Differential Prognostic Impact of Clinical Congestion between Preserved versus Reduced Ejection Fraction in Patients Hospitalized for Acute Decompensated Heart Failure: Findings from the Japanese KCHF registry.

BACKGROUNDS: Most patients hospitalized for heart failure (HF) present with signs of congestion. Prognostic significance of clinical congestion may vary depending on left ventricular ejection fraction (LVEF). This study aims to investigate the prognostic impact of congestion across different LVEF categories. METHODS AND RESULTS: Composite congestion scores (CCS) (0-9) derived from the severity of edema, jugular venous pressure, and orthopnea, were analyzed on admission and at discharge in 3787 patients hospitalized for HF (LVEF≥40%: n=2347, LVEF<40%: n=1440). The median admission CCS was 4 in both LVEF strata (P=0.64). Adjusted HRs (95%CI) of the moderate [CCS 4-6] and severe congestion [7-9] groups relative to the mild congestion [0-3] group on admission for a composite of all-cause death or HF re-hospitalization were 1.20 (1.04-1.39, P=0.01) and 1.54 (1.27-1.86, P<0.001) in the LVEF≥40% stratum, and 1.20 (1.01-1.44, P=0.04) and 0.82 (0.61-1.07, P=0.14) in the LVEF<40% stratum, respectively (Pinteraction<0.001). 16% of the patients with LVEF ≥40% and 14% with LVEF <40% had residual congestion (CCS ≥1) at discharge, which was associated with respective adjusted HR of 1.40 (1.18-1.65, P <0.001) and 1.25 (0.98-1.58, P=0.07) for post-discharge death or HF re-hospitalization (Pinteraction=0.63). CONCLUSION: The severity of clinical congestion on admission was associated with adverse clinical outcomes in patients with LVEF ≥40%, but no in those with LVEF <40%. These findings warrant further studies to better understand the detailed profile of congestion across the LVEF spectrum.

Prevalence and Factors Associated with Mental Health Complaints in Japanese Collegiate Athletes.

Investigations into mental health epidemiology in various cultural contexts were one of the main recommendations by the recent consensus statement on mental health in athletes, but the evidence in different sporting populations is rising slowly. This study aimed to investigate the prevalence of mental health complaints in Japanese collegiate athletes. The online survey was sent to the Japanese collegiate athletes associated with UNIVAS asking about the mental health complaints experienced during their sporting careers. Out of 10,999 athletes, 269 (2.4%) reported at least one complaint. Mental health complaints were more prevalent in female (3.6%) than male (1.5%) athletes. Skill sports had the highest prevalence (4.1%) of mental health complaints, and power sports had the lowest prevalence (1.5%) of mental health complaints. This study found a very low prevalence of self-reported mental health complaints in Japanese collegiate athletes. Preventive efforts should focus on monitoring early symptoms (rather than diagnoses), especially in skill sports and female athletes. Anxiety (38%) and depression (35%) were the most reported complaints and should be targeted first.

Utility of the modified Ottawa score for identification of more preferable candidates of extended anticoagulation therapy in cancer-associated isolated distal deep vein thrombosis: insight from the ONCO DVT Study.

BACKGROUND: The ONCO DVT study (Edoxaban for 12 Months Versus 3 Months in Patients With Cancer With Isolated Distal Deep Vein Thrombosis) revealed superiority of 12-month relative to 3-month edoxaban treatment for the thrombotic risk in cancer-associated isolated distal deep vein thrombosis. However, it is unknown whether the superiority could be common in different modified Ottawa score subgroups. OBJECTIVES: To identify more preferable candidates for extended anticoagulation in patients with cancer-associated isolated distal deep vein thrombosis using the modified Ottawa score. METHODS: In this post-hoc subgroup analysis of the ONCO DVT study, we stratified 601 patients into the low (≤-1, N = 126), intermediate (0, N = 323), and high (≥1, N = 152) modified Ottawa score subgroups and compared clinical outcomes between the 12-month and 3-month edoxaban treatment groups. RESULTS: The cumulative incidence of symptomatic recurrent venous thromboembolism or venous thromboembolism-related death was not different between the 12-month and 3-month edoxaban treatment groups in the low score subgroup (0.0% vs 2.2%), whereas it was lower in the 12-month than in the 3-month edoxaban treatment group in the intermediate (0.8% vs 7.6%) and high (3.1% vs 15.6%) score subgroups. There were no significant differences in the cumulative incidences of the major bleeding between the 12-month and 3-month edoxaban treatment groups in the low (10.1% vs 7.6%), intermediate (8.8% vs 5.0%), and high (13.9% vs 12.6%) score subgroups. CONCLUSION: A 12-month compared with 3-month edoxaban treatment showed a lower risk of thrombotic events in patients with cancer-associated isolated distal deep vein thrombosis in the intermediate and high modified Ottawa score subgroups but not in the low score subgroup, suggesting a limited benefit of extended anticoagulation therapy beyond 3 months in patients with low modified Ottawa score.

SMAD3 mediates the specification of human induced pluripotent stem cell-derived epicardium into progenitors for the cardiac pericyte lineage.

Understanding the molecular mechanisms of epicardial epithelial-to-mesenchymal transition (EMT), particularly in directing cell fate toward epicardial derivatives, is crucial for regenerative medicine using human induced pluripotent stem cell (iPSC)-derived epicardium. Although transforming growth factor ß (TGF-ß) plays a pivotal role in epicardial biology, orchestrating EMT during embryonic development via downstream signaling through SMAD proteins, the function of SMAD proteins in the epicardium in maintaining vascular homeostasis or mediating the differentiation of various epicardial-derived cells (EPDCs) is not yet well understood. Our study reveals that TGF-ß-independent SMAD3 expression autonomously predicts epicardial cell specification and lineage maintenance, acting as a key mediator in promoting the angiogenic-oriented specification of the epicardium into cardiac pericyte progenitors. This finding uncovers a novel role for SMAD3 in the human epicardium, particularly in generating cardiac pericyte progenitors that enhance cardiac microvasculature angiogenesis. This insight opens new avenues for leveraging epicardial biology in developing more effective cardiac regeneration strategies.

Selection of Home Treatment and Identification of Low-Risk Patients With Pulmonary Embolism Based on Simplified Pulmonary Embolism Severity Index Score in the Era of Direct Oral Anticoagulants.

BACKGROUND: The simplified Pulmonary Embolism Severity Index (sPESI) score could help identify low-risk patients with pulmonary embolism for home treatment. However, the application of the sPESI score and selection for home treatment have not been fully evaluated in the direct oral anticoagulants era. METHODS AND RESULTS: The COMMAND VTE (Contemporary Management and Outcomes in Patients With Venous Thromboembolism) Registry-2 is a multicenter registry enrolling consecutive patients with acute symptomatic venous thromboembolism. The current study population consists of 2496 patients with hemodynamically stable pulmonary embolism (2100 patients [84%] treated with direct oral anticoagulants), who were divided into 2 groups: sPESI scores of 0 and ≥1. We investigated the 30-day mortality, home treatment prevalence, and factors predisposing to home treatment using the Kaplan-Meier method and logistic regression model. Patients with an sPESI score of 0 accounted for 612 (25%) patients, and only 17% among 532 patients with out-of-hospital pulmonary embolism were treated at home. The cumulative 30-day mortality was lower in patients with an sPESI score of 0 than the score of ≥1 (0% and 4.8%, log-rank P<0.001). There was no patient with 30-day mortality with an sPESI score of 0. Independent factors for home treatment among out-of-hospital pulmonary embolism patients with an sPESI score of 0 were no transient risk factors for venous thromboembolism, no cardiac biomarker elevation, and direct oral anticoagulants use in the acute phase. CONCLUSIONS: The 30-day mortality rate was notably low in an sPESI score of 0. Nevertheless, only a minority of patients with an sPESI score of 0 were treated at home between 2015 and 2020 after the introduction of direct oral anticoagulants for venous thromboembolismin Japan.

Serum mature and furin-cleaved proprotein convertase subtilisin/kexin type 9 levels and their association with cardiovascular events in statin-treated patients with cardiovascular disease.

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.

Evaluation of the drug-drug interactions management system for appropriate use of nirmatrelvir/ritonavir: a retrospective observational study.

PURPOSE: While nirmatrelvir/ritonavir (NMV-r) has been positioned as a first-line treatment for mild to moderate COVID-19, it has multiple and significant drug-drug interactions (DDIs). The use of NMV-r in Japan has been limited compared to the United States. This study aimed to describe the distribution of DDIs with NMV-r and their management in patients with COVID-19 under the control of a management system for the appropriate use of NMV-r. METHODS: A retrospective observational study was conducted at a Japanese university hospital. The management system included a flowchart for selecting antivirals and a list for reviewing DDI management, based on the National Institutes of Health guidelines and the guidance of the Japanese Society of Pharmaceutical Health Care and Sciences. Patients with mild to moderate COVID-19 and prescribed NMV-r or molnupiravir (MOV) were included. The primary outcome was DDI management practices, including the selected COVID-19 medications. The secondary outcome included the distribution of DDI classification and the 30-day all-cause mortality. RESULTS: This study included 241 patients (median age of 60 years, 112 [46.5%] females), of whom 126 and 115 received NMV-r and MOV, respectively. Of the 241 patients, 145 (60.2%) received concomitant medications that have DDIs with NMV-r. All 30 patients with severe renal impairment or insufficient details on concomitant medications received MOV. Forty-nine patients with concomitant medications required alternative COVID-19 therapy consideration due to DDIs, of whom 42 (85.7%) patients received MOV. Eighty-one patients had concomitant medications requiring temporary adjustment, of whom 44 (54.3%) patients received NMV-r, and 42 of these patients temporarily adjusted these concomitant medications. Five patients with concomitant medications that can continued by monitoring the effects/adverse effects, of whom 4 (80.0%) patients received NMV-r. Seventy-six patients without concomitant medications requiring DDI management, of whom 71 (93.4%) patients received NMV-r. The 30-day all-cause mortality for eligible patients was 0.9% [95% confidence interval, 0.1-3.1]. CONCLUSIONS: Most patients received appropriate antivirals according to the classification of DDIs, and most patients with concomitant medications requiring temporary adjustment received the recommended DDI management. Our management system is effective in promoting the use of NMV-r in the appropriate patients and managing problematic DDIs.

Impact of Anemia on Clinical Outcomes of Patients With Cancer-Associated Isolated Distal Deep Vein Thrombosis Receiving Edoxaban　- Insights From the ONCO DVT Study.

BACKGROUND: The ONCO DVT study demonstrated potential benefits of extended edoxaban treatment in patients with isolated distal deep vein thrombosis in terms of thrombotic risk. However, the risk-benefit balance in patients with anemia remains unclear. METHODS AND RESULTS: This prespecified subgroup analysis included 601 patients, divided into anemia (n=402) and no-anemia (n=199) groups. The primary endpoint was symptomatic recurrent venous thromboembolism (VTE) or VTE-related death. Anemia was defined as hemoglobin <12 g/dL for women and <13 g/dL for men. In the anemia subgroup, the primary endpoint occurred in 3 (1.5%) and 17 (8.4%) patients in the 12- and 3-month edoxaban treatment groups, respectively (odds ratio [OR] 0.17; 95% confidence interval [CI] 0.05-0.58), compared with 0 and 5 (4.9%) patients, respectively, in the no-anemia subgroup (P interaction=0.997). Major bleeding occurred in 26 (13.1%) and 17 (8.4%) patients with anemia in the 12- and 3-month edoxaban treatment groups, respectively (OR 1.64; 95% CI 0.86-3.14), compared with 2 (2.1%) and 5 (4.9%) patients without anemia (OR 0.67; 95% CI 0.26-1.73; P interaction=0.13). CONCLUSIONS: Regardless of the presence of anemia, edoxaban treatment for 12 months was superior to treatment for 3 months in reducing thrombotic events, whereas the risk of major bleeding did not differ significantly between the 2 treatment groups.

Importance of non-cardiovascular comorbidities in atrial fibrillation and heart failure with preserved ejection fraction.

AIMS: Atrial fibrillation (AF) and heart failure (HF) with preserved ejection fraction (HFpEF) are interlinked and frequently coexisting conditions. To date, patients with AF and HFpEF have limited evidence guiding their management. This study aimed to investigate the predictors of adverse outcomes among patients with AF and HFpEF. METHODS: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. From the registry, we explored predictors for a composite of cardiac death or HF hospitalization among AF patients with HFpEF (defined as having a prior HF hospitalization or New York Heart Association class ≥2 in association with heart disease and left ventricular ejection fraction ≥50%). Besides, we investigated whether the scoring using the predictors identified by the Fushimi AF Registry could stratify the outcomes in patients with AF and HFpEF registered in another independent Kyoto Congestive Heart Failure Registry. RESULTS: Of 755 patients with AF and HFpEF [mean age: 77.5 ± 9.9 years; female: 391 (52%); paroxysmal AF: 258 (34%); and mean CHA2DS2-VASc score: 4.5 ± 1.5], cardiac death or HF hospitalization occurred in 246 patients (33%) during the median follow-up period of 4.4 years in the Fushimi AF Registry. Using multivariate Cox regression analysis, age ≥75 years [hazard ratio (HR): 1.72, 95% confidence interval (CI): 1.26-2.36] and non-cardiovascular comorbidities such as anaemia (HR: 1.83, 95% CI: 1.37-2.46), chronic kidney disease (HR: 1.69, 95% CI: 1.27-2.26), diabetes mellitus (HR: 1.55, 95% CI: 1.15-2.09) and chronic obstructive pulmonary disease (HR: 1.87, 95% CI: 1.08-3.22) were independent predictors of adverse outcomes. Meanwhile, cardiovascular comorbidities including coronary artery disease, valvular heart disease or cardiomyopathy were not significantly associated with adverse outcomes. These results were also the case when analysed for patients with AF and HFpEF who registered in the Kyoto Congestive Heart Failure registry (N = 878). The score assigning 1 point for each five predictors (age, anaemia, chronic kidney disease, diabetes mellitus and chronic obstructive pulmonary disease; ranging 0-5 points) stratified the incidence of adverse outcomes among patients with AF and HFpEF registered in the Kyoto Congestive Heart Failure Registry as well as among those in the Fushimi AF Registry (both log-rank; P < 0.001). CONCLUSIONS: Non-cardiovascular comorbidities such as anaemia, diabetes mellitus and kidney or pulmonary disease in addition to advanced age were independent predictors of adverse outcomes in patients with AF and HFpEF. Our study suggests the importance of focusing on these non-cardiovascular comorbidities for individualized risk stratification and optimal management in patients with AF and HFpEF.

1-Year Prevalence and Factors Related to Injuries and Illnesses in Japanese Judo Collegiate Athletes.

Despite its rich history and widespread participation, the research surrounding injuries and illness in judo remains relatively limited compared to other sports. The primary aim of this research was to investigate injuries and illness within a previous year in Japanese collegiate judo athletes and analyze possible factors associated with these. This was a cross-sectional observational study using a web-based survey to collect data on the 1-year prevalence of injuries and illness. This study involved 564 judo athletes (67% males), aged between 18 and 25 years. Of these, 344 athletes (61%) reported one or more injuries within the previous year, and 49 reported illness (9%). The more judo experiences the athlete acquired, the less likely they were to sustain an injury (OR: 0.9; 95% CI: 0.56-1.10; p-value < 0.05) or illness (OR: 0.9; 95% CI: 0.81-1.00; p-value < 0.05). Support of an athletic trainer was associated with 1.7 times increased odds of sustaining an injury (95% CI: 1.19-2.49; p-value < 0.05). Athletes with obese BMI status (BMI > 30) had 3.1 times higher odds of becoming ill (95% CI: 1.41-6.95; p-value = 0.005), and athletes training more than 5 days per week had the odds of becoming ill increased by 5.1 times (95% CI: 1.11-23.21; p-value = 0.036). Judokas with fewer years of experience and with obese status should be targeted in efforts to prevent injury and illness. Moreover, the support of an athletic trainer and the impact of weekly training days should be targeted in research efforts.

Online Intensive Cardiac Rehabilitation Program for Japanese Patients With Coronary Artery Disease　- A Pilot Study Protocol.

Background: A comprehensive cardiac rehabilitation (CR) program is recommended for coronary artery disease (CAD). However, many facilities do not have established programs for dietary guidance and patient education, resulting in an exercise-based CR program and limited efficacy for secondary prevention. Methods and Results: A pilot study will be conducted to develop an online Japanese-style intensive cardiac rehabilitation (J-ICR) program for Japanese patients with CAD and will examine adherence, safety, and efficacy. Twenty-four patients diagnosed with stable CAD will be randomly assigned in a 1 : 1 ratio to either an early or late-phase group. The program will comprise the following four parts: exercise sessions; dietary education centered on "the Japan diet"; mindfulness; and group support, with a frequency of 3 h per session, once a week for 12 weeks (a total of 36 h). The primary endpoint will be program feasibility, determined by examining its adherence. Physical examination and function, stress-coping skills, risk of classic CAD (e.g., lipid profile, glucose tolerance, and blood pressure), and dietary changes will be assessed as secondary endpoints. Conclusions: The online J-ICR program is designed as a comprehensive CR program for Japanese patients with CAD. If this program shows high adherence and an improvement in CAD risk factors, its secondary prevention effect should be verified with appropriately powered randomized trials at multiple centers.

[Effects of Introducing PBPM for Outpatient Cancer Drug Therapy and Its Impact on Physician Workload].

In May 2022, Hyogo Medical University Hospital introduced protocol-based pharmacotherapy management(PBPM), which is jointly planned by doctors and pharmacists, for certain cancer drug therapies. Colorectal cancer patients who underwent outpatient cancer chemotherapy in the Department of Lower Gastrointestinal Surgery from October to December 2021(before the introduction of PBPM)and from May to August 2022(after the introduction of PBPM)were retrospectively studied. The proportion of clinical examinations performed, number of prescription questions, and time taken by pharmacists to solve the prescription questions before and after the introduction of PBPM were compared. Additionally, the number of modifications made in the medical record by pharmacists on behalf of doctors in response to the prescription questions was assessed. The proportion of clinical examinations performed(clinical examinations actually performed/clinical examinations that should have been performed)improved from 93.2%(260/279)before to 98.8%(405/410)after the introduction of PBPM(p<0.001). The number of prescription questions decreased from an average of 64.7(±11.9)per month before to an average of 29.5(±3.4)per month after the introduction of PBPM. The average number of modifications made in the medical record by pharmacists on behalf of the doctors in response to the prescription questions was 25.8(±5.4)per month after the introduction of PBPM. There was no significant difference before and after the introduction of PBPM in regard to the median(interquartile range)time taken by pharmacists to solve the prescription questions (before PBPM: 1.88 minutes per case[1.70-2.28 minutes]; after PBPM: 1.71 minutes per case[1.61-2.06 minutes][p= 0.75]). The increased proportion of clinical examinations performed after the implementation of PBPM may have improved the safety of cancer drug management, and the decreased number of prescription questions is speculated to have led to a reduction in physician workload.

Aspirin versus Clopidogrel Monotherapy After Percutaneous Coronary Intervention: 1-Year Follow-up of the STOPDAPT-3 Trial.

BACKGROUND AND AIMS: There was no previous trial comparing aspirin monotherapy with a P2Y12 inhibitor monotherapy following short dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). METHODS: In the STOPDAPT-3, patients with acute coronary syndrome (ACS) or high bleeding risk (HBR) were randomly assigned to either 1-month DAPT with aspirin and prasugrel followed by aspirin monotherapy (aspirin group) or 1-month prasugrel monotherapy followed by clopidogrel monotherapy (clopidogrel group). This secondary analysis compared aspirin monotherapy with clopidogrel monotherapy by the 30-day landmark analysis. The co-primary endpoints were the cardiovascular endpoint defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischaemic stroke, and the bleeding endpoint defined as Bleeding Academic Research Consortium 3 or 5. RESULTS: Of 6002 assigned patients, 5833 patients (aspirin group: N = 2920 and clopidogrel group: N = 2913) were included in the 30-day landmark analysis. Median age was 73 (interquartile range 64-80) years, women 23.4%, ACS 74.6%, and HBR 54.1%. The assigned monotherapy was continued at 1 year in 87.5% and 87.2% in the aspirin and clopidogrel groups, respectively. The incidence rates beyond 30 days and up to 1 year were similar between the aspirin and clopidogrel groups for both cardiovascular endpoint (4.5 and 4.5 per 100 person-year, hazard ratio [HR] 1.00 [95% confidence interval (CI) 0.77-1.30], P = .97), and bleeding endpoint (2.0 and 1.9, HR 1.02 [95% CI 0.69-1.52], P = .92). CONCLUSIONS: Aspirin monotherapy compared to clopidogrel monotherapy was associated with similar cardiovascular and bleeding outcomes beyond 1 month and up to 1 year after PCI with DES.

Significance of Persistent Inflammation in Patients With Chronic Coronary Syndrome: Insights From the REAL-CAD Study.

Background: The prognostic implications of persistent low-grade inflammation in patients with chronic coronary syndrome (CCS) are underexplored. The REAL-CAD (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease) study demonstrated the benefit of higher intensity pitavastatin in Japanese patients with CCS. Objectives: This prespecified subanalysis of the REAL-CAD study aimed to assess the prognostic effect of the persistent low-grade inflammation represented by high-sensitivity C-reactive protein (hs-CRP) in CCS patients. Methods: The present analysis involved patients without events until 6 months after randomization and whose hs-CRP levels were available at baseline and 6 months (n = 10,460). The primary endpoint was the composite of cardiovascular mortality, myocardial infarction, stroke, and unstable angina hospitalization. Landmark analyses evaluated the prognostic impact of continuous inflammation in 4 groups based on the median levels of hs-CRP (0.5 mg/L for both) at baseline and 6 months. The 4 groups included patient with persistently low, elevated (increased), reduced, and persistently high hs-CRP. Results: Adjusted Cox proportional hazard analyses demonstrated an increased risk of the primary endpoint in the group with persistently high hs-CRP when compared to the group with persistently low hs-CRP as a reference (adjusted HR: 1.48, 95% CI: 1.18-1.89; P = 0.001), but with a similar risk in the group with elevated (HR: 1.07, 95% CI: 0.77-1.49, P = 0.68) and reduced (HR: 0.92; 95% CI: 0.66-1.27; P = 0.60) hs-CRP. Conclusions: The study shows that persistent low-grade inflammation is associated with poor outcomes and underscores the need to address residual inflammatory risk in CCS patients. (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease [REAL-CAD]; NCT01042730).

R2-CHA2DS2-VASc Score for Cardiovascular Event Prediction After Bioprosthetic Valve Replacement　- Subanalysis From the BPV-AF Registry.

Background: There are few studies evaluating the prognostic prediction method in atrial fibrillation (AF) patients after bioprosthetic valve (BPV) replacement. The R2-CHA2DS2-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 R2-CHA2DS2-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 R2-CHA2DS2-VASc score was 5.7±1.8. Low (scores 0-1), moderate (scores 2-4), and high (scores 5-11) R2-CHA2DS2-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 R2-CHA2DS2-VASc score group (log rank test; P<0.001). Multivariate Cox proportional hazards regression analysis revealed that the R2-CHA2DS2-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 R2-CHA2DS2-VASc score is useful for CV risk stratification in AF patients after BPV replacement.

Long-Term Effects of Proton Pump Inhibitors in Patients Undergoing Percutaneous Coronary Intervention in High-Risk Subgroups.

BACKGROUND: Proton pump inhibitors (PPIs) reportedly reduce upper gastrointestinal bleeding (UGIB) in patients undergoing percutaneous coronary intervention (PCI). However, whether the benefits of PPIs differ in high-risk subgroups is unknown. METHODS AND RESULTS: Among 24,563 patients undergoing first PCI in the CREDO-Kyoto registry Cohort-2 and -3, we evaluated long-term effects of PPI for UGIB, defined as GUSTO moderate/severe bleeding, in several potential high-risk subgroups. In the study population, 45.6% of patients were prescribed PPIs. Over a median 5.6-year follow-up, PPIs were associated with lower adjusted risk of UGIB (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.50-0.80; P<0.001) and a non-significant but numerically lower risk of any gastrointestinal bleeding (HR 0.84; 95% CI 0.71-1.01; P=0.06). PPIs were not associated with a lower risk of GUSTO moderate/severe bleeding (HR 1.04; 95% CI 0.94-1.15; P=0.40) or a higher adjusted risk of myocardial infarction or ischemic stroke (HR 1.00; 95% CI 0.90-1.12; P=0.97), but were associated with higher adjusted mortality risk (HR 1.18; 95% CI 1.09-1.27; P<0.001). The effects of PPIs for UGIB, myocardial infarction or ischemic stroke, and all-cause death were consistent regardless of age, sex, acute coronary syndrome, high bleeding risk, oral anticoagulant use, and type of P2Y12inhibitor. CONCLUSIONS: PPIs were associated with a lower risk of UGIB and a neutral risk of ischemic events regardless of high-risk subgroup.

Efficacy and safety of Saireito (TJ-114) in patients with atrial fibrillation undergoing catheter ablation procedures: A randomized pilot study.

BACKGROUND: Early arrhythmia recurrences commonly occur after atrial fibrillation (AF) ablation because of irritability and inflammation of left atrium. We hypothesized that short-term use of Saireito would be effective in reducing frequent atrial tachyarrhythmias in the early-phase post-ablation. METHODS: One hundred patients undergoing catheter ablation for symptomatic AF were randomly assigned to either a 30-day use of Saireito or control group. The primary endpoint was total number of episodes of frequent atrial tachyarrhythmias including definite recurrent AF and frequent premature atrial contractions during the 30-day treatment period post-ablation. RESULTS: Three (6.0%) out of 50 patients treated with Saireito discontinued the drug because of adverse symptoms. The Saireito group was associated with a numerically lower number of episodes of frequent atrial tachyarrhythmias than the control group (3.1 versus 5.2 times, P = 0.17). The mean daily episodes of frequent atrial tachyarrhythmias were significantly fewer in the Saireito group during Day-6 to Day-10 (0.12/day versus 0.27/day, P = 0.03), and during Day-11 to Day-15 (0.08/day versus 0.24/day, P = 0.001). The prevalence of adverse symptoms during the 30-day treatment period was significantly higher in the Saireito group (18.0% versus 2.0%, P = 0.005). CONCLUSIONS: Thirty-day use of Saireito following AF ablation was associated with a tendency toward reduced number of episodes of frequent atrial tachyarrhythmias during the treatment period, with more pronounced effect in the first two weeks.

Web-based survey on injuries among ultimate frisbee athletes in Japanese college sports: sex differences in injury location and onset.

BACKGROUND: Ultimate Frisbee (Ultimate) has gained significant popularity. However, a comprehensive understanding of injury characteristics, including sex differences in injury location and onset, remains unclear. This study aimed to investigate the injury profile of male and female athletes using data from the Japanese University Athletic Association survey. METHODS: Data were collected through a web-based survey conducted between June and October 2022, focusing on injuries sustained within the past year. Athletes provided detailed information, including injury location, severity, and onset pattern. This study utilized data collected through the UNIVAS survey, offering insights into the injury landscape among female Ultimate athletes. The study examined factors influencing lower limb injuries, including training days and the nature of contact during play. RESULTS: A total of 116 athletes participated in the survey with 57 (49.1%) reporting injuries, of which 42 injuries involved the lower limbs. Lower-extremity injuries exhibited a higher likelihood of occurrence in female compared to male athletes (p = 0.05, φ = 0.18). Athletes with lower limb injuries demonstrated significantly more training days (p = 0.01, Cohen's d = 0.76). Non-contact injuries were more prevalent than contact injuries (p < 0.01, φ = 0.53), with non-contact injuries often causing prolonged interruptions in competition. CONCLUSIONS: Female Ultimate athletes experienced a high frequency of severe lower extremity injuries, particularly those stemming from non-contact incidents. More training days were an independent factor associated with these outcomes.