 1.032–1.177]; p = 0.004) and follow-up ΔFFRCT/length (HR, 1.014 [95% CI, 1.006–1.023]; p = 0.001) were independently associated with MACE (c-index = 0.856). Time-dependent ROC analysis showed AUC was 0.787 (95% CI, 0.594–0.980) at 25 months to predict adverse outcome. After bootstrap validation with 1000 resamplings, the bias-corrected c-index was 0.846. Conclusions: Noninvasive ML-based FFRCT is feasible in patients following stents implantation and shows prognostic value in predicting adverse events after stents implantation in low-moderate risk patients. Key Points: • Machine-learning-based FFRCTis feasible to evaluate the functional significance of in-stent restenosis in patients with stent implantation. • Follow-up △FFRCTalong with the stent length might have prognostic implication in patients with stent implantation and low-to-moderate risk after 2 years follow-up. The prognostic role of FFRCTin patients with moderate-to-high or high risk needs to be further studied. • FFRCTmight refine the clinical pathway of patients with stent implantation to invasive catheterization. [ABSTRACT FROM AUTHOR]

The hemodynamic behavior following endovascular treatment of patients with peripheral arterial disease plays a significant role on the occurrence of restenosis in femoro-popliteal (FP) arteries. The atheroprone flow conditions that are generally accepted to promote restenosis can be calculated by computational fluid dynamics (CFD) analyses, and these results can be used to assess individualized treatment outcomes. However, the impact of endovascular therapy on the flow behaviors of FP arteries are still poorly understood, as the imaging modalities used in existing numerical works (X-ray angiography, computed tomography angiography) are unable to accurately represent the post-treatment arterial geometry due to their low resolutions. Therefore, this study proposes a new algorithm that combines intra-arterial lumen geometry obtained from high-resolution optical coherence tomography (OCT) images with centerlines generated from X-ray images to reconstruct the FP artery with an in-plane resolution of 10 µm. This superior accuracy allows modeling characteristic geometrical structures, such as angioplasty-induced arterial dissections, that are too small to be reconstructed with other imaging modalities. The framework is applied on the clinical data of patients treated either with only-percutaneous transluminal angioplasty (PTA) (n = 4) or PTA followed by stenting (n = 4). Based on the generated models, PTA was found to cause numerous arterial dissections, covering approximately 10% of the total surface area of the lumen, whereas no dissections were identified in the stented arteries. CFD simulations were performed to investigate the hemodynamic conditions before and after treatment. Regardless of the treatment method, the areas affected by low time-averaged wall shear stress (< 0.5 Pa) were significantly higher (p < 0.05) following endovascular therapy (pre-PTA: 0.95 ± 0.59 cm2; post-PTA: 2.10 ± 1.09cm2; post-stent: 3.10 ± 0.98 cm2). There were no statistical differences between the PTA and the stent groups. However, within the PTA group, adverse hemodynamics were mainly concentrated at regions created by arterial dissections, which may negatively impact the outcomes of a leave-nothing-behind strategy. These observations show that OCT-based numerical models have great potential to guide clinicians regarding the optimal treatment approach. [ABSTRACT FROM AUTHOR]

In-stent restenosis (ISR) represents a major complication after stenting of intracranial artery stenosis (ICAS). Biomarkers derived from routine blood sampling including C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and mean platelet volume (MPV) have been associated with progressive atherosclerosis. We investigated the role of CRP, NLR, PLR and MPV on the development of intracranial ISR and recurrent stroke risk. We retrospectively included all patients who had undergone stenting of symptomatic ICAS at our university hospital between 2005 and 2016. ISR (≥ 50% stenosis) was diagnosed by regular Duplex sonography follow-up studies and confirmed by digital subtraction angiography or computed tomography angiography (mean follow-up duration: 5 years). Laboratory parameters were documented before stenting, at the time of restenosis and at last clinical follow-up. Of 115 patients (mean age: 73 ± 13 years; female: 34%), 38 (33%) developed ISR. The assessed laboratory parameters did not differ between patients with ISR and those without (p > 0.1). While ISR was associated with the occurrence of recurrent ischemic stroke (p = 0.003), CRP, NLR, PLR and MPV were not predictive of such events (p > 0.1). Investigated blood biomarkers of progressive atherosclerosis were not predictive for the occurrence of ISR or recurrent ischemic stroke after ICAS stenting during a 5-year follow-up. [ABSTRACT FROM AUTHOR]

Understanding the effects of a stent design on the flow behaviour especially near the artery wall can lead to choosing or designing more haemodynamically compatible stents that can reduce the chances of restenosis inside the stented arteries. In this study, a novel technique is presented for the visualisation of the entire flow and the investigation of wall shear stress (WSS) within the stent struts without covering the field of view (FOV) inside a stented coronary artery model using particle image velocimetry. This novel technique is based on the construction of a transparent stented artery using silicone casted in one piece, instead of inserting a metal or non-metallic stent inside a casted artery model, which are translucent and distort the FOV. The effect of the stent pattern on the WSS and oscillatory shear index of a coronary artery is investigated for the models of four stents to identify the locations with the high chances of restenosis. The developed technique will help to improve the stent designs to achieve better patient outcome. [ABSTRACT FROM AUTHOR]

This study investigated factors affecting the safety and in-stent restenosis after intracranial stent angioplasty using the Enterprise stent for symptomatic intracranial atherosclerotic stenosis. Between January 2017 and March 2019, patients with intracranial atherosclerotic stenosis treated with Enterprise stent angioplasty were enrolled, including 400 patients in the modeling group and 89 patients in the validation group. The clinical factors affecting in-stent restenosis after Enterprise stent angioplasty in the modeling group were analyzed, and a logistic regression model of these factors was established and validated in the validation group. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were analyzed. In the modeling group with 400 patients, there were 410 lesions, including 360 stenotic lesions and 50 occluded lesions, with 176 (42.9%) lesions in the anterior circulation and 234 (57.1%) in the posterior circulation. Successful stenting was performed in 398 patients (99.5%). Stenosis was significantly (P < 0.05) improved after stenting compared with before stenting (27.7% ± 2.9% vs. 77.9% ± 8.0%). Periprocedural complications included ischemic stroke (3.25%), hemorrhagic stroke (0.75%), and death (0.50%), with a total periprocedural complication rate of 4.0%. The first follow-up angiography was performed in 348 (87.0%) patients with 359 lesions 3.5–14 months (mean 5.7 months) after stenting. In-stent restenosis occurred in 62 (17.3%) lesions, while the other 295 (82.7%) had no restenosis. Lesion location, calcification degree, balloon expansion pressure, residual stenosis, intraprocedural dissection, and cerebral blood flow TICI grade were significant (P < 0.05) risk factors for in-stent restenosis. The in-stent restenosis prediction model was established as follows: P = 1/[1 + e−(−6.070–1.391 location + 2.745 calcification + 4.117 balloon inflation pressure + 2.195 intraprocedural dissection + 1.163 residual stenosis + 1.174 flow TC grade)]. In the validation group, the AUC in the ROC curve analysis was 0.902 (95% CI: 0.836–0.969), and when the cutoff value was 0.50, the sensitivity and specificity of this model were shown to be 76.92% and 80.26%, respectively, in predicting in-stent restenosis at angiographic follow-up, with a total coincidence rate of 79.78%. In conclusion, in-stent restenosis after intracranial Enterprise stenting is affected by stenosis location, calcification, balloon inflation pressure, intraprocedural arterial dissection, residual stenosis, and cerebral flow grade, and establishment of a logistic model with these factors can effectively predict in-stent restenosis. [ABSTRACT FROM AUTHOR]

Percutaneous transluminal angioplasty (PTA) of stenotic arteriovenous fistulas (AVFs) is performed to maintain optimal function and patency. The one-year patency rate is 60% because of venous neointimal hyperplasia (VNH) and venous stenosis (VS) formation. Immediate early response gene X-1 (Iex-1) also known as Ier3 increases in response to wall shear stress (WSS), and can cause VNH/VS formation in murine AVF. In human stenotic samples from AVFs, we demonstrated increased gene expression of Ier3. We hypothesized that 1α, 25-dihydroxyvitamin D3, an inhibitor of IER3 delivered as 1α, 25-dihydroxyvitamin D3 encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles loaded in Pluronic F127 hydrogel (1,25 NP) to the adventitia of the stenotic outflow vein after PTA would decrease VNH/VS formation by reducing Ier3 and chemokine (C–C motif) ligand 2 (Ccl2) expression. In our murine model of AVF stenosis treated with PTA, increased expression of Ier3 and Ccl2 was observed. Using this model, PTA was performed and 10-μL of 1,25 NP or control vehicle (PLGA in hydrogel) was administered by adventitial delivery. Animals were sacrificed at day 3 for unbiased whole genome transcriptomic analysis and at day 21 for immunohistochemical analysis. Doppler US was performed weekly after AVF creation. At day 3, significantly lower gene expression of Ier3 and Ccl2 was noted in 1,25 NP treated vessels. Twenty-one days after PTA, 1,25 NP treated vessels had increased lumen vessel area, with decreased neointima area/media area ratio and cell density compared to vehicle controls. There was a significant increase in apoptosis, with a reduction in CD68, F4/80, CD45, pro-inflammatory macrophages, fibroblasts, Picrosirius red, Masson's trichrome, collagen IV, and proliferation accompanied with higher wall shear stress (WSS) and average peak velocity. IER3 staining was localized to CD68 and FSP-1 (+) cells. After 1,25 NP delivery, there was a decrease in the proliferation of α-SMA (+) and CD68 (+) cells with increase in the apoptosis of FSP-1 (+) and CD68 (+) cells compared to vehicle controls. RNA sequencing revealed a decrease in inflammatory and apoptosis pathways following 1,25 NP delivery. These data suggest that adventitial delivery of 1,25 NP reduces VNH and venous stenosis formation after PTA. [ABSTRACT FROM AUTHOR]

In 2013, a drug-coated balloon catheter (DCB) (SeQuent Please) for the treatment of coronary in-stent restenosis (ISR) was approved in Japan. The pre-marketing Japan domestic NP001 study demonstrated better outcomes of the DCB (n = 138) compared to plain balloon angioplasty (n = 72). After the introduction to marketing, a post-marketing surveillance (PMS) (n = 396) was conducted to evaluate the safety and efficacy of the DCB in Japanese routine clinical practice. The aim of this paper was to assess differences between the pre-marketing NP001 study and the PMS. Compared to the NP001 study, more complex lesions were treated in the PMS (type B2/C: 69.0% vs 20.4%, total occlusion: 11.2% vs 0%, p < 0.001, respectively) and target lesion was more frequently ISR related to drug-eluting stent (DES) (79.5% vs 39.4%, p < 0.001). Regarding clinical outcomes, the rate of target lesion revascularization (TLR) was higher in the PMS than in the NP001 study (TLR: 12.9% at 7 months and 17.6% at 12 months vs 2.8% at 6 months, p = 0.001, p < 0.001, respectively). Multivariable logistic regression analysis revealed that DES-ISR was a risk factor of TLR after DCB treatment for ISR (odds ratio: 5.77, 95% CI 1.75–18.95, p = 0.004). Among representative published trials using DCB for ISR, clinical outcomes are often worse in DES-ISR trials than those in bare metal stent-ISR trials. The rates of TLR in previous DES-ISR trials are similar to that in the current PMS (TLR at 12 months: 22.1% for ISAR-DESIRE 3, 15.3% for PEPCAD-DES, and 13.0% for RIBS IV). The effectiveness and safety of DCB for coronary ISR have been confirmed in the Japanese real-world survey. PMS would be useful to evaluate the safety and effectiveness of medical products throughout their total life cycles. [ABSTRACT FROM AUTHOR]

Neointima hyperplasia is a crucial component of restenosis after coronary angioplasty. We have hypothesized that enhanced generation of platelet-derived thromboxane (TX)A2 in response to vascular damage plays a critical role in neointimal hyperplasia and that antiplatelet agents may mitigate it. In cocultures of human platelets and coronary artery smooth muscle cells (CASMC), we found that platelets induced morphologic changes and enhanced the migration of CASMC. The exposure of platelets to Aspirin [an inhibitor of cyclooxygenase (COX)-1] reduced the generation of TXA2 and prevented the morphological and functional changes induced by platelets in CASMC. Platelet-derived TXA2 induced COX-2 and enhanced prostaglandin (PG)E2 biosynthesis in CASMC, a known mechanism promoting neointimal hyperplasia. COX-2 induction was prevented by different antiplatelet agents, i.e., Aspirin, the TP antagonist SQ29,548, or Revacept (a dimeric soluble GPVI-Fc fusion protein). The administration of the novel antiplatelet agent Revacept to C57BL/6 mice, beginning three days before femoral artery denudation, and continuing up to seven days after injury, prevented the increase of the systemic biosynthesis di TXA2 and reduced femoral artery intima-to-media area and the levels of markers of cell proliferation and macrophage infiltration. Revacept might serve as a therapeutic agent for percutaneous coronary angioplasty and stent implantation. [ABSTRACT FROM AUTHOR]

Device-related problems of drug-eluting stents, including stent thrombosis related to antiproliferative drugs and polymers, can cause adverse events such as inflammation and neointimal hyperplasia. Stent surface modification, wherein the drug and polymer are not required, may overcome these problems. We developed hydrophilic polyethylene glycol (PEG)-coating and hydrophobic octadecylthiol (ODT)-coating stents without a drug and polymer and evaluated their histopathologic response in a porcine coronary restenosis model. PEG-coating stents (n = 12), bare-metal stents (BMS) (n = 12), and ODT-coating stents (n = 10) were implanted with oversizing in 34 porcine coronary arteries. Four weeks later, the histopathologic response, arterial injury, inflammation, and fibrin scores were analyzed. A p value < 0.05 was considered statistically significant. There were significant differences in the internal elastic lamina area, lumen area, neointimal area, percent area of stenosis, arterial injury score, inflammation score, and fibrin score among the groups. Compared to the BMS or ODT-coating stent group, the PEG-coating stent group had significantly increased internal elastic lamina and lumen area (all p < 0.001) and decreased neointimal area and percent area of stenosis (BMS: p = 0.03 and p < 0.001, respectively; ODT-coating: p = 0.013 and p < 0.001, respectively). Similarly, the PEG-coating group showed significantly lower inflammation and fibrin scores than the BMS or ODT-coating groups (BMS: p = 0.013 and p = 0.007, respectively; ODT-coating: p = 0.014 and p = 0.008, respectively). In conclusion, hydrophilic PEG-coating stent implantation was associated with lower inflammatory response, decreased fibrin deposition, and reduced neointimal hyperplasia than BMS or hydrophobic ODT-coating stent implantation in the porcine coronary restenosis model. [ABSTRACT FROM AUTHOR]

Although stenting of non-branched arterial segments has acceptable clinical outcomes, in-stent restenosis (ISR) and stent thrombosis remain clinically significant issues for vascular bifurcations (15–28% restenosis). Local fluid and solid stresses appear to play an important role in restenosis and thrombosis. The combined role of wall shear stress (WSS) and circumferential wall stresses (CWS) is unclear in the case of stenting at vascular bifurcations. Using numerical simulations, we computed the fluid shear, solid stresses and the stress ratio at the the bifurcation region. Stenting of main vessel increased the maximum CWS in the the side branch (SB), resulting in a nearly two-fold increase of stress ratio in the SB compared to the MB (5.1 × 105 vs. 9.2 × 105). The existence of plaque decreased WSS and increased CWS near the carina, increasing the stress ratio at the SB. The changes of stress ratio were highly consistent with clinical data on bifurcation stenting. Fluid dynamics and solids mechanics should be considered in planning of stenting for a specific bifurcation, as their combined biomechanical effect may play an important role in stent restenosis and thrombosis. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the incidence of binary restenosis and its predictors in patients with ostial lesions of the right coronary artery (RCAos) who underwent percutaneous coronary intervention (PCI). RCAos are associated with a high incidence of restenosis, and the implantations of drug-eluting stents for RCAos have not been fully elucidated. The study participants included 75 patients (72.3 ± 9.5 years, 72% men) who underwent PCI for RCAos at our institution between November 2001 and May 2017. The angle between the greater curvature of the aortic wall and the right coronary artery take-off in the diastolic and systolic phases in the left anterior oblique position view was investigated. Clinical outcome was defined as binary restenosis at follow-up coronary angiography. We also evaluated target lesion failure (TLF) defined as a composite of cardiac mortality, target vessel myocardial infarction, and target lesion revascularization (TLR). The incidence of binary restenosis was 48.0% (n = 36) of the entire cohort. The incidence of TLF was 49.3% (n = 37) of the entire cohort, which was mainly driven by TLR (36.0%, n = 27). The area under the curve of the gap-angle ratio [(difference between the maximum and minimum angles)/(minimum angle); GAR] for binary restenosis was 0.73, and the cutoff value was 0.306 (sensitivity 67%, specificity 82%). The patients were divided into two groups: a low-GAR (< 0.306; n = 30) and high-GAR group (> 0.306; n = 45). Binary restenosis was more frequent in the high-GAR group than in the low-GAR group (76.7% vs. 28.9%, p = 0.007). The cumulative rate of TLF was significantly higher in the high-GAR group when compared with the low-GAR group (53.3% vs. 40.0%, p = 0.01), which was mainly driven by TLR (56.7% vs. 22.2%, p = 0.01). High-GAR (> 0.306) [OR 2.66 (1.34–5.31), p = 0.005] and stent under expansion [OR 2.37 (1.10–5.11), p = 0.03] were found to be independent predictors of binary restenosis after adjustment for multiple confounders. Multivariable analysis also revealed that high-GAR (> 0.306) [OR 2.06 (1.02–4.14), p = 0.03] and stent under expansion [OR 2.82 (1.28–6.19), p = 0.01] were independent predictors of TLF. We suggest that GAR (> 0.306) predicts binary restenosis and TLF in patients undergoing PCI for RCAos. [ABSTRACT FROM AUTHOR]

Aging and some lifestyle habits cause plaque accumulation in the blood vessels of the heart and this causes narrowing of the arteries. Stents are tiny wire mesh tubes which are used in balloon angioplasty to keep the vessels open. However, the stented vessel has a risk of re-narrowing due to the recovery response of the stented vessel segment and this is called in-stent-restenosis. The objective of this study is classifying patients according to their risks of restenosis. For this purpose, first a utilites additives discriminates model called parametrized classification model is developed, then to improve the classification performance of this model, a non-dominated sorting based multi-objective evolutionary algorithm (NSGA-II) is implemented. Finally, computational experiments are conducted with real life data to demonstrate the efficiency of proposed methods. [ABSTRACT FROM AUTHOR]

Drug-coated balloon (DCB) angioplasty has been shown to be a promising option for the treatment of coronary in-stent restenosis (ISR). We compared the clinical outcomes of patients with ISR who were treated with two commonly used paclitaxel-containing DCBs, the Pantera Lux (PL) and SeQuent Please (SP). A total of 491 patients with 507 ISR lesions [PL-DCB in 127 (26%) patients and SP-DCB in 364 (74%) patients] underwent DCB angioplasty for ISR lesions. The major adverse cardiac events (MACEs), including cardiac death, target lesion-related myocardial infarction, and target lesion revascularization, were assessed. There were no significant differences in each occurrence of MACE and cardiac death: 16 MACEs (61 per 1000 person-years) in the PL-DCB group and 55 (60 per 1000 person-years) MACEs in the SP-DCB group, log-rank p = 0.895, and three cardiac deaths (11 per 1000 person-years) in the PL-DCB group and ten cardiac deaths (11 per 1000 person-years) in the SP-DCB group, log-rank p = 0.849. Diabetes mellitus under insulin treatment [hazard ratio (HR) 2.71; 95% confidence interval (CI) 1.31–5.60; p = 0.007], chronic kidney disease (HR 1.99; 95% CI 1.01–3.92; p = 0.045), early-onset ISR (HR 1.99; 95% CI 1.18–3.36; p = 0.010), and recurrent ISR (HR 1.89; 95% CI 1.08–3.32; p = 0.026) were associated with the occurrence of MACE after DCB angioplasty. There was no significant difference of MACE between PL-DCB and SP-DCB treatment in patients with ISR. Patients with insulin-treated diabetes, chronic kidney disease, early-onset ISR, and recurrent ISR were at a higher risk of MACE after DCB angioplasty. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to evaluate the association of miRNA-146a G/C (rs2910164), and miRNA-196a2 C/T (rs11614913) polymorphisms with the presence of coronary artery disease (CAD) and/or restenosis in patients with coronary stent.Materials and methods: The polymorphisms were determined in 218 patients with CAD who underwent coronary artery stenting (66 with restenosis and 152 without restenosis) and 611 healthy controls using 5′ exonuclease TaqMan assays.Results: The distribution of both polymorphisms was similar in patients with and without restenosis. However, when the whole group of patients (with and without restenosis) was compared to healthy controls, under co-dominant, dominant and additive genetic models, the T allele of the miRNA-196a2 C/T (rs11614913) polymorphism was associated with increased risk of CAD (OR = 2.18, Pco-dom = 0.006, OR = 1.86, Pdom = 0.002, and OR = 1.52, Padd = 0.002, respectively). All models were adjusted for age, type 2 diabetes mellitus, dyslipidemia, hypertension and smoking habit. The "GT" haplotype was associated with increased risk of developing CAD (OR = 1.36, P = 0.046).Conclusions: Our data suggests that the T allele of the miRNA-196a2 C/T (rs11614913) polymorphism is associated with the risk of developing CAD, but no association with restenosis was observed. [ABSTRACT FROM AUTHOR]

The vascular endothelial growth factor (VEGF) family of peptides and caveolins (CAVs) are reported to contribute, in early graft failure in patients, a coronary artery bypass grafting (CABG). To investigate the possible association of ultimate luminal occlusion to VEGFs and CAVs expression, a functional analysis (based on the molecular biology, bioinformatics, histology, and clinical studies) was performed. Twenty-four hundred and sixty-eight CABG patients diagnosed with multivessel stable coronary artery disease (CAD) were enrolled into prospective study and assigned to two subgroups: double- and triple-vessel CAD subjects. Distal parts of all the harvested saphenous vein (SV) and internal thoracic artery (ITA) segments were used for further tests. ITA graft failure did not differ between double-vessel and triple-vessel CAD patients. The number of SV occlusions was significantly higher in triple-vessel CAD subjects. The microarray analysis performed on SV and ITA samples obtained exclusively from triple-vessel CAD patients who developed early graft occlusion revealed 383 genes with increased and 301 genes with decreased expression in ITA samples as compared to SV grafts. This was followed by functional analysis of ‘blood vessel development’ group of genes. Average VEGF-C expression in ITA grafts was higher than in corresponding SV grafts; FLT4 expression was significantly higher in SV than in ITA transplants. VEGFR-3 and CAV3 expression demonstrated immunohistochemically in SMCs of the tunica media of SV grafts predicted their early restenosis in triple-vessel CAD patients. CAV2 protein expression in SMCs of ITA grafts indicated the risk of early graft failure both in double-vessel and triple-vessel CAD subjects. [ABSTRACT FROM AUTHOR]

Thin-high signals (THS), detectable by optical coherence tomography (OCT), represent the paclitaxel coverage of in-stent restenotic tissue. This study was conducted to assess the relationship between THS and angiographic outcomes by means of quantified post-procedural frequency-domain OCT (FD-OCT) analysis. From January 2014 to July 2016, 41 patients underwent FD-OCT-guided percutaneous coronary intervention using paclitaxel-coated balloon (PCB) to prevent in-stent restenosis. Of these, we retrospectively enrolled 32 patients (38 lesions) who underwent a 6- to 9-month follow-up angiogram. THS were assessed quantitatively, as THS length and lumen perimeter length were measured using semi-automated software; %THS was calculated by the following formula; total THS area/lumen perimeter area × 100. THS were detected in all 38 lesions that had undergone PCB angioplasty. THS and %THS were significantly higher in lesions without binary restenosis (3.34 ± 2.11 vs. 11.48 ± 8.53 mm2, p = 0.001 and 1.49 ± 0.73 vs. 4.42 ± 2.71%, p = 0.001, respectively). Values for THS, which indicates the paclitaxel coverage on restenotic tissue, are associated with reducing restenosis after PCB for in-stent restenosis. [ABSTRACT FROM AUTHOR]

Background: The development of central airway obstruction during malignant diseases is an important cause of morbidity and mortality. Endobronchial therapies can decrease the patient's symptoms and improve quality of life. Here, we compare airway recanalization methods: argon plasma coagulation with mechanical tumor resection (APC + MTR) and cryorecanalization (CR efficiency, complications, restenosis rate, and time to restenosis) in patients with malignant exophytic endobronchial airway obstruction.Methods: A total of 89 patients were included who were admitted to our hospital between 2005 and 2012. The data were analyzed retrospectively. Initially, a CR procedure was performed in 52 patients using rigid bronchoscopy under general anesthesia; the APC + MTR procedure was performed in 37 patients with malignant airway obstruction.Results: The airway patency rate with APC + MTR was 97.3% (n = 36) and CR was 80.8% (n = 42). The APC + MTR procedure was more effective than CR for recanalization of malignant endobronchial exophytic airway obstruction. Additionally, the achievement rate of airway patency with APC + MTR was significantly higher in tumors with distal bronchial involvement. There was no statistically significant difference between groups in terms of complications, restenosis rate, and time to restenosis.Conclusions: The APC + MTR procedure is preferred over CR to introduce and maintain airway patency in patients with malignancy-related endobronchial exophytic airway obstruction. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the long-term outcomes at 2 years in patients in whom everolimus-eluting stents (EESs) were implanted in small and non-small vessels. A small vessel is an important risk factor for restenosis with BMSs, even in the first generation DESs. The 690 patients with 690 lesions implanted with an EES were enrolled and divided into two groups by vessel reference diameter (RD): >2.5 mm for non-small vessels (Non-S-group) and ≤2.5 mm for small vessels (S-group). Two years later, the 365 patients with no restenosis at 8 months who underwent angiography were enrolled into the late catch-up study. At the initial 8-month follow-up, the rates of restenosis and target lesion revascularization (TLR) of both groups were not significantly different (restenosis 3.9 vs 6.5%, p = 0.17; TLR 3.9 vs 6.5%, p = 0.17). At the late 2-year follow-up, there were no significant differences in the late loss (0.36 ± 0.66 vs 0.34 ± 0.50 mm, p = 0.14), net gain (1.50 ± 0.75 vs 1.26 ± 0.60 mm, p = 0.39), late catch-up restenosis rate (5.1 vs 3.4%, p = 0.38), TLR (4.9 vs 2.7%, p = 0.40), and delayed late loss (0.14 ± 0.58 vs 0.15 ± 0.49 mm, p = 0.10) between both groups. There is no correlation between delayed late loss and RD in all patients( r = −0.009) and in AMI patients ( r = −0.004). These results demonstrate that the initial and late catch-up restenosis rates of small coronary vessels with EES placement were excellent, the same as for non-small coronary vessels. We suggest that involvement of small coronary arteries may not be a risk factor for restenosis and results of stenting for small coronary arteries with EES placement were excellent. [ABSTRACT FROM AUTHOR]

This study aims to explore the effects of tumor necrosis factor alpha-stimulated gene-6 (TSG-6) on vascular inflammatory response and vascular injury in grafted vein wall of rats and its possible mechanism. Vascular grafting model was established by modified cuff. The effect of TSG-6 on the inflammatory response and vascular injury of vein graft was investigated. The activation of mast cells and macrophages after LPS stimulation was observed by lentivirus-mediated upregulation or downregulation of TSG-6 expression. The results showed that rhTSG-6 treatment could significantly inhibit the proliferation of venous bridge, decrease macrophage infiltration and smooth muscle cell proliferation. The expression levels of TNF-α and IL-1 in treated group were significantly lower than that of untreated group ( P < 0.05), while the expression of IL-10 in treated group were significantly higher than that of untreated group ( P < 0.05). The expression levels of P38, p-P38, JNK and p-JNK in venous bridge of rats were significantly lower than those of untreated rats ( P < 0.05), while there was no significant difference in the expression level of ERK and p-ERK ( P > 0.05). TSG-6 could inhibit the proliferation of mast cells and macrophages and the release of inflammatory cytokines by down regulating the expression levels of P38, p-P38, JNK and p-JNK. TSG-6 can inhibit the inflammatory response of transplanted vein grafts in rats and reduce vascular injury by downregulation of P38 and JNK signaling pathway. [ABSTRACT FROM AUTHOR]

Stent placement for treating superficial femoral artery (SFA) lesions has been approved. The Zilver PTX stent, a drug-eluting stent (DES) for treating SFA lesions, has been available in Japan since 2012. However, the penetration rate of this DES has not yet been reported. This prospective multicenter registry study enrolled 314 patients (354 limbs) to be treated by stent placement in 2014 (UMIN000011551). The primary endpoint was the measurement of the penetration rate of the DES. The secondary endpoints were measuring the freedom from restenosis, freedom from target lesion revascularization (TLR), freedom from major adverse limb event (MALE), and the survival rate at 12 months postoperatively. Female patients comprised 28% participants. The mean age was 73.1 ± 9.2 years. A total of 56% patients had diabetes mellitus (DM), 36% patients were receiving hemodialysis, and 30% used cilostazol at baseline. The mean lesion length was 156 ± 101 mm, and the percentage of TASC II C/D lesions was 58%. Critical limb ischemia (CLI) was observed in 32% limbs. The penetration rates of the Zilver PTX stent were only 8%. The primary patency rate was similar between DES and bare-metal stents (BMS) at 12 months postoperatively (77 vs. 84%, p = 0.52). In this study, the rates of freedom from restenosis, freedom from TLR, freedom from MALE, and the survival rate at 12 months postoperatively were 83, 86, 85, and 89%, respectively. The penetration rate of a first-generation DES placement for treating SFA lesions is low in Japan. On the other hand, BMS is well utilized and its primary patency is acceptable. [ABSTRACT FROM AUTHOR]

We compared the expression of signal molecules in the culture of human endothelial cells under normal conditions and in atherosclerosis and restenosis. Expression of connexin-37 and sirtuin-1 in atherosclerosis and restenosis surpassed the normal by 2 and 5 times, respectively, and expression of endothelin-1 3-fold surpassed the normal. In restenosis, changes in the expression connexin-37 and endothelin-1 became more pronounced in comparison with atherosclerosis. Connexin-37 and endothelin-1 can serve as predictive markers for prognosis of post-stenting complications in patients with atherosclerosis. [ABSTRACT FROM AUTHOR]

Although late restenosis is one of the long-term complications of stent implantation, its pathogenesis has not been fully elucidated. For consecutive patients who developed in-stent restenosis (ISR) after stent implantation, integrated backscatter (IB) intravascular ultrasound was performed for ISR lesions. The tissue characteristics of neointima within the stented segment were compared between lesions with early restenosis and those with late restenosis. Of 73 ISR lesions arising after sirolimus-eluting stent (SES; n = 25) or bare-metal stent (BMS; n = 48) implantation, early and late restenosis were documented in 52 and 21 lesions, respectively. A higher prevalence of late restenosis was observed after SES implantation than after BMS implantation (60.0 vs. 12.5 %; p < 0.001). The duration between stent implantation and late restenosis was significantly shorter after SES implantation than after BMS implantation (57.0 ± 22.1 vs. 124.4 ± 19.6 months; p < 0.001). Percent low-IB volume was significantly higher in the neointima of late restenosis than in that of early restenosis (29.9 ± 9.9 vs. 19.8 ± 11.3 %; p < 0.001). Significantly more low-IB tissue was observed in the neointima of late restenosis than in that of early restenosis, suggesting atherosclerotic progression in late phase after stent implantation as a possible mechanism of late restenosis. [ABSTRACT FROM AUTHOR]

Femoropopliteal artery (FPA) mechanics play a paramount role in pathophysiology and the artery's response to therapeutic interventions, but data on FPA mechanical properties are scarce. Our goal was to characterize human FPAs over a wide population to derive a constitutive description of FPA aging to be used for computational modeling. Fresh human FPA specimens ( $$n=579$$ ) were obtained from $$n=351$$ predominantly male (80 %) donors 54±15 years old (range 13-82 years). Morphometric characteristics including radius, wall thickness, opening angle, and longitudinal pre-stretch were recorded. Arteries were subjected to multi-ratio planar biaxial extension to determine constitutive parameters for an invariant-based model accounting for the passive contributions of ground substance, elastin, collagen, and smooth muscle. Nonparametric bootstrapping was used to determine unique sets of material parameters that were used to derive age-group-specific characteristics. Physiologic stress-stretch state was calculated to capture changes with aging. Morphometric and constitutive parameters were derived for seven age groups. Vessel radius, wall thickness, and circumferential opening angle increased with aging, while longitudinal pre-stretch decreased ( $$p<0.01$$ ). Age-group-specific constitutive parameters portrayed orthotropic FPA stiffening, especially in the longitudinal direction. Structural changes in artery wall elastin were associated with reduction of physiologic longitudinal and circumferential stretches and stresses with age. These data and the constitutive description of FPA aging shed new light on our understanding of peripheral arterial disease pathophysiology and arterial aging. Application of this knowledge might improve patient selection for specific treatment modalities in personalized, precision medicine algorithms and could assist in device development for treatment of peripheral artery disease. [ABSTRACT FROM AUTHOR]

Coronary artery disease, caused by the buildup of atherosclerotic plaques in the coronary vessel wall, is one of the leading causes of death in the world. For high-risk patients, coronary artery bypass graft is the preferred treatment. Despite overall excellent patency rates, bypasses may fail due to restenosis. In this context, the purpose of this work was to perform a parametric computational study of the fluid dynamics in patient-specific geometries with the aim of investigating a possible relationship between coronary stenosis degree and risk of graft failure. Firstly, we propose a strategy to prescribe realistic boundary conditions in the absence of measured data, based on an extension of Murray's law to provide the flow division at bifurcations in case of stenotic vessels and non-Newtonian blood rheology. Then, we carry out numerical simulations in three patients affected by severe coronary stenosis and treated with a graft, in which the stenosis degree is virtually varied in order to compare the resulting fluid dynamics in terms of hemodynamic indices potentially involved in restenosis development. Our findings suggest that low degrees of coronary stenosis produce a more disturbed fluid dynamics in the graft, resulting in hemodynamic conditions that may promote a higher risk of graft failure. [ABSTRACT FROM AUTHOR]

The study was carried out in 126 patients with stable angina pectoris, who underwent elective coronary artery stenting with drug-eluting stents and follow-up angiography within 6-12 months thereafter. Five significant risk factors of restenosis were identified by binary comparisons of different variables. The logistic regression equation that included the level of CD45-positive platelets, diabetes, small vessel stenting, number of simultaneously implanted stents in one patient, and lesion length demonstrates the highest level of prediction of in-stent restenosis (OR=22.8; p<0.001). ROC-analysis demonstrated high prognostic value of the logit model (area under ROC curve 0.87, p<0.001). The data suggest that a close relationship exists between the development of restenosis and the level of circulating CD45 platelets. [ABSTRACT FROM AUTHOR]

Aims: Percutaneous coronary intervention (PCI) of bifurcation lesions can be performed using various techniques. The aim of this study was to analyse the outcome of various techniques of bifurcation stenting in all patients undergoing bifurcation stenting at one large intervention centre in 2013, taking into account that more complex lesions might more often warrant a two-stent technique. Methods and results: This retrospective study included 260 consecutive patients who underwent non-primary PCI of a bifurcation lesion at the Catharina Hospital, Eindhoven, in 2013. Patients were classified into two groups: one-stent technique (provisional stenting), and two-stent techniques (culotte, crush and T-stenting). The primary endpoint was the rate of restenosis at 1 year. The secondary endpoints were procedural complications (side branch occlusion, periprocedural infarction, and death) and major adverse cardiac events (MACE) at 1 year. Periprocedural complications occurred in 15 patients (5.8 %) with no difference between the groups ( p = 0.27). After 1 year, restenosis occurred in 3.2 % of the patients in the one-stent technique group and 7.3 % in the two-stent technique group ( p = 0.20). MACE at 1 year did not differ between the groups at 11.9 % and 12.2 % respectively ( p = 1.00). Conclusions: This study shows that there is no significant difference between restenosis rate, or any other outcome parameter, with the different techniques of bifurcation stenting. Since provisional stenting is the simplest, most straightforward and cheapest approach, if technically feasible this technique has our preference as the initial approach, and an upgrade can be considered if the result is insufficient. [ABSTRACT FROM AUTHOR]

Drug-eluting balloons (DEBs) have emerged as a new application in percutaneous coronary intervention. DEBs have proven successful in the treatment of in-stent restenosis, but their role in de novo lesions is less clear. This paper provides a review of the current studies where DEBs have been used in coronary de novo lesions, either as part of a DEB-only strategy or in combination with another device, mainly a bare metal stent (BMS). By searching Pubmed and Embase we were able to identify 52 relevant studies, differing in design, intervention, and clinical setting, including patients with small vessel disease, bifurcation lesions, complex long lesions, acute myocardial infarction, diabetes mellitus, and elderly. In 23 studies, a DEB was combined with a BMS, 25 studies used a DEB-only strategy with only provisional BMS implantation, and four studies combined a DEB with a drug-eluting stent (DES). In the vast majority of studies, DEB in combination with BMS does not seem to improve clinical or angiographic outcome compared with DES, whereas a DEB-only strategy seems promising, especially when predilatation and geographical mismatch are taken into account. A lower risk of recurrent thrombosis with DEB compared with DES is not evident from the current studies. In conclusion, the main indication for DEB seems to be small vessel disease, especially in clinical scenarios in which a contraindication to dual antiplatelet therapy exists. The main approach should be a DEB-only strategy with only provisional bailout stenting, which has shown interesting results in different clinical scenarios. In general, larger randomized controlled studies with prolonged follow-up comparing DEB with best in class DES are warranted. Technical developments of DEBs including the use of different drugs might potentially improve the efficacy of such treatment. [ABSTRACT FROM AUTHOR]

We report a case of a 65-year-old female patient treated with an everolimus-eluting bioresorbable scaffold (BRS) after rotational atherectomy of a severely calcified lesion of the left anterior descending coronary artery. The implanted BRS restenosed 10 months after implantation and was treated with a scoring balloon followed by drug-eluting balloons with good immediate and long-term results. To the best of our knowledge, this is the first report of a balloon-only treatment of a restenosis occurring more than 6 months after BRS implantation; angiographic and optical coherence tomography images after treatment and at two-year follow-up are presented. [ABSTRACT FROM AUTHOR]

We sought to describe the use and outcomes of small, medium and large premounted stents in patients with congenital heart disease, including incidence of and risk factors for re-intervention and development of in-stent stenosis. Premounted stents offer several advantages over traditional manually crimped bare-metal stents, especially in small patients. There are no data describing the medium-term effectiveness and outcomes of premounted stents in congenital heart disease. We performed a single-center retrospective review of all small, medium and large premounted stents implanted over an 8-year period. Premounted stents were implanted in 71 vessels within 59 patients with a 97 % success rate. Regardless of implantation site, premounted stent implantation resulted in significant improvements in vessel size and pressure gradient ( p < 0.0001). Over a median follow-up duration of 3.1 years [interquartile range (IQR) 1.3-5.2], 25 patients (43 %) required re-intervention (18 catheter based, 3 surgical and 4 hybrid) at a median time of 1.4 years (IQR 0.9-3.0) from implant. Factors associated with re-intervention included age ≤1.9 years [hazard ratio (HR) 2.4, p = 0.03], weight ≤11.5 kg (HR 2.5, p = 0.03) and bare-metal premounted stents compared to covered premounted stents (HR 4.2, p = 0.001). In-stent stenosis was diagnosed in 42 % of premounted stents which underwent follow-up angiography. No identified characteristics were associated with in-stent stenosis, including 'oversizing' the premounted stent. Small, medium and large premounted stents are effective in treating vascular stenosis in congenital heart disease. Frequent follow-up is required, especially in smaller patients with expected somatic growth, and to evaluate for in-stent stenosis which occurs in nearly half of premounted stents. [ABSTRACT FROM AUTHOR]

Treatment of in-stent restenosis (ISR) is associated with a high incidence of recurrence. This study evaluated the clinical safety and 6-month efficacy of excimer laser coronary angioplasty (ELCA) before scoring balloon dilatation for the treatment of ISR. Twenty-three patients with ISR were included and treatment strategy of ISR was dependent on each operator. Twelve patients among those were treated with ELCA before scoring balloon dilatation (ELCA group) and 11 patients were treated with scoring balloon alone (non-ELCA group). Acute procedural results were evaluated by quantitative coronary angiography (QCA) and frequency domain optical coherence tomography (FD-OCT). Follow-up angiography was performed in all patients and the incidence of recurrent ISR and target lesion revascularization (TLR) was determined at 6 months after initial ISR treatment. Procedural success was achieved in all patients. Baseline clinical and angiographic characteristics were similar between groups. Maximum dilatation pressure of scoring balloon was significantly lower in the ELCA group than in the non-ELCA group (9.0 ± 3.1 vs. 14.9 ± 4.3 atm, p = 0.001). In follow-up angiography, the occurrence of TLR was similar between groups (16.7 vs. 45.5 %, p = 0.09), but the late luminal loss was significantly lower in the ELCA group (0.7 ± 0.6 vs. 1.3 ± 0.7 mm, p = 0.03). ELCA is a safe and feasible technique for the treatment of ISR and associated with a relatively low recurrent restenosis in comparison with scoring balloon dilatation alone. [ABSTRACT FROM AUTHOR]

To evaluate the feasibility of catheter down sizing for QCA, the reliability of a 4Fr catheter as a calibration device was evaluated. Repeated coronary angiograms of 9 lesions were obtained using 4Fr and 6Fr catheters under otherwise identical conditions. The calibration factor was measured 10 times by 4Fr and 6Fr catheters. QCA measurements including minimal lumen diameter (MLD), interpolated normal reference (Int N), percent diameter stenosis (%DS), and lesion length (LL) were performed by two technicians twice with a 3-month interval. The intraobserver and interobserver variability of each parameter was evaluated using intraclass correlation coefficients (ICCs). Mean of mean SD of calibration factor was significantly larger in 4Fr than in 6Fr in 9 lesions. The mean of mean coefficient of variance was significantly larger in 4Fr catheters vs in 6Fr catheters. A 6Fr catheter showed excellent reliability for both intraobserver and interobserver variability in MLD, Int N, %DS, and LL. In contrast, 4Fr showed that reliability in intraobserver variability depended on the analyst. Although reliability of interobserver variability in Int N measured by the 4Fr catheter was >0.80, the value was less than that by the 6Fr catheter. Taking these results into consideration, 4Fr catheters are less reliable than 6Fr catheters when measuring QCA data especially for follow-up data that need most accurate measurements of MLD and %DS. It would be better to use a 6Fr catheter to evaluate QCA measurements such as acute gain, late loss, restenosis rate, and device size. [ABSTRACT FROM AUTHOR]

Even though drug-coated balloon (DCB) angioplasty has emerged as a treatment option for drug-eluting stent in-stent restenosis (DES-ISR), the most effective treatment strategy for DES-ISR is still under debate. Therefore, we compared long-term clinical outcomes following DCB treatment of DES-ISR with those following 2nd-generation drug-eluting stent (DES) treatment. We identified 248 DES-ISR lesions in 238 patients that were treated with either 2nd-generation DES implantation ( n = 56) or DCB angioplasty ( n = 192). We compared the incidences of major adverse cardiac events (MACEs) in the two groups during the 2-year period following treatment. MACE was defined as cardiac death, non-fatal myocardial infarction, or target-vessel revascularization. The percentage of patients with diabetes and the mean age of patients in the DCB group were greater than in the DES group. The DCB group also had a smaller reference vessel diameter. The DES group had a larger post-intervention minimal luminal diameter. We found no significant difference in the MACE rate between the two groups during the 2 years following treatment (11.0 % in the DCB group vs. 8.9 % in the DES group, p = 0.660). Reference segment diameter was the only independent predictive factor for MACE in the post-treatment period (hazard ratio 0.35, 95 % confidence interval: 0.15-0.82, p = 0.016). Clinical efficacy of DCB angioplasty for treatment of DES-ISR was comparable to that of 2nd-generation DES implantation as measured by the rate of MACEs in the two groups. Reference segment diameter was the only statistically significant independent predictor for MACE in the 2-year period following treatment. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the feasibility and diagnostic accuracy of subtraction CTA on patients with highly calcified coronary artery disease (CAD) or previous implanted stents, in comparison with invasive coronary angiography (ICA).Materials and Methods: Twenty-three patients were recruited. All conventional and subtraction CTA exams were performed using a 320-row CT. Subjective image quality score was assessed for each segment using a 4-point scale: 1-uninterpretable to 4-good image quality.Results: A total of 129 calcified or stented coronary segments were studied. Mean coronary image quality with conventional CTA was 2.73 ± 0.97 and in subtracted CTA 3.3 ± 0.92 (p < 0.01). After metal subtraction, image quality in stented coronary segments with >3 mm of diameter improved from 2.69 ± 0.97 to 3.34 ± 0.89 (p = 0.01) and in those with <3 mm of diameter from 2.11 ± 0.78 to 2.67 ± 0.87 (p = 0.17). There was an improvement in diagnostic accuracy to detect ICA stenosis >50 % by subtraction CTA compared with conventional CTA (AUC 0.93 to 0.87; p = 0.02).Conclusion: Subtraction CTA is promising in overcoming limitations of conventional CTA due to calcium or metal artefacts, especially if no motion artefact is present or when stents > 3 mm are studied.Key Points: • Calcium and metal artefacts are still a limitation for conventional coronary CTA • Diagnostic accuracy is improved by subtraction as compared with conventional CTA • Subtraction CTA is a promising tool to overcome limitations of conventional CTA. [ABSTRACT FROM AUTHOR]

The measurement of high-density lipoprotein (HDL) functionality could be useful for identifying patients who have an increased risk of coronary restenosis after stent implantation. In the present study, we elucidates whether HDL functionality can predict restenosis. The participants included 48 consecutive patients who had stable angina and were successfully implanted with a drug-eluting stent (DES) or bare-metal stent. Follow-up coronary angiography was performed after 6-8 months of stenting. Cholesterol efflux and the anti-inflammatory capacity of HDL were measured before stenting (at baseline) and at follow-up. The mean age was 64 ± 11 years and the body mass index was 24 ± 3 kg/m. While HDL cholesterol (HDL-C) significantly increased from baseline to follow-up, there was no significant association between HDL-C level at baseline and in-stent late loss. Cholesterol efflux capacity was significantly increased from baseline to follow-up. The efflux capacity at baseline was negatively correlated with in-stent late loss, whereas the anti-oxidative activity of HDL at baseline was not associated with in-stent late loss. We analyzed the predictors of in-stent late loss using independent variables (efflux capacity and anti-oxidative capacity at baseline in addition to age, gender, HDL-C and low-density lipoprotein cholesterol at baseline, hypertension, diabetes mellitus, smoking, lesion length and DES implantation, history of myocardial infarction and prior percutaneous coronary intervention) by a multiple regression analysis. The efflux capacity at baseline was only independently associated with in-stent late loss. In conclusion, cholesterol efflux capacity at baseline could predict coronary restenosis in patients with successful stent implantation. [ABSTRACT FROM AUTHOR]

A 70-year-old man underwent stent implantation for right coronary artery (RCA) lesions with a bare metal stent (BMS) and two sirolimus-eluting stents (SES). However, as both the BMS and SES stented sites developed restenosis after 13 months, he underwent target lesion revascularization using directional coronary atherectomy (DCA). On histopathology, the restenosis lesion at the SES-deployed site showed greater inflammation and less re-endothelialization than that at the BMS-deployed site. Three months later, the SES-deployed site developed a second restenosis, in which paclitaxel-eluting stents (PES) were implanted (PES-in-SES), while the BMS-deployed site was restenosis free. Five years later, restenosis was absent in these RCA lesions. However, by optical coherence tomography and/or coronary angioscopy, the PES-in-SES site in the RCA showed poor neointimal coverage over the stent struts and yellowish neointima, suggesting lipid-rich neoatheroma formation, whereas at the BMS site appropriate white neointima formation was observed. Drug-eluting stents still have problems of persistent inflammation, inappropriate neointima formation, and neoatherosclerosis. Although we are now in the era of second generation DESs in which better stent performance would be promising, we should remember that we are obliged to continue to follow-up all patients in whom first generation DESs such as SES or PES have been placed. [ABSTRACT FROM AUTHOR]

Although drug-eluting stents (DES) for percutaneous coronary intervention (PCI) have dramatically reduced the incidence of in-stent restenosis, their deployment for large-size coronary lesions is still controversial because of problems such as late in-stent thrombosis and late catch-up in DES. We aimed to evaluate the long-term outcome beyond 2 years of bare metal stents (BMS) as compared with DES in large vessels. Consecutive 228 patients who underwent PCI with large-size stents (>3.5 mm in diameter) in our hospital were enrolled in this study. The end points of this study are target lesion revascularization (TLR) and occurrence of major adverse cardiac events (MACE) for subject patients. We analyzed 183 patients (152 men, mean age 65.8 ± 10.5 years) whose outcome could be followed up for at least 2 years. At the first 8-month follow-up, clinically driven TLR rate was significantly higher in patients who received BMS than those who received DES (17.2 vs. 2.2 %, p < 0.05), although the rate of TLR was not different between the 2 groups beyond 8 months. Thus, overall rate of TLR was higher in BMS than in DES (22.7 vs. 5.4 %, p < 0.05). Under these conditions, the higher rate of TLR for BMS was observed in simple as well as complex lesions with or without diabetes, although there were no significant differences in MACE between BMS and DES. Multivariate analysis showed that BMS was an only independent factor of TLR at the 8 month follow-up period [ p = 0.004, odds ratio 9.58, 95 % confidence interval (2.10-43.8)]. These results demonstrate that the rate of in-stent restenosis in large-size coronary lesions was transiently higher in the first 8 months for patients implanted with BMS compared with DES in which no in-stent thrombosis and TLR beyond 2 years were observed. We suggest using the DES even in large-size coronary lesions in terms of short- and long-term outcomes. [ABSTRACT FROM AUTHOR]

Drug eluting stents (DES) have shown efficacy in reducing restenosis after angioplasty followed by application of a coronary stent. However, polymer matrices typically used for immobilizing drugs on the stent surface may cause irritation and have limited drug loading capacity. In contrast, drug loading into micro- or nanopores created within the stent material could avoid these problems. We present a technology based on electrochemically induced pitting corrosion to form pores in medical grade steel, followed by loading with rapamycin. This process is applied to pore formation and drug loading in coronary stents consisting of L605 medical steel. Sustained release of the drug over 28 days at rates comparable to established DES was demonstrated. This technology is capable of creating pores with well-defined pore size and filling of these pores by a drug employing a crystallization process thus completely avoiding polymer matrices to immobilize drugs. Electrochemically induced pitting corrosion provides a generic means to introduce micro-pores suitable as drug reservoirs into medical grade steel without the need for any further matrix material. Further research will expand these findings to other materials and types of implants that could benefit from the additional function of drug release and/or improved implant/tissue integration. [ABSTRACT FROM AUTHOR]

Development of functional nanoparticles can be encumbered by unanticipated material properties and biological events, which can affect nanoparticle effectiveness in complex, physiologically relevant systems. Despite the advances in bottom-up nanoengineering and surface chemistry, reductionist functionalization approaches remain inadequate in replicating the complex interfaces present in nature and cannot avoid exposure of foreign materials. Here we report on the preparation of polymeric nanoparticles enclosed in the plasma membrane of human platelets, which are a unique population of cellular fragments that adhere to a variety of disease-relevant substrates. The resulting nanoparticles possess a right-side-out unilamellar membrane coating functionalized with immunomodulatory and adhesion antigens associated with platelets. Compared to uncoated particles, the platelet membrane-cloaked nanoparticles have reduced cellular uptake by macrophage-like cells and lack particle-induced complement activation in autologous human plasma. The cloaked nanoparticles also display platelet-mimicking properties such as selective adhesion to damaged human and rodent vasculatures as well as enhanced binding to platelet-adhering pathogens. In an experimental rat model of coronary restenosis and a mouse model of systemic bacterial infection, docetaxel and vancomycin, respectively, show enhanced therapeutic efficacy when delivered by the platelet-mimetic nanoparticles. The multifaceted biointerfacing enabled by the platelet membrane cloaking method provides a new approach in developing functional nanoparticles for disease-targeted delivery. [ABSTRACT FROM AUTHOR]