BACKGROUND:Few epidemiological studies have investigated the association between changes in serum N-terminal pro B-type natriuretic peptide (NT-proBNP) and mortality in the general Asian population. METHODS AND RESULTS:We followed 2,703 community-dwelling Japanese residents aged ≥40 years who had serum NT-proBNP concentrations measured in both 2002-2003 and 2007-2008 over a median period of 10.3 years. Changes in NT-proBNP were categorized as decreasing (change ≤-25%), no change (-25%<change<+25%), or increasing (change ≥+25%). Mortality hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. During the follow-up period, 497 deaths occurred (108 cardiovascular, 389 non-cardiovascular). Compared with the no-change group, multivariable-adjusted HRs in the increasing group were 1.73 (95% CI 1.37-2.17), 1.76 (95% CI 1.08-2.87), and 1.71 (95% CI 1.32-2.22) for all-cause, cardiovascular, and non-cardiovascular mortality, respectively. Subgroup analyses by baseline serum NT-proBNP concentration (2002-2003) showed consistent associations with all-cause mortality in both lower (<125 pg/mL) and higher (≥125 pg/mL) NT-proBNP groups, with a tendency towards stronger associations in the higher NT-proBNP group. CONCLUSIONS:Changes in serum NT-proBNP concentrations may indicate mortality risk in a community-dwelling Asian population.
BACKGROUND:Reliable preoperative risk assessment is essential in cardiac surgery. In Japan, coronary artery bypass grafting (CABG) risk models have been developed from the Japan Cardiovascular Surgery Database - Adult section (JCVSD-A), with JapanSCORE I and II released previously. To reflect contemporary practice, we developed and validated JapanSCORE III, an updated risk model for isolated CABG, using JCVSD-A. METHODS AND RESULTS:We identified patients undergoing isolated CABG between 2018 and 2023 in the JCVSD-A. The dataset was temporally split into development (2018-2022) and validation (2023) cohorts. A least absolute shrinkage and selection operator model was developed to predict operative mortality, incorporating imaging-based predictors and clinically relevant factors. Secondary outcome models were constructed for stroke, reoperation, prolonged ventilation, renal failure, deep sternal wound infection (DSWI), gastrointestinal complications, and intensive care unit stay >7 days. Model performance was assessed by areas under the curve (AUC) and calibration plots. Among 70,180 patients (mean age 69.3 years; 20% women), operative mortality was 2.7%. The incidence of stroke, reoperation, prolonged ventilation, renal failure, DSWI, gastrointestinal complications, and prolonged ICU stay was 1.8%, 1.5%, 3.7%, 2.0%, 1.1%, 1.3%, and 13.2%, respectively. Operative mortality and renal failure models demonstrated good discrimination (AUC >0.8) and calibration in validation. CONCLUSIONS:Operative outcomes remained stable despite increasing predicted risk. The JapanSCORE III models showed good predictive performance, providing valid tools for preoperative risk stratification.
BACKGROUND:Remote monitoring (RM) enables early detection of abnormalities in cardiac implantable electronic devices (CIED), but implementation remains suboptimal. METHODS AND RESULTS:We analyzed 396,296 patients hospitalized for CIED implantation and evaluated changes after RM reimbursement revision using an interrupted time-series analysis. The proportion increased by 4.89% (95% confidence interval [CI]: 3.71 to 6.06%) in the pacemaker implantation cohort, but no significant increase was observed in the implantable cardioverter defibrillator and cardiac resynchronization therapy cohort (0.79%; 95% CI: -1.12 to 2.71%). CONCLUSIONS:The effect of reimbursement policy changes on RM adoption may differ according to the type of CIED.
BACKGROUND:Small dense low-density lipoprotein cholesterol (sdLDL-C) is an established atherogenic marker; however, the association between estimated sdLDL-C (EsdLDL-C) and arterial stiffness remains unclear. METHODS AND RESULTS:We analyzed 23,623 participants (13,518 men, 10,105 women). EsdLDL-C was calculated using the Sampson equation, and arterial stiffness was defined as a brachial-ankle pulse wave velocity (baPWV) ≥1,400 cm/s. After adjustment for cardiovascular risk factors, higher EsdLDL-C levels were significantly associated with arterial stiffness in the overall population and in men, whereas the association in women did not reach statistical significance in the continuous analysis. Nevertheless, the risk of arterial stiffness increased in a stepwise manner across EsdLDL-C quartiles; the highest EsdLDL-C quartile had a significantly higher risk than the lowest in both men (odds ratio [OR] 1.91; 95% confidence interval [CI] 1.59-2.29) and women (OR 1.54; 95% CI 1.22-1.95). In a 4-group analysis, high EsdLDL-C significantly increased risk, regardless of whether estimated low-density lipoprotein cholesterol levels were below or above the median. Stratified analysis by systolic blood pressure (SBP; <120, 120-129, 130-139, and ≥140 mmHg) revealed that the association was significant across all categories in men, but was less consistent in women and was significant only in the strict normotensive group (SBP <120 mmHg). CONCLUSIONS:EsdLDL-C calculated from standard lipid parameters is significantly associated with arterial stiffness. This association is robust in men and evident in normotensive women, suggesting that EsdLDL-C is a useful indicator for arteriosclerotic risk assessment.
BACKGROUND:The cardiovascular-kidney-metabolic (CKM) framework emphasizes the interplay of metabolic, renal, and cardiovascular abnormalities in cardiovascular disease risk. We aimed to develop a CKM syndrome age algorithm using routinely collected health checkup and claims data in Japan. METHODS AND RESULTS:We conducted a cohort study of 376,612 men and 478,853 women aged 20-79 years in the DeSC database. Flexible parametric survival models were developed for 5 incident cardiovascular outcomes corresponding to CKM syndrome stage 4 (i.e., heart failure, myocardial infarction, atrial fibrillation, stroke, and peripheral arterial disease) and a composite outcome comprising these 5 outcomes. The models used available CKM-related variables obtained from health checkups and administrative claims data. Model performance was assessed using bootstrap internal validation. CKM syndrome age was defined as the age at which a hypothetical same-sex individual with an optimal CKM risk profile would have the same predicted 5-year risk as the participant. The developed prediction models showed acceptable discrimination across the 6 outcomes, with optimism-corrected Harrell's C-index ranging from 0.694 to 0.724 in men and from 0.653 to 0.716 in women. CKM syndrome age showed higher discrimination than chronological age alone across all outcomes and both sexes. CONCLUSIONS:CKM syndrome age may serve as an intuitive tool for communicating integrated cardiovascular risk beyond chronological age in health checkup settings.
BACKGROUND:Low body weight (BW) is reportedly associated with an increased risk of bleeding and mortality in venous thromboembolism (VTE). However, there are limited data on the impact of low BW on clinical outcomes among patients with cancer-associated VTE in the direct oral anticoagulants (DOACs) era. METHODS AND RESULTS:We analyzed 1,484 patients with symptomatic VTE and active cancer from the COMMAND VTE Registry-2, and divided the cohort into low (≤60 kg) and non-low (>60 kg) BW groups (n=969 and 515, respectively). The cumulative 3-year incidence of major bleeding was significantly higher in the low than non-low BW group (13.1% vs. 10.2%; Gray's P=0.04). However, after adjustment, the risk of major bleeding in the low BW was no longer significantly different to that in the non-low BW group (hazard ratio [HR] 1.36; 95% confidence interval [CI] 0.96-1.92). The cumulative 3-year incidence of recurrent VTE did not differ significantly between the low and non-low groups (5.2% vs. 5.4%, respectively; Gray's P=0.46; adjusted HR 0.71; 95% CI 0.42-1.18). The cumulative 3-year incidence of all-cause death was significantly higher in the low than non-low BW group (65.0% vs. 50.8%; log-rank P<0.001; adjusted HR 1.47; 95% CI 1.25-1.73). CONCLUSIONS:Low BW in cancer-associated VTE was not associated with major bleeding or recurrent VTE, but was associated with all-cause death, possibly reflecting cancer-related prognostic factors.
BACKGROUND:The true incidence of pulmonary vein (PV) stenosis after radiofrequency (RF) ablation for atrial fibrillation remains uncertain because routine imaging surveillance is not universally performed and many cases of PV stenosis are asymptomatic. METHODS AND RESULTS:This single-center retrospective study included atrial fibrillation ablation procedures with both pre- and postprocedural (based on clinical indication) cardiac computed tomography (CT) imaging ≥30 days after ablation. PV stenosis was defined as ≥50% luminal reduction and classified as moderate (50-89%), severe (90-98%), or complete (≥99%) occlusion. Among 303 RF procedures in 242 patients, PV stenosis occurred in 49 (16%) procedures, and severe stenosis or occlusion in 28 (9.2%), mostly asymptomatic. Although the overall incidence did not differ between high-power strategies, severe stenosis was more frequently observed with temperature-controlled RF catheters under very high-power, short-duration settings. No PV stenosis was observed after pulsed field ablation. CONCLUSIONS:In this CT-enriched cohort, the incidence of PV stenosis after RF ablation was higher than previously reported symptomatic rates, largely reflecting improved detection of subclinical PV injury. Specific catheter-energy combinations may be associated with severe PV stenosis. These findings suggest that not all high-power strategies are equivalent and that the interaction between the energy delivery profile and catheter technology may influence the risk of clinically significant PV injury. Procedural optimization and risk-adapted imaging follow-up may help mitigate PV-related complications.
BACKGROUND:The Asian Working Group for Sarcopenia (AWGS) updated its diagnostic criteria in 2025 by incorporating body mass index (BMI)-adjusted skeletal muscle mass. This revision may influence the prevalence and clinical interpretation of sarcopenic obesity in heart failure (HF). METHODS AND RESULTS:We conducted a single-center retrospective cohort study of 589 patients aged ≥65 years who were hospitalized for HF. Application of the AWGS 2025 criteria significantly altered classification, increasing the prevalence of sarcopenic obesity from 7.8% to 13.6%. Among the 4 groups defined by sarcopenia (AWGS 2025) and obesity, patients with sarcopenia without obesity had the worst prognosis, whereas those with sarcopenic obesity had preserved survival (log-rank P=0.038). Following the transition from the AWGS 2019 to AWGS 2025 criteria, newly classified patients with sarcopenic obesity were more frequently female and had a higher BMI with preserved height-adjusted muscle mass compared with patients with persistent sarcopenic obesity. Mortality and gait speed were comparable between the persistent and newly classified sarcopenic obesity groups (both P>0.05). The AWGS 2025 sarcopenia-obesity phenotype classification showed no improvement in discrimination or the Akaike information criterion for prognosis compared with the AWGS 2019 classification (both P>0.05). CONCLUSIONS:The AWGS 2025 criteria increase the prevalence of sarcopenic obesity by identifying a distinct phenotype in patients with HF. However, this expanded classification does not improve risk stratification.
BACKGROUND:Occlusion of the culprit artery (OCA) is observed in a substantial proportion of non-ST-segment elevation myocardial infarction (NSTEMI) patients, showing a poor clinical prognosis. NSTEMI management remains challenging, potentially due to pathophysiological mechanisms across different clinical phenotypes. This study investigated the morphological features of culprit plaque in NSTEMI with vs. without OCA. METHODS AND RESULTS:In all, 324 NSTEMI patients who underwent optical coherence tomography (OCT) imaging were enrolled in this study. Patients were divided into an OCA group (n=105; 32.4%) and a non-OCA group (n=219; 67.6%). Compared with the non-OCA group, the OCA group had significantly higher rates of plaque rupture (67.6% vs. 42.5%; P<0.001), lipid-rich plaque (81.0% vs. 67.1%; P=0.01), thin-cap fibroatheroma (48.6% vs. 25.1%; P<0.001), thrombus (88.6% vs. 66.7%; P<0.001), macrophage accumulation (92.4% vs. 76.7%; P<0.001), and cholesterol crystals (48.6% vs. 27.4%; P<0.001) on OCT. Symptom-to-catheter time was found to be an independent predictor of 2-year major adverse cardiovascular events for OCA patients. CONCLUSIONS:The underlying plaque morphologies were different between OCA and non-OCA patients. The OCA had a higher rate of plaque rupture, with more features (e.g., lipid-rich plaque, thin-cap fibroatheroma, thrombus, macrophage accumulation, cholesterol crystals) resembling ST-elevation myocardial infarction-like plaques. Symptom-to-catheter time was an independent predictor of major adverse cardiovascular events in the OCA group.
BACKGROUND:Because glucose fluctuations (GFs) are significantly associated with poor cardiovascular outcomes in patients with diabetes mellitus, we investigated their potential impact on the paracrine effects of human epicardial adipocytes on cardiomyocytes. METHODS AND RESULTS:Human epicardial adipose tissue (EAT) biopsies and isolated EAT-derived adipocytes were used to evaluate the direct impact of GFs. Mature adipocytes were exposed to media containing normal glucose (NG), high glucose (HG), or GFs. GFs altered the expression of 595 differentially expressed genes with an effect size greater than ±50% and a statistically significant difference (P<0.05) in human epicardial adipocytes, whereas continuous HG altered the expression of only 182 genes. Among the genes affected exclusively by GFs, the top 3 most affected were IL1β, IL33, and IL8. Coculture of human induced pluripotent stem cell-derived atrial cardiomyocytes and adipocytes treated with NG, HG, or GFs revealed that adipocytes exposed to GFs markedly increased oxidative stress in cardiomyocytes through paracrine effects. In a real-world clinical association study, IL1β mRNA expression in human EAT showed a significant positive correlation with the severity of GFs during hospitalization and with oxidative stress in the left atrial myocardium. CONCLUSIONS:GFs adversely affect the paracrine secretome profile of human epicardial adipocytes. IL1β may be a critical epicardial adipocyte-derived adipokine that is upregulated by GFs.
BACKGROUND:Although intensive care is considered important for cardiovascular emergencies, large-scale evidence comparing outcomes by initial admission ward remains limited in Japan. METHODS AND RESULTS:Using the JROAD database, we identified patients hospitalized for cardiovascular emergencies after ambulance transport between April 2016 and March 2024 and classified patients by initial ward (intensive care unit [ICU], high care unit [HCU], or general ward [GW]). Deaths within 24 h were excluded. Multivariable logistic regression analysis was performed with adjustment for demographics, comorbidities, acute therapies, and hospital cardiologist staffing. Among 1,211,636 admissions, there were 323,220 (26.7%) deaths within 24 h; thus, 888,416 admissions (ICU, 212,059; HCU, 124,468; GW, 551,889) were analyzed. In-hospital mortality was 10.8%, 9.7%, and 12.2% for patients admitted to the ICU, HCU, and GW, respectively. Compared with the GW, the adjusted odds of death were lower for the ICU (odds ratio [OR] 0.718; 95% confidence interval [CI] 0.703-0.734) and HCU (OR 0.928; 95% CI 0.906-0.950). A higher number of board-certified cardiologists was independently associated with lower in-hospital mortality (OR 0.977 per additional board-certified cardiologist; 95% CI 0.976-0.978). Findings were consistent for acute myocardial infarction, acute heart failure, aortic dissection, and pulmonary embolism. CONCLUSIONS:Higher-acuity admission and a higher number of cardiologists were independently associated with lower in-hospital mortality, supporting optimization of critical care access for high-risk cardiovascular emergencies in Japan.
BACKGROUND:Frailty is common in patients with heart failure and is associated with adverse outcomes. Although metabolic dysregulation has been implicated in frailty, the relationship between plasma amino acid profiles and frailty remains incompletely defined. METHODS AND RESULTS:We conducted a single-center ambispective cross-sectional study of 413 patients hospitalized for heart failure (median age 78 years). Plasma concentrations of 31 amino acids were measured. Frailty status was assessed using the Japanese version of the Cardiovascular Health Study criteria. An unbiased analytical framework integrating multivariate analyses and multivariable logistic regression was applied with adjustment for heart failure severity, renal function, nutritional status, and body composition. Associations with all-cause mortality were evaluated using Cox models. Frailty was present in 228 (55%) patients. Unbiased analyses identified urea cycle-related metabolites as key features associated with frailty. In fully adjusted models, higher plasma citrulline and ornithine concentrations were independently associated with frailty, whereas arginine concentrations were not. These associations were independent of nutritional indices, skeletal muscle mass, and established prognostic factors. Neither citrulline nor ornithine was independently associated with mortality. Pathway analysis demonstrated enrichment of arginine biosynthesis and arginine-proline metabolism. CONCLUSIONS:Elevated citrulline and ornithine were independently associated with frailty in patients with heart failure, suggesting that dysregulated arginine-related metabolism may represent a metabolic signature of the frailty phenotype distinct from mortality risk.
