The 2010s in clinical drug-eluting stent and bioresorbable scaffold research: a Dutch perspective.

Dutch researchers were among the first to perform clinical studies in bare metal coronary stents, the use of which was initially limited by a high incidence of in-stent restenosis. This problem was greatly solved by the introduction of drug-eluting stents (DES). Nevertheless, enthusiasm about first-generation DES was subdued by discussions about a higher risk of very-late stent thrombosis and mortality, which stimulated the development, refinement, and rapid adoption of new DES with more biocompatible durable polymer coatings, biodegradable polymer coatings, or no coating at all. In terms of clinical DES research, the 2010s were characterised by numerous large-scale randomised trials in all-comers and patients with minimal exclusion criteria. Bioresorbable scaffolds (BRS) were developed and investigated. The Igaki-Tamai scaffold without drug elution was clinically tested in the Netherlands in 1999, followed by an everolimus-eluting BRS (Absorb) which showed favourable imaging and clinical results. Afterwards, multiple clinical trials comparing Absorb and its metallic counterpart were performed, revealing an increased rate of scaffold thrombosis during follow-up. Based on these studies, the commercialisation of the device was subsequently halted. Novel technologies are being developed to overcome shortcomings of first-generation BRS. In this narrative review, we look back on numerous devices and on the DES and BRS trials reported by Dutch researchers.

How to define bifurcation lesion complexity and how to successfully perform percutaneous treatment.

Historically, percutaneous coronary interventions (PCI) of bifurcation lesions have been associated with a lower procedural success rate, a higher complication rate, and less favorable clinical outcomes, compared to PCI of non-bifurcation lesions. However, percutaneous treatment of coronary bifurcation lesions have been improved over the past decade due to improvements in stent design and the introduction of specific bifurcation stent techniques. Some even argue that PCI of bifurcation lesions should no longer be considered as being complex. However, recent studies have shown that there are still certain bifurcation lesion subtypes which are at higher risk for adverse cardiac events after PCI. Future efforts, including the development of a dedicated bifurcation device, should be focused on this specific high-risk subgroup, including distal left main bifurcations.

Novel bioresorbable scaffolds technologies: current status and future directions.

Over the past century, coronary artery disease (CAD) has remained a leading cause of death worldwide, managed with enormous progress by medicine, from the development of advanced drugs to highly sophisticated revascularization modalities. Among them, as confirmed by recent studies, bioresorbable scaffolds (BRSs) have shown to have the potential to overtake conventional stents. This review presents their material composition and properties, those currently used in clinical evaluation, and their current limitations and potential improvements.

Revascularization strategies for patients with stable coronary artery disease.

Patients with coronary artery disease who have prognostically significant lesions or symptoms despite optimum medical therapy require mechanical revascularization with coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) or both. In this review, we will evaluate the evidence-based use of the two revascularization approaches in treating patients with coronary artery disease. CABG has been the predominant mode of revascularization for more than half a century and is the preferred strategy for patients with multivessel disease, especially those with diabetes mellitus, left ventricular systolic dysfunction or complex lesions. There have been significant technical and technological advances in PCI over recent years, and this is now the preferred revascularization modality in patients with single-vessel or low-risk multivessel disease. Percutaneous coronary intervention can also be considered to treat complex multivessel disease in patients with increased risk of adverse surgical outcomes including frail patients and those with chronic obstructive pulmonary disease. Improvements in both CABG (including total arterial revascularization, off-pump CABG and 'no-touch' graft harvesting) and PCI (including newer-generation stents, adjunctive pharmacotherapy and intracoronary imaging) mean that they will continue to challenge each other in the future. A 'heart team' approach is strongly recommended to select an evidence-based, yet individualized, revascularization strategy for all patients with complex coronary artery disease. Finally, optimal medical therapy is important for all patients with coronary artery disease, regardless of the mode of revascularization.

1-Year clinical outcomes of diabeticpatients treated with everolimus-elutingbioresorbable vascular scaffolds: a pooled analysis of the ABSORB and the SPIRIT trials

Objectives The aim of this study was to evaluate 1-year clinical outcomes of diabetic patients treatedwith the Absorb bioresorbable vascular scaffold (BVS).Background Clinical outcomes of diabetic patients after BVS implantation have been unreported.Methods This study included 101 patients in the ABSORB Cohort B trial and the first consecutive 450patients with 1 year of follow-up in the ABSORB EXTEND trial. A total of 136 diabetic patients werecompared with 415 nondiabetic patients. In addition, 882 diabetic patients treated with everolimuselutingmetal stents (EES) in pooled data from the SPIRIT trials (SPIRIT FIRST [Clinical Trial of the AbbottVascular XIENCE V Everolimus Eluting Coronary Stent System], SPIRIT II [A Clinical Evaluation of the XIENCEV Everolimus Eluting Coronary Stent System], SPIRIT III [Clinical Trial of the XIENCE V Everolimus ElutingCoronary Stent System (EECSS)], SPIRIT IV Clinical Trial [Clinical Evaluation of the XIENCE V EverolimusEluting Coronary Stent System]) were used for the comparison by applying propensity score matching.The primary endpoint was a device-oriented composite endpoint (DoCE), including cardiac death, targetvessel myocardial infarction, and target lesion revascularization at 1-year follow-up.Results The cumulative incidence of DoCE did not differ between diabetic and nondiabetic patientstreated with the BVS (3.7% vs. 5.1%, p » 0.64). Diabetic patients treated with the BVS had a similarincidence of the DoCE compared with diabetic patients treated with EES in the matched study group(3.9% for the BVS vs. 6.4% for EES, p » 0.38). There were no differences in the incidence of definite orprobable scaffold/stent thrombosis (0.7% for both diabetic and nondiabetic patients with the BVS; 1.0%for diabetic patients with the BVS vs. 1.7% for diabetic patients with EES in the matched study group).Conclusions In the present analyses, diabetic patients treated with the BVS showed...

Long-term outcome of the unrestricted use of everolimus-eluting stents compared to sirolimus-eluting stents and paclitaxel-eluting stents in diabetic patients: the Bern-Rotterdam diabetes cohort study.

BACKGROUND: Newer generation everolimus-eluting stents (EES) improve clinical outcome compared to early generation sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). We investigated whether the advantage in safety and efficacy also holds among the high-risk population of diabetic patients during long-term follow-up. METHODS: Between 2002 and 2009, a total of 1963 consecutive diabetic patients treated with the unrestricted use of EES (n=804), SES (n=612) and PES (n=547) were followed throughout three years for the occurrence of cardiac events at two academic institutions. The primary end point was the occurrence of definite stent thrombosis. RESULTS: The primary outcome occurred in 1.0% of EES, 3.7% of SES and 3.8% of PES treated patients ([EES vs. SES] adjusted HR=0.58, 95% CI 0.39-0.88; [EES vs. PES] adjusted HR=0.29, 95% CI 0.13-0.67). Similarly, patients treated with EES had a lower risk of target-lesion revascularization (TLR) compared to patients treated with SES and PES ([EES vs. SES], 5.6% vs. 11.5%, adjusted HR=0.68, 95% CI: 0.55-0.83; [EES vs. PES], 5.6% vs. 11.3%, adjusted HR=0.51, 95% CI: 0.33-0.77). There were no differences in other safety end points, such as all-cause mortality, cardiac mortality, myocardial infarction (MI) and MACE. CONCLUSION: In diabetic patients, the unrestricted use of EES appears to be associated with improved outcomes, specifically a significant decrease in the need for TLR and ST compared to early generation SES and PES throughout 3-year follow-up.

DES the year in review: controversies.

Drug-eluting stents (DES) have transformed interventional cardiology over the past decade. Whilst their efficacy has rarely been called into question, there have been concerns over the safety of the early devices, which has prompted the development of new coronary stents. Many of these new devices have entered clinical practice, however questions remain as to whether they offer the improvements in clinical outcomes that were originally anticipated. In addition, there is a debate whether the reported high efficacy of these devices enables percutaneous coronary intervention (PCI) to be performed in patient and lesion sub-groups previous entirely the domain of the cardiac surgeon. This review paper addresses these outstanding questions.

Developments in coronary artery stenting: primum non nocere.

The occurrence of restenosis and acute vessel closure postballoon angioplasty was the driving force for the introduction of coronary artery stenting in the 1980s. Although the first generation of coronary artery stents were highly valuable and efficient in scaffolding (non-)threatened coronary vessels, they proved to be associated with iatrogenic side effects such as in-stent neointimal hyperplasia. The efforts to tackle these side-effects eventually lead to the most significant progress within the field of interventional cardiology in the past decennium, namely drug-eluting stents (DES). Analysts estimate that the total amount of DES implantations worldwide will be more than 5 million this year. Although this worldwide increase in percutaneous coronary interventions (PCI) is impressive, some pitfalls such as the incidence of neointimal hyperplasia, stent fracture and a local hypersensitivity reaction against the polymer coating are worrisome. According to critics, the possible causal relationship with higher rates of very-late stent thrombosis could be a ticking time bomb. These concerns paved the way for the development of novel stents, ranging from DES with biodegradable polymer coating to completely biodegradable stents. Like all progress in medical interventions, it is essential to not harm the patient throughout this complex evolvement process of coronary stents. The current review not only discusses the benefits and safety issues associated with currently utilized coronary stents but in particular highlights novel coronary stents that are being investigated in (pre-)clinical trials at this moment.

First-in-man, multicentre assessment of the novel Acrobat Svelt balloon-expandable stent-on-a-wire system

Recently developed, the Acrobat SOAW (Stent-On-A-Wire) coronarysystem combines a very-thin (81 μ) balloon-expandable, Cro-Co (L605) stentmounted on a delivery system with a 0.012” integrated guidewire tip (distance fromthe tip of the wire to the stent is 22mm). We sought to determine the efficacyprofile of this novel device.Methods and results: SVELTE trial is a multicenter, international (Brazil,Netherlands and Colombia), prospective, non-randomised, single-arm study of theAcrobat SOAW for the treatment of de novo coronary lesions no longer than 18mmand located in native vessels of 2.5 to 3.5mm. DS was highly recommended andpost-dilatation was at operator’s discretion. Patients were oriented to stay on dualanti-platelet regimen for at least 1 month. Main exclusion criteria were PCI in thesetting of acute ST-elevation MI and bifurcation lesions. All patients werescheduled to undergo angiographic follow-up at 6 months. The primary endpoint ofthe study was the survival-free of combined MACE (cardiac death, myocardiuminfarction and target-lesion revascularisation) at 30 days. Secondary endpointsincluded 6-month in-stent late lumen loss and binary restenosis as well ascombined MACE rate.A total of 46 patients were enrolled with mean age of 63years old, 76.6% of male and 21.3% of diabetics. Mean RVD and lesion lengthwere 3.03mm and 12.67mm, respectively. The Acrobat stent was deployed in100% of the cases (89.6% of DS) achieving a procedure success rate of 97.8%.Up to 30 days there were no deaths, Q-Wave MIs or urgent TLR. Six-monthinvasive follow-up is ongoing and complete QCA assessment will be available atthe meeting.Conclusions: The Acrobat SOAW may potentially facilitate PCI by reducingtime/cost and minimising peri-procedural complications. The present trialrepresents the first-in-man assessment of this innovative concept.

Complex coronary bifurcation lesions treated with the novelpolymer-free dedicated bifurcation paclitaxel-eluting stent (Nilepax): clinical and angiographic clinical results of theprospective, multicentre bipax clinical trial

Aims: We report the angiographic and clinical outcomes of patients with de novocoronary bifurcation lesions treated with the Nile PAX dedicated device.Methods and results: From Dec/08 to Mar/09, a total of 102 pts with singlebifurcation lesion were prospectively enrolled in this non-randomised, multicenter(10 sites in Europe/South America) study. Lesion criteria were vessel size 2.5-3.5mm in the parent vessel (PV) and 2.0-3.0 mm in the SB, and lesion length <14 mmin the PV. Clinical follow-up (FU) was scheduled at 1, 3, 6, 9 and 12 months, andyearly up to 5 years. Angiographic FU was scheduled at 9 months (primaryendpoint). Angiographic analysis was performed by an independent angiographiccore laboratory. Data analysis and management was performed by an independentdata coordinating center; also, all clinical events were independently adjudicatedby a clinical events committee. Mean age was 63 years, 29% had diabetes, 16previous MI, and 40% previous intervention. The LAD/Dg was the most prevalentlocation (75%), and 60% had significant involvement of both branches. In theprocedure, PV was predilated in 97%; the study stent was successfully attemptedand implanted in 99%. Overall, 25% of SB received an additional stent; and 94%of lesions had final kissing-balloon inflation. By quantitative coronary angiography,baseline mean lesion length, vessel diameter and% diameter stenosis were: 10.9mm, 2.99 mm and 72% in the PV, and 4.1 mm, 2.28 mm, and 38% in the SB, respectively. Angiographic success (residual stenosis <50%, final TIMI 3 flow, andabsence of dissection) was achieved in 98%. There was only 1 major adversecardiac event (MACE) during hospitalisation, which was adjudicated as a non-Qmyocardial infarction during hospitalisation, and no additional adverse events werereported up to 30 days...

Combined optical coherence tomography and intravascular ultrasound radio frequency data analysis for plaque characterization. Classification accuracy of human coronary plaques in vitro.

This study was performed to characterize coronary plaque types by optical coherence tomography (OCT) and intravascular ultrasound (IVUS) radiofrequency (RF) data analysis, and to investigate the possibility of error reduction by combining these techniques. Intracoronary imaging methods have greatly enhanced the diagnostic capabilities for the detection of high-risk atherosclerotic plaques. IVUS RF data analysis and OCT are two techniques focusing on plaque morphology and composition. Regions of interest were selected and imaged with OCT and IVUS in 50 sections, from 14 human coronary arteries, sectioned post-mortem from 14 hearts of patients dying of non-cardiovascular causes. Plaques were classified based on IVUS RF data analysis (VH-IVUS(TM)), OCT and the combination of those. Histology was the benchmark. Imaging with both modalities and coregistered histology was successful in 36 sections. OCT correctly classified 24; VH-IVUS 25, and VH-IVUS/OCT combined, 27 out of 36 cross-sections. Systematic misclassifications in OCT were intimal thickening classified as fibroatheroma in 8 cross-sections. Misclassifications in VH-IVUS were mainly fibroatheroma as intimal thickening in 5 cross-sections. Typical image artifacts were found to affect the interpretation of OCT data, misclassifying intimal thickening as fibroatheroma or thin-cap fibroatheroma. Adding VH-IVUS to OCT reduced the error rate in this study.

Adherence to patient selection criteria in patients undergoing transcatheter aortic valve implantation with the 18F CoreValve ReValving System.

BACKGROUND: Anecdotal evidence suggests that transcatheter aortic valve implantation (TAVI) is being used beyond pre-market label indications. METHODS: To assess the frequency and outcomes associated with "off-label" use of TAVI, we conducted a retrospective study, examining adherence to patient selection criteria in 63 patients undergoing implantation with the 18F CoreValve ReValving System (CRS). Label status (on-label vs off-label) was determined by following (1) inclusion/exclusion criteria indicated in the 18F CRS safety and efficacy trial and (2) a patient selection matrix indicating anatomical boundaries to guide patient selection. Off-label use was defined as the presence of at least one exclusion criterion or "non-acceptable" criteria based on the patient selection matrix. RESULTS: Off-label implantation was identified in 42 patients (67%)-40% had one, 19% had two and 8% had three or more off-label criteria. Baseline demographics were similar between the groups except for a higher logistic EuroSCORE in the on-label group (19.8 (11.2) vs 14.5 (7.3), p = 0.029). There was no significant difference in the procedural success rates between the on-label and off-label groups (91% vs 95%, respectively, p = 0.47). The frequency of angiographic moderate-severe aortic regurgitation, post-implant dilatation or implantation of a second valve was also similar between the groups. At 30 days, the cumulative death rate was 10%; there were four deaths in the "on-label" and three deaths in the "off-label" group. CONCLUSION: In this study we found that "off-label" implantation of the CRS was common. Further studies are needed to evaluate the consequences of "label status" for patients undergoing TAVI.

Imaging atherosclerotic plaque composition with intracoronary optical coherence tomography.

Optical coherence tomography (OCT) allows highly accurate diagnosis of atherosclerotic plaques, including measurement of the thickness of fibrous caps, permitting an assessment of the risk of rupture. While the OCT image presents morphological information in highly resolved detail, it relies on interpretation by trained readers for the identification of tissue type. We developed a method for quantitative classification of atherosclerotic plaque constituents. The optical attenuation coefficient mu(t) distinguishes different tissue types: necrotic core and macrophage infiltration exhibit strong attenuation, mu(t)>/=10 mm(-1), while calcific and fibrous tissue have a lower mu(t) approximately 2-5 mm(-1). (Neth Heart J 2009;17:448-50.).

Optical coherence tomography assessment of the acute effects of stent implantation on the vessel wall: a systematic quantitative approach.

OBJECTIVE: To observe and characterise vessel injury after stenting using optical coherence tomography (OCT), to propose a systematic OCT classification for periprocedural vessel trauma, to evaluate its frequency in stable versus unstable patients and to assess its clinical impact during the hospitalisation period. SETTING: Stenting causes vessel injury. DESIGN AND INTERVENTIONS: All consecutive patients in whom OCT was performed after stent implantation were included in the study. Qualitative and quantitative assessment of tissue prolapse, intra-stent dissection and edge dissection were performed. RESULTS: Seventy-three patients (80 vessels) were analysed. Tissue prolapse within the stented segment was visible in 78/80 vessels (97.5%). Median number of tissue prolapse sites was 8 (IQR 4-19), mean (SD) area 1.04 (0.9) mm(2). Intra-stent dissection flaps were visible in 69/80 vessels (86.3%) (median number 3 (IQR 1.25-6), maximum flap length 450 (220) microm). Fifty-five out of 80 vessels (68.8%) showed dissection cavities (median number 2 (IQR 0-4.75), maximum depth 340 (170) microm). Edge dissection was visible in 20 vessels (mean (SD) length flap 744 (439) microm). The frequency of tissue prolapse or intra-stent dissection was similar in stable and unstable patients (95.6% vs 100%, p = 0.5 for tissue prolapse; 91.1% vs 82.9%, p = 0.3 for intra-stent dissection). There were no events during the hospitalisation period. CONCLUSIONS: OCT allows a detailed visualisation of vessel injury after stent implantation and enables a systematic classification and quantification in vivo. In this study, frequency of tissue prolapse or intra-stent dissections after stenting was high, irrespective of the clinical presentation of the patients, and was not associated with clinical events during hospitalisation.

Sirolimus-eluting stents, bare metal stents or coronary artery bypass grafting for patients with multivessel disease including involvement of the proximal left anterior descending artery: analysis of the Arterial Revascularization Therapies study part 2 (ARTS-II).

OBJECTIVE: The The Arterial Revascularization Therapies Study (ARTS)-II trial found no differences in survival or overall adverse events between sirolimus-eluting stents (SES) and the surgical arm of ARTS-I. Nevertheless, existing data suggest that patients with disease of the proximal left anterior descending artery (LAD) may derive particular benefit from coronary artery bypass grafting (CABG). We therefore analysed the clinical outcome of patients in ARTS-I and ARTS-II with proximal LAD involvement. DESIGN: Multicentre observational study. SETTING: Forty-five European academic hospitals. PATIENTS: Patients with multivessel coronary artery disease. INTERVENTIONS: Patients in ARTS-II with proximal LAD disease treated with SES (289/607, 48%) were compared with 187/600 (31%) bare metal stent patients (ARTS-I BMS) and 206/605 (34%) surgical patients (ARTS-I CABG) with proximal LAD involvement from ARTS-I. MAIN OUTCOME MEASURES: Major adverse cardiac and cerebrovascular events after 3 years. RESULTS: The Arterial Revascularization Therapies study part 2 (ARTS-II) subgroup had better survival than both ARTS-I groups (ARTS-II 98.6% vs ARTS-I BMS 95.7%, p = 0.05 and vs ARTS-I CABG 94.7%, p = 0.01) and lower rates of the hard clinical composite endpoint of death or non-fatal myocardial infarction (ARTS-II 3.1% vs ARTS-I BMS 9.6%, p = 0.002 and vs ARTS-I CABG 9.7%, p = 0.002). Although the ARTS-I CABG patients had a lower need for repeat revascularisation than ARTS-II (5.3% vs 13.1%, p = 0.002), the overall composite adverse event rates (death, myocardial infarction, stroke or any repeat revascularisation) were not significantly different between the ARTS-I CABG and ARTS-II patients (15.0% vs 18.0%, p = 0.4). CONCLUSIONS: SES are not inferior to CABG or bare metal stents for the treatment of patients with multivessel coronary disease including involvement of the proximal LAD.

Impact of drug-eluting stent selection on long-term clinical outcomes in patients treated for unprotected left main coronary artery disease: the sirolimus vs paclitaxel drug-eluting stent for left main registry (SP-DELFT).

AIM: To compare the long-term relative efficacy and safety of SES and PES in patients undergoing percutaneous coronary intervention (PCI) for unprotected left main coronary artery (ULMCA) disease and to evaluate the role of lesion location and stenting technique in determining outcomes. METHODS AND RESULTS: From April 2002 to April 2004, 288 consecutive patients who underwent elective PCI with DES implantation for de novo lesions on ULMCA have been retrospectively selected and analyzed in seven European and US tertiary care centers. All patients had a minimum follow-up of 3 years. SES was used in 152 patients while 136 received PES. Isolated ostial-shaft disease was present in 27% of patients. Distal LM disease (73%) was treated with single and double stent approach in 29.5% and 43.4% of patients respectively. After 3 years, rates of survival free from any of the events investigated, were independent from lesion location and stenting approach and did not differ significantly between SES and PES groups. Freedom from MACE (SES vs. PES) was 76.3% vs. 83.1% in the ostial/shaft group, 80.3% vs. 72.8% in the distal-single stent group and 67.1% vs. 66.2% in the distal-double stent group. Definite stent thrombosis occurred only in 1(0.3%) patient at 439 days. CONCLUSIONS: In elective patients who underwent PCI for de novo lesions in the ostium, shaft or distal ULMCA, long-term clinical outcomes with SES and PES use were similar independently of lesion location and stenting technique.

Optical coherence tomography: clinical applications and the evaluation of DES.

Optical coherencet tomography (OCT) is a light-based imaging modality that can provide in vivo high-resolution images of the coronary artery. In the last years there has been a continuous technical development that has improved the image quality and has simplified the acquisition procedure in order to spread the clinical applicability of this technique. Due to its high resolution OCT, can be a very valuable tool for the evaluation of the coronary vessel wall, the acute and long-term impact of catheter-based intervention on plaque structure and vessel architecture and the assessment of stents. During stenting, OCT offers the possibility to evaluate stent apposition in great detail and can identify the presence of vessel injury due to stent implantation. At follow-up, the tissue coverage of individual struts can be imaged with OCT. This is of increasing interest in drug-eluting stents in which the neointimal proliferation is inhibited to such extent that it might not be visualized with conventional intracoronary imaging techniques such as IVUS. Regarding the analysis of the coronary vessel wall, OCT holds promise for the identification of thin cap fibroatheroma due to its ability to provide information about plaque composition, presence of macrophages and thickness of the fibrous cap.