Satoko Tahara

Strut Coverage and Vessel Wall Response to Zotarolimus-Eluting and Bare-Metal Stents Implanted in Patients With ST-Segment Elevation Myocardial Infarction The OCTAMI (Optical Coherence Tomography in Acute Myocardial Infarction) Study

OBJECTIVES Using optical coherence tomography, we assessed the proportion of uncovered struts at 6-month follow-up in zotarolimus-eluting stents (ZES), specifically Endeavor (Medtronic CardioVascular, Santa Rosa, California) stents, and identical bare-metal stents (BMS) implanted in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND Sirolimus- and paclitaxel-eluting stents implanted in STEMI have been associated with delayed healing and incomplete strut coverage. ZES are associated with a more complete and uniform strut coverage in stable patients, but whether this holds true also after STEMI is unknown. METHODS Forty-four patients with STEMI who underwent primary PCI were randomized to ZES or BMS (3:1 randomization). Angiographic, intravascular ultrasound, and optical coherence tomography follow-up was conducted at 6 months and clinical follow-up at 1 year. All images were analyzed by an independent core laboratory that was blind to stent assignments. RESULTS There were no differences between ZES and BMS in percentage of uncovered struts (median: 0.00% [interquartile range (IQR): 0.00% to 1.78%] vs. 1.98% [IQR: 0.21% to 7.33%], p = 0.13), maximum length of uncovered segments (0.00 [IQR: 0.00 to 1.19] mm vs. 1.38 [IQR: 0.65 to 3.30] mm, p = 0.10), percentage of malapposed struts (0.00% [IQR: 0.00% to 0.23%] vs. 0.15% [IQR: 0.00% to 5.81%], p = 0.16), and maximum length of malapposed segments (0.00 [IQR: 0.00 to 0.67] mm vs. 0.33 [IQR: 0.00 to 2.55] mm, p = 0.20). Neointimal response was similar between ZES and BMS (332 [IQR: 240 to 429] microm vs. 186 [IQR: 136 to 348] microm, p = 0.99) and evenly distributed. No late acquired malapposition was observed in both groups. There were no deaths, myocardial infarction, or stent thromboses at 1 year. CONCLUSIONS This optical coherence tomography study found no difference in strut coverage and similar vessel response to ZES, when compared with identical BMS, implanted during primary percutaneous coronary intervention in STEMI patients. (Six-Month Coverage and Vessel Wall Response of the Zotarolimus Drug-Eluting Stent Implanted in AMI Assessed by Optical Coherence Tomography [OCTAMI]; NCT00704561).

Impact of Drug Release Kinetics on Vascular Response to Different Zotarolimus-Eluting Stents Implanted in Patients With Long Coronary Stenoses: The LongOCT Study (Optical Coherence Tomography in Long Lesions)

OBJECTIVES We assessed the in vivo vascular response to a new generation of zotarolimus-eluting stents (ZES) with prolonged drug release (Resolute ZES-SR, Medtronic Vascular, Santa Rosa, California) compared with ZES with faster kinetics (Endeavor ZES-FR, Medtronic Vascular) by optical coherence tomography. BACKGROUND Local drug release kinetics has been implicated with antirestenosis efficacy of drug-eluting stents. However, the impact of different release kinetics on vascular response of diseased human coronary arteries remains to be investigated. METHODS The study population consisted of 43 patients with long lesions in native coronary vessels treated with multiple overlapping ZES. Twenty-one patients treated with ZES-SR were compared with 22 patients treated with ZES-FR from the ODESSA (Optical coherence tomography for DES SAfety) study. The primary endpoint was in-stent neointimal hyperplasia as assessed by optical coherence tomography at 6-month follow-up. Coprimary endpoints were the percentage of uncovered and malapposed struts. RESULTS Strut-level median neointimal thickness was 0.11 mm (interquartile range [IQR]: 0.07 to 0.15 mm) in ZES-SR and 0.31 mm (IQR: 0.27 to 0.42 mm) in ZES-FR, respectively (p < 0.001). The 6-month rate of uncovered struts per patient was 7.38% (IQR: 3.06% to 12.72%) in ZES-SR and 0.00% (IQR: 0.00% to 0.00%) in ZES-FR (p < 0.001); rate of malapposed and uncovered struts was 1.47% (IQR: 0.32% to 4.23%) in ZES-SR and 0.00% (IQR: 0.00% to 0.00%) in ZES-FR (p < 0.001). CONCLUSIONS This study demonstrated the impact of different release kinetics on human in vivo vascular response to ZES implantation. The new generation of ZES-SR compared with ZES-FR had better suppression of the neointimal response but higher proportion of uncovered and malapposed struts at 6-month optical coherence tomography follow-up. (Optical Coherence Tomography in Long Lesions [LongOCT]; NCT01133925).

Optical coherence tomography (OCT) strut-level analysis of drug-eluting stents (DES) in human coronary bifurcations

Aims: We sought to evaluate the vascular response of stent struts deployed in bifurcation segments using optical coherence tomography (OCT). Methods and results: This study is a sub-analysis of ODESSA, a prospective randomised trial designed to evaluate healing of overlapped drug-eluting stents (DES) vs. bare metal stents (BMS) (sirolimus SES: paclitaxel PES: zotarolimus ZES: Liberte BMS in a 2: 2: 2: 1 ratio) for de novo coronary artery stenosis. OCT was performed at 6-month follow-up. Bifurcation segments with side branch diameters larger than 1.5mm by angiography were analysed. The cross-sectional image at the bifurcation segment was divided into three regions: opposite to the ostium (OO), adjacent to the ostium (AO), or side-branch ostium (SO). Struts were classified in three categories: uncovered (U), covered (C), or proliferative (P). The incidence of each strut category was compared between regions and stent types. There were 12,656 struts in 61 bifurcation segments (PES: 16, SES: 14, ZES: 23, Liberte BMS: 8) from 46 patients obtained at six months. PES had the highest rate of U in SO region (PES 60.1, SES 17.0, ZES 13.2, BMS 12.3 (%), P<0.0001), whereas SES demonstrated the highest rate of U in OO (PES 3.8, SES 14.0, ZES 1.5, BMS 0.0 (%), P=0.0025). Conclusions: This study demonstrates a variable pattern of strut coverage in the bifurcation among stent technologies, with a high percentage of PES floating struts remaining uncovered at 6-month follow-up.

In vitro validation of new Fourier-domain optical coherence tomography

AIMS To validate the accuracy and evaluate the intra- and inter-observer variability of vascular measurements using novel Fourier-domain optical coherence tomography (FD-OCT) versus intravascular ultrasound (IVUS) in a coronary phantom model. METHODS AND RESULTS A dedicated cylindrical phantom comprised of four sections with differing dimensions was used to compare images generated by five FD-OCT and five IVUS catheters. Each FD-OCT catheter was tested using three different consoles, generating 15 imaging pullbacks. Two independent experts, blinded to the phantom data, performed measurements. There were 180 FD-OCT and 60 IVUS cross-sectional measurements of mean lumen diameter (MeanLD), minimal lumen diameter (MLD), maximum lumen diameter (MaxLD) and lumen area (LA) at three points in each section. FD-OCT measurements had excellent correlations with IVUS (concordance correlation coefficient [CCC]: ≥0.9769 for MeanLD, LA or longitudinal length [LL]) and phantom dimensions (CCCs for FD-OCT: ≥0.9958 for MeanLD, LA or LL). FD-OCT measurements were larger than IVUS (p<0.0001), but showed less measurement errors compared to IVUS (p<0.0001). Moreover, FD-OCT caused less discrepancy between MaxLD and MLD versus IVUS (p<0.0001). Intra- and inter-observer variability was low for both FD-OCT (CCCs for MeanLD, LA and LL ≥0.9996) and IVUS (≥0.9935). Image catheter position did not influence FD-OCT measurements. CONCLUSIONS FD-OCT was more accurate than IVUS and had similar high reproducibility to determine vascular dimensions in vitro. These results support the use of FD-OCT in the clinical setting.

Angiographic, IVUS and OCT evaluation of the long-term impact of coronary disease severity at the site of overlapping drug-eluting and bare metal stents: a substudy of the ODESSA trial

Background A potentially adverse vascular response to overlapping drug eluting stents (DES) has been suggested in current research. Objective To evaluate the impact of baseline disease severity at the site of stent overlap. Methods and results This is a substudy of ODESSA, a prospective, randomised controlled trial designed to evaluate healing of overlapping stents. 71/77 patients with a total of 86 overlapping stents were studied: 25 sirolimus, 24 paclitaxel, 26 zotarolimus-eluting stents; and 11 bare metal stents (BMS). Patients were categorised into high-grade stenosis (HGS, ≥70% diameter stenosis) and low-grade stenosis (LGS, <70%) at the site of stent overlap. Angiography and intravascular ultrasound were performed after stent deployment and repeated at 6 months, together with additional optical coherence tomography. Images were analysed by an independent core laboratory. End points were binary restenosis, percentage neointimal hyperplasia (%NIH), mean lumen and stent areas and degree of strut coverage/apposition at overlapping stents at 6 months. Stent overlaps occurred in 49 HGS and 37 LGS. Restenosis was found in 5/6 HGS versus 0/5 LGS treated with overlapping BMS (p=0.01) and 4/43 HGS versus 0/32 LGS treated with overlapping DES. There was a trend towards higher %NIH at BMS overlap in HGS versus LGS (p=0.07). DES overlaps had lower lumen and stent areas and similar %NIH in HGS versus LGS. Any uncovered or malapposed struts occurred more often in overlapping DES at LGS than at HGS (59.4% vs 32.6%, p=0.03). Conclusions Overlapping DES in normal-appearing coronary segments showed a higher incidence of uncovered or malapposed struts, while restenosis occurred exclusively in overlapping stents at HGS. These findings should be considered when deploying overlapping stents.

Intravascular Optical Coherence Tomography Detection of Atherosclerosis and Inflammation in Murine Aorta

Objective—The goal of this study was to evaluate the feasibility of imaging the aorta of apolipoprotein E–deficient (ApoE–/–) mice for the detection of atherosclerosis and macrophages using optical coherence tomography (OCT) compared with histology. Methods and Results—Atherosclerosis was induced by high-fat diet in 7-week-old ApoE–/– mice for 10 (n=7) and 22 (n=7) weeks. Nine-week-old ApoE–/– mice (n=7) fed a standard chow diet were used as controls. OCT images of a 10-mm descending aorta in situ were performed in 4 mice for each, and plaque and macrophages were determined at 0.5-mm intervals. Automated detection and quantification of macrophages were performed independently using a customized algorithm. Coregistered histological cross-sections were stained with hematoxylin-eosin, Mac-3, and von Kossa. Three mice in each group had en face OCT imaging to detect macrophages, which were compared with lipid-positive area with Sudan IV. OCT images were successfully acquired in all mice. OCT and histology were able to discriminate macrophages and plaque among the 3 groups and showed excellent correlation for (1) visual detection of plaque (r=0.98) and macrophages (r=0.93), (2) automated detection and quantification of macrophages by OCT versus Mac-3-positive area (r=0.92), and (3) en face OCT detection of macrophages versus Sudan IV–positive area (r=0.92). Conclusion—Murine intra-aortic OCT is feasible and shows excellent correlation with histology for detection of atherosclerotic plaque and macrophages.

Serial Assessment of Coronary Artery Response to Paclitaxel-Eluting Stents Using Optical Coherence Tomography

Background— The paucity of longitudinal, serial high-resolution imaging studies has limited our understanding of in vivo arterial response to drug-eluting stents. We sought to investigate the human coronary response to paclitaxel-eluting stent implantation, using serial optical coherence tomography assessments. Methods and Results— Thirty patients with at least 2 significant coronary lesions in different vessels were treated with a paclitaxel-eluting stent. The most severe stenosis (lesion A) was treated at the initial procedure, and the second target vessel (lesion B) was stented 3 months later. Optical coherence tomography was performed at baseline, 3-, and 9-month follow-up for lesions A and baseline and 6 months for lesions B. Prespecified end points were percent of uncovered and malapposed struts over time. In lesions A, uncovered struts were 3.77±4.94% and 3.02±4.35% at 3 versus 9 months (P=NS). Malapposed struts were 3.55±5.16% at post-procedure, 1.51±3.52% at 3 months, and 0.60±1.82% at 9 months (P<0.05, at 3 versus 9 months). Strut-level neointimal thickness was 0.19±0.09 mm and 0.20±0.11 mm (P=NS) over time. Newly acquired malapposition was detected in 10.4% and 3.3% of 2.5-mm segments at 3- and 9-month follow-up. In lesions B, uncovered struts were 2.91±5.47% at 6-months. Malapposed struts were 4.94±6.70% post-procedure and 1.01±3.11% at 6 months (P<0.01), with 0.19±0.09-mm neointimal thickness at follow-up. Conclusions— Optical coherence tomography imaging suggested the first 3 months to be the period with most biological activity after paclitaxel-eluting stent implantation, when the proliferative reaction mainly occurs and malapposition resolves. A less active, yet continuous, dynamic arterial response, with resolution and development of malapposition, occurs through 9 months post-treatment. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00704145.

Impact of different stent alloys on human vascular response to everolimus‐eluting stent: An optical coherence tomography study: The OCTEVEREST

New generation drug‐eluting stents (DES) incorporate thinner struts and novel alloys to improve clinical performance. Nevertheless, the impact of novel stent materials and designs on human vascular response to DES remains elusive. We sought to evaluate the in‐vivo coronary artery response to platinum‐chromium (PtCr) versus cobalt‐chromium (CoCr) stents featuring the same durable polymer and antiproliferative drug by optical coherence tomography (OCT).

Difference in vascular response between sirolimus-eluting- and everolimus-eluting stents in ostial left circumflex artery after unprotected left main as observed by optical coherence tomography

BACKGROUND Kissing-balloon technique (KBT) is commonly performed during percutaneous coronary intervention of distal unprotected left main coronary artery (ULM) aiming at obtaining optimal opening of the side branch (left circumflex artery; LCX) ostium. Nonetheless, detailed evaluation of vascular response to stents in LCX ostium is lacking. We therefore evaluated the vascular response to different drug-eluting stents (DES) in ostial LCX after ULM by means of optical coherence tomography (OCT). METHODS We prospectively enrolled 38 consecutive patients with ULM disease, who were treated with single-stent procedure using DES, crossover the ULM-left anterior descending artery (LAD) followed by KBT. Twelve patients were treated with sirolimus-eluting stents (SES) and 26 patients were treated with everolimus-eluting stents (EES). OCT was conducted at post-PCI and 9-month follow-up. We evaluated the DES-vessel interactions and number of stent struts at the side branch (LCX) ostium (SO) at post-PCI, and compared the narrowing of ostial area at LCX between SES and EES. RESULTS Post-procedure, the number of stent struts at SO was significantly higher in SES compared to EES (median 14.47% vs 0.19%, p<0.001). The narrowing of LCX ostial area at follow-up was more pronounced in SES compared with EES (29.16% vs 2.46%, respectively, p<0.001). Linear regression analysis showed a high correlation between the number of stent struts in LCX ostium and ostial area narrowing (r=0.771, p<0.001). CONCLUSIONS OCT showed differences between EES- and SES-vessel interactions at ULM bifurcation PCI. Number of LCX ostium struts at post-PCI impacted the narrowing of ostial area at 9-month follow-up.

Identificação de genes envolvidos na síntese de proteínas de células musculares lisas com expressão aumentada em placas ateromatosas associados a hiperplasia neointimal após implante de stents não-farmacológicos: estudo GENESIS-R

BACKGROUND: Coronary restenosis is a poorly understood phenomenon that remains a challenge even in the drug-eluting stent era. This study is aimed at identifying the genes involved in structural and functional protein synthesis of smooth muscle cells with increased expression in human atheromatous plaques associated to neointimal hyperplasia after bare-metal stent implantation. METHODS: Atheromatous plaques were obtained by directional atherectomy prior to stenting. Gene expression analysis was performed using the Affymetrix GeneChip system. Patients were submitted to intravascular ultrasound 6 months after the procedure for in-stent volumetric analysis. We evaluated the correlation between gene expression in atheromatous plaques and the percentage of in-stent intimal hyperplasia. RESULTS: Most patients were male (85.7%), with 60.2 ± 11.4 years of age, 35.7% were diabetic and the percentage of in-stent intimal hyperplasia was 29.9 ± 18.7%. There was no change in the percentage of in-stent intimal hyperplasia in patients with or without diabetes (29.5% vs. 30.7%; P = 0.89). There was no correlation between stent length and the percentage of in-stent intimal hyperplasia (r = -0.26; P = 0.26) or between stent diameter and the percentage of in-stent intimal hyperplasia (r = 0.14; P = 0.56). Eight genes related to smooth muscle cell structural and functional protein synthesis had a positive correlation with the percentage of in-stent intimal hyperplasia. CONCLUSIONS: De novo coronary lesions show increased expression of genes related to smooth muscle cell structural and functional protein synthesis associated to future significant in-stent neointimal hyperplasia, emerging as novel therapeutic targets.