Junya Shite

Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation.

OBJECTIVES The purpose of this document is to make the output of the International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT) Standardization and Validation available to medical and scientific communities, through a peer-reviewed publication, in the interest of improving the diagnosis and treatment of patients with atherosclerosis, including coronary artery disease. BACKGROUND Intravascular optical coherence tomography (IVOCT) is a catheter-based modality that acquires images at a resolution of ~10 μm, enabling visualization of blood vessel wall microstructure in vivo at an unprecedented level of detail. IVOCT devices are now commercially available worldwide, there is an active user base, and the interest in using this technology is growing. Incorporation of IVOCT in research and daily clinical practice can be facilitated by the development of uniform terminology and consensus-based standards on use of the technology, interpretation of the images, and reporting of IVOCT results. METHODS The IWG-IVOCT, comprising more than 260 academic and industry members from Asia, Europe, and the United States, formed in 2008 and convened on the topic of IVOCT standardization through a series of 9 national and international meetings. RESULTS Knowledge and recommendations from this group on key areas within the IVOCT field were assembled to generate this consensus document, authored by the Writing Committee, composed of academicians who have participated in meetings and/or writing of the text. CONCLUSIONS This document may be broadly used as a standard reference regarding the current state of the IVOCT imaging modality, intended for researchers and clinicians who use IVOCT and analyze IVOCT data.

Feasibility of combined use of intravascular ultrasound radiofrequency data analysis and optical coherence tomography for detecting thin-cap fibroatheroma

AIMS To evaluate the feasibility of the combined use of virtual histology (VH)-intravascular ultrasound (IVUS) and optical coherence tomography (OCT) for detecting in vivo thin-cap fibroatheroma (TCFA). METHODS AND RESULTS In 56 patients with angina, 126 plaques identified by IVUS findings were analysed using both VH-IVUS and OCT. IVUS-derived TCFA was defined as an abundant necrotic core (>10% of the cross-sectional area) in contact with the lumen (NCCL) and %plaque-volume >40%. OCT-derived TCFA was defined as a fibrous cap thickness of <65 microm overlying a low-intensity area with an unclear border. Plaque meeting both TCFA criteria was defined as definite-TCFA. Sixty-one plaques were diagnosed as IVUS-derived TCFA and 36 plaques as OCT-derived TCFA. Twenty-eight plaques were diagnosed as definite-TCFA; the remaining 33 IVUS-derived TCFA had a non-thin-cap and eight OCT-derived TCFA had a non-NCCL (in discord with NCCL visualized by VH-IVUS, mainly due to misreading caused by dense calcium). Based on IVUS findings, definite-TCFA showed a larger plaque and vessel volume, %plaque-volume, higher vessel remodelling index, and greater angle occupied by the NCCL in the lumen circumference than non-thin-cap IVUS-derived TCFA. Conclusion Neither modality alone is sufficient for detecting TCFA. The combined use of OCT and VH-IVUS might be a feasible approach for evaluating TCFA.

Local Determinants of Thrombus Formation Following Sirolimus-Eluting Stent Implantation Assessed by Optical Coherence Tomography

OBJECTIVES We conducted this study to assess the prevalence and determinants of subclinical thrombus after sirolimus-eluting stent (SES) implantation. BACKGROUND Angioscopic analyses have demonstrated the presence of thrombus is more common than the clinical incidence of SES thrombosis. METHODS Fifty-three patients (53 lesions) underwent 6-month follow-up optical coherence tomography. A stent eccentricity index ([SEI] minimum/maximum stent diameter) was determined in each cross section. To evaluate unevenness of neointimal thickness, a neointimal unevenness score ([NUS] maximum neointimal thickness in the cross section/average neointimal thickness of the same cross section) was calculated for each cross section. Average SEI and NUS were calculated for each stent. Major adverse cardiac events were defined as a composite of death, myocardial infarction, and target vessel revascularization. RESULTS Fourteen cases of thrombus (26%) were detected by optical coherence tomography (thrombus: n = 14 vs. nonthrombus: n = 39). The percentage of thrombus was associated with longer stents (36.4 +/- 20.2 mm vs. 25.1 +/- 9.8 mm; p = 0.008), a larger number of uncovered struts (17 +/- 16 vs. 8 +/- 11; p = 0.03), smaller average SEI (0.89 +/- 0.04 vs. 0.92 +/- 0.03; p = 0.001), and greater average NUS (2.22 +/- 0.24 vs. 2.00 +/- 0.33; p = 0.03). A significant relationship existed between average SEI and average NUS (p < 0.0001, R = 0.68), and between average SEI and the number of uncovered struts (p < 0.0006, R = 0.46). There was no significant difference in major adverse cardiac events during follow-up (median: 485 days, 7.1% vs. 12.8%; p > 0.99). CONCLUSIONS Longer stents and greater asymmetric stent expansion may be important determinants of thrombus formation after SES implantation. In this small cohort, the presence of thrombus did not increase the risk of major adverse cardiac events.

OCT Compared With IVUS in a Coronary Lesion Assessment The OPUS-CLASS Study

OBJECTIVES The aim of this study was to investigate the reliability of frequency domain optical coherence tomography (FD-OCT) for coronary measurements compared with quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS). BACKGROUND Accurate luminal measurement is expected in FD-OCT because this technology offers high resolution and excellent contrast between lumen and vessel wall. METHODS In 5 medical centers, 100 patients with coronary artery disease were prospectively studied by using angiography, FD-OCT, and IVUS. In addition, 5 phantom models of known lumen dimensions (lumen diameter 3.08 mm; lumen area 7.45 mm(2)) were examined using FD-OCT and IVUS. Quantitative image analyses of the coronary arteries and phantom models were performed by an independent core laboratory. RESULTS In the clinical study, the mean minimum lumen diameter measured by QCA was significantly smaller than that measured by FD-OCT (1.81 ± 0.72 mm vs. 1.91 ± 0.69 mm; p < 0.001) and the minimum lumen diameter measured by IVUS was significantly greater than that measured by FD-OCT (2.09 ± 0.60 mm vs. 1.91 ± 0.69 mm; p < 0.001). The minimum lumen area measured by IVUS was significantly greater than that by FD-OCT (3.68 ± 2.06 mm(2) vs. 3.27 ± 2.22 mm(2); p < 0.001), although a significant correlation was observed between the 2 imaging techniques (r = 0.95, p < 0.001; mean difference 0.41 mm(2)). Both FD-OCT and IVUS exhibited good interobserver reproducibility, but the root-mean-squared deviation between measurements was approximately twice as high for the IVUS measurements compared with the FD-OCT measurements (0.32 mm(2) vs. 0.16 mm(2)). In a phantom model, the mean lumen area according to FD-OCT was equal to the actual lumen area of the phantom model, with low SD; IVUS overestimated the lumen area and was less reproducible than FD-OCT (8.03 ± 0.58 mm(2) vs. 7.45 ± 0.17 mm(2); p < 0.001). CONCLUSIONS The results of this prospective multicenter study demonstrate that FD-OCT provides accurate and reproducible quantitative measurements of coronary dimensions in the clinical setting.

Original ResearchOCT Compared With IVUS in a Coronary Lesion Assessment: The OPUS-CLASS Study

OBJECTIVES The aim of this study was to investigate the reliability of frequency domain optical coherence tomography (FD-OCT) for coronary measurements compared with quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS). BACKGROUND Accurate luminal measurement is expected in FD-OCT because this technology offers high resolution and excellent contrast between lumen and vessel wall. METHODS In 5 medical centers, 100 patients with coronary artery disease were prospectively studied by using angiography, FD-OCT, and IVUS. In addition, 5 phantom models of known lumen dimensions (lumen diameter 3.08 mm; lumen area 7.45 mm(2)) were examined using FD-OCT and IVUS. Quantitative image analyses of the coronary arteries and phantom models were performed by an independent core laboratory. RESULTS In the clinical study, the mean minimum lumen diameter measured by QCA was significantly smaller than that measured by FD-OCT (1.81 ± 0.72 mm vs. 1.91 ± 0.69 mm; p < 0.001) and the minimum lumen diameter measured by IVUS was significantly greater than that measured by FD-OCT (2.09 ± 0.60 mm vs. 1.91 ± 0.69 mm; p < 0.001). The minimum lumen area measured by IVUS was significantly greater than that by FD-OCT (3.68 ± 2.06 mm(2) vs. 3.27 ± 2.22 mm(2); p < 0.001), although a significant correlation was observed between the 2 imaging techniques (r = 0.95, p < 0.001; mean difference 0.41 mm(2)). Both FD-OCT and IVUS exhibited good interobserver reproducibility, but the root-mean-squared deviation between measurements was approximately twice as high for the IVUS measurements compared with the FD-OCT measurements (0.32 mm(2) vs. 0.16 mm(2)). In a phantom model, the mean lumen area according to FD-OCT was equal to the actual lumen area of the phantom model, with low SD; IVUS overestimated the lumen area and was less reproducible than FD-OCT (8.03 ± 0.58 mm(2) vs. 7.45 ± 0.17 mm(2); p < 0.001). CONCLUSIONS The results of this prospective multicenter study demonstrate that FD-OCT provides accurate and reproducible quantitative measurements of coronary dimensions in the clinical setting.

Possible Role of Brain-Derived Neurotrophic Factor in the Pathogenesis of Coronary Artery Disease

Background— The neurotrophin (NT) family, including nerve growth factor NT-3 and brain-derived neurotrophic factor (BDNF), has a critical role in the survival, growth, maintenance, and death of central and peripheral neurons. NTs and their receptors are expressed in atherosclerotic lesions; however, their significance in cardiovascular disease remains unclear. Methods and Results— To clarify the role of NTs in the pathogenesis of coronary artery disease, NT plasma levels in the aorta, coronary sinus, and peripheral veins of patients with unstable angina (n=38), stable effort angina (n=45), and non–coronary artery disease (n=24) were examined. In addition, regional expression of BDNF in coronary arteries was examined in autopsy cases and patients with angina pectoris by directional coronary atherectomy. The difference in BDNF levels, but not NT-3, between the coronary sinus and aorta was significantly greater in the unstable angina group compared with the stable effort angina and non–coronary artery disease groups. Immunohistochemical investigations demonstrated BDNF expression in the atheromatous intima and adventitia in atherosclerotic coronary arteries. BDNF expression was enhanced in macrophages and smooth muscle cells in atherosclerotic coronary arteries. Stimulation with recombinant BDNF significantly enhanced NAD(P)H oxidase activity and the generation of reactive oxygen species in cultured human coronary artery smooth muscle cells. Conclusions— BDNF has an important role in atherogenesis and plaque instability via the activation of NAD(P)H oxidase.

Delayed Neointimalization on Sirolimus-Eluting Stents : 6-Month and 12-Month Follow up by Optical Coherence Tomography

BACKGROUND Sirolimus-eluting stents (SES) have incomplete neointimal coverage at 6-month follow up as determined with optical coherence tomography (OCT). The long-term detailed changes of neointima in SES remains to be clarified. METHODS AND RESULTS Serial changes in neointimal coverage of SES from 6 months to 12 months using OCT were examined. Of 21 SES in 13 patients, OCT was used to visualize 2,321 stent struts at 6 months and 2,285 stent struts at 12 months. The frequency of struts without neointimal coverage decreased from 6 months to 12 months (from 10.4 to 5.7%). The frequency of malapposed struts decreased from 6 months to 12 months (from 1.7 to 0.2%). The average thickness of the neointima increased (from 112 +/-123 to 120 +/-130 microm). The frequency of struts located at the side branch orifice without neointima decreased (from 4 out of 17 (24%) to 0 out of 17 (0%)). Complete coverage with neointima was observed in 14% (3 of 21 SES) at 6 months, and 24% (5 of 21 SES) at 12 months. CONCLUSIONS Additional neointimal coverage was observed between 6 and 12 months, with a small increase in the neointimal thickness. The incidence of complete coverage, however, was still low at 12 months. These findings suggest delayed neointimalization on SES.

Optical coherence tomography imaging during percutaneous coronary intervention impacts physician decision-making: ILUMIEN I study

Aims ILUMIEN I is the largest prospective, non-randomized, observational study of percutaneous coronary intervention (PCI) procedural practice in patients undergoing intra-procedural pre- and post-PCI fractional flow reserve (FFR) and optical coherence tomography (OCT). We report on the impact of OCT on physician decision-making and the association with post-PCI FFR values and early clinical events. Methods and results Optical coherence tomography and documentary FFR were performed pre- and post-PCI in 418 patients (with 467 stenoses) with stable or unstable angina or NSTEMI. Based on pre-PCI OCT, the procedure was altered in 55% of patients (57% of all stenoses) by selecting different stent lengths (shorter in 25%, longer in 43%). After clinically satisfactory stent implantation using angiographic guidance, post-PCI FFR and OCT were repeated. Optical coherence tomography abnormalities deemed unsatisfactory by the implanting physician were identified: 14.5% malapposition, 7.6% under-expansion, 2.7% edge dissection and prompted further stent optimization based on OCT in 25% of patients (27% of all stenoses) using additional in-stent post-dilatation (81%, 101/124) or placement of 20 new stents (12%). Optimization subgroups were identified post hoc: stent placement without reaction to OCT findings (n = 137), change in PCI planning by pre-PCI OCT (n = 165), post-PCI optimization based on post-PCI OCT (n = 41), change in PCI planning, and post-PCI optimization based on OCT (n = 65). Post-PCI FFR values were significantly different (P = 0.003) between optimization groups (lower in cases with pre- and post-PCI reaction to OCT) but no longer different after post-PCI stent optimization. MACE events at 30 days were low: death 0.25%, MI 7.7%, repeat PCI 1.7%, and stent thrombosis 0.25%. Conclusion Physician decision-making was affected by OCT imaging prior to PCI in 57% and post-PCI in 27% of all cases. ClinicalTrials.gov Identifier NCT01663896, Observational Study of Optical Coherence Tomography (OCT) in Patients Undergoing Fractional Flow Reserve (FFR) and Percutaneous Coronary Intervention (ILUMIEN I).

Natural consequence of post-intervention stent malapposition, thrombus, tissue prolapse, and dissection assessed by optical coherence tomography at mid-term follow-up

Aims We performed this study to clarify natural consequences of abnormal structures (stent malapposition, thrombus, tissue prolapse, and stent edge dissection) after percutaneous coronary intervention (PCI). Methods and results Thirty-five patients treated with 40 drug-eluting stents underwent serial optical coherence tomography (OCT) imaging immediately after PCI and at the 8-month follow-up. Among a total of 73 929 struts in every frame, 431 struts (26 stents) showed malapposition immediately after PCI. Among these, 49 remained malapposed at the follow-up examination. The mean distance between the strut and vessel wall (S–V distance) of persistent malapposed struts on post-stenting OCT images was significantly longer than that of resolved malapposed struts (342 ± 99 vs. 210 ± 49 μm; P <0.01). Based on receiver-operating characteristic curve analysis, an S–V distance ≤260 µm on post-stenting OCT images was the corresponding cut-off point for resolved malapposed struts (sensitivity: 89.3%, specificity: 83.7%, area under the curve = 0.884). Additionally, 108 newly appearing malapposed struts were observed on follow-up OCT, probably due to thrombus dissolution or plaque regression. Thrombus was observed in 15 stents post-PCI. Serial OCT analysis revealed persistent thrombus in 1 stent, resolved thrombus in 14 stents, and late-acquired thrombus in 8 stents. Tissue prolapse observed in 38 stents had disappeared at the follow-up. All eight stent edge dissections were repaired at the follow-up. Conclusion Most cases of stent malapposition with a short S–V distance, thrombus, tissue prolapse, or minor stent edge dissection improved during the follow-up. These OCT-detected minor abnormalities may not require additional treatment.

Optical coherence evaluation of everolimus-eluting stents 8 months after implantation

Objective The aim of this study was to evaluate detailed vessel response after everolimus-eluting stents (EES) implantation in human de novo coronary lesions by optical coherence tomography (OCT). Design, setting and patients Between November 2008 and October 2009, 25 patients (14 men, 65.5±8.6 years) with de novo native coronary artery lesions were implanted with 30 EES, and OCT was performed at 8 months post-implantation. Main outcome measures Neointimal thickness (NIT) on each strut, strut apposition to the vessel wall, the frequency of struts surrounded by low intensity area and the incidence of intra-stent thrombus were analysed. To evaluate the radial unevenness of NIT, the difference between the maximum and minimum NIT (dNT) was calculated for each cross-section. Results At 236±39 days after implantation, there were no major adverse cardiac events, nor target vessel revascularisation. A total of 5931 struts was evaluated by OCT. The median NIT was 80 μm (25th and 75th percentile 50 μm and 140 μm) and average NIT was 100±74 μm. The number of neointima-covered struts was 5834 (98.4%), and 31 (0.52%) struts showed malapposition without neointimal coverage. The number of struts surrounded by low intensity area was 452 (7.62%). Eleven EES (37%) showed full neointimal coverage. No intra-stent thrombus was detected. The average dNT was 108±77 μm. Conclusions Most EES struts were covered with uniform and thin neointima. The frequency of low-intensity neointima was very low, which may be a result of promoted vessel healing. These results may support improved clinical outcomes with EES in clinical trials.