Search

To investigate the effect of heart rate and virtual monoenergetic image (VMI) on coronary stent imaging in dual-source photon-counting detector computed tomography (PCD-CT). A dynamic cardiac phantom was used to vary the heart rate at 50 beats per minute (bpm), 70 bpm, and 90 bpm. Five types of stents (4.0 mm, 3.5 mm, 3.0 mm, 2.75 mm, and 2.5 mm diameter) were scanned at three different locations and reconstructed VMI at 70 keV. In addition, 50% stenosis was assessed for 3.0 mm and 4.0 mm stents. To assess in-stent stenosis, 40 keV, 70 keV, and 100 keV images were compared. Measurable lumen and contrast to noise ratio (CNR) from lumen to stenosis were evaluated quantitatively. A-4-point scale was used for the qualitative image quality of in-stent stenosis. The measurable lumen had no significant differences among heart rates in patent stents (p = 0.55). In-stent stenosis, the residual lumen was significantly larger in 40 keV [27.5% (20.8-32.3%)] than in 70 keV [11.5% (10.0-23.0%), p < 0.05] and 100 keV [0% (0-5.2%), p < 0.05]. The CNR was higher in 40 keV [12.5 (7.5-18.2)] than in 70 keV [5.3 (2.9-7.7), p < 0.05] and 100 keV [1.3 (0.5-2.7), p < 0.05]. The image quality was better in 40 keV (3.4 ± 0.7) than in 70 keV [(2.6 ± 0.8), p < 0.05] and 100 keV [(1.3 ± 0.4), p < 0.05]. Dual-source PCD-CT maintains a measurable lumen even at high heart rates. Adjusting the VMI can be helpful in visualizing the in-stent stenosis., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Cluster of differentiation 47 (CD47) plays an important role in the pathophysiology of various diseases including atherosclerosis but its role in neointimal hyperplasia which contributes to restenosis has not been studied. Using molecular approaches in combination with a mouse vascular endothelial denudation model, we studied the role of CD47 in injury-induced neointimal hyperplasia. We determined that thrombin-induced CD47 expression both in human aortic smooth muscle cells (HASMCs) and mouse aortic smooth muscle cells. In exploring the mechanisms, we found that the protease-activated receptor 1-Gα protein q/11 (Gαq/11)-phospholipase Cβ3-nuclear factor of activated T cells c1 signaling axis regulates thrombin-induced CD47 expression in HASMCs. Depletion of CD47 levels using its siRNA or interference of its function by its blocking antibody (bAb) blunted thrombin-induced migration and proliferation of HASMCs and mouse aortic smooth muscle cells. In addition, we found that thrombin-induced HASMC migration requires CD47 interaction with integrin β3. On the other hand, thrombin-induced HASMC proliferation was dependent on CD47's role in nuclear export and degradation of cyclin-dependent kinase-interacting protein 1. In addition, suppression of CD47 function by its bAb rescued HASMC efferocytosis from inhibition by thrombin. We also found that vascular injury induces CD47 expression in intimal SMCs and that inhibition of CD47 function by its bAb, while alleviating injury-induced inhibition of SMC efferocytosis, attenuated SMC migration, and proliferation resulting in reduced neointima formation. Thus, these findings reveal a pathological role for CD47 in neointimal hyperplasia., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Limited data are available on long-term outcomes and health status in the treatment of in-stent coronary chronic total occlusion (IS-CTO) and de novo coronary chronic total occlusion (de novo CTO). This study compared the long-term clinical outcomes and health status of percutaneous coronary intervention (PCI) for patients with IS-CTO versus patients with de novo CTO in the drug-eluting stent era. We screened 483 consecutive patients with 1 CTO lesion, including 81 patients with IS-CTO and 402 patients with de novo CTO. Propensity score matching was used to balance baseline characteristics between the 2 groups. The clinical end point was major adverse cardiac events (MACE). The success rates of CTO lesion revascularization were similar in both groups. In the propensity score-matched patients, after a median follow-up of 36 months, MACE was observed in 32.8% of patients with IS-CTO versus 13.5% of the patients with de novo CTO ( P < .001), mainly driven by target-vessel revascularization (21.9% vs 6.7%; P < .01). Moreover, patients with IS-CTO had significantly worse Seattle Angina Questionnaire anginal stability scores than the patients with de novo CTO. In conclusion, patients with IS-CTO after PCI had a worse clinical outcome, mainly MACE, and a poorer anginal stability in the long term than patients with de novo CTO.

Abstract: Atherosclerosis remains a leading cause of morbidity and mortality, with revascularization remaining a cornerstone of management. Conventional revascularization modalities remain challenged by target vessel reocclusion-an event driven by mechanical, thrombotic, and proliferative processes. Despite considerable advancements, restenosis remains the focus of ongoing research. Adjunctive agents, including dipyridamole, offer a multitude of effects that may improve vascular homeostasis. We sought to quantify the potential therapeutic impact of dipyridamole on vascular occlusion. We performed a literature search (EMBASE and MEDLINE) examining studies that encompassed 3 areas: (1) one of the designated medical therapies applied in (2) the setting of a vascular intervention with (3) an outcome including vascular occlusion rates and/or quantification of neointimal proliferation/restenosis. The primary outcome was vascular occlusion rates. The secondary outcome was the degree of restenosis by neointimal quantification. Both human and animal studies were included in this translational analysis. There were 6,839 articles screened, from which 73 studies were included, encompassing 16,146 vessels followed up for a mean of 327.3 days (range 7-3650 days). Preclinical studies demonstrate that dipyridamole results in reduced vascular occlusion rates {24.9% vs. 48.8%, risk ratio 0.53 [95% confidence interval (CI) 0.40-0.70], I2 = 39%, P < 0.00001}, owing to diminished neointimal proliferation [standardized mean differences -1.13 (95% CI -1.74 to -0.53), I2 = 91%, P = 0.0002]. Clinical studies similarly demonstrated reduced occlusion rates with dipyridamole therapy [23.5% vs. 31.0%, risk ratio 0.77 (95% CI 0.67-0.88), I2 = 84%, P < 0.0001]. Dipyridamole may improve post-intervention vascular patency and mitigate restenosis. Dedicated studies are warranted to delineate its role as an adjunctive agent after revascularization., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The inflammatory events related to prostaglandins may play an important role in the progression of vessel stenosis. The aim of this study was to investigate the monocyte PTGES and 15-PGDH gene expression levels and the serum 13,14-dihyro-15-keto-PGF2α value involved in PGE2 metabolism in patients with coronary artery stenosis and restenosis. Moreover, the effects of miR-520, miR-1297 and miR-34 were studied on the gene expression levels. A total of sixty subjects referred for coronary angiography including healthy controls (stenosis <5%), subjects with stent no restenosis) SNR, stenosis <5%) and subjects in stent restenosis (ISR, restenosis >70%) were participated in the study. The gene expression levels and the serum 13,14-dihyro-15-keto- PGF2α value were measured by RT-qPCR and ELISA techniques, respectively. Moreover, the effects of miRNAs on the gene expression levels were investigated by the monocyte transfection of miR/PEI complexes. The PTGES and 15-PGDH gene expression levels and serum 13,14-dihyro-15-keto- PGF2α value increased significantly (P <0.05). Based on the miR-520 and miR-34 expression levels, the miR/PEI transfection studies were confirmed significantly the gene expression changes. The monocyte PGE2 synthesis pathway is actively considered in the SNR and ISR patients and might be related to miR-34 and miR-520 functions., (Copyright © 2020. Published by Elsevier B.V.)

Background: Evidence shows that long-stranded non-coding RNA (LncRNA) can predict coronary artery restenosis in patients suffering from coronary heart disease after percutaneous coronary intervention, suggesting that LncRNA may become a promising biomarker for the diagnosis of coronary artery restenosis after percutaneous coronary intervention. However, its accuracy has not been systematically evaluated. Therefore, it is necessary to perform meta-analysis to certify the diagnostic value of LncRNA on coronary artery restenosis after percutaneous coronary intervention., Methods: PubMed, EMBASE, Cochrane Library, and Web of Science were searched for relevant studies to explore the potential diagnostic values of LncRNA on coronary artery restenosis after percutaneous coronary intervention from inception to December 2020. Data were extracted by two experienced researchers independently. The risk of bias about the meta-analysis was confirmed by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Data was synthesized and heterogeneity was investigated as well. All of the above statistical analysis was carried out with Stata 14.0., Results: This study proved the pooled diagnostic performance of LncRNA on coronary artery restenosis after percutaneous coronary intervention., Conclusion: This study clarified confusions about the specificity and sensitivity of LncRNA on coronary artery restenosis after percutaneous coronary intervention, thus further guiding their promotion and application., Ethics and Dissemination: Ethical approval is not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms. This review would be disseminated in a peer-reviewed journal or conference presentations., Osf Registration Number: DOI 10.17605/OSF.IO/4QT2P., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Although the coronary arteries are uniformly exposed to systemic cardiovascular risk factors, atherosclerosis development has a non-random distribution, which follows the local mechanical stresses including flow-related hemodynamic forces. Among these, wall shear stress plays an essential role and it represents the major flow-related factor affecting the distribution of atherosclerosis in coronary bifurcations. Furthermore, an emerging body of evidence suggests that hemodynamic factors such as low and oscillating wall shear stress may facilitate the development of in-stent restenosis and stent thrombosis after successful drug-eluting stent implantation. Drug-eluting stent implantation represents the gold standard for bifurcation interventions. In this specific setting of interventions on bifurcated lesions, the impact of fluid dynamics is expected to play a major role and constitutes substantial opportunity for future technical improvement. In the present review, available data is summarized regarding the role of local fluid dynamics in the clinical outcome of patients with bifurcated lesions.

Background: To explore the clinical benefits of revascularization in patients with different levels of left ventricular ejection fraction (LVEF) from the perspective of quantitative flow ratio (QFR)., Methods: Patients who underwent successful percutaneous coronary intervention (PCI) and one-year angiographic follow-up were retrospectively screened and computed by QFR analysis. Based on their LVEF, 301 eligible patients were classified into reduced LVEF (≤ 50%, n = 48) and normal LVEF (> 50%, n = 253) groups. Pre-PCI QFR, post-PCI QFR, follow-up QFR, late lumen loss (LLL), LVEF and major adverse cardiovascular and cerebrovascular events (MACCEs) at one year were compared between groups., Results: The reduced LVEF group had a lower mean pre-PCI QFR than the normal LVEF group (0.67 ± 0.16 vs. 0.73 ± 0.15, p = 0.004), but no significant difference was found in the post-PCI or one-year follow-up QFR. No association was found between LVEF and QFR at pre-PCI or follow-up. The reduced LVEF group had greater increases in QFR (0.27 ± 0.18 vs. 0.22 ± 0.15, p = 0.043) and LVEF (6.05 ± 9.45% vs. - 0.37 ± 8.11%, p < 0.001) than the normal LVEF group. The LLL results showed no difference between the two groups, indicating a similar degree of restenosis. The reduced LVEF group had a higher incidence of MACCEs (14.6% vs. 4.3%, p = 0.016), which was mainly due to the higher risk of heart failure (6.3% vs. 0%, p = 0.004)., Conclusion: Compared to the corresponding normal LVEF patients, patients with reduced LVEF who underwent successful PCI were reported to have greater increases in QFR and LVEF, a similar degree of restenosis, and a higher incidence of MACCEs due to a higher risk of heart failure. It seems that patients with reduced LVEF gain more coronary benefits from successful revascularization from the perspective of flow physiology evaluations.

Development and application of advanced mechanical models of soft tissues and their growth represent one of the main directions in modern mechanics of solids. Such models are increasingly used to deal with complex biomedical problems. Prediction of in-stent restenosis for patients treated with coronary stents remains a highly challenging task. Using a finite element method, this paper presents a mechanistic approach to evaluate the development of in-stent restenosis in an artery following stent implantation. Hyperelastic models with damage, verified with experimental results, are used to describe the level of tissue damage in arterial layers and plaque caused by such intervention. A tissue-growth model, associated with vessel damage, is adopted to describe the growth behaviour of a media layer after stent implantation. Narrowing of lumen diameter with time is used to quantify the development of in-stent restenosis in the vessel after stenting. It is demonstrated that stent designs and materials strongly affect the stenting-induced damage in the media layer and the subsequent development of in-stent restenosis. The larger the artery expansion achieved during balloon inflation, the higher the damage introduced to the media layer, leading to an increased level of in-stent restenosis. In addition, the development of in-stent restenosis is directly correlated with the artery expansion during the stent deployment. The correlation is further used to predict the effect of a complex clinical procedure, such as stent overlapping, on the level of in-stent restenosis developed after percutaneous coronary intervention.

Purpose: As the promoter of the stent expansion, the balloon plays a very important role, offering a strong influence on the deployment process. Balloon-artery interaction is pointed as a probable cause of restenosis, stressing the relevance of balloon modeling when simulating the stenting procedure. In this work, an in-silico study of the balloon modeling strategies is performed., Methods: Ultrasonic-microcasting is a novel technology that allows obtaining stents manufactured in magnesium alloys, being suggested as a promising solution. However, this technique demands superior stent strut thickness, which may have an impact on the stent deployment procedure. The influence of the balloon modeling is studied through the simulation of different balloon geometries (open- or taper-ended) and material constitutive model (linear elastic or hyperelastic) on the expanded configuration of a stent manufactured through ultrasonic-microcasting., Results: The results obtained suggest that the choice of balloon type has small impact in terms of demanded pressure to inflate the balloon and in the stent final radius achieved at fully-expanded configuration. Additionally, it was proved that the balloon-type influences the stent expanded profile along its length and diameter as a result of the different deformation behavior exhibited by the balloon., Conclusion: The hyperelastic taper-ended balloon suggests being the model that better correlates with both experimental and clinical results regarding the expanded balloon profile during the procedure.

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 × 10 5 vs. 9.2 × 10 5 ). 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.

Background: Percutaneous coronary intervention represents the most important treatment modality of coronary artery stenosis. In-stent restenosis (ISR) is still a limitation for the long-term outcome despite the introduction of drug eluting stents. It has been shown that adipokines directly influence vessel wall homeostasis by influencing the function of endothelial cells and arterial smooth muscle cells. Visceral adipose tissue-derived serpin vaspin was recently identified as a member of serine protease inhibitor family and serveral studies could demonstrate a relation to metabolic diseases. The aim of this study was to investigate a role of vaspin in the development of in-stent restenosis in vivo and on migration of smooth muscle cells and endothelial cells in vitro., Methods: We studied 85 patients with stable coronary artery disease who underwent elective and successful PCI with implatation of drug eluting stents. Blood samples were taken directly before PCI. Vaspin plasma levels were measured by specific ELISA. ISR was evaluated eight months later by coronary angiography. Human coronary artery smooth muscle cells (HCASMC) and human umbilical vein endothelial cells (HUVEC) migration was analyzed by an in-vitro migration assay with different concentrations (0.004ng/mL up to 40ng/mL) of vaspin as well as by an scratch assay. For proliferation an impedance measurement with specialiced E-Plates was performed., Results: During the follow up period, 14 patients developed ISR. Patients with ISR had significantly lower vaspin plasma levels compared to patients without ISR (0.213 ng/ml vs 0.382 ng/ml; p = 0.001). In patients with plasma vaspin levels above 1.35 ng/ml we could not observe any restenosis. There was also a significant correlation of plasma vaspin levels and late lumen loss in the stented coronary segments. Further we could demonstrate that vaspin nearly abolishes serum induced migration of HCASMC (100% vs. 9%; p<0.001) in a biphasic manner but not migration of HUVEC. Proliferation of HCASMC and HUVEC was not modulated by vaspin treatment., Conclusion: We were able to show that the adipokine vaspin selectively inhibits human coronary SMC migration in vitro and has no effect on HUVEC migration. Vaspin had no effect on proliferation of HUVEC which is an important process of the healing of the stented vessel. In addition, the occurrence of ISR after PCI with implantation of drug eluting stents was significantly associated with low vaspin plasma levels before intervention. Determination of vaspin plasma levels before PCI might be helpful in the identification of patients with high risk for development of ISR after stent implantation. In addition, the selective effects of vaspin on smooth muscle cell migration could potentially be used to reduce ISR without inhibition of re-endothelialization of the stented segment., Competing Interests: The authors have declared that no competing interests exist.

Endothelial dysfunction (EnD) is a hallmark feature of coronary artery disease (CAD), representing the key early step of atherosclerotic plaque development and progression. Percutaneous coronary intervention (PCI) is performed daily worldwide to treat symptomatic CAD, however a consistent proportion of patients remain symptomatic for angina despite otherwise successful revascularization. EnD plays a central role in the mechanisms of post-PCI angina, as it is strictly associated with both structural and functional abnormalities in the coronary arteries that may persist, or even accentuate, following PCI. The assessment of endothelial function in patients undergoing PCI might help to identify those patients at higher risk of future cardiovascular events and recurrent/persistent angina who might therefore benefit more from an intensive treatment. In this review, we address the role of EnD in determining angina after PCI, discussing its pathophysiological mechanisms, diagnostic approaches and therapeutic perspectives., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: The goal of this study was to assess the diagnostic performance of coronary computed tomography angiography (CTA) alone, adenosine-stress myocardial perfusion assessed by computed tomography (CTP) alone, and coronary CTA + CTP by using a 16-cm Z-axis coverage scanner versus invasive coronary angiography (ICA) and fractional flow reserve (FFR) as the clinical standard., Background: Diagnostic performance of coronary CTA for in-stent restenosis detection is still challenging. Recently, CTP showed additional diagnostic power over coronary CTA in patients with suspected coronary artery disease. However, few data are available on CTP performance in patients with previous stent implantation., Methods: Consecutive stable patients with previous coronary stenting referred for ICA were enrolled. All patients underwent stress myocardial CTP and rest CTP + coronary CTA. Invasive FFR was performed during ICA when clinically indicated. The diagnostic rate and diagnostic accuracy of coronary CTA, CTP, and coronary CTA + CTP were evaluated in stent-, territory-, and patient-based analyses., Results: In the 150 enrolled patients (132 men; mean age 65.1 ± 9.1 years), the CTP diagnostic rate was significantly higher than that of coronary CTA in all analyses (territory based [96.7% vs. 91.1%; p < 0.0001] and patient based [96% vs. 68%; p < 0.0001]). When ICA was used as gold standard, CTP diagnostic accuracy was significantly higher than that of coronary CTA in all analyses (territory based [92.1% vs. 85.5%, p < 0.03] and patient based [86.7% vs. 76.7%, p < 0.03]). The concordant coronary CTA + CTP assessment exhibited the highest diagnostic accuracy values versus ICA (95.8% in the territory-based analysis). The diagnostic accuracy of CTP was significantly higher than that of coronary CTA (75% vs. 30.5%; p < 0.001). The radiation exposure of coronary CTA + CTP was 4.15 ± 1.5 mSv., Conclusions: In patients with coronary stents, CTP significantly improved the diagnostic rate and accuracy of coronary CTA alone compared with both ICA and invasive FFR as gold standard., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Coronary artery disease (CAD) remains one of the most important causes of morbidity and mortality worldwide, and the availability of percutaneous or surgical revascularization procedures significantly improves survival. However, both strategies are daunted by complications which limit long-term effectiveness. In-stent restenosis (ISR) is a major drawback for intracoronary stenting, while graft failure is the limiting factor for coronary artery bypass graft surgery (CABG), especially using veins. Conversely, internal thoracic artery (ITA) is known to maintain long-term patency in CABG. Understanding the biology and pathophysiology of ISR and vein graft failure (VGF) and mechanisms behind ITA resistance to failure is crucial to combat these complications in CAD treatment. This review intends to provide an overview of the biological mechanisms underlying stent and VGF and of the potential therapeutic strategy to prevent these complications. Interestingly, despite being different modalities of revascularization, mechanisms of failure of stent and saphenous vein grafts are very similar from the biological standpoint., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objective: This study aimed to compare the effectiveness of drug-coated balloons (DCB) with everolimus-eluting stents (EES) in the treatment of in-stent restenosis (ISR) and the differential relative effect of DCB in patients with drug-eluting stents (DES)-ISR and bare metal stents (BMS)-ISR., Background: The efficiency and safety of DCB and EES need to be assessed for the treatment of ISR., Methods: A systematic literature search was conducted using PubMed and EMBASE to identify all relevant studies. Angiographic results and clinical events were separately assessed. Subgroup meta-analyses were performed according to the type of restenosed stent., Results: Six randomized trials with 1134 patients were included. The overall pooled outcomes indicated that DCB was associated with lower minimum lumen diameter (mean difference ( MD ) = -0.17, 95% CI  = -0.29 to -0.05, P = 0.006) and higher target lesion revascularization (risk ratio ( RR ) = 2.38, 95% CI  = 1.36 to 4.18, P = 0.002) than EES. However, the subgroup meta-analyses showed that DCB was inferior to EES only in DES-ISR patients, with lower minimum lumen diameter ( MD = -0.25, 95% CI  = -0.37 to -0.14, P < 0.001), higher percent diameter stenosis ( MD = 5.37, 95% CI  = 1.33 to 9.42, P = 0.009), more binary restenosis ( RR = 2.07, 95% CI  = 1.20 to 3.58, P = 0.009), and higher incidence of target vessel revascularization ( RR = 2.07, 95% CI  = 1.22 to 3.50, P = 0.007) and target lesion revascularization ( RR = 2.43, 95% CI  = 1.28 to 4.22, P = 0.002). No differences in angiographic results and clinical events were found between DCB and EES in BMS-ISR patients., Conclusions: DCB was inferior to EES in DES-ISR and comparable in BMS-ISR in terms of angiographic results and clinical events., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Nina Peng et al.)

Purpose: In-stent restenosis (ISR) is related to local haemodynamics in the arteries after stent intervention. However, the haemodynamics of stents implanted into tapered vessels is rarely studied and remains unclear. This study aimed to study the haemodynamic performance of a stent in a tapered artery to reveal the haemodynamic differences between tapered and cylindrical stents after stent implantation and guide the stent selection for the treatment of coronary artery stenosis., Methods: Cylindrical and tapered stents were implanted into the tapered arteries. A model of a cylindrical stent implanted into a cylindrical artery was established as the contrast model. Using the finite element method, the flow velocity and wall shear stress distribution of the three models were compared., Results: At t 1 , t 2 , t 3 and t 4 , the flow rate of the tapered artery with tapered stents (TT) after the implantation increased by 8.59, 3.80, 12.81 and 3.66%, respectively. In addition, the wall shear stress in the tapered arteries of TT was 23.48, 36.67, 13.00 and 8.06% higher than that of the tapered arteries with cylindrical stents (TC)., Conclusions: The implantation of a tapered stent in the tapered artery can effectively improve intravascular haemodynamics. The tapered stent allows the tapered artery to obtain better haemodynamics and reduces the probability of ISR.

Endovascular therapy in patients suffering from peripheral arterial disease shows high rates of restenosis. The poor clinical outcomes are commonly explained by the demanding mechanical environment due to leg movements, but the mechanisms responsible for restenosis remain unknown. In this study, we hypothesized that restenosis following revascularization is associated with hemodynamical markers derived from blood flow during leg flexion. Therefore, we performed personalized computational fluid dynamics (CFD) analyses of 20 patients, who underwent routine endovascular femoro-popliteal interventions. The CFD analyses were conducted using 3D models of the arterial geometry in straight and flexed positions, which were reconstructed from 2D angiographic images. Based on restenosis rates reported at 6-month follow-up, logistic regression analyses were performed to predict restenosis from hemodynamical parameters. Results showed that severe arterial deformations, such as kinking, induced by leg flexion in stented arteries led to adverse hemodynamic conditions that may trigger restenosis. A logistic regression analysis based solely on hemodynamical markers had an accuracy of 75%, which showed that flow parameters are sufficient to predict restenosis (p = 0.031). However, better predictions were achieved by adding the treatment method in the model. This suggests that a more accurate image acquisition technique is required to capture the localized modifications of blood flow following intervention, especially around the stented artery. This approach, based on the immediate postoperative configuration of the artery, has the potential to identify patients at increased risk of restenosis. Based on this information, clinicians could take preventive measures and more closely follow these patients to avoid complications.

Background: Fractional flow reserve derived from computed tomography (FFRct) has shown higher accuracy for detection of significant coronary artery disease (CAD) compared to coronary computed tomography angiography (CCTA). The performance of a combined comprehensive qualitative interpretation of both CCTA and FFRct in patient management is unknown. We aimed to explore the clinical application of this combined approach., Methods: We retrospectively reviewed cases referred to FFRct testing at our institution over a one-year period. Patients had documentation of whether invasive coronary angiography (ICA) was performed and revascularization were needed. Interpretations and recommendations of the adopted comprehensive approach (C-FFRct), that took into account focal versus diffuse disease, depth of ischemia and myocardium at risk, were compared to those of CCTA (binary > 50% stenosis) alone and FFRct binary approach (FFRct ≤ 0.8). C-FFRct performance was measured against the decision made upon revascularization., Results: A total of 207 cases were referred to FFRct testing, 163 (79%) accepted and 44 (21%) rejected for quality. C-FFRct changed interpretations and recommendations of 39 (24%) and 14 (9%) CCTA and FFRct, respectively. ICA was deferred in 32 (59%) and 13 (32%) cases; whereas ICA referral rate was 7 (6%) and 1 (0.8%) cases, based on CCTA and FFRct, respectively. No major cardiac events were observed during follow up time (median = 6 months). C-FFRct sensitivity, specificity, and accuracy compared to decision upon revascularization were 89%, 79% and 82%. C-FFRct number needed to treat was 4, and 6, compared to CCTA and FFRct, respectively., Conclusion: FFRct is a feasible tool to improve the diagnostic performance of CCTA in CAD real-world workup. However, qualitative interpretation of the FFRct report combined with CCTA findings may yield more impactful results on patient management. Further prospective studies are warranted to validate the application of this approach and better define its components., (Copyright © 2019. Published by Elsevier Inc.)

Longitudinal stent deformation is a recognized complication of coronary angioplasty; however, it is difficult to detect angiographically. This case illustrates the value of OCT to identify and correctly diagnose longitudinal stent deformation.

Background: Percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) usually involves multiple overlapping stents implantation to cover long coronary segments. A higher rate of restenosis has been described with stent overlapping. Recently, new long tapered stents emerged as a potential tool for treating long coronary lesions. Feasibility of using these new devices for the CTO PCI has not been described. The aim of this work was to describe our initial experience with 50 and 60 mm-long tapered sirolimus-eluting stents (SES) in CTO PCI., Methods: We included 54 consecutive patients who underwent a CTO PCI and in whom an attempt to implant a 50 or 60 mm-long tapered SES was performed. Baseline clinical, angiographic, and procedural characteristics were recorded., Results: The median (IQR) age was 64 (58-73) years, and 45 (83.3%) patients were male. The tapered SES 50 and 60 mm-long was successfully implanted in 51 (94.4%) patients. In three patients, a 60 mm-long stent could not be implanted, and two or three overlapped shorter drug-eluting stents were deployed instead. An average of 1.4 ± 0.6 stents per patient was implanted. A single stent was deployed in 32 (59.3%) patients. During a median follow-up of 330 (149-551) days, repeat PCI in the target vessel was performed in two patients., Conclusions: The use of the new BioMime Morph™ tapered SES for the treatment of CTO appears to be feasible in a high proportion of procedures. Further studies confirming the feasibility of this approach and its potential clinical advantages are needed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Everolimus-eluting stent (EES) is effective for treating in-stent restenosis (ISR). However, the long-term incidence of target lesion revascularization (TLR) is unknown. Further, the role of post-intervention minimal stent area (MSA) measured by intravascular ultrasound (IVUS) in TLR is unknown in this setting., Patients and Methods: Overall, 223 ISR lesions (192 patients) that were treated with EES between 2010 and 2016 were analyzed retrospectively. Lesions were divided into two groups according to the post-intervention MSA [ ≤ 5.3 mm: 72 lesions (67 patients), and > 5.3 mm: 151 lesions (138 patients)]. The cut-off point was determined on the basis of receiver operating characteristic curve analysis., Results: The cumulative 5-year incidence of TLR was significantly higher in the group with MSA of 5.3 mm or less than in the group with MSA more than 5.3 mm (15.8 and 7.2%, P = 0.01). After adjusting for confounders, the excess risk of the group with MSA of 5.3 mm or less relative to the group with MSA more than 5.3 mm for TLR remained significant [hazard ratio: 3.07, 95% confidence interval (CI): 1.17-8.51, P = 0.02]. Using multivariate logistic regression analysis, we identified female sex (odds ratio: 2.39, 95% CI: 1.06-5.49, P = 0.04) and stent size of 3.0 mm or less (odds ratio: 13.43, 95% CI: 6.23-32.38, P < 0.0001) as independent predictors of MSA of 5.3 mm or less., Conclusion: EES implantation for ISR was associated with an acceptable rate of TLR through long-term follow-up. Postintervention MSA of 5.3 mm or less was associated independently with a higher risk for TLR.

Objectives: Individual randomized trials comparing drug-eluting balloons (DEB) versus everolimus-eluting stents (EES) for in-stent restenosis (ISR) were underpowered for clinical end-points. The objective of this study was to compare the clinical outcomes of DEB versus EES for any ISR., Materials & Methods: Electronic databases were searched for randomized trials which compared DEB versus EES for any ISR (i.e., drug eluting or bare metal stents). Summary estimate risk ratios (RRs) were constructed using a DerSimonian and Laird random effects model., Results: Five trials with 962 patients were included. In-segment minimum lumen diameter (MLD) was lower with DEB (standardized mean difference -0.24, 95% confidence interval [CI] -0.46 - -0.01) on angiographic follow-up at a mean of 8.6 months. There was no statistically significant difference in the risk of target vessel revascularization (TVR) at 1 year (RR 1.15, 95% CI 0.60-2.19), but TVR was increased with DEB at 3 years (RR 1.87, 95% CI 1.15-3.03). The risk of target lesion revascularization (TLR) was statistically increased with DEB (RR 2.17, 95% CI 1.13-4.19) at a mean of 24.4 months. There was no difference in the risk of MI, stent thrombosis, cardiac mortality and all-cause mortality between both groups., Conclusion: In patients with any type of ISR, DEB was associated a similar risk of TVR at 1-year, but increased risk of TVR and TLR at longer follow-up, as compared with EES. The quality of evidence was moderate, suggesting the need for further randomized trials with longer follow-up to confirm the role of DEB in the management of ISR., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The recognition that obstructive disease of the epicardial coronary arteries, causing ischaemic heart disease, can be treated with a percutaneous coronary intervention (PCI) has been a major discovery in cardiology in the last 40 years contributing, in particular, to the reduction of mortality associated to acute myocardial infarction (AMI). However, even in the era of drug-eluting stent (DES) implantation, a sizable proportion of patients who undergo PCI may develop late or very late post-implantation complications, that occur in the form of restenosis, neoatherosclerosis, and/or in-stent thrombosis. Such complications are clinically relevant since they can cause AMI and negatively impact on the outcome. The underlying pathophysiological mechanisms are complex but related to inhibition of neointimal proliferation by DES that, on the hand, reduces the rate of in-stent restenosis, but, on the other hand, causes dysfunctional vessel healing, persistent inflammation, platelet activation, and adverse immunological responses. Multiple approaches have been developed or are under evaluation to target DES-related complications including pharmacotherapy, procedure-related imaging methods, novel stent designs, and drug-delivery methods. The aim of this review is to provide an update on the latest preclinical, translational, and clinical pharmacotherapeutic developments in this setting that target novel cellular mechanisms and pathways that might contribute to neoatherosclerosis. Due to the importance of secondary prevention in the reduction of DES-associated complications, this review also provides a short overview of pharmacological agents that are established or currently being investigated in this regard., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Vascular smooth muscle cell (VSMC) migration and the subsequent intimal thickening play roles in vascular restenosis. We previously reported that an exchange protein activated by cAMP 1 (Epac1) promotes platelet-derived growth factor (PDGF)-induced VSMC migration and intimal thickening. Because basic fibroblast growth factor (bFGF) also plays a pivotal role in restenosis, we examined whether Epac1 was involved in bFGF-mediated VSMC migration. bFGF-induced lamellipodia formation and migration were significantly decreased in VSMCs obtained from Epac1 -/- mice compared to those in Epac1 +/+ -VSMCs. The bFGF-induced phosphorylation of Akt and glycogen synthase kinase 3β (GSK3β), which play a role in bFGF-induced cell migration, was attenuated in Epac1 -/- -VSMCs. Intimal thickening induced by the insertion of a large wire was attenuated in Epac1 -/- mice, and was accompanied by the decreased phosphorylation of GSK3β. These data suggest that Epac1 deficiency attenuates bFGF-induced VSMC migration, possibly via Akt/GSK3β pathways.

Finite element analysis (FEA) can be implemented along with Agent-based model (ABM) to investigate the biomechanical and mechanobiological mechanisms of pathophysiological processes. However, traditional ABM-FEA approaches are often partially coupled and lack the feedback responses from biological analysis. To overcome this problem, a fully coupled ABM-FEA framework is developed in this paper by linking the macro-scale and cell-scale modules bi-directionally. Numerical studies of the in-stent restenosis process are conducted using the proposed approach and comparisons are made between the two types of frameworks. A reduction in lumen loss rate, which is possibly caused by the time-varying stresses, is observed in the fully coupled simulations. The re-endothelialisation process is also simulated under different frameworks and the simulation results show strong inhibition of endothelial cells to vascular restenosis. The proposed method is proved to be effective to explain the biomechanical-mechanobiological coupling characteristics of the restenosis problem and can be utilized for stent design and optimization.

Restenosis is a major problem after percutaneous coronary intervention (PCI) treatment. Inflammation is one of the major core mechanisms involved in the occurrence of restenosis, and plays an important role in intimal hyperplasia. Detoxification and activating blood circulation decoction (DABCD) is a traditional Chinese medicine that is used in the treatment and prevention of atherosclerotic and inflammatory diseases. Our previous studies demonstrated that DABCD-mediated cardioprotection involves anti-inflammatory mechanisms and could be developed as a novel drug for the treatment of vascular smooth muscle cell (VSMC) proliferation and aortic restenosis. A rat model of postoperative restenosis after PCI was generated by balloon injury to determine the protective effects and potential mechanisms of DABCD. The injured segments of aortae were collected on days 14 and 28 after the operation to observe the morphological changes in the vascular structure and measure the proportion of inflammatory factors in plasma and vascular tissues, as well as test the proliferative activity of VSMCs. The expression of related proteins, namely, Toll-like receptor (TLR) 4 and nuclear factor (NF)-κB, in the mechanistic study was clarified by western blot analysis. We tested the hypothesis that the cardioprotective effects of DABCD on aortic restenosis are associated with the inhibition of aortic intimal hyperplasia in this model. Our results showed that DABCD has protective effect on rat aortic restenosis and the anti-inflammatory mechanism of DABCD on balloon-induced restenosis in rat may be due to its ability to inhibit TLR4-mediated NF-κB signaling pathways. DABCD may be a potential therapeutic agent against restenosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aims: To evaluate image quality, interpretability, diagnostic accuracy and radiation exposure of coronary CT angiography (CCTA) performed with a new scanner equipped with 0.23-mm spatial resolution, new generation iterative reconstruction, 0.28-second gantry rotation time and intra-cycle motion-correction algorithm in consecutive patients with coronary stents, including those with high heart rate (HR) and atrial fibrillation (AF)., Materials and Methods: We enrolled 100 consecutive patients (85 males, mean age 65 ± 10 years) with previous coronary stent implantation scheduled for clinically indicated non-emergent invasive coronary angiography (ICA). Image quality, coronary interpretability and diagnostic accuracy vs. ICA were evaluated and the effective dose (ED) was recorded., Results: Mean HR during the scan was 67 ± 13 bpm. Twenty-six patients had >65 bpm HR during scanning and 13 patients had AF. Overall, image quality was high (Likert = 3.2 ± 0.9). Stent interpretability was 95.8% (184/192 stents). Among 192 stented segments, CCTA correctly identified 22 out of 24 with >50% in-stent restenosis (ISR) (sensitivity 92%). In a stent-based analysis, specificity, positive and negative predictive values and diagnostic accuracy for ISR detection were 91%, 99%, 60% and 91%, respectively. In a patient-based analysis, CCTA diagnostic accuracy was 85%. Overall, mean ED of CCTA was 2.4 ± 1.2 mSv., Conclusions: A whole-organ CT scanner was able to evaluate coronary stents with good diagnostic performance and low radiation exposure, also in presence of unfavorable HR and heart rhythm., Translational Aspect: The present study is the first to evaluate the CCTA capability of detecting in-stent restenosis in consecutive patients, including those with high HR and AF, using a recent scanner generation that combines improved spatial and temporal resolution with wide coverage. Using the whole-organ high-definition CT scanner we obtained high quality images of coronary stents with good interpretability and diagnostic accuracy combined with low radiation exposure, even in patients with unfavorable HR or heart rhythm for CCTA evaluation., (Copyright © 2018. Published by Elsevier B.V.)

Purpose: Coronary artery stenosis, or abnormal narrowing, is a widespread and potentially fatal cardiac disease. After treatment by balloon angioplasty and stenting, restenosis may occur inside the stent due to excessive neointima formation. Simulations of in-stent restenosis can provide new insight into this process. However, uncertainties due to variability in patient-specific parameters must be taken into account., Methods: We performed an uncertainty quantification (UQ) study on a complex two-dimensional in-stent restenosis model. We used a quasi-Monte Carlo method for UQ of the neointimal area, and the Sobol sensitivity analysis (SA) to estimate the proportions of aleatory and epistemic uncertainties and to determine the most important input parameters., Results: We observe approximately 30% uncertainty in the mean neointimal area as simulated by the model. Depending on whether a fast initial endothelium recovery occurs, the proportion of the model variance due to natural variability ranges from 15 to 35%. The endothelium regeneration time is identified as the most influential model parameter., Conclusion: The model output contains a moderate quantity of uncertainty, and the model precision can be increased by obtaining a more certain value on the endothelium regeneration time. We conclude that the quasi-Monte Carlo UQ and the Sobol SA are reliable methods for estimating uncertainties in the response of complicated multiscale cardiovascular models.

Background: To investigate the effects of a Chinese herbal medicine Fufang-Zhenzhu Tiaozhi Capsule (FTZ) on restenosis and elucidate the mechanism of action., Methods: A restenosis model was established by balloon rubbing the endothelium of the abdominal aorta followed by high fat diet. Rabbits were divided into blank control group, restenosis group, FTZ group (0.66 mg/kg/day), atorvastatin group (5 mg/kg/day) and FTZ + atorvastatin group (n = 8). Vascular stenosis was analyzed by X-ray. Serum levels of chemokines and cytokines interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-12 (IL-12), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) were measured by ELISA. The levels of NF-κB, IκB-α, P-IκBα, IKK-α, and P-IKKα/β from injured abdominal arteries were detected by Western blotting., Results: Restenosis was induced successfully via abdominal artery balloon injuries and high fat diet. Restenosis was significantly decreased in FTZ group compared with restenosis group (P < 0.05). FTZ group had markedly reduced serum lipid levels (P < 0.05). In addition, the levels of TNF-α, IL-1, IL-6, IL-8, IL-12, ICAM-1 and MCP-1 decreased by FTZ treatment (P < 0.05). The expression of NF-κB in the atherosclerotic lesions was significantly attenuated in FTZ group (P < 0.05)., Conclusion: FTZ could reduce restenosis via reducing NF-κB activity and inflammatory factor expression within the atherosclerotic lesion in a rabbit restenosis model. FTZ may be a new therapeutic agent for restenosis.

Background: The aim of this study was to delineate impacts of percutaneous coronary intervention (PCI), flow demand, and status of myocardium on graft flow., Methods: We retrospectively assessed 736 individual coronary artery bypass grafts that had been created as the sole bypass graft for a vascular region in 405 patients. The grafts comprised 334 internal thoracic artery (ITA) to left anterior descending (LAD), 129 ITA and 65 saphenous vein grafts (SVG) to left circumflex (LCX), and 142 gastroepiploic artery (GEA) and 66 SVG to right coronary artery (RCA). Minimal luminal diameter, size of revascularized area, history of myocardial infarction, and PCI in the relevant area were examined to determine whether these factors are associated with flow insufficiency (FI), which was defined as ≤ 20 mL/min., Results: FI developed in 123/736 grafts (16.7%) and correlated significantly with stenosis in the distal portion (23.0% vs. 12.8%, p = 0.0003). Prior myocardial infarction significantly correlated with FI in GEA-RCA (p = 0.002) and ITA-LCX grafts (p = 0.04). There was a history of PCI to the LAD (PCI group) in 54 ITA to LAD bypass grafts (16.2%), whereas the remaining 280 had no history of PCI to the LAD (no-PCI group). Graft flow was significantly greater in the no-PCI than in the PCI group (53 ± 29 vs. 42 ± 27; p = 0.006). The incidences of FI and graft failure were significantly higher in the PCI than the no-PCI group (22.2%, vs. 8.2%; p = 0.003; 9.2% vs. 1.8%; p = 0.003, respectively)., Conclusions: Prior PCI has a negative impact on graft flow. The influences of small revascularized area, myocardial infarction, and PCI are greater, necessitating consideration of factors associated with flow demand or microvasculature when planning revascularization.

Background: Recent studies demonstrated a significant improvement in the diagnostic performance of coronary CT angiography (CCTA) for the evaluation of in-stent restenosis (ISR). However, coronary stent assessment is still challenging, especially because of beam-hardening artifacts due to metallic stent struts and high atherosclerotic burden of non-stented segments. Adenosine-stress myocardial perfusion assessed by CT (CTP) recently demonstrated to be a feasible and accurate tool for evaluating the functional significance of coronary stenoses in patients with suspected coronary artery disease (CAD). Yet, scarce data are available on the performance of CTP in patients with previous stent implantation., Aim of the Study: We aim to assess the diagnostic performance of CCTA alone, CTP alone and CCTA plus CTP performed with a new scanner generation using quantitative invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR) as standard of reference., Methods: We will enroll 300 consecutive patients with previous stent implantation, referred for non-emergent and clinically indicated invasive coronary angiography (ICA) due to suspected ISR or progression of CAD in native coronary segments. All patients will be subjected to stress myocardial CTP and a rest CCTA. The first 150 subjects will undergo static CTP scan, while the following 150 patients will undergo dynamic CTP scan. Measurement of invasive FFR will be performed during ICA when clinically indicated., Results: The primary study end points will be: 1) assessment of the diagnostic performance (diagnostic rate, sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy) of CCTA, CTP, combined CCTA-CTP and concordant CCTA-CTP vs. ICA as standard of reference in a territory-based and patient-based analysis; 2) assessment of sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of CCTA, CTP, combined CCTA-CTP and concordant CCTA-CTP vs. invasive FFR as standard of reference in a territory-based analysis., Conclusions: The ADVANTAGE study aims to provide an answer to the intriguing question whether the combined anatomical and functional assessment with CCTA plus CTP may have higher diagnostic performance as compared to CCTA alone in identifying stented patients with significant ISR or CAD progression., (Copyright © 2018. Published by Elsevier Inc.)

Objectives: To assess the safety and efficacy of everolimus-eluting bioresorbable scaffolds (BRS) in the treatment of chronic total occlusions (CTO) using noninvasive multislice computed tomography (MSCT) angiography at one-year follow-up., Background: Current evidence regarding the safety and efficacy of BRS for the percutaneous treatment of CTO is limited., Methods: Between September 2013 and January 2016, patients who received one or more ABSORB BRSs were included at three centers. MSCT (including quantitative analysis) and clinical follow-up were performed at one year., Results: Forty-one CTO patients were included. Mean age was 60 ± 11 years and the majority was male (83%). Average Japanese CTO (J-CTO) score was 0.9 ± 0.9. Seventy-one BRS were implanted in total with, on average, 1.7 ± 0.8 scaffolds/patient, and a total length of 43 ± 20 mm and diameter of 3.1 ± 0.4 mm. One noncardiac death took place. MSCT angiography was performed in 34 (83%) patients: all scaffolds were patent, except in one patient, in whom a patent target vessel was present on subsequent diagnostic angiography. MSCT quality was sufficient for quantitative analyses in 27 patients (46 scaffolds): median reference versus scaffold minimal lumen diameter and minimal lumen area were measured, and showed a small difference of 0.1 mm (-0.2-0.4) (lumen diameter stenosis = 3.0%) and 0.5 mm 2 (-1.0-2.0) (lumen area stenosis = 4.2%)., Conclusions: The low number of events and high patency rate at 1 year are encouraging the further use of the ABSORB scaffold for CTOs with low J-CTO score. Noninvasive MSCT angiography is a valid tool to assess scaffold patency, although its image resolution limits the use for quantitative measurements., (© 2017 Wiley Periodicals, Inc.)

Background: Antiproliferative drugs in drug eluting stents (DES) are associated with complications due to impaired re-endothelialization. Additionally, adventitial neovascularization has been suggested to contribute to in-stent restenosis (ISR). Since Vascular Endothelial Growth Factors (VEGFs) are the key mediators of angiogenesis, we investigated feasibility and efficacy of local gene therapy for ISR utilizing soluble decoy VEGF receptors to reduce biological activity of adventitial VEGFs., Method: Sixty-nine adult WHHL rabbit aortas were subjected to endothelial denudation. Six weeks later catheter-mediated local intramural infusion of 1.5x10e10 pfu adenoviruses encoding soluble VEGF Receptor-1 (sVEGFR1), sVEGFR2, sVEGFR3 or control LacZ and bare metal stent implantation were performed in the same aortic segment. Marker protein expression was assessed at 6d in LacZ cohort. Immunohistochemistry, morphometrical analyses and angiography were performed at d14, d42 and d90., Results: Transgene expression was localized to adventitia. All decoy receptors reduced the size of vasa-vasorum at 14d, AdsVEGFR2 animals also had reduced density of adventitial vasa-vasorum, whereas AdsVEGFR3 increased the density of vasa-vasorum. At d42, AdsVEGFR1 and AdsVEGFR2 reduced ISR (15.7 ± 6.9% stenosis, P < 0.01 and 16.5 ± 2.7%, P < 0.05, respectively) vs. controls (28.3 ± 7.6%). Moreover, AdsVEGFR-3 treatment led to a non-significant trend in the reduction of adventitial lymphatics at all time points and these animals had significantly more advanced neointimal atherosclerosis at 14d and 42d vs. control animals., Conclusions: Targeting adventitial neovascularization using sVEGFR1 and sVEGFR2 is a novel strategy to reduce ISR. The therapeutic effects dissipate at late follow up following short expression profile of adenoviral vectors. However, inhibition of VEGFR3 signaling accelerates neoatherosclerosis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Drug-eluting stents (DES) significantly reduced the incidence of in-stent restenosis (ISR). However, ISR still exists in the contemporary DES era. Previously deemed to be a benign process, ISR leads to complex presentation and intervention. This study aimed to compare the presentation and outcome of DES-ISR versus de novo lesions. We performed a retrospective analysis of 11,666 patients receiving percutaneous coronary intervention from 2003 to 2017 and divided them into 2 groups by de novo stenosis and ISR. They were matched based on common cardiovascular risk factors at a 4:1 ratio, respectively. After matching, a total of 1,888 patients with 3,126 de novo lesions and 472 patients with 508 ISR lesions were analyzed. Patients with ISR presented more often with unstable angina (61% vs 45%, p <0.001) and less often with myocardial infarction (6% vs 14%, p <0.001). One-year composite major adverse cardiovascular event, defined as death, Q-wave myocardial infarction, and target vessel revascularization, was 10% in the de novo group and 17% in the ISR group (hazard ratio 1.98, 95% confidential interval 1.58 to 2.46, p <0.001). After adjusting for myocardial infarction presentation, hazard ratio of major adverse cardiovascular events was still higher for the ISR group at 1 year (2.03, 95% confidential interval 1.62 to 2.55, p <0.001). ISR of DES remains a therapeutic challenge and leads to complex presentation and worse outcomes compared with matched de novo patients. These data show that DES-ISR demands better appreciation and prevention with more precise stent technique and should motivate the continued development of fully bioresorbable scaffolds., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Percutaneous treatment of the unprotected left main trunk (ULM), defined as a vessel without patent bypass graft either to the left circumflex (LCX) or left anterior descending (LAD) artery, has gained a precise role thanks to recent scientific evidence. Although new generation drug-eluting stents have already proven to be safer, there is still a consistent risk of restenosis and late adverse events. The optimal management of a ULM restenosis is still debated. Here we aim at presenting a review of the available data in literature and show our choice for treating it., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Competing Interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: none.

Background/purpose: Multiple BRSs and specifically the Absorb scaffold (BVS) (Abbott Vascular, Santa Clara, CA USA) have been often used to treat long diffuse coronary artery lesions. We evaluate by a computational fluid dynamic(CFD) study the impact on the intravascular fluid rheology on multiple bioabsorbable scaffolds (BRS) by standard overlapping versus edge-to-edge technique., Methods/materials: We simulated the treatment of a real long significant coronary lesion (>70% luminal narrowing) involving the left anterior descending artery (LAD) treated with a standard or edge-to-edge technique, respectively. Simulations were performed after BVS implantations in two different conditions: 1) Edge-to-edge technique, where the scaffolds are kissed but not overlapped resulting in a luminal encroachment of 0.015cm (150μm); 2) Standard overlapping, where the scaffolds are overlapped resulting in a luminal encroachment of 0.030cm (300μm). After positioning the BVS across the long lesion, the implantation procedure was performed in-silico following all the usual procedural steps., Results: Analysis of the wall shear stress (WSS) suggested that at the vessel wall level the WSS were lower in the overlapping zones overlapping compared to the edge-to-edge zone (∆=0.061Pa, p=0.01). At the struts level the difference between the two WSS was more striking (∆=1.065e-004 p=0.01) favouring the edge-to-edge zone., Conclusions: Our study suggested that at both vessel wall and scaffold struts levels, there was lowering WSS when multiple BVS were implanted with the standard overlapping technique compared to the "edge-to-edge" technique. This lower WSS might represent a substrate for restenosis, early and late BVS thrombosis, potentially explaining at least in part the recent evidences of devices poor performance., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Percutaneous coronary intervention (PCI) for the treatment of right coronary artery (RCA) ostial in-stent restenosis (ISR) can be challenging. The technical difficulties are compounded by excessive stent protrusion into the aorta, preventing coaxial engagement of the guiding catheter and wiring through the central stent lumen. Through this review, we aim to highlight the practical challenges encountered during the treatment of ostial RCA ISR through PCI and evaluate the various interventional techniques that have been used. We describe the first reported case of a GuideLiner extension catheter-facilitated side-strut stenting for the treatment of ostial RCA ISR and demonstrate the safety and feasibility of this novel technique., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Percutaneous balloon pulmonary valvuloplasty (PBPV) is the preferred therapy for pulmonary valve stenosis (PVS). This study retrospectively reviewed recent PBPV outcomes in infants with PVS. The aim of this study was to evaluate factors associated with immediate therapeutic outcomes and restenosis during medium-term follow-up., Methods: The study included 158 infants with PVS who underwent PBPV from January 2009 to July 2015. Demographic characteristics and patient records were reviewed, including detailed hospitalization parameters, hemodynamic data before and immediately after balloon dilation, cineangiograms, and echocardiograms before PBPV and at each follow-up. All procedures were performed by more than two experienced operators., Results: Immediately after balloon dilation, the pressure gradient across the pulmonary valve decreased from 73.09 ± 21.89 mmHg (range: 43-151 mmHg) to 24.49 ± 17.00 mmHg (range: 3-92 mmHg; P < 0.001) and the right ventricular systolic pressure decreased from 95.34 ± 23.44 mmHg (range: 60-174 mmHg) to 52.07 ± 18.89 mmHg (range: 22-134 mmHg; P < 0.001). Residual transvalvular pressure gradients of 67.31 ± 15.19 mmHg (range: 50-92 mmHg) were found in 8.2% of patients, indicating poor therapeutic effects; 6.4% of patients had variable-staged restenosis at follow-up and 3.8% underwent reintervention by balloon dilation or surgical repairs. Further analysis demonstrated that the balloon/annulus ratio showed statistically significant differences (P < 0.05) among groups with different therapeutic effects and between the restenosis and no-stenosis groups. Binary logistic regression analysis further revealed that higher balloon/annulus ratio (odds ratio: 0.005, 95% confidence interval: 0-0.39) was an independent protective factor for restenosis. The rate of severe complications was 1.9%., Conclusions: PBPV is a definitive therapy for infants with PVS based on its effectiveness, feasibility, and safety. Restenosis upon medium-term follow-up is relatively rare.

Local hemodynamic forces are well-known to modulate atherosclerotic evolution, which remains one of the largest cause of death worldwide. Percutaneous coronary interventions with stent implantation restores blood flow to the downstream myocardium and is only limited by stent failure caused by restenosis, stent thrombosis, or neoatherosclerosis. Cumulative evidence has shown that local hemodynamic forces affect restenosis and the platelet activation process, modulating the pathophysiological mechanisms that lead to stent failure. This article first covers the pathophysiological mechanisms through which wall shear stress regulates arterial disease formation/neointima proliferation and the role of shear rate on stent thrombosis. Subsequently, the article reviews the current evidence on (1) the implications of stent design on the local hemodynamic forces, and (2) how stent/scaffold expansion can influence local flow, thereby affecting the risk of adverse events., (© 2017 American Heart Association, Inc.)

Objectives: The aim of this study is to evaluate the role of drug-coated balloons (DCB) for the management of bioresorbable vascular scaffold (BVS) restenosis., Methods and Results: In a series of 25 BVS restenosis discovered during systematic angiographic follow up of 246 consecutive BVS implantations at our institution, DCB was used as a primary therapeutic tool in 9 patients and 3 different types of DCB were used. Follow-up coronary angiography at 12months after DCB treatment was performed to all the patients. Among the 9 patients treated with DCB, angiographic follow up revealed failure in two patients that experienced type III restenosis (both of them treated with the same type of DCB). Both patients were treated with drug eluting stent implantation., Conclusions: In this case series of consecutive patients with BVS restenosis, the use of certain types of DCB is safe and effective in order to maintain vessel patency at mid-term follow up. Despite the small sample size and the study limitations, DCB can provide therefore an alternative treatment option in this setting, avoiding the implantation of further metallic stents in a patient where a different strategy was initially planned., (Copyright © 2017 Elsevier Inc. All rights reserved.)

To assess the accuracy of cardiac magnetic resonance (CMR) for the diagnosis of angiographic stenosis after percutaneous coronary intervention (PCI) of left main coronary artery (LMCA). Patients undergone in the last year PCI of unprotected LMCA and scheduled for conventional X-ray coronary angiography (CXA) were evaluated with stress perfusion CMR within 2 weeks before CXA. Main contraindications to CMR were exclusion criteria. Stress perfusion CMR was performed to follow a bolus of contrast Gadobutrol after 3 min of adenosine infusion. Between the 50 patients enrolled, only 1 did not finish the CMR protocol and 49 patients with median age 71 (65-75) years (38 male, 11 female) were analyzed. Between 784 coronary angiographic segments evaluated we found 75 stenosis or occlusions (prevalence 9.5%), but only 13 stenosis or occlusions in proximal segments (prevalence 6.6%). Patients with coronary stenosis (n = 12, 24%) showed a significantly (p = 0.002) higher prevalence of diabetes (7 of 12, 58%). At CMR examination, late gadolinium enhancement was present in 25 (51%), reversible perfusion defects in 12 (24%), and fixed perfusion defects in 6 subjects (12%). The only patient with LMCA restenosis resulted positive at perfusion CMR. The accuracy of stress perfusion CMR in diagnosis of coronary stenosis was higher when the analysis was performed only in proximal coronary arteries (95%, CI 86-99) compared to overall vessels (84%, CI 70-92). Stress perfusion CMR could strongly reduce the need for elective CXA in follow up of LMCA PCI and should be validated in further multicenter prospective studies.

Background: Endothelial shear stress (ESS) may play a key role in the pathobiology of stent restenosis (SR). Nevertheless, limited data are available about ESS and its relation to SR., Patients and Methods: We enrolled 14 patients who underwent successful percutaneous coronary intervention (PCI) in this study. Three-dimensional (3D) reconstruction of 14 coronary arteries before and after stent implantation was performed. Using computational fluid dynamics, mean ESS was calculated proximally, in tertiles within and distal to the stent, both before and after stent implantation., Results: Stent implantation resulted in a significant ESS decrease in the entire atherosclerotic lesion (1.83 vs. 1.26 Pa, p = 0.02). Regarding the five territories in which the entire lesion was divided, ESS decrease was marginally significant in the area of the second in-stent tertile, and in the area 5 mm distal to the stent, whereas ESS decrease was not significant in the area 5 mm proximal to the stent, and in the area of the first and third in-stent tertile. At 12 months, two patients had SR, but restenosis was not related to ESS decrease., Conclusion: ESS decreases after stent implantation but not uniformly, with the major reduction being in the middle tertile of the stent, and distal to the stent. In-stent ESS decrease may create local hemodynamic conditions leading to in-stent and in-segment restenosis.