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Background: Quantitative coronary angiography (QCA) offers objective and reproducible measures of coronary lesions. However, significant inter- and intra-observer variability and time-consuming processes hinder the practical application of on-site QCA in the current clinical setting. This study proposes a novel method for artificial intelligence-based QCA (AI-QCA) analysis of the major vessels and evaluates its performance., Methods: AI-QCA was developed using three deep-learning models trained on 7658 angiographic images from 3129 patients for the precise delineation of lumen boundaries. An automated quantification method, employing refined matching for accurate diameter calculation and iterative updates of diameter trend lines, was embedded in the AI-QCA. A separate dataset of 676 coronary angiography images from 370 patients was retrospectively analyzed to compare AI-QCA with manual QCA performed by expert analysts. A match was considered between manual and AI-QCA lesions when the minimum lumen diameter (MLD) location identified manually coincided with the location identified by AI-QCA. Matched lesions were evaluated in terms of diameter stenosis (DS), MLD, reference lumen diameter (RLD), and lesion length (LL)., Results: AI-QCA exhibited a sensitivity of 89% in lesion detection and strong correlations with manual QCA for DS, MLD, RLD, and LL. Among 995 matched lesions, most cases (892 cases, 80%) exhibited DS differences ≤10%. Multiple lesions of the major vessels were accurately identified and quantitatively analyzed without manual corrections., Conclusion: AI-QCA demonstrates promise as an automated tool for analysis in coronary angiography, offering potential advantages for the quantitative assessment of coronary lesions and clinical decision-making., Competing Interests: Declaration of competing interest Jihoon Kweon, Jung-Min Ahn, Young-Hak Kim report a relationship of consulting and advisory with Medipixel. All other authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Electronic medical records(EMR) have considerable potential to advance healthcare technologies, including medical AI. Nevertheless, due to the privacy issues associated with the sharing of patient's personal information, it is difficult to sufficiently utilize them. Generative models based on deep learning can solve this problem by creating synthetic data similar to real patient data. However, the data used for training these deep learning models run into the risk of getting leaked because of malicious attacks. This means that traditional deep learning-based generative models cannot completely solve the privacy issues. Therefore, we suggested a method to prevent the leakage of training data by protecting the model from malicious attacks using local differential privacy(LDP). Our method was evaluated in terms of utility and privacy. Experimental results demonstrated that the proposed method can generate medical data with reasonable performance while protecting training data from malicious attacks., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: This study investigated the sexual differences of coronary artery disease (CAD) prevalence and its association with cardiovascular risk factors in the asymptomatic population., Methods: In total 6434 asymptomatic participants without known CAD (1740 women and 4694 men) underwent coronary computed tomography angiography (CCTA). The prevalence of significant CAD (diameter stenosis ≥50%) and other CCTA findings were compared by sex, and its influence on CAD was investigated in groups stratified by the number of cardiovascular risk factors, including age (>55 years), hypertension, diabetes, dyslipidemia, and current smoking., Results: The prevalence of current smokers, hypertension, and diabetes were higher in men than women. The mean coronary artery calcium score was 13.1 ± 58.4 for women and 51.1 ± 158.2 for men; the coronary atherosclerosis burden indices were significantly higher in men than women. Significant CAD was identified in 65 women (3.7%) and 429 men (9.1%), showing a significant association (adjusted odds ratio [OR] 2.38, P < 0.001). The relatively higher risk for significant CAD in men was observed in patients with fewer risk factors, and the risk difference was not significant in patients with many risk factors (adjusted ORs: 7.69, 3.37, 1.71, 1.31, and 0.88 in patients with 0, 1, 2, 3, and 4-5 risk factors, respectively). The association between sex and risk factor groups was significant (P < 0.001)., Conclusions: In the asymptomatic population, a significantly higher CAD prevalence was noted in men than women. However, women with a high number of cardiovascular risk factors showed a CAD prevalence similar to that of men., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: About 10% of patients with locally advanced NSCLC (LA-NSCLC) harbor EGFR mutation and recent reports suggested the declined benefit with an immune checkpoint inhibitor in this population. The attempt that introduces EGFR tyrosine kinase inhibitor into the treatment of LA-NSCLC with EGFR mutation has been warranted., Methods: Chemotherapy-naive patients with unresectable LA-NSCLC with sensitive EGFR mutation (exon 19 deletion or exon 21 L858R point mutation) were enrolled. Patients were treated with gefitinib (250 mg/d for 2 y) plus concurrent thoracic radiotherapy (64 Gy/32 fractions). The primary end point was progression-free survival (PFS) at 2 years (trial identifier, UMIN000008366)., Results: Between August 2012 and November 2017, a total of 28 patients were enrolled and 27 were eligible. The median age was 67 years (range: 45-74); never/current or former smoker in 15/12 patients, respectively; Eastern Cooperative Oncology Group performance status of 0/1 in 19/8; EGFR exon 19 deletion/exon 21 L858R in 13/14; and c-stage IIIA/IIIB in 14/13. The PFS rate at 2 years by independent review was 29.6% (one-sided 95% confidence interval [CI]: 17.6%-). The overall response rate was 81.5% (95% CI: 63.3%-91.3%), median PFS was 18.6 months (95% CI: 12.0-24.5 mo), and median overall survival was 61.1 months (95% CI: 38.1 mo-not reached). Approximately half of the patients exhibited solitary brain metastasis as their first site of relapse. Adverse events greater than or equal to grade 3 were fatigue, skin reaction, and appetite loss (3.7% each)., Conclusions: This prospective study revealed the tolerability and the possible efficacy of gefitinib plus concurrent thoracic radiotherapy in patients with LA-NSCLC having EGFR mutation., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Objectives: This study evaluated the association between elevated levels of lipoprotein(a) [Lp(a)] and risk of recurrent ischemic events in patients who underwent percutaneous coronary intervention (PCI)., Background: Elevated levels of Lp(a) have been identified as an independent, possibly causal, risk factor for atherosclerotic cardiovascular disease in a general population study., Methods: A prospective single-center registry was used to identify 12,064 patients with baseline Lp(a) measurements who underwent PCI between 2003 and 2013. The primary outcomes were a composite of cardiovascular death, spontaneous myocardial infarction, and ischemic stroke., Results: From the registry, 3,747 (31.1%) patients had high Lp(a) (>30 mg/dL) and 8,317 (68.9%) patients had low Lp(a) (≤30 mg/dL). During a median follow-up of 7.4 years, primary outcomes occurred in 1,490 patients, and the incidence rates of primary outcomes were 2.0 per 100 person-years in the high-Lp(a) group and 1.6 per 100 person-years in the low-Lp(a) group (adjusted hazard ratio [aHR]: 1.17; 95% confidence interval [CI]: 1.05-1.30; P = 0.004). Increased risk of recurrent ischemic cardiovascular events in the high-Lp(a) group was consistent in various subgroups including patients receiving statin treatment at discharge (aHR: 1.18; 95% CI: 1.03-1.34; P = 0.011). In addition, the risk of repeated revascularization was significantly higher in the high-Lp(a) group (aHR: 1.13; 95% CI: 1.02-1.25; P = 0.022)., Conclusions: Elevated levels of Lp(a) were significantly associated with the recurrent ischemic events in patients who underwent PCI. This study provides a rationale for outcome trials to test Lp(a)-lowering therapy for secondary prevention in patients undergoing PCI., Competing Interests: Funding Support and Author Disclosures This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HC19C0022), and by the CardioVascular Research Foundation. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Data on the risk factors for symptomatic radiation pneumonitis (RP) in non-small-cell lung cancer (NSCLC) patients treated with concurrent chemoradiotherapy (CCRT) and consolidation durvalumab are limited; we aimed to investigate these risk factors., Materials and Methods: This multicenter retrospective study, conducted at 15 institutions in Japan, included patients who were ≥20 years of age; who started definitive CCRT for NSCLC between July 1, 2018, and July 31, 2019; and who then received durvalumab. The primary endpoint was grade 2 or worse (grade 2+) RP., Results: In the 146 patients analyzed, the median follow-up period was 16 months. A majority of the patients had stage III disease (86%), received radiation doses of 60 to 66 Gy equivalent in 2-Gy fractions (93%) and carboplatin and paclitaxel/nab-paclitaxel (77%), and underwent elective nodal irradiation (71%) and 3-dimensional conformal radiotherapy (75%). RP grade 2 was observed in 44 patients (30%); grade 3, in four patients (3%); grade 4, in one patient (1%); and grade 5, in one patient (1%). In the multivariable analysis, lung V20 was a significant risk factor, whereas age, sex, smoking history, irradiation technique, and chemotherapy regimen were not. The 12-month grade 2+ RP incidence was 34.4% (95% confidence interval [CI], 26.7%-42.1%); the values were 50.0% (95% CI, 34.7%-63.5%) and 27.1% (95% CI, 18.8%-36.2%) in those with lung V20 ≥ 26% and < 26%, respectively (P = .007)., Conclusion: The incidence of grade 2+ RP was relatively high in this multicenter real-world study, and its risk increased remarkably at elevated lung V20. Our findings can aid in RP risk prediction and the safe radiotherapy treatment planning., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: The aim of this study was to develop pre-procedural intravascular ultrasound (IVUS)-based models for predicting the occurrence of stent underexpansion., Background: Although post-stenting IVUS has been used to optimize percutaneous coronary intervention, there are no pre-procedural guidelines to estimate the degree of stent expansion and provide preemptive management before stent deployment., Methods: A total of 618 coronary lesions in 618 patients undergoing percutaneous coronary intervention were randomized into training and test sets in a 5:1 ratio. Following the coregistration of pre- and post-stenting IVUS images, the pre-procedural images and clinical information (stent diameter, length, and inflation pressure; balloon diameter; and maximal balloon pressure) were used to develop a regression model using a convolutional neural network to predict post-stenting stent area. To separate the frames with from those without the occurrence of underexpansion (stent area <5.5 mm 2 ), binary classification models (XGBoost) were developed., Results: Overall, the frequency of stent underexpansion was 15% (5,209 of 34,736 frames). At the frame level, stent areas predicted by the pre-procedural IVUS-based regression model significantly correlated with those measured on post-stenting IVUS (r = 0.802). To predict stent underexpansion, maximal accuracy of 94% (area under the curve = 0.94) was achieved when the convolutional neural network- and mask image-derived features were used for the classification model. At the lesion level, there were significant correlations between predicted and measured minimal stent area (r = 0.832) and between predicted and measured total stent volume (r = 0.958)., Conclusions: Deep-learning algorithms accurately predicted incomplete stent expansion. A data-driven approach may assist clinicians in making treatment decisions to avoid stent underexpansion as a preventable cause of stent failure., Competing Interests: Funding Support and Author Disclosures This study was supported by grants from the Korea Healthcare Technology R&D Project, Ministry for Health & Welfare Affairs, Republic of Korea (HI17C1080) and the Ministry of Science and ICT (NRF-2017R1A2B4005886). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021. Published by Elsevier Inc.)

Background and Aims: Although plaque characterization by intravascular ultrasound (IVUS) is important for risk stratification, frame-by-frame analysis of a whole vascular segment is time-consuming. The aim was to develop IVUS-based algorithms for classifying attenuation and calcified plaques., Methods: IVUS image sets of 598 coronary arteries from 598 patients were randomized into training and test sets with 5:1 ratio. Each IVUS frame at a 0.4-mm interval was circumferentially labeled as one of three classes: attenuated plaque, calcified plaque, or plaque without attenuation or calcification. The model was trained on multi-class classification with 5-fold cross validation. By converting from Cartesian to polar coordinate images, the class corresponding to each array from 0 to 360° was plotted., Results: At the angle-level, Dice similarity coefficients for identifying calcification vs. attenuation vs. none by using ensemble model were 0.79, 0.74 and 0.99, respectively. Also, the maximal accuracy was 98% to classify those groups in the test set. At the frame-level, the model identified the presence of attenuation with 80% sensitivity, 96% specificity, and 93% overall accuracy, and the presence of calcium with 86% sensitivity, 97% specificity, and 96% overall accuracy. In the per-vessel analysis, the attenuation and calcification burden index closely correlated with human measurements (r = 0.89 and r = 0.95, respectively), as did the maximal attenuation and calcification burden index over 4 mm (r = 0.82 and r = 0.91, respectively). The inference times were 0.05 s per frame and 7.8 s per vessel., Conclusions: Our deep learning algorithms for plaque characterization may assist clinicians in recognizing high-risk coronary lesions., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Restoration of anterograde blood flow leads to alterations in vascular wall stress that may influence lumen size distal to chronic total occlusion (CTO) lesions. We sought to assess changes in lumen diameter of segments distal to the stent segment of successfully recanalized CTO., Methods: We analyzed 507 consecutive CTO cases with stent implantation that underwent follow-up angiography at a single high-volume center (mean follow-up of 13.5 months). Segments ≤40 mm distal to the stent edge were analyzed using quantitative coronary angiography., Results: At follow-up, lumen diameters significantly increased; diameter changes of 0.26 ± 0.47 (percent diameter change of 18.2%) at 5 mm distal, mean lumen diameter changes of 0.23 ± 0.35 (14.3%) and minimal lumen diameter changes of 0.22 ± 0.80 (24.7%) (all p < 0.001). Lumen enlargement was similar between visually shrunken and stenosed vessels (degree of stenosis ≥20% with luminal irregularities) distal to stents; 5 mm distal (0.32 ± 0.48 vs. 0.30 ± 0.48, p = 0.76), mean lumen diameter changes (0.26 ± 0.37mm vs. 0.26±0.33 mm, p = 0.94), minimal lumen diameter changes (0.28 ± 0.43 mm vs. 0.22 ± 1.30 mm, p = 0.48). There was no association between degree of in-stent narrowing and changes in distal lumen diameter (Spearman r = -0.02, p = 0.59). Multivariate logistic regression for the predictors of greater lumen enlargement indicated that patients with left ventricle dysfunction (ejection fraction ≤45%) had greater enlargement [odds ratio (OR): 2.53, 95% confidence interval (CI): 1.23-5.23, p = 0.01]. Conversely, a low hematocrit (male <40%, and female <35%) was associated with attenuated lumen enlargement (OR: 0.68 95% CI: 0.47-0.98; p = 0.04)., Conclusions: Lumen diameter distal to CTO lesions significantly increased following successful revascularization, regardless of diseased status of the distal bed or degree of in-stent narrowing. These findings implicate appropriate determination of stent size, stent coverage length, as well as management strategies of distal vessels., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: There are limited data regarding the relation between serum phosphorus concentration (SPC) and subclinical coronary atherosclerosis in the asymptomatic healthy population without kidney dysfunction., Objectives: We aimed to investigate the relation between SPC and characteristics of atherosclerotic plaques and cardiac events according to SPCs using a large cohort of asymptomatic Korean individuals., Methods: We evaluated 6329 asymptomatic Korean individuals [mean age: 53.6 ± 7.6 y, 4611 men (72.9%)] without kidney dysfunction and coronary artery disease who voluntarily underwent coronary computed tomography angiography (CCTA) as part of a general health examination. Study participants were stratified into quartiles according to their SPCs (≤3.0, 3.1-3.3, 3.4-3.7, ≥3.8 mg/dL). The degree and extent of subclinical coronary atherosclerosis were evaluated with CCTA. Stenosis of diameter ≥50% was defined as significant. A cardiac event was defined as a composite of all-cause death, myocardial infarction, unstable angina, and coronary revascularization., Results: After adjustment for cardiovascular disease risk factors, the risk of any atherosclerotic plaque was significantly higher with increasing SPC quartiles (P = 0.001). In particular, the risk of calcified plaque increased in the second (OR: 1.27; 95% CI: 1.07, 1.51; P = 0.006), third (OR: 1.39; 95% CI: 1.17, 1.64; P < 0.001), and fourth SPC quartiles (OR: 1.50; 95% CI: 1.24, 1.82; P < 0.001) compared with that in the first quartile. However, there were no significant differences in the adjusted ORs for noncalcified plaque, mixed plaque, or significant stenosis. During a follow-up of median 5.4 y, there was no significant difference in cardiac events between the SPC quartiles., Conclusions: In asymptomatic Korean individuals without kidney dysfunction, a high SPC was an independent predictor of calcified plaques without any difference in cardiac events. Further long-term prospective studies are required to validate these results., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Objectives: We conducted a subanalysis of data from the multicentre, retrospective observational Nivolumab Japan Real World (CA209-9CR) study to evaluate nivolumab effectiveness and safety in elderly patients (aged ≥75 years) with advanced/metastatic non-small cell lung cancer., Materials and Methods: Medical record data of patients initiating nivolumab treatment between April 2016 and December 2016 were collected using electronic data capture from 23 cancer hospitals in Japan between March 2017 and August 2018. Nivolumab treatment data were collected to investigate the treatment patterns by age group (<75 and ≥75 years), and the effectiveness and safety of nivolumab treatment., Results: Of the 901 patients evaluated, 178 (19.8%) were aged ≥75 years. Overall, patients received a median of five nivolumab treatments regardless of age group. Comparable progression-free survival was observed, with a median of 2.1 months in patients aged <75 years and 2.1 months in patients aged ≥75 years (p=0.5441). No significant differences were found in duration of response, overall response rate or disease control rate between the two age groups. Median overall survival in patients aged <75 and ≥75 years was 14.7 months and 12.3 months, respectively. Grade ≥3 adverse events (AEs) occurred in 29.2% and 28.1% of patients aged <75 and ≥75 years, respectively. Immune-related AEs decreased slightly with increasing age; time to onset and rates of improvement were similar for patients aged <75 and ≥75 years. The most common grade 3-4 AEs were interstitial lung disease in both age groups (4.0% in patients aged <75 years and 2.8% in those aged ≥75 years). Poor performance status was associated with worse outcomes in both age groups., Conclusion: Based on Japanese real-world data, the effectiveness and safety of nivolumab were confirmed regardless of age., Competing Interests: Competing interests: KO reports personal fees from Ono Pharmaceutical Co, Ltd and MSD K.K. outside the submitted work; JS reports personal fees from Bristol-Myers Squibb K.K. and Ono Pharmaceutical CO, Ltd outside the submitted work; HS reports grants from Chugai Pharmaceutical Co, Ltd, AstraZeneca K.K. and MSD K.K. and personal fees from Ono Pharmaceutical Co, Ltd, Nippon Boehringer Ingelheim Co, Ltd and Novartis Pharma K.K. outside the submitted work; HS reports personal fees from Ono Pharmaceutical Co, Ltd and Bristol-Myers Squibb K.K. during the conduct of the study, personal fees from Chugai Pharmaceutical Co, Ltd and MSD K.K. outside the submitted work; OS reports other from Ono Pharmaceutical Co, Ltd during the conduct of the study, personal fees and other from Novartis Pharma K.K., Nippon Boehringer Ingelheim Co, Ltd and AstraZeneca K.K. and other from Kyorin Pharmaceutical Co, Ltd, Bayer Health, Daiichi Sankyo Co, Ltd, GlaxoSmithKline K.K. and Ono Pharmaceutical Co, Ltd outside the submitted work; MY reports personal fees from Chugai Pharmaceutical Co, Ltd, Ono Pharmaceutical Co, Ltd and AstraZeneca K.K. outside the submitted work; MN reports grants and non-financial support from Ono Pharmaceutical Co, Ltd during the conduct of the study, grants and personal fees from Ono Pharmaceutical Co, Ltd, Bristol-Myers Squibb K.K., Pfizer Japan Inc, Chugai Pharmaceutical Co, Ltd, Eli Lilly Japan K.K., Taiho Pharmaceutical Co, Ltd, AstraZeneca K.K., MSD K.K., Novartis Pharma K.K., Takeda Pharmaceutical Co, Ltd and Daiichi Sankyo Healthcare Co, Ltd and grants from Merck Serono Co, Ltd (currently Merck Biopharma Co, Ltd) and personal fees from Nippon Boehringer Ingelheim Co, Ltd outside the submitted work; KA reports grants and personal fees from Ono Pharmaceutical Co, Ltd, Bristol-Myers Squibb K.K., AstraZeneca K.K. and Eli Lilly Japan K.K. and grants from MSD K.K. and Novartis Pharma K.K. outside the submitted work; TK reports grants and personal fees from Ono Pharmaceutical Co, Ltd, AstraZeneca K.K., Taiho Pharmaceutical Co, Ltd, MSD K.K., Novartis Pharma K.K., Nippon Boehringer Ingelheim Co, Ltd, Eli Lilly Japan K.K., Pfizer Japan Inc and Chugai Pharmaceutical Co, Ltd, and grants from Takeda Pharmaceutical Co, Ltd, Regeneron Pharmaceuticals, Inc and Merck Serono Co, Ltd (currently Merck Biopharma Co, Ltd) and personal fees from Teijin Pharma Ltd and Bristol-Myers Squibb K.K. outside the submitted work; SO reports grants and personal fees from Bristol-Myers Squibb K.K. and Ono Pharmaceutical Co, Ltd during the conduct of the study, grants and personal fees from AstraZeneca K.K., Chugai Pharmaceutical Co, Ltd and Taiho Pharmaceutical Co, Ltd and grants from Kyowa Hakko Kirin Co, Ltd (currently Kyowa Kirin Co, Ltd) and Merck Serono Co, Ltd (currently Merck Biopharma Co, Ltd) and personal fees from MSD K.K. and Eli Lilly Japan K.K. outside the submitted work; DF reports personal fees from Ono Pharmaceutical Co, Ltd and Bristol-Myers Squibb K.K. during the conduct of the study, personal fees from AstraZeneca K.K., Taiho Pharmaceutical Co, Ltd, Chugai Pharmaceutical Co, Ltd, MSD K.K., Nippon Boehringer Ingelheim Co, Ltd and Eli Lilly Japan K.K. outside the submitted work; HT reports grants and personal fees from Bristol-Myers Squibb K.K., Eli Lilly Japan K.K., MSD K.K., Taiho Pharmaceutical Co, Ltd, Pfizer Japan Inc, Chugai Pharmaceutical Co, Ltd, Ono Pharmaceutical Co, Ltd, AstraZeneca K.K. and Nippon Boehringer Ingelheim Co, Ltd and grants from Merck Serono Co, Ltd (currently Merck Biopharma Co, Ltd) and personal fees from Novartis Pharma K.K. outside the submitted work; TK reports grants and personal fees from Chugai Pharmaceutical Co, Ltd, AstraZeneca K.K., Eli Lilly Japan K.K. and Bristol-Myers Squibb K.K., and personal fees from Taiho Pharmaceutical Co, Ltd, Ono Pharmaceutical Co, Ltd, MSD K.K., Pfizer Japan Inc, Kyowa Hakko Kirin Co, Ltd (currently Kyowa Kirin Co, Ltd), Nippon Boehringer Ingelheim Co, Ltd, and Nippon Kayaku Co, Ltd and grants from Merck Serono Co, Ltd (currently Merck Biopharma Co, Ltd) outside the submitted work; HS reports other from Mebix, Inc during the conduct of the study, personal fees from AstraZeneca K.K. outside the submitted work; IS reports grants from Nippon Boehringer Ingelheim Co, Ltd during the conduct of the study, grants and personal fees from AstraZeneca K.K., Taiho Pharmaceutical Co, Ltd, Nippon Boehringer Ingelheim Co, Ltd, Ono Pharmaceutical Co, Ltd, MSD K.K, Eli Lilly Japan K.K., Bristol-Myers Squibb K.K. and Chugai Pharmaceutical Co, Ltd and grants from Astellas Pharma Inc, Novartis Pharma K.K. and AbbVie GK, and personal fees from Pfizer Japan Inc outside the submitted work; YO reports grants and personal fees from Ono Pharmaceutical Co, Ltd and Bristol-Myers Squibb K.K. during the conduct of the study, grants and personal fees from AstraZeneca K.K., Chugai Pharmaceutical Co, Ltd, Eli Lilly Japan K.K., Pfizer Japan Inc, MSD K.K., Kyorin Pharmaceutical Co, Ltd, Takeda Pharmaceutical Co, Ltd, Novartis Pharma K.K., Taiho Pharmaceutical Co, Ltd, and AbbVie GK, and personal fees from Celltrion Healthcare Co, Ltd, Amgen Inc, and Nippon Boehringer Ingelheim Co, Ltd, and grants from Kissei Pharmaceutical Co, Ltd, Loxo Oncology, Inc, and Janssen Pharmaceutical K.K. outside the submitted work; HH is an employee of Bristol-Myers Squibb K.K.; NY is an employee of Ono Pharmaceutical Co, Ltd; RM, YHK, OS, KK, HT, KM, TM and TH have nothing to declare., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Objectives: This study compared the 3-year outcomes of intracoronary imaging-guided pre-dilation, stent sizing, and post-dilation (iPSP) for patients with complex coronary artery lesions., Background: The long-term effects of the optimal drug-eluting stent implantation technique in complex coronary artery disease have not been evaluated., Methods: From the IRIS-DES (Interventional Cardiology Research In-cooperation Society-Drug-Eluting Stents) registry, the study evaluated 9,525 patients who underwent percutaneous coronary intervention for left main, bifurcation, long or diffuse (>30 mm), or angiographically severely calcified lesions. The primary outcome was a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization. The inverse probability of treatment weighting method was used to adjust for confounding factors., Results: At the index procedure, intravascular ultrasound assessment PSP were performed in 8,522 (89.5%) patients, 5,141 (54.0%) patients, and 5,531 (58.1%) patients, respectively; overall, 3,374 (35.4%) patients underwent stent implantation using all 3 parts of the iPSP strategy and were defined as the iPSP group. At 3 years, the adjusted rate of the primary outcome was significantly lower in iPSP group (5.6% vs 7.9%; adjusted hazard ratio: 0.71; 95% confidence interval: 0.63 to 0.81; p < 0.001)., Conclusions: Among patients undergoing drug-eluting stent implantation in complex coronary artery stenosis, iPSP was associated with a lower risk of cardiac events at 3 years. Therefore, physicians should apply iPSP more actively for the treatment of complex coronary artery stenoses, even in the current era. (Evaluation of the First, Second, and New Drug-Eluting Stents in Routine Clinical Practice [IRIS-DES]; NCT01186133)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study was conducted to investigate the influence of coronary artery calcium (CAC) score on the diagnostic performance of machine-learning-based coronary computed tomography (CT) angiography (cCTA)-derived fractional flow reserve (CT-FFR)., Background: CT-FFR is used reliably to detect lesion-specific ischemia. Novel CT-FFR algorithms using machine-learning artificial intelligence techniques perform fast and require less complex computational fluid dynamics. Yet, influence of CAC score on diagnostic performance of the machine-learning approach has not been investigated., Methods: A total of 482 vessels from 314 patients (age 62.3 ± 9.3 years, 77% male) who underwent cCTA followed by invasive FFR were investigated from the MACHINE (Machine Learning based CT Angiography derived FFR: a Multi-center Registry) registry data. CAC scores were quantified using the Agatston convention. The diagnostic performance of CT-FFR to detect lesion-specific ischemia was assessed across all Agatston score categories (CAC 0, >0 to <100, 100 to <400, and ≥400) on a per-vessel level with invasive FFR as the reference standard., Results: The diagnostic accuracy of CT-FFR versus invasive FFR was superior to cCTA alone on a per-vessel level (78% vs. 60%) and per patient level (83% vs. 73%) across all Agatston score categories. No statistically significant differences in the diagnostic accuracy, sensitivity, or specificity of CT-FFR were observed across the categories. CT-FFR showed good discriminatory power in vessels with high Agatston scores (CAC ≥400) and high performance in low-to-intermediate Agatston scores (CAC >0 to <400) with a statistically significant difference in the area under the receiver-operating characteristic curve (AUC) (AUC: 0.71 [95% confidence interval (CI): 0.57 to 0.85] vs. 0.85 [95% CI: 0.82 to 0.89], p = 0.04). CT-FFR showed superior diagnostic value over cCTA in vessels with high Agatston scores (CAC ≥ 400: AUC 0.71 vs. 0.55, p = 0.04) and low-to-intermediate Agatston scores (CAC >0 to <400: AUC 0.86 vs. 0.63, p < 0.001)., Conclusions: Machine-learning-based CT-FFR showed superior diagnostic performance over cCTA alone in CAC with a significant difference in the performance of CT-FFR as calcium burden/Agatston calcium score increased. (Machine Learning Based CT Angiography Derived FFR: a Multicenter, Registry [MACHINE] NCT02805621)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Intravascular ultrasound (IVUS)-derived morphological criteria are poor predictors of the functional significance of intermediate coronary stenosis. IVUS-based supervised machine learning (ML) algorithms were developed to identify lesions with a fractional flow reserve (FFR) ≤0.80 (vs. >0.80)., Methods: A total of 1328 patients with 1328 non-left main coronary lesions were randomized into training and test sets in a 4:1 ratio. Masked IVUS images were generated by an automatic segmentation model, and 99 computed IVUS features and six clinical variables (age, gender, body surface area, vessel type, involved segment, and involvement of the proximal left anterior descending artery) were used for ML training with 5-fold cross-validation. Diagnostic performances of the binary classifiers (L2 penalized logistic regression, artificial neural network, random forest, AdaBoost, CatBoost, and support vector machine) for detecting ischemia-producing lesions were evaluated using the non-overlapping test samples., Results: In the classification of test set lesions into those with an FFR ≤0.80 vs. >0.80, the overall diagnostic accuracies for predicting an FFR ≤0.80 were 82% with L2 penalized logistic regression, 80% with artificial neural network, 83% with random forest, 83% with AdaBoost, 81% with CatBoost, and 81% with support vector machine (AUCs: 0.84-0.87). With exclusion of the 28 lesions with borderline FFR of 0.75-0.80, the overall accuracies for the test set were 86% with L2 penalized logistic regression, 85% with an artificial neural network, 87% with random forest, 87% with AdaBoost, 85% with CatBoost, and 85% with support vector machine., Conclusions: The IVUS-based ML algorithms showed good diagnostic performance for identifying ischemia-producing lesions, and may reduce the need for pressure wires., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Aims: There are limited data on the association between serum uric acid (SUA) level and subclinical coronary atherosclerosis. This study investigated the influence of SUA level on subclinical coronary atherosclerosis, as detected by coronary computed tomography angiography (CCTA), in an asymptomatic population., Methods: We evaluated 6431 asymptomatic individuals (mean age 53.6 ± 7.6 years, 4691 men [72.9%]) with no prior history of coronary artery disease, who voluntarily underwent laboratory tests and CCTA as part of a general health examination. The participants were stratified into quartiles according to their SUA levels. Coronary atherosclerotic plaques (calcified, mixed, and non-calcified plaques) were assessed using CCTA. Logistic regression analysis was used to determine the association between SUA levels and subclinical coronary atherosclerosis., Results: The prevalence of any atherosclerotic, calcified, mixed, and non-calcified plaques increased with SUA quartiles (all p < 0.001). After adjustment for cardiovascular risk factors, there were no statistically significant differences in the adjusted odds ratios for calcified plaque (1.19; 95% CI 0.98-1.46; p = 0.080) and mixed plaque (1.25; 95% CI 0.94-1.67; p = 0.132) in the fourth SUA quartile compared to the first quartile. However, the adjusted odds ratios for any atherosclerotic plaque (1.39; 95% CI 1.16-1.68; p < 0.001) and non-calcified plaque (1.38; 95% CI 1.11-1.72; p = 0.004) were significantly higher in the fourth SUA quartile., Conclusions: In asymptomatic individuals, high SUA level was an independent predictor of non-calcified plaques, suggesting an increased cardiovascular risk., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Aims: Although grayscale intravascular ultrasound (IVUS) is commonly used for assessing coronary lesion morphology and optimizing stent implantation, detection of vulnerable plaques by IVUS remains challenging. We aimed to develop machine learning (ML) models for predicting optical coherence tomography-derived thin-cap fibroatheromas (OCT-TCFAs)., Methods: In 517 patients with angina, 414 and 103 coronary lesions were randomized into training vs. test sets. Each of the IVUS-OCT co-registered frames (including 32,807 for training and 8101 for test) was labeled according to the presence vs. absence of OCT-TCFA. Among 1449 computed IVUS features based on two-dimensional geometry and texture, 17 features were finally selected and used in supervised ML with artificial neural network (ANN), support vector machine (SVM), and naïve Bayes., Results: IVUS sections with (vs. without) OCT-TCFA showed a larger plaque burden, and a smaller and eccentric lumen. TCFA-containing sections were characterized by increased ratios of variance, entropy, and kurtosis; reduced ratio of homogeneity within the superficial to the deeper plaque; and decreased smoothness within the fibrous cap. In addition, OCT-TCFA was associated with low ratios of gamma-beta, Nakagami-μ and Nakagami-ω, and a high ratio of Rayleigh-b within the superficial to the deeper region. With a 5-fold cross-validation, the averaged accuracies were 81 ± 5% for ANN (area under the curve [AUC] = 0.80 ± 0.08), 77 ± 4% for SVM (AUC = 0.74 ± 0.05), and 78 ± 2% for naïve Bayes (AUC = 0.77 ± 0.04) for predicting OCT-TCFA. In the test set, ANN and naïve Bayes showed the overall accuracies of >80%., Conclusions: Supervised ML algorithms with computed IVUS features predicted the presence of OCT-TCFA. This data-driven approach may help clinicians in recognizing high-risk coronary lesions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To use adenosine-induced stress CT myocardial perfusion imaging (CT-MPI) to determine normal reference values for left ventricle (LV) wall thickness (WT) and motion parameters., Methods: This study included 106 Korean subjects (52 men and 54 women) who underwent CT-MPI due to chest pain, but were not found to have any detectable mild or severe coronary artery disease or myocardial perfusion defect. The following quantitative parameters were assessed on the CT-MPI according to a 17-segment model: LV myocardial thickness at end-systolic (WT ES ) and end-diastolic (WT ED ) phases, systolic wall thickening (SWT), and wall motion (WM). The associations of the measured parameters with the subjects' demographic characteristics and comorbidities were also analyzed., Results: Septal wall (7.2 mm) and basal-level (7.7 mm) LV myocardium demonstrated significantly higher WT (p < 0.001). SWT was highest in lateral (77.8%, p < 0.014) and apical (78.9%, p = 0.009) myocardium, while lateral (7.7 mm) and basal (6.7 mm) myocardium exhibited the greatest WM (p < 0.001). WT was significantly higher in men and younger (<60 years) subjects (all, p < 0.001). Hypertensive individuals presented with significantly higher SWT (79.9%, p = 0.024). LV WT exhibited statistically significant correlations (all positive, except for age) with age, height, weight, body surface area, body mass index, and systolic blood pressure (all, p < 0.010)., Conclusions: The present study provides CT-MPI reference values for LV myocardial WT, SWT, and WM measured on an adult Korean population. Knowledge of such normal reference measurements would be beneficial for the efficient interpretation of CT-MPI examinations in populations of Asian ethnicity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: This study examined the incremental value of subtended myocardial mass (V sub ) as assessed by coronary computed tomography angiography (CTA) for identifying lesion-specific ischemia verified by invasive fractional flow reserve (FFR) in quantitative coronary CTA., Background: FFR is determined not only by coronary stenosis severity, but also by V sub . One-step evaluation of combined V sub and coronary lesion morphology may improve the accuracy of coronary CTA for identifying ischemia-producing lesions., Methods: A total of 246 intermediate coronary artery lesions (30% to 80% diameter stenosis) in 220 patients (mean age 61.7 years, 168 men) interrogated by FFR were retrospectively studied. Coronary CTA data were used to assess the V sub by coronary artery stenosis, minimal lumen area (MLA), percentage of aggregated plaque volume (%APV), positive remodeling, and low-attenuation plaque. The ability of V sub /MLA 2 to discriminate lesions with FFR ≤0.80 was examined. Diagnostic performance, odds ratios, and category-less net reclassification improvements of coronary CTA parameters for FFR-verified (≤0.80) ischemia were evaluated. On-site computed tomography (CT) derived-FFR (CT-FFR) and quantitative coronary angiography (QCA) data were also compared., Results: Of 246 lesions, 84 (34.1%) showed an FFR ≤0.80. V sub was independently associated with an FFR ≤0.80 (odds ratio: 1.04/1 cm 3 ; p = 0.032) and showed incremental value over MLA. V sub /MLA 2 >4.16 was the best single parameter for discriminating an FFR ≤0.80 with 83.3% sensitivity and 67.9% specificity. The area under the curve (AUC) of V sub /MLA 2 >4.16 (0.80 [95% confidence interval: 0.75 to 0.85]) was better than that of MLA (change in [Δ]AUC: 0.069; p < 0.001), %APV (ΔAUC: 0.096; p = 0.017), and diameter stenosis of QCA (ΔAUC: 0.080; p = 0.037) and was comparable to that of CT-FFR (AUC 0.77; ΔAUC: 0.035; p = 0.304)., Conclusions: V sub is an independent determinant of an FFR ≤0.80. The mathematical index of V sub /MLA 2 >4.16 assessed by coronary CTA shows better diagnostic performance for the detection of ischemia-producing lesions than CT-derived MLA alone or %APV and QCA parameters and was comparable to that of on-site CT-FFR., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Nivolumab is effective in the treatment of previously treated patients with advanced NSCLC. However, its radiological evaluation is challenging because of atypical patterns of response such as pseudoprogression. We examined the characteristics and outcomes of previously treated patients with NSCLC who were treated with nivolumab and experienced development of pseudoprogression., Methods: We conducted a 15-center retrospective cohort study of previously treated patients with advanced NSCLC who received nivolumab monotherapy. For the patients who showed pseudoprogression, we defined progression-free survival 1 (PFS1) as the time to Response Evaluation Criteria in Solid Tumors-defined first progressive disease and progression-free survival 2 (PFS2) as the time to Response Evaluation Criteria in Solid Tumors-defined second progressive disease or death., Results: Among the 542 patients included, 20% and 53% showed a typical response and progression, respectively. Of the 14 (3%) patients who showed pseudoprogression, most (n = 10) showed a response within 3 months of nivolumab treatment. The median PFS1 and PFS2 were 1.0 and 7.3 months, respectively. The median PFS2 was significantly shorter in the patients who showed pseudoprogression than the PFS of the patients with a typical response (p < 0.001). In contrast, patients showing pseudoprogression had significantly longer overall survival than did patients showing typical progression (p = 0.001)., Conclusions: Pseudoprogression was uncommon, and the duration of response in patients who showed pseudoprogression was shorter than that in patients who showed a typical response. However, the survival benefit of pseudoprogression was markedly better than that of typical progression. Further research is required to elucidate the characteristics of and mechanisms underlying pseudoprogression., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: We aimed to compare the myocardial ischemic burden assessed using semi-quantitative and quantitative analysis of computed tomography-myocardial perfusion imaging (CT-MPI) with that of single-photon emission computed tomography (SPECT)., Methods: From 2011 to 2013, 97 patients who underwent CT-MPI and SPECT were evaluated. The extent and severity of perfusion defects were assessed on a 5-point scale using a standard 16-segment model, and were expressed as summed stress score (SSS) and summed difference score (SDS). Receiver operating characteristic (ROC) curves for quantitative parameters were generated for the diagnosis of abnormal perfusion defect (SSS ≥ 4) and presence of ischemia (SDS ≥ 2) on SPECT., Results: On CT-MPI, 298 (19.2%) of the 1552 segments showed perfusion abnormalities during stress, whereas perfusion abnormalities were shown in 179 (11.5%) segments on SPECT-MPI. On a per-person basis, there was good agreement, with intraclass correlation coefficients of 0.78 for SSS and 0.72 for SDS. A significant reduction of attenuation in stress and myocardial perfusion reserve index, along with an increase in % defect volume of CT-MPI, were demonstrated as the degree of perfusion defect or ischemia on SPECT increased. On the ROC curves, % defect volume on CT-MPI demonstrated the highest area under the curve: 0.91 for abnormal perfusion defect and 0.89 (all p < 0.001) for the presence of ischemia on SPECT., Conclusions: Semi-quantitative analysis of CT-MPI showed good accordance with SPECT. A quantitative approach for CT-MPI, especially % defect volume, may provide additional value in the identification of myocardial perfusion abnormalities., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01696006., (Copyright © 2018. Published by Elsevier B.V.)

Backgrounds: Cancer immunotherapy using immune checkpoint inhibitors has received a remarkable amount of attention in patients with non-small cell lung cancer (NSCLC). The unique adverse effects known as immune-related adverse events (irAEs) associated with immune checkpoint inhibitors are not known however, and neither is the incidence of infectious disease among patients receiving immune checkpoint inhibitors. The aims of this study were to investigate the incidence of infections during nivolumab treatment, and the risk factors associated with infections., Methods: We retrospectively reviewed NSCLC patients who received nivolumab in two teaching hospitals (National Hospital Organization Kyoto Medical Center and Kyoto University Hospital, Kyoto, Japan) between December 2015 and June 2017. We counted any infectious diseases occurring at any time after the initiation of nivolumab until 3 months after its discontinuation. In the current study, "infectious disease" was defined as any infection requiring the administration of any antimicrobial agent., Results: Of a total of 167 NSCLC patients reviewed, 32 (19.2%) experienced infectious diseases. Of the 33 infections in 32 patients, 25 were bacterial, 2 were fungal, and 6 were viral. Twenty-seven of the patients with infections used corticosteroids during their treatment course. There was no statistically significant difference in the use of immunosuppressive agents between patients with and without infections. A history of diabetes mellitus was significantly associated with infection (odds ratio 3.61, 95% confidence interval 1.14-11.4, p = 0.028)., Conclusions: Lung cancer patients receiving nivolumab have a certain level of risk for developing infectious diseases. In the current study, a history of diabetes mellitus was an independent risk factor for infectious disease development. Clinicians should pay attention to occult infectious diseases in patients receiving lung cancer treatment with immune checkpoint inhibitors, especially those with the history of diabetes mellitus., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Numerous randomised trials have compared coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) for patients with coronary artery disease. However, no studies have been powered to detect a difference in mortality between the revascularisation strategies., Methods: We did a systematic review up to July 19, 2017, to identify randomised clinical trials comparing CABG with PCI using stents. Eligible studies included patients with multivessel or left main coronary artery disease who did not present with acute myocardial infarction, did PCI with stents (bare-metal or drug-eluting), and had more than 1 year of follow-up for all-cause mortality. In a collaborative, pooled analysis of individual patient data from the identified trials, we estimated all-cause mortality up to 5 years using Kaplan-Meier analyses and compared PCI with CABG using a random-effects Cox proportional-hazards model stratified by trial. Consistency of treatment effect was explored in subgroup analyses, with subgroups defined according to baseline clinical and anatomical characteristics., Findings: We included 11 randomised trials involving 11 518 patients selected by heart teams who were assigned to PCI (n=5753) or to CABG (n=5765). 976 patients died over a mean follow-up of 3·8 years (SD 1·4). Mean Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score was 26·0 (SD 9·5), with 1798 (22·1%) of 8138 patients having a SYNTAX score of 33 or higher. 5 year all-cause mortality was 11·2% after PCI and 9·2% after CABG (hazard ratio [HR] 1·20, 95% CI 1·06-1·37; p=0·0038). 5 year all-cause mortality was significantly different between the interventions in patients with multivessel disease (11·5% after PCI vs 8·9% after CABG; HR 1·28, 95% CI 1·09-1·49; p=0·0019), including in those with diabetes (15·5% vs 10·0%; 1·48, 1·19-1·84; p=0·0004), but not in those without diabetes (8·7% vs 8·0%; 1·08, 0·86-1·36; p=0·49). SYNTAX score had a significant effect on the difference between the interventions in multivessel disease. 5 year all-cause mortality was similar between the interventions in patients with left main disease (10·7% after PCI vs 10·5% after CABG; 1·07, 0·87-1·33; p=0·52), regardless of diabetes status and SYNTAX score., Interpretation: CABG had a mortality benefit over PCI in patients with multivessel disease, particularly those with diabetes and higher coronary complexity. No benefit for CABG over PCI was seen in patients with left main disease. Longer follow-up is needed to better define mortality differences between the revascularisation strategies., Funding: None., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The clinical outcomes for women compared with men undergoing left main PCI were sparse. We compared the characteristics and long-term outcomes in women versus men after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) for unprotected left main CAD., Methods: We identified 2328 patients (545 women; 1783 men) with unprotected left main CAD who received PCI with DES between January 2007 and December 2013 in the Interventional Cardiology Research In-cooperation Society-left MAIN revascularization (IRIS-MAIN) registry. The primary outcome was a composite of death from any cause, myocardial infarction, or stroke., Results: The median follow-up time was 2.9years (interquartile range: 1.0-4.1years). Women were older, had a higher incidence of insulin-requiring diabetes mellitus and hypertension, and more commonly presented with acute coronary syndrome than men. Left main ostial lesion was more common in women, whereas left main bifurcation lesion with more extensive CAD was more common in men. The incidence of primary outcome was similar between the two groups (10.8% vs. 10.8%, respectively, log-rank p=0.587). The results were similar after adjustment for baseline variables and consistent across major subgroups. The need for target lesion revascularization was significantly higher in women than in men (8.8% vs. 5.7%, respectively, p<0.05) but the sex bias was not confirmed after adjusting for confounders., Conclusions: Women, as compared to men, had different clinical and lesion characteristics but similar long-term outcomes after PCI with DES for left main CAD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: There are limited data regarding the influence of glycemic status on the risk of subclinical coronary atherosclerosis on coronary computed tomographic angiography (CCTA) in asymptomatic individuals., Methods: We analyzed 6434 asymptomatic individuals who underwent CCTA. The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA, and ≥50% diameter stenosis was defined as significant. Of study participants, 2197 (34.1%), 3122 (48.5%), and 1115 (17.3%) were categorized as normal, prediabetic and diabetic individuals, respectively., Results: Compared with normal individuals, there were no statistically differences in the adjusted odds ratios of prediabetic individuals for significant coronary artery stenosis (0.98, 95% confidence interval [CI] 0.80-1.22, p=0.888), any plaque (0.96, 95% CI 0.86-1.07, p=0.483), calcified plaque (0.90, 95% CI 0.79-1.01, p=0.080), non-calcified plaque (1.02, 95% CI 0.88-1.17, p=0.803), and mixed plaque (1.00, 95% CI 0.82-1.22, p=0.983). However, adjusted odds ratios for significant coronary artery stenosis (1.71, 95% CI 1.34-2.19, p<0.001), any plaque (1.45, 95% CI 1.26-1.68, p<0.001), calcified plaque (1.35, 95% CI 1.15-1.57, p<0.001), non-calcified plaque (1.33, 95% CI 1.11-1.59, p=0.002), and mixed plaque (1.64, 95% CI 1.30-2.07, p<0.001) of diabetic individuals were significantly higher than those of the normal individuals., Conclusion: In asymptomatic individuals, diabetic individuals had a higher risk for subclinical coronary atherosclerosis, but prediabetic individuals were not associated with an increased risk of subclinical coronary atherosclerosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Some patients with advanced or recurrent, epidermal growth factor receptor (EGFR) mutation-positive (EGFR M+) non-small-cell lung cancer (NSCLC) continue to receive EGFR tyrosine kinase inhibitors (TKIs) beyond radiological progression., Methods: We analysed a cohort of 577 patients with EGFR M+ NSCLC, who had received a first-line EGFR-TKI. We classified patients according to clinical course and treatment patterns at Response Evaluation Criteria in Solid Tumors (RECIST) progressive disease (PD). We evaluated the period from RECIST PD to TKI discontinuation or clinical PD and also evaluated survival after RECIST PD and compared it between groups., Results: RECIST PD was documented in 451 cases, of which 283 (62.7%) were clinically stable. 186 (65.7%) discontinued and 97 (34.3%) continued the EGFR-TKI. In those who continued EGFR-TKI, median time between RECIST PD and clinical PD or TKI discontinuation was 5.1 months. Median survival after RECIST PD in patients who discontinued and continued EGFR-TKI after clinically stable RECIST PD was 14.6 and 15.3 months (p=0.5489), respectively. In multivariate analysis, continuing EGFR-TKI therapy, female gender, better performance status and exon 19 deletion subtype were likely positive predictive factors for survival after clinically stable RECIST PD., Conclusion: Our study suggests that some patients could benefit from receiving an EGFR-TKI beyond radiological progression., Competing Interests: Competing interests: YG has received personal fees as honoraria from Pfizer Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Eli Lilly Japan, AstraZeneca, Boehringer Ingelheim Japan, Ono Pharmaceutical, Novartis Pharma, GlaxoSmithKline and Bristol-Myers Squibb. His institution has received research funding from Merck Serono, Pfizer Japan, Taiho Pharmaceutical, Eisai, Chugai Pharmaceutical, Eli Lilly Japan, AstraZeneca, Boehringer Ingelheim Japan, Ono Pharmaceutical, Novartis Pharma, Daiichi Sankyo, GlaxoSmithKline, Yakult Honsha, Quintiles, Astellas Pharma and Bristol-Myers Squibb. KY has received personal fees as honoraria from Chugai Pharmaceutical, Eli Lilly Japan, AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim Japan, Bristol-Myers Squibb, Ono Pharmaceutical and Pfizer Japan. YH has received personal fees as honoraria from AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb and Boehringer Ingelheim Japan. TK has received personal fees as honoraria from Chugai Pharmaceutical, Roche, Boehringer Ingelheim Japan, Ono Pharmaceutical, Eli Lilly Japan, AstraZeneca, Taiho Pharmaceutical, Pfizer Japan and Kyowa Hakko Kirin. His institution has received research funding from Chugai Pharmaceutical, MSD, Takeda Pharmaceutical, Kyowa Hakko Kirin, Daiichi Sankyo, Yakult Honsha, Boehringer Ingelheim Japan, Pfizer Japan, Taiho Pharmaceutical, Shionogi, AstraZeneca, Eli Lilly Japan and Bristol-Myers Squibb. MN has received personal fees as honoraria from Pfizer Japan, Chugai Pharmaceutical, Eli Lilly Japan, Taiho Pharmaceutical, Nichirei Biosciences, Elekta, AstraZeneca, Sanofi, Bristol-Myers Squibb and Ono Pharmaceutical and consulting fees from Novartis, Ono Pharmaceutical, Chugai Pharmaceutical, Eli Lilly Japan, Taiho Pharmaceutical, Daiichi Sankyo and Pfizer Japan. His institution has received research funding from Novartis, Ono Pharmaceutical, Chugai Pharmaceutical, Bristol-Myers Squibb, Takeda Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Eli Lilly Japan and Pfizer Japan. YHK has received personal fee as Speakers’ Bureau from Chugai Pharmaceutical, AstraZeneca and Boehringer Ingelheim Japan. AI has received personal fee as honoraria from AstraZeneca. YH has received personal fees as honoraria from AstraZeneca, Chugai Pharmaceutical and Boehringer Ingelheim Japan. His institution has received research funding from AstraZeneca, Chugai Pharmaceutical and Boehringer Ingelheim Japan. HI institution has received research funding from Ono Pharmaceutical, Takeda Pharmaceutical and MSD. KM institution has received research funding from Ono Pharmaceutical and Chugai Pharmaceutical. KY has received personal fees as honoraria from Pfizer Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Eli Lilly Japan, AstraZeneca, Ono Pharmaceutical and Bristol-Myers Squibb. YO has stock in Statcom and received personal fees as executive salaries from Statcom; honoraria from Sanofi and Eisai; consulting fees from Chugai Pharmaceutical, Taiho Pharmaceutical, Shionogi, Kowa and Eisai; and travel expenses from Yakult Honsha and Takeda Pharmaceutical. His institution has received research funding from Eisai. HK has received personal fees as honoraria from AstraZeneca, Taiho Pharmaceutical, Sanofi, Johnson & Johnson, Eli Lilly Japan, Ono Pharmaceutical, Chugai Pharmaceutical, Pfizer Japan, Boehringer Ingelheim Japan, MSD, Dainippon Sumitomo, Daiichi Sankyo, Bristol-Myers Squibb, Novo Nordisk Pharma, Nippon Chemiphar, Nihon Medi-Physics, Kyorin Pharmaceutical, Nippon Kayaku and Kyowa Hakko Kirin and travel expense from Taiho Pharmaceutical. No other disclosures are reported.

Background: Although studies have demonstrated comparable efficacy and safety profiles of everolimus- and zotarolimus-eluting stents (EES and ZES, respectively) for a broad spectrum of coronary artery diseases, there is paucity of data concerning their safety and efficacy for coronary chronic total occlusions (CTOs). This study compared the clinical performance of EES and ZES following successful percutaneous coronary intervention for CTOs., Methods: The cohort included 539 consecutive CTO patients who underwent successful PCI using EES (n=313) and ZES (n=226) between September 2006 and August 2014. The primary outcome was defined as the composite of death, myocardial infarction, and target vessel revascularization., Results: During a median follow-up of 3.3years, in both groups, the primary outcome occurred in 12.2% of patients. After multivariable adjustment, no significant difference was observed between the two groups in the risk of primary outcome [hazard ratio (HR) 1.03, 95% confidence interval (CI) 0.59-1.79, P=0.930 for ZES compared with EES]. Similarly, there were no significant differences in the risk of death (adjusted HR 0.96, 95% CI 0.43-2.15, P=925), death or myocardial infarction (adjusted HR 0.93, 95% CI 0.46-1.88, P=0.829), and target vessel failure (adjusted HR 0.96, 95% CI 0.51-1.82, P=0.902). The incidence of definite/probable stent thrombosis was relatively low [0% (ZES) vs. 1.0% (EES), P=0.19]., Conclusion: No significant differences were observed between EES and ZES in terms of clinical outcomes for coronary CTOs at 3.3years., (Copyright © 2017. Published by Elsevier B.V.)

Objectives: This study sought to estimate the differential incidence and prognostic significance of periprocedural myocardial infarction (MI) according to various definitions., Background: In trials comparing percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), the primary composite endpoint is very sensitive to the definition of MI. Especially, the definition of periprocedural MI has considerably varied, and uniform criteria are still unsettled., Methods: We evaluated 7,697 patients with multivessel disease who received PCI (n = 4,514) or underwent CABG (n = 3,183) between 2003 and 2013, and for whom serial measurement of creatine kinase-MB was available. According to various MI definitions (second and third universal definitions and the Society for Cardiovascular Angiography and Interventions definition), we assessed the prevalence and prognostic significance of periprocedural MI after both PCI and CABG. Patients were followed for major cardiovascular events (death from cardiovascular causes and spontaneous MI) and death for a median of 4.7 years., Results: According to various definitions of MI, there was a substantial difference in the rates of periprocedural MI after PCI and CABG (18.7% vs. 2.9% by second universal; 3.2% vs. 1.9% by third universal; and 5.5% vs. 18.3% by Society for Cardiovascular Angiography and Interventions definition). The presence of periprocedural MI was associated with increased risks of major cardiovascular events after both PCI and CABG regardless of MI definition. The risk-adjusted 5-year rates of future major cardiovascular events after occurrence of periprocedural MI were similar after PCI and CABG in second and third universal definition. However, using Society for Cardiovascular Angiography and Interventions definition, the rates of major cardiovascular events were significantly higher after PCI than after CABG (24.3% vs. 20.4%; hazard ratio: 1.61; 95% confidence interval: 1.07 to 2.41; p = 0.02)., Conclusions: There were substantial differences in incidence and clinical relevance of periprocedural MI according to various contemporary, widely used definitions of MI., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to compare long-term survival between patients with severe coronary artery disease undergoing coronary artery bypass grafting (CABG) and those undergoing percutaneous coronary intervention (PCI) achieving complete revascularization (CR) or incomplete revascularization., Background: The importance of CR in decision making regarding revascularization strategy in patients with severe coronary artery disease is unknown., Methods: Data were pooled from the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery), PRECOMBAT (Premier of Randomized Comparison of Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease), and BEST (Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease) trials. The primary outcome was death from any cause and was compared in an as-treated analysis., Results: The rate of CR was 61.7% (57.2% with PCI and 66.8% with CABG). During a median 4.9-year follow-up period (interquartile range: 4.5 to 5.0 years), compared with patients undergoing CABG with CR, those undergoing PCI with incomplete revascularization had a higher risk for death from any cause (adjusted hazard ratio [aHR]: 1.43; 95% confidence interval [CI]: 1.03 to 2.00; p = 0.036) and the composite of death, myocardial infarction, and stroke (aHR: 1.48; 95% CI: 1.14 to 1.92; p = 0.003). However, there was no significant difference between patients undergoing CABG with CR and those undergoing PCI with CR regarding the risk for death from any cause (aHR: 1.16; 95% CI: 0.83 to 1.63; p = 0.39) and the composite of death, myocardial infarction, and stroke (aHR: 1.14; 95% CI: 0.87 to 1.48; p = 0.35). Subgroup analysis of multivessel coronary disease, high SYNTAX score (>32), and diabetes showed consistent findings., Conclusions: For the treatment of left main or multivessel coronary artery disease, PCI resulting in CR was associated with a similar long-term survival rate to CABG resulting in CR. Therefore, the ability to achieve CR should enter into the decision algorithm for choice of revascularization strategy., (Copyright © 2017. Published by Elsevier Inc.)

Objectives: The aim of this study was to evaluate the long-term outcomes and predictors of adverse events following successful "full metal jacket" (FMJ) (stent length ≥60 mm without gap) procedures using drug-eluting stents to treat coronary chronic total occlusions (CTOs)., Background: The FMJ stenting procedure is often required to treat CTOs, but its clinical efficacy and safety remain unknown., Methods: In total, 1,126 successful CTO procedures (1,107 consecutive patients) performed between May 2003 and March 2015 were studied. The primary endpoint was target lesion failure, a composite of cardiac death, target vessel-related myocardial infarction, or target lesion revascularization or reocclusion., Results: Overall, 406 patients (36.7%) underwent the FMJ procedure, increasing in frequency over time (28.5% from 2003 to 2006 and 41.7% after 2011). The mean stent length was 76.8 ± 14.6 mm (range 60 to 122 mm), and the average number of stent overlaps was 2.5 ± 0.6 (range 2 to 4). A total of 127 patients (31.3%) had persistent luminal narrowing at the distal reference segment after stenting. During the median follow-up period of 5.1 years, target lesion failure occurred in 16.0% of patients. There were 17 cases of total reocclusion and 5 cases of stent thrombosis. Multivariate analysis confirmed that the number of implanted stents (hazard ratio: 1.72; 95% confidence interval: 1.16 to 2.54; p = 0.006) and persistent distal luminal narrowing (hazard ratio: 2.73; 95% confidence interval: 1.66 to 4.47; p < 0.001) were predictors of increased risk for target lesion failure., Conclusions: The FMJ procedure using drug-eluting stents for CTOs provides acceptable long-term clinical results. Persistent distal luminal narrowing increases the future likelihood of adverse events despite procedural success., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Alectinib, a potent, highly selective, CNS-active inhibitor of anaplastic lymphoma kinase (ALK), showed promising efficacy and tolerability in the single-arm phase 1/2 AF-001JP trial in Japanese patients with ALK-positive non-small-cell lung cancer. Given those promising results, we did a phase 3 trial to directly compare the efficacy and safety of alectinib and crizotinib., Methods: J-ALEX was a randomised, open-label, phase 3 trial that recruited ALK inhibitor-naive Japanese patients with ALK-positive non-small-cell lung cancer, who were chemotherapy-naive or had received one previous chemotherapy regimen, from 41 study sites in Japan. Patients were randomly assigned (1:1) via an interactive web response system using a permuted-block method stratified by Eastern Cooperative Oncology Group performance status, treatment line, and disease stage to receive oral alectinib 300 mg twice daily or crizotinib 250 mg twice daily until progressive disease, unacceptable toxicity, death, or withdrawal. The primary endpoint was progression-free survival assessed by an independent review facility. The efficacy analysis was done in the intention-to-treat population, and safety analyses were done in all patients who received at least one dose of the study drug. The study is ongoing and patient recruitment is closed. This study is registered with the Japan Pharmaceutical Information Center (number JapicCTI-132316)., Findings: Between Nov 18, 2013, and Aug 4, 2015, 207 patients were recruited and assigned to the alectinib (n=103) or crizotinib (n=104) groups. At data cutoff for the second interim analysis, 24 patients in the alectinib group had discontinued treatment compared with 61 in the crizotinib group, mostly due to lack of efficacy or adverse events. At the second interim analysis (data cutoff date Dec 3, 2015), an independent data monitoring committee determined that the primary endpoint of the study had been met (hazard ratio 0·34 [99·7% CI 0·17-0·71], stratified log-rank p<0·0001) and recommended an immediate release of the data. Median progression-free survival had not yet been reached with alectinib (95% CI 20·3-not estimated) and was 10·2 months (8·2-12·0) with crizotinib. Grade 3 or 4 adverse events occurred at a greater frequency with crizotinib (54 [52%] of 104) than alectinib (27 [26%] of 103). Dose interruptions due to adverse events were also more prevalent with crizotinib (77 [74%] of 104) than with alectinib (30 [29%] of 103), and more patients receiving crizotinib (21 [20%]) than alectinib (nine [9%]) discontinued the study drug because of an adverse event. No adverse events with a fatal outcome occurred in either treatment group., Interpretation: These results provide the first head-to-head comparison of alectinib and crizotinib and have the potential to change the standard of care for the first-line treatment of ALK-positive non-small-cell lung cancer. The dose of alectinib (300 mg twice daily) used in this study is lower than the approved dose in countries other than Japan; however, this limitation is being addressed in the ongoing ALEX study., Funding: Chugai Pharmaceutical Co, Ltd., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: This study sought to investigate the incidence, management, and clinical relevance of atrial fibrillation (AF) during and after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and evaluate outcomes of different antithrombotic strategies., Background: Uncertainty exists regarding the optimal antithrombotic strategy in patients with AF who are undergoing PCI with DES., Methods: Using a consecutive series of 10,027 patients who underwent DES implantation between 2003 and 2011, we evaluated the overall prevalence and clinical impact of AF. In addition, we compared the efficacy and safety of dual antiplatelet therapy (DAPT) (aspirin plus clopidogrel) and triple therapy (DAPT plus warfarin) among patients with AF. The primary outcome was a composite of cardiovascular death, myocardial infarction, or stroke., Results: Overall, 711 (7.1%) patients had a diagnosis of AF at the index PCI. Patients with AF were older, had more comorbid conditions, and more often had a history of strokes; most patients with AF (88.4%) received DAPT rather than triple therapy (10.5%) at discharge. The rate of primary outcome after PCI during the 6-year follow-up period was significantly higher in patients with AF than in those without AF (22.1% vs. 8.0%; p < 0.001). This trend was consistent for major bleeding (4.5% vs. 1.5%; p < 0.001). After multivariable adjustment, the presence of AF was significantly associated with a higher risk of primary outcome (hazard ratio [HR]: 2.33; 95% confidence interval [CI]: 1.95 to 2.79; p < 0.001) and major bleeding (HR: 2.01; 95% CI: 1.32 to 3.06; p = 0.001). Among patients with AF, adjusted risk for the primary outcome was similar between the DAPT group and the triple therapy group (HR: 1.01; 95% CI: 0.60 to 1.69; p = 0.98), but triple therapy was associated with a significantly higher risk of hemorrhagic stroke (HR: 7.73; 95% CI: 2.14 to 27.91; p = 0.002) and major bleeding (HR: 4.48; 95% CI: 1.81 to 11.08; p = 0.001)., Conclusions: Among patients receiving DES implantation, AF was not rare and was associated with increased ischemic and bleeding risk. In patients with AF, triple therapy was not associated with decreased ischemic events but was associated with increased bleeding risk compared to DAPT., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The authors undertook a patient-level meta-analysis to compare long-term outcomes after coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in 3,280 patients with left main or multivessel coronary artery disease (CAD)., Background: The relative efficacy and safety of CABG versus PCI with DES for left main or multivessel CAD remain controversial., Methods: Data were pooled from the BEST (Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease), PRECOMBAT (Premier of Randomized Comparison of Bypass Surgery vs. Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease), and SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trials. The primary outcome was a composite of all-cause death, myocardial infarction, or stroke., Results: The median follow-up was 60 months, and follow-up was completed for 96.2% of patients. The rate of primary outcome was significantly lower with CABG than with PCI (13.0% vs. 16.0%; hazard ratio [HR]: 0.83; 95% confidence interval [CI]: 0.69 to 1.00; p = 0.046). The difference was mainly driven by reduction in myocardial infarction (HR: 0.46; 95% CI: 0.33 to 0.64; p < 0.001). There was significant interaction between treatment effect and types of CAD, showing CABG to be superior compared with PCI with DES in patients with multivessel CAD (p = 0.001), but no between-group difference in those with left main CAD (p = 0.427). The rates for all-cause death and stroke were similar between the 2 groups. By contrast, the need for repeat revascularization was significantly lower in the CABG group compared with the PCI group., Conclusions: CABG, as compared with PCI with DES, reduced long-term rates of the composite of all-cause death, myocardial infarction, or stroke in patients with left main or multivessel CAD. The advantage of CABG over PCI with DES was particularly pronounced in those with multivessel CAD., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The study sought to investigate the impact of different computing methods for composite endpoints other than time-to-event (TTE) statistics in a large, multicenter registry of unprotected left main coronary artery (ULMCA) disease., Background: TTE statistics for composite outcome measures used in ULMCA studies consider only the first event, and all the contributory outcomes are handled as if of equal importance., Methods: The TTE, Andersen-Gill, win ratio (WR), competing risk, and weighted composite endpoint (WCE) computing methods were applied to ULMCA patients revascularized by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) at 14 international centers., Results: At a median follow-up of 1,295 days (interquartile range: 928 to 1,713 days), all analyses showed no difference in combinations of death, myocardial infarction, and cerebrovascular accident between PCI and CABG. When target vessel revascularization was incorporated in the composite endpoint, the TTE (p = 0.03), Andersen-Gill (p = 0.04), WR (p = 0.025), and competing risk (p < 0.001) computing methods showed CABG to be significantly superior to PCI in the analysis of 1,204 propensity-matched patients, whereas incorporating the clinical relevance of the component endpoints using WCE resulted in marked attenuation of the treatment effect of CABG, with loss of significance for the difference between revascularization strategies (p = 0.10)., Conclusions: In a large study of ULMCA revascularization, incorporating the clinical relevance of the individual outcomes resulted in sensibly different findings as compared with the conventional TTE approach. In particular, using the WCE computing method, PCI and CABG were no longer significantly different with respect to the composite of death, myocardial infarction, cerebrovascular accident, or target vessel revascularization at a median of 3 years., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to evaluate the determinants and prognostic implications of periprocedural myocardial injury (PMI) in successful percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs)., Background: There are limited studies addressing the risk factors and clinical implication of PMI in patients undergoing CTO-PCI., Methods: We examined 1,058 consecutive CTO patients who underwent successful drug-eluting stent implantation and serial measurements of creatine kinase-myocardial band (CK-MB) values between March 2003 and August 2014. PMI was defined as elevations of CK-MB >3 times the upper reference limit (URL)., Results: PMI occurred in 121 patients (11.4%). Multivariable analysis revealed that the presence of renal failure (odds ratio [OR]: 4.25; 95% confidence interval [CI]: 1.59 to 11.35; p = 0.004), attempted retrograde approach (OR: 2.27; 95% CI: 1.34 to 3.84; p = 0.002), concomitant non-target lesion intervention (OR: 1.74; 95% CI: 1.17 to 2.59; p = 0.006), and stent number (OR: 1.38; 95% CI: 1.08 to 1.77; p = 0.011) were predictors associated with PMI. During a median follow-up of 4.4 years, PMI was associated with an increased risk of mortality (adjusted hazard ratio: 1.86; 95% CI: 1.09 to 3.17; p = 0.02). These findings were also consistent when higher CK-MB cutoff was used to define PMI. Although there was a trend toward higher all-cause mortality with increasing peak CK-MB levels, in multivariable analyses, this association was statistically significant only for peak CK-MB levels of >10 times the URL., Conclusions: PMI was associated with an increased risk of long-term mortality after successful CTO-PCI. Patients with renal insufficiency, those who require more stents, multiple lesion treatment, and retrograde approach have a higher likelihood of having PMI., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to evaluate the long-term prognostic value of coronary computed tomography angiography (CTA) in asymptomatic patients with type 2 diabetes mellitus., Background: There are limited data on the long-term prognostic impact of coronary CTA in asymptomatic patients with type 2 diabetes mellitus., Methods: This study analyzed clinical outcomes of 591 consecutive asymptomatic patients with type 2 diabetes mellitus who underwent coronary CTA (mean age 62.2 ± 8.3 years and 352 men [59.6%]). A cardiac event was defined as a composite of cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, or late coronary revascularization. Patients were categorized into 3 groups according to severity of coronary artery disease (CAD) on coronary CTA: normal coronary arteries, nonobstructive CAD (<50%), and obstructive CAD (≥50%)., Results: One hundred sixty-eight patients (28.4%) had normal coronary arteries, whereas 236 (39.9%) patients had nonobstructive CAD and 187 (31.6%) had obstructive CAD. During the follow-up period (median 5.3 years [interquartile range: 4.7 to 5.8 years]), 37 cardiac events occurred in 29 patents: 10 cardiac deaths, 2 nonfatal myocardial infarctions, 8 cases of unstable angina, and 17 late coronary revascularizations. The 6-year event-free survival rates were 99.3 ± 0.7% in patients with normal coronary arteries, 96.7 ± 1.2% in patients with nonobstructive CAD, and 86.2 ± 3.0% in patients with obstructive CAD (log-rank p < 0.001)., Conclusions: Asymptomatic patients with type 2 diabetes mellitus with normal coronary arteries or nonobstructive CAD on coronary CTA show excellent clinical outcomes over a follow-up period of more than 5 years, whereas prognosis is worse in patients with obstructive CAD. These findings suggest long-term prognostic value of coronary CTA for asymptomatic type 2 diabetes mellitus., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Aims: We aimed to determine whether finite element analysis (FEA)-derived plaque structural stress (PSS) analysis can predict serial changes in atheroma volume, type, and tissue composition within a fibroatheroma-containing target segment., Methods: Overall, 210 patients (210 untreated coronary artery lesions) underwent serial (baseline and 12-month follow-up) grayscale- and virtual histology (VH)-intravascular ultrasound (IVUS). Baseline PSS was assessed at the minimal lumen and at the maximum necrotic core (NC) sites., Results: Overall, there was a significant decrease in %NC volume. The highest PSS tertile was associated with a smaller on-statin reduction in %NC volume (-1.55 ± 1.03% in the highest vs. -5.18 ± 1.12% in the lowest tertile, p = 0.025). Of the 115 lesions with baseline VH-thin cap fibroatheroma (TCFA), 36 (31%) showed persistent VH-TCFA at follow-up. Five of the 95 lesions with baseline thick-cap fibroatheroma evolved into VH-TCFA. Independent predictors of VH-TCFA at follow-up (including persistent and new VH-TCFAs) were diabetes mellitus (odds ratio [OR] = 3.87, 95% CI = 1.58-9.47), a large MLA (OR = 1.39, 95% CI = 1.10-1.75), a greater percent atheroma volume (OR = 1.12, 95% CI = 1.05-1.19), VH-TCFA at baseline (OR = 8.01, 95% CI = 2.73-23.50), and a higher superficial PSS at the maximum NC site (OR = 1.02, 95% CI = 1.00-1.03), (all p < 0.05). Independent determinants of the serial change in %NC volume were high-sensitive C-reactive protein (β = -2.79, 95% CI = -5.31 to -0.27), baseline %NC volume (β = -0.70, 95% CI = -0.84 to -0.56), and superficial PSS at the maximum NC site (β = 0.05, 95% CI = 0.01-0.08), (all p < 0.05)., Conclusions: An elevated PSS was more likely associated with an increase in atheroma volume, a smaller on-statin reduction in %NC volumes, and the presence of VH-TCFA at follow-up. Morphologic and hemodynamic assessment by utilizing VH-IVUS may help understand and predict atherosclerotic progression., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)