Drug Eluting Research Articles

Long-Term Outcome of Drug-Coated Balloon vs Drug-Eluting Stent for Small Coronary Vessels: PICCOLETO-II 3-Year Follow-Up

BackgroundNative vessel coronary artery disease represents 1 of the most attractive fields of application for drug-coated balloons (DCBs). To date, several devices have been compared with drug-eluting stents (DESs) in this setting with different outcomes. ObjectivesThe authors sought to compare the short- and long-term performance of the paclitaxel DCB with the everolimus-eluting stent in patients with de novo lesions in small coronary vessel disease. MethodsPICCOLETO II (Drug Eluting Balloon Efficacy for Small Coronary Vessel Disease Treatment) was an academic, international, investigator-driven, multicenter, open-label randomized clinical trial in which patients were allocated to a DCB (n = 118) or DES (n = 114). We previously reported the superiority of DCBs regarding in-lesion late lumen loss at 6 months. Herein we report the final 3-year clinical follow-up with the occurrence of major adverse cardiac events (MACEs), a composite of cardiac death, nonfatal myocardial infarction, target lesion revascularization, and its individual components. ResultsThe 3-year clinical follow-up (median 1,101 days; IQR: 1,055-1,146 days) was available for 102 patients allocated to DCB and 101 to DES treatment. The cumulative rate of all-cause death (4% vs 3.9%; P = 0.98), cardiac death (1% vs 1.9%; P = 0.56), myocardial infarction (6.9% vs 2%; P = 0.14), and target lesion revascularization (14.8% vs 8.8%; P = 0.18) did not significantly differ between DCBs and DESs. MACEs and acute vessel occlusion occurred more frequently in the DES group (20.8% vs 10.8% [P = 0.046] and 4% vs 0% [P = 0.042], respectively). ConclusionsThe long-term clinical follow-up of the PICCOLETO II randomized clinical trial shows a higher risk of MACEs in patients with de novo lesions in small vessel disease when they are treated with the current-generation DES compared with the new-generation paclitaxel DCB. (Drug Eluting Balloon Efficacy for Small Coronary Vessel Disease Treatment [PICCOLETO II]; NCT03899818)

Machine Learning Identifies New Predictors on Restenosis Risk after Coronary Artery Stenting in 10,004 Patients with Surveillance Angiography.

Machine learning (ML) approaches have the potential to uncover regular patterns in multi-layered data. Here we applied self-organizing maps (SOMs) to detect such patterns with the aim to better predict in-stent restenosis (ISR) at surveillance angiography 6 to 8 months after percutaneous coronary intervention with stenting. In prospectively collected data from 10,004 patients receiving percutaneous coronary intervention (PCI) for 15,004 lesions, we applied SOMs to predict ISR angiographically 6-8 months after index procedure. SOM findings were compared with results of conventional uni- and multivariate analyses. The predictive value of both approaches was assessed after random splitting of patients into training and test sets (50:50). Conventional multivariate analyses revealed 10, mostly known, predictors for restenosis after coronary stenting: balloon-to-vessel ratio, complex lesion morphology, diabetes mellitus, left main stenting, stent type (bare metal vs. first vs. second generation drug eluting stent), stent length, stenosis severity, vessel size reduction, and prior bypass surgery. The SOM approach identified all these and nine further predictors, including chronic vessel occlusion, lesion length, and prior PCI. Moreover, the SOM-based model performed well in predicting ISR (AUC under ROC: 0.728); however, there was no meaningful advantage in predicting ISR at surveillance angiography in comparison with the conventional multivariable model (0.726, p = 0.3). The agnostic SOM-based approach identified-without clinical knowledge-even more contributors to restenosis risk. In fact, SOMs applied to a large prospectively sampled cohort identified several novel predictors of restenosis after PCI. However, as compared with established covariates, ML technologies did not improve identification of patients at high risk for restenosis after PCI in a clinically relevant fashion.

Drug eluting chest tube with sustained release of local anesthetic agents for pain reduction

Chest tubes are frequently used in patients following major cardiothoracic surgeries to remove fluid and air from the pleural space. Tube implantation in the intercostal space and the irritation of the mucous membranes by the tube in the pleural space results in significant pain to the patient that often requires systemic treatment with narcotics to control. Opioid use often leads to extended hospital stays and increased risk of addiction. In this work, we created and optimized a drug eluting chest tube that can release anesthetic agents locally to reduce the need for systemic opioid use following chest tube implantation. The drug eluting chest tube consists of a porous polymer tube made from sintered ultra-high molecular weight polyethylene. The porous of this tube are loaded with bupivacaine in solid cast poly(lactic-co-glycolic acid) or loaded in to PLGA microparticles. This approach is advantageous in allowing a large amount of drug to be loaded into the tube and to protect the drug eluting polymer from damage during implantation or due to patient motion. The microparticle approach was effective in releasing drug from the tube but not in the amounts needed for long term effectiveness following implantation. The solid casting strategy released high amounts of the drug for at least 14 days. For a typical length of tubing, the dose released was equivalent to the maximal daily recommended dose of bupivacaine. We also tested the mechanical properties of the tubes and optimized processing conditions to reduce their stiffness. Our work demonstrates a robust and simple strategy for creating chest tubes that release local anesthetic agents while protecting the drug during tube insertion and following implantation.

Perivascular patch using biodegradable polymers: Investigation of mechanical and drug elution characteristics

Intimal hyperplasia (IH) is the primary cause for the vascular graft stenosis. Perivascular devices offer a potential treatment option to reduce the impact of intimal hyperplasia by providing mechanical support and local administration of therapeutic agents to control cellular overgrowth. In the present study, a perivascular patch primarily made up of biodegradable polymer, Poly L-Lactide, has been designed with adequate mechanical strength and ability for sustained drug elution of anti-proliferative drug (Paclitaxel). The elastic modulus of the polymeric film has been optimized by blending the base polymer with different grades of biocompatible polyethylene glycols. Using design of experiments, the optimized parameters were obtained as PLLA with 2.5% PEG-6000 and have shown 3.14 MPa elastic modulus. The film prepared based on optimum conditions has been employed for prolonged drug delivery (about four months) under simulated physiological conditions. The addition of drug release rate enhancer (polyvinyl pyrrolidone K90F) has improved the drug elution rate and ∼83% drug was released over entire study period. The molecular weight of the base biodegradable polymer was estimated by gel permeation chromatography (GPC) which remained unchanged during the drug release study duration. Evidences of Paclitaxel drug crystallization were found to contribute to the sustained drug elution. The SEM examination of the surface morphology post-incubation revealed micropores on the surface, contributing to the overall drug release rate. The study concluded that perivascular biodegradable films could be tailored for their mechanical properties, and sustained drug elution could also be formulated with reasonable choices of biodegradable polymer and biocompatible additives.

ERYTHROMYCIN-DOPED NANOFIBRE COATING ENHANCES OSSEOINTEGRATION AND INHIBITS STAPHYLOCOCCUS AUREUS-INDUCED OSTEOLYSIS

Failure of osseointegration and periprosthetic joint infection (PJI) are the two main reasons of implant failure after total joint replacement (TJR). Nanofiber (NF) implant surface coating represents an alternative local drug eluting device that improves osseointegration and decreases the risk of PJI. The purpose of this study was to investigate the therapeutic efficacies of erythromycin (EM)-loaded coaxial PLGA/PCL-PVA NF coating in a rat S. aureus-infected tibia model.NF coatings with 100mg and 1000mg EM were prepared. NF without EM was included as positive control. 56 Sprague Dawley rats were divided into 4 groups. A titanium pin (1.0-mm x 8 mm) was placed into the tibia through the intercondylar notch. S. aureus (SA) was introduced by both direct injection of 10 μl broth (1 × 104 CFU) into the medullary cavity and single dip of Ti pins into a similar solution prior to insertion. Rats were sacrificed at 8 and 16 weeks after surgery. The outcome measurements include μCT based quantitative osteolysis evaluation and hard tissue histology.Results: EM-NF coating (EM100 and EM1000) reduced osteolysis at 8 and 16 weeks, compared to EM0 and negative control. The effective infection control by EM-NFs was further confirmed by hard tissue section analysis. The Bone implant contact (BIC) and bone area fraction Occupancy (BAFO) within 200 µm of the surface of the pins were used to evaluate the osseointegration and new bone formation around the implants. At 16 weeks, the bone implant contact (BIC) of EM 100 (35.08%) was higher than that of negative control (3.43%) and EM0 (0%). The bone area fraction occupancy within 200 µm (BAFO) of EM100 (0.63 mm2) was higher than that of negative control (0.390 mm2) and EM0 (0.0 mm2). The BAFO of EM100 was also higher than that of EM1000 (0.3mm2).There was much less osteolysis observed with EM100 and EM1000 NF coatings at 16 weeks, as compared to EM0 positive control, p=0.08 and p=0.1, respectively. Osseointegration and periprosthetic bone formation was enhanced by EM-NFs, especially EM100. Data from this pilot study is promising for improving implant surface fabrication strategies.

Transarterial Chemoembolization With Drug-Eluting Beads Versus Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Outcomes From a Multicenter, Randomized, Phase 2 Trial (the TRENDY Trial)

To compare transarterial chemoembolization delivered with drug eluting beads (TACE-DEB) with stereotactioc body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC) in a multicenter randomized trial. Patients were included if they were eligible for TACE. They could also be recruited if they required treatment prior to liver transplantation. A maximum of four TACE-DEB procedures and ablation after incomplete TACE-DEB were both allowed. SBRT was delivered in six fractions of 8-9Gy. Primary end point was time to progression (TTP). Secondary endpoints were local control (LC), overall survival (OS), response rate (RR), toxicity, and quality of life (QoL). The calculated sample size was 100 patients. Between May 2015 and April 2020, 30 patients were randomized to the study. Due to slow accrual the trial was closed prematurely. Two patients in the SBRT arm were considered ineligible leaving 16 patients in the TACE-DEB arm and 12 in the SBRT arm. Median follow-up was 28.1 months. Median TTP was 12 months for TACE-DEB and 19 months for SBRT (p=0.15). Median LC was 12 months for TACE-DEB and >40 months (not reached) for SBRT (p=0.075). Median OS was 36.8 months for TACE-DEB and 44.1 months for SBRT (p=0.36). A post-hoc analysis showed 100% for SBRT 1- and 2-year LC, and 54.4% and 43.6% for TACE-DEB (p=0.019). Both treatments resulted in RR>80%. Three episodes of possibly related toxicity grade ≥3 were observed after TACE-DEB. No episodes were observed after SBRT. QoL remained stable after both treatment arms. In this trial, TTP after TACE-DEB was not significantly improved by SBRT, while SBRT showed higher local antitumoral activity than TACE-DEB, without detrimental effects on OS, toxicity and QoL. To overcome poor accrual in randomized trials that include SBRT, and to generate evidence for including SBRT in treatment guidelines, international cooperation is needed.

Abstract 5261: Prostate specific sustained anti androgen delivery to delay early stage prostate cancer progression

Abstract Prostate cancer is the most common cancer in men. Commensurate with risk, current approaches to localized prostate cancer include prostatectomy, prostate radiation with or without radiation therapy or active surveillance. Recent data suggest that systemic anti-androgen therapy with enzalutamide reduced the risk of prostate cancer progression in men on active surveillance but was associated with considerable side effects. We developed a novel polymer-based drug delivery method to provide sustained localized drug administration of anti-androgens selectively to the prostate. In vitro and in vivo mouse and canine studies show that this drug eluting implant delivers sustained high prostate to plasma therapeutic anti-androgen levels for an anticipated range of 2 years while preventing accumulation of anti-androgens in the liver, lungs, heart and brain. We performed a proof of concept study in a canine prostate model implanting an 15mm x 1mm bicalutamide eluting implant into each lobe of the prostate. Bicalutamide levels in the prostate measured near the implant at 6 months were 3250 ± 1622 ng/g, n = 3 compared to 3809 ± 638 ng/g, n = 3 to those achieved at steady-state oral administration. Plasma and other off target levels were over 1000-fold lower in the implant cohort compared to oral administration: Plasma: 5.9 ± 0.2 ng/ml, liver: 11.3 ±4.3 ng/g, and brain: 5.4 ±0.8 ng/g versus plasma: 18170 ± 3820 ng/ml, liver: 35407 ±8510 ng/g, and brain: 8870 ±1797 ng/g. The implants were well tolerated without local toxicity and imaged easily with ultrasound. The design characteristics of the implant facilitates minimally invasive surgical implantation under standard image guidance and withstands the concomitant use of prostate radiation. This novel technology warrants future clinical exploration of prostate specific anti-androgen therapy for (neo)adjuvant therapy or in active surveillance. Tissue Bicalutamide oral (2m)(ng/g) Bicalutamide implant (6m)(ng/g) Plasma 18,170 (3820) 5.9 (0.2) Prostate 3,809 (638) 3,250 (1622) Liver 35,407 (8510) 11.3 (4.3) Cerebrum 8,870 (1797) 5.4 (0.8) Cerebellum 8,737 (1550) 6.2 (1.3) Spleen 7,727 (1288) 4.2 (0.9) Lung 27,013 (2896) 11.3 (4.3) Heart 11,737 (3491) 10.0 (1.9) Kidneys 17,413 (6581) 8.5 (2.0) Citation Format: Pujan Desai, Maithili Rairkar, Nela Pawlowska, Scott Thomas, Pamela N. Munster. Prostate specific sustained anti androgen delivery to delay early stage prostate cancer progression. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5261.

Assessment of Paclitaxel Drug-Coated Balloon Only Angioplasty in STEMI

BackgroundPrimary percutaneous coronary intervention (pPCI) with drug-eluting stents (DES) has emerged as the standard of care, but stent-related events have persisted. Drug-coated balloon (DCB)–only angioplasty is an emerging technology, although it is not fully evaluated compared with DES in the context of pPCI. ObjectivesThe aim of this study was to investigate the safety of DCB-only angioplasty compared with second-generation DES in pPCI. MethodsAll-cause mortality and net adverse cardiac events (cardiovascular mortality, acute coronary syndrome, ischemic stroke or transient ischemic attack, major bleeding, and unplanned target lesion revascularization [TLR]) were compared among all patients treated with DCBs only or with second-generation DES only for first presentation of ST-segment elevation myocardial infarction (STEMI) due to de novo disease between January 1, 2016, and November 15, 2019. Patients treated with both DCBs and DES were excluded. Data were analyzed using Cox regression models, Kaplan-Meier estimator plots and propensity score matching. ResultsAmong 1,139 patients with STEMI due to de novo disease, 452 were treated with DCBs and 687 with DES. After a median follow-up period of >3 years, all-cause mortality was 49 of 452 and 62 of 687 in the DCB and DES groups, respectively (P = 0.18). On multivariable Cox regression analysis, there was no difference in mortality between DCBs and DES in the full and propensity score–matched cohorts. Age, frailty risk, history of heart failure, and family history of ischemic heart disease remained significant independent predictors of mortality. There was no difference in any of the secondary endpoints, including unplanned TLR. ConclusionsDCB-only angioplasty appears safe compared with DES for STEMI in terms of all-cause mortality and all net adverse cardiac events, including unplanned TLR. DCB may be an efficacious and safe alternative to DES in selected patient groups. (Drug Coated Balloon Only vs Drug Eluting Stent Angioplasty; NCT04482972)

Comparison of Early and Late Surgeries after Coronary Stent Implantation in Patients with Normal Preoperative Troponin Level: A Retrospective Study

Current guidelines recommend delaying noncardiac surgery for 6 months after drug eluting stent implantation. However, this recommendation is largely based on limited evidence and various event definitions. Whether early surgery within 6 months of coronary stent implantation increases myocardial injury in patients with normal preoperative high-sensitivity cardiac troponin I (hs-cTnI) has not yet been investigated. This retrospective study assessed patients who received coronary stent implantation and underwent noncardiac surgery (vascular, abdominal, or thoracic) between 2010 and 2017 with normal preoperative hs-cTnI (n = 186). Patients were divided into early (within 6 months of PCI) and late (after 6 months of PCI) groups. The primary endpoint was the incidence of myocardial injury as diagnosed by hs-cTnI within 3 days post-operation. The secondary outcomes were myocardial infarction, stent thrombosis, emergent coronary revascularization, major bleeding (bleeding requiring transfusion or intracranial bleeding), stroke, renal failure, heart failure, or death within 30 days post-operation. Inverse probability treatment weighting (IPTW) was carried out to adjust for the intergroup baseline differences. Myocardial injury occurred in 28.6% (8/28) and 27.8% (44/158) of the early and late groups, respectively, with no difference between groups (odds ratio [OR] 1.067, 95% confidence interval [CI] 0.404, 2.482; p = 0.886). Secondary outcomes did not differ between the groups. IPTW analysis also showed no differences in myocardial injury and secondary outcomes between the groups. In conclusion, early surgery within 6 months after coronary stent implantation did not increase the incidence of myocardial injury in patients with normal preoperative hs-cTnI.

Management of In-stent Restenosis

Despite recent improvements in percutaneous coronary intervention (PCI), in-stent restenosis (ISR) — which accounts for 5–10% of all PCI procedures in contemporary clinical practice remains a substantial problem and the most frequent reason for stent failure. While the absolute number of ISR-PCI operations performed in contemporary practice has increased as a result of rising procedural volume and complexity, the relative rate of ISR has decreased with newer-generation drug eluting stents (DESs) in comparison to the bare metal stent (BMS) period. While BMS ISR is usually early and characterized by neointimal hyperplasia, DES ISR tends to be late with neoatherosclerosis as a characteristic feature. According to recent research, drug-coated balloons or DESs are the most effective therapy options for the majority of ISR cases. Future ISR interventional paradigms may be influenced by intravascular imaging (IVI) ISR tissue patterns. IVI can provide useful information to guide treatment options in ISR-PCI.

Engineering a drug eluting ocular patch for delivery and sustained release of anti-inflammatory therapeutics.

Ocular inflammation is commonly associated with eye disease or injury. Effective and sustained ocular delivery of therapeutics remains a challenge due to the eye physiology and structural barriers. Herein, we engineered a photocrosslinkable adhesive patch (GelPatch) incorporated with micelles (MCs) loaded with Loteprednol etabonate (LE) for delivery and sustained release of drug. The engineered drug loaded adhesive hydrogel, with controlled physical properties, provided a matrix with high adhesion to the ocular surfaces. The incorporation of MCs within the GelPatch enabled solubilization of LE and its sustained release within 15 days. In vitro studies showed that MC loaded GelPatch supported cell viability and growth. In addition, subcutaneous implantation of the MC loaded GelPatch in rats confirmed its in vivo biocompatibility and stability within 28 days. This non-invasive, adhesive, and biocompatible drug eluting patch can be used as a matrix for the delivery and sustained release of hydrophobic drugs.

What is the role of drug-coated balloons in chronic total occlusion percutaneous coronary intervention?

Key Points Placement of drug eluting stents after successful lesion crossing is the current standard of care in chronic total occlusion percutaneous coronary intervention. A drug‐coated balloon only strategy may be feasible in chronic total occlusion percutaneous coronary intervention, especially with intraplaque crossing. More studies are needed on when and how to use drug‐coated balloons in chronic total occlusion percutaneous coronary intervention.

Clinical Outcomes of Unprotected Left Main Stem Stenting: An Observational Single-Centre Study

Objectives: To know the clinical outcomes of percutaneous intervention (PCI) with drug eluting stents (DES) in patients with unprotected left main stem disease. Materials and Methods: This single-centre, prospective, observational study was conducted on 133 patients, who underwent PCI using DES to an unprotected LMS at Kuwait teaching Hospital Peshawar, between 2018 to 2022. Patients were followed in OPD and clinics or they were traced through calls at monthly and yearly intervals, after the procedure. A team, which comprised of a cardiac interventionist and a cardiac surgeon, scrutinised patients for the eligibility of either procedure. Ethical Committee approval was granted by the Institutional Ethics committee. Results: At 1month follow up, the composite end point occurred in 13 (11.58%) patients, whereas individual secondary end points including death from all-cause mortality was reported in 5 (4.7%), stroke in 1 (0.9 %), MI in 4 (3.73 %) and repeat vascularisation in 3 (2.25%) patients. The annual incidence of composite end point occurred in 27.58%patients, whereas individual secondary end points including death from all-cause mortality was reported in 10 (8.27%), stroke in 3 (2.25 %), MI in 09 (6.76%) and repeat vascularisation in 11 (10.3%) patients, Conclusion: PCI to LMS can be performed safely in centres having no cardiac surgery backup and newer imaging modalities with results comparable to the centres having the luxury of such facilities, provided that operators are skilled enough with sufficient expertise and knowledge.

Animal model assessment of a new design for a coated mitomycin-eluting biodegradable ureteral stent for intracavitary instillation as an adjuvant therapy in upper urothelial carcinoma.

A major limitation in the treatment of upper urinary tract urothelial carcinoma is the limited use of adjuvant therapy due to the drawbacks of current techniques for intracavitary instillation. The aim was to assess, in a large animal model, a biodegradable ureteral stent coated with silk fibroin for mitomycin release, i.e. BraidStent-SF-MMC. A total of 14 female pigs with a solitary kidney underwent initial urinalysis, blood chemistry, nephrosonographic, and contrast fluoroscopy assessment of the urinary tract. Later, the BraidStent-SF-MMC was placed retrogradely to assess the mitomycin urine concentration from 0-48 hours. Follow-up was performed weekly until complete stent degradation to assess the macroscopic and microscopic changes in the urinary tract, stent complications. The drug eluting stent released mitomycin for the first 12 h. The main complication was the release of obstructive ureteral coating fragments during the first to third week in 28.5 and 7.1% of animals, respectively, related to urinary pH<7.0, which destabilized the stent coating. Another complication was ureteral strictures between the fourth and sixth week in 21%. The stents were completely degraded by 6-7 weeks. There were no stent-related systemic toxic effects. The success rate was 67.5% and the complication rate was 25.7%. For the first time, we have shown that a biodegradable anti-cancer drug eluting stent, BraidStent-SF-MMC, provides controlled and well-tolerated release of mitomycin into the upper urinary tract in an animal model. Mitomycin release from a silk fibroin coating could be a compelling approach for adjuvant chemotherapy instillation in upper tract urothelial carcinoma management.

Mallory Weiss Tear - An Uncommon Cause of Upper G.I Bleeding in a Cardiac Patient with Successful Dual Intervention

Introduction: Primary Percutaneous Coronary Intervention (PPCI) with stenting, especially with Drug eluting stents (DES), is the most widely accepted strategy globally for patients presented with STEMI, which necessitates a long duration of Dual antiplatelet therapy (DAPT) to prevent stent thrombosis. Potent P2Y12 inhibitors for DAPT are preferred in view of their superior protection against thrombosis but at the expense of increased bleeding risks. Early therapeutic intervention in the event of acute GI bleed has beneficial outcome while on active cardiac intervention.&#x0D; Case Presentation: A 67-year-old patient, who underwent PPCI with DES stent, incidentally developed Mallory-Weiss (MW) tear, which manifested as severe hematemesis when loaded with DAPT consisting of Aspirin and Ticagrelor. The therapy was withheld until the clipping of the tear was done. Single antiplatelet therapy (SAPT) with Aspirin was reinstituted after a day and DAPT with Aspirin plus Clopidogrel after a week.&#x0D; Conclusion: A careful assessment of the risks and benefits of acute coronary interventions need to consider complications and timely interventions thus individualizing and curating the DAPT as deemed necessary.

Abstract No. 133 Fabrication and Characterization of Highly Radiopaque Microspheres for Prostate Cancer Chemoembolization

The purpose of this study was to develop and characterize embolic microspheres that are highly radiopaque, such that they could be used for prostate cancer chemo-embolization. The goals are that the spheres can be visualized during injection on fluoroscopic imaging without additional contrast media (with reasonable injection force), and that they can be imaged (with C-arm CT or MSCT) within the prostate and other non-target organs, both during and after the procedure. Finally, these spheres should be loadable with long-release chemotherapeutic agents. A process was developed to manufacture polyethylene glycol (PEG) microspheres where one of two radiopaque agents were added during the manufacturing process. The process was based on droplet generation microfluidics using an olive oil base. The first type had 1 um barium sulfate particles added at 40% wbv. The second type had 100 nm zirconium oxide particles added at 50% wbv. After curing, particles were washed to remove the olive oil. Sphere diameter was measured using light microscopy. The spheres' radiopacity were evaluated individually using microCT, and in aggregate, within a 3D printed vascular phantom, using MSCT. Injection force from a syringe was measured. Finally, the spheres were imaged with x-ray fluoroscopy during injection, using a body-sized, water-filled, vascular phantom. The barium and zirconium spheres measured 111 ± 14 um and 73 ± 18 um respectively. MicroCT measurements of individual sphere radiopacity were 6772 ± 501 HU and 13,486 ± 638 HU. MSCT radiopacity values in a 0.5 mm vessel were 264 HU and 226 HU. The measured injection force from a 3-cc syringe was 20 N, compared with 25 N for commercial microspheres with 50% contrast agent. The detectability on the microspheres on fluoroscopy was very similar to that of commercial microspheres with 50% contrast agent, approximately a 30 pixel-value enhancement over the background value. This project demonstrated the ability to produce highly radiopaque microspheres that have reasonable injection force and are visible both during injection using fluoroscopy, without additional contrast agent, and using MSCT. The HU values in MSCT are lower that microCT due to the lower tube voltage in microCT and also due to the limited spatial resolution (partial volume effect) of MSCT, but these small vessels are nevertheless visible within a 0-100 HU prostate gland. Further work is underway to evaluate drug elution characteristics.

Prevalence, Management and Outcomes of Percutaneous Coronary Intervention for Coronary In-Stent Restenosis: Insights From the France PCI Registry

BackgroundDespite the evolution of stent technology, there is a non-negligible risk of in-stent restenosis (ISR) after Percutaneous coronary intervention (PCI). Large-scale registry data on the prevalence and clinical management of ISR is lacking. MethodsThe aim was to describe the epidemiology and management of patients with ≥1 ISR lesions treated with PCI (ISR PCI). Data on characteristics, management and clinical outcomes were analyzed for patients undergoing ISR PCI in the France-PCI all-comers registry. ResultsBetween January 2014 and December 2018, 31,892 lesions were treated in 22,592 patients, 7.3 % of whom underwent ISR PCI. Patients undergoing ISR PCI were older (68.5 vs 67.8; p < 0.001), and more likely to have diabetes (32.7 % vs 25.4 %, p < 0.001), chronic coronary syndrome or multivessel disease. ISR PCI concerned drug eluting stents (DES) ISR in 48.8 % of cases. Patients with ISR lesions were more frequently treated with DES than drug eluting balloon or balloon angioplasty (74.2 %, 11.6 % and 12.9 %, respectively). Intravascular imaging was rarely used. At 1 year, patients with ISR had higher target lesion revascularization rates (4.3 % vs. 1.6 %; HR 2.24 [1.64–3.06]; p < 0.001). ConclusionsIn a large all-comers registry, ISR PCI was not infrequent and associated with worse prognosis than non-ISR PCI. Further studies and technical improvements are warranted to improve the outcomes of ISR PCI.

Timing of Complete Revascularization in Patients with STEMI and Multivessel Disease: A Systematic Review and Meta-Analysis.

About half of patients with ST-segment Elevation Myocardial Infarction (STEMI) have multivessel coronary artery disease (MVD). Our aim was to provide a quantitative comparison of single-stage complete revascularization during the index revascularization versus deferred staged complete revascularization in STEMI patients with MVD. All studies evaluating patients with STEMI and MVD were included. The primary endpoint was a composite of all-cause death, myocardial infarction and repeat revascularization. Secondary endpoints were cardiovascular death, acute kidney injury and trial defined major bleeding. Eight studies and 2256 patients with STEMI and MVD were included. No difference was evident in the rate of the primary composite endpoint among the study group (Risk Ratio 0.95; 95% CI 0.71-1.27, p = 0.74), while meta-regression showed a significant interaction with drug eluting stent (DES) use (Coefficient -0.005; 95% CI -0.01 to -0.001; p = 0.007). Higher rates of cardiovascular (CV) death were found in the immediate complete revascularization group (5.0% vs 2.6%; Risk Ratio 0.39; 95% CI 0.25-0.62; p 0.01). Our analysis documented similar clinical outcomes with either single-stage immediate complete revascularization and delayed staged complete revascularization. Secondary analyses suggest that an increase in cardiovascular death might be expected with single-stage percutaneous coronary intervention (PCI). While new randomized trials on the topic are ongoing, revascularization can be personalized and guided by the acute clinical setting, patients'-related factors and workflow logistics.

Multi-vessel Disease Percutaneous Coronary Intervention versus Coronary Artery Bypass Grafting in Patients with Chronic Kidney Disease

Background: Revascularization of the coronary arteries is associated with better short term and long term prognosis in patients having multivessel coronary artery disease (MV-CAD) and chronic kidney disease (CKD). However, whether revascularization using coronary artery bypass grafting (CABG) surgery or percutaneous coronary intervention (PCI) using drug eluting stents (DES) is better remains unknown.&#x0D; Objectives: To compare the outcomes of revascularization by multi-vessel PCI using DES versus revascularization by CABG in patients with CKD having multivessel CAD, regarding in-hospital and one-year major adverse cardiovascular and cerebrovascular events (MACCE).&#x0D; Methods: This was a retrospective analysis of the data of a group of patients having CKD with eGFR less than 60 ml/min with multivessel CAD who underwent revascularization by PCI or revascularization by CABG and were compared as regards in-hospital and one-year MAACE.&#x0D; Results: A total of 565 patients were reviewed in this study, 230 patients had multivessel PCI using DES while 335 patients had CABG. Comparing both revascularization groups regarding in-hospital MACCE, patients who had mutli-vessel PCI had significantly lower in-hospital mortality, cerebrovascular events (stroke/TIA) and lower total MACCE than patients who had CABG (P-value = 0.03 &amp; 0.01 &amp; 0.04 respectively). When comparing both revascularization groups regarding one-year MACCE, patients who had mutli-vessel PCI had significantly lower cerebrovascular events and total MACCE than those patients who had CABG (P-value = 0.02 &amp; 0.03 respectively).&#x0D; Conclusion: This is a retrospective study to determine which strategy is better for revascularization of CKD patients having multivessel CAD; we can conclude that multi-vessel PCI using DES for CKD patients and multivessel CAD had advantages over CABG regarding in-hospital and one-year cerebrovascular accidents (TIA/stroke) and regarding total MACCE. Larger randomized controlled trials are required to confirm our findings.

Impact of Endothelial Dysfunction on Long-Term Clinical Outcomes in Patients With Chronic Coronary Syndromes Treated With Second Generation Drug-Eluting Stent Implantation

BackgroundStudies investigating clinical outcomes of patients with or without endothelial disfunction (ED) treated with percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) using second generation drug eluting stents (DES) are lacking. MethodsWe prospectively collected data from 109 patients undergoing PCI with second generation DES due to stable CAD between December 2014 and September 2016. ED was evaluated evaluating the flow mediated dilation (FMD) at the brachial artery level and defined by an FMD < 7 %. Primary outcome were major adverse cardiovascular events (MACE), secondary outcomes were target vessel failure (TVR), myocardial infarction (MI) and all-cause death. ResultsFive-year follow-up was available in all patients. Median FMD didn't significantly differ between patients who experienced the outcome and those who didn't [no TVR vs. TVR: p = 0.358; no MI vs. MI: p = 0.157; no death vs. death: p = 0.355; no MACE vs. MACE: p = 0.805]. No association between ED and an increased risk for the primary outcome as well as for the secondary ones was evident [MACE: 17.0 % vs. 14.3 %, HR 0.87 (0.33–2.26), log rank p = 0.780; TVR: 9.4 % vs. 5.4 %, HR 0.53 (0.12–2.24), log rank p = 0.384; MI: 3.7 % vs. 8.9 %, HR 2.46 (0.47–12.76), log rank p = 0.265; death: 7.5 % vs. 3.6 %, HR 0.53 (0.09–2.90), log rank p = 0.458]. These findings were confirmed using a lower threshold of FMD to define ED and at one-year landmark analysis. ConclusionsED is not associated with an increased risk of adverse events at long-term follow-up in a contemporary cohort of patients undergoing PCI with second generation DES.