IntroductionChronic thromboembolic pulmonary hypertension (CTEPH) is a treatable cause of pulmonary hypertension but remains under-recognized and is often diagnosed with delay. Limited access to lung ventilation-perfusion (V/Q) scintigraphy, especially outside tertiary centers, is one contributor. Dynamic chest radiography (DCR), with a pulmonary circulation analysis program, can provide a rapid, non-invasive, and widely deployable assessment of pulmonary perfusion. We describe the protocol of a multicenter reader study testing whether adding DCR-based analysis to standard initial work-up improves diagnostic accuracy for CTEPH among patients with echocardiographically suspected pulmonary hypertension.Methods and analysisThis investigator-initiated, multicenter, assessor-blinded, case-wise randomized superiority reader study compares standard initial work-up (blood tests, chest X-ray, ECG, pulmonary function tests, and transthoracic echocardiography per guidelines) with standard work-up plus DCR-based pulmonary circulation analysis. The primary endpoint is diagnostic accuracy for discrimination between CTEPH and non-CTEPH in the intention-to-treat set. The final diagnosis of CTEPH versus non-CTEPH will be defined as the reference standard according to the Japanese and European guidelines for pulmonary hypertension. Secondary endpoints include sensitivity, specificity, positive and negative predictive values; agreement with V/Q scintigraphy regarding regional perfusion defects using κ statistics; and STARD-conformant academic performance evaluation of DCR-based pulmonary circulation analysis and lung perfusion scintigraphy in relation to the site-level final diagnosis of CTEPH versus non-CTEPH in a full analysis set. Safety endpoints include adverse events during DCR acquisition and device malfunctions. The target sample size is 108 cases with 1:1 allocation. Recruitment started on 30/07/2025 and is expected to continue until 28/02/2027, with overall study completion planned for 31/05/2027.DiscussionThis multicenter reader study addresses a key limitation of current CTEPH diagnostic pathways-reliance on V/Q scintigraphy, which may be delayed or unavailable outside tertiary centers-by evaluating whether DCR-based pulmonary circulation analysis can improve early discrimination of CTEPH and support timely referral.Trial registration numberJapan Registry of Clinical Trials (jRCT), jRCT2072250027.

Background: Acute coronary syndrome (ACS) is the critical situation caused by decreased blood flow of the coronary arteries. The most recent clinical guideline compiled by the Japanese Circulation Society (JCS) recommends lowering low-density lipoprotein cholesterol (LDL-C) to <70 mg/dL in patients with ACS, because of the lack of clinical evidence. It has been shown that there are substantial numbers of patients with familial hypercholesterolemia (FH) among ACS patients. On this basis, we intend assembling a multicenter registry to establish the evidence for lowering LDL-C <55 mg/dL while also clarifying the proportion of FH patients among Japanese ACS patients using a prespecified clinical pathway. Methods and Results: The Hokuriku-plus ACS registry is a prospective, observational, multicenter cohort study, enrolling consecutive ACS patients from 14 participating hospitals in Hokuriku region of Japan from October 2025 to September 2027. A total of 1,000 patients will be enrolled followed over 1 year. The primary endpoint is the proportion of patients who attain LDL-C <55 mg/dL at 4 weeks. This study has been registered at the Japan Registry of Clinical Trials (jRCT1040250123). Conclusions: We will disseminate the final results at international conferences and in a peer-reviewed journal.

Background: Cardiovascular disease (CVD) is a leading global health concern. Traditional models often miss nonlinear dependencies among physiological and behavioral factors. We hypothesized that a Transformer-based deep learning model, which excels at capturing complex patterns in structured data trained on large-scale health check-up records, would improve long-term CVD risk prediction. Methods: We analyzed longitudinal health records (2010?2024) from the Hokuriku Health Service Association (n = 100,056 without baseline CVD; development cohort). Incident CVD was defined as the first self-reported physician diagnosis of heart disease or stroke during the 10-year follow-up and was modeled as right-censored survival data. An external evaluation cohort comprised 79,756 Kanazawa City participants with health records. A Transformer model was trained using anthropometric, laboratory, and self-reported lifestyle data. Benchmarks included Cox regression, XGBoost survival embeddings, multilayer perceptron, the Framingham Risk Score, and the Hisayama Risk Score. Performance was evaluated using time-dependent area under the receiver operating characteristic curve (ROC-AUC) with a primary focus on the 10-year ROC-AUC, precision?recall AUC (PR-AUC), and concordance index (C-index). Interpretability was assessed through SHapley Additive exPlanations (SHAP) and a Feature-level Attention Network (FAN), visualizing the top 12 SHAP-ranked features to highlight key interactions. Results: In the development cohort, 4,113 CVD events (4.1%) occurred. The Transformer model achieved the best internal performance: 10-year ROC-AUC 0.821 (95% confidence interval [CI], 0.816?0.826), PR-AUC 0.427 (CI, 0.419?0.435), and C-index 0.781 (CI, 0.775?0.787). Performance remained robust externally (21,179 CVD events, 26.6%): ROC-AUC, 0.762; PR-AUC, 0.500; and C-index, 0.744. Regarding interpretability, SHAP identified age, electrocardiogram abnormality, antihypertensive medication, and sex as the most critical predictors. Notably, FAN elucidated the prognostic value of self-reported lifestyle factors. For example, daily exercise and weight gain modulated the model?s assessment of age-related risk. Within the attention network, age served as a central hub, linking these behavioral habits with physiological features. Conclusion: The Transformer-based model outperformed conventional methods in predicting long-term CVD risk. Model interpretation demonstrated the predictive utility of self-reported lifestyle factors, such as weight gain and daily exercise. These findings may support personalized CVD prevention and population-level risk stratification using routinely collected health checkup data.

Aims According to the latest Japanese Guidelines for the Prevention of Atherosclerotic Disease, the target for secondary prevention of low-density lipoprotein cholesterol (LDL-C) is <100 mg/dL in patients with coronary artery disease and <70 mg/dL in patients with acute coronary syndrome, familial hypercholesterolemia, diabetes, or atherothrombotic cerebral infarction. However, it is still unclear if the LDL-C treatment target attainment rates are in an upward trend and what are the factors associated with target attainment. This study aimed to investigate the trends and factors associated with LDL-C treatment target attainment. Methods Using the Health Checkup data in Kanazawa City in 2008, 2012, 2017, and 2022 (n = 38,146-51,969), we analyzed the trends of secondary prevention of LDL-C treatment target attainment rates using the Cochran-Armitage trend test and the factors associated with target attainment by a logistic regression analysis from the 2022 health examination. Results We found that the attainment rates showed a significant upward trend over time (p<0.001), and we also found that a male sex (odds ratio: 2.64, 95% CI: 1.72-4.06, p<0.001) and several lifestyle factors, such as walking or any equivalent amount of physical activity for more than one hour a day, were significantly associated with LDL-C target attainment. Conclusions The LDL-C treatment target attainment rates tended to increase over time, and several factors were associated with LDL-C target attainment.

Background: We aimed to clarify the impact of genetic testing on major adverse cardiovascular events (MACE) among patients with heterozygous familial hypercholesterolemia (HeFH) using data from the Hokuriku-plus FH Registry (UMIN000038210). Methods and Results: In all, 431 patients were enrolled in the study, with a median follow-up of 3.9 years. The primary outcome was time to first MACE, defined as cardiovascular death, non-fatal myocardial infarction, coronary revascularization, or non-fatal stroke. Using Cox proportional hazards regression models, we examined whether undergoing genetic testing was associated with a reduced risk of MACE. Among the 431 patients, sufficient data were available for 386 with HeFH, of whom 202 (52.3%) underwent genetic testing. Low-density lipoprotein cholesterol (LDL-C) levels at follow-up were significantly lower in group that underwent genetic testing than in the group that did not (median 102 vs. 130 mg/dL, respectively; P<0.001). During follow-up, 23 MACE occurred (18 in the non-testing group and 5 in the genetic testing group). Notably, undergoing genetic testing was significantly associated with a reduced risk of MACE, even after adjusting for LDL-C levels (hazard ratio 0.66; 95% confidence interval 0.20-0.92; P=0.033). Conclusions: Genetic testing in patients with HeFH was associated with a reduced risk of MACE independent of LDL-C. Randomized controlled trials will be needed to clarify whether providing genetic testing can reduce MACE among patients with HeFH.

LDL cholesterol (LDL-C) is the central causal factor for atherosclerotic cardiovascular disease (ASCVD), and its reduction is a cornerstone of both primary and secondary prevention. Since the introduction of statins more than three decades ago, LDL-C-lowering therapy has expanded substantially, now encompassing ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9)-targeting agents, bempedoic acid, and other emerging modalities. This expanding therapeutic landscape has improved the feasibility of achieving guideline-recommended LDL-C targets, but it has also increased the complexity of clinical decision making. This review provides a contemporary and practical overview of the LDL-C-lowering strategies, beginning with the initial evaluation of patients with elevated LDL-C, including differentiation between primary and secondary causes and the identification of familial hypercholesterolemia (FH). We summarize the current treatment targets for primary and secondary prevention, highlight the optimal selection and use of statins, and discuss the assessment and management of statin intolerance, including the role of the nocebo effect. Non-statin therapies, including ezetimibe, bile acid sequestrants, PCSK9 inhibitors, inclisiran, and bempedoic acid, are reviewed with an emphasis on their mechanisms, efficacy, and clinical positioning. Advanced therapies for severe dyslipidemia, such as lipoprotein apheresis, lomitapide, and evinacumab, are also discussed in this review. Finally, we outline the future directions, including oral PCSK9 inhibitors, next-generation cholesteryl ester transfer protein (CETP) inhibitors, lipoprotein(a)-lowering agents, and genome-editing approaches. Collectively, these developments offer new opportunities to address unmet clinical needs, particularly in patients with FH, statin intolerance, and residual cardiovascular risk. A comprehensive understanding of these therapies is essential for further reducing the burden of ASCVD in the coming decades.

Introduction The subcutaneous adipose-tissue-derived stromal vascular fraction (Sa-SVF) contains stem/progenitor cells that rarely transdifferentiate into beating cardiomyocytes. Previously, we developed a culture protocol in which adult murine inguinal Sa-SVF cells reproducibly transdifferentiate into beating cardiomyocyte-like cells (beating CMs) without any specific induction in the primary culture. However, the mechanism underlying the differentiation of the Sa-SVF toward the cardiac lineage is unclear. Methods To identify a key regulator of cardiac differentiation, we investigated sequential changes in global gene expression profiles of Sa-SVF cells during primary culture. Sa-SVF cells were isolated from adult murine inguinal subcutaneous fat pads and cultured using our beating CM induction method. At six time points during primary culture, total RNA was extracted and subjected to RNA-sequencing and quantitative polymerase chain reaction analysis. Results Beating CMs appeared on day 14. Of 14,574 prefiltered genes, 749 showed significant expression changes (153 upregulated and 596 downregulated, > 2-fold) between days 7 and 14, coinciding with the appearance of beating CMs. Gene ontology analysis highlighted histone deacetylase (HDAC)-associated genes, expression of which was transiently suppressed during the period when cardiac sarcomere-related genes and the transcription factor Mef2c were upregulated. Treatment with an HDAC inhibitor increased cardiac troponin T expression on day 28. Furthermore, treatment of Mef2c-transduced Sa-SVF cells with an HDAC inhibitor markedly augmented cardiac troponin T expression (18-fold vs. control). Conclusions These findings suggest that transient epigenetic modulation, particularly involving class II HDACs, is associated with and may facilitate cardiomyocyte-like differentiation of Sa-SVF cells. This study provides a mechanistic framework for combining epigenetic modulation with transcriptional programming to enhance SVF-based cardiac regenerative strategies.

Background: Anemia, a common comorbidity in older patients with heart failure (HF) and atrial fibrillation (AF), is associated with an increased risk of adverse events. This study evaluated the prognostic effects of longitudinal changes in anemia status on clinical outcomes in patients with AF. Methods and Results: We prospectively evaluated data of 1,388 patients with AF from the Hokuriku-Plus AF Registry (1,010 men; mean [+/- SD] age 72.3 +/- 9.7 years) and recorded the incidence of death, HF, thromboembolism, and major bleeding. Of these patients, the 1,233 for whom hemoglobin levels were available at baseline and at the 1-year follow-up were further evaluated. Patients were categorized into 3 groups based on longitudinal changes in 1-year anemia status: Group 1, AF without anemia; Group 2, AF with improved anemia; and Group 3, AF with sustained or new-onset anemia. Over the 1-5 years of follow up, the incidences of death, HF, thromboembolism, and major bleeding were significantly higher among patients with than without anemia. In addition, the incidence of death or HF was significantly higher in Group 3 than in Groups 1 and 2. Multivariate analysis revealed no anemia or improvement in anemia in 1 year as an independent predictor for a favorable prognosis for cardiovascular death and HF. Conclusions: Recovery from anemia may be associated with a favorable clinical course of AF.

Introduction: Mammalian sterile 20-like kinase 1 (Mst1), a major component of the Hippo pathway, promotes cell death and differentiation while inhibiting cell growth, thereby contributing to the development of heart failure. We recently discovered that Mst1 phosphorylates protein kinase RNA-like endoplasmic reticulum kinase (PERK), a kinase responsible for the integrated stress response (ISR). Methods and results: Mst1 induces phosphorylation of the cytoplasmic domain of PERK, leading to its activation. To evaluate the role of phosphorylation of PERK in the heart, we generated knock-in mice expressing a PERK mutant that is not phosphorylated by Mst1 (PERK-KI). Although PERK was activated by tunicamycin, an ER stress inducer, it was not activated by transverse aortic constriction (TAC) in PERK-KI mice in vivo , suggesting that Mst1 mediates activation of PERK during TAC. To investigate the effect of Mst1-induced PERK phosphorylation on cardiac function, cardiac-specific Mst1 transgenic mice (Tg-Mst1) were crossed with heterozygous (h) PERK-KI mice (Tg-Mst1-hPERK-KI). The level of phosphorylation of eIF2α was decreased in Tg-Mst1-hPERK-KI mice compared to in Tg-Mst1 mice (0.45-fold, p<0.05), confirming that Mst1-induced activation of PERK is inhibited in hPERK-KI mice. Decreases in left ventricular ejection fraction (LVEF) in Tg-Mst1 was alleviated in Tg-Mst1-hPERK-KI mice (46% vs Tg-Mst1 34%, p<0.05), which was accompanied by reduced fibrosis (3.5% vs Tg-Mst1-hPERK-KI 2.2%, p<0.05) in the heart. Since Mst1 is activated by TAC (2.4-fold), we investigated the effect of TAC in hPERK-KI mice. Cardiac dysfunction induced by 8 weeks of TAC was also alleviated in hPERK-KI mice (LVEF: 67% vs WT 46%, p<0.05). It has been shown that the protein level of angiotensin II type 1 receptor (AT1R), a critical mediator of pathological cardiac hypertrophy, is increased by the ISR. We found that AT1R expression was increased in Tg-Mst1 mice but attenuated in Tg-Mst1-hPERK-KI mice (2.18-fold, p<0.05). Conclusion: Mst1 mediates pathological hypertrophy through activation of PERK. Mst1-induced activation of PERK was accompanied by upregulation of AT1R, a protein known to be regulated by the ISR.

The combination of immunosuppressive therapy (IST) and pulmonary artery vasodilators has demonstrated potential effectiveness in treating pulmonary arterial hypertension (PAH) associated with connective tissue diseases (CTD-PAH) other than systemic sclerosis (SSc). However, large-scale studies of this topic are limited. This study aimed to evaluate the effectiveness of early IST in treating PAH in patients diagnosed with non-SSc CTD-PAH. Clinical data for patients with non-SSc CTD-PAH were collected from the Japan Pulmonary Hypertension Registry spanning 2008–2021. Early IST was defined as the initiation or intensification of therapy within 3 months of PAH diagnosis. The study included 141 patients (mean age 51 ± 16.7 years; 95

Cardiac cachexia, characterized by adipose tissue atrophy, has the most unfavorable outcome in heart failure (HF). Adipose dysfunction might worsen HF as adipose tissue has been found to have cardioprotective effects mediated through its metabolic and endocrine functions, and therefore, could serve as a novel therapy target. In the context of adipose tissue homeostasis, adipocyte progenitor cells (APCs) play critical roles in maintaining the number and function of mature adipocytes, including lipid metabolism and hormone secretion. However, the mechanism by which HF affects APCs has not been elucidated. In this study, we aimed to evaluate the number and functions of Lin-CD24+ APCs in the subcutaneous adipose tissue of mice subjected to transverse aortic constriction-induced HF. This HF model greatly reduced the number of APCs and increased their apoptosis, resulting in lipodystrophy. In vitro assays revealed that HF limited APC proliferation and senescence. With respect to the mechanism of impaired APC function in HF, we identified that augmented sympathetic nerve activity partially mediated the decrease in APC counts via unilateral adipose tissue denervation (ATD). Furthermore, ATD mitigated HF-induced APC senescence. We elucidated that HF and excess sympathetic nerve activity impaired the adipogenic differentiation capacity of APCs. In conclusion, HF induced APC loss and senescence by augmenting sympathetic nerve activity. The impaired adipogenic capacity of APCs results in reduced healthy adipose tissue mass, suggesting that this phenomenon could be responsible for the worsening of HF.NEW & NOTEWORTHY Our work elucidated the negative feedback between heart failure (HF) and the number and function of adipocyte progenitor cells (APCs). HF drastically decreases CD24+ APC number and proliferative capacity. Furthermore, we discovered that HF impaired the capacity of APCs to differentiate into mature adipocytes. In conclusion, impaired APC function in HF would be a new research target to ameliorate severe HF outcomes in patients with cachexia.

Background: The prevalence of heart failure (HF) is rising, highlighting the need for early detection and intervention. Current Japanese HF guidelines define a B-type natriuretic peptide (BNP) ≥100 pg/mL and a N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥300 pg/mL as indicators of high HF probability. We developed and validated deep learning models using ECG to predict elevated BNP or NT-proBNP levels based on guideline-recommended cutoffs, thereby facilitating early HF detection. Methods: We developed prediction models for elevated BNP (≥100 pg/mL) and NT-pro BNP (≥300 pg/mL) using a one-dimensional convolutional neural network (1D-CNN). The models used 12-lead ECGs and corresponding same-day BNP or NT-proBNP measurements, along with age and sex. Data were collected from patients (aged ≥18 years) at Kanazawa University Hospital, Japan between January 1, 2010, and December 31, 2023. The dataset was divided into training, internal validation, and testing sets (7:2:1 ratio). The 1D-CNN model was constructed for BNP and NT-proBNP classification. Furthermore, we developed and evaluated models using single-lead ECG data. The primary performance metrics on the test dataset were area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and F1 score, reported with 95% confidence intervals (CIs). Results: The BNP and NT-proBNP prediction model included 73719 ECGs from 21806 patients (training, 53296 ECGs in 15700 patients; validation, 13122 ECGs in 3925 patients; testing, 7373 ECGs in 2181 patients). Using 12-lead ECG data, the BNP and NT-proBNP prediction model achieved an AUC of 0.820 (95% CI, 0.809-0.830). With single-lead ECG data, the BNP and NT-proBNP prediction model yielded an AUC of 0.811 (CI, 0.801–0.821), accuracy of 74.1% (CI, 73.2–75.1), sensitivity of 57.3% (CI, 55.5–59.1), specificity of 84.4% (CI, 83.3–85.4), and F1 score of 62.7% (CI, 61.2–64.3). Conclusions: The deep learning models using not only 12-lead ECGs but also single-lead ECGs demonstrated favorable performance in identifying patients with elevated BNP and NT-proBNP on the HF guideline cutoffs. These findings highlight ECG-based deep learning’s potential as a tool for opportunistic screening and early detection of high-risk HF individuals.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has become an established treatment option in patients with severe AS, and the indication for the procedure has recently expanded. Cardiac sympathetic nerve activity (CSN) dysfunction and its improvement after TAVI have been reported in patients with severe AS. However, previous studies often included patients with advanced heart failure, potentially confounding the accurate assessment of CSN. These patient characteristics may not reflect the typical profile of real-world AS candidates undergoing TAVI. The primary objective of this study was to evaluate the neurological effects of TAVI on skin sympathetic nerve activity (SKNA) in severe AS patients reflecting real-world TAVI backgrounds and to identify clinical predictors of SKNA changes. METHODS: This prospective, single-center observational cohort study enrolled severe AS patients undergoing TAVI at Kanazawa University Hospital (Aug 2022-Apr 2025). Key inclusion criteria were severe AS and TAVI suitability. Patients with conditions affecting sympathetic nerves were excluded. The primary exposure was TAVI; the primary outcome was the change in SKNA Burst amplitude pre- and post-procedure. SKNA was recorded 2-5 days before and after TAVI was performed. Paired tests compared SKNA parameters. Multivariate regression identified predictors of Burst amplitude change, including baseline Burst amplitude and cardiac output index. RESULTS: TAVI significantly decreased Burst amplitude (from median 1.330 µV [IQR 1.008-2.107] to 1.082 µV [IQR 0.839-1.220], p<0.05)(Image 1,2). On multivariate analysis, baseline Burst amplitude was independently associated with the degree of its change after TAVI (β = -0.608, p = 0.001), indicating that higher baseline CSN predicted greater postprocedural improvement(Image 3). Furthermore, when examining hemodynamic parameters, cardiac output index measured by Swan-Gantz catheter showed the strongest association with baseline Burst amplitude (β=-1.242, p= 0.003), indicating that low cardiac output is associated with higher baseline CSN. CONCLUSION: In patients with severe AS, TAVI significantly decreased SKNA, particularly in those with elevated CSN before the procedure, which was linked to low cardiac output. These findings suggest that TAVI-induced CSN reduction depends on the baseline hemodynamic severity of AS, potentially guiding clinical decision-making in these patients.

BACKGROUND AND AIMS:In 2022, the Japan Atherosclerosis Society (JAS) revised clinical diagnostic criteria of familial hypercholesterolemia (FH), adopting the use of definite, probable, possible, and unlikely FH categories following the Dutch Lipid Clinic Network (DLCN) FH criteria. However, whether these strata would be useful for the risk stratification of coronary artery disease (CAD) events among patients with hypercholesterolemia is unclear. METHODS:We retrospectively reviewed the data of patients with hypercholesterolemia (LDL cholesterol ≥180 mg/dL) aged ≥15 years (N = 1,273, male = 631) admitted to Kanazawa University Hospital between 2000 and 2022. Using the Cox proportional hazard model, we assessed whether factors, including the diagnostic strata of FH, were associated with CAD events. RESULTS:We identified 572, 174, 196, and 331 patients with definite, probable, possible, and unlikely FH, respectively. The prevalence of the pathogenic variant of FH was 71.0 %, 25.9 %, 11.7 %, and 1.5 %, respectively, among patients with definite, probable, possible, and unlikely FH (p < 0.001). We identified 144 CAD events during the 12.4 year median follow-up. Compared with the reference group of unlikely FH, subjects with definite, probable, and possible FH had significantly higher hazard ratios (HRs) of developing CAD events (HR, 6.44; 95 % confidence interval [CI], 2.64-10.24; p < 0.001 and HR, 3.10; 95 % CI, 1.51-4.51; p < 0.001, and HR, 1.88; 95 % CI, 1.08-2.60; p = 0.02, respectively). CONCLUSION:Among patients with hypercholesterolemia, the JAS clinical diagnostic strata of FH are useful for risk discrimination beyond their diagnosis as FH.

Aim: We aimed to clarify the degree and factors associated with low-density lipoprotein (LDL)-cholesterol treatment target attainment among patients with heterozygous familial hypercholesterolemia (HeFH) using the Hokuriku-plus FH registry. Methods: The Hokuriku-plus FH registry (UMIN000038210) was a prospective, observational, multicenter cohort study that enrolled consecutive patients with FH who fulfilled the clinical criteria for FH in Japan from 37 participating hospitals, mostly in the Hokuriku region, from April 2020 to March 2024. This registry collects data on clinical parameters, including lipid levels, physical findings, genetic background, and clinical events. In total, 431 patients were enrolled, and the median followup period was 3.1 years. We assessed the degree and factors associated with LDL-cholesterol treatment target attainment among patients with HeFH using the Hokuriku-plus FH registry. Results: Among the 431 patients, sufficient data were collected from 386 patients. Logistic regression analysis revealed that male sex (odds ratio [OR] = 2.16, 95% confidence interval [CI]: 1.14-3.18, p<0.001) and genetic testing (OR = 1.68, 95% CI: 1.10-2.26, p<0.001) were significantly associated with LDL-cholesterol treatment target attainment. In fact, female patients were less likely to attain LDL-cholesterol treatment target than male patients (24.0% vs. 38.1%, p<0.001), and patients who did not undergo genetic testing were less likely to attain LDL-cholesterol treatment target than those who underwent genetic testing (24.5% vs. 37.1%, p<0.001). Conclusion: Sex bias and masked genetic status are significant barriers to the clinical management of patients with HeFH.

Background Limited data are available on sex‐specific associations between daily step counts and cardiovascular events in middle‐aged adults. Methods This study used the KenCoM Healthcare Database to evaluate sex‐specific differences in cardiovascular event risk associated with daily step counts (DSC). The database incorporates DSC data from the KenCoM smartphone app, along with health checkup records and Japanese health insurance claims data. We recruited and enrolled participants using the KenCoM app, registering them in our database between January 2016 and September 2021. The primary outcome was the 5‐year cumulative incidence of composite cardiovascular events, including myocardial infarction, stroke, angina pectoris, heart failure, and atrial fibrillation. We compared event rates across quintiles of DSC. The quintiles were defined as follows: Group 1 (<4000 steps/d), Group 2 (4000–5999 steps/d), Group 3 (6000–7999 steps/d), Group 4 (8000–9999 steps/d), and Group 5 (≥10 000 steps/d). Results This study included 73 975 participants (55 612 men and 18 363 women) with a mean age of 44.1±10.1 years. The adjusted risk of 5‐year cardiovascular events was significantly lower in Group 5 compared with Group 1 in the entire cohort (adjusted hazard ratio, 0.87 [95% CI, 0.77–0.98]; P=0.02). Sex‐specific analysis showed that the adjusted risk of cardiovascular events was significantly lower in Group 5 compared with Group 1 in men (adjusted hazard ratio, 0.82 [95% CI, 0.72–0.94]; P=0.004), but this effect was not observed in women. Conclusions The highest DSC was associated with a lower risk of cardiovascular events compared with the lowest DSC in men, but not in women, within a middle‐aged population.

Background:Heart failure (HF) hospitalization is increasing in Japan's aging population. Current guidelines recommend daily biometric monitoring for patients with HF to facilitate early clinical intervention. However, promoting patient self-management remains insufficient. Therefore, we assessed the usefulness of the LAVITA telemonitoring system, which automatically obtains and stores the biometric data of patients with HF via wireless devices. Methods and Results:This prospective, single-arm, multicenter cohort study enrolled patients with HF. Patients were introduced to the LAVITA telemonitoring system and trained to measure body weight, blood pressure, pulse rate, oxygen saturation (SpO2), physical activity with activity trackers (AT), and electronic patient-reported outcomes (ePRO). The primary outcome was the measurement rate of each cetology at 9-12 weeks post-discharge. The secondary outcomes included the subgroup analyses by age, sex, and left ventricular function. Thirty patients continued to use the system at home. The measurement rates of patient data were as follows: body weight 92.4% (interquartile range [IQR] 83.3-97.8%); blood pressure 95.6% (IQR 84.8-98.5%); pulse rate 96.5% (IQR 86.5-98.8%); SpO2 93.1% (IQR 76.6-97.9%); AT 88.4% (IQR 31.3-98.5%); and ePRO 76.9% (IQR 26.4-95.9%). The subgroup analysis did not significantly differ. Conclusions:The LAVITA telemonitoring system had high measurement rates for the biometric data of patients with HF, including elderly patients. Hence, it can possibly improve patient self-management and facilitate early clinical intervention.

Background: Heart failure (HF) is an increasing public health concern in Japan, largely related to the aging population. This protocol describes the rationale, objectives, and methods of the Hokuriku-plus Heart Failure Registry (HpHFR), designed to establish a comprehensive clinical and digital database to assess novel prognostic indicators in patients with HF. Methods and Results: HpHFR is a prospective, multicenter observational cohort study that has enrolled patients with acute or chronic HF from 5 Japanese centers. Eligible patients provided informed consent and underwent baseline clinical, laboratory, and biometric assessment, including digital phonocardiography and wearable device data. Follow-up assessment will be conducted at 4, 12, 26, and 52 weeks. Primary outcomes include all-cause death, HF-related hospitalization, and worsening HF. Secondary outcomes are the changes in clinical parameters over time. A digital substudy will investigate continuous biometric monitoring, and a genomic substudy explores the loss of chromosome Y as a prognostic biomarker. Conclusions: In conclusion, this study protocol summarizes the development of a valuable prospective cohort resource. This registry will provide a unique dataset enabling multifaceted investigations to improve HF prediction and management by systematically integrating comprehensive clinical and laboratory data with biometric indicators derived from digital devices and genomic markers.

BACKGROUND:Data on the appropriate timing and impact of atherosclerosis assessment in patients with heterozygous familial hypercholesterolemia (HeFH) are limited. OBJECTIVES:The authors aimed to determine when atherosclerotic changes occur and the utility of triple assessments of carotid plaque, coronary plaque, and coronary artery calcium (CAC) in patients with HeFH. METHODS:Data from patients with HeFH in the primary prevention setting admitted to Kanazawa University Hospital between 2000 and 2020 who underwent triple atherosclerosis assessment and were followed up were retrospectively reviewed (n = 622, male = 306, mean age = 54 ± 13 years). Risk factors for coronary heart disease events were determined using the Cox proportional hazard model. Carotid plaque, coronary plaque, and CAC scores were plotted against age. RESULTS:We found that the age was independently associated with coronary heart disease events. Regression equations of carotid plaque, coronary plaque, and CAC scores against age were Y = 0.12X - 2.07 (β coefficient = 0.12 [95% CI: 0.09-0.15]; r2 = 0.12), Y = 0.36X - 9.30 (β coefficient = 0.36 [95% CI: 0.26-0.46]; r2 = 0.14), and Y = 2.48X - 77.23 (β coefficient = 0.07 [95% CI: 0.04-0.10]; r2 = 0.23) in men and Y = 0.12X - 3.60 (β coefficient = 0.12 [95% CI: 0.08-0.16]; r2 = 0.18), Y = 0.33X - 11.75 (β coefficient = 0.33 [95% CI: 0.29-0.37]; r2 = 0.17), and Y = 2.23X - 89.47 (β coefficient = 0.09 [95% CI: 0.06-0.12]; r2 = 0.34) in women, respectively. Significant differences of cardiovascular events were observed among the groups according to atherosclerotic burden. CONCLUSIONS:On average, carotid plaque, coronary plaque, and CAC may develop at ages 17, 26, and 31 years in male patients and 30, 36, and 40 years in female patients with HeFH, respectively, based on regression equations. Furthermore, triple assessments help in risk stratification.