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Modeling and simulation of coronary artery disease (CAD) is of great importance for supporting and predicting the outcome of percutaneous coronary intervention (PCI). However, an in silico model generally requires heavy computational resources. An effective reduced order surrogate model is indispensable in this context. This study aims to develop a non‐intrusive data‐driven reduced order surrogate model for coronary in‐stent restenosis (ISR) incorporating anti‐inflammatory drugs embedded in the drug‐eluting stents. The constitutive model includes a detailed multiphysics approach based on partial differential equations (PDEs), which include descriptions of platelet aggregation, growth‐factor release, cellular motility and drug deposition. Dimensionality reduction is carried out based on a 3D convolutional autoencoder, which comprises an encoder and decoder. The former condenses the full‐order solution into a lower‐dimensional latent space, while the latter recovers the full solution from the latent space. Special attention is paid to handle the multidimensional outputs and network architecture. [ABSTRACT FROM AUTHOR]

Background Drug-coated balloons (DCBs) offer an appealing therapeutic alternative for the treatment of patients with coronary in-stent restenosis (ISR). In-segment late lumen loss, translating into recurrent ISR and the clinical need for target lesion revascularization, represents a well-established and thoroughly investigated limitation of DCB in this setting. However, abrupt vessel occlusion, clinically presenting as ST-segment elevation myocardial infarction (STEMI), has not been previously described after DCB therapy for ISR. Case summary We herein present the case of a 70-year-old patient that underwent percutaneous coronary intervention (PCI) with DCB for ISR. Despite achieving an excellent acute angiographic result (with no flow-limiting dissection and minimal angiographic residual stenosis), the patient presented 3 months later with STEMI due to occlusion of the previously treated segment. After adequate lesion preparation, a drug-eluting stent was implanted with optimal final angiographic result. The patient was discharged 2 days after the PCI without any post-procedural complications and remained asymptomatic at 6-month clinical follow-up. Discussion This case report is the first description of an abrupt vessel occlusion presenting as STEMI following a DCB angioplasty for ISR. This exceptional presentation does not dismount the solid evidence supporting the long-term safety of DCB in these challenging patients. [ABSTRACT FROM AUTHOR]

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]

Background Left main coronary bifurcation lesions account for 50% of left main coronary artery disease cases. Although a drugcoated balloon (DCB) has the advantages of immediate release of the drug to the arterial wall and no remaining struts, there is no conclusive evidence to support DCB use. Methods & Results We conducted a systematic review in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. Eighteen retrospective studies and two prospective studies in which left main bifurcation lesions were treated with DCBs were included in our qualitative analysis. The studies were divided into two groups according to the type of DCB used: DCB only and DCB + stent. At the midterm follow-up, the use of DCBs had noninferior or even superior angiographic and clinical outcomes in treating left main bifurcation lesions compared with the use of drug-eluting stents or conventional balloons, whether for de novo or in-stent restenosis lesions. Additionally, side branch late lumen enlargement was observed in several of the included studies, which indicates that DCBs may have the advantage of side branch protection. Conclusions According to our descriptive analysis, the DCB technique has a favorable safety and efficacy profiles for the treatment of left main bifurcation lesions. However, additional studies, especially randomized controlled trials, are needed to establish standards for the DCB technique. [ABSTRACT FROM AUTHOR]

Background: Elevated lipoprotein(a) (Lp[a]) is a risk factor for first atherosclerotic thrombosis events, but the role of elevated Lp(a) in secondary prevention is controversial. This study aimed to retrospectively investigate the influence of elevated Lp(a) levels on the prognosis of patients with coronary artery disease. Methods: The team collected and compared clinical information of patients hospitalized during percutaneous coronary intervention (PCI). This study used a multivariate logistic regression model to evaluate the relationships between Lp(a) levels, cardiovascular risk factors, and the prognosis of coronary artery disease in patients undergoing PCI. Results: There were no statistically significant differences between patients grouped according to Lp(a) level in terms of sex; age; body mass index and obesity; hyperuricemia; smoking; cardiac insufficiency; acute myocardial infarction; multivessel lesion; in-stent restenosis; secondary PCI; apolipoprotein AI level; incidence of high total cholesterol or high low-density lipoprotein cholesterol; or family history of hypertension, diabetes, or coronary artery disease. The average Lp(a) concentration did not statistically significantly decrease after 1 year of statin treatment after PCI. One year after patients began statins, there were no significant differences between Lp(a) groups in the incidence of high triglycerides (P = .13), high total cholesterol (P = .52), or high low-density lipoprotein cholesterol (P = .051). Multivariate logistic regression analysis indicated that diabetes (P = .02) was associated with in-stent restenosis, whereas diabetes (P = .02) and multivessel lesions (P < .001) were associated with secondary PCI in patients who underwent coronary angiography 1 year after PCI. Compared with normal Lp(a) levels, high Lp(a) levels did not significantly increase the incidence of in-stent restenosis or secondary PCI in patients who underwent coronary angiography 1 year after PCI. Conclusion: Sustained high concentrations of Lp(a) did not significantly increase the incidence of in-stent restenosis or secondary PCI in patients who underwent coronary angiography 1 year after PCI.

Background: The optimal therapeutic strategy for coronary intervention in edge in-stent restenosis (edge ISR) remains less well-defined. Aim: The aim of this study was to assess 12-month outcomes of re-stenting using drug-eluting stents (DESs) versus using drug-eluting balloon (DEB) for managing coronary edge ISR. Patients and Methods: One hundred and four patients with edge ISR were randomly assigned to either DES or DEB. The primary endpoint was stent failure at 12-month follow-up. Results: Significantly lower target vessel revascularization among the DEB group compared to restenting group, (7.7% vs. 23.1%, P = 0.04). Likewise, target vessel-related myocardial infarction rate was significantly lower among the DEB group than restenting (5.7% vs. 23.1%, P = 0.04). On the other hand, there were no significant differences in the rates of deaths or restenosis between the two groups. Conclusion: The DEB is superior to the DES with better both safety and efficacy. [ABSTRACT FROM AUTHOR]

• Evidence before this study. • Previous studies have demonstrated the association between residual inflammation and adverse clinical outcomes in patients with de novo lesions treated with PCI and statins. However, in patients with ISR, whether clinicians should choose a second LDL-C lowering agent, or alternatively initiate the anti-inflammatory therapy, remains uncertain and controversial. • Added value of this study. • Among 2079 patients who were undergoing PCI for ISR lesions, residual inflammatory risk (as measured by hsCRP) was a stronger predictor of adverse cardiovascular outcomes compared with residual cholesterol risk (as detected by LDL-C). • Implications of all the available evidence. • In patients with ISR underwent successful PCI, inflammation appears to be a stronger driver of residual cardiovascular event than cholesterol level. These data have substantial implications for the anti-inflammation as a therapeutic target to improve long-term outcomes in this special population. To evaluate the relationships between residual inflammatory risk [assessed by high-sensitivity C-reactive protein (hsCRP)], residual cholesterol risk [assessed by low-density lipoprotein cholesterol (LDL-C)] and clinical outcomes among patients who underwent percutaneous coronary intervention (PCI) for in-stent restenosis (ISR) lesions. Between January 2017 and December 2018, a total of 2079 patients who underwent PCI for ISR were consecutively enrolled. The primary outcome was the rate of major adverse cardiac events (MACE), defined as a composite endpoint of all-cause death, spontaneous myocardial infarction (MI), or repeat revascularization. During a median follow-up of 36 months, 436 MACEs occurred. Baseline hsCRP was significantly associated with MACE (highest versus lowest quartile, adjusted hazard ratio [aHR] 1.90 [95% CI, 1.39–2.59]; P < 0.001). By contrast, the baseline LDL-C quartile was not associated with MACE (highest versus lowest quartile, aHR 0.93 [95% CI, 0.71- 1.22]; P = 0.59). Compared with patients without residual risk (hsCRP <2 mg/L and LDL-C < 70 mg/dL), participants with both residual inflammatory and LDL-C risk (hsCRP ≥2 mg/L and LDL-C ≥ 70 mg/dL) (aHR, 1.39 [95% CI, 1.06–1.83]; P = 0.02) and those with residual inflammatory risk only (hsCRP ≥2 mg/L and LDL-C < 70 mg/dL) (aHR, 1.34 [95% CI, 1.01–1.72]; P = 0.04) had significantly higher risks of MACE. In the current cohort of patients after ISR PCI, inflammation assessed by hsCRP predicted higher risk of adverse clinical outcomes, whereas the level of LDL-C was not associated with adverse prognosis. [ABSTRACT FROM AUTHOR]

BACKGROUND:PCI for UDLM-ISR can be complex. Limited information is available on procedural and clinical outcomes. OBJECTIVES: The present study aimed to analyse the management, immediate angiographic results, and long-term clinical outcomes, as well as to evaluate the outcomes of the different treatment strategies, in patients undergoing PCI for instent restenosis (ISR) in cases with a stented UDLM. The goal of this study was to assess the immediate and long term outcomes in patients undergoing percutaneous coronary intervention (PCI) for in-stent restenosis (ISR) in an unprotected distal left main coronary artery (UDLM). METHODS: Between May 2002 and February 2011, UDLM-ISR after drug-eluting stent implantation was observed in 79 of 1,102 patients (7%). Seventy-five were treated by repeat PCI using a simple approach (balloon/in-stent implantation) or a complex strategy (additional stent/double-stenting technique). A diagnosis of mild or severe restenosis was considered depending on the number of bifurcation segments affected (1 vs. >1). Major adverse cardiac events (MACE) were defined as cardiac death, target lesion revascularization, and myocardial infarction. RESULTS: ISR treatment was performed using a simple approachin 44 (58%) patients, and using a complex strategy in 31 (42%). After 46-26 months, the MACE rate was 22%. Patients treated with a simple approach had a lower incidence of MACE at follow-up compared with patients treated with a complex strategy, regardless of the restenosisextent (mild restenosis: 93% vs. 67%, p < 0.05; severe: 70% vs. 23%, p < 0.05). On Cox regression analysis, diabetes was the only predictor of MACE (hazard ratio [HR]: 4.94; 95% confidence interval [CI]: 1.03 to 23.70; p < 0.05), whereas a simple strategy for ISR treatmentwas associated with lower risk (HR: 0.25; 95% CI: 0.08 to 0.79; p ¼ 0.02). CONCLUSIONS:PCI for UDLM-ISR is safe and feasible, with a high rate of procedural success and an acceptable long-term MACE rate. A simple strategy, when applicable, appears to be a good treatment option, associated with a lower event rate at 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]

BackgroundImaging factors, specifically baseline plaque features on high-resolution magnetic resonance vessel wall imaging (HR-VWI) that could be associated with in-stent restenosis (ISR), are still unknown. We aimed to investigate the presenting clinical and plaque features on HR-VWI associated with ISR.MethodsSixty-four patients with intracranial stent placement for intracranial atherosclerotic stenosis who had pre- and post-contrast T1-weighted HR-VWI on 3.0T prior to stenting were included in this analysis. Student's t-test, Mann-Whitney U test, χ2 test, or the Cochran-Mantel-Haenszel (CMH) test were used to compare clinical and baseline HR-VWI characteristics of the patients between the ISR and non-ISR groups. Univariable and multivariable logistic analysis were used to test the clinical and imaging factors associated with ISR.ResultsAmong the 64 patients, 9 patients (14.06%) developed ISR during the 2-year follow-up period. Plaque burden (median 0.89 vs 0.92, P=0.04), minimum lumen area (0.009 cm2 vs 0.006 cm2, P=0.04), plaque eccentricity (55.6% vs 89.1%, P＜0.01), enhancement ratio (1.36 vs 0.84, P＜0.01), and enhancement involvement (type 2 represents ≥50% cross-sectional wall involvement; 100% vs 63.6%, P=0.03) all significantly differed between patients with and without ISR. Multivariable analysis revealed that lower frequency of plaque eccentricity (OR 0.18, 95% CI 0.04 to 0.96, P=0.04) and higher enhancement ratio (OR 3.57, 95% CI 1.02 to 12.48, P=0.04) were independently associated with ISR.ConclusionsPreliminary findings showed that ISR was independently associated with plaque concentricity and higher enhancement ratios on pre-stenting HR-VWI for patients with symptomatic intracranial atherosclerotic stenosis.

Purpose: The systemic inflammation response index (SIRI) and the systemic immune inflammation index (SII) are indicators that reflect the body's overall systemic inflammatory response. Inflammation plays an important role in the pathogenesis of in-stent restenosis (ISR). The aim of this study was to investigate the predictive value of preoperative SIRI and SII for the occurrence of ISR in patients undergoing coronary stent implantation. Materials and Methods: We retrospectively analyzed the clinical, hematological, and angiographic data of 387 patients who underwent coronary angiography for recurrent angina after coronary stent implantation at Qilu Hospital of Shandong University. Receiver operating characteristic curve (ROC) analysis was used to determine the optimal cutoff values for SIRI and SII to predict ISR. Based on the optimal cutoff values for SIRI and SII, patients were categorized into high-SIRI, low-SIRI, high-SII, and low-SII groups. Multivariate logistic regression models were constructed to assess the predictive value of SIRI and SII for ISR > 50% and ISR > 70%. Results: This study included a total of 387 patients who underwent coronary angiography and follow-up at Qilu Hospital of Shandong University. Patients in the high-SIRI group had a higher incidence of ISR than those in the low-SIRI group (ISR > 50%: 44.8% vs 30.7%, p = 0.018; ISR > 70%: 41.5% vs 4.5%, p < 0.001). In addition, ISR occurred more frequently in patients with a higher SII than in patients with a lower SII (ISR > 50%: 52.6% vs 35.7%, p = 0.001; ISR > 70%: 51.9% vs 23%, p < 0.001). In multivariate logistic regression analysis, SIRI and SII were found to be independent predictive factors for ISR, both as continuous and categorical variables. In the ROC analysis, the optimal cutoff value for SIRI was set at 0.54 (sensitivity: 84.5%, specificity: 27%), and the optimal cutoff value for SII was set at 545.29 (sensitivity: 44.1%, specificity: 71.7%). Conclusion: Elevated preoperative SIRI and SII values help predict ISR and may serve as a useful screening tool to perform interventional procedures based on the patient's risk of ISR after stent implantation. [ABSTRACT FROM AUTHOR]

Background: The triglyceride–glucose index (TyG) is a reliable indicator for predicting the prognosis of patients with coronary heart disease (CAD) after percutaneous coronary intervention (PCI). However, its influence on patients with in-stent restenosis (ISR) is unclear. This study was designed to evaluate the association between the TyG index and the occurrence of major adverse cardiovascular events (MACEs) after PCI in patients with ISR. Methods: This retrospective study included 1654 patients who underwent PCI between 2016 and 2022 at Nanjing First Hospital. Patients were stratified into three groups based on the quantile level of the TyG index. The TyG index was determined as Ln (triglycerides [mg/dL] × fasting plasma glucose [mg/dL]/2). Results: Individuals with the highest TyG index showed an increased risk of MACEs compared to those with the lowest level of the TyG index (HR 1.60; 95% CI 1.11– 2.30; P = 0.01). When analyzing the TyG index as a continuous variable, each standard deviation increase was associated with an HR of 1.51 (95% CI: 1.11– 2.05; P = 0.01). For the male subgroup and the diabetes subgroup, this trend was even more pronounced (HR 1.269; 95% CI 1.055– 1.527; P = 0.011; HR 1.385; 95% CI 1.125– 1.706; P = 0.002). Additionally, the landmark analysis showed that patients with the highest level of TyG had an increased risk of MACEs 6 months after the PCI (P = 0.019). Conclusion: Elevated TyG index is associated with increased risk of adverse cardiovascular events in patients with ISR, and the extent of increase in the risk is more significant in male patients with diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Left atrial appendage (LAA) closure (LAAC) is considered a viable alternative to anticoagulation therapy for stroke prevention in nonvalvular atrial fibrillation, we report a case with a less common shunt resulting from a device‐ related coronary artery‐appendage fistula (CAAF) following LAAC. Methods and Results: A 67‐year‐old male with a history of LAAC was referred to our emergency room with recurrent chest pain and palpitations and was diagnosed with ischemic angina pectoris. Subsequent coronary angiography (CAG) revealed 70% in‐stent restenosis and an abnormal shunt of contrast originating from the left circumflex artery (LCA) to the LAA tip which did not exist before. The restenosis was successfully dilated using a drug‐coated balloon, the procedure was safely completed without pericardial effusion. The patient had been implanted with a LAmbre occluder (Lifetech Scientific Corp.) in the previous LAAC procedure. This occluder had a lobe‐disk design, and the distal umbrella was not fully opened after release, particularly in the lower portion. This could make the hooks embedded on the umbrella contact the LAA wall more tightly, possibly resulting in microperforation and coincidental impingement of the LCA. The epicardial adipose and hyperplastic tissue then chronically wrapped the perforated site, prevented blood outflow into the epicardium, and ultimately formed a CAAF. Conclusion: CAAF is a rare complication after LAAC but may be underestimated, especially for lobe‐disk designed occluders. Therefore, CAG is perhaps necessary to detect this complication. [ABSTRACT FROM AUTHOR]

The management of intracranial atherosclerotic disease (ICAD) has been evolving with advanced imaging, refinements of best medical treatment, and the development of endovascular options. There has been a significant increase in the use of endovascular therapy for symptomatic ICAD in the USA over the past 6 years. The rationale for this review is to update neurointerventionalists in these areas so that evidence-based decisions can be considered when counseling potential patients regarding their risks, benefits, and potential complications. The landmark SAMMPRIS trial demonstrated superiority of aggressive medical management (AMM) over intracranial stenting as an initial treatment. However, the risk of disabling or fatal stroke remains high in patients presenting with stroke treated with AMM. Recent studies showed a significantly lower rate of periprocedural complications from intracranial stenting. Patients who have failed medical treatment may therefore benefit from intracranial stenting, particularly in those with hemodynamic compromise and large vessel embolic stroke. Drug coated angioplasty balloons and drug eluting stents may potentially reduce the risk of in-stent re-stenosis. Large vessel occlusion (LVO) due to underlying ICAD is seen in a subset of thrombectomy-eligible patients. The use of stenting as a rescue therapy in LVO thrombectomy has also shown promising early results. [ABSTRACT FROM AUTHOR]

Treatment of patients with coronary artery disease commonly involves the use of balloon-expandable stent placements, currently recognized as the most prevalent approach for coronary artery revascularization. Nevertheless, the occurrence of restenosis remains a significant complication following percutaneous coronary interventions. The diagnostic role of coronary CT angiography (CCTA) in detecting stent restenosis has limitations primarily attributable to challenges in accurately discerning the lumen, due to issues such as blooming and motion artifacts. As a result, many cases often necessitate a transition to conventional coronary angiography. However, recent advancements in CT technology have led to notable improvements in both sensitivity and specificity, underscoring the growing significance of CCTA as a diagnostic tool. The consistent reporting of high negative predictive value is particularly noteworthy. This review aims to explore the historical context, current status, and recent trends in diagnosing coronary artery stent restenosis using CCTA.

Underexpansion is an important issue for interventional cardiologists in terms of long term results. Herein we report a successful rotablation of an under-expended stent struts. The patient was a 75 years old female with a history of Percutaneous Coronary Intervention (PCI) on Left Anterior Descending Artery (LAD) with 2 overlapping drug eluting stents a week ago in another center. Unfortunately, the stents were deployed without proper lesion preparation in heavily calcified lesions and hence the stents couldn't be dilated properly after deployment. The stent struts were successfully rotablated with 1.5 and 1.75 burrs respectively followed by subsequent stenting. The patient was discharged uneventfully. Under-expansion of a stent generally arises from inadequate lesion preparation. Impaired healing secondary to under-expanded stent struts is the main cause of re-stenosis in the short term. Hence adequate pre-dilatation especially in heavily calcified lesions is of quite importance. More sophisticated techniques such as Non-Compliant balloon (OPN), rotablation, shock wave balloon and laser should be used for adequate pre-dilatation when conventional balloon pre-dilatation methods fail. These methods can also be used for dilatation of an under-expanded stent. Consequently, under-expansion of a stent is one of the leading causes of stent restenosis. Rota-ablation can be used to debulk the under-expanded stent struts and hence prevent possible short term restenosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Targeting TNF-α was found to be helpful in alleviating inflammation. With TNF-α being a master regulator of inflammation, drugs that target TNF-α can help treat many diseases such as cancer and cardiovascular diseases, where TNF-α plays a critical role. Currently, anti-TNF-α drugs are not approved for treating vascular restenosis. This review article highlights the specific role of TNF-α in promoting proliferation, migration, phenotype switch, and cellular processes in vascular smooth muscle cells, which are the basis for restenosis. Molecular pathways and other mediators associated with TNF-α-induced mechanisms are discussed, which may help to develop a better strategy to use TNF-α antagonists for the treatment of restenosis. TNF-α functions as a master regulator of inflammation, and it plays a prominent role in several immunological diseases. By promoting important cellular mechanisms, such as cell proliferation, migration, and phenotype switch, TNF-α induces its exacerbating effects, which are the underlying cause of many proliferative diseases such as cancer and cardiovascular disease. TNF-α primarily alters the immune component of the disease, which subsequently affects normal functioning of the cells. Monoclonal antibodies and synthetic drugs that can target TNF-α and impair its effects have been developed and are currently used in the treatment of a few select human diseases. Vascular restenosis is a proliferative disorder that is initiated by immunological mechanisms. In this review, the role of TNF-α in exacerbating restenosis resulting from neointimal hyperplasia, as well as molecular mechanisms and cellular processes affected or induced by TNF-α, are discussed. As TNF-α-targeting drugs are currently not approved for the treatment of restenosis, the summation of the topics discussed here is anticipated to provide information that can emphasize on the use of TNF-α-targeting drug candidates to prevent vascular 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]

The article presents the discussion on In-stent restenosis (ISR) remains a significant problem even in the modern drug-eluting stent (DES) era. Topics include implantation of an additional DES remains the most commonly used tactic for dealing with these cases, with efficacy that is greater than plain balloon angioplasty alone; and improved options for lesion preparation and emphasis on the use of intravascular imaging, which can reduce the occurrence of ISR.

Key Points: Question: Is treatment with a coronary paclitaxel-coated balloon superior to an uncoated balloon for 1-year target lesion failure in patients undergoing percutaneous coronary intervention for in-stent restenosis? Findings: In a multicenter randomized trial of 600 patients designed to support US regulatory approval, target lesion failure was significantly lower in the paclitaxel-coated balloon group (17.9%) compared with the uncoated balloon group (28.6%) (P =.003). Ischemia-driven target lesion revascularization and target vessel myocardial infarction were also lower after treatment with a paclitaxel-coated balloon. Meaning: Treatment with a paclitaxel-coated balloon offers an effective treatment strategy for the management of coronary in-stent restenosis. Importance: Drug-coated balloons offer a potentially beneficial treatment strategy for the management of coronary in-stent restenosis. However, none have been previously evaluated or approved for use in coronary circulation in the United States. Objective: To evaluate whether a paclitaxel-coated balloon is superior to an uncoated balloon in patients with in-stent restenosis undergoing percutaneous coronary intervention. Design, Setting, and Participants: AGENT IDE, a multicenter randomized clinical trial, enrolled 600 patients with in-stent restenosis (lesion length <26 mm and reference vessel diameter >2.0 mm to ≤4.0 mm) at 40 centers across the United States between May 2021 and August 2022. One-year clinical follow-up was completed on October 2, 2023. Interventions: Participants were randomized in a 2:1 allocation to undergo treatment with a paclitaxel-coated (n = 406) or an uncoated (n = 194) balloon. Main Outcomes and Measures: The primary end point of 1-year target lesion failure—defined as the composite of ischemia-driven target lesion revascularization, target vessel–related myocardial infarction, or cardiac death—was tested for superiority. Results: Among 600 randomized patients (mean age, 68 years; 157 females [26.2%]; 42 Black [7%], 35 Hispanic [6%] individuals), 574 (95.7%) completed 1-year follow-up. The primary end point at 1 year occurred in 17.9% in the paclitaxel-coated balloon group vs 28.6% in the uncoated balloon group, meeting the criteria for superiority (hazard ratio [HR], 0.59 [95% CI, 0.42-0.84]; 2-sided P =.003). Target lesion revascularization (13.0% vs 24.7%; HR, 0.50 [95% CI, 0.34-0.74]; P =.001) and target vessel–related myocardial infarction (5.8% vs 11.1%; HR, 0.51 [95% CI, 0.28-0.92]; P =.02) occurred less frequently among patients treated with paclitaxel-coated balloon. The rate of cardiac death was 2.9% vs 1.6% (HR, 1.75 [95% CI, 0.49-6.28]; P =.38) in the coated vs uncoated balloon groups, respectively. Conclusions and Relevance: Among patients undergoing coronary angioplasty for in-stent restenosis, a paclitaxel-coated balloon was superior to an uncoated balloon with respect to the composite end point of target lesion failure. Paclitaxel-coated balloons are an effective treatment option for patients with coronary in-stent restenosis. Trial Registration: ClinicalTrials.gov Identifier: NCT04647253 This clinical trial compares a paclitaxel-coated balloon vs an uncoated balloon in patients with in-stent restenosis undergoing percutaneous coronary intervention. [ABSTRACT FROM AUTHOR]

Background: Supraflex (Sahajanand Medical Technologies Limited, Surat, India) is a newgeneration, biodegradable polymer-coated sirolimus-eluting stent (SES) designed on an ultrathin (60 µm) cobalt-chromium platform with a flexible "S-link." The S-FLEX Slovakia registry aimed to assess the safety and effectiveness of Supraflex SES in an all-comers population, with a subgroup of diabetic patients. Methods: This was a prospective, observational, multi-center, post-market registry conducted between February 2018 and May 2019. All consecutive patients with symptomatic coronary artery disease scheduled for percutaneous coronary intervention with Supraflex SES were enrolled. The primary endpoint was target lesion failure (TLF), defined as a composite of cardiac death, target vessel myocardial infarction (TV-MI), or clinically indicated target lesion revascularization (CI-TLR) by percutaneous or surgical methods at 1-year follow-up. Stent thrombosis was a safety endpoint. Results: A total of 413 patients was assessed (145 diabetics and 268 nondiabetics). At 1-year follow-up, the primary endpoint of TLF occurred in 5.1% patients, comprised of 3.9% cardiac deaths, 0.5% TV-MI, and 0.7% CI-TLR. Overall stent thrombosis occurred in 0.5% patients at 1-year follow-up. In the subgroup analysis, TLF occurred in 6.2% diabetics and 4.5% nondiabetics (P = .433) and comprised 4.8% and 3.4% cardiac deaths (P = .447), 0.7% and 0.4% TV-MI (P = .653), and 0.7%, and 0.7% CI-TLR (P = .952) in diabetics and nondiabetics, respectively. Overall stent thrombosis occurred in 0.7% diabetic and 0.4% nondiabetic patient (P = .659). Conclusion: This registry demonstrates favourable clinical outcomes after the implantation of the ultrathin biodegradable polymer coated Supraflex SES in an all-comers population, with event rates that were similar in diabetic and nondiabetic patients. [ABSTRACT FROM AUTHOR]

Treatment of patients with coronary artery disease commonly involves the use of balloon-expandable stent placements, currently recognized as the most prevalent approach for coronary artery revascularization. Nevertheless, the occurrence of restenosis remains a significant complication following percutaneous coronary interventions. The diagnostic role of coronary CT angiography (CCTA) in detecting stent restenosis has limitations primarily attributable to challenges in accurately discerning the lumen, due to issues such as blooming and motion artifacts. As a result, many cases often necessitate a transition to conventional coronary angiography. However, recent advancements in CT technology have led to notable improvements in both sensitivity and specificity, underscoring the growing significance of CCTA as a diagnostic tool. The consistent reporting of high negative predictive value is particularly noteworthy. This review aims to explore the historical context, current status, and recent trends in diagnosing coronary artery stent restenosis using CCTA. [ABSTRACT FROM AUTHOR]

To investigate the role of pentraxin 3 (PTX3) in atherosclerotic disease progression and plaque destabilization, as well as in coronary restenosis after directional coronary atherectomy (DCA). PTX3 contents of early and advanced atherosclerotic lesions of the aorta obtained at autopsy were determined by ELISA and Western blot. Also, coronary plaques of patients with acute coronary syndrome (ACS) or stable angina pectoris (SAP) obtained by DCA were analyzed by immunohistochemistry for PTX3. The effects of PTX3 on smooth muscle cells (SMCs) and thrombogenesis were investigated with cultured human coronary artery SMCs and a flow chamber system, respectively. Advanced atherosclerotic lesions contained a significantly larger amount of PTX3 than early lesions (ELISA: 9.96 ± 2.77 ng/100 mg tissue, n = 8 vs 0.24 ± 0.18 ng/100 mg tissue, n = 6, P = 0.0097). Also, ACS plaques contained a significantly larger amount of PTX3 than SAP plaques (PTX3 immunohistochemistry–positive area percentage: 2.88 ± 0.53 %, n = 22 vs 0.67 ± 0.27 %, n = 23, P = 0.0009). Curiously, the patients who would remain free of post-DCA restenosis (n = 19) had plaques with a significantly higher PTX3 immunohistochemistry–positive area percentage than those who would develop restenosis (n = 12) (2.32 ± 0.49 % vs 0.49 ± 0.17 %, P = 0.002). In the mechanistic part of the study, PTX3 inhibited SMC proliferation and migration. PTX3 also inhibited platelet thrombus formation in the condition simulating arterial blood flow. PTX3 is increased in advanced (vs early) atherosclerotic lesions and unstable (vs stable) coronary plaques. The inhibitory effects of PTX3 on SMCs and thrombogenesis suggest that intraplaque PTX3 might have atheroprotective effects. [Display omitted] • Intraplaque CRP is known to promote atherosclerosis, but pentraxin 3 may not. • Pentraxin 3 in plaque increases as atherosclerosis progresses. • Pentraxin 3 inhibited SMC proliferation and migration in vitro. • Flow chamber system study showed pentraxin 3 inhibits thrombus formation. • Intraplaque pentraxin 3 might have atheroprotective effects. [ABSTRACT FROM AUTHOR]

Background: Fibromuscular dysplasia is an idiopathic, segmental, nonatherosclerotic, noninflammatory vascular disease that can lead to arterial stenosis, tortuosity, occlusion, aneurysms, and dissection. Fibromuscular dysplasia is a rare cause of hypertension that can easily be missed. To date, there has been no definitive treatment for fibromuscular dysplasia. Case report: In this report, we present an uncommon case of renovascular hypertension in a 21-year-old non-white female with a 3-year history of hypertension secondary to fibromuscular dysplasia involving bilateral renal arteries. Computed tomography angiography during the arterial phase revealed distal focal narrowing of the right main renal artery, distal focal narrowing of the left main renal artery, and proximal focal narrowing of the left accessory lower renal artery. Percutaneous balloon dilatation of the stenotic lesion was performed successfully up to 1 year After the procedure, the arterial blood pressure was within the normal range (110/70 to 125/75 mmHg) without medication. After 1 year of follow-up, CTA revealed re-stenosis in left main renal artery without clinical symptoms and normal blood pressure. Repeated procedure was done successfully. Conclusions: This case report highlights the difficulty in the diagnosis and treatment of focal fibromuscular dysplasia in young non-white female patients. Computerized tomographic angiography is a useful tool for identifying the cause and showing the benefit of percutaneous transluminal renal angioplasty treatment for this rare entity, as an early percutaneous angioplasty intervention may have a clinical cure for hypertension. [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]

Coronary in-stent restenosis (ISR) remains a challenge in interventional cardiology. We investigated the relationship between angiographic pre-interventional grade of lesion stenosis (LS) and the prognosis of late ISR. After exclusions, 110 patients with ISR and 109 patients without ISR were compared. In the ISR group, the grade of LS was greater (P <.001) and the length of the critical segment (LCS) was longer (P <.001). Stent length was longer in the ISR group (P =.008). Compared with the LCS, the grade of LS above 87.5% is 6.9 times more predictive of ISR than the LCS >10.5 mm. Kaplan–Meier curve analysis showed that the grade of initial LS >87.5% had a higher ISR rate than the grade of LS <87.5% (log-rank test P <.001) and critical lesion length over 10.5 mm had a higher ISR rate than critical lesion length under 10.5 mm (log-rank test P <.001). The present study found that the angiographic pre-interventional grades of LS and LCS were important predictors of ISR. Pre-interventional angiographic stenosis >87.5% was significantly predictive of late ISR. [ABSTRACT FROM AUTHOR]

Background Although the technology of bioresorbable vascular scaffold (BVS) aroused the peak of interest a few years ago and currently remains available only as part of experimental research, patients who have had BVS implanted should be still carefully monitored to detect possible long-term complications. Case summary We present the case of a 47-year-old man who had received BVS implantation for ST-segment elevation myocardial infarction. Six years later, computed tomography coronary angiography (CTCA) demonstrated in-segment restenosis in between two newly formed coronary aneurysms at the site of the implanted BVS. The patient received successful optical coherence tomography–guided percutaneous intervention with a new metallic drug-eluting stent implantation. Discussion Our case demonstrates that coronary aneurysms can be well characterized with CTCA and are often incidentally discovered as they cause no symptoms. The incidence of coronary aneurysm at the site of a previously implanted BVS is not defined, and little is known about the pathophysiology and evolution of these lesions. Therefore, the decision to proceed with conservative management or intervention must be tailored to the clinical conditions of the patient, the anatomy, the rapidity of growth, and the possible thrombotic burden. [ABSTRACT FROM AUTHOR]

Although platelet bioenergetic dysfunction is evident early in the pathogenesis of diabetic macrovascular complications, the bioenergetic characteristics in type 2 diabetic patients who developed coronary in-stent restenosis (ISR) and their effects on platelet function remain unclear. Here, we performed platelet bioenergetic profiling to characterize the bioenergetic alterations in 28 type 2 diabetic patients with ISR compared with 28 type 2 diabetic patients without ISR (non-ISR) and 28 healthy individuals. Generally, platelets from type 2 diabetic patients with ISR exhibited a specific bioenergetic alteration characterized by high dependency on fatty acid (FA) oxidation, which subsequently induced complex III deficiency, causing decreased mitochondrial respiration, increased mitochondrial oxidant production, and low efficiency of mitochondrial ATP generation. This pattern of bioenergetic dysfunction showed close relationships with both α-granule and dense granule secretion as measured by surface P-selectin expression, ATP release, and profiles of granule cargo proteins in platelet releasates. Importantly, ex vivo reproduction of high dependency on FA oxidation by exposing non-ISR platelets to its agonist mimicked the bioenergetic dysfunction observed in ISR platelets and enhanced platelet secretion, whereas pharmaceutical inhibition of FA oxidation normalized the respiratory and redox states of ISR platelets and diminished platelet secretion. Further, causal mediation analyses identified a strong association between high dependency on FA oxidation and increased angiographical severity of ISR, which was significantly mediated by the status of platelet secretion. Our findings, for the first time, uncover a pattern of bioenergetic dysfunction in ISR and enhance current understanding of the mechanistic link of high dependency on FA oxidation to platelet abnormalities in the context of diabetes.

BackgroundThere is limited "real-world" evidence examining treatment modalities and outcomes in patients with symptomatic peripheral arterial disease undergoing endovascular treatment of femoropopliteal (FP) in-stent restenosis (ISR).Materials and methodsWe compared outcomes in 2,895 patients from the XLPAD registry (NCT01904851) between 2006 and 2019 treated for FP ISR (n = 347) and non-ISR (n = 2,548) lesions. Primary endpoint included major adverse limb events (MALE) at 1 year, a composite of all-cause death, target limb repeat revascularization, or major amputation.ResultsISR patients were more frequently on antiplatelet (94.5% vs 89.4%, p=0.007) and statin (68.9% vs 60.3%, p=0.003) therapies. Lesion length was similar (ISR: 145 ± 99 mm vs. non-ISR: 142 ± 99 mm, p=0.55). Fewer treated ISR lesions were chronic total occlusions (47.3% vs. 53.7%, p=0.02) and severely calcified (22.4% vs. 44.7%, p < 0.001). Atherectomy (63.5% vs. 45.0%, p < 0.001) and drug-coated balloons (DCB; 4.7% vs. 1.7%, p < 0.001) were more frequently used in ISR lesions. The distal embolization rate was higher in ISR lesions (2.4% vs. 0.9%, p=0.02). Repeat revascularization (21.5% vs. 16.7%, p=0.04; Figure) was higher and freedom from MALE at 1 year was significantly lower (87% vs. 92.5%, p < 0.001) in the ISR group.ConclusionAtherectomy and DCB are more frequently used to treat FP ISR lesions. Patients with FP ISR have more intraprocedural distal embolization, higher repeat revascularization procedures, and lower freedom from MALE at 1 year.