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.

Are BVS suitable for ACS patients? Support from a large single center real live registry.

OBJECTIVES: To investigate one-year outcomes after implantation of a bioresorbable vascular scaffold (BVS) in patients presenting with acute coronary syndrome (ACS) compared to stable angina patients. BACKGROUND: Robust data on the outcome of BVS in the setting of ACS is still scarce. METHODS: Two investigator initiated, single-center, single-arm BVS registries have been pooled for the purpose of this study, namely the BVS Expand and BVS STEMI registries. RESULTS: From September 2012-October 2014, 351 patients with a total of 428 lesions were enrolled. 255 (72.6%) were ACS patients and 99 (27.4%) presented with stable angina/silent ischemia. Mean number of scaffold/patient was 1.55±0.91 in ACS group versus 1.91±1.11 in non-ACS group (P=0.11). Pre- and post-dilatation were performed less frequent in ACS patients, 75.7% and 41.3% versus 89.0% and 62.0% respectively (P=0.05 and P=0.001). Interestingly, post-procedural acute lumen gain and percentage diameter stenosis were superior in ACS patients, 1.62±0.65mm (versus 1.22±0.49mm, P<0.001) and 15.51±8.47% (versus 18.46±9.54%, P=0.04). Major adverse cardiac events (MACE) rate at 12months was 5.5% in the ACS group (versus 5.3% in stable group, P=0.90). One-year definite scaffold thrombosis rate was comparable: 2.0% for ACS population versus 2.1% for stable population (P=0.94), however, early scaffold thromboses occurred only in ACS patients. CONCLUSIONS: One-year clinical outcomes in ACS patients treated with BVS were similar to non-ACS patients. Acute angiographic outcomes were better in ACS than in non-ACS, yet the early thrombotic events require attention and further research.

OCT demonstrating neoatherosclerosis as part of the continuous process of coronary artery disease.

Although the advent of drug-eluting stents has reduced the rates of target vessel revascularization, there are observations of ongoing stent failure occurring very late after stent implantation and presenting as very late restenosis or as very late stent thrombosis. The de novo development of atherosclerosis within the neointimal region, called neoatherosclerosis, has been identified as one of the pathomechanisms of these observed late stent failures. The mechanisms of neoatherosclerosis development and its association with stent failure are currently the subject of intensive research. Optical coherence tomography (OCT) is an invasive imaging modality that allows us to visualize the micromorphology of coronary arteries with near-histological resolution, thus providing detailed assessment of the morphological characteristics of the neointima after stent implantation, including neoatherosclerosis. Several OCT studies have tried to provide in vivo insights in the mechanisms of neoatherosclerosis development and its association with late stent failure. This review summarizes the current insights into neoatherosclerosis obtained with OCT and discusses the association of neoatherosclerosis with late stent failure.

Positive remodeling at 3 year follow up is associated with plaque-free coronary wall segment at baseline: a serial IVUS study.

AIMS: At present it is unknown what limits the arterial remodeling process during atherosclerotic plaque formation. In healthy arteries remodeling is regulated by the shear stress induced response by the endothelium. As endothelium at the plaque site is assumed to be dysfunctional, we tested the hypothesis that plaque free wall (PFW) determines vascular remodeling during atherosclerotic plaque build-up. METHODS & RESULTS: 66 human coronary ROIs (38 patients) were studied at baseline and at 3 years follow up applying intravascular ultrasound (IVUS). From the IVUS images the lumen and external elastic membrane contours were delineated to assess wall thickness (WT), vessel area (VA), Plaque Area (PA) and plaque burden (PA/VA*100%). WT < 0.5 mm was defined as normal and determined the arc of the PFW (0-360°). Positive remodeling was defined as relative difference of VA over time >5%. At baseline, IVUS-PFW was inversely related to plaque burden (p < 0.05). Positive remodeling was most frequently observed in ROIs with IVUS-PFW > 180° (i.e. larger than half of the circumference) compared to PFW < 180° (55% vs. 12%, p < 0.05). Accordingly, plaques with IVUS-PFW > 180° at baseline had the largest change in VA (1.1 ± 2.1 vs. -0.4 ± 0.6 mm(2), p < 0.05) with an odds ratio of 9.2 to develop positive remodeling. CONCLUSIONS: Our serial IVUS data show that IVUS-PFW is a determinant of vascular remodeling. ROIs with PFW > 180 at baseline had the highest probability to undergo positive remodeling.

The impact of Fourier-Domain optical coherence tomography catheter induced motion artefacts on quantitative measurements of a PLLA-based bioresorbable scaffold.

Intracoronary Fourier-Domain optical coherence tomography (FD-OCT) enables imaging of the coronary artery within 2-4 seconds, a so far unparalleled speed. Despite such fast data acquisition, cardiac and respiratory motion can cause artefacts due to longitudinal displacement of the catheter within the artery. We studied the influence of longitudinal FD-OCT catheter displacement on serial global lumen and scaffold area measurements in coronary arteries of swine that received PLLA-based bioresorbable scaffolds. In 10 swine, 20 scaffolds (18 × 3.0 mm) were randomly implanted in two epicardial coronary arteries. Serial FD-OCT imaging was performed immediately after implantation (T1) and at 3 (T2) and 6 months (T3) follow-up. Two methods for the selection of OCT cross-sections were compared. Method A did not take into account longitudinal displacement of the FD-OCT catheter. Method B accounted for longitudinal displacement of the FD-OCT catheter. Fifty-one OCT pullbacks of 17 scaffolds were serially analyzed. The measured scaffold length differed between time points, up to one fourth of the total scaffold length, indicating the presence of longitudinal catheter displacement. Between method A and B, low error was demonstrated for mean area measurements. Correlations between measurements were high: R2 ranged from 0.91 to 0.99 for all mean area measurements at all time points. Considerable longitudinal displacement of the FD-OCT catheter was observed, diminishing the number of truly anatomically matching cross-sections in serial investigations. Global OCT dimensions such as mean lumen and scaffold area were not significantly affected by this displacement. Accurate co-registration of cross-sections, however, is mandatory when specific regions, e.g. jailed side branch ostia, are analyzed.

Interstudy reproducibility of the second generation, Fourier domain optical coherence tomography in patients with coronary artery disease and comparison with intravascular ultrasound: a study applying automated contour detection.

Recently, Fourier domain OCT (FD-OCT) has been introduced for clinical use. This approach allows in vivo, high resolution (15 micron) imaging with very fast data acquisition, however, it requires brief flushing of the lumen during imaging. The reproducibility of such fast data acquisition under intracoronary flush application is poorly understood. To assess the inter-study variability of FD-OCT and to compare lumen morphometry to the established invasive imaging method, IVUS. 18 consecutive patients with coronary artery disease scheduled for PCI were included. In each target vessel a FD-OCT pullback (MGH system, light source 1,310 nm, 105 fps, pullback speed 20 mm/s) was acquired during brief (3 s) injection of X-ray contrast (flow 3 ml/s) through the guiding catheter. A second pullback was repeated under the same conditions after re-introduction of the FD OCT catheter into the coronary artery. IVUS and OCT imaging was performed in random order. FD-OCT and IVUS pullback data were analyzed using a recently developed software employing semi automated lumen contour and stent strut detection algorithms. Corresponding ROI were matched based on anatomical landmarks such as side branches and/or stent edges. Inter-study variability is presented as the absolute difference between the two pullbacks. FD-OCT showed remarkably good reproducibility. Inter-study variability in native vessels (cohort A) was very low for mean and minimal luminal area (0.10 ± 0.38, 0.19 ± 0.57 mm(2), respectively). Likewise inter-study variability was very low in stented coronary segments (cohort B) for mean lumen, mean stent, minimal luminal and minimal stent area (0.06 ± 0.08, 0.07 ± 0.10, 0.04 ± 0.09, 0.04 ± 0.10 mm(2), respectively). Comparison to IVUS morphometry revealed no significant differences. The differences between both imaging methods, OCT and IVUS, were very low for mean lumen, mean stent, minimal luminal and minimal stent area (0.10 ± 0.45, 0.10 ± 0.36, 0.26 ± 0.54, 0.05 ± 0.47 mm(2), respectively). FD-OCT shows excellent reproducibility and very low inter-study variability in both, native and stented coronary segments. No significant differences in quantitative lumen morphometry were observed between FD-OCT and IVUS. Evaluating these results suggest that FD-OCT is a reliable imaging tool to apply in longitudinal coronary artery disease studies.

Invasive imaging of the coronary atherosclerotic plaque.

Coronary atherosclerosis has a high prevalence and is known as the leading cause of death worldwide. Clinically, coronary atherosclerosis is routinely evaluated by coronary angiography, which provides a luminogram of the coronary artery and allows for recognizing lumen narrowing. However, angiography does not allow for the direct assessment of the disease process within the coronary vessel wall. Today, a number of catheter-based imaging methods can overcome this shortcoming and provide physicians with additional information on specific morphological components of atherosclerotic lesions. This article discusses the abilities of intravascular imaging techniques such as intravascular ultrasound (IVUS), IVUS-VH, iMAP, integrated backscatter-IVUS, intravascular optical coherence tomography, near-infrared spectroscopy and angioscopy, to diagnose coronary atherosclerosis and their potential to guide clinical decision making.

The diagnostic value of intracoronary optical coherence tomography.

Optical coherence tomography (OCT) is a novel light-based imaging modality for application in the coronary circulation. Compared to conventional intravascular ultrasound, OCT has a ten-fold higher image resolution. This advantage has seen OCT successfully applied in the assessment of atherosclerotic plaque, stent apposition, and tissue coverage, heralding a new era in intravascular coronary imaging. The present article discusses the diagnostic value of OCT, both in cardiovascular research as well as in potential clinical application.The unparalleled high image resolution and strong contrast between the coronary lumen and the vessel wall structure enable fast and reliable image interpretation. OCT makes it possible to visualize the presence of atherosclerotic plaque in order to characterize the structure and extent of coronary plaque and to quantify lumen dimensions, as well as the extent of lumen narrowing, in unprecedented detail. Based on optical properties, OCT is able to distinguish different tissue types, such as fibrous, lipid-rich, necrotic, or calcified tissue. Furthermore, OCT is able to cover the visualization of a variety of features of atherosclerotic plaques that have been associated with rapid lesion progression and clinical events, such as thin cap fibroatheroma, fibrous cap thickness, dense macrophage infiltration, and thrombus formation. These unique features allow the use of OCT to assess patients with acute coronary syndrome and to study the dynamic nature of coronary atherosclerosis in vivo and over time. This permits new insights into plaque progression, regression, and rupture, as well as the study of effects of therapies aimed at modulating these developments.Today's OCT technology allows high detail resolution as well as fast and safe clinical image acquisition. These unique features have established OCT as the gold standard for the assessment of coronary stents. This technique makes it possible to study stent expansion, peri-procedural vessel trauma, and the interaction of the stent with the vessel wall down to the level of individual stent struts, both acutely as well as in the long term, where it is has proven extremely sensitive to the detection of even minor amounts of tissue coverage. These qualities render OCT indispensable to addressing vexing clinical questions such as the relationship of drug-eluting stent deployment, vascular healing, the true time course of endothelial stent coverage, and late stent thrombosis. This may also better guide the optimal duration of dual anti-platelet therapy that currently remains unclear and relatively empirical.In the future, OCT might emerge, parallel to its undisputed position in research, as the tool of choice in all clinical scenarios where angiography is limited by its nature as a two-dimensional luminogram.

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.

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.

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.

First-In-Man application of a miniature self-contained intracoronary magnetic resonance probe. A multi-centre safety and feasibility trial.

AIMS: To assess safety and feasibility of intracoronary Magnetic Resonance (MR) Spectroscopy in living patients, using a self-contained MR catheter. METHODS AND RESULTS: Prospective, multi-centre study in patients with stable or unstable angina that were scheduled for percutaneous coronary diagnostic or therapeutic catheterization. We assessed the feasibility of an intravascular MR catheter, capable of analysing the arterial wall without external magnets or coils, by differentiating lipid rich, intermediate and fibrotic areas of the atherosclerotic plaque on the basis of differential water diffusion.Twenty-nine patients were included at 4 centres. The intracoronary MR-spectroscopy procedure was well tolerated; no MACE and no device related serious adverse event was observed. The MR catheter was successfully advanced into the lesion in 28 patients. Introduction of the MR catheter was not possible in one patient with a tortuous proximal right coronary artery. MR data were obtained in 22 patients. According to the predominant MR pattern, lesions were classified as fibrous plaque in 4 patients, as intermediate plaque in 4 patients and as lipid-rich plaque in 8 patients. Six patients were excluded from analysis because artifacts impeded the quality of the MR signal. Plaque type did not show a correlation with angina status (p=0.552; all groups) or angiographic parameters, such as minimal lumen diameter and diameter stenosis. CONCLUSIONS: This prospective, multi-centre study demonstrates for the first time that coronary artery assessment of potentially vulnerable, non-flow limiting lesions using a dedicated intravascular MR catheter, free of external magnets or coils, is feasible in clinical practice. Assessment of the coronary wall may provide important data regarding the composition of the atherosclerotic lesion, which then could contribute to predicting the likelihood of eventual rupture and clinical instability.

Methodological considerations and approach to cross-technique comparisons using in vivo coronary plaque characterization based on intravascular ultrasound radiofrequency data analysis: insights from the Integrated Biomarker and Imaging Study (IBIS).

Grey scale intravascular ultrasound (IVUS) is a valuable clinical tool to assess the extent and severity of coronary atheroma. However, it cannot reliably identify plaques with a high-risk of future clinical events. Serial IVUS studies to assess the progression and/or regression of atherosclerotic plaques demonstrated only modest effects, of pharmacological intervention on plaque burden, even when clinical efficacy is documented. Spectral analysis of radiofrequency ultrasound data (IVUS-virtual histology (IVUS-VH), Volcano Therapeutics, Rancho Cordova, CA) has the potential to characterize accurately plaque composition. The Integrated Biomarker and Imaging Study (IBIS) evaluated both invasive and non-invasive imaging techniques along with the assessment of novel biomarkers to characterize sub-clinical atherosclerosis. IVUS-VH was not included at the start of the IBIS protocol. The purpose of this paper is to describe the methodology we used to obtain and analyse IVUS-VH images and the approach to cross-correlations with the other techniques.

One year clinical follow up of paclitaxel eluting stents for acute myocardial infarction compared with sirolimus eluting stents.

OBJECTIVE: To compare clinical outcome of paclitaxel eluting stents (PES) versus sirolimus eluting stents (SES) for the treatment of acute ST elevation myocardial infarction. DESIGN AND PATIENTS: The first 136 consecutive patients treated exclusively with PES in the setting of primary percutaneous coronary intervention for acute myocardial infarction in this single centre registry were prospectively clinically assessed at 30 days and one year. They were compared with 186 consecutive patients treated exclusively with SES in the preceding period. SETTING: Academic tertiary referral centre. RESULTS: At 30 days, the rate of all cause mortality and reinfarction was similar between groups (6.5% v 6.6% for SES and PES, respectively, p = 1.0). A significant difference in target vessel revascularisation (TVR) was seen in favour of SES (1.1% v 5.1% for PES, p = 0.04). This was driven by stent thrombosis (n = 4), especially in the bifurcation stenting (n = 2). At one year, no significant differences were seen between groups, with no late thrombosis and 1.5% in-stent restenosis (needing TVR) in PES versus no reinterventions in SES (p = 0.2). One year survival free of major adverse cardiac events (MACE) was 90.2% for SES and 85% for PES (p = 0.16). CONCLUSIONS: No significant differences were seen in MACE-free survival at one year between SES and PES for the treatment of acute myocardial infarction with very low rates of reintervention for restenosis. Bifurcation stenting in acute myocardial infarction should, if possible, be avoided because of the increased risk of stent thrombosis.

Sonotherapy, antirestenotic therapeutic ultrasound in coronary arteries: the first clinical experience.

We studied the safety and feasibility of intracoronary sonotherapy (IST) and its effect on the coronary vessel at 6 months. Thirty-seven patients with stable or unstable angina were included (40 lesions). The indication was de novo lesion (n = 26), restenosis (n = 2), in-stent restenosis (n = 11), and a total occlusion of a venous bypass graft. After successful angioplasty, IST was performed using a 5 Fr catheter with three serial ultrasound transducers operating at 1 MHz. IST was successfully performed in 36 lesions (success rate, 90%). IST exposure time per lesion was 718 +/- 127 sec. During hospital stay, one patient died due to a bleeding complication. At 6-month follow-up, one patient experienced acute myocardial infarction, eight patients underwent repeat PTCA. No patient underwent CABG. Late lumen loss was 1.05 +/- 0.70 mm with a restenosis rate of 25%. IVUS analysis revealed a neointima burden of 25% +/- 11%. IST can be applied safely and with high acute procedural success. Sonotherapy-related major adverse events were not observed. Late lumen loss and neointimal growth were similar to conventional PTCA approaches. These results justify the initiation of randomized clinical efficacy studies.