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Background: There is a scarcity of data evaluating the effect of peripheral artery disease (PAD) on long-term mortality after percutaneous coronary intervention (PCI) relative to coronary artery bypass grafting (CABG) in patients with severe coronary artery disease in real-world practice., Methods: Among 14,867 consecutive patients who underwent their first coronary revascularization with PCI or isolated CABG between 2011 and 2013 in the CREDO-Kyoto PCI/CABG registry Cohort-3, the current study population consisted of 3380 patients with three-vessel coronary artery disease or left main coronary artery disease. Long-term clinical outcomes were compared between PCI and CABG stratified by the presence or absence of PAD. Median clinical follow-up was 5.9 (IQR: 5.1-6.8) years., Results: There were 461 patients with PAD (PCI: N = 307, CABG: N = 154), and 2919 patients without PAD (PCI: N = 1823, CABG: N = 1096). The cumulative 5-year mortality after coronary revascularization was 31.2 % in patients with PAD and 16.2 % in those without PAD (p < 0.0001). There was a higher risk of PCI relative to CABG for all-cause death in patients with and without PAD (adjusted HR, 1.59; 95%CI, 0.99-2.53; p = 0.054, and HR, 1.25; 95%CI, 1.01-1.56; p = 0.04) without interaction (p interaction p = 0.48); Nevertheless, there was no excess risk of PCI relative to CABG for cardiovascular death regardless of PAD., Conclusions: The long-term mortality after coronary revascularization was significantly higher in severe CAD patients with PAD than those without PAD. There was a higher mortality risk of PCI relative to CABG in patients with and without PAD without interaction, which was mainly driven by excess non-cardiovascular deaths., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The impact of very low baseline levels of low-density lipoprotein cholesterol (LDL-C) on patients with coronary artery disease remains unclear., Method: We enrolled 39,439 patients of the pooled population from the CREDO-Kyoto registries Cohorts 1, 2, and 3. The study population consisted of 33,133 patients who had undergone their first coronary revascularization. We assessed the risk for mortality and cardiovascular events according to quintiles of the baseline LDL-C levels., Results: Patients in the very low LDL-C quintile (<85 mg/dL) had more comorbidities than those in the other quintiles. Lower LDL-C levels were strongly associated with anemia, thrombocytopenia, and end-stage renal disease. The cumulative 4-year incidence of all-cause death increased as LDL-C levels decreased (very low: 19.4 %, low: 14.5 %, intermediate: 11.1 %, high: 10.0 %, and very high: 9.2 %; p < 0.001), which was driven by both the early and late events. After adjusting for baseline characteristics, the adjusted risks of the very low and low LDL-C quintiles relative to the intermediate LDL-C quintile remained significant for all-cause death (very low: HR 1.29, 95 % CI 1.16-1.44, p < 0.001; low: HR 1.15, 95 % CI 1.03-1.29, p = 0.01). The excess adjusted risks of the lowest LDL-C quintile relative to the intermediate LDL-C quintile were significant for clinical outcomes such as cardiovascular death (HR 1.17, 95 % CI 1.01-1.35), non-cardiovascular death (HR 1.35, 95 % CI 1.15-1.60), sudden death (HR 1.44, 95 % CI 1.01-2.06), and heart failure admission (HR 1.11 95 % CI 1.01-1.22), while there was no excess risk for the lowest LDL-C quintile relative to the intermediate LDL-C quintile for myocardial infarction and stroke., Conclusions: Lower baseline LDL-C levels were associated with more comorbidities and a significantly higher risk of death, regardless of cardiovascular or non-cardiovascular causes, in patients who underwent coronary revascularization., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Primary percutaneous coronary intervention (PCI) for ST-segment-elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS) may reduce the risk of subsequent cardiovascular events but remains challenging. The study aim was to evaluate the clinical characteristics and long-term outcomes of patients undergoing primary PCI for STEMI with CS., Methods: We conducted an observational cohort study of patients with STEMI who underwent primary PCI between April 2004 and December 2017 at Juntendo University Shizuoka Hospital. The primary outcome was cardiovascular death (CVD) during the median 3-year follow-up. We performed a landmark analysis for the incidence of CVD from 0 day to 1 year and from 1 to 10 years., Results: Among the 1758 STEMI patients in the cohort, 212 (12.1 %) patients with CS showed significantly higher 30-day CVD rate on admission than those without (26.4 % vs 2.9 %). Landmark Kaplan-Meier analysis showed that CVD from day 0 to year 1 was significantly higher in the patients with CS (log-rank p < 0.0001). Multivariate Cox regression analysis showed that CS was significantly associated with higher cardiovascular mortality (adjusted hazard ratio, 11.8; 95%confidence intervals, 7.78-18.1; p < 0.0001), but the mortality rates from 1 to 10 years were comparable (log-rank p = 0.68)., Conclusion: The cardiovascular 1-year mortality rate for patients with STEMI was higher for those with CS on admission than without, but the mortality rates of >1 year were comparable. Surviving the early phase is essential for patients with STEMI and CS to improve long-term outcomes., Competing Interests: Disclosures None. Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Standard modifiable cardiovascular risk factors (SMuRFs; hypertension, diabetes mellitus, dyslipidemia, and smoking) are widely recognized as risk factors for coronary artery disease. However, the associations between absence of SMuRFs and long-term clinical outcomes in ST-segment elevation myocardial infarction (STEMI) patients are unclear., Methods: Consecutive STEMI patients who underwent primary percutaneous coronary intervention (PCI) between 1999 and 2015 were retrospectively analyzed. The primary endpoint was up to 5-year all-cause mortality. Clinical characteristics and outcomes were compared between patients with at least one of the SMuRFs and those without any SMuRFs., Results: Of 1963 STEMI patients, 126 (6.4 %) did not have any SMuRFs. Patients without SMuRFs were significantly older, had lower body mass index, and were more likely to be female. During a median follow-up period of 4.9 years, the cumulative incidence of death was significantly higher in patients without SMuRFs than in those with SMuRFs (log-rank p < 0.0001). Landmark analysis showed that patients without SMuRFs had higher mortality within 30 days of STEMI onset (log-rank p = 0.0045) and >30 days after STEMI onset (log-rank p = 0.0004). Multivariable Cox hazards analysis showed that absence of SMuRFs was associated with a higher risk of mortality (hazard ratio, 1.59; 95 % confidence interval, 1.14-2.21; p = 0.006)., Conclusions: Of STEMI patients undergoing primary PCI, patients without any SMuRFs had higher mortality than those with at least one of the SMuRFs. Patients without any SMuRFs have a poor prognosis and require more attention., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: There was no study evaluating the effects of an aspirin-free strategy in patients undergoing complex percutaneous coronary intervention (PCI)., Objectives: The authors aimed to evaluate the efficacy and safety of an aspirin-free strategy in patients undergoing complex PCI., Methods: We conducted the prespecified subgroup analysis based on complex PCI in the STOPDAPT-3 (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3), which randomly compared low-dose prasugrel (3.75 mg/d) monotherapy to dual antiplatelet therapy (DAPT) with low-dose prasugrel and aspirin in patients with acute coronary syndrome or high bleeding risk. Complex PCI was defined as any of the following 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or a target of chronic total occlusion. The coprimary endpoints were major bleeding events (Bleeding Academic Research Consortium 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month., Results: Of the 5,966 study patients, there were 1,230 patients (20.6%) with complex PCI. Regardless of complex PCI, the effects of no aspirin relative to DAPT were not significant for the coprimary bleeding (complex PCI: 5.30% vs 3.70%; HR: 1.44; 95% CI: 0.84-2.47; P = 0.18 and noncomplex PCI: 4.26% vs 4.97%; HR: 0.85; 95% CI: 0.65-1.11; P = 0.24; P for interaction = 0.08) and cardiovascular (complex PCI: 5.78% vs 5.93%; HR: 0.98; 95% CI: 0.62-1.55; P = 0.92 and noncomplex PCI: 3.70% vs 3.10%; HR: 1.20; 95% CI: 0.88-1.63; P = 0.25; P for interaction = 0.48) endpoints without significant interactions., Conclusions: The effects of the aspirin-free strategy relative to standard DAPT for the cardiovascular and major bleeding events were not different regardless of complex PCI. (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3 [STOPDAPT-3]; NCT04609111)., Competing Interests: Funding Support and Author Disclosures This study was funded by Abbott Medical Japan. Dr Natsuaki has received honoraria from Abbott Medical Japan, Daiichi-Sankyo, Medtronic, Terumo, Japan Lifeline, Asahi Intecc, Bristol Myers Squibb, Otsuka, Amgen, Sanofi, Takeda, and Bayer. Dr Watanabe has received personal fees from Abbott Medical Japan during the conduct of the study as well as personal fees from Daiichi-Sankyo, Kowa, Abiomed, Bayer, Pfizer, Bristol Myers Squibb, and Otsuka outside the submitted work. Dr Morimoto has received lecturer fees from AstraZeneca, Bristol Myers Squibb, Daiichi-Sankyo, Japan Lifeline, Kowa, Pfizer, and Tsumura; has received manuscript fees from Bristol Myers Squibb and Pfizer; and has served on the Advisory Boards for Novartis and Teijin. Dr Suwa has received personal fees from Abbott Medical Japan and Daiichi-Sankyo outside the submitted work. Dr Kimura has received grants from Abbott Medical Japan and Boston Scientific; and has served on the Advisory Boards of Abbott Medical Japan and Terumo Japan. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Recent clinical trials have shown that percutaneous coronary intervention (PCI) for non-culprit lesions (NCLs) reduces the risk of adverse events in patients with ST-segment elevation myocardial infarction (STEMI), but the effect on long-term outcomes remains unclear in acute coronary syndrome (ACS) patients and a real-world clinical setting., Methods: A retrospective observational cohort study of ACS patients who underwent primary PCI between April 2004 and December 2017 at Juntendo University Shizuoka Hospital, Japan, was performed. The primary endpoint was the composite of cardiovascular disease death (CVD death) and non-fatal myocardial infarction (MI) during the mean follow-up period of 2.7 years, and a landmark analysis for the incidence of the primary endpoint from 31 days to 5 years between the multivessel PCI group and the culprit only PCI group was performed. Multivessel PCI was defined as PCI including non-infarct-related coronary arteries within 30 days after the onset of ACS., Results: Of the 1109 ACS patients with multivessel coronary artery disease of the current cohort, multivessel PCI was performed in 364 (33.2 %) patients. The incidence of the primary endpoint from 31 days to 5 years was significantly lower in the multivessel PCI group (4.0 % vs. 9.6 %, log-rank p = 0.0008). Multivariate Cox regression analysis showed that multivessel PCI was significantly associated with fewer cardiovascular events (HR 0.37, 95 % CI 0.19-0.67, p = 0.0008)., Conclusion: In ACS patients with multivessel coronary artery disease, multivessel PCI may reduce the risk of CVD death and non-fatal MI compared to culprit-lesion-only PCI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The impact of shorter door-to-balloon (DTB time on long-term outcomes in ST-segment elevation myocardial infarction (STEMI treated with primary percutaneous coronary intervention (PPCI has not been fully elucidated., Methods: We investigated 3283 consecutive patients with acute myocardial infarction selected from a prospective, nationwide, multicenter registry (J-MINUET database comprising 28 institutions in Japan between July 2012 and March 2014. Among the study population, we analyzed 1639 STEMI patients who had PPCI within 12 h of onset. Patients were stratified into four groups (DTB time < 45 min, 45-60 min, 61-90 min, >90 min. The primary endpoint was a composite of all-cause death, non-fatal MI, non-fatal stroke, cardiac failure, and urgent revascularization for unstable angina up to 3 years. We performed landmark analysis for incidence of the primary endpoint from 31 days to 3 years among the four groups., Results: The primary endpoint rate from 31 days to 3 years increased significantly and time-dependently with DTB time (10.2 % vs. 15.3 % vs. 16.2 % vs. 19.3 %, respectively; log-rank p = 0.0129. Higher logarithm-transformed DTB time was associated with greater risk of a primary endpoint from 31 days to 3 years, and the increased number of adverse long-term clinical outcomes persisted even after adjusting for other independent variables., Conclusion: Shorter DTB time was associated with better long-term clinical outcomes in STEMI patients treated with PPCI in contemporary clinical practice. Further efforts to shorten DTB time are recommended to improve long-term clinical outcomes in STEMI patients., Trial Registration: UMIN Unique trial Number: UMIN000010037., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Yukio Ozaki has received several research grants from Bayer Yakuhin, Ltd., Research Institute for Production Development, Daiichi-Sankyo Co., Ltd., and Dainippon Sumitomo Co., Ltd. Kazuo Kimura has received honoraria from AstraZeneca, Toa Eiyo Ltd., MSD K.K., Bayer Yakuhin, Ltd., and Daiichi-Sankyo Co., Ltd., and has received several research grants from MSD K.K., Daiichi-Sankyo Co., Ltd., Ono Pharmaceutical Co., Pfizer Japan Inc., Bayer Yakuhin Ltd., Takeda Pharmaceutical Co., Ltd., Boehringer Ingelheim Japan, Tanabe Mitsubishi, and Astellas Pharma Inc. Wataru Shimizu has received honoraria from Daiichi-Sankyo Co., Ltd., Boehringer Ingelheim Japan, Bayer Yakuhin Ltd., Bristol, and Ono Pharmaceutical Co., and has received several research grants from Daiichi-Sankyo Co., Ltd., Boehringer Ingelheim Japan, Ono Pharmaceutical Co., Otsuka Pharmaceutical Co., Eisai Co., Mitsubishi Tanabe Pharma Co., Asterllas Pharma Inc., and St Jude Medical. Yoshihiko Saito has received honoraria from Otsuka Pharmaceutical Co., Ltd., Kowa Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., and Novartis Pharma K.K., and has received several research grants from Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., Ono Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Eisai Co., Ltd., ZERIA Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Astellas Pharma Inc., Daiichi Sankyo Co., Ltd., and Boston Scientific Japan K.K. Toshiaki Mano has received a research grant from Abbot Vascular Japan. Kengo Tanabe has received honoraria from Abbot Vascular Japan, Mitsubishi Tanabe Pharma Co., and Daiichi Sankyo Co., Ltd. and has received several research grants from Kaneka and Terumo. Kenichi Tsujita has received honoraria from Amgen Astellas Bio Pharma K.K., Bayer Yakuhin, Ltd., Daiichi Sankyo Co., Ltd., MSD K.K., and Sanofi K.K., and has received several research grants from AstraZeneca K.K., Astellas Pharma Inc., Bayer Yakuhin, Ltd., Boehringer Ingelheim Japan, Boston Scientific Japan K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Kowa Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., MSD K.K., Pfizer Japan Inc., Sanofi K.K., Shionogi & Co., Ltd., and Takeda Pharmaceutical Co., Ltd. Masaharu Ishihara has received honoraria from Bayer Yakuhin Ltd., MSD K.K., Astra Zeneca, and Astellas Pharma Inc. and has received several research grants from Abbott Vascular Japan, Boston Scientific Japan K.K., Sanofi K.K., MSD K.K., Astellas Pharma Inc., Bayer Yakuhin Ltd., Pfizer, Daiichi Sankyo Co., Ltd., MID, and Goodman. No funders played any role in this study., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The type of atrial fibrillation (AF) (paroxysmal or non-paroxysmal) is important in determining its therapeutic management. However, the prognostic impact of AF type on the incidence of cardiovascular events remains uncertain., Methods: We investigated patients with AF who were selected from an observational, multicenter, prospective registry (RAFFINE) comprising 4 university hospitals and 50 general hospitals/clinics in Japan between 2013 and 2015. In this subanalysis study, patients were divided into two groups according to their AF pattern at the time of enrollment. The primary outcome was the composite of death, ischemic stroke, and heart-failure-related hospitalization., Results: Among 3845 patients, 1472 (38.3 %) and 2373 (61.7 %) had paroxysmal and non-paroxysmal type AF, respectively. Patients with non-paroxysmal AF were older and had higher CHADS 2 score and prevalence of comorbidities. During median follow-up of 3.7 years, 681 (17.7 %) primary endpoints were identified. Cumulative incidences of the primary endpoint were significantly higher in the non-paroxysmal AF group; however, rates of bleeding events were not significantly different between the groups. Multivariate Cox hazard analysis showed that non-paroxysmal AF had significantly higher risk of cardiovascular events compared with paroxysmal AF (hazard ratio, 1.38; 95 % confidence interval, 1.17-1.64; p = 0.0002)., Conclusions: Non-paroxysmal AF was significantly associated with cardiovascular events. Long-term clinical outcomes might be improved if transition from paroxysmal to non-paroxysmal AF can be prevented., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Diabetes was reported to be associated with an impaired response to clopidogrel., Objectives: The aim of this study was to evaluate the safety and efficacy of clopidogrel monotherapy after very short dual antiplatelet therapy (DAPT) in patients with diabetes undergoing percutaneous coronary intervention (PCI)., Methods: A subgroup analysis was conducted on the basis of diabetes in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2) Total Cohort (N = 5,997) (STOPDAPT-2, n = 3,009; STOPDAPT-2 ACS [Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 for the Patients With ACS], n = 2,988), which randomly compared 1-month DAPT followed by clopidogrel monotherapy with 12-month DAPT with aspirin and clopidogrel after cobalt-chromium everolimus-eluting stent implantation. The primary endpoint was a composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) or bleeding (TIMI [Thrombolysis In Myocardial Infarction] major or minor) endpoints at 1 year., Results: There were 2,030 patients with diabetes (33.8%) and 3967 patients without diabetes (66.2%). Regardless of diabetes, the risk of 1-month DAPT relative to 12-month DAPT was not significant for the primary endpoint (diabetes, 3.58% vs 4.12% [HR: 0.87; 95% CI: 0.56-1.37; P = 0.55]; nondiabetes, 2.46% vs 2.49% [HR: 0.99; 95% CI: 0.67-1.48; P = 0.97]; P interaction  = 0.67) and for the cardiovascular endpoint (diabetes, 3.28% vs 3.05% [HR: 1.10; 95% CI: 0.67-1.81; P = 0.70]; nondiabetes, 1.95% vs 1.43% [HR: 1.38; 95% CI: 0.85-2.25; P = 0.20]; P interaction  = 0.52), while it was lower for the bleeding endpoint (diabetes, 0.30% vs 1.50% [HR: 0.20; 95% CI: 0.06-0.68; P = 0.01]; nondiabetes, 0.61% vs 1.21% [HR: 0.51; 95% CI: 0.25-1.01; P = 0.054]; P interaction  = 0.19)., Conclusions: Clopidogrel monotherapy after 1-month DAPT compared with 12-month DAPT reduced major bleeding events without an increase in cardiovascular events regardless of diabetes, although the findings should be considered as hypothesis generating, especially in patients with acute coronary syndrome, because of the inconclusive result in the STOPDAPT-2 ACS trial. (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 [STOPDAPT-2], NCT02619760; Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 for the Patients With ACS [STOPDAPT-2 ACS], NCT03462498)., Competing Interests: Funding Support and Author Disclosures This work (STOPDAPT-2 and STOPDAPT-2 ACS) was supported by Abbott Vascular Japan. The study sponsor is not involved in the implementation of the study, data collection, event fixation and statistical analysis. However, approval of the study sponsor should be obtained for presentation in scientific meetings and submission of papers. Dr H. Watanabe has received honoraria from Abbott Medical, Abiomed, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Kowa, Pfizer, and Otsuka; and has received support for attending meetings from Abbott Medical. Dr Morimoto has received lecture fees from Bristol Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Kyocera, Novartis, and Toray; has received manuscript fees from Bristol Myers Squibb and Kowa; and has participated on an advisory board for Sanofi. Dr Natsuaki has received honoraria from Abbott Medical. Dr Ogita has received honoraria from Abbott Medical, Daiichi Sankyo, and Japan Lifeline. Dr Suwa has received honoraria from Abbott Medical and Daiichi Sankyo. Dr Kimura has received research grant support from Abbott Medical and Boston Scientific; has received honoraria from Abbott Medical, Boston Scientific, Daiichi Sankyo, Sanofi, and Terumo; and has participated on advisory boards for Abbott Medical, Boston Scientific, and Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Beta-blockers are associated with several clinical benefits in patients with reduced left ventricular ejection fraction (REF) after acute myocardial infarction (AMI), such as lower rates of mortality, recurrence of myocardial infarction, and heart failure. However, the long-term prognosis of beta-blockers has rarely been investigated in patients with non-REF after AMI. This study aimed to investigate the clinical benefits of beta-blockers in these patients., Methods: A total of 3281 consecutive patients who were hospitalized within 48 h after AMI were registered in the J-MINUET study. Patients who underwent primary percutaneous coronary intervention (PCI) and had a left ventricular ejection fraction ≥40 % were enrolled, and patients who died during admission were excluded. Included patients were divided into two groups according to the prescription of beta-blockers at discharge. Their characteristics and clinical outcomes were compared., Results: The number of AMI patients treated with beta-blockers was 1353 (70.4 %). Patients who received beta-blockers were younger and had a higher incidence of hypertension, dyslipidemia, and ST-segment elevation myocardial infarction than those who did not receive beta-blockers. The peak creatine kinase level after primary PCI was significantly higher in patients who received beta-blockers. These patients also had a lower incidence of a composite of all-cause death, myocardial infarction, and stroke compared to those that did not receive beta-blockers (7.3 % vs. 11.9 %, p = 0.001). Multivariate analysis showed that beta-blocker use was an independent factor for better clinical outcomes., Conclusions: The J-MINUET study revealed the clinical benefit of beta-blockers in AMI patients with non-REF after primary PCI., Competing Interests: Declaration of competing interest Yoshihiko Saito: grants from MEXT KAKENHI Grant Number JP19155855, grants from Health Labour Sciences Research Grant Number 19189094, grants from Health Labour Sciences Research Grant Number 17933459, grants from AMED under Grant Number JP19ek0210080, grants from AMED under Grant Number JP19ek0210118, grants from AMED under Grant Number JP19ek0210121, grants from AMED under Grant Number JP19ek0210115, grants from AMED under Grant Number JP19ek0109367, grants from AMED under Grant Number JP19ek0109406, grants from AMED under Grant Number JP19km0405009, during the conduct of the study; grants and personal fees from Otsuka Pharmaceutical Co., Ltd., grants and personal fees from Ono Pharmaceutical Co., Ltd., grants from Takeda Pharmaceutical Co., Ltd., grants and personal fees from Daiichi Sankyo Co., Ltd., grants and personal fees from Mitsubishi Tanabe Pharma Corporation, grants and personal fees from Bristol-Myers Squibb Company, grants from Actelion Pharmaceuticals Japan Ltd., grants from Kyowa Kirin Co., Ltd., grants and personal fees from Kowa Pharmaceutical Co., Ltd., grants from Shionogi & Co., Ltd., grants from Dainippon Sumitomo Pharma Co., Ltd., grants and personal fees from Teijin Pharma Ltd., grants from Chugai Pharmaceutical Co., Ltd., grants from Eli Lilly Japan K.K., grants from Nihon Medi-Physics Co., Ltd., grants, personal fees and other from Novartis Pharma K.K., grants and personal fees from Pfizer Japan Inc., grants from Fuji Yakuhin Co., Ltd., grants, personal fees and other from Bayer Yakuhin, Ltd., other from Amgen Astellas BioPharma K.K., other from Actelion Pharmaceuticals Japan Ltd., other from Roche Diagnostics K.K., personal fees from Alnylam Japan K.K., personal fees from AstraZeneca K.K., personal fees from Tsumura & Co., personal fees from Toa Eiyo Ltd., personal fees from Nippon Shinyaku Co., Ltd., personal fees from Nippon Boehringer Ingelheim Co., Ltd., personal fees from Mochida Pharmaceutical Co., Ltd. Kengo Tanabe: personal fees from Abbott Vascular, personal fees from Boston Scientific, personal fees from Medtronic, personal fees from Terumo, personal fees from Kaneka, from Japan Lifeline. Hisao Ogawa: personal fees from Towa Pharmaceutical Co., Ltd., personal fees from Bristol-Meyers Squibb Co., Ltd., personal fees from Pfizer Co., Ltd., personal fees from Toa Eiyo Co., Ltd., personal fees from Bayer Yakuhin Co., Ltd., personal fees from Novartis Pharma Co., Ltd. Masaharu Ishihara: grants from Abbott Vascular Japan Co., Ltd., grants and personal fees from Amgen Astellas Bio Pharma K.K., grants from Astellas Pharma Inc., grants and personal fees from Bayer Yakuhin, Ltd., grants from Boston Scientific Japan K.K., grants and personal fees from Daiichi Sankyo Company, Limited, grants from Fukuda Denshi Co., Ltd., grants from Goodman Co., LTD., grants from Japan Lifeline Co., Ltd., grants from Kowa Pharmaceutical Co., Ltd., grants from MID, Inc., grants from Mitsubishi Tanabe Pharma Corporation, grants and personal fees from MSD K.K., grants from Nippon Shinyaku Co., Ltd., grants from Nipro Corporation, grants from Otsuka Pharmaceutical Co., Ltd., grants from Ono Pharmaceutical Co., Ltd., grants from Pfizer Japan Inc., grants and personal fees from Sanofi K.K., grants from Shionogi & Co., Ltd., grants from Sumitomo Dainippon Pharma Co., Ltd., grants from Takeda pharmaceutical Co. Ltd., grants from Teijin Pharma Ltd., grants from Terumo Corporation, grants from Abbott Medical Japan Co., Ltd., grants from Medtronic Japan Co., Ltd., grants from Nippon Boehringer Ingelheim Co., Ltd., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Recent retrospective investigations have suggested that optical coherence tomography (OCT) enables the diagnosis of underlying acute coronary syndrome (ACS) causes such as plaque rupture, plaque erosion, and calcified nodule. The relationships of these etiologies with clinical outcomes, and the clinical utility of OCT-guided primary percutaneous coronary intervention (PCI) are not systematically studied in real-world ACS treatment settings., Methods: The TACTICS registry is an investigator-initiated, prospective, multicenter, observational study to be conducted at 21 hospitals in Japan. A total of 700 patients with ACS (symptom onset within 24 h) undergoing OCT-guided primary PCI will be enrolled. The primary endpoint of the study is to identify the underlying causes of ACS using OCT-defined morphological assessment of the culprit lesion. The key secondary clinical endpoints are hazard ratios of the composite of cardiovascular death, non-fatal myocardial infarction, heart failure, or ischemia-driven revascularization in patients with underlying etiologies at the 12- and 24-month follow-ups. The feasibility of OCT-guided primary PCI for ACS will be assessed by the achievement rates of optimal post-procedural results and safety endpoints., Conclusion: The TACTICS registry will provide an overview of the underlying causes of ACS using OCT, and will reveal any difference in clinical outcomes depending on the underlying causes. The registry will also inform on the feasibility of OCT-guided primary PCI for patients with ACS., Competing Interests: Declaration of competing interest Masahiko Ochiai, lecture fee – Abbott Medical Japan LLC., Asahi Intecc, Boston Scientific, and Terumo; Hiromasa Otake, lecture fee - Abbott Medical Japan LLC. and Terumo; Toshiro Shinke, personal fees and research grant - Abbot Japan LLC. The rest of the authors have none to disclose., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The management of non-valvular atrial fibrillation (AF) has evolved with the development of direct oral anticoagulants (DOACs). However, data regarding the effectiveness and safety of DOACs outside clinical trial settings are limited, and off-label dosing of DOACs has not been thoroughly investigated., Methods: We examined the clinical outcomes of patients with non-valvular AF in the RAFFINE registry, a prospective registry of Japanese patients with AF who were followed-up for more than 3 years., Results: Among 3706 patients with non-valvular AF, 42.5% received warfarin and 44.7% received DOACs at baseline. The administration of DOACs increased annually. The mean CHADS 2 and HAS-BLED scores were significantly higher in the warfarin group. The unadjusted all-cause mortality, cardiovascular mortality, and incidence of major bleeding events were higher in the warfarin group. The incidence of ischemic stroke/systemic embolism was not different between groups. After adjustment for baseline characteristics, the incidence of these events was not different between groups. Off-label dosing was performed for 32% of patients in the DOAC group, but this did not affect clinical outcomes., Conclusions: The all-cause mortality, cardiovascular mortality, and incidence of major bleeding events were higher in the warfarin group than in the DOAC group. After adjustment, warfarin use was not associated with an increase in these events. Off-label dosing of DOACs is not rare and is not associated with reduced effectiveness. The impact of off-label dosing of each DOAC on clinical events should be assessed using a larger population., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Percutaneous coronary intervention (PCI) is a standard treatment in patients with stable coronary artery disease (CAD); however, periprocedural myocardial infarction (PMI) remains a common complication of PCI. Aggressive lipid-lowering therapy with statin has shown to reduce the incidence of PMI by preventing coronary microvascular dysfunction. It is unclear whether evolocumab, a potent lipid-lowering agent, could diminish microvascular damage after PCI. The EVOCATION trial (jRCTs051180022) is a multicenter, randomized, open-label, active-controlled, parallel-group, exploratory, investigator-initiated clinical study to evaluate whether pretreatment with evolocumab could decrease the index of microvascular resistance (IMR) after PCI in patients with stable CAD. This study population consists of 100 patients with stable CAD who will undergo PCI and have high low-density lipoprotein cholesterol levels despite administration of maximum tolerated dose of statins for at least 2 weeks. Eligible patients are randomized in a 1:1 ratio to receive either evolocumab 140 mg every 2 weeks in addition to standard of care treatment or standard of care treatment only for 2-6 weeks before PCI. The primary endpoint is IMR after PCI. The EVOCATION trial will evaluate whether pretreatment with evolocumab reduces periprocedural microvascular damage in patients with stable CAD undergoing PCI., (Copyright © 2021. Published by Elsevier Ltd.)

Background: The prevalence of acute myocardial infarction (AMI) in elderly people is increasing worldwide. However, their characteristics and prognosis have been rarely investigated. This study aimed to investigate the characteristics and prognosis in elderly patients with cardiac troponin-positive AMI., Methods: Consecutive patients with AMI from the J-MINUET study were divided into the following 3 groups: patients aged less than 65 years, those aged between 65 and 79 years, and those aged 80 years or over. Their characteristics and in-hospital outcomes were compared., Results: Patients with AMI aged 80 years or over had the highest incidence of female gender, and the highest incidence of hypertension, chronic kidney disease, and cardiovascular disease, such as peripheral artery disease, atrial fibrillation, and stroke, whereas they had the lowest body mass index, and the lowest incidence of current smoker, diabetes mellitus, and dyslipidemia. Patients with AMI aged 80 years or over had significantly longer onset to door time and longer door to device time, and lower peak creatine kinase (CK). The incidence of ST-segment elevation myocardial infarction (STEMI) was the lowest in the AMI patients aged 80 years or over, but the patients had a higher incidence of in-hospital death and cardiac failure than the other two groups. In addition, the presentation with STEMI and non-ST-segment elevation myocardial infarction with CK elevation among patients aged 80 years or over showed the highest incidence of in-hospital death and cardiac failure., Conclusions: J-MINUET showed different clinical characteristics between the aged and younger populations. The incidence of in-hospital death and cardiac failure in patients aged 80 years or over with AMI was poorer than their younger counterparts., (Copyright © 2020. Published by Elsevier Ltd.)

Background: The European Society of Cardiology (ESC) recommends a 0-h/1-h (0/1-h) algorithm to classify patients with suspected non-ST-segment elevation myocardial infarction (NSTEMI). However, reliable evidence about patients who present early after the onset of symptoms is limited, likely because high-sensitivity cardiac troponin (hs-cTn) values cannot increase sufficiently within that time. This study aimed to evaluate the outcomes in real-world situations that utilized the 0/1-h algorithm., Methods: In a prospective, international, multicenter cohort study that enrolled 1638 patients presenting with acute chest pain to the emergency department, we assessed the performance of the 0/1-h algorithm using hs-cTnT and the associated 30-day rates of major adverse cardiac events: death and acute myocardial infarction (AMI)., Results: Among 1074 patients, the prevalence of AMI was 16.0%. An approximately 60.1% (n = 645) of patients visited the hospital within 3 h after onset of chest pain (less than 1 h; 18.2% [n = 196], less than 2 h; 27.5% [n = 295], and less than 3 h; 14.3% [n = 154]). Moreover, the prevalence rates of AMI were similar at all times (1 h, 16.8%; 1-2 h, 20.7%; 2-3 h, 18.2%; p = .5). According to the ESC 0/1-h algorithm, the distribution patterns of rule-out, observe, and rule-in groups were similar; however, none of the patients was diagnosed with AMI or cardiac death in the rule-out group., Conclusion: This study revealed the applicability of the 0/1-h algorithm for the management of early presenters., Competing Interests: Declaration of Competing Interest Dr. Inoue received a research grant from Grant-in-Aid for Scientific Research (C), Roche Diagnostics, SB Bioscience Co., Ltd., Fujirebio Inc., Bayel, and Kanto Chemical Co., Inc. Dr. Daida received a research grant from Public Health Research Foundation, Actelion Pharmaceuticals Japan, Otsuka Parmaceuticals Co., Ltd., Nihon Medi-physics Co., Ltd., Teijin Parma, HeartFlo Japan GK, Novo Nordisk, Sumitomo-Dainippon Co., Ltd., Fukuda Denshi, ResMed, and Philips Japan. The other authors report no relationships that could be construed as a conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Patients with peripheral artery disease (PAD) are at high risk of cardiovascular events, including myocardial infarction (MI), stroke, and cardiovascular death. However, the impact of PAD on prognosis in Japanese patients with acute MI remains unclear., Methods: The Japanese registry of acute Myocardial INfarction diagnosed by Universal dEfiniTion (J-MINUET) is a prospective multicenter registry that registered 3283 patients with acute MI. Among them, 2970 patients with available data of PAD were divided into the following 4 groups: 2513 patients without prior MI or PAD (None group), 320 patients with only prior MI (Prior MI group), 100 patients with only PAD (PAD group), and 37 patients with both previous MI and PAD (Both group). The primary endpoint was a composite of all-cause death, non-fatal MI, non-fatal stroke, cardiac failure, and urgent revascularization for unstable angina., Results: The 3-year cumulative incidence of the primary endpoint was 26.9% in None group, 41.4% in Prior MI group, 48.0% in PAD group, and 60.3% in Both group (p < 0.001). In multivariate analysis, hazard ratio using None group as reference was 1.55 (95% confidence intervals 1.25-1.91; p < 0.001) for MI group, 2.26 (1.61-3.07; p < 0.001) for PAD group, and 2.52 (1.52-3.90; p < 0.001) for Both group., Conclusions: Concomitant PAD was associated with poor prognosis in Japanese patients with acute MI., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: The use of serial intravascular ultrasound (IVUS) for coronary atherosclerosis has offered valuable insight into plaque regression (PR) or progression. However, the beneficial effects of PR on the long-term clinical outcomes in patients with acute coronary syndrome (ACS) remain unclear. We aimed to evaluate the impact of coronary plaque change in patients following primary percutaneous coronary intervention., Methods: We retrospectively analyzed data from 4 prospective clinical trials involving 173 patients with ACS who underwent serial IVUS of non-culprit lesions on statin treatment at baseline and at 6 or 8 months of follow-up. The relationship of the IVUS findings with the change in percent atheroma volume (PAV), on-treatment low-density lipoprotein cholesterol (LDL-C), and major adverse cardiac and cerebrovascular events (MACCE) were investigated., Results: In our serial IVUS analysis, baseline plaque volume and PAV were 79.6mm 3 and 46.0%, respectively. The overall change in PAV was -1.5% [interquartile range (IQR): -4.1% to 1.0%], and PR (i.e. PAV change from baseline <0) was observed in 67.1% of patients. They were followed up observationally for a mean of 3.5 years and a total of 37 MACCE occurred. The rate of MACCE tended to be lower in patients with PR than in those without PR (18.1% vs. 28.7%, p=0.14). A multivariate Cox hazard model analysis demonstrated that achievement of both PR and on-treatment low LDL-C levels (<70mg/dL) was the only significant independent predictor of MACCE (hazard ratio: 0.42, 95% confidence interval: 0.19-0.88; p=0.02)., Conclusions: Achievement of both PR and sufficient lowering of the LDL-C was clinically important in post-ACS management., (Copyright © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Suvorexant, an orexin receptor antagonist, is known as a safe and effective sleep medication. Many patients with heart failure (HF) have sleep-disordered breathing (SDB) and are short sleepers, and it is unknown whether suvorexant is effective in HF patients and can improve insomnia safely. The aim of this study is to examine the effect of suvorexant on SDB in patients with HF., Methods: The Heart Failure with Insomnia and Suvorexant trial of Juntendo University Hospital and Juntendo Shizuoka Hospital (J-FLAVOR trial) is a multicenter trial with a randomized double crossover design. We will enroll a total of 30 HF patients treated in the Juntendo University Hospital and Juntendo Shizuoka Hospital. Eligible patients will undergo portable sleep monitoring twice with or without oral administration of suvorexant in a randomly assigned order. Before the study night, patients in the suvorexant first group will receive suvorexant for 4 consecutive days. There are at least 3 wash-out days between the study nights with and without suvorexant. Primary outcome measures of the non-inferiority trial of suvorexant include the apnea-hypopnea index and the severity of SDB, and the results will be compared between the study nights with and without suvorexant., Conclusion: The present study can determine whether suvorexant can be used in HF patients without affecting their SDB. This is a pilot study to primarily assess whether suvorexant affects the severity of SDB in patients with HF. Therefore, further study is warranted to investigate whether suvorexant alters short- and long-term clinical outcomes by providing longer and better sleep in patients with HF., (Copyright © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to compare 7-year outcomes between the first-generation sirolimus-eluting stent (SES) and the new-generation everolimus-eluting stent (EES) in a randomized clinical trial., Background: There is a scarcity of very long-term (beyond 5 years) data from clinical trials investigating whether new-generation drug-eluting stents have clear clinical advantages over first-generation drug-eluting stents., Methods: RESET (Randomized Evaluation of Sirolimus-Eluting Versus Everolimus-Eluting Stent Trial) is the largest randomized trial comparing EES with SES (NCT01035450). Among a total of 3,197 patients in the original RESET population from 100 centers, the present extended 7-year follow-up study was conducted in 2,667 patients from 75 centers after excluding those patients enrolled from centers that denied participation. Complete 7-year follow-up was achieved in 91.5% of patients., Results: The cumulative 7-year incidence of the primary efficacy endpoint of target lesion revascularization was not significantly different between EES and SES (10.2% vs. 11.7%; hazard ratio: 0.87; 95% confidence interval: 0.68 to 1.10; p = 0.24). The risk for the primary safety endpoint of death or myocardial infarction trended lower with EES than with SES (20.6% vs. 23.6%; hazard ratio: 0.85; 95% confidence interval: 0.72 to 1.005; p = 0.06). The cumulative 7-year incidence of definite stent thrombosis was very low and similar between EES and SES (0.9% vs. 1.0%; p = 0.82). The lower risk of EES relative to SES was significant for the composite secondary endpoint of target lesion failure (13.3% vs. 18.1%; hazard ratio: 0.72; 95% confidence interval: 0.59 to 0.88; p = 0.001)., Conclusions: During 7 years of follow-up, the risk for target lesion revascularization was not significantly different between the new-generation EES and the first-generation SES., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: C-reactive protein (CRP) is an established marker for vascular inflammation and predictor of adverse cardiovascular events, but the prognostic value of preprocedural CRP in coronary artery disease (CAD) patients who have undergone percutaneous coronary intervention (PCI) remains controversial. Furthermore, the impact of CRP levels during follow-up in CAD patients after PCI on long-term adverse clinical outcomes is uncertain. We evaluated the association between high-sensitivity (hs)-CRP values at follow-up angiography and long-term clinical outcomes in CAD patients after coronary intervention., Methods: We prospectively enrolled 3507 consecutive CAD patients who underwent first PCI between 1997 and 2011 at our institution. We identified 2509 patients (71.5%) who underwent follow-up angiography (6-8 months after PCI). Of those, 1605 patients (45.8%) who had data available for hs-CRP at follow-up angiography were stratified into three groups according to tertiles of hs-CRP level at the time of follow-up angiography. The primary endpoint was composite of all-cause death and non-fatal acute coronary syndrome (ACS)., Results: Median follow-up was 1716 days. The cumulative incidence of all-cause death and ACS differed significantly among groups (log-rank, p=0.0002). Multivariate Cox regression analysis showed that a higher hs-CRP level at follow-up angiography was associated with a greater risk of all-cause death and ACS [adjusted hazard ratio (HR) for all-cause death and ACS 2.14, 95% confidence interval (CI) 1.43-3.27, p=0.0002., Conclusion: Elevated hs-CRP levels during follow-up were significantly associated with higher frequencies of adverse long-term clinical outcomes in patients with CAD after PCI., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Although an elevated mean platelet volume (MPV) has been associated with poor clinical outcomes after acute coronary syndrome (ACS), the association between MPV and long-term outcomes in patients with stable coronary artery disease (CAD) remains uncertain. We aimed to investigate the impact of pre-procedural MPV levels in patients following elective percutaneous coronary intervention (PCI)., Methods: We studied 2872 stable CAD patients who underwent their first PCI and who had available data on pre-procedural MPV between 2002 and 2016. Patients were divided into quartiles based on their MPV. The incidences of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction, were evaluated., Results: The median MPV was 10.4 fL (interquartile range: 9.8-11.0). During a median follow-up of 5.6 years, 498 (17.3%) MACE were identified, with a cumulative incidence significantly higher in the lowest MPV group than in other groups (p < 0.01). After adjustment for platelet count and the other cardiovascular risk factors, the lowest MPV group had a significantly higher risk of MACE compared with the highest MPV groups (hazard ratio: 1.43, 95% confidence interval 1.10-1.86, p = 0.009). Decreasing MPV as a continuous variable was associated with the incidence of MACE (hazard ratio: 1.16 per 1 fL decrease, 95% confidence interval 1.04-1.30, p = 0.007)., Conclusions: Contrary to previous studies on ACS patients, this study showed that a low MPV was associated with worse clinical outcomes among stable CAD patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Malnutrition has recently been reported to correlate with prognosis in patients with heart failure. However, the prognostic significance of nutritional status in patients with stable coronary artery disease (CAD) is unknown. The present study sought to examine the association between nutritional status assessed by the prognostic nutritional index (PNI) and cardiovascular outcomes in patients with stable CAD., Methods: A total of 1988 patients with stable CAD who underwent elective percutaneous coronary intervention (PCI) between 2000 and 2011 were examined. The PNI was calculated as 10×serum albumin (g/dL)+0.005×total lymphocyte count (per mm 3 ). Patients were assigned to tertiles based on their PNI. The incidence of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction, was evaluated., Results: The median PNI was 48.9 (interquartile range: 45.5-52.1). During the median follow-up of 7.5 years, Kaplan-Meier analysis showed that patients with lower PNI tertiles had higher rates of MACE (PNI <46.7: 35.5%; 46.7-50.8: 22.3%; >50.8: 16.0%; log-rank p<0.0001). After adjusting for other risk factors, the PNI was independently associated with MACE (hazard ratio 2.05 per 10 PNI decrease, 95% confidence interval: 1.66-2.54, p<0.0001). Adding the PNI to a baseline model with established risk factors improved the C-index (p=0.03), net reclassification improvement (p=0.03), and integrated discrimination improvement (p=0.0001)., Conclusions: The PNI was significantly associated with long-term cardiovascular outcomes in patients with stable CAD. Assessing PNI may be useful for risk stratification of CAD patients undergoing elective PCI., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: The management of atrial fibrillation (AF) has evolved with the development of direct oral anticoagulants (DOACs), but data on their clinical effectiveness and safety outside clinical trial settings are limited., Method: The RAFFINE registry is an observational, multicenter, prospective registry of Japanese patients with AF, designed to follow clinical events over 3 years. Patient enrollment was conducted from 2013 to 2015 at university hospitals, general hospitals, and private clinics to ensure inclusion of a broad spectrum of representative AF patients. The primary outcome events in this study will be ischemic stroke, systemic embolism, and major bleeding., Result: We enrolled 3901 ambulatory patients with AF from 4 university hospitals and 50 general hospitals/clinics in Japan. The mean patient age was 72.6 years and 68.5% were male. The type of AF was paroxysmal in 37.8%, persistent in 9.3%, and permanent in 51.7%. Major coexisting diseases were hypertension (72.7%), diabetes mellitus (30.3%), congestive heart failure (23.8%), history of ischemic stroke or transient ischemic attack (15.1%), and coronary artery disease (13.7%). Of the entire cohort, 44.6% were treated with warfarin and 43.0% were treated with DOACs. The prescription of DOACs exceeded that of warfarin in the general hospitals and clinics. Risk scores such as CHADS 2 score, CHA 2 DS 2 -VASc score, and HAS-BLED score were higher in patients at university hospitals than in patients at general hospitals or clinics., Conclusion: The RAFFINE registry at baseline described the current status of anticoagulation therapy in Japan and long-term follow-up data will identify how outcomes vary between stratified groups in patients with AF in the DOAC era (UMIN Clinical Trials Registry UMIN000009617)., (Copyright © 2018. Published by Elsevier Ltd.)

Background: A rapid rule-out or rule-in protocol based on the 0-hour/1-hour algorithm using high-sensitivity cardiac troponin T is recommended by the European Society of Cardiology. However, Asian data are not available., Methods: This prospective cohort study included 413 patients with suspected non-ST elevation myocardial infarction in 3 hospitals in Japan and Taiwan from November 2014 to April 2017. Patients were divided into 3groups-rule-out, observe, and rule-in-according to the algorithm. Major adverse cardiovascular events were evaluated at the 30-dayfollow-up., Results: The algorithm ruled out acute myocardial infarction (AMI) in 171 patients with a negative predictive value and sensitivity of 100% (95% confidential interval [CI], 96.8%-100%) and 100% (95% CI, 88.0%-100%), respectively, in the rule-out group. None of the patients were diagnosed with AMI. Among the 127 patients classified into the rule-in group, 47 were diagnosed as having AMI. The positive predictive value and specificity were 33.1% (95% CI, 25.1%-41.9%) and 66.3% (95% CI, 60.2%-72.0%), respectively. Elective catheter intervention was required in 13 patients (5 in the rule-out group, 8 in the observe group) by the 30-dayfollow-up. The Framingham Risk Score (FRS) identified moderate risk in 5 patients and high risk in 8, while the Global Registry of Acute Coronary Events (GRACE) 2.0 risk score identified low risk in 6 patients and moderate risk in 7., Conclusion: The ESC0-hour/1-hour algorithm could be sufficient in Asian patients. The combination with FRS may be more precise than that with the GRACE 2.0 risk score., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Background: The association between patients with acute myocardial infarction (AMI) who present during off-hours and clinical outcomes has not been fully elucidated., Methods: We investigated 3283 consecutive patients with AMI who were selected from a prospective, nationwide, multicenter registry (J-MINUET) database comprising 28 institutions in Japan between July 2012 and March 2014 to determine the current impact of off-hours presentation on in-hospital mortality among Japanese patients with AMI., Results: Among the patients, 52% presented in off-hours. Baseline characteristics were comparable, although those who presented during off-hours were younger and had a higher incidence of ST-elevation myocardial infarction and advanced Killip Class. The time from symptom onset to presentation time was shorter in off-hour patients (120min, interquartile range 60 to 256 vs. 215min, interquartile range 90 to 610, p<0.0001). In contrast, 85% of patients underwent primary percutaneous coronary intervention (PCI) and door to balloon time was comparable between the groups (74min, interquartile range 52 to 113 vs. 75min, interquartile range 52 to 126, p=0.34). The rates of in-hospital mortality were comparable (6.2% vs 6.8%, p=0.39). Multivariate logistic regression analysis revealed that off-hours presentation was not significantly associated with in-hospital mortality [odds ratio (OR) 0.94; 95% CI, 0.68-1.30, p=0.70]., Conclusion: The clinical impact of presenting during off-hours or regular hours on AMI patients in Japan is comparable in contemporary practice., Trial Registration: UMIN Unique trial Number: UMIN000010037., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: An elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with worse clinical outcomes in patients with acute coronary syndrome. However, the long-term prognostic value of NLR in stable coronary artery disease (CAD) after percutaneous coronary intervention (PCI) has not been fully investigated. The aim of this study was to determine whether NLR is an independent predictor of long-term cardiac outcomes after PCI., Methods: A total of 2070 patients with CAD who underwent elective PCI were enrolled in the study. Patients were divided into three groups by NLR tertile (<1.7, 1.7-2.5, and 2.5<). Incidences of all-cause death and cardiac death were evaluated., Results: During follow-up (median, 7.4 years), 300 patients (14.5%) died. Kaplan-Meier curves revealed ongoing divergence in rates of all-cause death and cardiac death among tertiles (both log-rank p < 0.01). In multivariate analysis, using the lowest tertile as reference, the highest tertile remained significantly associated with greater incidences of all-cause death (hazard ratio (HR), 1.73; 95% confidence interval (CI), 1.29-2.34; p = 0.0002). Continuous NLR values were also an independent predictor of all-cause death (HR, 1.87 per log NLR 1 increase; 95% CI, 1.50-2.32; p < 0.0001) and cardiac death (HR, 2.11; 95% CI, 1.46-3.05; p < 0.0001). Adding NLR values to a baseline model with established risk factors improved the C-index (p = 0.002), net reclassification improvement (p = 0.008) and integrated discrimination improvement (p = 0.0001) for all-cause death., Conclusions: Elevated NLR was an independent predictor of long-term cardiovascular outcomes after elective PCI. Assessing pre-PCI NLR may be useful for risk stratification of stable CAD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Limited data exist regarding the association between symptom presentation of acute myocardial infarction (AMI) and in-hospital outcomes., Methods: We analyzed data of the Japanese registry of acute Myocardial INfarction diagnosed by Universal dEfiniTion (J-MINUET). This was a prospective and multicenter registry consisting of 3085 AMI patients with available data of symptoms, who were hospitalized within 48h from onset during July 2012 to March 2014. We defined typical symptoms as any of chest pain or pressure due to myocardial ischemia., Results: Of this study population, 642 patients (20.8%) had atypical symptoms (atypical group) and the remaining 2443 patients (79.2%) showed typical symptoms (typical group). Compared to the typical group, the atypical group was associated with higher age, more females, hypertension, diabetes, chronic kidney disease, history of cardiovascular disease, non-ST elevation MI, and Killip class ≥2. In the atypical group, urgent percutaneous coronary intervention was less frequently performed than in the typical group, and in STEMI patients door-to-balloon time was longer in the atypical than typical group. Atypical group had larger infarct size than typical group. Furthermore, in-hospital mortality was significantly higher in atypical than in typical group (19.5% vs. 3.3%, p<0.001). In multivariable analysis, presence of atypical symptoms was an independent predictor of in-hospital mortality (odds ratio 3.12, 95% confidence interval 2.19 to 4.47, p<0.001). Moreover, the association between atypical symptoms and mortality was consistent across each subgroup., Conclusions: Atypical symptoms of AMI were associated with less invasive therapy and poor outcome. Attention should be directed to these high-risk patients., (Copyright © 2016. Published by Elsevier Ltd.)

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors have anti-atherosclerotic and cardioprotective effects in vitro. However, the impact of DPP-4 inhibitors on coronary plaque remains unclear. We sought to assess the effect of sitagliptin on coronary plaque volume (PV) and stabilization in diabetic patients with acute coronary syndrome (ACS)., Methods: The ESPECIAL-ACS was a prospective, randomized, open-label, parallel group study at 4 Japanese centers to assess the effect of 6-month treatment with sitagliptin on coronary plaque changes in non-culprit lesion in diabetic patients with ACS using serial intravascular ultrasound (IVUS) and integrated backscatter IVUS (IB-IVUS) analysis., Results: A total of 41 patients were randomly allocated to either sitagliptin group (diet and exercise with sitagliptin 50-100mg daily, n=21) or control group (diet and exercise, n=20) within 72h after percutaneous coronary intervention, and underwent volumetric IVUS and IB-IVUS analyses at baseline and 6-month follow-up. At 6-month follow-up, the percent change in PV as primary endpoint was larger in the sitagliptin group than in the control group, but the difference was not statistically significant (-4.0±8.5% vs. -1.4±8.8%, p=0.35). In IB-IVUS analysis, the percent change in lipid PV significantly decreased in the sitagliptin group compared with the control group (-7.1±21.5% vs. 15.6±41.8%, p=0.03)., Conclusions: Compared with diet and exercise therapy, sitagliptin did not significantly reduce coronary PV in diabetic patients with ACS at 6-month follow-up. However, the percent change in lipid PV significantly decreased in the sitagliptin group, suggesting that sitagliptin has a potential to stabilize the plaque vulnerability., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Risk scores and cardiac biomarker tests allow clinicians to accurately diagnose acute coronary syndrome (ACS) and perform early risk stratification. However, few investigations have evaluated the use of these risk scores and biomarkers for predicting risk of cardiovascular events in drug-eluting stent (DES) era., Methods: This prospective cohort study included 861 patients with ACS. Three risk scores-Global Registry of Acute Coronary Events (GRACEs), Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin, and Thrombolysis In Myocardial Infarction-and levels of four biomarkers-N-terminal pro-B-type natriuretic peptide (NT pro-BNP), high-sensitivity troponin T, heart-fatty acid binding protein, and high-sensitivity C-reactive protein-were recorded on admission. Major adverse cardiac events (MACE) (death, cardiovascular events) were evaluated at 30-day and 1-year follow-up., Results: At 30-day follow-up, there were 23 (3.1%) deaths from cardiovascular events and 4 (0.5%) cerebral accidents. NT pro-BNP levels and GRACE score were strong MACE predictors, with adjusted odds ratios (ORs) (95% CI) of 2.90 (1.63-5.20) and 1.01 (1.00-1.02), respectively, in logistic model. The C-statistic of NT pro-BNP (0.77; 95% CI, 0.67-0.86) was similar to that of GRACE score (0.76; 95% CI, 0.66-0.87); however, the combined C-statistic was higher (0.81), yielding a net reclassification improvement of 13% (p<0.01). At 1-year follow-up, there were 51 (6.8%) deaths and 10 (1.3%) cerebral accidents., Conclusion: In the DES era, GRACE score and biomarkers can still predict major cardiac events in patients with ACS for both acute and long-term prognoses., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Three-year clinical follow-up of patients with diabetes mellitus (DM) in the Japan-Drug Eluting Stents Evaluation; a Randomized Trial (J-DESsERT) using 2 different drug eluting stents (DES). A recent study demonstrated that efficacy of sirolimus eluting stents (SES) attenuated over time in diabetic patients., Methods: In the largest trial of its kind, 1724 DM patients out of 3533 enrolled patients were randomized to either SES or paclitaxel eluting stents (PES)., Results: There were no significant differences in baseline clinical characteristics aside from hypertension. Incidence of major adverse cardiac cerebrovascular events (MACCE) mainly due to higher target vessel failure (TVF) initially indicated a benefit in SES (MACCE rate at 1 year: SES 9.4%, PES 12.2%, p=0.08); however this had attenuated by the time of the 3-year follow-up (MACCE rate from 1 to 3 years: SES 8.4%, PES 6.1%, p=0.10). A similar pattern was observed in insulin-treated patients: MACCE rate from 1 to 3 years was 10.5% in SES and 6.4% in PES (p=0.25). Angiographic follow-up also resulted in higher major adverse cardiac event (MACE) rates at 1 year (presence 11.5%, absence 8.3%, p=0.04); however by 3 years rates were similar regardless of the presence of angiographic follow-up (MACE rate at 3 years: presence 16.0%, absence 14.5%, p=0.35)., Conclusions: The superiority of SES over PES in MACCE at 1 year had attenuated by 3-year follow-up. Eventually, the 3-year safety and efficacy profiles were similar regardless of insulin treatment., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: LR11, a member of LDL receptor family, is a novel marker of the proliferation of intimal smooth muscle cells (SMCs). LR11 is released in soluble form (sLR11) by proteolytic shedding and has biological activity toward SMC migration. We previously showed that circulating sLR11 positively correlates with carotid intima-medial thickness (IMT) independently of classical atherosclerotic risk factors and that it significantly associates with the severity of CAD. However, the association between sLR11 and long-term clinical outcomes remain uncertain., Methods and Results: This study included 438 consecutive patients (mean age, 65.8 ± 9.6 y; male, 82.4%) who underwent coronary intervention between March 2003 and December 2004 at our institution. The patients were assigned to quartiles according to pre-procedural sLR11 values. The primary endpoints were composite cardiovascular disease (CVD) endpoints including cardiovascular death, non-fatal acute coronary syndrome and non-fatal stroke. During median follow-up of 2876 days, composite CVD endpoints occurred 97 (22.1%) patients including 41 (9.4%) with cardiovascular disease (CVD)-related death, 36 (8.2%) non-fatal ACS and 20 (4.6%) non-fatal strokes. The hazard ratio (HR) for composite CVD endpoints significantly and dose-dependently increased with sLR11 levels (p for trend = 0.0077). A higher logarithm-transformed sLR11 value was associated with a greater risk of composite CVD endpoints, and the increased number of adverse long-term clinical outcomes persisted even after adjustment for other independent variables (HR 1.87 95%CI 1.02-3.31, p = 0.0435)., Conclusions: Elevated sLR11 levels were significantly associated with higher long-term adverse cardiac events in patients with CAD. Further extensive studies are expected to elucidate the mechanistic role of sLR11 and its clinical value as a prognostic marker in the development of atherosclerosis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)