Prevention of restenosis in coronary arteries: ionic radiation, non-ionic radiation and drug eluting stents

Over the last decade, coronary stents have revolutionized the field of interventional cardiology. Stent implantation has become the new standard angioplasty procedure1-3. This popularity has grown because of 2 main reasons: first, the unique capability to master a major complication of balloon angioplasty - (sub) acute vessel closure - and second, a superior long-term outcome in comparison to balloon angioplasty4-8. The high reliability of the acute angioplasty result allowed for a continuos expansion of the indication for catheter-based intervention (including ostial lesions9, bifurcation lesions10, 11, left main lesions12, 13, multiple lesions14). In-stent restenosis However, in-stent restenosis remains the major limitation of coronary stenting. The absolute number of in-stent restenotic lesions is increasing in parallel with the steadily increasing number of stenting procedures and with the complexity of culprit lesions. The treatment of instent restenosis is technically challenging and costly. In subsets of lesions (such as small vessel size and diffuse disease) an anticipated high risk for restenosis may even prevent the use of stents. Restenosis represents a local vascular manifestation of the general biologic response to injury15. Injury consists of denuding the intima and stretching the media. Current concepts describe three mechanisms of the restenotic process: early elastic recoil, late vessel remodeling and neointimal growth16, 17. We could demonstrate (chapter 2) that coronary stents provide mechanical scaffolding that virtually eliminates recoil and remodeling18. However, neointimal growth continues to be a major problem. New strategies for the prevention of in-stent restenosis Over the last 2 decades, efforts for the prevention of restenosis were focused on optimizing stent characteristics and implantation technique19, 20. The growing understanding of vascular biology and the observation that exaggerated neointimal formation shows similarities to tumor growth triggered the development of new treatment strategie

Stent development and local drug delivery

Stent implantation has become the new standard angioplasty procedure. Instent re-stenosis remains the major limitation of coronary stenting. Re-stenosis is related to patient-, lesion- and procedure-specific factors. Patient-specific factors can not be influenced to any extent. Procedure-specific factors are affected by implantation technique and stent characteristics. Design and material influence vascular injury and humoral and cellular response. Radiation has been shown to have inhibitory effects on smooth muscle cell growth and neo-intima formation, but in clinical trials the outcome has been hampered by re-stenosis at the edges of the radioactive stent ('candy wrapper'). New approaches target pharmacological modulation of local vascular biology by local administration of drugs. This allows for drug application at the precise site and time of vessel injury. Systemic release is minimal and this may reduce the risk of toxicity. The drug and the delivery vehicle must fulfil pharmacological, pharmacokinetic and mechanical requirements and the application of eluting degradable matrices seems to be a possible solution. Numerous pharmacological agents with antiproliferative properties are currently under clinical investigation, e.g. actinomycin D, rapamycin or paclitaxel. Another approach is for stents to be made of biodegradable materials as an alternative to metallic stents. Their potential long-term complications, such as in-stent resteno

Association of systemic inflammatory biomarkers with morphological characteristics of coronary atherosclerotic plaque by intravascular optical coherence tomography

Despite significant advances in preventive, medical, and interventional management, coronary artery disease remains the leading cause of death worldwide. We now know that in the majority of acute coronary syndromes, a thrombotic event is triggered either by the rupture or erosion of the so-called high-risk or ‘vulnerable’ plaque. However, accurately identifying the individual who is at significant risk of acute event remains the holy grail of preventive cardiology. To better stratify an individual's risk of developing and suffering a cardiovascular event, biomarkers are needed that can accurately predict coronary events and, if possible, monitor disease activity in response to medical or interventional therapies. In order to be able to understand the association of these biomarkers with the morphological substrate of high-risk plaques, intravascular imaging modalities can provide invaluable assistance. Novel imaging tools such as optical coherence tomography (OCT) have not only helped in identifying atherosclerotic plaque characteristics that are unstable but also in estimating global plaque burden. In this study, we provide an overview of our current knowledge of association of various inflammatory markers with atherosclerotic plaque characteristics seen on OCT

Quantification of fibrous cap thickness in intracoronary optical coherence tomography with a contour segmentation method based on dynamic programming

OBJECTIVES: Fibrous cap thickness is the most critical component of plaque stability. Therefore, in vivo quantification of cap thickness could yield valuable information for estimating the risk of plaque rupture. In the context of preoperative planning and perioperative decision making, intracoronary optical coherence tomography imaging can provide a very detailed characterization of the arterial wall structure. However, visual interpretation of the images is laborious, subject to variability, and therefore not always sufficiently reliable for immediate decision of treatment. METHODS: A novel semiautomatic segmentation method to quantify coronary fibrous cap thickness in optical coherence tomography is introduced. To cope with the most challenging issue when estimating cap thickness (namely the diffuse appearance of the anatomical abluminal interface to be detected), the proposed method is based on a robust dynamic programming framework using a geometrical a priori. To determine the optimal parameter settings, a training phase was conducted on 10 patients. RESULTS: Validated on a dataset of 179 images from 21 patients, the present framework could successfully extract the fibrous cap contours. When assessing minimal cap thickness, segmentation results from the proposed method were in good agreement with the reference tracings performed by a medical expert (mean absolute error and standard deviation of [Formula: see text] ) and were similar to inter-observer reproducibility ([Formula: see text] , R = .74), while being significantly faster and fully reproducible. CONCLUSION: The proposed framework demonstrated promising performances and could potentially be used for online identification of high-risk plaques

Is it safe to implant bioresorbable scaffolds in ostial side-branch lesions? Impact of 'neo-carina' formation on main-branch flow pattern. Longitudinal clinical observations

Formation of a 'neo-carina' has been reported after bioresorbable vascular scaffolds (BVS) implantation over side-branches. However, as this 'neo-carina' could protrude into the main-branch, its hemodynamic impact remains unknown. We present two cases of BVS implantation for ostial side-branch lesions, and investigate the flow patterns at follow-up and their potential impact. Computational fluid dynamics analysis was performed, using a 3D mesh created by fusion of 3-dimensional angiogram with optical coherence tomography images. In our first case, mild disturbances were seen when 'neo-carina' did not protrude perpendicularly into the main branch. In the second case, extensive flow re-distribution was observed due to a more pronounced protrusion of the 'neo-carina'. Importantly, these areas of hemodynamic disturbance were observed together with lumen narrowing in a non-stenotic vessel segment. Our case observations highlight the importance of investigating the hemodynamic consequences of BVS implantation in bifurcation lesions and illustrate a novel method to do so invivo

Two decades after coronary radiation therapy: A single center longitudinal clinical study

Objectives: The aim of this study was to evaluate the very long-term clinical outcome after radioactive stent (RS) implantation and intracoronary β radiation brachytherapy (IRBT). Background: Radioactive stents (RS) and intracoronary β radiation brachytherapy (IRBT) were introduced to prevent restenosis after percutaneous coronary intervention (PCI). Both techniques were associated with a higher incidence of major adverse cardiac events (MACE) in the short and intermediate-term follow up as compared to conventional PCI. Methods: One hundred and thirty-three patients received radioactive stents (32P) and 301 patients were treated with IRBT adjunctive to PCI. These groups were propensity matched to respectively 266 and 602 control patients who were treated with routine PCI during the same inclusion period. Endpoints were all-cause mortality and MACE, defined as all-cause death, any myocardial infarction or any revascularization. Results: Median follow-up duration was 17 years. All-cause mortality rates were similar in all groups. Adjusted hazard ratios for MACE and mortality in the RS cohort were 1.55 (95% CI 1.20–2.00) and 0.92 (95% CI 0.63–1.34), respectively. Adjusted hazard ratios for MACE and all-cause mortality in the IRBT cohort were 1.41 (95% CI 1.18–1.67) and 0.95 (95% CI 0.74–1.21), respectively. The difference in MACE rates was predominantly driven by coronary revascularizations in both groups, with a higher MI rate in the IRBT group as well. Conclusions: Coronary radiation therapy was associated with early increased MACE rates, but the difference in MACE rates decreased beyond 2 years, resulting in a comparable long-term clinical outcome. Importantly, no excess in mortality was observed

In vivo variability in quantitative coronary ultrasound and tissue characterization measurements with mechanical and phased-array catheters

Background: Both mechanical and phased-array catheters are used in clinical trials to assess quantitative parameters. Only limited evaluation of the in vivo agreement of volumetrical measurements between such systems has been performed, despite the fact that such information is essential for the conduction of atherosclerosis regression trials. Methods and results: We prospectively evaluated the agreement in morphometric measurements and intravascular ultrasound (IVUS)-based plaque characterization between a 40 MHz rotating transducer (3.2 F Atlantis, Boston Scientific Corp.) and a 20 MHz phased-array catheter (2.9 F Eagle Eye, Volcano Therapeutics, Rancho Cordova, California) in 16 patients. Lumen (7.3 ± 2.0 mm2 vs. 6.7 ± 1.8 mm2, p = 0.001) and vessel (11.8 ± 3.3 mm2 vs. 11.0 ± 2.9 mm2, p = 0.02) cross-sectional areas (CSA) were significantly greater with the 20 MHz system. Plaque CSA measurements showed no significant difference between systems (4.4 ± 2.3 mm2 vs. 4.4 ± 2.1). The relative differences were less than 10% for the three variables. On IVUS-based tissue characterization (13 patients), calculated percentage hypoechogenic volume was significantly higher for the 20 MHz system (96.7 ± 2.38 vs. 88.4 ± 5.53, p < 0.0001). Conclusions: Quantitative IVUS analyses display significant catheter type-dependent variability. It is unclear whether the variability reflects overestimation of measurements with the phased-array or underestimation with the mechanical system. Although plaque burden measurements did not differ significantly between systems, it appears prudent to recommend the use of a single system for progression/ regression studies

Optical Coherence Tomography: Potential Clinical Applications

Optical coherence tomography (OCT) is a novel intravascular imaging modality using near-infrared light. By OCT it is possible to obtain high-resolution cross-sectional images of the vascular wall structure and assess the acute and long-term effects of percutaneous coronary intervention. For the time being OCT has been mainly used in research providing new insights into the pathophysiology of the atheromatic plaque and of the vascular res