Article

Optical Coherence Tomographic Results at Six-Month Follow-Up Evaluation of the CATANIA Coronary Stent System With NanoThin Polyzene-F Surface Modification (from the Assessment of The LAtest Non-Thrombogenic Angioplasty Stent [ATLANTA] Trial)

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Abstract

Drug-eluting stents were devised as an answer to restenosis, but research has shown that the eluting drug can interfere with the blood vessel's healing process, thus increasing the risk of stent thrombosis. A stent coated with the new proprietary polymer Polyzene-F, is a novel technical solution that promises to decrease in-stent restenosis and tackle the risk of thrombosis. Fifty-five patients were enrolled in the first clinical human study (ATLANTA registry), addressing the short-term follow-up results of the CATANIA stent with Polyzene-F. As a part of the study protocol, 15 patients were randomly assigned to optical coherence tomographic (OCT) examination at 6-month follow-up. Optical coherence tomograms were obtained using a Lightlab M2 system with a motorized pull-back at 2.0 mm/s. OCT images were acquired at 15.6 frames/s. A total of 1,904 cross-sectional images with 19,028 struts were analyzed. The rate of covered struts was 99.5%, whereas malapposed struts accounted for 0.15%. Area measurements were performed in 476 cross sections. Neointimal hyperplasia (NIH) area and percent NIH area were 3.2 +/- 1.4 mm2 and 38 +/- 17%, respectively. Percent NIH area was comparable between diabetics and nondiabetics. Qualitative assessment of OCT images demonstrated neither occurrence of stent fractures nor thrombus. In conclusion, OCT assessment of the Polyzene-F-covered stent at follow-up showed a small percentage of neointima. Also, almost complete stent strut coverage was revealed by optical coherence tomography. These figures indicate that the CATANIA stent with Polyzene-F is a promising solution for decreasing late stent restenosis and preventing thrombosis.

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... All angiograms and OCT images were digitally stored and independently analyzed offline in a validated core laboratory (Rome Heart Research, Italy) [14,15], by observers blinded to treatment assignment. ...
... Thrombus was measured along the stented segment (mean thrombus area) and at the cross section with maximal thrombus encroachment. Inter-observer and intra-observer variability for the Rome Heart Research core lab has been already reported elsewhere [14,15,21]. ...
Article
The persistence of thrombus inside stent struts is a frequent event in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI), and this phenomenon might be associated with an increased risk of stent thrombosis. We sought to quantify by means of optical coherence tomography (OCT) the presence of in-stent thrombus after achievement of an optimal angiographic result in patients with ACS undergoing PCI. In addition, we evaluated the feasibility and safety of an OCT-guided strategy of in-stent thrombus removal. Eighty consecutive patients with ACS undergoing PCI were treated with two different strategies equally divided into two groups: angio-guided PCI, and OCT-guided PCI, in which additional OCT-driven in-stent balloon dilatation was adopted to reduce thrombus encroachment of the lumen. Overall in-stent thrombus area was 4.3 % with a maximal thrombus encroachment of 16.7 %. In the OCT-guided group, use of high pressure intra-stent dilatation led to a significant increase in stented area (9.6 ± 2.4 vs. 9.1 ± 2.49 mm(2), p = 0.002) and lumen area (9.2 ± 2.4 vs. 8.7 ± 2.3 mm(2), p < 0.001) and also significantly decreased in-stent thrombus area in absolute (0.35 ± 0.29 vs. 0.42 ± 0.30 mm(2), p = 0.001) and relative terms (3.58 ± 3.25 vs. 4.53 ± 3.01 %, p = 0.001). Values of TIMI flow, frame count and blush grade, as well as clinical outcomes were not detrimentally affected by such additional dilatations. The use of additional OCT-driven in-stent balloon dilatations is feasible, safe and might be effective in the treatment of in-stent thrombus for patients with ACS.
... Bu yeni geliştirilen koroner stentin insanlardaki uygulamasının fizibilitesini, güvenilirliğini ve etkinliğini klinik değerlendirme, kantitatif koroner anjiyografi, IVUS ve OCT kullanarak değerlendiren ATLANTA çalışmasının sonucunda bu stentlerin de-novo koroner arter lezyonlarının tedavisinde erken ve orta-dönem sonuçlarının güvenlik açısından mükemmel olduğu sonucuna varılmış ve PzF polimeriyle yüzeyi kaplanmış bu yeni nesil stentin geç lümen kaybı, restenoz ve hedef damar revaskülarizasyon oranlarında azalmayla ilişkili bulunup uzun dönem DAPT gerektirmediğinden hem ÇMS'lere hem de DES'lere avantajlı bir alternatif olarak kullanılabileceği belirtilmiştir [14]. Bu yeni nesil stentin, implantasyonu takiben 6. aydaki OCT sonuçlarının değerlendirildiği çalışmada, [15] strutların %99,5'inin endotelize olarak tam damar iyileşmesi görülmüş, çok düşük oranda (%0,15) malapozisyona rastlanmış, neointimal hiperplazi alanı diyabetik olan ve olmayan hasta gruplarında benzer bulunmuş ve 4 haftalık DAPT tedavisine rağmen hastaların hiçbirinin OCT görüntülerinde tromboz lehine bir bulguya rastlanmamıştır. Bu sonuçların da PzF kaplı stentlerin KAH tedavisinde kullanımının geç stent restenozunu azaltmada ve stent trombozunu önlemede gelecek vadeden bir çözüm olabileceği bildirilmiştir [15]. ...
... Bu yeni nesil stentin, implantasyonu takiben 6. aydaki OCT sonuçlarının değerlendirildiği çalışmada, [15] strutların %99,5'inin endotelize olarak tam damar iyileşmesi görülmüş, çok düşük oranda (%0,15) malapozisyona rastlanmış, neointimal hiperplazi alanı diyabetik olan ve olmayan hasta gruplarında benzer bulunmuş ve 4 haftalık DAPT tedavisine rağmen hastaların hiçbirinin OCT görüntülerinde tromboz lehine bir bulguya rastlanmamıştır. Bu sonuçların da PzF kaplı stentlerin KAH tedavisinde kullanımının geç stent restenozunu azaltmada ve stent trombozunu önlemede gelecek vadeden bir çözüm olabileceği bildirilmiştir [15]. Bizim çalışmamızda 1. grupta daha yüksek oranda MACE görüldü ise de bu fark istatistiksel olarak anlamlı değildi. ...
Article
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Objective: The intra-coronary stents provided great benefit after percutaneous transluminal coronary angioplasty (PTCA); however, high in-stent restenosis rates, even up to 25-30%, is the the main concern. Cytotoxic drug-eluting stents were developed to overcome this challenge. Whereas, they interfered vessel healing and endothelization process which led to increased risk of stent thrombosis. A bioinert molecule, polyzene-F(PzF), was applied to the surface of a new generation stent to provide anti-inflammatory and anti-thrombogenic property. We aimed to compare the sirolimus-eluting stent with PzF-coated cobalt-chrome stent in terms of early inflammatory response and long-term major adverse cardiac events (MACE) rates. Methods: Stable coronary artery disease patients treated with PzF-coated cobalt-chrome stent formed the 1st group (n=19), and those received sirolimus-eluting stent (n=13) formed the 2nd group. Serum hsCRP and IL-6 levels were measured before percutaneous coronary intervention (pre-PCI), and after 1st and 10th days (post-PCI 1, and post-PCI 10, respectively) of PCI. The patients were followed-up to 1 year in terms of MACE experience. Results: The study groups were comparable in terms of pre-PCI, post-PCI-1 and post-PCI-10 serum hsCRP and IL-6 levels. Four of 19 patients (21%) in the 1st group and 1 of 13 patients (8%) in the 2nd group experienced MACE during 1-year follow-up; whereas this difference was not statistically significant (p=0.26). Conclusion: Although, the PzF-coated cobalt-chrome stent was claimed to have lower anti-inflammatory and anti-thrombogenic properties, we showed similar inflammatory response and long-term MACE rates compared to sirolimus-eluting stent. Prospective, randomized, large scale studies are needed to clarify this issue. J Clin Exp Invest 2015; 6 (2): 159-164
... There are several clinical studies assessing the first generation stent nanocoated with PzF polymer and COBRA-PzF stent [46][47][48][49][50]. Tamburino et al. reported first-in-man 1-year clinical outcomes of the first-generation device coated with PzF polymer in a prospective, single-center, nonrandomized, single-arm study of 55 patients with symptomatic ischemic heart disease with de novo, obstructive lesions of native coronary arteries (Assessment of The LAtest Non-Thrombogenic Angioplasty Stent Trial; the ATLANTA Trial) [46]. ...
... The incidence of target lesion revascularization (TLR) at 12 months was clinically driven TLR 3.6% and nonclinically driven TLR 7.3%. Substudy using optical coherence tomography at 6 months showed that the rate of covered struts was 99.5% [48]. Tamburino et al. also performed the ATLANTA 2 registry to assess the first generation stent coated with PzF polymer in real world clinical practice, which was a prospective, nonrandomized, single-arm study of patients with symptomatic ischemic heart disease and de novo lesions of native coronary arteries [49]. ...
Article
The COBRA-PzF™ (CeloNova BioSciences, Inc., TX, USA) is a new type of coronary stent composed of a cobalt chromium metallic backbone surrounded by a nanothin layer of Polyzene-F (PzF) without any added drug. Evidence from basic studies supports antithrombotic and anti-inflammatory properties for the PzF surface coating. Preclinical studies support the thromboresistance of PzF coated surfaces and clinical studies have shown good outcomes for patients receiving this device with very low rates of stent thrombosis. COBRA-PzF may be especially useful in patients at high-risk for bleeding. Ongoing clinical trials will determine whether shortening the duration of dual antiplatelet therapy to less than 1 month is feasible and these data may represent a new paradigm with regards to patients at high-risk for bleeding.
... Stent-based release of a selective PDGF-receptor blocker from the bis-indolylmethanon class has been found to inhibit restenosis in a rabbit model [28]. Polyzene-F–coated stent, which prevents thrombosis, was also developed [29]. ...
Article
Drug-eluting stents (DES) reduce coronary restenosis significantly; however, late stent thrombosis (LST) occurs, which requires long-term antiplatelet therapy. Angioscopic grading of neointimal coverage of coronary stent struts was established, and it was revealed that neointimal formation is incomplete and prevalence of LST is higher in DES when compared to bare-metal stents. It was also observed that the neointima is thicker and LST is less frequent in paclitaxel-eluting and zotarolimus-eluting stents than in sirolimus-eluting stents. Many new stents were devised and they are now under experimental or clinical investigations to overcome the shortcomings of the stents that have been employed clinically. Endothelial cells are highly anti-thrombotic. Neo-endothelial cell damage is considered to be caused by friction between the cells and stent struts due to the thin neointima between them which might act as a cushion. Therefore, development of a DES that causes an appropriate thickness (around 100 μm) of the neointima is a potential option with which to prevent neo-endothelial cell damage and consequent LST while preventing restenosis.
... Evaluation of cobalt chromium stents nanocoated with polyzene-F in an animal model yielded favorable results [92]. Preliminary studies evaluating the Catania™ (Celo-Nova Biosciences, Newnan, GA, USA) stent in humans demonstrated a good safety profile and high-level efficacy [93,94]. ...
Article
Percutaneous coronary intervention (PCI) has become the most common revascularization procedure for coronary artery disease. The use of stents has reduced the rate of restenosis by preventing elastic recoil and negative remodeling. However, in-stent restenosis remains one of the major drawbacks of this procedure. Drug-eluting stents (DESs) have proven to be effective in reducing the risk of late restenosis, but the use of currently marketed DESs presents safety concerns, including the non-specificity of therapeutics, incomplete endothelialization leading to late thrombosis, the need for long-term anti-platelet agents, and local hypersensitivity to polymer delivery matrices. In addition, the current DESs lack the capacity for adjustment of the drug dose and release kinetics appropriate to the disease status of the treated vessel. The development of efficacious therapeutic strategies to prevent and inhibit restenosis after PCI is critical for the treatment of coronary artery disease. The administration of drugs using biodegradable polymer nanoparticles as carriers has generated immense interest due to their excellent biocompatibility and ability to facilitate prolonged drug release. Despite the potential benefits of nanoparticles as smart drug delivery and diagnostic systems, much research is still required to evaluate potential toxicity issues related to the chemical properties of nanoparticle materials, as well as to their size and shape. This review describes the molecular mechanism of coronary restenosis, the use of DESs, and progress in nanoparticle drug- or gene-eluting stents for the prevention and treatment of coronary restenosis.
... Target lesion revascularization rate at 12 months was 6.5% and no late stent thrombosis was recorded up to 12 months, even though dual antiplatelet therapy (DAPT) was prescribed for only 1 month post procedure (unless patients had a myocardial infarction) in the 300 patients recruited for ATLANTA 2 [33]. Adding to these promising results, a substudy in 15 patients from ATLANTA reported 99.5% covered struts, assessed by optical coherence tomography, at 6 months follow-up [34]. ...
Article
Major advances have been made in coronary artery stent technology over the last decades. Drug-eluting stents reduced in-stent restenosis and have shown better outcomes compared with bare metal stents, yet some limitations still exist to their use. Because they delay healing of the vessel wall, longer dual antiplatelet therapy is mandatory to mitigate against stent thrombosis and this limitation is most concerning in subjects at high risk for bleeding. The COBRA PzF nanocoated coronary stent has been associated with accelerated endothelialization relative to drug-eluting stents, reduced inflammation and thromboresistance in preclinical studies, suggesting more flexible dual antiplatelet therapy requirement with potential benefits especially in those at high bleeding risk. Here, we discuss the significance of COBRA PzF in light of recent experimental and clinical studies.
... Napovědět nám mohou data z patologickoanatomické práce Finna a spol., v níž autoři zjistili devětkrát vyšší riziko pozdní trombózy lékových stentů, jestliže přítomnost nepokrytých strutů stentu přesahuje 30 %. 14 Další studie srovnávaly hojení stentů mezi sebou v určitém časovém úseku od implantace. [15][16][17][18][19] Jiné se zabývaly hojením jednoho stentu v průběhu času. 20 Kubo a spol. ...
Article
Full-text available
Optical coherence tomography is a new, very fast developing method in interventional cardiology. It gives us the opportunity to assess the inner structures of coronary artery wall, to evaluate the characteristics of atherosclerotic plaques, quality of stent implantation and its healing. The authors present current knowledge of optical coherence tomography and their own experience with this method.
... We know from the pathological study done by Finn AV et al., that patients have 9 times higher risk of late stent thrombosis if the presence of uncovered stent struts exceeds 30% [14]. Other studies compared stent healing among different types of stents at the same time after implantation [15][16][17][18][19]. Others studied stent healing of the same stent at different time intervals after implantation [20]. ...
Article
Full-text available
Coronary angiography is still the most widely used method for the assessment of lumen of coronary arteries and for diagnosis and treatment of coronary artery disease. New imaging modalities of coronary arteries play an increasing role in interventional cardiology. Intravascular ultrasound (IVUS) is the oldest technology, however due to its high tissue penetration remains very important for imaging of left main coronary artery and saphenous vein grafts. IVUS was used in many clinical trials and clinical experience with it is huge. Optical coherence tomography (OCT) is a new, very fast developing method. It has ten times higher axial resolution than IVUS. It gives us the opportunity to assess the inner structures of coronary artery wall, to evaluate the characteristics of atherosclerotic plaques, quality of stent implantation and its healing. It helps us to find the culprit lesion of acute coronary syndrome in some cases, to diagnose the cause of stent thrombosis, and to evaluate stent apposition which has a direct relation to prognosis. We use it to perform complex percutaneous coronary interventions and after heart transplantation to diagnose the vascular graft disease. We strongly believe that OCT is important for the assessment of plaque instability and patient´s prognosis. Near infrared spectroscopy combined with IVUS can distinguish fibrous from lipid core plaques. Lipid core burden index is in relation to a risk of periprocedural myocardial infarction and to prognosis. It is the only method which can sufficiently detect the amount of lipids in coronary wall.
... This observation is thought to be responsible, in part, for the positive clinical results seen with Polyzene-F material on the Catania™ stent in the ATLANTA and ATLANTA 2 studies that demonstrated a 3.6% clinically-driven target lesion restenosis rate, with no deaths, strokes or myocardial infarctions (MIs), in 55 patients and 6.5% all target lesion restenosis rate in 300 patients with 0% late stent thrombosis (N30 days) recorded at 12 months in both studies [15,16]. With respect to atherothrombotic events, it has been shown that an increased risk of late stent thrombosis is associated with a morphometrically determined ratio, i.e., uncovered to total struts per section [17]. An optical coherence tomographic comparison, within the same patients, of stent endothelialization showed greater coverage on the Polyzene-F coated struts at 7-10 days and at 28-32 days post implantation when compared to DES and BMS struts and a lower uncovered to total strut ratio for the Polyzene-F coated stents at all time points, except when it was not different from the DES struts at the later time point [18,19]. ...
Article
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Because of anticipated antiplatelet medication risks, patients who are not DES candidates or who are at particularly high risk for bleeding events have been targeted initially for treatment with the COBRA PzF Coronary Stent System. We report the case of a successful experience with a new, Polyzene™-F COBRA PzF™ Coronary Stent System, designed to impart thrombo-resistance and reduce inflammation, to achieve shorter dual antiplatelet therapy duration while reducing restenosis incidence in a high risk patient with atrial fibrillation.
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The Rapid Evaluation of Vessel Healing after Angioplasty (REVEAL) trial was the first study to investigate the very early kinetics of neointimal proliferation after percutaneous coronary intervention. Two different types of stents were simultaneously implanted in the same patient, thus limiting the multifactorial inter-individual influence on endothelial growth and allowing an objective comparison of the healing characteristics of different stent platforms. The REVEAL study used optical coherence tomography end points owing to the ability of this technique to assess the initial phases of stent-strut endothelization. Two follow-up time points were prespecified to obtain serial morphological information about the post-stenting vessel healing phenomenon of three different types of stent (the CATANIA™ stent, a drug-eluting stent and bare-metal stents). Of note, one of the implanted stents was always a CATANIA stent with the aim of evaluating the favorable biomimetic proprieties of this new technology, as implicated by previous studies.
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Despite all the benefits of drug-eluting stents (DES), concerns have been raised over their long-term safety, with particular reference to stent thrombosis. In an effort to address these concerns, newer stents have been developed that include: DES with biodegradable polymers, DES that are polymer free, stents with novel coatings, and completely biodegradable stents. Many of these stents are currently undergoing pre-clinical and clinical trials; however, early results seem promising. This paper reviews the current status of this new technology, together with other new coronary devices such as bifurcation stents and drug-eluting balloons, as efforts continue to design the ideal coronary stent.
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Introduction: Uncoverage and malapposition of stent struts at optical coherence tomography (OCT) have been associated with stent thrombosis. Stent uncoverage by OCT is being used as a surrogate to address the propensity of a stent to develop thrombosis. We aimed to appraise early vessel healing in patients with ST-elevation myocardial infarction (STEMI) treated with the novel Avantgarde stent. Methods: Patients with STEMI and multivessel disease were enrolled. The stent deployed on the infarct-related artery was imaged by frequency domain-OCT during deferred intervention (4-7 days apart). The primary end-point was the percentage of uncovered struts. Secondary end-points were the percentage of malapposed struts and struts covered with thrombus. Results: Twenty patients (20 lesions) were enrolled, with 18 (18 stents) achieving a complete OCT pull-back and thus entering the final analysis (1497 cross-sections, 11 446 struts). Uncovered struts were 3.9%, whilst 8.0% of struts were malapposed and 2.6% were covered by thrombus. At per-stent analysis, all stents but two had a homogeneous distribution of strut coverage (i.e. % of uncovered struts ≥10). Conclusions: This study, originally exploiting OCT data early after stenting in STEMI patients, shows that the Avantgarde stent is associated with favourable vessel healing features.
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Strut coverage represents the most powerful morphometric predictor of stent thrombosis and the best surrogate indicator of endothelization. The aim of this study was to get new insights on temporal patterns of vessel healing after stenting with different types of stent. Optical coherence tomography (OCT) was used to investigate the early strut coverage of lesions treated with CATANIA (CAT) stent, drug-eluting stent (DES) or cobalt-chromium bare metal stent (BMS). Two cohorts of 10 and 24 patients underwent OCT follow-up at 7-10 and 28-32 days after stenting, respectively. In each cohort, patients were randomly assigned to receive a CAT stent in one lesion and a BMS or a DES in a separate lesion. A total of 7975 and 8406 struts were analyzed for the comparisons of CAT stent vs. DES and CAT stent vs. BMS at 7-10 days, respectively. A total of 21 123 and 25 069 struts were analyzed for the comparisons of CAT stent vs. DES and CAT stent vs. BMS at 28-32 days, respectively. At 7-10 days, the CAT stent showed higher coverage rates compared with DES (90.0 vs. 85.9%, P < 0.0001) and BMS (90.2 vs. 83.6%, P < 0.0001). Similarly, at 28-32 days, the coverage rate was higher with CAT stent compared with DES (97.7 vs. 90.5%, P < 0.0001) and BMS (97.2 vs. 96.5%, P < 0.0001). The CAT stent yields quicker and more complete strut coverage than DES and BMS in the early phases of vessel healing following stent implantation.
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Coronary artery disease (CAD) has been reported to be a major cause of death worldwide. Current treatment methods include atherectomy, coronary angioplasty (as a percutaneous coronary intervention), and coronary artery bypass. Among them, the insertion of stents into the coronary artery is one of the commonly used methods for CAD, although the formation of in-stent restenosis (ISR) is a major drawback, demanding improvement in stent technology. Stents can be improved using the delivery of DNA, siRNA, and miRNA rather than anti-inflammatory/anti-thrombotic drugs. In particular, genes that could interfere with the development of plaque around infected regions are conjugated on the stent surface to inhibit neointimal formation. Despite their potential benefits, it is necessary to explore the various properties of gene-eluting stents. Furthermore, multifunctional electronic stents that can be used as a biosensor and deliver drug- or gene-based on physiological condition will be a very promising way to the successful treatment of ISR. In this review, we have discussed the molecular mechanism of restenosis, the use of drug- and gene-eluting stents, and the possible roles that these stents have in the prevention and treatment of coronary restenosis. Further, we have explained how multifunctional electronic stents could be used as a biosensor and deliver drugs based on physiological conditions.
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Ultrapure poly[bis(trifluoroethoxy)phosphazene] is a novel biocompatible, anti-inflammatory, antithrombogenic polymer which has the potential to cover stent devices without elution of a cell cycle inhibiting drug. The properties of polyphosphazene are likely to extend its use to a broad array of promising applications. This article reviews the features of the polymer and some recent patents related to use of poly[bis(trifluoroethoxy)phosphazene] in coating, its relevance as compared to other polymers, current evidence on pre-clinical and clinical performance, and future perspectives.
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Background: Novel approaches to modify stents have been developed to address the limitations of bare-metal stents (BMS) and drug-eluting stent (DES), aiming for ideal features, such as decreased restenosis rates with decreased thrombogenicity and without the need for long-term dual antiplatelet therapy. Rationale: The Assessment of The LAtest Non-Thrombogenic Angioplasty Stent (ATLANTA) trial was the first-in-man study to show the safety and efficacy of the Polyzene-F coated CATANIA stent (CeloNova BioSciences, Newnan, Georgia, USA) as an alternative to both BMS and DES. The stent was found to be associated with a good clinical outcome with no vessel thrombosis and a modest growth of late neointima. A subgroup undergoing optical coherence tomography late assessment showed almost complete stent strut coverage at 6 months. However, whether the CATANIA stent is superior in promoting a greater stent strut coverage rate both at 7 and 30 days with respect to DES and BMS is unknown. Methods: The Rapid Evaluation of Vessel HEaling After AngiopLasty (REVEAL) trial will be a prospective, randomized study providing new evidence on early vessel healing and thrombus development after stenting with different stent types. Optical coherence tomography examination at 7-10 days or 28-32 days after implantation will evaluate strut coverage and vessel healing. The primary endpoint will be a comparison of the percentage of 'healed stent struts' at 28-32 days, identified by the presence of an evenly apposed rim of tissue on stent struts, and without apposition of thrombotic material, on the total amount of analyzed struts for the stent groups.
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The potential for the CATANIA (CAT) stent to be an alternative to both bare-metal stents (BMS) and drug-eluting stents (DES) has been recently demonstrated in the Assessment of The LAtest Non-Thrombogenic Angioplasty stent (ATLANTA) first-in-human study. The aim of the present study was to compare short-term outcomes of patients treated with the CAT stent with those treated with BMS. Based on an internal registry, the 30-day and 6-month risk-adjusted outcomes for patients who received the CAT stent (n=254) were compared against outcomes of a historical cohort of patients who received BMS (n=552) between January 2001 and December 2001. At 30 days, use of BMS vs. the CAT stent resulted in borderline significant differences with respect to major adverse cardiac and cerebrovascular events (MACCE) and cardiac death or myocardial infarction. At 6 months, BMS showed a statistically significant higher adjusted risk of MACCE (HR 2.79, 95% CIs 1.20-6.48, P=.017) and no differences with respect to the subcomponent end points. The cumulative incidence of definite stent thrombosis (Academic Research Consortium defined) at 6 months was 0.39% for the CAT stent and 2.35% for the BMS. This study confirms the favorable early and mid-term safety profile and the high-level efficacy of the CAT stent in the treatment of de novo coronary lesions seen in the ATLANTA trial. The use of stents with a nanothin Polyzene-F surface treatment provided improved results with respect to BMS and lower risk of acute and subacute stent thrombosis.
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Aims: To facilitate OCT images acquisition we developed a novel, simplified, non-occlusive technique based on manual infusion of a viscous isosmolar solution. The aims of the present study was to address the safety and efficacy of non-occlusive OCT images acquisition modality in a patient population with complex coronary lesions, and in various clinical scenarios. Methods and results: OCT assessment was performed with the LightLab OCT Imagewire in 64 patients. The imaging acquisition technique was aimed at target lesion and proximal and distal reference segments. OCT images were deemed of good quality if they allowed both an accurate measurement of luminal area and a qualitative classification of the superficial plaque components.In 60 patients (93.7%), the procedure was successful. The mean images acquisition time was 5.3+/-1.4 minutes. No major complications such as death, myocardial infarction or major arrhythmias were recorded. The average length of imaged segments was 28.6+/-6.1 mm and 95.1% of the imaged segments were deemed of sufficient quality to evaluate luminal area and plaque morphology (intra-observer and inter-observer variability 0.71, p<0.0001 and 0.68, p<0.0001 respectively).Conclusions. The non-occlusive modality of OCT image acquisition is safe and effective, and promises to simplify the complex current occlusive technique, leading to a marked reduction of procedural time.
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Since the intravascular ultrasound (IVUS) cannot detect neointimal layers in the majority of sirolimus-eluting stents (SES) at the chronic phase, it is still controversial to what extent SES remain uncovered. However, optical coherence tomography (OCT) with excellent resolution may be able to detect thinner neointima. A total of 34 patients (57 SES) underwent OCT and IVUS evaluations at 6-month follow-up. The thickness of neointima on each SES strut cross-section and strut apposition to the vessel wall was evaluated. By OCT evaluation, the median (25th, 75th percentiles) neointima thickness was 52.5 microm (28.0 microm, 147.6 microm) and the prevalence of struts covered by thin neointima undetectable by IVUS was 64%. The average rate of neointima-covered struts in an individual SES was 89%. Nine SES (16%) showed full coverage by neointima, whereas the remaining stents had partially uncovered strut lesions. Among the 6840 struts visualized by OCT in all of the SES, 79 struts showed malapposition without neointimal coverage, and were frequently observed in the areas of SES overlap. At 6 months, most of the SES were covered with thin neointima, but few showed full coverage.
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To verify whether optical coherence tomography (OCT) can accurately monitor the occurrence of arterial healing after stenting. Delayed stent endothelialisation may predispose to stent thrombosis. OCT is a high-resolution intravascular imaging technique that accurately identifies stent struts and arterial tissues. Eight New Zealand white rabbits underwent the implantation of single bare metal stents (diameter 2-2.5 mm, length 8-13 mm) in the right common carotid artery through the external carotid artery. After a median of 11 days (range 2-28), the stented arteries were visualised by OCT, with images acquired at a pull-back speed of 0.5 mm/sec. The rabbits were then euthanised, vessels were formalin-fixed and finally processed for histopathology. We analysed 32 cross-sections from eight stented carotid arteries, for a total of 384 stent struts. OCT detected all of the stent struts in 30 of 32 cross-sections (93.7%), and correctly identified the presence/absence of tissue for every strut. Histological and OCT measurements of mean neointima thickness (0.135 (SD 0.079) mm and 0.145 (SD 0.085) mm, respectively, p = NS) were similar and closely related (r = 0.85, p<0.001). Neointima area progressively increased with longer time intervals from stent deployment to sacrifice; histological and OCT measurements were similar for each time interval. The intra-observer and interobserver reproducibility of OCT neointima measurements were excellent (R2 = 0.90 and 0.88, respectively). OCT is a promising means for monitoring stent strut coverage and vessel wall healing in vivo, the relevance of which will become even more significant with the increasing use of drug-eluting stents.
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Background Optical coherence tomography (OCT), a high resolution intravascular imaging technique, requires blood displacement for reliable image acquisition and the current technique uses a soft occlusion balloon plus saline injection in the coronary artery. A non-occlusive technique based on manual infusion of a viscous iso-osmolar solution has been developed and tested and validated through a 2-phase study. Methods and Results OCT assessment was performed with the M2 LightLab OCT (LightLab Imaging, Westford, MA, USA) image-wire in 3 swine by infusing 30 ml of each of 3 solutions differing in viscosity, osmolarity and electrolytic composition (A: iodixanol 320 and Lactated Ringer's; B: iodixanol 320 and 50% albumin; C: iodixanol 320). Image quality and adverse effects were evaluated. The solution with the best image quality/side-effect ratio was tested in 44 patients. The best image quality/side-effect ratio was obtained in the swine model with solution C, which enabled the study of arterial segments of 29.8±2.1 mm in length. The results were confirmed in the human study (average length of 28.3±2.5 mm and absence of major complications and/or major arrhythmias). Repeated OCT pull-back in the first 10 patients enabled comparison of 1,572 matched cross-sections with an excellent correlation for reproducibility (R=0.96; p<0.001). Conclusions The non-occlusive technique using iodixanol 320 has an excellent ratio of safety, feasibility and efficacy. (Circ J 2008; 72: 839 - 843)
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Stent expansion, apposition and symmetry were the three criteria of intravascular ultrasound (IVUS) guided optimal stent deployment in the bare metal stent era1, with at least the criterion of stent expansion maintaining its clinical relevance in the drug-eluting stent (DES) era2. Two prospective studies showed that stent malapposition immediately following DES implantation was not associated with increased adverse clinical events3,4. Thus, initial concerns that immediate stent malapposition would affect drug delivery to the vessel wall and lead to DES failure appeared to be unfounded. Coronary IVUS, however, formerly the gold standard for assessing stent strut apposition, is imprecise in the detection of stent malapposition observed in around 7% of lesions3,4, a figure which is probably grossly underestimated. This is due to the limited axial and lateral resolution of the ultrasound waves (100-150 microm) and the constant presence of artefacts around stent struts (side-lobes, shadowing). Optical coherence tomography (OCT) uses infrared light with the advantage of greater resolution (10-15 microm) and less strut induced artefacts compared with IVUS5,6. Unlike the first OCT prototypes used by Jang et al5,6, new commercial systems (LightLab Imaging Inc., Westford, MA, USA) can acquire contiguous images with a motorised pullback system as used with IVUS7. Still, OCT has some disadvantages including a more complex process of image acquisition that requires transient proximal flow occlusion with a balloon. Since there is definite learning curve to achieve optimal image quality, this article will focus on methods and techniques to attain optimal assessment of stent strut apposition, using the current OCT system.
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This study sought to assess safety and efficacy of implantation of the Catania Coronary Stent System with Nanothin Polyzene-F (CeloNova BioSciences, Newnan, Georgia) in human coronary arteries with clinical data and comprehensive intracoronary imaging. Novel approaches to modify stents (e.g., bioactive agents, coatings) have been developed to address the limitations of bare-metal and drug-eluting stents (e.g., restenosis, target lesion revascularization [TLR], late thrombosis). This first-in-man study using the Catania stent is a prospective, single center, nonrandomized, single-arm study of 55 patients with symptomatic ischemic heart disease with de novo, obstructive lesions of native coronary arteries. Acute angiographic success was 100%. A core laboratory analyzed quantitative coronary angiography and intravascular ultrasound data immediately after stenting and at 6-month follow-up. Late lumen loss was 0.60 +/- 0.48 mm and the percent neointimal hyperplasia volume was 27.9 +/- 16.1%. In 15 of 55 randomly selected patients, 1,904 cross-sections (19,028 struts) were analyzed at 6 months by optical coherence tomography. Overall, 99.5% of struts were covered. Only 29 of 19,028 struts (0.15%) were malapposed. Binary angiographic restenosis was 6.8%. No death, myocardial infarction, or Academic Research Consortium-defined stent thrombosis was observed at 12 months. The incidence of TLR at 12 months was clinically driven TLR 3.6% (2 of 55) and nonclinically driven TLR 7.3% (4 of 55). This first-in-man showed an excellent early and mid-term safety profile and high-level efficacy of the new Catania stent in the treatment of de novo coronary lesions in a fairly complex population. Polyzene-F coated stents may be an alternative to both bare-metal and drug-eluting stents with reduced late loss, restenosis, and the TLR without long-term dual antiplatelet therapy.
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An optical coherence tomography system comprising a light source (a) and a probe (e) that has a window at a front facing end. The window has an inner face (i) that has an anti-reflection surface and allows light from the source to pass through it, and an outer face (j) that reflects some of the light from the source and transmits some of the light to and from the sample (k). The reflected light acts as a reference.
Article
The purpose of this study was to evaluate optical coherence tomography (OCT) for detecting small degrees of in-stent neointima (ISN) after stent implantation compared with intravascular ultrasound (IVUS). The importance of detecting neointimal coverage of stent struts has grown with the appreciation of the increased risk for late stent thrombosis after drug-eluting stent (DES) implantation. Intravascular ultrasound, the current standard for evaluating the status of DES, lacks the resolution to detect the initial neointimal coverage. Optical coherence tomography has greater resolution but has not yet been compared with IVUS in vivo with histological correlation for validation. Intravascular ultrasound and OCT were performed with motorized pullback imaging in 6 pigs across 33 stents, 1 month after implantation. Each pig was euthanized, and histological measurements of vessel, stent, and lumen dimensions were performed in 3 sections of each stent. A small degree of ISN was defined as occupying <30% of the stent area measured with histology. The IVUS, OCT, and histological assessment of ISN were compared in matched cross-sections of the stents with a small degree of ISN. Eleven stents had a small degree of ISN (average ISN area: 1.26 +/- 0.46 mm(2), and percent area obstruction: 21.4 +/- 5.2%). Compared with histology, the diagnostic accuracy of OCT (area under the receiver operating characteristic curve [AUC] = 0.967, 95% confidence interval [CI] 0.914 to 1.019) was higher than that of IVUS (AUC = 0.781, 95% CI 0.621 to 0.838). Optical coherence tomography detects smaller degrees of ISN more accurately than IVUS and might be a useful method for identifying neointimal coverage of stent struts after DES implantation.
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We sought to evaluate the new polymer PTFEP (poly(bis(trifluoroethoxy)phosphazene) for (1) its ability to reduce thrombogenicity and late in-stent stenosis and (2) its effect on endothelialization in a rabbit iliac artery model. Nanocoated ( approximately 50 nm) and bare stainless-steel stents were implanted bilaterally in the iliac arteries of 30 New Zealand White rabbits (1, 4, 8, 12, and 16 weeks follow-up) and evaluated by angiography, light, and scanning electron microscopy. Bilateral stent placement was successful in 27 of 30 rabbits. Thrombus depositions occurred in none of the 27 coated but in 4 of the 27 bare stents (P=0.037). A normal angiogram was obtained in 18 of 22 coated stents at risk for restenosis (follow-up >or=4 weeks) but only in 13 of 22 bare stents (P=0.023). Marked restenosis (luminal loss >30%) was found in 6 bare stents (P=0.011) but not in any coated stents. The neointima was 47.7-73.9 mum on coated and 66.9-115.2 mum on bare stents (statistically significant at 4, 8, and 16 weeks). Scanning electron microscopy detected full endothelialization in all stents from 4 weeks on (22 stents in both groups). PTFEP nanocoating successfully showed thromboresistance and reduced late in-stent stenosis. Endothelialization was equal in both stent types. Studies in more human-like models and human feasibility studies in human arteries are encouraged.
Article
Stent thrombosis is a safety concern associated with use of drug-eluting stents. Little is known about occurrence of stent thrombosis more than 1 year after implantation of such stents. Between April, 2002, and Dec, 2005, 8146 patients underwent percutaneous coronary intervention with sirolimus-eluting stents (SES; n=3823) or paclitaxel-eluting stents (PES; n=4323) at two academic hospitals. We assessed data from this group to ascertain the incidence, time course, and correlates of stent thrombosis, and the differences between early (0-30 days) and late (>30 days) stent thrombosis and between SES and PES. Angiographically documented stent thrombosis occurred in 152 patients (incidence density 1.3 per 100 person-years; cumulative incidence at 3 years 2.9%). Early stent thrombosis was noted in 91 (60%) patients, and late stent thrombosis in 61 (40%) patients. Late stent thrombosis occurred steadily at a constant rate of 0.6% per year up to 3 years after stent implantation. Incidence of early stent thrombosis was similar for SES (1.1%) and PES (1.3%), but late stent thrombosis was more frequent with PES (1.8%) than with SES (1.4%; p=0.031). At the time of stent thrombosis, dual antiplatelet therapy was being taken by 87% (early) and 23% (late) of patients (p<0.0001). Independent predictors of overall stent thrombosis were acute coronary syndrome at presentation (hazard ratio 2.28, 95% CI 1.29-4.03) and diabetes (2.03, 1.07-3.83). Late stent thrombosis was encountered steadily with no evidence of diminution up to 3 years of follow-up. Early and late stent thrombosis were observed with SES and with PES. Acute coronary syndrome at presentation and diabetes were independent predictors of stent thrombosis.
Article
Late stent thrombosis (LST) after Cypher and Taxus drug-eluting stent placement has emerged as a major concern. Although the clinical predictors of LST have been reported, specific morphological and histological correlates of LST remain unknown. From a registry totaling 81 human autopsies of drug-eluting stents, 46 (62 lesions) had a drug-eluting stent implanted >30 days. We identified 28 lesions with thrombus and compared those with 34 of similar duration without thrombosis using computer-guided morphometric and histological analyses. LST was defined as an acute thrombus within a coronary artery stent in place >30 days. Multiple logistic generalized estimating equations modeling demonstrated that endothelialization was the best predictor of thrombosis. The morphometric parameter that best correlated with endothelialization was the ratio of uncovered to total stent struts per section. A univariable logistic generalized estimating equations model of occurrence of thrombus in a stent section versus ratio of uncovered to total stent struts per section demonstrated a marked increase in risk for LST as the number of uncovered struts increased. The odds ratio for thrombus in a stent with a ratio of uncovered to total stent struts per section >30% is 9.0 (95% CI, 3.5 to 22). The most powerful histological predictor of stent thrombosis was endothelial coverage. The best morphometric predictor of LST was the ratio of uncovered to total stent struts. Heterogeneity of healing is a common finding in drug-eluting stents with evidence of LST and demonstrates the importance of incomplete healing of the stented segment in the pathophysiology of LST.
Article
Confirming complete neointimal coverage after implantation of a drug-eluting stent is clinically important because incomplete stent coverage is responsible for late thrombosis and sudden cardiac death. Optical coherence tomography is a high-resolution (approximately 10 microm) imaging technique capable of detecting a thin layer of neointimal hyperplasia (NIH) inside a sirolimus-eluting stent (SES) and stent malapposition. This investigation evaluated stent exposure and malapposition 3 months after SES implantation using optical coherence tomography in a different clinical presentations, such as acute coronary syndrome (ACS) and non-ACS. Motorized optical coherence tomographic pullback (1 mm/s) was performed at 3-month follow-up to examine consecutive implanted 31 SESs in 21 lesions in 21 patients (9 with ACS and 12 with non-ACS). NIH thickness inside each strut and percent NIH area in each cross section were measured. In total, 4,516 struts in 567-mm single-stented segments were analyzed. Overall, NIH thickness and percent NIH area were 29 +/- 41 microm and 10 +/- 4%, respectively. Rates of exposed struts and exposed struts with malapposition were 15% and 6%, respectively. These were more frequent in patients with ACS than in those with non-ACS (18% vs 13%, p <0.0001; 8% vs 5%, p <0.005, respectively). In conclusion, neointimal coverage over a SES at 3-month follow-up is incomplete in ACS and non-ACS. Our study suggests that dual antiplatelet therapy might be continued >3 months after SES implantation.
Article
No detailed data regarding neointimal coverage of bare-metal stents (BMSs) at 3 months after implantation was reported to date. This investigation was designed to evaluate the neointimal coverage of BMSs compared with sirolimus-eluting stents (SESs) using optical coherence tomography. A prospective optical coherence tomographic follow-up examination was performed 3 months after stent implantation for patients who underwent BMS (n = 16) or SES implantation (n = 24). Neointimal hyperplasia (NIH) thickness on each stent strut and percentage of NIH area in each cross section were measured. Malapposition of stent struts to the vessel wall and the existence of in-stent thrombi were also evaluated. There were 5,076 struts of SESs and 2,875 struts of BMSs identified. NIH thickness and percentage of NIH area in the BMS group were higher than in the SES group (351 +/- 248 vs 31 +/- 39 mum; p <0.0001; 45.0 +/- 14% vs 10.0 +/- 4%; p <0.0001, respectively). The frequency of uncovered struts was higher in the SES group than the BMS group (15% vs 0.1%; p <0.0001). Malapposed struts were observed more frequently in the SES group than the BMS group (15% vs 1.1%; p <0.0001). In conclusion, there was no difference in incidence of in-stent thrombus between the 2 groups (14% vs 0%; p = 0.23). The present study showed almost all BMS struts to be well covered at a 3-month follow-up, suggesting that patients receiving BMS stents may not require dual-antiplatelet therapy >3 months after implantation.
Task Force for the Redefinition of Myocardial Infarction. Universal defini-tion of myocardial infarction
  • K Thygesen
  • Js Alpert
  • White Hd
  • Esc Joint
  • Accf
  • Aha
  • Whf
Thygesen K, Alpert JS, White HD, Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal defini-tion of myocardial infarction. Eur Heart J 2007;28:2525–2538.