Optical Coherence Tomography Endpoints Research Articles

A randomized control trial to assess optical coherence tomography parameters of the Xlimus drug-eluting stent: the XLIMIT trial.

Third generation drug-eluting stents (DES) potentially offer better technical performance and reduced neointimal proliferation than previous generation DES. The XLIMIT non-inferiority trial evaluated the performance of the Xlimus (a novel sirolimus-eluting coronary stent system) in terms of endothelialization and tissue healing compared to the bioresorbable polymer Synergy DES. A total of 177 patients undergoing percutaneous coronary intervention (PCI) were randomized in a 2:1 ratio (2 Xlimus: 1 Synergy). The primary endpoints, defined as the in-stent neointimal volume weighted by the sum of the lengths of the implanted stent (ISNV) and the in-stent neointimal percent volume obstruction (%VO) were evaluated at 6-9 months by means of optical coherence tomography (OCT). Additional OCT parameters as well as clinical endpoints were also collected. Most of the patients were males (77.4%), and the mean age was 64 years. One third of the population had stable angina/silent ischemia. A total of 300 stents (237 lesions) were analyzed: 198 (152 lesions) were in the Xlimus group, and 102 (85 lesions) in the Synergy group. The ISNV in the Xlimus group was 30.7 ± 24.5 mm3 while in the Synergy group it was 26.5 ± 26.7 mm3: the difference between the two means was 0.08 (-0, 04-0, 45), p = 0.018, thus meeting the non-inferiority hypothesis. The %VO was 16.3% ± 10.4% and 13.3% ± 10.8% in the Xlimus and Synergy groups, respectively: the difference between the two means was 3.0 (-0, 06-4, 2), (p = 0.01), thus meeting the non-inferiority hypothesis. No difference was found with respect to the secondary OCT endpoints as well as for clinical endpoints. The study results confirm that the biological interaction of the Xlimus and Synergy DES with the coronary artery is comparable, and that translates in very reassuring OCT parameters at follow-up: as such, the Xlimus is non-inferior to the Synergy. ClinicalTrials.gov, identifier (NCT03745053).

Sample Size Requirements of Glaucoma Clinical Trials When Using Combined Optical Coherence Tomography and Visual Field Endpoints

Glaucoma clinical trials using visual field (VF) endpoints currently require large sample sizes because of the slowly-progressive nature of this disease. We sought to examine whether the combined use of VF testing and non-invasive optical coherence tomography (OCT) imaging of the neuroretinal tissue could improve the feasibility of such trials. To examine this, we included 192 eyes of 121 glaucoma participants seen at ≥5 visits over a 2-year period to extract real-world estimates of the rates of change and variability of VF and OCT imaging measurements for computer simulations to obtain sample size estimates. We observed that the combined use of VF and OCT endpoints led to a 31–33% reduction in sample size requirements compared to using VF endpoints alone for various treatment effect sizes. For example, 189 participants would be required per group to detect a 30% treatment effect with 90% power with combined VF and OCT endpoints, whilst 276 and 285 participants would be required when using VF and OCT endpoints alone respectively. The combined use of OCT and VF endpoints thus has the potential to effectively improve the feasibility of future glaucoma clinical trials.

Routine use of optical coherence tomography in bioresorbable vascular scaffold implantation: insights on technique optimization and long-term outcomes.

Data from prior studies have shown increased risk of adverse outcomes with bioresorbable vascular scaffolds (BVS) compared with drug-eluting stents. The objective of this study was to study the long-term outcomes with routine use of optical coherence tomography (OCT) for optimization of BVS implantation. Clinical, procedural, and outcome data were collected for all patients who received ABSORB BVS between February 2014 and March 2016 in our tertiary center (n=86). Preimplantation and postimplantation OCT was performed in all cases. Outcomes of interest included acute device success and long-term clinical outcomes including cardiac mortality, target vessel myocardial infarction, ischemia-driven target lesion revascularization, and scaffold thrombosis. A total of 86 patients were included (106 lesions, 115 BVS implanted). Mean age was 59.5±10.9 years, with 66% men. Mean lesion length was 25.2±15.6 mm and mean reference vessel diameter was 3.42±0.45 mm. Type B2/C accounted for 40% of the lesions. All scaffold implantations followed the predilation, proper sizing, and postdilation strategy. Of the 115 scaffolds analyzed, 11 (9.5%) required further intervention based on prespecified OCT endpoints. On multivariate regression analysis, complex coronary lesion (type B2/C) was the single independent predictor of OCT use in scaffold optimization (odds ratio=6.3, 95% confidence interval: 1.3-7.8, P=0.02). At a mean follow-up duration of 31±7.1 months, no cases of cardiac mortality, target vessel myocardial infarction, ischemia-driven target lesion revascularization, or scaffold thrombosis were reported. Operators may consider OCT use for optimization of BVS implantation particularly in patients with complex coronary lesions.

Abstract 21211: Serial OCT Evaluation of Stent Apposition and Longitudinal Deformation of Cobalt-Chromium versus Platinum-Chromium Everolimus Eluting Stents

Introduction: Despite advances in coronary stent design, restenosis and thrombosis remain rare but potentially serious complications that may be related to stent malapposition and longitudinal deformation. As such, the aim of this study was to evaluate stent apposition, tissue coverage and longitudinal deformation in two second-generation everolimus-eluting stents (EES) with serial optical coherence tomography (OCT). Methods: Sixty patients recruited from 5 interventional cardiology centers were randomized (1:1) to receive either the cobalt-chromium (CoCr) EES or platinum-chromium (PtCr) EES (n=30 in each group). Patients had OCT imaging after nominal and high-pressure post-dilation and at 6 months, with 12 month clinical follow up. Strut apposition and stent length were measured by OCT at each time point. The primary endpoint was the percentage of struts malapposed before and after optimal post-dilation. Secondary OCT endpoints were percent of struts apposed and covered at 6 months and percent change in stent length, classified as mild (<5%), moderate (5-10%) or severe (>10%). Results: All results are presented as CoCr-EES versus PtCr-EES. A total of 38,948 struts were analysed by OCT. After nominal dilation, the percent of malapposed struts was 12.4% versus 15.8% (p=0.34). After post-dilation the percentage malapposition was 9.5% versus 10% (p=0.81). At 6 months, the percentage of struts covered and apposed was 81.7% versus 81% (p=0.87). There was no significant difference between groups in the mean change in stent length (nominal: 6.38% versus 4.26%, p=0.24; post-dilation: 4.18% versus 4.97%, p=0.52; 6 months: 6.91% versus 8.61%, p=0.49). However, at 6 months the PtCr-EES manifested significantly more cases of severe change in stent length (>10%) than the CoCr-EES (2 versus 8 cases, p=0.03) but were not associated with adverse clinical events during the study period. Conclusions: Both CoCr-EES and PtCr-EES stents demonstrate high rates of apposition and tissue coverage over 6 months with no significant differences in clinical outcomes. The PtCr-EES stent may be more susceptible to late stent deformation at 6 months but the true incidence, mechanisms, and clinical significance are as yet unclear.

Differential healing response attributed to culprit lesions of patients with acute coronary syndromes and stable coronary artery after implantation of drug-eluting stents: An optical coherence tomography study

BackgroundPathology studies have shown delayed arterial healing in culprit lesions of patients with acute coronary syndrome (ACS) compared with stable coronary artery disease (CAD) after placement of drug-eluting stents (DES). It is unknown whether similar differences exist in-vivo during long-term follow-up. Using optical coherence tomography (OCT), we assessed differences in arterial healing between patients with ACS and stable CAD five years after DES implantation. Methods and resultsA total of 88 patients comprised of 53 ACS lesions with 7864 struts and 35 stable lesions with 5298 struts were suitable for final OCT analysis five years after DES implantation. The analytical approach was based on a hierarchical Bayesian random-effects model. OCT endpoints were strut coverage, malapposition, protrusion, evaginations and cluster formation. Uncovered (1.7% vs. 0.7%, adjusted p=0.041) or protruding struts (0.50% vs. 0.13%, adjusted p=0.038) were more frequent among ACS compared with stable CAD lesions. A similar trend was observed for malapposed struts (1.33% vs. 0.45%, adj. p=0.072). Clusters of uncovered or malapposed/protruding struts were present in 34.0% of ACS and 14.1% of stable patients (adj. p=0.041). Coronary evaginations were more frequent in patients with ST-elevation myocardial infarction compared with stable CAD patients (0.16 vs. 0.13 per cross section, p=0.027). ConclusionUncovered, malapposed, and protruding stent struts as well as clusters of delayed healing may be more frequent in culprit lesions of ACS compared with stable CAD patients late after DES implantation. Our observational findings suggest a differential healing response attributable to lesion characteristics of patients with ACS compared with stable CAD in-vivo.

Randomized trial of standard versus ClearWay-infused abciximab and thrombectomy in myocardial infarction

Patients with ST-elevation myocardial infarction (STEMI) are at substantial risk of suboptimal procedural results and late adverse events. Angiography and optical coherence tomography (OCT) studies have identified residual coronary thrombus and microcirculatory injury as potential culprits for these adverse outcomes. We hypothesized that coronary thrombectomy and local infusion of glycoprotein IIb/IIIa inhibitors by means of a dedicated infusion device can synergistically improve results of percutaneous coronary intervention (PCI) for STEMI, as appraised by OCT. A total of 128 patients with STEMI will be randomized, to one of the following: abciximab infusion with the ClearWay coronary catheter (C), standard abciximab infusion (A), thrombectomy followed by abciximab infusion with the ClearWay catheter (T+C), or thrombectomy followed by standard abciximab infusion (T+A). The primary objective is to demonstrate that abciximab infusion with the ClearWay catheter with or without manual thrombus aspiration (groups C or T+C) will result in a significant reduction of intrastent thrombus formations when compared with intravenous or intracoronary abciximab with or without thrombectomy (groups A or T+A). The primary endpoint will be the number of cross-sections with thrombus area more than 10% immediately after stent implantation as assessed with OCT. Additional angiographic, ECG and clinical endpoints will be collected and adjudicated. This trial will provide important mechanistic insights on the most appropriate invasive treatment strategy for patients with STEMI and significant thrombus burden, by exploiting its factorial design and reliance on sensitive OCT endpoints.

Optical Coherence Tomography Grading Reproducibility during the Comparison of Age-related Macular Degeneration Treatments Trials

To report reading center reproducibility during grading of Stratus optical coherence tomography (OCT) (Carl Zeiss Meditec, Dublin, CA) images obtained during the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Prospective, clinical trial. Independent reading teams reevaluated 270 OCT scans randomly sampled from the first 2 years of CATT enrollment. To assess temporal drift, a cohort of 23 scans submitted during the initial portion of the CATT study was longitudinally followed with serial reproducibility analysis. The CATT readers performed standardized grading of OCT images. A reader team, composed of 2 independent readers and a senior reader, evaluated each scan. Grading included the CATT OCT end points of total thickness at the foveal center point and intraretinal fluid (IRF), subretinal fluid (SRF), and subretinal pigment epithelium (RPE) fluid. Independent reading teams masked to the results of initial grading reevaluated scans to determine the reproducibility of qualitative grading and measurements. Categorical grading agreement was reported using percent agreement and kappa statistic, and measurement agreement was reported using intraclass correlations and paired differences. Reading center teams reproducibly graded IRF (percent agreement = 73%, kappa = 0.48; 95% confidence interval [CI], 0.38-0.58), SRF (percent agreement = 90%; kappa = 0.80; 95% CI, 0.73-0.87), and sub-RPE fluid (percent agreement 88%; kappa = 0.75; 95% CI, 0.67-0.83). For independent reading center team measurements of total thickness at the foveal center point, the intraclass correlation was 0.99 (95% CI, 0.99-0.99), and the mean paired difference between reading center teams was 4 μm (95% limits of agreement, -55 to 47 μm). There was no qualitative or quantitative grading drift. The standardized protocols used to evaluate OCT scans from the CATT study were reproducible. The methods used are suitable to monitor OCT imaging data from a large, neovascular age-related macular degeneration, interventional, multicenter study. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The Rapid Evaluation of Vessel Healing after Angioplasty (REVEAL) trial

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 impl...

A prospective randomised study using optical coherence tomography to assess endothelial coverage and neointimal proliferation at 6-months after implantation of a coronary everolimus-eluting stent compared with a bare metal stent postdilated with a paclitaxel-eluting balloon (OCTOPUS Trial): rationale, design and methods

Safety concerns regarding use of drug-eluting stent systems (DES) are related mostly to late stent thrombosis, which is facilitated by incomplete stent endothelial coverage. Specific information about time course and amount of endothelial strut coverage of different DES is required, in order to further refine the concept of antiplatelet therapy after DES implantation. Optical coherence tomography (OCT) is emerging as a new gold standard for endovascular imaging of stents, atherosclerosis progression, vulnerable plaque, and neointimal proliferation. The aim of this study is a comparative evaluation using OCT of the XIENCE V everolimus-eluting stent (Abbot Vascular, Santa Clara, CA, USA) on one hand, and the bare metal stent Coroflex Blue postdilated with the paclitaxel-eluting balloon Sequent Please (both from B Braun Melsungen AG, Melsungen, Germany) on the other hand, with respect to endothelial coverage and neointimal proliferation. Eighty patients scheduled for elective percutaneous coronary intervention (PCI) of a native coronary stenosis suitable for DES implantation and OCT imaging are scheduled to be openly randomised 1:1 to either XIENCE or Coroflex Blue/Sequent Please. The study is conducted prospectively at a university high-volume PCI centre with OCT expertise. Angiographic follow-up and time-domain OCT imaging with motorised pull-back at 1 mm/s are planned six months after study stent implantation in all patients. OCT endpoints are: (1) endothelial coverage, expressed as % of struts without coverage and % of stent length containing non-covered struts, and respectively (2) neointimal proliferation, given as % neointimal volumetric proliferation within the whole stent and also as peak focal % neointimal area proliferation. The study is not powered for clinical endpoints, which are: subacute or late stent thrombosis and need for revascularisation of the stent segment. Given the high number of measurements (15 cross-section images / 1 mm stent length), OCT endpoints are likely to reach significance at the level p <0.05, if the drop-out rate in follow-up does not exceed 20%. The study is currently on-going and its termination is scheduled for February 2010. (ClinicalTrials.gov identifier: NCT01056744).

Optical coherence tomography endpoints in stent clinical investigations: strut coverage

Late stent thrombosis (LST) and very LST (VLST) are infrequent complications after drug-eluting stent (DES) implantation, but they carry a significant risk for patients. Delayed healing, which may be represented by incomplete stent coverage, has been observed in necropsy vessel specimens treated with DES. As a result, in vivo assessment of stent coverage, as well as stent apposition using optical coherence tomography (OCT), have been recently used as surrogate safety endpoints in clinical trials testing DES platforms. By adopting strut coverage assessed by OCT, one can assess the safety profile of the new generation of DES in preregistration studies. This article focuses on stent strut coverage as a central predictor of late DES thrombosis from the histopathological point of view, discusses the limitations of the current imaging modalities and presents the technical characteristics of OCT for the detection of neointimal coverage after stent implantation. We also review the preclinical and clinical investigations using this novel imaging modality.