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Background: Multi-parametric assessment, including heart sounds in addition to conventional parameters, may enhance the efficacy of noninvasive telemonitoring for heart failure (HF). We sought to assess the feasibility of self-telemonitoring with multiple devices including a handheld heart sound recorder and its association with clinical events in patients with HF., Methods: Ambulatory HF patients recorded their own heart sounds, mono‑lead electrocardiograms, oxygen saturation, body weight, and vital signs using multiple devices every morning for six months., Results: In the 77 patients enrolled (63 ± 13 years old, 84 % male), daily measurements were feasible with a self-measurement rate of >70 % of days in 75 % of patients. Younger age and higher Minnesota Living with Heart Failure Questionnaire scores were independently associated with lower adherence (p = 0.002 and 0.027, respectively). A usability questionnaire showed that 87 % of patients felt self-telemonitoring was helpful, and 96 % could use the devices without routine cohabitant support. Six patients experienced ten HF events of re-hospitalization and/or unplanned hospital visits due to HF. In patients who experienced HF events, a significant increase in heart rate and diastolic blood pressure and a decrease in the time interval from Q wave onset to the second heart sound were observed 7 days before the events compared with those without HF events., Conclusions: Self-telemonitoring with multiple devices including a handheld heart sound recorder was feasible even in elderly patients with HF. This intervention may confer a sense of relief to patients and enable monitoring of physiological parameters that could be valuable in detecting the deterioration of HF., Competing Interests: Declaration of competing interest NK, TK, and HD are affiliated with a department endowed by Philips, Fukuda Denshi, KYOCERA, InterReha, and AMI Inc. based on collaborative research. NK receives an honorarium from Novartis Japan and research grants from AMI Inc. and EchoNous Inc. outside this work. NY and NM are employees of Asahi Kasei Corporation. TY is an employee of Philips Japan. KI has received research grant from Roche Diagnostics, SB Bioscience Co., Ltd., Fujirebio Inc., Bayel Sysmex, and Kanto Chemical Co. Inc. outside this work. YM received honoraria from Otsuka Pharmaceutical Co., Novartis Pharma K.K., Bayer Inc., and AstraZeneca and research grants from Pfizer Japan Inc., Otsuka Pharmaceutical Co., EN Otsuka Pharmaceutical Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The importance of health literacy in medical imaging is well recognized, yet the current landscape remains inadequately understood. This study aims to explore the extent of health literacy studies contextualized to medical imaging., Study Design: Scoping review., Methods: A scoping review was conducted using three online bibliographic databases namely, PubMed, ScienceDirect, and CINAHL. We have adopted the concept of health literacy, as a clinical risk and personal asset, to guide this review., Results: Of 311 unique articles, 39 met our selection criteria. Five themes (categories) were identified by the authors: appropriate communication with patients who receive medical imaging test results, appropriate usage of medical imaging, classes and characteristics of eHealth literacy, disease/deterioration prevention, and patient education. Additionally, 17 health literacy assessment tools were identified, including 11 original creations. Finally, 11 recommendations have emerged from this scoping review, offering valuable insights into methods, considerations, and strategies for promoting health literacy., Conclusions: Health literacy studies in medical imaging cover both clinical and public health perspectives, benefiting diverse populations, regardless of underlying medical conditions. Notably, the majority of assessment tools used in these studies were author-generated, hindering cross-study comparisons. Given the innate capacity of medical images to convey intuitive information, those images do not solely benefit the patients who are given medical imaging examinations, but they also hold significant potential to enhance public health literacy. Health literacy and medical imaging are closely associated and mutually reinforce each other., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: The purpose of this study was to examine the relationship between responsiveness to prehabilitation and postoperative recovery of physical function in cardiac surgery patients., Methods: Ninety-three cardiac surgery patients (mean age: 76.4 years) were included in this retrospective cohort study. Preoperative physical function was measured using the Short Physical Performance Battery (SPPB), and a prehabilitation exercise program was implemented for the SPPB domains with low scores. Among the patients, those whose SPPB score was over 11 from the start of prehabilitation and remained over 11 on the day before surgery were defined as the high-functioning group, and those whose SPPB score improved by 2 points or more from the start of prehabilitation and exceeded 11 points were defined as the responder group. Those whose SPPB score did not exceed 11 immediately before surgery were classified as non-responders. The characteristics of each group and postoperative recovery of physical function were investigated., Results: There were no serious adverse events during prehabilitation. Mean days of prehabilitation was 5.4 days. The responder group showed faster improvement in postoperative physical function and shorter time to ambulatory independence than the non-responder group. The non-responder group had lower preoperative skeletal muscle index, more severe preoperative New York Heart Association classification, and a history of musculoskeletal disease or stroke., Conclusion: There were responders and non-responders to prehabilitation among cardiac surgery patients. Cardiac surgery patients who respond to prehabilitation had faster recovery of physical function. Further research is needed to determine what type of prehabilitation is more effective in postoperative recovery of physical function in cardiac surgery patients., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Aims: Previous studies have not found a consistent association between circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and the risk of cardiovascular events partly due to measurement methods that cannot distinguish between uncleaved and furin-cleaved forms of PCSK9., Methods: This is a prespecified sub-study of the REAL-CAD study which is a prospective, multicenter, randomized trial to compare high- versus low-dose statin in patients with stable coronary artery disease (CAD). The primary endpoint was major adverse cerebrovascular and cardiovascular events (MACCE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. In this case-cohort study, serum mature (uncleaved) and furin-cleaved PCSK9 levels obtained at 6 months after randomization were measured among 426 participants who developed MACCE (cases) and 1,478 randomly selected participants (sub-cohort)., Results: From 1,478 patients in sub-cohort, the Cox proportional hazards models with a pseudolikelihood method for case-cohort design revealed that the risk of the primary endpoint in patients with the highest quartile of mature PCSK9 levels was similar to that in the lowest quartile (hazard ration [HR] 0.809; 95% confidence intervals [CI], 0.541-1.209). Similarly, the HR for the highest to lowest quartiles of furin-cleaved PCSK9 was 0.948 [95% CI, 0.645-1.392] (P = 0.784). Compared to the lowest quartile, neither serum mature nor furin-cleaved PCSK9 levels predicted MACCE., Conclusions: In a large-scale secondary prevention cohort, serum mature and furin-cleaved PCSK9 levels did not provide useful information for predicting future cardiovascular events in statin-treated patients with stable CAD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kiyoshi Hibi reports financial support was provided by the Public Health Research Foundation. Kiyoshi Hibi reports financial support was provided by Kowa. Kiyoshi Hibi reports a relationship with Abbott Medical that includes: speaking and lecture fees. Kiyoshi Hibi reports a relationship with Daiichi Sankyo that includes: speaking and lecture fees. Kiyoshi Hibi reports a relationship with Medtronic that includes: speaking and lecture fees. Kiyoshi Hibi reports a relationship with the Research Institute for Production Development that includes: funding grants. Kiyoshi Hibi reports a relationship with Japan Medical Device Corporation that includes: funding grants. Kiyoshi Hibi reports a relationship with Abbott Medical that includes: funding grants. Kiyoshi Hibi reports a relationship with NIPRO that includes: funding grants. If there are other authors, they 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 © 2024. Published by Elsevier Inc.)

Background: This study aimed to examine whether high-sensitivity cardiac troponin-I (hsTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) could predict future major adverse cardiovascular events (MACE) in stable coronary artery disease (CAD) patients with high- or low-dose of pitavastatin., Methods: This was a case-cohort analysis of the REAL-CAD study, a randomized trial of high- or low-dose (4 or 1 mg/day) pitavastatin therapy in patients with stable CAD. We examined the MACE risk according to the quartile of hsTnI and NT-proBNP at baseline., Results: A total of 1336 and 1396 patients including 582 MACE cases were randomly examined into the hsTnI and NT-proBNP cohort, respectively. Both higher levels of hsTnI and NT-proBNP at baseline were significantly associated with increased risk of MACE (p < 0.001, respectively). When separately analyzed in statin dose, the higher marker levels were significantly associated with higher MACE risk in all cohorts (p < 0.001 in all cohorts). After multivariable adjustment, hsTnI levels were significantly associated with MACE risk in low-dose statin group (HR 2.54, p = 0.0001); however, in high-dose pitavastatin therapy, a significant association was diminished in MACE risk among the quartiles of baseline hsTnI levels (p = 0.154). Conversely in the NT-proBNP cohort, the association between NT-proBNP levels and MACE risk was constantly observed regardless of pitavastatin dose even after multivariable adjustment (both p < 0.0001)., Conclusions: Patients with high hsTnI levels had high risk of MACE in low-dose statin group, but not in high-dose, suggesting that high-dose statin treatment might decrease MACE risk in stable CAD patients with high hsTnI levels., Competing Interests: Declaration of Competing Interest Dr. J. Ishii received a research grant from Sysmex Corp. and honoraria from Daiichi Sankyo Co. Ltd., Kowa Pharmaceutical Co. Ltd., Siemens Healthineers Japan, and LSI Medience Corp. Dr. Fukumoto received research grant from Sanofi KK, Shionogi & Co, Ltd., honoraria from Public Health Research Foundation, AstraZeneca KK, Eisai Co, Ltd., Kowa Pharmaceutical Co Ltd., research grant and honoraria from MSD KK, Otsuka Pharmaceutical Co, Ltd., Daiichi Sankyo Co, Ltd., Sumitomo Dainippon Pharma Co, Ltd., Teijin Pharma Ltd., Bayer Yakuhin, Ltd., Mochida Pharmaceutical Co, Ltd., Astellas Pharma Inc., Sanwa Kagaku Kenkyusho Co, Ltd., Takeda Pharmaceutical Co Ltd., Mitsubishi Tanabe Pharma Corp, Pfizer Japan Inc., Ono Pharmaceutical Co Ltd., AstraZeneca KK. Dr. Ozaki received research grant and honoraria from Mochida Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Company Limited, Sanofi K.K., Shionogi & Co., Ltd., MSD K.K., Mitsubishi Tanabe Pharma Corporation, Otsuka Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., research grant, other reserch support and honoraria from Public Health Research Foundation. Dr. Iimuro received research grant from Amgen Astellas BioPharma K.K., research grant and honoraria from Public Health Research Foundation. Dr. Iwata received other research support from Public Health Research Foundation, honoraria from Bayer Yakuhin, Ltd., Daiichi Sankyo Company, Limited, Takeda Pharmaceutical Company Limited, MSD K.K., Kowa Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation. Dr. Sakuma received honoraria from GlaxoSmithKline, AstraZeneca, Takeda, Bayer, Pfizer, Bristol-Myers Squibb, Boehringer lngelheim, MSD, Kyowa Hakko Kirin, Daiichi Sankyo, Novartis, Sanofi, Kowa, Shionogi, Kissei, Astellas, Amgen, Ono, Otsuka, Novonordisk, Mochida, Teijin, Sysmex, Nipro, Kyorin, Fuji and Sumitomo Dainippon, research grants from Public Health Research Foundation, Kowa, National Cerebral and Cardiovascular Center and Medical Informatics Study Group. Dr. Nakagawa received honoraria from Kowa Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Bayer Yakuhin, Ltd., Sanofi K.K., Daiichi Sankyo Company, Limited, Shionogi & Co., Ltd., Astellas Pharma Inc., MSD K.K., Mitsubishi Tanabe Pharma Corporation, Sumitomo Dainippon Pharma Co., Ltd., AstraZeneca K.K., Amgen Astellas BioPharma K.K., Eisai Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., research grant, other research support and honoraria from Public Health Research Foundation. Dr. Hibi received research grants from Public Health Research Foundation, Abott Vascular Japan Co. Ltd., and Sanofi KK. Dr. Hiro received research grants from Otsuka Pharmaceutical Co. Ltd., Shionogi & Co. Ltd., and Takeda Pharmaceutical Co. Ltd., honoraria from Amgen Astellas BioPharma KK, Kowa Pharmaceutical Co. Ltd., Kissei Pharmaceutical Co. Ltd., and Chugai Pharmaceutical Co. Ltd., research grants and honoraria from Astellas Pharma Inc., Eisai Co. Ltd., MSD KK, Sanofi KK, Daiichi Sankyo Co. Ltd., Sumitomo Dainippon Pharma Co. Ltd., Mitsubishi Tanabe Pharma Corp., Bayer Yakuhin, Ltd., Pfizer Japan Inc., and AstraZeneca KK, and research grant, other research support, and honoraria from Public Health Research Foundation. Dr. Hokimoto received honoraria from Daiichi Sankyo Co. Ltd. and AstraZeneca KK. Dr. Miyauchi received honoraria from Sanofi KK, Daiichi Sankyo Co. Ltd., AstraZeneca KK, Amgen Astellas BioPharma KK, Takeda Pharmaceutical Co. Ltd., Bayer Yakuhin, Ltd., and MSD KK. Dr. Daida received honoraria from Amgen Astellas BioPharma KK, Daiichi Sankyo Co., Ltd., Kowa Pharmaceutical Co., Ltd., MSD KK, and research grant from Canon, and scholarship grant from Otsuka Pharmaceutical Co., Ltd., Sanofi KK, MSD KK, Pfizer Japan Inc., Mitsubishi Tanabe Pharma Corp., Astellas Pharma Inc., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., Shionogi & Co., Ltd., Actelion Pharmaceuticals Japan, Ltd. Bayer Yakuhin, Ltd., Boehringer Ingelheim Japan Co., Ltd., and courses endowed by Phillips, Resmed, Fukuda Denshi, Asahikasei, Inter-Reha. Dr. Shimokawa received research grant from Shionogi & Co, Ltd., Teijin Pharma Ltd., Astellas Pharma Inc., Otsuka Pharmaceutical Co, Ltd., honoraria from Kowa Pharmaceutical Co Ltd., Sanofi KK, AstraZeneca KK, Bayer Yakuhin, Ltd., research grant and honoraria from MSD KK, Mitsubishi Tanabe Pharma Corp, Daiichi Sankyo Co, Ltd., research grant, other research support, and honoraria from Public Health Research Foundation. Dr. Saito received honoraria from Otsuka Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corp., Mochida Pharmaceutical Co. Ltd., and Kowa Pharmaceutical Co. Ltd. and other research support and honoraria from Public Health Research Foundation. Dr. Kimura received research grant from Sumitomo Dainippon Pharma Co, Ltd., Astellas Pharma Inc., Otsuka Pharmaceutical Co, Ltd., Mitsubishi Tanabe Pharma Corp, Takeda Pharmaceutical Co Ltd., other research support and honoraria from Kowa Pharmaceutical Co Ltd., Bayer Yakuhin, Ltd., research grant, other research support, and honoraria from MSD KK, Sanofi KK, Mochida Pharmaceutical Co, Ltd., Daiichi Sankyo Co, Ltd., Public Health Research Foundation, Amgen Astellas BioPharma KK. Dr. Matsuzaki received honoraria from Mochida Pharmaceutical Co. Ltd. Dr. Nagai received honoraria from Kowa Pharmaceutical Co Ltd., Takeda Pharmaceutical Co Ltd., Bayer Yakuhin, Ltd., Daiichi Sankyo Co, Ltd., Shionogi & Co, Ltd., MSD KK, Mitsubishi Tanabe Pharma Corp, Amgen Astellas BioPharma KK, Eisai Co, Ltd., Astellas Pharma Inc., Sumitomo Dainippon Pharma Co, Ltd., Mochida Pharmaceutical Co, Ltd., honoraria and expert witness from Public Health Research Foundation. Other coauthors report no conflicts., (Copyright © 2023 The Author(s). Published by Elsevier B.V. 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 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 and Aims: The relationship of apolipoprotein A-I (ApoA-I) and renal function in patients after intervention remain unclear, thus, we aimed to evaluate the combined impacts of ApoA-I and kidney disease (K D )., Material and Methods: Altogether, 4101 consecutive patients who underwent intervention between 2000 and 2016 were included. The patients were divided into four groups based on the median ApoA-I values and presence of K D . We evaluated the incidence of major adverse cardiac and cerebrovascular events (MACCE), including cardiovascular death, non-fatal acute coronary syndrome and non-fatal stroke, and all-cause death., Results: During the median follow-up period of 6.2 years, 618 patients (15.1%) developed MACCE, and 627 patients (15.3%) died. ApoA-I level was significantly related to estimated glomerular filtration rate, and ApoA-I levels and K D status interaction term was statistically significant. Kaplan-Meier analysis revealed that the low ApoA-I with K D had the significantly highest cumulative incidence rate of MACCE and all-cause death compared to the other three groups. Additionally, ApoA-I levels and K D status were independent predictors of MACCE and all-cause death in multivariable Cox hazard analysis., Conclusion: The combined impacts of ApoA-I and renal function could be useful for evaluating cardiovascular and life prognoses in patients undergoing intervention., 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 © 2022 Elsevier B.V. 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.)

Background & Aims: Coexistence of obesity and decreased muscle strength, defined as sarcopenic obesity, is often observed in the older adults. The present study investigated whether sarcopenic obesity, defined as reduced handgrip strength and increased body mass index (BMI), is associated with cognitive impairment., Methods: Study participants include 1615 older adults aged 65-84 years who lived in an urban area of Tokyo, Japan and participated in the Bunkyo Health Study. Mild cognitive impairment (MCI) and dementia were defined based on ≤22 points of Montreal Cognitive Assessment and ≤23 points of the Mine-Mental State Examination, respectively. Handgrip strength was measured using a dynamometer in a standing position. We divided participants into four groups according to their sarcopenia (probable) (handgrip strength <28 kg in men and <18 kg in women) and obesity status (BMI ≥25 kg/m 2 ) as control, obesity, sarcopenia and sarcopenic obesity, and investigated the association between cognitive function, sarcopenia, and obesity status., Results: Mean age was 73.1 ± 5.4 years, and 57.6% of study participants were female. The prevalence of control, obesity, sarcopenia, and sarcopenic obesity was 59.4%, 21.2%, 14.6%, and 4.7%, respectively. The prevalence of MCI and dementia, respectively, was highest in participants with sarcopenic obesity, followed by those with sarcopenia, obesity, and control. After multivariate adjustment, sarcopenic obesity was independently associated with increased odds of MCI and dementia compared with the control (MCI: 2.11 [95% confidence interval, 1.12-3.62]; dementia: 6.17 [2.50-15.27])., Conclusions: Sarcopenic obesity was independently associated with MCI and dementia among Japanese older adults. Future studies are necessary to clarify the causal relationship., Competing Interests: Conflict of Interest The authors have nothing to disclose., (Copyright © 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Inflammatory status is associated with cardiovascular events in patients with coronary artery disease (CAD) and renal function impairment. Chronic kidney disease (CKD) increases the incidence of cardiovascular events. However, whether the presence of residual inflammatory risk (RIR) and CKD together has a synergistic effect on the long-term clinical outcomes of patients with stable CAD undergoing percutaneous coronary intervention (PCI) remains unclear., Methods: We assessed 2,948 consecutive patients with stable CAD who underwent the first PCI from 2000 to 2016. Of these, we analyzed the data of patients (2,087) with measurements of high-sensitivity C-reactive protein (hs-CRP) available at follow-up (6-9 months later). High RIR was defined as hs-CRP of >0.6 mg/L according to the median value at follow-up. Patients were classified into four groups: Group 1 (low RIR, non-CKD), Group 2 (high RIR, non-CKD), Group 3 (low RIR, CKD), and Group 4 (high RIR, CKD). We evaluated all-cause mortality and major adverse cardiac events (MACE). The median follow-up period was 5.2 (interquartile range, 1.9-9.9) years., Results: In total, 189 (16.1%) and 128 (11.2%) cases of all-cause mortality and MACE, respectively, were identified during follow-up. The rates of all-cause mortality and MACE were significantly higher in Group 4 than those in the other groups (p<0.001). There was a stepwise increase in the incidence of all-cause mortality and MACE. Upon adjustment for important covariates, the presence of high RIR and/or CKD showed an independent association with a high incidence of MACE and all-cause mortality., Conclusions: The presence of high RIR and CKD conferred a synergistic adverse effect on the long-term clinical outcomes of patients undergoing PCI., Competing Interests: Disclosure The authors declare that there is no conflict of interest., (Copyright © 2021. Published by Elsevier Ltd.)

Background and Aims: Little is known about the long-term impact of apolipoprotein E (apoE) on residual cardiovascular risk in patients with chronic coronary syndrome (CCS) receiving statin treatment., Methods: A total of 1109 consecutive patients (mean age, 67 ± 10 years; 83% men) with CCS who underwent their first intervention between 2000 and 2016 were included in this study. All patients had achieved low-density lipoprotein cholesterol (LDL-C) <100 mg/dL on statin treatment and were divided into two groups based on median serum apoE values. We evaluated the incidence of major adverse cardiovascular events (MACEs), including cardiovascular death, non-fatal acute coronary syndrome, and target vessel revascularization., Results: A total of 552 and 557 patients were categorized to the higher and lower apoE groups, respectively. There were significant relationships between apoE levels and total cholesterol levels, triglyceride levels, high-density lipoprotein cholesterol levels, and estimated remnant cholesterol, except for LDL-C levels. During the median follow-up period of 5.1 years, 195 patients (17.6%) developed MACEs. Kaplan-Meier analysis revealed that the cumulative incidence of MACEs in the higher apoE group was significantly higher than in the lower apoE group (29.5% vs.23.8% log-rank test, p = 0.019). Using multivariable Cox hazard analysis, serum apoE level (1-mg/dL increase) (hazard ratio 1.15; 95% confidence interval 1.03-1.29, p = 0.013) was the strongest independent predictor of MACEs., Conclusions: Serum apoE level could be a strong predictor of residual cardiovascular risk in patients with CCS long-term, even if LDL-C levels are controlled with statin treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Endovascular treatment (EVT) for femoropopliteal artery disease is common in clinical practice. However, little is known about its prognostic factors, causes of death, and long-term clinical outcomes., Methods: Two hundred eighty-five consecutive patients (mean age, 72±8 years, 73% men) undergoing their first EVT for de-novo femoropopliteal artery disease from 2009 to 2018 were studied. Patients were divided in two groups according to the presence of critical limb ischemia (CLI). We evaluated the incidence of major adverse limb events (MALE) including clinically driven target vessel revascularization and target limb major amputation, and all-cause death., Results: The procedure was successful in 97.9% of cases. The non-CLI group comprised 205 patients (72%), and the CLI group comprised 80 patients (28%). The CLI group exhibited higher high-sensitivity C-reactive protein (hs-CRP) levels and a higher rate of hemodialysis than the non-CLI group. During the median follow-up period of 3.5 years, there were 62 deaths (21.8%) including cardiovascular (32.3%), infection (32,3%), and malignancy-related (22.6%) deaths. Kaplan-Meier analysis revealed that the CLI group had a significantly higher incidence of MALE and all-cause death (log-rank, both p<0.001, respectively). The leading causes of death in the CLI group were cardiovascular- and infection-related death; the leading cause of death in the non-CLI group was malignancy-related. On multivariate Cox hazard analysis, hemodialysis, TASC II classification C/D lesions, and CLI were significant predictors of MALE (p<0.001, p=0.005, and p=0.012, respectively). Hemodialysis, age, higher hs-CRP levels, and CLI were significant predictors of all-cause death (p<0.001, p=0.003, p=0.009, and p=0.021, respectively)., Conclusions: Although EVT for femoropopliteal artery disease appears feasible with a high rate of procedural success, a high incidence of MALE and all-cause death was observed. Further studies are needed to improve the outcomes in patients with CLI., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Fractional flow reserve (FFR) is an established method for assessing functional myocardial ischemia. Recently, the resting full-cycle ratio (RFR) has been introduced as a non-hyperemic index of functional coronary stenosis. However, the effects of clinical characteristics on discordance between RFR and FFR have not been fully evaluated. We aimed to identify clinical characteristics that influence FFR-RFR concordance., Methods: We included 410 patients with 573 intermediate coronary lesions who underwent clinically indicated invasive coronary angiography, as well as assessments of FFR and RFR. Receiver-operating characteristic (ROC) curves were created to assess the optimal cut-off values of RFR for predicting FFR ≤0.80., Results: RFR exhibited a strong correlation with FFR (r = 0.66, p < 0.0001). ROC analysis identified an optimal RFR cut-off value of 0.92 for categorization based on an FFR cut-off value of 0.8. The discordance of FFR >0.8 and RFR ≤0.92 (high FFR/low RFR) was observed in 112 lesions (20.9%), whereas the discordance of FFR ≤0.8 and RFR >0.92 (low FFR/high RFR) was observed in 35 lesions (6.5%). Higher rate of hemodialysis and lower hemoglobin levels were observed in the high FFR/low RFR group. Multivariate analyses identified female sex, left anterior descending artery (LAD) lesions, and hemodialysis as significant predictors of high FFR/low RFR. Conversely, body surface area and non-LAD lesions were significantly associated with low FFR/high RFR. Hemodialysis [odds ratio (OR): 2.41, 95% confidence interval (CI) 1.31-4.41; p = 0.005] and LAD lesions (OR: 1.86, 95% CI: 1.25-2.79; p = 0.002) were identified as independent predictors of overall FFR-RFR discordance., Conclusions: RFR exhibited good diagnostic performance in the identification of functionally significant stenosis. However, RFR may overestimate functional severity in patients undergoing hemodialysis or in those with LAD lesions. Further prospective trials are required to demonstrate the non-inferiority of RFR to FFR., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Whether coronary plaque characteristics assessed in coronary computed tomography angiography (CCTA) in association with the coronary artery calcium score (CACS) have predictive value for coronary events is unclear. We aimed to examine the predictive value of the CACS and plaque characteristics for the occurrence of coronary events., Methods: Among 2802 patients who were analyzed in the PREDICT registry, 2083 with suspected coronary artery disease (CAD) were studied using post hoc analysis. High-risk plaques were defined as having ≥2 adverse characteristics, such as low computed tomographic attenuation, positive remodeling, spotty calcification, and napkin-ring sign. An adjudicative composite of coronary events (cardiac death, nonfatal acute coronary syndrome, and coronary revascularization ≥3 months after indexed CCTA) were analyzed., Results: Seventy-three (3.5%) patients had coronary events and 313 (15.0%) had high-risk plaques. Multivariate Cox proportional hazard analysis showed that high-risk plaques remained an independent predictor of coronary events (adjusted hazard ratio [HR] 1.95, 95% confidence interval [CI] 1.13-3.34, P ​= ​0.0154), as well as the log-transformed CACS (adjusted HR 1.24, 95% CI 1.11-1.39, P ​= ​0.0002) and the presence of obstructive stenosis (adjusted HR 5.63, 95% CI 3.22-10.12, P 0.0001). In subgroup analyses, high-risk plaques were independently predictive only in the low CACS class (<100)., Conclusion: This study shows that assessment of adverse features by coronary plaque imaging independently predicts coronary events in patients with suspected CAD and a low CACS. Our findings suggest that the clinical value of high-risk plaques to CACS and stenosis assessment appears marginal., Competing Interests: Declaration of competing interest Yasuki Kihara received grants from Astellas Pharma, Actelion, Otsuka, MSD, Sanofi, Bayer, Shionogi, Saint-Judo Medical, Daiichi Sankyo, Takeda, Nippon Shinyaku Pharm, Boehringer-Ingelheim Japan, Biotonic, Bayer, Pfizer, Mochida Pharm, and Roche Diagnostics. Shinichiro Fujimoto received grants from HeartFlow Japan G.K, Canon Medical Systems Corporation, and Edwards LifeSciences Ltd., Hiroyuki Daida received remuneration for lectures from Amgen Astellas Biopharma K.K., Sanofi K.K., Daiichi-Sankyo Pharmaceutical Company Ltd., Terumo Corporation, Boehringer Ingelheim GmbH, Bayer AG, MSD K.K., Mitsubishi Tanabe Parma, Fujifilm, Fuji Chemical Co., Pfizer Pharmaceutical Company Ltd., and Canon Medical Systems Corporation. Shinichiro Fujimoto also received research grants from Nihon Medi-Physics Company Ltd., Kowa Pharmaceutical Company Ltd., Daiichi-Sankyo Company Ltd., Canon Medical Systems Corporation, Philips Respironics Ltd., Astellas Pharma Inc., Otsuka Pharmaceutical Company Ltd., Sanofi K.K., Boehringer Ingelheim GmbH, Bayer AG, Teijin Ltd., MSD K.K., Pfizer Pharmaceutical Company Ltd., HeartFlow, Novartis Pharma, Nihon Shinyaku, Fujifilm RI Pharm, and Actelion Pharmaceuticals Japan Ltd. Hiroyuki Daida is affiliated with some endowed departments, including Philips Respironics Ltd., Fukuda Denshi Company Ltd., and ResMed Ltd. Shunichi Miyazaki received grants from Boehringer-Ingelheim Japan, MSD, Astellas Pharma, Daiichi Sankyo, and Bayer. Tomohiro Kawasaki received grants from Abbot Vascular Japan, Boston Scientific Japan, Daiichi Sankyo Co., Japan Lifeline, and Astellas Amgen BioPharma. All other authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

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: We aimed to assess the impact of scoring balloon angioplasty (SBA) after rotational atherectomy (RA) on long-term clinical outcomes in patients who underwent percutaneous coronary intervention (PCI) using second-generation drug-eluting stents (DES). The long-term outcomes associated with SBA after RA in severely calcified lesions is unknown., Methods: Using the J2T ROTA registry data, we evaluated the clinical events of patients who underwent PCI using RA for heavily calcified lesions from January 2004 to December 2015. A total of 307 patients who underwent PCI with second-generation DES were analyzed and divided into the SBA (n = 96) and conventional balloon angioplasty (CBA) groups (n = 211). Eighty-two and 189 patients comprised the "SBA after small burr (SBA-SB)" and "CBA after small burr (CBA-SB)" subgroups, respectively, for the subgroup analysis. Study endpoints were incidence of 3-year major adverse cardiac events (MACE), target vessel revascularization (TVR), and target lesion revascularization (TLR)., Results: Kaplan-Meier analysis revealed that the incidence of 3-year cumulative MACE, TVR, and TLR were comparable between groups, and that the incidences of 3-year cumulative MACE, TVR, and TLR were significantly lower in the SBA-SB subgroup than in the CBA-SB subgroup (log-rank p = 0.008; log-rank p = 0.047; log-rank p = 0.045; respectively). Multivariate Cox regression model indicated that SBA after RA was an independent predictor of MACE (hazard ratio: 0.337; 95% confidence interval: 0.139 to 0.817; p = 0.016)., Conclusions: Additional SBA following RA was associated with lower MACE incidence in patients undergoing RA with a small-sized burr., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The emerging burden and need of hospital admission due to adult congenital heart disease (ACHD) will need many facilities with expertise in ACHD. Regional specialized ACHD centers are carrying this increasing patient burden. Although these centers are considered to perform better management than other institutes, their impact on outcome has not been fully evaluated., Methods: We used the Japanese Registry of All cardiac and vascular Diseases (JROAD) and the JROAD Diagnosis Procedure Combination (DPC)/Per Diem Payment System dataset and certification data. We only analyzed adult (≥15 years old) patients with ACHD, defined by the International Classification of Diseases, Tenth Revision, diagnosis codes, between April 1, 2013, and March 31, 2014. We defined a "minimal essential regional ACHD (MER-ACHD) center" as an education institute accredited by adult and pediatric cardiology societies. The primary outcome is 30-day mortality. We investigated the impact of MER-ACHD centers on 30-day mortality by using generalized estimating equations., Results: Of the 538 hospitals registered at JROAD that agreed to participate in the DPC discharge database study, 65 (12.1%) were MER-ACHD centers. Of 4818 patients (46.8% male; age, 50.1±21.4 years), 45.5% were admitted to a MER-ACHD center. Nearly half (48.1%) of the admissions were cases of atrial septal defect, followed by ventricular septal defect, tetralogy of Fallot, and congenital insufficiency of the aortic valve or bicuspid aortic valve. Multivariate analysis revealed a negative impact of emergency admission [1.051 (1.042-1.061)] and a positive impact of MER-ACHD centers [0.986 (0.973-0.999)] on 30-day mortality after adjustment of disease severity., Conclusion: We noted the impact of MER-ACHD centers on 30-day mortality. Further investigation is needed to establish appropriate regional ACHD center criteria to deliver appropriate ACHD management., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Catheter ablation (CA) has been reported to reduce risk of stroke in patients with nonvalvular atrial fibrillation (NVAF) in retrospective studies. However, the risks and benefits of CA have not been well elucidated in patients with NVAF and who have suffered a recent ischemic stroke in prospective randomized trials. Thus, the aim of the STABLED clinical trial is to investigate the efficacy and safety of CA with anticoagulant therapy using edoxaban in patients with NVAF and a history of recent ischemic stroke., Methods and Design: The STABLED trial is a multicenter, prospective, randomized, open-label, standard medication-controlled study in Japan. The target patient number is 250, comprising 125 patients receiving standard medication and 125 receiving CA. For patients allocated to the CA group, ablation is to be performed between 1 to 6 months from the onset of index stroke. The observation period will be 3 years from the day of random allocation of the final patient to any of the groups. The primary outcome measure is the composite of recurrence of ischemic stroke, systemic embolism, all-cause death, and hospitalization for heart failure., Conclusion: This study will investigate the effectiveness and safety of CA and basic anticoagulation treatment with edoxaban for patients with NVAF who have suffered a recent ischemic stroke. The aim is to determine the best evidence for an optimal treatment strategy for patients with NVAF and recent stroke., Trial Registration: UMIN000031424/NCT03777631., (Copyright © 2019 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.)

Background: Hemodialysis (HD) patients have heavy calcium deposits in their stenotic coronary arteries and worse post-percutaneous coronary intervention (PCI) prognoses than those who do not undergo HD. Rotational atherectomy (RA) facilitates PCI success in severely calcified lesions. We aimed to identify clinical and procedural characteristics that predict HD patients' long-term prognoses after PCI that included RA in the drug-eluting stent (DES) era., Methods: This study included 302 patients who underwent regular HD from J2T Multicenter Registry database of 1090 consecutive patients who underwent RA to treat de novo calcified lesions at three university hospitals between 2004 and 2015. The primary endpoint was cardiovascular (CV) death., Results: During the 5-year observation period, 59 CV deaths (19.5%) occurred. The CV death group and non-CV death group had comparable profiles except significantly lower left ventricular ejection fraction, higher brain natriuretic peptide (BNP), lower rate of RA burr upsizing, and lower rate of final thrombolysis in myocardial infarction (TIMI) 3 flow achievement in the CV death group. Cox regression analysis revealed that increasing ablation burr size (hazard ratio [HR]: 0.33; 95% confidence interval [CI]: 0.13-0.81), final TIMI 3 flow (HR: 0.07; 95% CI: 0.02-0.28), lower BNP level, and optimal medication were independently associated with better CV mortality in HD patients., Conclusion: In the DES era, oral medications at the time of PCI and stepwise calcium ablation were associated with improved long-term CV mortality in HD patients who are scheduled to undergo RA to treat severely calcified coronary artery stenoses, as therapeutic strategies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Although subtraction coronary computed tomography angiography (S-CCTA) has recently been developed to improve the diagnostic ability in patients with severe calcification, increase in radiation exposure remains a concern. The usefulness of S-CCTA using a low-radiation dose protocol was investigated., Methods: S-CCTA in 320-row area detector CT was performed on 84 consecutive patients with suspected obstructive coronary artery disease with Agatston score ≥100. Reconstruction and radiation dose were changed according to the slow filling time (SF) (137.5ms

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: Sleep-disordered breathing (SDB) is a novel cardiovascular risk factor. To date, the effects of continuous positive airway pressure (CPAP) on coronary plaque atheroma in SDB patients with coronary artery disease (CAD) have remained unclear. The CPAP Effects on Atherosclerotic Plaques in Patients with Sleep-Disordered Breathing and Coronary Artery Disease (ENTERPRISE) trial was designed to evaluate the effects of CPAP treatment in addition to optimal medical treatment on coronary plaque regression in SDB patients., Methods: This study is planned as a prospective, randomized, open-label, single-center study. The presence of SDB is defined as a 3% oxygen desaturation index (ODI) of ≥15 events/h as measured by nocturnal pulse oximetry. A total of 100 eligible SDB patients undergoing intravascular ultrasound (IVUS)-guided percutaneous coronary intervention will be randomly assigned to either CPAP as add-on therapy or no CPAP for SDB (1:1 ratio for CPAP vs. no CPAP). The intervention will consist of 12 months of CPAP treatment. The primary endpoint will be percentage changes in plaque atheroma volume of the non-culprit lesion segment as measured by IVUS. A specialist sleep cardiology team will carefully monitor patients receiving CPAP treatment in order to quickly detect and resolve problems, and to motivate patients to continue treatment., Conclusion: This study will provide novel information on the effects of SDB and its treatment with CPAP on coronary plaque stability with regard to secondary prevention of CAD., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Angiotensin II (Ang II) activates components of the inflammatory cascade, which promotes hypertension and development of abdominal aortic aneurysm (AAA). This study aimed to elucidate the effects of an IL-1 receptor antagonist (IL-1Ra) and an anti-IL-1β antibody (01BSUR) on Ang II-induced AAA., Methods and Results: Male wild-type (WT) and IL-1Ra-deficient (IL-1Ra - / - ) mice were infused with Ang II (1000 ng/kg/min) using subcutaneous osmotic pumps for 28 days. Fourteen days post-infusion, both systolic blood pressure (SBP) (Ang II-treated IL-1Ra - / - :149 ± 2 vs. Ang II-treated WT:126 ± 3 mm Hg, p < 0.001) and abdominal aortic width (0.94 ± 0.09 vs. 0.49 ± 0.03 mm, p < 0.001) were significantly higher in IL-1Ra - / - mice than in WT mice. Because 28-day infusion with Ang II in IL-1Ra -/- mice significantly increased the occurrence of fatal aortic rupture (89% vs. 6%, p < 0.0001), both types of mice were infused with Ang II for only 14 days, and histological analyses were performed at 28 days. Interestingly, AAA increased more significantly in IL-1Ra - / - mice than in WT mice (p < 0.001), although SBP did not differ at 28 days in IL-1Ra - / - and WT mice (117 ± 4 vs. 115 ± 3 mm Hg, p = 0.71 (after cessation of Ang II infusion)). Histological analyses showed numerous inflammatory cells around the abdominal aorta in IL-1Ra - / - mice, but not in WT mice. Finally, compared with IgG2a treatment, treatment with 01BSUR decreased Ang II-induced AAA in IL-1Ra - / - mice., Conclusions: The present study demonstrates that inhibition of IL-1β significantly suppresses AAA formation after Ang II infusion, suggesting that suppression of IL-1β may provide an additional strategy to protect against AAA in hypertensive patients., (Copyright © 2018 Elsevier B.V. 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: The prognostic long-term impact of body mass index (BMI) on East Asian patients with coronary artery disease remains unclear., Methods: An observational retrospective cohort study was carried out involving 3571 patients who had undergone percutaneous coronary intervention (PCI) from 2000 to 2013. Patients were divided into the following five groups according to baseline BMI: Group 1 (underweight 1, BMI ≤20.0kg/m 2 ); Group 2 (underweight 2, BMI=20.1-22.5kg/m 2 ); Group 3 (normal weight, BMI=22.6-25.0kg/m 2 ); Group 4 (overweight 1, BMI=25.1-27.5kg/m 2 ); and Group 5 (overweight 2, BMI ≥27.6kg/m 2 ). We then evaluated the association between BMI and both all-cause and cardiac death after PCI., Results: The ratio of patients in the five groups was as follows: Group 1, 9.2%; Group 2, 21.6%; Group 3, 34.1%; Group 4, 21.1%; and Group 5, 14.5%. A decrease in age was observed from underweight to overweight, as was an increased prevalence of hypertension, diabetes mellitus, dyslipidemia, and smoking. The median follow-up period was 6.3 years (interquartile range, 3.2-9.6 years). In total, 473 deaths (frequency, 13.2%) were identified, including 183 (5.1%) cardiac deaths during follow-up. In unadjusted Cox proportional hazard analysis, using normal weight as the reference, underweight, but not overweight, was associated with a greater risk of both all-cause and cardiac death. In an adjusted model, Group 1 had the highest risk for all-cause death (hazard ratio, 1.58; 95% confidence interval, 1.19-2.10; p=0.0019); however, no significant differences were found for the risk of all-cause and cardiac death between normal weight and overweight patients., Conclusion: The results of the present long-term follow-up study do not support the so-called "obesity paradox," but rather, suggest that underweight Japanese patients are at greater risk for all-cause mortality following PCI., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Coronary computed tomography angiography (CCTA) not only provides information regarding luminal stenoses but also allows for visualization of mural atheromatous changes (coronary plaques)., Objective: We sought to elucidate whether plaques seen on CCTA enable prediction of 2-year outcomes in patients with suspected and known coronary artery disease (CAD)., Methods: Of 3015 patients who underwent CCTA, the images and 2-year clinical courses of 2802 patients were independently analyzed. The primary endpoint was the composite of all-cause death and acute coronary syndrome., Results: During the 2-year observation period, 49 (1.7%) patients developed the primary outcome. The 2-year rates of the primary outcome in the normal (n = 515, no mural lesions), calcium (n = 654, calcified lesion alone), and plaque groups (n = 1633, presence of noncalcified or partially calcified plaques) were 0.2%, 2.0%, and 2.1%, respectively (P = 0.0028). Adverse plaque features such as low attenuation, positive remodeling, spotty calcification, and the napkin-ring sign (low-attenuation core with a higher-attenuation rim) were assessed by an independent core laboratory. Stepwise multivariate Cox proportional hazard analysis showed that a plaque with two or more characteristics (adjusted hazard ratio, 1.98; 95% confidence interval, 1.09-3.60; P = 0.0254), age of ≥67 years (mean), statin treatment after CCTA, and obstructive stenosis remained independent predictors of the primary outcome., Conclusions: Plaque imaging in CCTA has predictive value for the 2-year outcome and is a useful identifier for high-risk patients among those with known and suspected CAD., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Antithrombotic therapy with oral anticoagulants (OAC) in patients with atrial fibrillation (AF) after stent implantation, where dual antiplatelet therapy (DAPT) is also recommended, is not established. Antithrombotic therapies prescribed vary widely among cardiologists and may change year by year, according to the accumulation of new evidence., Methods: A questionnaire-based survey concerning the antithrombotic therapy prescribed for OAC-treated AF patients who underwent stent implantation was conducted from 2014 to 2016. The survey was completed by the Fellows of the Japanese College of Cardiology (FJCC)., Results: The questionnaire was sent to 1023 fellows in 2014, a total of 1057 fellows in 2015, and 1073 fellows in 2016; 268 (26%), 418 (40%), and 416 (39%) answers were obtained, respectively. The duration of DAPT did not change in patients with bare metal stents; however, it tended to become shorter with the use of the drug-eluting stent (DES). Significant shortening of DAPT duration was observed with DES for stable coronary artery disease from 2015 to 2016. A similar tendency was observed for acute coronary syndrome (ACS); however, this was not significant between 2015 and 2016. A shorter duration of DAPT is preferred by electrophysiologists rather than by interventionalists and general cardiologists. OAC monotherapy is not popular one year after stent implantation, although the prevalence of its use increased year by year. Aspirin and thienopyridines are used equally as a single antiplatelet in DAPT, and clopidogrel is also a popular agent. The prevalence of direct OAC use increased year by year., Conclusions: The questionnaire showed variation in antithrombotic therapy used for OAC-treated AF patients after stenting, and how it changes year by year. Although the duration of DAPT tended to shorten, variations are still observed, i.e. the selection of a single antiplatelet or OAC., (Copyright © 2018. Published by Elsevier Ltd.)

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.)

Objective: No nutritional index has been firmly established yet in patients with coronary artery disease (CAD). In this study, we propose a simple to calculate nutritional indicator in patients who underwent percutaneous coronary intervention (PCI) by using parameters routinely measured in CAD and evaluated its prognostic implication., Methods: This study is a retrospective observational analysis of a prospective database. The subjects were consecutive 3567 patients underwent their first PCI between 2000 and 2013 at Juntendo University Hospital in Tokyo. The median of the follow-up period was 6.3 years (range: 0-13.6 years). The novel nutritional index was calculated by the formula; Triglycerides (TG) × Total Cholesterol (TC) × Body Weight (BW) Index (TCBI) = TG × TC × BW / 1000 (TG and TC: mg/dl, and BW: kg)., Results: The Spearman non-parametric correlation coefficient between TCBI and the most often used conventional nutritional index, Geriatric Nutritional Risk Index (GNRI), was 0.355, indicating modest correlation. Moreover, Unadjusted Kaplan-Meier analysis showed higher all-cause mortality, cardiovascular mortality, and cancer mortality in patients with low TCBI. Consistently, elevation of TCBI was associated with reduced all-cause (hazard ratio: 0.86, 95%CI: 0.77-0.96, p < 0.001), cardiovascular (0.78, 0.66-0.92, p = 0.003), and cancer mortality (0.76, 0.58-0.99, p = 0.041) in patients after PCI by multivariate Cox proportional hazard analyses., Conclusion: TCBI, a novel and easy to calculate nutrition index, is a useful prognostic indicator in patients with CAD., (Copyright © 2018 Elsevier B.V. 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: Limited data are available regarding the presence of sleep-disordered breathing (SDB) assessed using polysomnography in patients hospitalized with left ventricular (LV) systolic dysfunction after acute decompensated heart failure (ADHF). We investigated the prevalence and clinical correlates of SDB in patients hospitalized with ADHF and LV systolic dysfunction., Methods: Prospectively collected data from 105 consecutive patients with an LV ejection fraction < 50% who were hospitalized with ADHF from May 2012 to July 2014 were retrospectively assessed. Polysomnography was performed during the initial hospitalization after the initial improvement in ADHF acute signs and symptoms. The apnea-hypopnea index (AHI), including obstructive or central AHI, was computed as a severity of obstructive or central sleep apnea. Echocardiography and blood sampling for various parameters, such as B-type natriuretic peptide level, were performed systematically., Results: The proportions of patients with an AHI ≥ 5 events per hour and those with an AHI ≥ 15 events per hour were 93% and 69%, respectively, and central sleep apnea was predominant (66% and 44%, respectively). In the multivariate analysis, only body mass index (BMI) was independently correlated with AHI, whereas age, BMI, and E/e' level were independently correlated with obstructive AHI. In addition, use of loop diuretics and E/e' level were independently correlated with central AHI., Conclusions: SDB determined using polysomnography was common in hospitalized patients with ADHF and LV systolic dysfunction. Age, BMI, and E/e' levels were significantly correlated with obstructive sleep apnea severity, whereas E/e' levels and use of loop diuretics were significantly correlated with central sleep apnea severity., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: The GRACE risk score was developed to predict in-hospital mortality for acute coronary syndrome (ACS) using multinational registries, but did not include Japanese data. Therefore, GRACE risk scores are not extensively used in Japan. The present study aimed to evaluate the relationship between the GRACE risk score and in-hospital mortality among Japanese patients with ACS using the Tokyo CCU (cardiovascular care unit) Network Database., Methods and Results: A total of 9460 patients with ACS hospitalized at 67 Tokyo CCUs between January 2011 and December 2013 were retrospectively reviewed and GRACE risk scores were calculated. Patients in the Tokyo CCU Network database had more severe conditions compared to those of the original GRACE study. There was a strong correlation between the GRACE risk score and in-hospital mortality for patients with ST-segment elevation myocardial infarction (STEMI) or non ST-segment elevation myocardial infarction (NSTEMI) (r=0.99, p<0.001); however, the correlation was not significant for patients with unstable angina (r=0.35, p=0.126). For STEMI+NSTEMI patients, the discrimination ability of the GRACE risk score was excellent, with a c statistic of 0.87 (95% confidence interval, 0.86-0.89)., Conclusions: The GRACE risk score is a good predictor of in-hospital mortality for Japanese patients with STEMI or NSTEMI, and can help clinicians stratify patients by risk for optimal patient triage and early treatment management., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Low serum albumin level is reportedly associated with worse clinical outcomes in patients with chronic kidney disease (CKD). However, associations between decreased serum albumin level and outcomes in non-CKD patients with coronary artery disease (CAD) remain unclear. Therefore, we aimed to evaluate the prognostic value of serum albumin concentrations in stable CAD patients with preserved renal function., Methods and Results: We studied 1316 patients with CAD and preserved renal function (estimated glomerular filtration rate ≥60 mL/min/1.73 m 2 ) who underwent their first PCI between 2000 and 2011 and had data available for pre-procedural serum albumin. Patients were assigned to quartiles based on pre-procedural albumin concentrations. The incidence of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction, was evaluated. Mean albumin concentration was 4.1 ± 0.4 g/dL. During the median follow-up of 7.5 years, 181 events occurred (13.8%). Kaplan-Meier curves revealed that patients with decreased serum albumin concentrations showed a higher event rate for MACE (log-rank, p < 0.0001). Using the highest tertiles (>4.3 g/dL) as reference, adjusted hazard ratios were 1.97 (95% CI, 1.12-3.55), 1.77 (95% CI, 0.99-3.25), and 1.19 (95% CI, 0.68-2.15) for serum albumin concentrations of <3.9, 3.9-4.0, and 4.1-4.3 g/dL, respectively. Decreased serum albumin concentration was associated with MACE even after adjusting for other independent variables (HR, 2.21 per 1-g/dL decrease; 95% CI, 1.37-3.56, p = 0.001)., Conclusion: Decreased serum albumin concentration independently predicted worse long-term prognosis in non-CKD patients after PCI. Pre-procedural serum albumin concentration could offer a useful predictor for patients with CAD and preserved renal function., (Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

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 and Aims: Lipopolysaccharide (LPS) is a main component of the Gram-negative bacterial cell wall and is associated with a greater risk of atherosclerosis development in periodontal disease. LPS has been reported to increase both CD36 and CD204 expression and enhance the uptake of modified low-density lipoprotein (LDL). However, the signaling pathways by which LPS enhances these expression levels and function have not been fully elucidated, although the clarification of these signaling pathways is important for identifying therapeutic targets for atherosclerosis., Methods and Results: We have shown here that LPS activated the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway, increased both CD204 and CD36 expression, and enhanced the uptake of acetylated-LDL (Ac-LDL) in mouse bone marrow macrophages. The MAPK/ERK kinase (MEK) inhibitors, U0126 (1 μM) and PD0325901 (10 nM), did not affect the expression of either CD36 or CD204 or the uptake of Ac-LDL under normal conditions (no treatment with LPS). In contrast, U0126 (1 μM) and PD0325901 (10 nM) blocked the LPS-induced increase in Ac-LDL uptake and CD204 expression but not CD36 expression., Conclusions: These results suggest that LPS may increase Ac-LDL uptake and enhance CD204 expression through MAPK/ERK activation and CD36 expression through an ERK-independent pathway. Since MEK inhibitors block CD204 expression in mouse BM macrophages only under LPS treatment but not under normal conditions, a MEK inhibitor might be a good candidate compound for the treatment of LPS-induced atherosclerosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Bone marrow stromal cells (BMSCs) are common progenitors of both adipocytes and osteoblasts. We recently suggested that increased [Ca 2+ ] o caused by bone resorption might accelerate adipocyte accumulation in response to treatment with both insulin and dexamethasone. In this study, we investigated the mechanism by which high [Ca 2+ ] o enhances adipocyte accumulation. We used primary mouse BMSCs and evaluated the levels of adipocyte accumulation by measuring Oil Red O staining. CaSR agonists (both Ca 2+ and Sr 2+ ) enhanced the accumulation of adipocytes among BMSCs in response to treatment with both insulin and dexamethasone. We showed that high [Ca 2+ ] o decreases the concentration of cAMP using ELISA. Real-time RT-PCR revealed that increasing the intracellular concentration of cAMP (both chemical inducer (1μM forskolin and 200nM IBMX) and a cAMP analog (10μM pCPT-cAMP)) suppressed the expression of PPARγ and C/EBPα. In addition, forskolin, IBMX, and pCPT-cAMP inhibited the enhancement in adipocyte accumulation under high [Ca 2+ ] o in BMSCs. However, this inhibited effect was not observed in BMSCs that were cultured in a basal concentration of [Ca 2+ ] o . We next observed that the accumulation of adipocytes in the of bone marrow of middle-aged mice (25-40 weeks old) is higher than that of young mice (6 weeks old) based on micro CT. ELISA results revealed that the concentration of cAMP in the bone marrow mononuclear cells of middle-aged mice is lower than that of young mice. These data suggest that increased [Ca 2+ ] o caused by bone resorption might accelerate adipocyte accumulation through CaSR following a decrease in cAMP., (Copyright © 2017 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: Numerous studies have reported the relationship between elevated homocysteine (Hcy) levels and the risk of coronary artery disease. However, there is insufficient information about the effects of Hcy levels on long-term clinical outcomes in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI)., Methods: In the Juntendo-registry cohort from 2003 to 2004, pre-procedural Hcy levels and Hcy thiolactonase activity (HTlase) were measured in 315 consecutive all-comer patients who underwent PCI for stable coronary artery disease or acute coronary syndrome (ACS). Receiver-operating characteristic (ROC) curves were created to assess the optimal cut-off values of Hcy and HTlase. Multivariable Cox proportional hazard regression analysis was used to identify the predictors of clinical outcome. The primary endpoint was all-cause mortality., Results: The patients' mean age was 66±9 years, and 82.5% were males. The median follow-up period was 10.5 years, and overall mortality was 24.5% (73 deaths). On ROC analysis, the optimal cut-off values of Hcy and HTlase were 13.5μmol/L and 230IU/L, respectively. Kaplan-Meier survival analysis showed associations of both higher Hcy levels and lower HTlase activity with worse prognosis (both log-rank p<0.001). On multivariate Cox proportional hazard regression analysis, higher Hcy was strongly associated with the primary outcome, and the adjusted hazard ratio was 3.3 (95% confidence interval, 1.8-5.6; p<0.001)., Conclusions: Pre-procedural high Hcy levels and low HTlase activity were associated with worse long-term mortality in Japanese patients undergoing PCI. Moreover, Hcy levels are strongly predictive for mortality, independent of traditional risk factors. This may have implications for risk stratification and the therapeutic approach in this PCI era., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: We aimed to assess the effects of cholesteryl ester transfer protein inhibitor anacetrapib added to statin ± other lipid-modifying therapies (LMT) in Japanese patients with dyslipidemia who were not at their LDL-C goal., Methods: Patients on a stable dose of statin ± other LMT with LDL-C ≥100 mg/dL to <145 mg/dL, ≥120 mg/dL to <165 mg/dL, ≥140 mg/dL or ≥160 mg/dL for patients with a history of coronary heart disease (CHD), high-, moderate- and low-risk patients respectively, were randomized 2:1, stratified by background therapy, to double-blind anacetrapib 100 mg (n = 204) or placebo (n = 103) for 24 weeks, followed by a 28-week open-label extension phase (anacetrapib 100 mg) and a 12-week off-drug safety follow-up phase. The primary endpoint was percent change from baseline in LDL-C (beta-quantification method), as well as the safety profile of anacetrapib at Week 24; HDL-C was a key secondary endpoint., Results: Anacetrapib 100 mg further reduced LDL-C (38.0%), non-HDL-C (35.1%), ApoB (28.7%), and Lp(a) (48.3%) and increased HDL-C (148.9%) and ApoAI (50.7%) versus placebo (p < 0.001 for all). There were no meaningful differences between the groups in the proportion of patients with liver enzymes elevations (2.0% vs. 0%), creatine kinase elevations overall (0.5% vs. 0%) or with muscle symptoms (0.5% vs. 0%), blood pressure, electrolytes or adjudicated cardiovascular events (0.5% vs. 0%). In the open-label period, sustained effects on lipid parameters were observed with anacetrapib and the treatment was generally well tolerated., Conclusions: Long-term treatment with anacetrapib 100 mg substantially reduced LDL-C, increased HDL-C and was well tolerated in Japanese patients with dyslipidemia (ClinicalTrials.gov number NCT01760460)., (Copyright © 2017 Tamio Teramoto, Hiroyuki Daida, Katsunori Ikewaki, Hidenori Arai, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Published by Elsevier B.V. All rights reserved.)

Background: The effect of elevated blood glucose (BG) levels on the long-term prognosis of acute decompensated heart failure (ADHF) patients has not been well defined. The purpose of this study is to evaluate the long-term prognosis of ADHF with elevated BG., Methods: A cohort of patients consecutively admitted to the cardiac intensive care unit from 2007 to 2011 was studied. Among these, 495 patients who met the criteria were divided into 4 groups based on their BG level and diabetes mellitus (DM) status. The risks for all-cause mortality in each group were assessed using the multivariate Cox proportional hazards model., Results: At a median follow-up of 1.8 years, 148 patients had died. There were 168 patients without either BG elevation or DM, 67 without BG elevation but with DM, 105 with BG elevation but not DM, and 155 with both BG elevation and DM. In a multivariate model, those with BG elevation, regardless of DM status, showed a greater risk of increased mortality when compared with patients without either BG elevation or DM [hazard ratio (HR), 1.79; p=0.042 for BG elevation without DM and HR, 1.73; p=0.048 for BG elevation with DM]., Conclusion: Elevated BG levels, irrespective of the DM status, at the time of admission in patients with ADHF, appear to be a prognostic marker for ADHF., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Lysophosphatidic acids (LysoPAs) and lysophosphatidylserine (LysoPS) are emerging lipid mediators proposed to be involved in the pathogenesis of acute coronary syndrome (ACS). In this study, we attempted to elucidate how LysoPA and LysoPS become elevated in ACS using human blood samples collected simultaneously from culprit coronary arteries and peripheral arteries in ACS subjects. We found that: 1) the plasma LysoPA, LysoPS, and lysophosphatidylglycerol levels were not different, while the lysophosphatidylcholine (LysoPC), lysophosphatidylinositol, and lysophosphatidylethanolamine (LysoPE) levels were significantly lower in the culprit coronary arteries; 2) the serum autotaxin (ATX) level was lower and the serum phosphatidylserine-specific phospholipase A 1 (PS-PLA 1 ) level was higher in the culprit coronary arteries; 3) the LysoPE and ATX levels were significant explanatory factors for the mainly elevated species of LysoPA, except for 22:6 LysoPA, in the peripheral arteries, while the LysoPC and LysoPE levels, but not the ATX level, were explanatory factors in the culprit coronary arteries; and 4) 18:0 and 18:1 LysoPS were significantly correlated with PS-PLA 1 only in the culprit coronary arteries. In conclusion, the origins of LysoPA and LysoPS might differ between culprit coronary arteries and peripheral arteries, and substrates for ATX, such as LysoPC and LysoPE, might be important for the generation of LysoPA in ACS., (Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.)

Objectives: The purpose of this study was to evaluate long-term clinical impact of routine follow-up coronary angiography (FUCAG) after percutaneous coronary intervention (PCI) in daily clinical practice in Japan., Background: The long-term clinical impact of routine FUCAG after PCI in real-world clinical practice has not been evaluated adequately., Methods: In this prospective, multicenter, open-label, randomized trial, patients who underwent successful PCI were randomly assigned to routine angiographic follow-up (AF) group, in which patients were to receive FUCAG at 8 to 12 months after PCI, or clinical follow-up alone (CF) group. The primary endpoint was defined as a composite of death, myocardial infarction, stroke, emergency hospitalization for acute coronary syndrome, or hospitalization for heart failure over a minimum of 1.5 years follow-up., Results: Between May 2010 and July 2014, 700 patients were enrolled in the trial among 22 participating centers and were randomly assigned to the AF group (n = 349) or the CF group (n = 351). During a median of 4.6 years of follow-up (interquartile range [IQR]: 3.1 to 5.2 years), the cumulative 5-year incidence of the primary endpoint was 22.4% in the AF group and 24.7% in the CF group (hazard ratio: 0.94; 95% confidence interval: 0.67 to 1.31; p = 0.70). Any coronary revascularization within the first year was more frequently performed in AF group than in CF group (12.8% vs. 3.8%; log-rank p < 0.001), although the difference between the 2 groups attenuated over time with a similar cumulative 5-year incidence (19.6% vs. 18.1%; log-rank p = 0.92)., Conclusions: No clinical benefits were observed for routine FUCAG after PCI and early coronary revascularization rates were increased within routine FUCAG strategy in the current trial. (Randomized Evaluation of Routine Follow-up Coronary Angiography After Percutaneous Coronary Intervention Trial [ReACT]; NCT01123291)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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: Although a cardioprotective effect of estrogen has been suggested by experimental studies, clinical data on the influence of estrogen on left ventricular (LV) diastolic function are sparse. The LV untwisting rate obtained by 2D speckle tracking echocardiography (2D-STE) is correlated with the time constant of LV pressure decay (tau), and this correlation is independent of left atrial pressure. Therefore, we used conventional Doppler echocardiography and 2D-STE to investigate changes in LV diastolic function during a single menstrual cycle in premenopausal women., Methods: Twenty healthy premenopausal woman (mean age, 28.1±2.7 years) were enrolled. Clinical and echocardiographic data were obtained during the follicular phase (F-phase) and luteal phase (L-phase) of a single menstrual cycle. We compared the clinical and echocardiographic data, and estrogen levels between the two phases., Results: There were no significant differences in LV diastolic parameters derived from Doppler echocardiography (E/A, p=0.295; E/e', p=0.449, DcT, p=0.178) or 2D-STE (peak untwisting rate, p=0.892; time-to-peak untwisting, p=0.951) between the two phases of the menstrual cycle. However, there was a significant decrease in estrogen levels between the F- and L-phases (177±119pg/ml vs. 35±12pg/ml, p<0.0001)., Conclusions: LV diastolic function in healthy premenopausal women did not significantly change during the menstrual cycle. Estrogen does not appear to have a significant acute effect on LV diastolic function in premenopausal woman., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Triple antithrombotic therapy increases the risk of bleeding events in patients undergoing percutaneous coronary intervention (PCI) compared with dual anti-platelet therapy (DAPT). However, whether warfarin control is associated with reduced cardiovascular events and major bleeding events in patients undergoing PCI with triple antithrombotic therapy is uncertain., Methods: We investigated 1207 consecutive patients who underwent PCI between 2004 and 2011. Major bleeding complications and major adverse cardiac and cerebrovascular events (MACCE) defined as all-cause death, acute coronary syndrome, target vessel revascularization, and stroke were compared between groups of patients who received either triple antithrombotic therapy or DAPT., Results: Triple antithrombotic therapy was administered to 95 (7.9%) patients. The mean international normalized ratio of prothrombin time (PT-INR) was 1.8. The target PT-INR level was set between 1.6 and 2.6 and the ratio (%) of time in the therapeutic range (TTR) was calculated. The median TTR was 78.4% (interquartile range, 67.4-87.6%). Kaplan-Meier survival curves showed that warfarin therapy was not associated with MACCE (p=0.89) and major bleeding (p=0.80). Multivariable Cox regression analysis revealed that triple antithrombotic therapy was not an independent predictor of MACCE and major bleeding., Conclusions: Triple antithrombotic therapy does not increase the occurrence of MACCE and major bleeding complications, if the warfarin dose is tightly controlled with a lower INR., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)