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Background: Data on the impact of valve position on clinical outcomes in patients with atrial fibrillation (AF) and bioprosthetic valves (BPVs) are limited., Methods and Results: The BPV-AF Registry was a multicenter, prospective, observational study involving 894 patients with BPVs and AF. In this post-hoc substudy, patients were classified according to BPV position: aortic (n=588; 65.8%), mitral (n=195; 21.8%), or both (n=111; 12.4%). The primary outcome was a composite of stroke/systemic embolism, major bleeding, heart failure requiring hospitalization, all-cause death, or BPV reoperation. During a mean follow up of 15.3±4.0 months, the primary outcome occurred in 90 (15.3%) patients (12.7/100 patient-years) in the aortic group, 25 (12.8%; 10.2/100 patient-years) in the mitral group, and 16 (14.4%; 11.8/100 patient-years) in the both-valves group (log-rank P=0.621). The unadjusted and adjusted risks were not significant for the mitral and both-valves groups relative to the aortic group (unadjusted hazard ratio [95% confidence interval] 0.80 [0.52-1.25] and 0.92 [0.54-1.57]; adjusted hazard ratio 0.89 [0.51-1.54] and 1.10 [0.58-2.09], respectively). There was no significant difference in the incidence of stroke/systemic embolism or major bleeding among the 3 groups (log-rank P=0.651 and 0.156, respectively)., Conclusions: In patients with BPVs and AF, the risk for the composite outcome was comparable regardless of the BPV position., Competing Interests: H.T. has received remuneration from AstraZeneca plc, Ono Pharmaceutical Company, Limited, Pfizer Inc, Otsuka Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Boehringer Ingelheim GmbH, Abbott Japan LLC, and Novartis International AG. K.A. has received remuneration from Japan Lifeline, Abbott Medical Japan, Medtronic Japan, BIOTRONIK Japan, TERUMO, and Novartis Pharma. M.I. has received consultancy fees from Abbott Medical Japan LLC, and remuneration from Edwards Lifesciences Corporation. T. Kimura has received remuneration from Abbott Medical Japan LLC, research funding from Research Institute for Production Development, EP-CRSU Co., Ltd, Edwards Lifesciences Corporation, and Kowa Pharmaceutical Co., Ltd, and scholarship funds or donations from Nippon Boehringer Ingelheim Co., Ltd, Otsuka Pharmaceutical Co., Ltd, Daiichi Sankyo Co., Ltd, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Limited, Bayer Yakuhin Ltd, and Research Institute for Production Development. T.S. has received remuneration from Medtronic Japan Co., Ltd. K.M. has received scholarship funds or donations from Edwards Lifesciences Corporation, Terumo Co., Ltd, and Japan Lifeline Co., Ltd. K.T. has received remuneration from Amgen K.K., Bayer Yakuhin Ltd, Daiichi Sankyo Co., Ltd, Kowa Pharmaceutical Co. Ltd, Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd, and Pfizer Japan Inc., research funding from AMI Co., Ltd, Bayer Yakuhin Ltd, Bristol-Myers Squibb K.K., EA Pharma Co., Ltd, and Mochida Pharmaceutical Co., Ltd, scholarship funding from AMI Co., Ltd, Bayer Yakuhin Ltd, Nippon Boehringer Ingelheim Co., Ltd, Chugai Pharmaceutical Co., Ltd, Daiichi Sankyo Co., Ltd, Edwards Lifesciences Corporation, Johnson & Johnson K.K., Ono Pharmaceutical Co., Ltd, Otsuka Pharmaceutical Co., Ltd, and Takeda Pharmaceutical Co., Ltd, and is affiliated with the endowed department sponsored by Abbott Japan Co., Ltd, Boston Scientific Japan K.K., Fides-one Inc., GM Medical Co., Ltd, ITI Co., Ltd, Kaneka Medix Co., Ltd, Nipro Corporation, Terumo Co., Ltd, Abbott Medical Co., Ltd, Cardinal Health Japan LLC, Fukuda Denshi Co., Ltd, Japan Lifeline Co., Ltd, Medical Appliance Co., Ltd, and Medtronic Japan Co., Ltd. Y. Sakata has received remuneration from Daiichi Sankyo Co., Ltd, and Nippon Boehringer Ingelheim Co., Ltd, and scholarship funding from Nippon Boehringer Ingelheim Co., Ltd, Bayer Yakuhin Ltd, and Daiichi Sankyo Co., Ltd. M.F. is an employee of Daiichi Sankyo Co., Ltd. T.T. has received remuneration from Daiichi Sankyo Co., Ltd, and Bayer Yakuhin Ltd. K.N. has received research funding from Philips Japan Ltd, Terumo Co., Ltd, TEPCO Power Grid Inc., and Asahi Kasei Pharma Co. Y.F. has received remuneration from Daiichi Sankyo Co., Ltd, Bayer Yakuhin Ltd, and Novartis Pharma K.K. C.I. has received remuneration and research funding from Daiichi Sankyo Co., Ltd. K.T. is a member of Circulation Reports’ Editorial Team. The other authors have no conflicts of interest to disclose., (Copyright © 2024, THE JAPANESE CIRCULATION SOCIETY.)

Background: Current guidelines recommend direct oral anticoagulants (DOACs) and warfarin for patients with atrial fibrillation (AF) who have a bioprosthetic valve (BPV). However, the data related to elderly patients (aged ≥80 years) with BPV replacement and AF are limited., Methods: This post-hoc subgroup analysis of a BPV-AF Registry enrolled 752 patients with BPV replacement and AF. The primary net outcome was a composite of cardiac death, stroke, systemic embolism, major bleeding, and cardiovascular events., Results: Among 752 patients, 429 (57%) patients were ≥ 80 and 323 (43%) were < 80 years old. The higher risk in patients aged ≥80 than <80 years was significant for the net outcome (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.31-3.17; P = 0.001). After adjustment for confounders, there was no statistically significant difference between warfarin (reference) and DOAC users in the risk of net outcomes (adjusted HR, 1.26; 95% CI, 0.71-2.24; P = 0.44), stroke and systemic embolism (adjusted HR, 2.01; 95% CI, 0.48-8.38; P = 0.34), and major bleeding (adjusted HR, 0.73; 95% CI, 0.11-4.98; P = 0.75) in patients aged ≥80 years old as well as those aged <80 years. Among 489 warfarin users, the cumulative incidence of net outcomes tended to be higher in patients aged ≥80 than <80 years (12.2% vs. 5.7% at 1 year, log-rank P = 0.002). Among 263 DOAC users, however, it was similar between patients aged ≥80 and < 80 years., Conclusions: The present study demonstrated that DOAC showed similar efficacy and safety compared with warfarin even in elderly patients aged ≥80 years with BPV replacement and AF., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Few studies have investigated the clinical characteristics and in-hospital outcomes of patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) using real-world databases in the coronary intervention era., Methods and Results: We conducted a retrospective analysis of 22,236 patients (mean [±SD] age 68±13 years, 23.4% female) enrolled in the Japan Acute Myocardial Infarction Registry (JAMIR) between 2011 and 2016. Based on urgent coronary angiography findings, 286 (1.3%) patients were diagnosed as MINOCA, and the remaining 21,950 (98.7%) as MI with obstructive coronary artery disease (MI-CAD). MINOCA patients were characterized by younger age, fewer coronary risk factors, lower rate of ST-elevation myocardial infarction, lower Killip classification, and lower peak creatinine phosphokinase levels than MI-CAD patients. In-hospital all-cause mortality did not differ between the MINOCA and MI-CAD groups (5.2% vs. 5.7%, respectively; P=0.82). Comparing cause-specific mortality, non-cardiac mortality was higher in the MINOCA than MI-CAD group (4.2% vs. 1.6%; P<0.01). Importantly, non-cardiac death was more prevalent among elderly (≥65 years) than younger (<65 years) patients in the MI-CAD group, whereas this trend was not observed in the MINOCA group., Conclusions: Analysis of the real-world JAMIR database revealed a relatively high prevalence of non-cardiac death among MINOCA patients, underscoring the need for comprehensive management to improve disease prognosis, particularly in younger patients.

Background: Stage B heart failure (HF) refers to structural heart disease without signs or symptoms of HF, so that early intervention may delay or prevent the onset of overt HF. However, stage B HF is a very broad concept, and risk stratification of such patients can be challenging., Methods and Results: We conducted a prospective study of data for 1646 consecutive patients with HF from the KUNIUMI (Kobe University Heart Failure Registry in Awaji Medical Center) registry chronic cohort. The definition of HF stages was based on current guidelines for classification of 29 patients as stage A HF, 761 as stage B HF, 827 as stage C HF, and 29 patients as stage D HF. The primary end point was the time-to-first-event defined as cardiovascular death or HF hospitalization within 2.0 years of follow-up. A maximum of 6 adjustment factor points was assigned based on Cox proportional hazards analysis findings for the hazard ratio (HR) of independent risk factors for the primary end point: 1 point for anemia, estimated glomerular filtration rate <45 mL/min per 1.73 m 2 , brain natriuretic peptide ≥150 pg/mL, and average ratio of early transmitral flow velocity to early diastolic mitral annular velocity >14, and 2 points for clinical frailty scale >3. Patients with stage B HF were stratified into 3 groups, low risk (0-1 points), moderate risk (2-3 points), and high risk (4-6 points). Based on this scoring system (BEEAF 2 [brain natriuretic peptide, estimated glomerular filtration rate, ratio of early transmitral flow velocity to early diastolic mitral annular velocity, anemia, and frailty]), the outcome was found to become worse in accordance with risk level. High-risk patients with stage B HF and patients with stage C HF showed similar outcomes., Conclusions: Our scoring system offers an easy-to-use evaluation of risk stratification for patients with stage B HF.

Background: Approximately 15% to 20% of patients clinically diagnosed with long QT syndrome (LQTS) are genotype-negative (GEN-). Whether they have a different arrhythmic risk or should be managed differently remains unclear, often leading to incomplete treatment., Objectives: The purpose of this study was to compare clinical aspects of GEN- and genotype-positive (GEN+) LQTS patients., Methods: We retrospectively evaluated 832 LQTS patients genetically screened in Japan (n = 347) and Italy (n = 485), including 698 with a disease-causing variant in the KCNQ1, KCNH2, and SCN5A genes (GEN+), and 134 without variants in these LQTS-related genes (GEN-)., Results: At diagnosis, the Japanese patients were more often probands (86% vs 60%), symptomatic (39% vs 18%), and of younger age than the Italian patients; conversely, they used less β-blockers (65% vs 95%), more rarely had a family history (FH) of LQTS (42% vs 73%), and had more cardiac events during follow-up (13% vs 4%) (P < 0.001 for all comparisons). Within the Japanese cohort, the GEN- had more cardiac arrests, used less β-blockers, and had much less FH for LQTS compared their GEN+ counterpart. The Italian cohort was more homogeneous, with just more LQTS FH among the GEN+. QTc shortening (close to 30 ms in all groups) during follow-up was similar between Japanese and Italian patients, irrespective of their being GEN+ or GEN-. In both cohorts, during an average follow-up of 6 and 7 years, respectively, GEN+ and GEN- patients showed a comparable clinical outcome., Conclusions: Arrhythmic risk is similar between GEN+ and GEN- LQTS patients; they should be managed and treated in the same way., Competing Interests: Funding Support and Author Disclosures This work has been partially supported by a grant from Health Science Research Grant from the Ministry of Health, Labor and Welfare of Japan (21FC1004, 23FC1003 to Dr Aiba), a Japanese Circulation Society research grant for genome analysis project in cardiovascular diseases (to Drs Horie and Aiba), the Italian Ministry of Health Ricerca Corrente grant ‘Registry of Cardiac Channelopathies’, the EJP RD Joint Transnational Call for Proposals 2019–Project LQTS-NEXT–EJPRD19-187, and the Fondation Leducq grant 18CVD05 “Towards Precision Medicine with Human iPSCs for Cardiac Channelopathies” (to Drs Crotti and Schwartz). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Aims: This study evaluated the safety and efficacy of catheter ablation in treating atrial fibrillation (AF) among the elderly population., Methods: A total of 170 017 AF ablation procedures prospectively enrolled from 482 facilities between 2017 and 2020 were analysed. They were stratified into six age groups, ranging from < 65 to ≥ 85 years, in 5-year increments. A cut-off of 80 years was set for dividing participants into two groups. The primary endpoints included procedure-related complications and 1-year arrhythmia recurrence after a 3-month blanking period., Results: Patients ≥ 80 years constituted 7.2% of procedures in 2017, which significantly increased to 9.6% by 2020 (p < 0.001). This older group predominantly comprised women, with smaller stature and body mass index, a higher prevalence of paroxysmal AF, and a higher rate of initial ablation procedures. The overall complication rate was 2.8%, showing a positive correlation with age (p < 0.001), peaking at 4.3% for patients ≥ 85 years. Older age remained a significant independent risk factor for complications (odds ratio: 1.36 [1.24, 1.49], p < 0.001). Cardiac tamponade, ischemic stroke, and sick sinus syndrome were more common in the elderly. The recurrence rate in the total population was 16.0% and did not differ significantly between age groups (log-rank p = 0.473), remaining consistent even after adjusting for multiple variables., Conclusions: Although age increases complication risk, recurrence rates remained steady across age groups, suggesting that AF ablation is a reasonable option for elderly individuals, contingent on careful patient selection for safety. (ClinicalTrials.gov: NCT03729232)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The comparative efficacy and safety of adjusted- and standard-dose prasugrel in East Asian patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) remain unclear. This study aimed to comparatively assess the ischaemic and bleeding outcomes of adjusted-dose (maintenance dose: 3.75 mg) and standard-dose (maintenance dose: 10 mg) prasugrel in East Asian patients with AMI undergoing PCI., Methods: From a combined dataset sourced from nationwide AMI registries in Japan and South Korea (n = 17,118), patients treated with either adjusted- or standard-dose prasugrel were identified. Patients who did not undergo emergent PCI, those on oral anticoagulants, and those meeting the criteria of contraindication of prasugrel in South Korea (age ≥ 75 years, body weight < 60 kg, or history of stroke) were excluded. Major adverse cardiovascular events (MACE) and Thrombolysis in Myocardial Infarction (TIMI) major bleeding events were compared between the adjusted-dose (n = 1160) and standard-dose (n = 1086) prasugrel groups., Results: Within the propensity-matched cohort (n = 702 in each group), no significant difference was observed in the in-hospital MACE between the adjusted- and standard-dose prasugrel groups (1.85% vs. 2.71%, odds ratio [OR] 0.68, 95% confidence interval [CI] 0.33-1.38, p = 0.286). However, the incidence of in-hospital major bleeding was significantly lower in the adjusted-dose prasugrel group than in the standard-dose group (0.43% vs. 1.71%, OR 0.25, 95% CI 0.07-0.88, p = 0.031). The cumulative 12-month incidence of MACE was equivalent in both groups (4.70% vs. 4.70%, OR 1.00, 95% CI 0.61-1.64, p = 1.000)., Conclusions: Among East Asian patients with AMI undergoing PCI, those administered adjusted-dose prasugrel exhibited a lower risk of in-hospital bleeding events than those administered standard-dose prasugrel, while maintaining a comparable 1-year incidence of MACE., Competing Interests: Declaration of competing interest Dr. Yasuda reports remuneration for lectures from Takeda, Daiichi Sankyo, and Bristol-Myers Squibb and trust research/joint research funds from Takeda and Daiichi Sankyo; Dr. Takayama reports lecture fees from Daiichi Sankyo; and Dr. Ogawa reports lecture fees and research grants from Abbot Medical Japan, Bayer, Daiichi Sankyo, Eisai, Kowa, Takeda Pharmaceutical, and Teijin. Other authors have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Pregnant women with end-stage kidney disease who undergo peritoneal dialysis have lower pregnancy rates and higher obstetric risk than their peers undergoing hemodialysis. Although there has been some improvement in pregnancy rates and outcomes due to the intensification of dialysis prescriptions, there is currently a lack of guidelines for optimizing peritoneal dialysis regimens for pregnant women with end-stage kidney disease. Besides, there is limited data available regarding pregnancy outcomes in women with end-stage kidney disease undergoing peritoneal dialysis. We report the case of a 23-year-old Hispanic woman with end-stage kidney disease caused by focal and segmental glomerulosclerosis. She became pregnant while undergoing successful treatment with an intensified automated peritoneal dialysis regimen. The patient gave birth to a live female preterm infant weighing 938 g during the 28th week of her pregnancy. The baby required neonatal intensive care due to prematurity, extremely low birth weight, and respiratory distress syndrome., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Aims: The incidence and prognosis of symptomatic heart failure following acute myocardial infarction (AMI) in the primary percutaneous coronary intervention era have rarely been reported in the literature. This study aimed to (i) determine the incidence of heart failure admission among AMI survivors, (ii) compare 1 year outcomes between patients with heart failure admission and those without, and (iii) identify the independent risk factors associated with heart failure admission., Methods and Results: The Japan Acute Myocardial Infarction Registry is a prospective multicentre registry from which data on consecutively enrolled patients with AMI from 50 institutions between 2015 and 2017 were obtained. Among the 3411 patients enrolled, 3226 who survived until discharge were included in this study. The primary endpoint was all-cause mortality. The secondary endpoints were major adverse cardiovascular events (defined as cardiovascular mortality, non-fatal myocardial infarction, or non-fatal cerebral infarction) and major bleeding events corresponding to Bleeding Academic Research Consortium Type 3 or 5. Clinical outcomes were compared between the patients who were and were not admitted for heart failure. Over a median follow-up of 12 months, 124 patients (3.8%) were admitted due to heart failure. Independent risk factors for heart failure admission included older age, female sex, Killip class ≥2 on admission, left ventricular ejection fraction <40%, estimated glomerular filtration rate ≤30 mL/min/1.73 m 2 , a history of malignancy, and non-use of angiotensin-converting enzyme inhibitors at discharge. The cumulative incidence of all-cause mortality was significantly higher in the heart failure admission group than in the no heart failure admission group (11.3% vs. 2.5%, P < 0.001). The rates of major adverse cardiovascular events (16.9% vs. 2.7%, P < 0.001) and major bleeding (6.5% vs. 1.6%, P < 0.001) were significantly higher in the heart failure admission group. Heart failure admission was associated with a higher risk of all-cause mortality, even after adjusting for potential confounders (adjusted hazard ratio: 2.41, 95% confidence interval: 1.33-4.39, P = 0.004)., Conclusions: Utilizing real-world data of the contemporary percutaneous coronary intervention era from the Japan Acute Myocardial Infarction Registry database, this study demonstrates that the heart failure admission of AMI survivors was significantly associated with higher all-cause mortality rates., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: There are few studies evaluating the prognostic prediction method in atrial fibrillation (AF) patients after bioprosthetic valve (BPV) replacement. The R 2 -CHA 2 DS 2 -VASc score is increasingly used for the prediction of cardiovascular (CV) events in patients with AF, device implantation, and acute coronary syndrome. We aimed to evaluate the predictive value of the R 2 -CHA 2 DS 2 -VASc score for future CV events in AF patients after BPV replacement., Methods and Results: The BPV-AF, an observational, multicenter, prospective registry, enrolled AF patients who underwent BPV replacement. The primary outcome measure was a composite of stroke, systemic embolism, CV events including heart failure requiring hospitalization, and cardiac death. A total of 766 patients was included in the analysis. The mean R 2 -CHA 2 DS 2 -VASc score was 5.7±1.8. Low (scores 0-1), moderate (scores 2-4), and high (scores 5-11) R 2 -CHA 2 DS 2 -VASc score groups consisted of 12 (1.6%), 178 (23.2%), and 576 (75.2%) patients, respectively. The median follow-up period was 491 (interquartile range 393-561) days. Kaplan-Meier analysis showed a higher incidence of the composite CV events in the high R 2 -CHA 2 DS 2 -VASc score group (log rank test; P<0.001). Multivariate Cox proportional hazards regression analysis revealed that the R 2 -CHA 2 DS 2 -VASc score as a continuous variable was an independent predictor of composite CV outcomes (hazard ratio 1.36; 95% confidence interval 1.18-1.55; P<0.001)., Conclusions: The R 2 -CHA 2 DS 2 -VASc score is useful for CV risk stratification in AF patients after BPV replacement., Competing Interests: H.T. has received consultancy fees from AstraZeneca PLC and Ono Pharmaceutical Co., Ltd. K.A. has received remuneration from Japan Lifeline Co., Ltd, Terumo Corporation, and Medtronic Japan Co., Ltd. M.I. has received consultancy fees from Abbott Medical Japan LLC, and remuneration from Edwards Lifesciences Corporation. T.S. has received remuneration from Medtronic Japan Co., Ltd. K.M. has received scholarship funds or donations from Edwards Lifesciences Corporation, Terumo Co., Ltd, and Japan Lifeline Co., Ltd. K.M. has received scholarship funds or donations from Edwards Lifesciences Corporation, Terumo Co., Ltd., and Japan Lifeline Co., Ltd. K.T. is a member of Circulation Reports’ Editorial Team, and has received remuneration from Amgen K.K., Bayer Yakuhin Ltd, Daiichi Sankyo Co., Ltd, Kowa Pharmaceutical Co. Ltd, Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd, and Pfizer Japan Inc.; research funding from AMI Co., Ltd, Bayer Yakuhin Ltd, Bristol-Myers Squibb K.K., EA Pharma Co., Ltd, and Mochida Pharmaceutical Co., Ltd; scholarship funding from AMI Co., Ltd, Bayer Yakuhin Ltd, Nippon Boehringer Ingelheim Co., Ltd, Chugai Pharmaceutical Co., Ltd, Daiichi Sankyo Co., Ltd, Edwards Lifesciences Corporation, Johnson & Johnson K.K., Ono Pharmaceutical Co., Ltd, Otsuka Pharmaceutical Co., Ltd, and Takeda Pharmaceutical Co., Ltd; and is affiliated with the endowed department sponsored by Abbott Japan Co., Ltd, Boston Scientific Japan K.K., Fides-one Inc., GM Medical Co., Ltd, ITI Co., Ltd, Kaneka Medix Co., Ltd, Nipro Corporation, Terumo Co., Ltd, Abbott Medical Co., Ltd, Cardinal Health Japan LLC, Fukuda Denshi Co., Ltd, Japan Lifeline Co., Ltd, Medical 3 Appliance Co., Ltd, and Medtronic Japan Co., Ltd. Y. Sakata has received remuneration from Daiichi Sankyo Co., Ltd, and Nippon Boehringer Ingelheim Co., Ltd; and scholarship funding from Nippon Boehringer Ingelheim Co., Ltd, Bayer Yakuhin Ltd, and Daiichi Sankyo Co., Ltd. K.S. is an employee of Daiichi Sankyo Co., Ltd. K.N. has received research funding from Philips Japan Ltd, Terumo Co., Ltd, TEPCO Power Grid Inc., and Asahi Kasei Pharma Co. C.I. has received remuneration and research funding from Daiichi Sankyo Co., Ltd. Y.F. has received remuneration from Daiichi Sankyo Co., Ltd, and Bayer Yakuhin Ltd. All other authors have no conflicts of interest to disclosure., (Copyright © 2024, THE JAPANESE CIRCULATION SOCIETY.)

Background: Preplanning of care is necessary for patients with endstage heart failure (HF), but advance care planning (ACP) before the loss of a patient's comprehensive capacity is not yet routine for the public or the medical community. The challenge in accurately predicting a patient's prognosis is a strong barrier to implementing ACP. To address this problem, several models for risk stratification have been proposed and are available in clinical settings. Methods and Results: We randomized the procedure to provide estimated patient survival information to attending physicians and then assessed whether there was a change in (1) the frequency of ACP initiation occurred (physician-side evaluation), and/or (2) the patients' quality of life, including mental state (patient-side evaluation). Conclusions: This multicenter, open-label, single-blinded randomized clinical trial aims to assess the hypothesis that providing information on the estimated survival of a patient to the attending physicians will improve the frequency of ACP initiation and quality of life in patients with HF., Competing Interests: All authors have nothing to declare conflict of interest/competing interests in connection with this article., (Copyright © 2024, THE JAPANESE CIRCULATION SOCIETY.)

Objectives: Intracerebral hemorrhage (ICH) and cerebral microbleeds (CMB) in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy are more common in East Asian populations than in people of white European ancestry. We hypothesized that the ethnic difference is explained by the East Asian-specific NOTCH3 p.R75P mutation., Methods: This retrospective observational study included 118 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in Japanese and Korean cohorts. We investigated whether the p.R75P mutation is associated with symptomatic ICH and multiple CMB (>5) using quasi-Poisson regression models. We predicted the NOTCH3 extracellular domain protein structures in silico and graded NOTCH3 extracellular domain immunostaining in skin vessels of some patients, with subsequent comparisons between p.R75P and other conventional mutations., Results: Among 63 Japanese patients (median age 55 years; 56% men), 15 had a p.R75P mutation, significantly associated with symptomatic ICH (adjusted relative risk 9.56, 95% CI 2.45-37.31), multiple CMB (3.00, 1.34-6.71), and absence of temporopolar lesions (4.91, 2.29-10.52) after adjustment for age, sex, hypertension, and antithrombotics. In the Korean cohort (n = 55; median age 55 years; 51% men), the p.R75P mutation (n = 13) was also associated with symptomatic ICH (8.11, 1.83-35.89), multiple CMB (1.90, 1.01-3.56), and absence of temporopolar lesions (2.32, 1.08-4.97). Structural analysis revealed solvent-exposed free cysteine thiols in conventional mutations, directly causing aggregation, whereas a stereochemically incompatible proline residue structure in p.R75P lowers correct disulfide bond formation probability, indirectly causing aggregation. Pathologically, the p.R75P mutation resulted in less vascular NOTCH3 extracellular domain accumulation than the other conventional mutations., Interpretation: NOTCH3 p.R75P mutation is associated with hemorrhagic presentations, milder temporopolar lesions, and distinct mutant protein structure properties. ANN NEUROL 2024;95:1040-1054., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: This post hoc subanalysis aimed to investigate the impact of polyvascular disease (PolyVD) in patients with acute myocardial infarction (AMI) in the contemporary era of percutaneous coronary intervention (PCI)., Methods and results: The Japan Acute Myocardial Infarction Registry (JAMIR), a multicenter prospective registry, enrolled 3,411 patients with AMI between December 2015 and May 2017. Patients were classified according to complications of a prior stroke and/or peripheral artery disease into an AMI-only group (involvement of 1 vascular bed [1-bed group]; n=2,980), PolyVD with one of the complications (2-bed group; n=383), and PolyVD with both complications (3-bed group; n=48). The primary endpoint was all-cause death. Secondary endpoints were major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and major bleeding. In the 1-, 2-, and 3-bed groups, the cumulative incidence of all-cause death was 6.8%, 17.5%, and 23.7%, respectively (P<0.001); that of MACE was 7.4%, 16.4%, and 33.8% (P<0.001), respectively; and that of major bleeding was 4.8%, 10.0%, and 13.9% (P<0.001), respectively. PolyVD was independently associated with all-cause death (hazard ratio [HR] 2.21; 95% confidence interval [CI], 1.48-3.29), MACE (HR 2.07; 95% CI 1.40-3.07), and major bleeding (HR 1.68; 95% CI 1.04-2.71)., Conclusions: PolyVD was significantly associated with worse outcomes, including thrombotic and bleeding events, in the contemporary era of PCI in AMI patients.

Background: Outpatient cardiac rehabilitation (CR) is a promising tool for improving functional outcome in stroke survivors, however, evidence for improving emotional health is limited. We aimed to clarify the effects of outpatient CR following in-hospital stroke rehabilitation on health-related quality of life (HRQOL) and motor function., Methods: Patients with acute ischemic stroke or transient ischemic attack discharged directly home were recruited, and 128 patients who fulfilled criteria for insurance coverage of CR were divided into the CR (+) group (n = 46) and CR (-) group (n = 82). All patients underwent in-hospital stroke rehabilitation, and within 2 months after stroke onset, patients in the CR (+) group started a 3-month outpatient CR program of supervised sessions. Changes of motor function and HRQOL assessed by the short form-36 version 2 (SF-36) from discharge to 3 months post-discharge were compared between the two groups., Results: Twenty-six patients in the CR (+) group completed the program and 66 patients in the CR (-) group were followed up at a 3-month examination. Least-square mean changes in 6-minute walk distance and isometric knee extension muscle strength were significantly higher in the CR (+) group than the CR (-) group (52.6 vs. 16.3 m; 10.1 vs. 3.50 kgf/kg). Improvement of HRQOL at 3 months was not observed in the CR (+) group., Conclusions: Outpatient CR following in-hospital stroke rehabilitation within 2 months after stroke onset improved exercise tolerance and functional strength but not HRQOL assessed by the SF-36 after completion of CR in the present cohort., 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 © 2024 Elsevier Ltd. All rights reserved.)

Phosphorylation of proteins on tyrosine (Tyr) residues evolved in metazoan organisms as a mechanism of coordinating tissue growth 1 . Multicellular eukaryotes typically have more than 50 distinct protein Tyr kinases that catalyse the phosphorylation of thousands of Tyr residues throughout the proteome 1-3 . How a given Tyr kinase can phosphorylate a specific subset of proteins at unique Tyr sites is only partially understood 4-7 . Here we used combinatorial peptide arrays to profile the substrate sequence specificity of all human Tyr kinases. Globally, the Tyr kinases demonstrate considerable diversity in optimal patterns of residues surrounding the site of phosphorylation, revealing the functional organization of the human Tyr kinome by substrate motif preference. Using this information, Tyr kinases that are most compatible with phosphorylating any Tyr site can be identified. Analysis of mass spectrometry phosphoproteomic datasets using this compendium of kinase specificities accurately identifies specific Tyr kinases that are dysregulated in cells after stimulation with growth factors, treatment with anti-cancer drugs or expression of oncogenic variants. Furthermore, the topology of known Tyr signalling networks naturally emerged from a comparison of the sequence specificities of the Tyr kinases and the SH2 phosphotyrosine (pTyr)-binding domains. Finally we show that the intrinsic substrate specificity of Tyr kinases has remained fundamentally unchanged from worms to humans, suggesting that the fidelity between Tyr kinases and their protein substrate sequences has been maintained across hundreds of millions of years of evolution., (© 2024. The Author(s).)

Purpose: Little is known about the outcomes of patients with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI) who undergo coronary artery bypass grafting (CABG) in the current percutaneous coronary intervention (PCI) era., Methods: We analyzed 25120 acute myocardial infarction (AMI) patients hospitalized between January 2011 and December 2016. In-hospital outcomes were compared between patients who underwent CABG during hospitalization and those who did not undergo CABG in the STEMI group (n = 19428) and NSTEMI group (n = 5692)., Results: Overall, CABG was performed in 2.3% of patients, while 90.0% of registered patients underwent primary PCI. In both the STEMI and NSTEMI groups, patients who underwent CABG were more likely to have heart failure, cardiogenic shock, diabetes, left main trunk lesion, and multivessel disease than those who did not undergo CABG. In multivariable analysis, CABG was associated with lower all-cause mortality in both the STEMI group (adjusted odds ratio [OR] = 0.43, 95% confidence interval [CI] 0.26-0.72) and NSTEMI group (adjusted OR = 0.34, 95% CI 0.14-0.84)., Conclusion: AMI patients undergoing CABG were more likely to have high-risk characteristics than those who did not undergo CABG. However, after adjusting for baseline differences, CABG was associated with lower in-hospital mortality in both the STEMI and NSTEMI groups.

The use of the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) for research has increased over time. Researchers need to understand the characteristics of the data to generate quality-assured evidence from the NDB. In this review, we mapped and characterized the limitations and related strategies using the NDB for research based on the descriptions of published NDB studies. To find studies that used Japanese healthcare claims data, we searched MEDLINE, EMBASE, and Ichushi-Web up to June 2023. Additionally, we hand-searched the NDB data publication list from the Ministry of Health, Labour and Welfare (2017-2023). We abstracted data based on the NDB data type, research themes, age of the study sample or population, targeted disease, and the limitations and strategies in the NDB studies. Ultimately, 267 studies were included. Overall, the most common research theme was describing and estimating the prescriptions and treatment patterns (125 studies, 46.8%). There was a variation in the frequency of themes according to the type of NDB data. We identified the following categories of limitations: (1) lack of information on confounders/covariates, outcomes, and other clinical content, (2) limitations regarding patients not included in the NDB, (3) misclassification of data, (4) lack of unique identifiers and register of beneficiaries, and (5) others. Although the included studies noted several limitations of using the NDB for research, they also provided some strategies to address them. Organizing the limitations of NDB in research and the related strategies across research fields can help support high-quality NDB studies., Competing Interests: None, (Copyright © Japan Medical Association.)

Background: The number of patients with remnant gastric cancer (RGC) following gastrectomy for gastric cancer (GC) is increasing due to the increasing number of patients undergoing function-preserving gastrectomy and improved outcomes for patients with GC. A few studies involving a small number of cases reported male sex, old age, differentiated type, tumor depth and synchronous multiple GC were associated with RGC development. However, the risk factors for RGC development had not been fully understood. This study aimed to examine the clinicopathological features, followed up patients with GC after they underwent distal gastrectomy (DG), and evaluated the potential risk factors for RGC development., Methods: A retrospective database review of 438 patients who underwent DG for GC at a single institution, from 2006 to 2017, was conducted. We investigated the relationship of clinicopathological features, operative findings, and postoperative course with RGC development was estimated using Cox proportional hazard analysis. The cumulative incidences of RGC were calculated using the Kaplan-Meier method., Results: We retrospectively analyzed 405 cases. The median patient age was 69 years, and the patient cohort consisted of 263 men and 142 women. The Billroth-I reconstruction method was used in 204 cases, Billroth-II method was used in 3 cases, and Roux-en Y method was used in 198 cases. RGC was diagnosed in 11 of the 405 patients. The median follow-up period was 5 years. The cumulative incidences of RGC calculated by the Kaplan-Meier method were 3.0%, 4.1%, and 10.5% at 5, 10, and 15 years after DG, respectively. During the initial surgery, differentiated type was significantly associated with RGC development [hazard ratio (HR): 4.71, 95% confidence interval (CI): 1.02-21.80, P=0.05]. Male sex (HR: 2.97, 95% CI: 0.64-13.75, P=0.16), old age (≥70 years) (HR: 2.72, 95% CI: 0.78-9.47, P=0.11), and synchronous multiple GC (HR: 1.31, 95% CI: 0.28-6.08, P=0.73) were not associated with RGC development., Conclusions: Patients who have undergone DG for differentiated type GC were statistically significantly associated with developing RGC. Intensive endoscopic surveillance would be needed for the patients who underwent DG for differentiated type GC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-545/coif). The authors have no conflicts of interest to declare., (2023 Journal of Gastrointestinal Oncology. All rights reserved.)

Aims: ST-segment elevation myocardial infarction complicated by cardiogenic shock (STEMICS) is associated with substantial mortality. As life expectancy increases, percutaneous coronary intervention (PCI) is being performed more frequently, even in elderly patients with acute myocardial infarction (AMI). This study sought to investigate the characteristics and impact of PCI on in-hospital mortality in patients with STEMICS., Methods and Results: The Japan AMI Registry (JAMIR) is a retrospective, nationwide, real-world database. Among 46 242 patients with AMI hospitalized in 2011-2016, 2760 patients with STEMICS (median age, 72 years) were studied. We compared 2396 (86.8%) patients who underwent PCI with 364 (13.2%) patients who did not. The percentage of mechanical circulatory support use in patients with STEMICS was 69.3% and in-hospital mortality was 34.6%. Compared with patients who did not undergo PCI, patients undergoing PCI were younger and had a higher rate of intra-aortic balloon pump use. A higher proportion was male or current smokers. In-hospital mortality was significantly lower in the PCI group than in the no-PCI group (31.3% vs. 56.0%, P < 0.001). Percutaneous coronary intervention was independently associated with lower in-hospital mortality [adjusted odds ratio (OR), 0.508; 95% confidence interval (CI), 0.347-0.744]. In 789 (28.6%) patients aged ≥80 years, PCI was associated with fewer in-hospital cardiac deaths (adjusted OR, 0.524; 95% CI, 0.281-0.975), but was not associated with in-hospital mortality (adjusted OR, 0.564; 95% CI, 0.300-1.050)., Conclusion: In Japan, PCI was effective in reducing in-hospital cardiac death in elderly patients with STEMICS. Age alone should not preclude potentially beneficial invasive therapy., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Cognitive impairment and functional status are both important determinants of poor outcomes in heart failure (HF). However, little is known about how functional status impacts the changes in cognitive status during the disease course. This study aimed to describe the cognitive transitions in patients with HF and assess the relationship of these transitions to functional status, which was assessed by the dependency of activities of daily living (ADL)., Methods and Results: This retrospective cohort study included 1764 patients with an International Classification of Diseases-10 code of HF (≥65 years, mean age 82.3 ± 7.9 years, 39% male) from a long-term care and medical insurance database from Nobeoka city, a rural city of south-western Japan. Cognitive status at baseline and 6, 12, 18, and 24 month time points was collected, and participants were stratified based on ADL status at baseline. Generalized estimating equations and multi-state modelling were used to examine associations between ADL dependency and cognitive changes/mortality. Transition probabilities were estimated using multi-state modelling. At baseline, there were 1279 (73%) and 485 (27%) patients with independent and dependent ADL, respectively. In overall patients, 1656 (93.9%) patients had normal/mild cognitive status and 108 (6%) patients had a moderate/severe cognitive status at baseline. The majority [104 (96%) patients] of patients with moderate/severe cognitive status at baseline had dependent ADL. In patients with moderate/severe cognitive status, the number of patients with dependent ADL always outnumbered that of the independent ADL throughout the follow-up. Multi-state modelling estimated that patients with dependent ADL and normal/mild cognitive status at baseline had 47% probability of maintaining the same cognitive status at 24 months, while the probability of maintaining the same cognitive status was 86% for those with independent ADL. Patients with normal/mild cognitive status in the dependent ADL group at baseline had a higher risk of experiencing a transition to moderate/severe cognitive status at any time point during 24 months compared with those with independent ADL [hazard ratio 5.24 (95% confidence interval 3.47-7.90)]., Conclusions: In older patients with HF, the prevalence of cognitive impairment was always higher for those with reduced functional status. Despite having a normal/mild cognitive status at baseline, patients with dependent ADL are at high risk of experiencing cognitive decline over 24 months with substantially less chance of maintaining their cognitive status. ADL dependency was an important risk factor of cognitive decline in patients with HF., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Cerebral microbleeds (CMBs) influence long-term prognoses of stroke patients. Streptococcus mutans expressing the collagen-binding protein Cnm induces cerebrovascular inflammation, impairing blood brain barrier integrity and causing cerebral bleeding. Here, we examine the association of Cnm-positive S. mutans with CMBs., Methods: Acute stroke patients were selected from a single-center registry database. Oral carriage of Cnm-positive or Cnm-negative S. mutans was determined using polymerase chain reaction assays. The associations of Cnm-positive S. mutans with CMB number and specifically the presence of >10 CMBs were examined using quasi-Poisson and logistic regression models, respectively., Results: This study included 3154 stroke patients, of which 428 patients (median [interquartile range] age, 73.0 [63.0-81.0] years; 269 men [62.9%]) underwent oral bacterial examinations. In total, 326 patients harbored S. mutans. After excluding four patients without imaging data, we compared patients with Cnm-positive (n = 72) and Cnm-negative (n = 250) S. mutans. Harboring Cnm-positive S. mutans was independently associated with the presence of >10 CMBs (adjusted odds ratio 2.20 [1.18-4.10]) and higher numbers of deep and lobar CMBs (adjusted risk ratio 1.61 [1.14-2.27] for deep; 5.14 [2.78-9.51] for lobar), but not infratentorial CMBs, after adjusting for age, sex, hypertension, stroke type, National Institutes of Health Stroke Scale score, and cerebral amyloid angiopathy., Conclusions: Harboring Cnm-positive S. mutans was independently associated with a higher number of CMBs in deep and lobar locations. Reducing Cnm-positive S. mutans in the oral cavity may serve as a novel therapeutic approach for stroke., (© 2023 European Academy of Neurology.)

Aims/introduction: Dapagliflozin is used for individuals with type 1 diabetes, although the effect of this medication on skeletal muscle mass is not well established. In addition, there are few studies examining the effects of good glycemic control on skeletal muscle mass in type 1 diabetes patients. We investigated changes in glycemic control and skeletal muscle mass with dapagliflozin in individuals with type 1 diabetes, and the association between these changes., Materials and Methods: This was a post-hoc analysis of a multicenter, open-label, non-randomized, prospective, interventional study in individuals with type 1 diabetes. The participants received dapagliflozin at 5 mg/day for 4 weeks, and were reviewed before and after treatment. Weight- and height-corrected appendicular skeletal muscle mass (ASM) were calculated as indices of skeletal muscle mass using bioelectrical impedance analysis., Results: A total of 36 individuals were included in the analysis. After the 4 weeks of dapagliflozin treatment, ASM/height 2 decreased in the body mass index <23 group (P = 0.004). ASM / weight decreased in all men aged >60 years. The change in ASM / weight (%) was negatively correlated with the change in glycated hemoglobin (%;P = 0.023). The change in ASM / height 2 (kg/m 2 ) was also positively correlated with the change in time within the glucose range of 70-180 mg/dL (P = 0.036)., Conclusion: Dapagliflozin treatment of individuals with type 1 diabetes, particularly non-obese individuals and older men, might result in loss of skeletal muscle mass. However, good glycemic control during treatment might prevent the onset and progression of sarcopenia., (© 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

The Japanese Catheter Ablation (J-AB) registry, started in August 2017, is a voluntary, nationwide, multicenter, prospective, observational registry, performed by the Japanese Heart Rhythm Society (JHRS) in collaboration with the National Cerebral and Cardiovascular Center using a Research Electronic Data Capture system. The purpose of this registry is to collect the details of target arrhythmias, the ablation procedures, including the type of target arrhythmias, outcomes, and acute complications in the real-world settings. During the year of 2021, we have collected a total of 89 609 procedures (mean age of 66.1 years and 65.9% male) from 506 participant hospitals. Detailed data are shown in Figures and Tables., Competing Interests: Kengo Kusano: Speaker honoraria from DAIICHI SANKYO COMPANY, Ltd., Bayer Yakuhin, and Medtronic Japan, and research grants from Medtronic Japan, HITACHI, and JSR. Teiichi Yamane: Speaker honoraria from Medtronic Japan, and BEG, and research grants from Japan Lifeline. Koichi Inoue: Speaker honoraria from DAIICHI SANKYO COMPANY, Ltd., Bristol Myers Squibb, Bayer Yakuhin, Nippon Boehringer Ingelheim, Johnson & Johnson KK, Medtronic Japan, and Boston Scientific Japan. Koji Miyamoto received research fundings irrelevant to this study from Abbott, Japan Lifeline, Boston and lecture fees from Abbott, Nihon‐koden, Johnson & Johnson KK, Medtronic Japan, DAIICHI SANKYO COMPANY, Ltd., Brystol Myer Squibb, Pfizer, Bayer Yakuhin. Seiji Takatsuki received research fundings irrelevant to this study from Nippon Boehringer Ingelheim, Japan Lifeline, Eizai, Boston Scientific Japan, Johnson & Johnson KK and lecture fees from Medtronic Japan, Japan Lifeline, DAIICHI SANKYO COMPANY, Ltd., Pfizer, Boston Scientific Japan, Bayer Yakuhin, Biotronik Japan, Nippon Boehringer Ingelheim, Brystol Myers Squibb, Nihon‐koden. Wataru Shimizu: Research grant from DAIICHI SANKYO COMPANY, Ltd., and Nippon Boehringer Ingelheim, and Speaker honoraria from DAIICHI SANKYO COMPANY, Ltd., Bristol Myers Squibb, Bayer Yakuhin, Nippon Boehringer Ingelheim, Ono Pharmaceutical Co, Ltd, Pfizer, Novartis Pharma K.K., and Medtronic Japan. None: M.T., M.K, M.N, K.K, R.T, Y.I, K.N., (© 2023 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)