Background: Endomyocardial biopsy (EMB) remains the gold standard for diagnosing acute myocarditis (AM); however, its prognostic value has not been fully established. We investigated the prognostic impact of EMB, with a focus on fulminant myocarditis (FM).

Methods and Results: We included 841 AM patients across 7 hospitals who were categorized having undergone EMB (n=268) or not (n=573). The primary outcome was in-hospital death; the secondary outcome was a composite of all-cause death, cardiac transplantation, or left ventricular assist device implantation. In-hospital mortality was lower in the EMB group (6.3% vs. 11.5%; P=0.019), with a similar reduction in the EMB group among patients with FM (11.3% vs. 23.7%; P=0.002), despite a higher rate of extracorporeal membrane oxygenation. During a median follow-up of 447 days, the composite outcome was also lower in the EMB group among patients with FM (P=0.031). In multivariable analyses, EMB was independently associated with lower in-hospital mortality in both the overall cohort and the FM subgroup. Outcomes did not differ substantially across histopathologic subtypes, although patients with giant cell myocarditis had a worse prognosis.

Conclusions: In patients with AM, EMB was associated with lower in-hospital mortality and improved long-term outcomes, particularly among those with FM. Further well-designed prospective studies are warranted to evaluate the clinical impact of EMB and its potential role in improving outcomes.

Background: Syncope is common in patients with congenital long QT syndrome (LQTS). However, not all episodes of syncope or loss of consciousness are caused by torsades de pointes (TdP); some are attributable to bradycardia or non-cardiac causes. This study investigated the clinical utility of implantable loop recorders (ILRs) in patients with LQTS presenting with unexplained syncope.

Methods and Results: We retrospectively studied 18 patients with LQTS (7 with LQTS type (LQT) 1, 3 with LQT2, 1 with LQT3, and 7 genotype-negative LQTS) who underwent ILR implantation for recurrent syncope. Multiple causes of syncope were suspected in each patient; there were 14 cases of arrhythmia, 4 of epilepsy, 8 of neurally mediated syncope (NMS), and 9 of unknown cause. During a mean (±SD) follow-up of 37±22 months after ILR implantation, 8 (44%) patients experienced recurrent syncope. Four episodes were caused by TdP and the remaining 4 episodes were attributed to epilepsy or NMS (cardioinhibitory type). No significant difference was observed in baseline clinical characteristics between patients with and without TdP following ILR implantation, but female sex (P=0.051) and a higher Schwartz score (P=0.08) tended to be associated with TdP.

Conclusions: Syncope in patients with LQTS is not always attributable to TdP, and non-arrhythmic causes should be considered. Although ILRs may aid in diagnostic evaluation, careful risk stratification remains essential in patients with suspected arrhythmic syncope.

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: 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: 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: The KUROSIO study (UMIN000023747) previously demonstrated the efficacy and safety of direct oral anticoagulants (DOACs) over 52 weeks in patients with acute venous thromboembolism (VTE). However, the long-term outcomes of anticoagulation therapy in real-world practice remain unclear.

Methods and Results: We conducted a prespecified analysis with a 156-week clinical observation period. The primary efficacy outcome was symptomatic recurrent VTE, and the primary safety outcome was major bleeding at 156 weeks. Between September 2016 and November 2018, the study enrolled 1,017 patients, of whom 993 were eligible for analysis. The cumulative incidence of recurrent VTE and major bleeding at 52 weeks was 3.2% and 2.2%, respectively. The mean duration of DOAC therapy was 458.0 days. Symptomatic recurrent VTE occurred in 50 (5.0%) patients, including pulmonary embolism in 46 (4.6%) and deep vein thrombosis in 4 (0.4%). Major bleeding occurred in 26 (2.6%) patients. Multivariable analysis identified chemotherapy (hazard ratio [HR] 3.580) as a factor associated with recurrent VTE. For major bleeding, multivariable analysis identified lower baseline hemoglobin (HR 0.657), history of cerebral infarction (HR 7.250), and concomitant use of non-steroidal anti-inflammatory drugs other than aspirin at enrollment (HR 7.481) as significant risk factors.

Conclusions: DOAC therapy showed sustained effectiveness and acceptable safety over 156 weeks in Japanese patients with VTE, supporting individualized decisions regarding treatment duration and bleeding risk.

Background: Sex differences in outcomes after transcatheter aortic valve implantation (TAVI) for aortic stenosis in Japan have not been fully investigated.

Methods and Results: Using a nationwide registry, we evaluated sex differences in post-TAVI outcomes. In all, 36,353 patients (23,978 women, 12,375 men) were included. Women were older (84.9 vs. 83.5 years; P<0.001), had a smaller body surface area (BSA; 1.38 vs. 1.60 m²; P<0.001), and a lower prevalence of comorbidities than men. In-hospital mortality was comparable between women and men (1.2% vs. 1.3%, respectively; P=0.367). Women had higher rates of major red cell concentrate (RCC) transfusion (10.1% vs. 8.7%; P<0.001) and permanent pacemaker implantation (PPI; 7.1% vs. 5.9%; P<0.001). In multivariable analysis, BSA was inversely associated with in-hospital mortality (adjusted odds ratio [aOR] 0.84 per 0.1-m²increase; 95% confidence interval [CI] 0.77–0.91; P<0.001). Female sex was independently associated with lower risks of in-hospital mortality (aOR 0.60; 95% CI 0.45–0.81) and major RCC transfusion (aOR 0.79; 95% CI 0.71–0.89), but a higher risk of PPI (aOR 1.15; 95% CI 1.02–1.30).

Conclusions: In a Japanese TAVI registry, crude mortality was comparable between the sexes, but women had higher major RCC transfusion and PPI rates. After adjusting for BSA and available measured covariates, female sex was associated with lower in-hospital mortality. Combined sex and BSA assessment appears important for predicting post-TAVI outcomes.

Takayasu arteritis (TAK) is a chronic, refractory large-vessel vasculitis designated as a Designated Intractable Disease in Japan. The Japanese diagnostic criteria for TAK, last revised in 2017, have been updated to the 2026 version as part of the Japanese Circulation Society 2026 guidelines on the management of large vessel vasculitis, and are presented here in English for the first time. The revision was conducted through a 3-round modified Delphi process involving a panel of 21 experts, supplemented by email discussion and an in-person meeting. The updated criteria incorporate 3 major changes: new symptoms were added and a qualifying statement introduced in Section A; pulmonary artery involvement was elevated to a main criterion in Section B; and IgG₄-related periaortitis, Cogan syndrome, and drug-induced aortitis were added in Section C. These updates reflect advances in imaging technology and international classification frameworks, with an emphasis on improving diagnostic sensitivity to reduce missed diagnoses.

Background: Aortic dissection and aneurysm are major causes of early mortality in Turner syndrome. However, data on aortic dissection in Turner syndrome remain limited compared with those for Marfan syndrome. We evaluated the associations of Turner syndrome and Marfan syndrome with in-hospital mortality among female patients hospitalized for aortic dissection or aneurysm, using patients without either syndrome as the common reference group for both comparisons.

Methods and Results: This retrospective cohort study used data from the Diagnosis Procedure Combination, a national inpatient database in Japan. Adult female patients hospitalized for first-time aortic dissection or aneurysm between 2010 and 2022 were included, with in-hospital mortality as the primary outcome. Associations between Turner/Marfan syndrome and mortality were evaluated using multivariable logistic regression analysis. Of 10,927 eligible female patients aged 16–61 years, 29 (0.27%) had Turner syndrome and 686 (6.3%) had Marfan syndrome. In-hospital mortality was higher for Turner syndrome (odds ratio [OR] 5.35; 95% confidence interval [CI] 1.61–17.8) compared with the group without either syndrome. In contrast, Marfan syndrome was not significantly associated with mortality (OR 0.72; 95% CI 0.44–1.17). Unscheduled admission was similar in Turner syndrome, but less frequent in Marfan syndrome, compared with the group without either syndrome.

Conclusions: In-hospital mortality was higher among patients with Turner syndrome admitted for aortic dissection or aneurysm, highlighting the need to raise awareness of aortic risk in this high-risk population.

Background: Diastolic dysfunction is a recognized chronic allograft complication, and a restrictive left ventricular filling pattern is associated with adverse outcomes. However, the underlying pathophysiological mechanisms remain unclear.

Methods and Results: This study included 32 heart transplant recipients with a normal filling pattern at 1-year after transplantation. Five-year echocardiography classified patients into restrictive (n=12) and non-restrictive (n=20) groups. All patients underwent right heart catheterization and right ventricular endomyocardial biopsy at 1 and 5 years. Bulk RNA sequencing was performed on paired biopsy samples from 10 patients with available tissue. From 1 to 5 years, the restrictive group demonstrated significantly greater increases in pulmonary artery wedge pressure and the E/A and E/e′ ratios, with no histopathological evidence of rejection and similar myocardial interstitial fibrosis in the 2 groups (P=0.81). Transcriptome analysis demonstrated that there was significant enrichment of immune and inflammatory pathways, including gene sets annotated as allograft rejection and T cell receptor signaling (P_adjusted<0.05), in the restrictive group at 5 years. Temporal analysis revealed that these pathways were downregulated from 1 to 5 years in the non-restrictive group but remained persistently activated in the restrictive group.

Conclusions: The development of a restrictive filling pattern is associated with elevated intracardiac pressures and a persistent immune-related transcriptome signature, despite no histological evidence of rejection.

Background: Data on asymptomatic deep vein thrombosis (DVT) remain limited. This prospective study investigated the incidence of cancer-associated venous thromboembolism (CA-VTE) in patients receiving cancer treatment with scheduled DVT monitoring.

Methods and Results: Patients with newly diagnosed locally advanced, recurrent, or metastatic solid cancers without prior VTE were enrolled. Mandatory baseline venous ultrasonography excluded pre-existing DVT. VTE was assessed at Weeks 12, 24, 36, 48, 72, and 96 by lower-extremity ultrasonography, supplemented by contrast-enhanced computed tomography. The primary endpoint was the incidence of CA-VTE within 24 weeks, and a key secondary endpoint was the incidence within 96 weeks. Cox proportional hazards regression was used to explore factors predictive of newly developed VTE. Among 178 patients (median age 68 years; 32% female), the most common primary site of cancer was the gastrointestinal tract (38%). Adenocarcinoma and squamous cell carcinoma each accounted for 43% of enrolled cases. VTE occurred in 23 (12.9%) and 36 (20.2%) patients within 24 and 96 weeks, with most being asymptomatic (91.3% and 69.4%, respectively). CA-VTE incidence did not differ by tumor site or histology, and no predictive factors were identified. Eleven patients required anticoagulation at VTE diagnosis, and 3 further patients required anticoagulation after progression of initially asymptomatic distal DVT.

Conclusions: CA-VTE incidence was alarmingly high, regardless of tumor site or histology. Because anticoagulation was required in a considerable proportion of patients who developed VTE, scheduled DVT monitoring may be warranted.

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: 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.

Background: This study investigated the ability of coronary computed tomography angiography (CCTA)-derived computational fluid dynamics (CFD) parameters to identify lesions associated with subsequent acute coronary syndrome (ACS).

Methods and Results: The study included 37 patients with well-documented ACS and available CCTA performed at least 1 week before the event. Lesions identified on CCTA were classified as culprit (n=37) or non-culprit (n=42). Information on clinical characteristics and anatomical features was collected. CFD analysis was performed to compute wall shear stress (WSS) and axial plaque stress (APS) at both the segment (seg) and arc levels, with minimum (min) and maximum (max) values recorded. Univariate and multivariate logistic regression analyses were used to identify predictors of ACS. Significant stenosis was more frequent in culprit than non-culprit lesions (P=0.033). Compared with non-culprit lesions, culprit lesions had lower min(APS_seg) values but higher max(|APS|_seg) and max(WSS_seg), although the differences were not statistically significant. In multivariate analysis, vessel location, min(APS_seg) (odds ratio [OR] 3.17, P=0.047), and max(WSS_seg) (OR 6.99, P=0.020) were independently associated with the occurrence of ACS events. Incorporating CFD parameters max(|APS|_seg), min(APS_seg) and max(WSS_seg) into a model containing clinical and anatomical variables significantly improved ACS prediction (area under the curve 0.862 vs. 0.781; P=0.044).

Conclusions: CCTA-derived CFD parameters are independently associated with the development of ACS. Integrating multiple CFD metrics enhances the predictive performance beyond traditional clinical and anatomical characteristics, supporting their potential role in risk stratification.

Background: Using the Japan Organ Transplant Network national waitlist, this study investigated confounding factors for waitlist mortality and transplant probability among adult heart transplant candidates, focusing on heart disease and change in status (from registration to observation on June 30, 2024), to provide insights into the use of underlying heart disease or severity in the current revision of the heart transplant allocation criteria.

Methods and Results: All-cause waitlist mortality and heart transplantation probability were assessed using Gray’s test, as well as univariate and multivariate Fine–Gray subdistribution hazard regression models. After excluding heart–lung transplantation candidates, patients with missing data, patients who were never on the waitlist after revision of the Organ Transplant Act, and patients aged <18 and ≥60 years at the time of registration, 1,522 patients were included in the final cohort. Heart transplant candidates with congenital heart disease had a higher risk of mortality, whereas patients waiting for retransplantation had no chance of transplantation and all died. The mortality rate was significantly higher for patients listed as Status 2 (unchanged) at observation than those listed as Status 1 (unchanged).

Conclusions: Prioritization of candidates with congenital heart disease should be considered to reduce the risk of mortality while patients are on the transplant waitlist.

Background: The clinical consequences of discontinuing proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have not been elucidated.

Methods and Results: We analyzed 208 patients with coronary artery disease treated with PCSK9 inhibitors. During a median follow-up of 1,096 days, 94 patients discontinued treatment and they had a higher incidence of major adverse cardiovascular events (MACE) than those who continued. Event curves diverged approximately 3 years after discontinuation. Multivariable Cox analysis showed that discontinuation was associated with a higher incidence of MACE.

Conclusions: Discontinuation of PCSK9 inhibitors was associated with worse cardiovascular outcomes.

Background: Cardiac allografts show poorer long-term survival and decreased tolerance compared to renal allografts, but the underlying mechanisms remain unclear.

Methods and Results: We established heterotopic heart and kidney allotransplantation models in Bama miniature pigs. Single-cell RNA sequencing (scRNA-seq) was performed to analyze normal heart/kidney tissues and allografts. Transcription factor analysis focused on T-cell subsets, with key findings validated using clinical human heart tissues (normal vs. acute rejection) and a mouse heart transplantation model (to test MYC inhibition). T/NK (TNK) subsets in cardiac allografts exhibited higher expression of genes linked to immune system activation, mature B-cell differentiation, and immune memory. The TNFRSF4+ CD4+ T-cell subset was selectively expanded in cardiac allografts (but reduced in renal allografts) during acute rejection, with transcriptional analysis identifying MYC as a master regulator of glycolysis-related genes in this subset. In the mouse heart transplant model, inhibition of MYC (via 10058-F4) reduced the proportion of TNFRSF4+ CD4+ T cells and significantly prolonged cardiac allograft survival.

Conclusions: Our study identified a MYC-driven, glycolysis-dependent expansion of TNFRSF4+ CD4+ T cells as a key mechanism contributing to the heightened rejection susceptibility of cardiac allografts (vs. renal allografts). These findings provide a rationale for developing cardiac-targeted immunosuppressive strategies.

Background: Early detection of subclinical worsening heart failure (HF) is essential to enable timely, proactive treatment that may alter the clinical course and prevent hospitalization. This study demonstrates how early non-invasive telemonitoring of respiratory stability time (RST) can detect subclinical worsening HF.

Methods and Results: Daily RST was calculated automatically from all-night respiratory signals in 66 patients. Subclinical worsening was detected by declines in RST preceding overt worsening HF in the control group (blinded to RST; n=35) and in the RST group (RST monitored daily by clinicians; n=31). The RST recovery zone sufficient to avert hospitalization was determined by RST responses to treatment escalation for overt worsening HF. Two clinically relevant RST thresholds were identified: RST <20 s, indicating a high-risk zone for subclinical worsening preceding hospitalization; and RST ≥30 s, defining a recovery target zone associated with hospitalization avoidance. The duration of subclinical worsening HF from the onset of RST decline <20 s to overt worsening was 40.0 days in the control group. In contrast, the interval from the onset of overt worsening HF to hospitalization was markedly shorter (control group, 7.5 days; RST group, 8.0 days).

Conclusions: Noninvasive RST telemonitoring enables early detection of the prolonged subclinical worsening phase of HF and provides a clinically actionable biological target for proactive intervention aimed at preventing HF-related hospitalization.

Background: Heart failure (HF) is a progressive disease characterized by an increasing incidence of hospitalization over time. HeartLogic^TM(HL) is a multiparametric remote monitoring system designed to detect early signs of HF decompensation. Using a multicenter database, this real-world study evaluated whether responses to HL alerts could reduce HF-related hospitalization.

Methods and Results: We retrospectively analyzed 246 patients implanted with an HL-enabled implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator across 8 Japanese centers. Patients were categorized as alert-responsive (AR; n=167) or non-responsive (NR; n=79). Alert responses included multidisciplinary review and telephone triage to determine the need for clinical visits. HF hospitalization rates during the alert-off (before activation) and the alert-on (after alert activation) periods were compared. During the alert-off period, 50 hospitalizations occurred over 648 person-years (77.1 per 1,000 person-years); during the alert-on, 91 hospitalizations occurred over 498 person-years (182.6 per 1,000 person-years). From the alert-off to the alert-on period, HF hospitalization increased 3.24-fold (95% confidence interval [CI] 1.63–6.41) in the NR group, but only 1.28-fold (95% CI 0.81–2.03) in the AR group. The relative increase in HF hospitalization was significantly attenuated in the AR group (adjusted relative ratio 0.40; 95% CI 0.18–0.89; P=0.025).

Conclusions: Although HF-related hospitalizations progressively increase as the disease advances, real-world alert responses may reduce hospitalizations and healthcare costs in clinical practice.

Background: Beyond low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C) is a residual risk factor for atherosclerotic cardiovascular disease. However, whether sdLDL-C levels can predict the development of chronic kidney disease remains unclear.

Methods and Results: We investigated the association between the sdLDL-C level calculated using Sampson’s equation and the progression of renal impairment in 16,814 Japanese individuals (10,806 men, 6,008 women; mean age: 47 years) who underwent annual health checkups. Participants were divided into 4 groups according to high (H) or low (L) sdLDL-C and LDL-C levels. Over a 10-year follow-up period, 2,533 participants progressed renal impairment, defined as an estimated glomerular filtration rate <60 mL/min/1.73 m²or positive for urine protein. Cox proportional hazards model with a restricted cubic spline after adjustment for confounders showed a gradual increase in the hazard ratio (HR) for renal impairment with high levels of sdLDL-C. Compared with the L-sdLDL-C/L-LDL-C group (reference) the adjusted HRs for renal impairment were significantly higher in the H-sdLDL-C/H-LDL-C and H-sdLDL-C/L-LDL-C groups (1.13 [95% confidence interval 1.03–1.25] and 1.15 [95% confidence interval 1.03–1.29], respectively). The addition of a high sdLDL-C level (≥35.7 mg/dL) to traditional risk factors significantly improved the discriminatory capacity for renal impairment.

Conclusions: A high calculated sdLDL-C level was an independent predictor for the progression of renal impairment regardless of LDL-C level in a general Japanese population.

Background: ¹⁸F-FDG PET/CT patterns in cardiac sarcoidosis (CS) across diagnostic subgroups are incompletely characterized.

Methods and Results: We analyzed 221 patients with definite CS (DCS), probable CS with active extracardiac sarcoidosis (PCS-A), or probable CS without extracardiac involvement (PCS-N). DCS exhibited more severe perfusion defects than PCS-A and PCS-N. FDG uptake was similar in DCS and PCS-A, but lower in PCS-N. Abnormalities predominated in the basal/mid-septum and apical cap.

Conclusions: Distinct PET patterns characterize CS diagnostic categories and support current diagnostic criteria.

Background: The aim of this study was to investigate changes in cortical thickness in patients with cardiac allograft vasculopathy (CAV) using magnetic resonance imaging (MRI), and links to myocardial fibrosis and cognitive function.

Methods and Results: In all, 77 patients after heart transplantation (35 with CAV, 42 without CAV), as well as 45 healthy controls (HC), underwent brain MRI and cardiac MRI (CMR). Analysis of covariance (ANCOVA), partial correlation and mediation analyses were performed. The CAV group exhibited significant cortical thinning in several brain regions, including the bilateral superior frontal gyrus, left angular gyrus, and left supramarginal gyrus (false discovery rate [FDR] P<0.05). Cortical thickness in the left cingulate gyrus (r=−0.377, P=0.015) and right cuneus (r=−0.297, P=0.009) was negatively correlated with extracellular volume (FDR P<0.05). Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination scores were lower in the CAV than non-CAV and HC groups. Cortical thickness in the bilateral inferior frontal gyrus, left cingulate gyrus, right angular gyrus, and right postcentral sulcus was positively correlated with MoCA scores (FDR P<0.05). The cortical thickness of the left cingulate gyrus partially mediated the association between extracellular volume and MoCA scores (β=−0.135; 95% confidence interval −0.323, −0.025).

Conclusions: Our findings reveal a cardiocerebral interaction, highlighting cortical thinning as a neuroimaging marker for CAV-related myocardial fibrosis and cognitive decline.

Background: Patients with heart failure with preserved ejection fraction (HFpEF) and right ventricular (RV)–pulmonary arterial (PA) uncoupling, as assessed by a decrease ratio of tricuspid annular plane systolic excursion (TAPSE) to PA systolic pressure (PASP) on echocardiography, have poorer outcomes than patients without RV-PA uncoupling.

Methods and Results: The MONACO trial was an adaptive, randomized, double-blind, placebo-controlled study that enrolled hospitalized patients with HFpEF admitted to 12 centers in Japan. Patients who had left ventricular ejection fraction ≥50% and TAPSE/PASP <0.57 mm/mmHg at discharge were randomized 1 : 1 to receive pimobendan 1.25 mg b.i.d. or placebo. The primary objective was to evaluate changes from baseline (day 0) to day 30 in exercise capacity measured by the 6-minute walking test. Enrollment was terminated due to the invalid result of the planned interim analysis. The median age of participants was 82 years and 46% were women. Pimobendan (n=24) or placebo (n=26) was administrated orally. At day 30, mean changes in 6-minute walking distance in patients who received pimobendan (+26.9 m [95% confidence interval; −2.0, +55.8]) or placebo (+21.4 m [95% confidence interval; −14.3, +57.2]) were not significantly different (P=0.402).

Conclusions: Among patients with HFpEF and RV-PA uncoupling, administration of pimobendan for 30 days did not result in significant improvement in exercise capacity compared with placebo.

Background: Nationwide data on in-hospital deaths and complications between leadless pacemakers (LPMs) and transvenous pacemakers (TVPMs) in Japan remain limited.

Methods and Results: Using a nationwide database, we identified adults who underwent TVPM or LPM implantation between 2017 and 2023. LPM implantation increased from 0.5% to 25% (P for trend <0.001). LPMs were selected more often as patient age increased and those undergoing dialysis or with dementia and atrial fibrillation (P<0.001). After propensity score matching (12,599 per group), composite outcomes (in-hospital deaths and all complications) were comparable between the LPM and TVPM groups (5.41% vs. 5.59%, respectively; P=0.44; odds ratio [OR] 0.95; 95% confidence interval [CI] 0.84–1.07). All-cause in-hospital death did not differ between groups (LPM, 1.09%; TVPM, 1.05%; P=0.55; OR 1.07; 95% CI 0.83–1.38), whereas all-cause death within 7 days after implantation was higher in the LPM group (0.58% vs. 0.33%; P=0.003; OR 1.80; 95% CI 1.21–2.67). All complications was comparable between the LPM and TVPM groups (LPM, 4.78%; TVPM, 4.82%; P=0.59; OR 0.96; 95% CI 0.85–1.09), but cardiac tamponade was more frequent in the LPM group (0.29% vs. 0.06%; P<0.001; OR 5.42; 95% CI 2.38–12.32).

Conclusions: Composite outcomes were comparable between the LPM and TVPM groups, but the rates of cardiac tamponade and all-cause death within 7 days after implantation were higher in the LPM group.

Background: Effective imaging is lacking for intravascular lesions in pulmonary vascular diseases. Optical coherence tomography (OCT) offers micron-level resolution, enabling improved diagnosis and treatment guidance. This study aimed to evaluate pulmonary arterial lesions using OCT.

Methods and Results: This retrospective study reviewed consecutive patients with pulmonary arterial lesions undergoing OCT at The First Affiliated Hospital of Guangzhou Medical University between August 2022 and November 2024. Patients with chronic thromboembolic pulmonary disease, Takayasu arteritis, Behçet’s disease, or fibrosing mediastinitis were included in the study. Arterial lesions assessed included fresh, subacute, and chronic thrombus, vascular dissection, and other OCT findings. Seventy-two patients (median age 57.5 years [interquartile range 48.0–66.0 years]; 39 [54.17%] males) were included in the study. The OCT features were as follows: fresh thrombus showed irregular regions with marked signal attenuation; subacute thrombus appeared as intraluminal clumps surrounding the catheter; chronic thrombus presented as multichambered mesh-like structures; Takayasu arteritis and Behçet’s disease exhibited bead-like eccentric intimal thickening with vacuole-like changes; fibrosing mediastinitis showed an irregular lumen with high attenuation behind the wall; and vascular dissection presented as dark areas with occasional lumen communication and a streak-like longitudinal appearance.

Conclusions: OCT yields high-resolution imaging for detailed assessment of pulmonary vascular diseases and holds promise for clinical application.

Background: Clinical outcome determinants in cardiac stereotactic body radiotherapy (cardiac-SBRT)/stereotactic arrhythmia radioablation (STAR), a minimally invasive therapy for refractory ventricular tachycardia (VT), remain unclear. We report the final analysis of Japan’s first prospective study following a previously published interim report.

Methods and Results: Between 2019 and 2024, 8 patients with recurrent VT refractory to medical therapy and unsuitable for or refractory to catheter ablation were enrolled. Primary endpoints were safety and VT suppression. Exploratory analyses examined irradiation distribution and autonomic function. Median age was 69 years (75% male), ejection fraction 25%, and median follow-up 2.2 years. Targets were defined using multimodal assessment, with a median planning target volume of 88.9 cc. Treatment-related adverse events included only grade 1 nausea (n=1). Implantable cardioverter-defibrillator shock suppression was 73.6% at 6 months and 76.8% at 1 year. Antitachycardia pacing suppression reached 97.9%, with near-complete suppression in 5 survivors. Analyses remained descriptive and hypothesis-generating. Heart rate variability suggested increased parasympathetic activity, and ¹²³I-metaiodobenzylguanidine imaging indicated reduced washout rate. Three patients died within 2 years but had advanced preexisting heart failure; irradiation more often involved inferior segments. Survival differences were not explained by cohort-level B-type natriuretic peptide levels or systolic function changes.

Conclusions: Cardiac-SBRT/STAR achieved sustained arrhythmia suppression. Heart failure severity, irradiation location, and autonomic function, with their interaction, may be associated with clinical outcomes.

Background: Cardiovascular disease (CVD) is an increasingly important contributor to maternal morbidity and mortality worldwide, but contemporary nationwide data in Japan remain limited.

Methods and Results: We conducted a retrospective cohort study using the Japan Society of Obstetrics and Gynecology Perinatal Database from 2014 to 2023. Among 2,189,852 registered pregnancies, 26,894 (1.23%) were complicated by maternal CVD. Pregnancies with CVD were compared with the low-risk population (pregnancies without any medical comorbidities; n=1,882,896). Pregnancies with CVD had lower parity and more frequently required cesarean delivery, general anesthesia, and labor analgesia than the low-risk population. Maternal cardiovascular complications, including hypertensive disorders of pregnancy, pulmonary embolism and pulmonary edema, occurred at higher rates among pregnancies with CVD. Maternal death was rare in both groups, but was more frequent in pregnancies with CVD than in the low-risk population (0.03% vs 0.01%, P<0.001). Neonatal outcomes were generally similar between groups.

Conclusions: In this nationwide registry analysis, approximately 1% of pregnancies in Japan were complicated by maternal CVD. Women with CVD underwent more obstetric and anesthetic interventions and had a modestly higher risk of maternal morbidity and mortality. These findings underscore the importance of continued registry surveillance and may help inform risk-stratified perinatal management.

Background: Heart failure (HF) is characterized by recurrent clinical deterioration, and multidimensional frailty (i.e., functional status, nutritional status, sarcopenia-related phenotypes, and cognitive impairment) is a key determinant of prognosis. We explored longitudinal changes in these multidimensional domains across recurrent hospitalizations for HF.

Methods and Results: This single-center retrospective cohort study analyzed 337 patients initially hospitalized for HF between 2016 and 2024 who subsequently experienced ≥1 rehospitalization (total 780 admissions). Longitudinal changes across repeated hospitalizations were evaluated using age- and sex-adjusted linear mixed-effects models. The median age was 83 years, and 47.2% were women. Across repeated hospitalizations, frailty and functional status worsened (Clinical Frailty Scale, β=0.40, P<0.001; Barthel Index, β=−4.21, P<0.001; Short Physical Performance Battery score, β=−0.56, P=0.043). Gait speed also declined, although this trend did not reach statistical significance (β=−0.03, P=0.089). Nutritional status deteriorated (Controlling Nutritional Status score, β=0.56, P<0.001; Geriatric Nutritional Risk Index, β=−2.37, P<0.001). Sarcopenia-related indices deteriorated (appendicular skeletal muscle index, β=−2.79, P=0.006; grip strength, β=−4.64%, P<0.001). Cognitive function assessed by the Mini-Mental State Examination showed no significant longitudinal change (β=0.11, P=0.501).

Conclusions: Many domains of frailty deteriorated across recurrent hospitalizations for HF, suggesting cumulative frailty progression.

Background: Heart failure (HF) is associated with poor clinical outcomes and is classified into Stages A–D. Estimated plasma volume (ePV) is a marker of plasma volume expansion. Prognostic markers applicable across all HF stages may enable the early identification of patients at high risk of adverse clinical outcomes. This study evaluated the impact of ePV on clinical outcomes in patients with Stage A–D HF.

Methods and Results: ePV was measured using the PRIME Plus analyzer in 494 patients with HF (Stage A, n=78; Stage B, n=274; Stage C/D, n=142) admitted to our hospital in 2022. Over a median follow-up of 3 years, 95 HF-related events, defined as HF rehospitalization and deaths, and 43 all-cause deaths occurred. Kaplan–Meier analysis demonstrated that patients in the highest ePV tertile had the greatest risk of HF-related events and all-cause deaths. Multivariable Cox proportional hazards regression analysis identified ePV as an independent predictor of HF-related events (hazard ratio [HR] 1.48; 95% confidence interval [CI] 1.26–1.73; P<0.0001) and all-cause deaths (HR 1.35; 95% CI 1.06–1.73; P=0.0158). The addition of ePV to established cardiovascular risk factors significantly improved the C-statistic (0.7009 vs. 0.7415; P=0.0260), net reclassification index, and integrated discrimination index.

Conclusions: This study demonstrates that ePV is a feasible prognostic marker for HF-related events and all-cause deaths in patients with Stage A–D HF.