Drug Eluting Research Articles

Investigating the bone regeneration activity of PVA nanofibers scaffolds loaded with simvastatin/chitosan nanoparticles in an induced bone defect rabbit model

This study aims at preparing electrospun PVA NFs incorporating simvastatin/chitosan nanoparticles (SIM CS NPs) as a controlled drug eluting scaffold for bone regeneration. Optimization was performed by Design Expert® software through establishing two factor, three level factorial design, where the independent variables were the applied voltage, flow rate and PVA solution/SIM CS NPs ratio. Formulation variables values for the optimized formula were 18KV, 0.5 mL/h, and 3:1 respectively. NFs diameter and mesh pore size were chosen as the dependent variables. The optimized NFs were evaluated morphologically, chemically, and physically. Additionally, in-vitro SIM release from the scaffolds was investigated along 24 days. Optimum NFs possessed 136 nm diameter size and 6.5 nm porosity. Also, they showed sustained SIM release for 24 days to achieve the desired goal in bone regeneration. The optimized NFs were implanted within induced bone defects in rabbits. In-vivo assessments were performed through cone beam computed tomography 3D images, bone density measurements, histological analysis and bone morphogenetic protein 2 (BMP 2) level. The obtained results proved the high potential of the optimized NFs in promoting bone regeneration compared to untreated group, non-medicated NFs group, free SIM group and NFs loaded with SIM group after 6 weeks of implantation.

Prevalence and impact of TWILIGHT criteria in all-comer patients undergoing percutaneous coronary intervention

Abstract Background The Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention (TWILIGHT) randomized clinical trial demonstrated that in selected high risk patients who took ticagrelor and aspirin for 3 months after percutaneous coronary intervention (PCI), continuing ticagrelor alone was associated with significantly less bleeding events than ticagrelor plus aspirin and did not lead to ischemic harm over a period of 1 year (1). The prevalence and risk of adverse events of patients fulfilling the TWILIGHT inclusion criteria in real-world setting is unclear. Purpose To elucidate the prevalence and prognosis of patients fulfilling the TWILIGHT inclusion criteria. Methods Patients that received at least one drug eluting stent in a coronary artery at a large tertiary center (Mount Sinai Hospital, New York) were considered for inclusion. As in the TWILIGHT trial, individuals on chronic oral anticoagulation treatment, with STEMI, cardiogenic shock, on dialysis, with prior stroke, or platelet count <100,000 were excluded. Patients were stratified in two groups: 1) TWILIGHT-like patients, who met at least one clinical (age ≥65 years, female sex, established vascular disease, diabetes mellitus, estimated glomerular fraction rate <60mL/min, acute coronary syndrome with troponin increase) and one angiographic (multivessel coronary artery disease [CAD], stent length >30mm, thrombotic target lesion, bifurcation requiring 2 stents, left main or proximal left anterior descending artery lesion, atherectomy device use, SYNTAX score ≥23) TWILIGHT inclusion criterion; 2) Non-TWILIGHT-like patients, who did not fulfil at least one clinical and one angiographic TWILIGHT inclusion criterion. The primary outcome was a composite of death, myocardial infarction (MI), stroke. Secondary outcomes included bleeding, components of the primary outcome, target vessel and target lesion revascularization, stent thrombosis. All events were assessed at 1 year after PCI. Results Out of 30,470 patients undergoing PCI between 2012 and 2019, 13,236 were included in the current analysis. TWILIGHT criteria were met in 11,018 (83%) patients. Established vascular disease and multivessel CAD were the most frequently fulfilled criteria. At 1 year, TWILIGHT-like patients were at higher risk for the primary outcome (3.2% vs 1.1%, HR 2.85, 95% CI 1.83–4.44), severe bleeding (3.3% vs 1.8%, HR 1.86, 95% CI 1.32–2.62), all-cause death (1.4% vs 0.4%, HR 3.63, 95% CI 1.70–7.77), myocardial infarction (1.8% vs 0.6%, HR 2.81 95% CI 1.56–5.04), TVR (7.8% vs 4.1%, HR 1.94, 95% CI 1.53–2.47), TLR (5.1% vs 1.7%, HR 2.98 95% CI 2.07–4.29). Stent thrombosis and stroke rate were generally low and did not differ between patients meeting or not the TWILIGHT inclusion criteria. Conclusion Among all-comer patients undergoing PCI, the fulfillment of the TWILIGHT inclusion criteria is frequent and is associated with a higher risk of death, ischemic and bleeding complications Funding Acknowledgement Type of funding sources: None.

Impact of body mass index on outcomes in patients undergoing percutaneous coronary intervention for in-stent restenosis

Abstract Background Recent advances in drug eluting stents (DES) design have significantly decreased the rates of in-stent restenosis (ISR). Nonetheless, ISR remains a major problem, affecting 5–10% of patients undergoing percutaneous coronary intervention (PCI). Furthermore, PCI for ISR is often a poor prognostic factor for outcomes after the procedure. Historically, obese patients tended to have better outcomes when undergoing PCI, however it is unclear if this trend continues for the same population undergoing PCI for ISR. Purpose Investigate the outcomes of patients undergoing PCI for ISR in the overweight and normal weight population. Methods All patients undergoing PCI with DES implantation at a tertiary care center from January 2012 to December 2019 were included. Normal weight was defined as a body mass index (BMI) greater than or equal to 18.5 kg/m2 and less than 25 kg/m2, while overweight was defined as a BMI greater than or equal to 25 kg/m2. Patients with BMI <18.5 kg/m2, underwent PCI for acute myocardial infarction (MI), or received a bare metal stent (BMS) were excluded. The primary outcome was major events (MACE), a composite of all-cause mortality, myocardial infarction (MI), and target vessel revascularization (TVR) up to one year after PCI. Secondary outcomes included individual components of the primary endpoint. Results Out of 16,234 patients with available data on BMI, 12,444 (76.7%) were overweight and 3,790 (23.3%) were normal weight. Among overweight patients, 2,879 (23.1%) underwent PCI for ISR versus 815 (21.5%) of normal weight patients. Regardless of BMI status, patients undergoing PCI for ISR had higher rates of co-morbidities such as hypertension, hyperlipidemia, and diabetes mellitus than non-ISR counterparts. At one year post PCI, both overweight and normal weight patients undergoing PCI for ISR had increased risk of MACE (overweight: 18.4% vs. 6.7%; HR 2.83; 95% CI 2.50–3.20; normal weight: 18.8% vs. 7.8%, HR 2.43, 95% CI 1.95–3.04) when compared to non-ISR counterparts, mostly driven by TVR (overweight: 16% vs. 4.6%; HR 3.58; 95% CI 3.11–4.13; normal weight: 15.2% vs. 4.1%; HR 3.69; 95% CI 2.80–4.86). However, only overweight patients undergoing PCI for ISR had higher risk of all cause mortality (2.2% vs. 1.5%; HR 1.42; 95% CI 1.03–1.95) and MI (3.0% vs. 1.3%, HR 2.22; 95% CI 1.64–2.99) when compared to non-ISR counterparts (Figure 1). Conclusions PCI for ISR was associated with increased risk of MACE, irrespective of body weight. The risks of all-cause mortality and MI in ISR vs non-ISR patients only reached statistical significance in overweight patients. Funding Acknowledgement Type of funding sources: None.

Determinants of neointimal strut coverage in bio-degradable polymer coated ultrathin strut stent

Abstract Introduction Incomplete strut coverage (ISC) is the most important morphometric determinant of stent thrombosis. Determinants of ISC have been studied in thick and thin strut stents. Purpose To identify morphometric factors causing ISC in the biodegradable polymer-coated ultra-thin strut drug eluting stent (BP-UTS-DES) that are designed to encourage better strut coverage. Methods Patients undergoing implantation of a 65μm BP-UTS-DES had opportunistic OCT during staged PCI to assess strut coverage at 90 days. Images were analysed offline by experienced operators blinded to patient and procedural data. Neointimal thickness (NIT, μm) was measured as the minimum endoluminal distant between the strut and lumen border. All malapposed struts were considered uncovered. ISC was defined as <100% covered struts in a frame. Stepwise logistic regression using multiple morphometric variables was used to identify independent determinants of ISC including markers of circumferential distribution of neointimal growth (CVS,NUS,RUS), symmetry of stent expansion (SEI, AVS, MAS) in each cross section and the geographical location of the frame along the axis of the stent. Results We analysed 11652 frames of 65 stents (1976 mm) in 46 arteries of 40 patients. All stents were post dilated. 95.6% arteries had >20mm stents, 39.1% were overlapped and 15.2% were chronic total occlusions. Malapposition was seen in 2.6% of all struts and 39.2% of uncovered struts. The proportion of covered struts decreased as indices of circumferential uniformity of distribution of neointimal hyperplasia increased (CVS: r=0.37, p<0.001; RUS: r=0.36, p<0.001; NUS: r=0.52, p<0.001). As uniformity of stent expansion improved (SEI increased) strut coverage and circumferential uniformity of neointimal hyperplasia increased (CVS, NUS and RUS decreased) suggesting that distribution of neointimal growth becomes homogeneous as uniformity of stent expansion improves (Fig. 1). Determinants ISC is shown in Table 1. Conclusion SEI but not AVS or MAS determines ISC. Compared to the distal third of the stent frames in the middle third had lower and the proximal third had high risk of ISC. Funding Acknowledgement Type of funding sources: None.

Prognostic implication of platelet reactivity according to disease entity after drug eluting stent implantation: results from the PTRG-DES consortium

Abstract Background Relationship between the level of antiplatelet effect and clinical event appears weak in East Asian patients. In addition prognostic implication of platelet reactivity may differ according to index presentation of disease entity (AMI vs. non-AMI). Methods PTRG-PFT consortium was established to determine the linkage of platelet function with long-term clinical outcome during DAPT (aspirin+clopidogrel) in DES-treated East Asian patients (n=11,714). Platelet reactivity was measured using the VerifyNow P2Y12 assay and its level was divided according to quartile distribution (≤168, 169–220, 221–271, ≥272 P2Y12 reaction unit [PRU]). Primary endpoints were incidences of major adverse cardiac and cerebrovascular events (MACCE) post-PCI. Results Impact of platelet reactivity on MACCE occurrence appeared proportionally increased irrespective of type of disease entity, but their relationship was relatively stronger in the AMI vs. non-AMI group (Figure 1A and B). The cutoff of high-risk platelet reactivity was lower in the AMI group compared with the non-AMI group (225 vs. 245 PRU), and the cutoff of low-risk platelet reactivity (immunity zone) was similar between the groups (175 vs. 170 PRU). In the AMI patients (28.5%), 3rd and 4th quartiles significantly increased MACCE rate (HRadjusted 2.19 and 2.24) (Figure 1C and D). However, 4th quartile only was significantly associated with increased risk of MACCE among the non-AMI patients (71.5%) (HRadjusted 2.19). Conclusion Close associations between platelet reactivity and MACCE occurrence were observed irrespective of type of disease entity. In addition, the targeted antiplatelet level to prevent platelet-centric events appeared similar between the AMI and non-AMI patients. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Korean Society of Intervention Cardiology

Outcomes of drug coated balloon only angioplasty for stable angina in routine clinical practice

Abstract Introduction The recent BASKETSMALL2 trial demonstrated safety and efficacy of drug coated balloon (DCB) angioplasty for de novo small vessel disease. Registry data have demonstrated that DCB angioplasty is safe; however, the majority of these studies are limited due to long recruitment time and small number of patients with DCB compared to drug eluting stents (DES). Our aim was to investigate if DCB-only strategy is safe to incorporate in routine clinical practice. Methods We identified all patients treated for stable angina and de novo disease in our institution from January 2015 till November 2019. During that period an equivalent number of patients were treated with DCB-only or DES-only strategy on a yearly basis. The primary endpoint was all cause mortality. The secondary endpoints were cardiovascular mortality, acute coronary syndrome (ACS), ischaemic stroke, major bleeding and target lesion revascularisation (TLR). Data were obtained from the hospital episodes statistics from NHS digital. Clinical and angiographic data were collected from our prospectively collated database and supplemented from electronic records as required. All angiograms were reviewed to confirm accuracy of angiographic data and determine TLR. On multivariable COX regression analysis (Table 1) age, frailty and hypercholesterolaemia were the only independent predictors of all cause mortality. Results A total of 1302 patients were identified. HES data were not obtained for 65 patients who had opted-out, therefore 1237 were included in the analysis; 544 were treated with DCB and 693 with DES. The average age for the DCB-group was 67.9±10.2 years old (79% male); while for the DES group it was 67.9±9.7 years old (78.1% male). The average follow up was 1339±514 days and 1354±527 days for the DCB and DES group respectively. Table 1 shows the differences between the groups in terms of clinical and angiographic characteristics. The DES group had more patients with history of COPD (6.3% vs 3%; p=0.01) and larger average vessel diameter (3.46±0.58 vs 3.09±0.53mm; p<0.001). The DCB group had more patients with true bifurcation disease and TIMI 0 or 1 pre-PCI (11.6% vs 8.1%; p=0.04) and TIMI 0 or 1 pre-PCI (11.7% vs 6.6%; p=0.001). Furthermore, more than 70% of patients in the DCB group had vessel diameter ≥3mm indicating that large vessels were treated. The all cause mortality was 35 (6.4%) and 59 (8.5%) for the DCB and DES group respectively. Kaplan Meier estimator plot did not show a significant difference between the groups. There was no difference between the groups in any of the secondary endpoints (cardiovascular mortality, ACS, stroke, major bleeding and TLR). Conclusion Our real world data from a large, contemporary cohort of stable angina patients, including predominantly large vessels, demonstrate that DCB only angioplasty is safe compared to DES in terms of all major cardiovascular endpoints including TLR. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): B Braun - investigator initiated research

Feasibility and clinical outcomes of 48 mm drug eluting stents in management of patients with coronary artery disease

Abstract Background Long Coronary lesions represent a formidable challenge during percutaneous coronary intervention (PCI). Implantation of multiple contiguous stents may result in sections of overlapping stents or gaps of unstented segments and is an independent predictor of restenosis and major adverse cardiovascular events (MACEs). Objectives To assess the feasibility, and short-term clinical outcomes of implanting 48mm drug eluting stents (DES) in treatment of long lesions in patients with coronary artery disease (CAD). Methods A prospective study enrolling 300 patients, with a single CAD planned to undergo PCI with 48mm DES. Clinical data, procedural outcomes and follow-up to 6 months were obtained. MACEs were considered the combined study end point defined as cardiac death, non-fatal myocardial infarction, unstable angina and the need for target lesion revascularization (TLR). Results Among the 300 subjects enrolled, 80% were males, mean age was 60.8±8.6 years. Procedural success rate was 97.3%. Failure of crossing was encountered in 4 patients due to severe tortuosity. Six-month clinical outcome was compared between diabetic (DM) (n=90) and non-DM patients; 6-month cumulative MACEs were significantly lower in the non-DM than in DM group (2.9% in non-DM vs. 13.3% in DM, p=0.013). Clinically driven TLR was 4% and two cardiac deaths were reported. The independent predictors of repeat revascularization were insulin treated type 2 DM, and reference vessel diameter (RVD) ≤2.75 mm. Conclusion The use of 48mm DES is feasible, safe and cost effective in treatment of long coronary lesions. Independent predictors of repeat revascularization are type 2 diabetes mellitus, and RVD ≤2.75mm. Funding Acknowledgement Type of funding sources: None.

Correlation of FFR measured after DES implantation with clinical parameters and long-term clinical outcome

Abstract Introduction The role of fractional flow reserve (FFR) measured directly after drug eluting stent (DES) implantation (post-PCI FFR) is not clear in predicting major adverse cardiac events (MACE), and it is not known which clinical parameters affect post-PCI FFR. Aim We aimed to clarify the relationship between post-PCI FFR and clinical parameters, post-PCI FFR and long-term MACE and determine the best post-PCI FFR cut-off in MACE prediction. Method Patients who underwent post-PCI (DES) FFR measurement at our center between March 2009 and January 2021 were included. We examined the relationship between post-PCI FFR and gender, age, hypertension, diabetes mellitus, hyperlipidemia, indication (acute (ACS) vs. chronic coronary syndrome (CCS)), stent diameter, in-stent restenosis vs de novo lesion category, proximal vs. non-proximal lesion location, LAD (vs. non-LAD) location, and pre-PCI FFR. We sought to determine the correlation between post-PCI FFR and target vessel-related MACE (cardiovascular death (CVD), non-fatal myocardial infarction (MI), recurrent revascularization (TVR)). Optimal cut-off was determined by ROC curves. Results Post-PCI FFR measurement was performed in 500 coronary arteries of 434 patients. LAD location (0.86 vs. non-LAD 0.91, p<0.001), male gender (0.87 vs. 0.89, p=0.001), younger age (p=0.0215), smaller stent diameter (p=0.0028) and lower pre-PCI FFR (p=0.0006) proved to be independent predictors of lower post-PCI FFR, no other parameter showed a significant correlation with post-PCI FFR. During a median follow-up of 37 months, 24 CVD, 15 MI and 47 TVR occurred. Follow-up was complete in 96.2% of patients. There was a significant inverse correlation between post-PCI FFR and MACE (p<0.001). Diabetes mellitus (p=0.0024) and in-stent restenosis (0.0356) were also independent predictors of MACE. The best post-PCI FFR cut-off for the total patient population, LAD and non-LAD lesions were 0.83 (p<0.0001), 0.83 (p<0.0001), and 0.88 (p=0.0091), respectively. Conclusion LAD location, male gender, younger age, smaller stent diameter and lower pre-PCI FFR value result in lower post-PCI FFR. There is no significant difference between post-PCI FFR measured in ACS vs. CCS. FFR measured after PCI, diabetes mellitus and in-stent restenosis are significant predictors of MACE-free long-term survival. The best post-PCI FFR cut-off to predict MACE was 0.83 for the whole patient population and for LAD and 0.88 for non-LAD lesions. Funding Acknowledgement Type of funding sources: None.

BUBBLING OVER: A CASE OF SUBCONJUNCTIVAL EMPHYSEMA AND PNEUMOMEDIASTINUM FOLLOWING LAPAROSCOPIC PROSTATECTOMY

BUBBLING OVER: A CASE OF SUBCONJUNCTIVAL EMPHYSEMA AND PNEUMOMEDIASTINUM FOLLOWING LAPAROSCOPIC PROSTATECTOMY

Coronary Revascularization in Diabetes Patients

India has become the diabetes capital of the world. Coronary artery disease in diabetes patients are often silent and complex. Incidence of diffuse and multi vessel disease are more predominant in diabetes patients. Triple vessel disease and diffuse disease are common and often bring challenges in selecting treatment option. The incidence of stent thrombosis, in stent restenosis and repeat interventional procedures are more common in diabetes patients. Though coronary artery bypass surgery is known to achieve better long -term outcome in triple vessel disease in diabetes patients but coronary interventions with latest generation drug eluting stents are also shown to achieve similar type of outcome. Careful selection of cases with consideration of coronary anatomy and a multidisciplinary approach in treatment of complex coronary disease are the keys of success and better long -term result.

ASSESSMENT OF VASCULAR RESPONSE OF N-DEAVOUR® DRUG ELUTING STENT VS. XIENCE PRO™ DRUG ELUTING STENT AND MULTILINK VISION BARE METAL STENT IN THE PORCINE CORONARY ARTERY MODEL

Objectives: The objectives of the study were to evaluate the vascular and tissue response of Pakistani manufactured novel drug eluting stent (called N-DEAVOUR®) on a swine model and compare the results with XIENCE PRO™. Methodology: A total of 10 animals were used for the study and assigned randomly to each time-point group. The test articles were administered percutaneously and each animal was implanted with one stent in each one of the coronary arteries (3 in total) LCA (left circumflex artery), LAD (left anterior descending coronary artery), and RCA (right coronary artery). Additionally, a second test stent was implanted in some animals (4 in total). QCA (Quantitative Coronary Angiography) technique was used for measurements of the vessel at the target site. OCT (Optical Coherence Tomography) was performed only at follow up time-points which were 30, 90 and 180 days. Results: At 30 DFU, parameters for N-DEAVOUR® were comparable to those of both control (XIENCE PROTM and VISION) stents. At 90 days follow-up N-DEAVOUR® showed no statistically significant difference in performance for values of lumen area, stent area, area stenosis, and neointimal area against XIENCE PRO™. With reference to stent area, at 90 DFU, N-DEAVOUR® performed better than XIENCE PRO™ (p=0.0056). For neo-intimal area, area stenosis and lumen area, the differences between XIENCE PRO™ and N-DEAVOUR® were non-significant (p=0.13; p=0.9; p=0.086) respectively. These results indicate the positive potential of N-DEAVOUR® to be successfully implanted in clinical settings after necessary randomized clinical trials are executed. Conclusion: This study proved that the drug eluting stent examined in the present study is both safe and feasible. This study supports that this stent can move forward for human trials.

Efficacy analysis following polymer coated drug eluting stent and bare metal stent deployment for femoropopliteal arterial disease.

The objective is to assess the performance of the Eluvia polymer coated drug eluting stent (DES) compared to a bare metal stent (BMS) platform in patients with femoropopliteal arterial disease. This is a retrospective, single-center analysis. Patients treated with the Eluvia DES (group Eluvia) or the EverFlex BMS (group BMS) for femoropopliteal disease between January 2013 and December 2019 were included. Primary measure outcome of this analysis was the overall mortality. The PTX specific mortality, the primary patency, the amputation free survival (AFS), and the target lesion revascularization (TLR) rates were additionally evaluated. A total of 124 patients were treated by BMS deployment, while the Eluvia platform was preferred in 75 subjects. In both groups the majority presented with lifestyle limiting claudication (BMS: 84% vs Eluvia: 73%, p = 0.73). Chronic total occlusions were more frequent in patients treated by BMS (BMS: 71% vs Eluvia: 84%, p = 0.027), whereas the calcification burden (BMS: 81% vs Eluvia: 76%, p = 0.43) and the median lesion length (in mm, IQR) (BMS: 160 (100 to 240) vs Eluvia: 140 (80 to 229), p = 0.17) were comparable. At 24 months, the overall survival (BMS: 93% vs Eluvia: 89%, hazard ratio (HR): 1.20, 95% confidence interval (CI): 0.55 to 2.64, p = 0.64) and the PTX specific survival (BMS: 95% vs Eluvia: 95%, HR: 1.28, 95% CI: 0.41 to 4.02, p = 0.67) did not differ significantly between the two platforms. No significant difference was observed regarding the 24 months primary patency rate (BMS: 66% vs Eluvia: 78%, HR: 0.65, 95% CI: 0.37 to 1.15, p = 0.18), the freedom from TLR (BMS: 83% vs Eluvia: 89%, HR: 0.81, 95% CI: 0.39 to 1.68, p = 0.572), and the AFS (BMS: 93 vs Eluvia: 89%, HR: 1.20, 95% CI: 0.55 to 2.64). The Cox regression analysis revealed a higher mortality risk among patients with chronic limb-threatening ischemia (CLTI) (HR: 3.14, 95% CI: 1.61 to 6.14, p = 0.008), chronic obstructive pulmonary disease (COPD) (HR: 4.65, 95% CI: 2.14 to 10.09, p = 0.001), in octagenerians (HR: 4.40, 95% CI: 1.92 to 10.44, p = 0.005), and in patients not on statins at baseline (HR: 2.44, 95% CI: 1.19 to 4.99, p=0.014). In this cohort, the use of the Eluvia DES did not increase the risk for mortality compared to BMS deployment. CLTI, COPD, advanced age, and the lack of statin therapy at baseline were associated with a higher risk for death.

An intricate interplay between stent drug dose and release rate dictates arterial restenosis.

Since the introduction of percutaneous coronary intervention (PCI) for the treatment of obstructive coronary artery disease (CAD), patient outcomes have progressively improved. Drug eluting stents (DES) that employ anti-proliferative drugs to limit excess tissue growth following stent deployment have proved revolutionary. However, restenosis and a need for repeat revascularisation still occurs after DES use. Over the last few years, computational models have emerged that detail restenosis following the deployment of a bare metal stent (BMS), focusing primarily on contributions from mechanics and fluid dynamics. However, none of the existing models adequately account for spatiotemporal delivery of drug and the influence of this on the cellular processes that drive restenosis. In an attempt to fill this void, a novel continuum restenosis model coupled with spatiotemporal drug delivery is presented. Our results indicate that the severity and time-course of restenosis is critically dependent on the drug delivery strategy. Specifically, we uncover an intricate interplay between initial drug loading, drug release rate and restenosis, indicating that it is not sufficient to simply ramp-up the drug dose or prolong the time course of drug release to improve stent efficacy. Our model also shows that the level of stent over-expansion and stent design features, such as inter-strut spacing and strut thickness, influence restenosis development, in agreement with trends observed in experimental and clinical studies. Moreover, other critical aspects of the model which dictate restenosis, including the drug binding site density are investigated, where comparisons are made between approaches which assume this to be either constant or proportional to the number of smooth muscle cells (SMCs). Taken together, our results highlight the necessity of incorporating these aspects of drug delivery in the pursuit of optimal DES design.

Imbalance of Pro- and Anti-inflammatory Cytokines Induced Different Types of Recurrent Atrial Arrhythmias after Drug Eluting Coronary Stent Implantation.

Atrial arrhythmias are associated with an increased risk of stroke and death in the elderly. The risk and predictive factors of recurrent atrial arrhythmias in elderly patients after coronary stenting are not well known. This research sought to investigate the roles of pro- and anti-inflammatory cytokine imbalances in different types of recurrent atrial arrhythmias in elderly patients defined as individuals aged 65 years or older after sirolimus eluting stent (Cordis, Warren, New Jersey) implantation. We measured interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-17 (IL-17), interleukin-13 (IL-13) and interleukin- 37 (IL-37) in elderly patients with recurrent atrial arrhythmias and assessed the impact of pro- and antiinflammatory cytokine imbalances on recurrent atrial arrhythmias in elderly patients after coronary stenting. Levels of IL-1 β, IL-6, IL-8, and TNF-α were remarkably increased (p<0.001), and IL-10, IL- 17, IL-13, and IL-37 were remarkably lowered (p<0.001) in elderly patients with recurrent atrial arrhythmias after coronary stent implantation. Imbalance of pro- and anti-inflammatory cytokines induced recurrent atrial arrhythmias after coronary stenting. Pro- and anti-inflammatory cytokine imbalances may be used to identify elderly patients who have an increased risk of developing recurrent atrial arrhythmias after coronary stenting. The imbalance of pro- and anti-inflammatory cytokines was associated with recurrent atrial arrhythmias in elderly patients after coronary stenting. Pro- and anti-inflammatory cytokines may be clinically useful biomarkers for predicting recurrent atrial arrhythmias in elderly patients after coronary stent implantation.

Optimize PLA/EVA Polymers Blend Compositional Coating for Next Generation Biodegradable Drug-Eluting Stents.

In this research work, polymer blends of poly-lactic acid (PLA)/ethylene vinyl acetate (EVA) were prepared as the drug carrier materials for a bi-layer drug-loaded coating film for coronary stents. Different optimum compositions of blends were prepared by using an intense mixer. Then, the blends were hot-pressed and later cold-pressed to prepare for films of different thickness. The changes in weight, surface analysis and biodegradability with increasing time were studied using Scanning electron microscopy (SEM), weight loss and biodegradability tests. The mechanical and thermal properties of drug-loaded films were studied through universal testing machine (UTM) and thermo-gravimetric analysis (TGA). The effects of PLA, EVA and drug contents on in-vitro drug contents were investigated through the Ultraviolet-Visible Spectroscopy (UV-VIS) chemical analysis technique. The results obtained clearly showed that the addition of PLA promoted the unleashing of the drug whereas the addition of EVA nearly did not have the same affect. The mechanical properties of these various films can be tuned by adjusting the contents of blend parts. The factors affecting the unleashing of the drug became a serious matter of concern in evaluating the performance of bio-resorbable drug eluting stents. As a result, today’s chemical blends may be useful drug carrier materials for drug-loaded tube coatings capable delivering purgative drug in an incredibly tunable and regulated manner.

Comparison of three methods for assessment of drug elution: In vitro elution of gentamicin from a collagen-based scaffold

In vitro drug elution experiments are commonly performed when evaluating the fitness of drug delivery devices for in vivo use. Evaluation of drug elution characteristics spans many drug delivery applications including local delivery of antimicrobials and chemotherapeutics, and is of particular interest for prevention and treatment of orthopedic infections. Despite widespread utility, there is little agreement on methodology to perform such studies, and there are recognized limitations in published works. We evaluated three of the most commonly reported in vitro drug elution methods. We utilized a commercially available collagen matrix (Fibro-Gide®, Geistlich) and an antibiotic that is widely used for local antimicrobial therapy (gentamicin). The protocols used are: 1. complete replacement of media and washing of device, 2. complete replacement of media without washing, or 3. partial replacement of media. The results show statistically significant differences in elution characteristics among the three methods utilizing this delivery vehicle and drug. These results may provide the framework for moving toward more consistent methodology for in vitro elution experiments and address certain acknowledged limitations in the literature.

Integrated hydrogel sensor-actuator for glucose sensitivity and drug elution

Integrated hydrogel sensor-actuator for glucose sensitivity and drug elution

Evaluation of the safety of paclitaxel eluting medical devices to treat peripheral arterial disease – The DETECT “Drug EluTing dEvices FrenCh safeTy survey” national study

A meta-analysis published in 2018 concluded that mid-term and long-term mortality was higher in patients treated with paclitaxel eluting balloons and stents than in those treated with bare devices after the endovascular treatment of femoropopliteal lesions. There are no national data concerning the safety of these devices. We designed the DETECT (Drug EluTing dEvices FrenCh safeTy survey) study in order to compare the risk of mortality in patients treated with paclitaxel eluting balloons and/or stents or with bare devices.

Second generation drug eluting stent: The longer, the better?

Carlo Di Mario has received institutional research grants from AMGEN, Abbott Vascular, Behring, Boston Scientific, Chiesi Pharmaceuticals, Daiichi-Sankyo, Edwards Lifescience, Medtronic, Shockwave Medical, Volcano Philips. Selcuk Kucukseymen is the recipient of the clinical fellowship grant from the European Association of Percutaneous Cardiovascular Interventions (EAPCI).

Meta-Analysis of Provisional Versus Systematic Double-Stenting Strategy for Left Main Bifurcation Lesions

ObjectiveWe sought to compare the clinical outcomes with provisional versus double-stenting strategy for left main (LM) bifurcation percutaneous coronary intervention (PCI). BackgroundDespite two recent randomized controlled trials (RCTs) and several observational reports, the optimal LM bifurcation PCI technique remains controversial. MethodsPubMed, Cochrane Central Register of Controlled-Trials (CENTRAL), Clinicaltrials.gov, International Clinical Trial Registry Platform were leveraged for studies comparing PCI bifurcation techniques for LM coronary lesions using second-generation drug eluting stents (DES). The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes of interest were all-cause mortality, cardiovascular mortality, myocardial infarction (MI), target vessel or lesion revascularization, and stent thrombosis. ResultsTwo RCTs and 10 observational studies with 7105 patients were included. Median follow-up duration was 42 months (IQR: 25.7). Double stenting was associated with a trend towards higher incidence of MACE (odds ratio [OR] 1.20; 95 % confidence interval [CI] 0.94 to 1.53) compared with provisional stenting. This was mainly driven by higher rates of target lesion revascularization (TLR) (OR 1.50; 95 % CI 1.07 to 2.11). There were no statistically significant differences in the incidence of all-cause mortality, cardiovascular mortality, MI, or stent thrombosis. On subgroup analysis according to the study type, provisional stenting was associated with lower MACE and TLR in observational studies, but not in RCTs. ConclusionFor LM bifurcation PCI using second-generation DES, a provisional stenting strategy was associated with a trend towards lower incidence of MACE driven by statistically significant lower rates of TLR, compared with systematic double stenting. These differences were primarily driven by observational studies. Further RCTs are warranted to confirm these findings.