Renal denervation is a catheter-based therapy that interrupts renal sympathetic traffic and lowers blood pressure through durable neuromodulation. Contemporary catheter-based systems deliver energy to the periadventitial space with an acceptable safety profile. Across blinded placebo-controlled trials in off-medication and on-medication settings, renal denervation achieves greater reductions in ambulatory and office blood pressure than placebo, with a uniform 24-h effect that includes night-time and early-morning periods. Long-term follow-up data from randomized programs and large registries show sustained separation in blood pressure between renal denervation and control groups, preserved renal function, and low re-intervention rates over several years, with select cohorts approaching a decade. This review summarizes the mechanism and target anatomy of renal denervation, key features and results of placebo-controlled trials, and practical considerations for integrating the procedure with contemporary pharmacologic therapy in patients with uncontrolled hypertension.

Background: To provide evidence from randomized controlled trials (RCTs) for large-vessel vasculitis (LVV), including Takayasu arteritis (TAK) and giant cell arteritis (GCA), to inform the forthcoming 2026 Japanese Circulation Society (JCS) clinical practice guideline.

Methods and Results: We drafted 4 and 7 clinical questions for TAK and GCA, respectively. A systematic review (SR) of RCTs was conducted using PubMed, CENTRAL, EMBASE, and the Japan Medical Abstracts Society through March 2024. Assessed with the GRADE approach, the certainty of evidence was very low for the most critical outcomes, low for some outcomes, and moderate for only 1 outcome. Evidence for TAK was limited. Tocilizumab (TCZ) resulted in a numerically lower relapse rate vs. placebo (risk ratio (RR) 0.73, 95% confidence interval (CI) 0.39–1.37) and was similar to adalimumab. No clear difference between mycophenolate mofetil (MMF) and methotrexate (MTX), or between abatacept (ABA) and placebo was observed. In GCA, TCZ reduced relapse (RR 0.29, 95% CI 0.09–0.98) and increased remission (RR 3.56, 95% CI 2.29–5.54) over placebo at 52 weeks. Tumor necrosis factor inhibitor, ABA, and MTX showed no benefit in cranial GCA. Serious adverse events were comparable between treatment groups. Geographic variation and differences in entry criteria were noted.

Conclusions: This SR was comprehensive synthesis of evidence from RCTs for LVV therapies to support the 2026 JCS guideline.

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 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: The interventricular septum contributes 30–60% of right ventricular (RV) output. However, few studies have assessed the prognostic value of RV septal strain in pulmonary embolism (PE). We hypothesized that RV septal strain would predict 30-day mortality in patients with intermediate-risk PE.

Methods and Results: This retrospective cohort study analyzed consecutive patients with intermediate-risk PE admitted to the Penn State Health Milton S. Hershey Medical Center between 2010 and 2018. The primary outcome was 30-day all-cause mortality. RV septal strain was measured within the RV endocardium and was defined as the mean of basal, mid, and apical septal longitudinal strain. Among 251 patients, 31 (12.4%) died within 30 days of PE diagnosis. RV strain analysis was feasible in 230 (91.6%) patients. RV septal strain was significantly lower in those who died and was independently associated with 30-day mortality (P<0.001). Receiver operating characteristic curve analysis indicated 14.4% as the optimal RV septal strain cut-off value (area under the curve 0.816). Kaplan–Meier curves demonstrated that 30-day mortality risk was higher among patients with low (≤14.4%) than high (>14.4%) RV septal strain (hazard ratio 9.29; P<0.001).

Conclusions: RV septal strain is a feasible and reproducible parameter with strong prognostic value in patients with intermediate-risk PE. These findings highlight the central role of the interventricular septum in RV function and risk stratification.

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: 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: 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: 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: Abdominal aortic aneurysm (AAA) is a severe aortic disease with limited pharmacological treatment to prevent its progression. Whether early prevention of aortic lesions inhibits later formation of AAAs remains unclear. Therefore, this study aimed to investigate whether early intervention could prevent aortic lesion progression and AAA formation, and to explore the underlying molecular mechanisms.

Methods and Results: Genome-wide RNA sequencing of aortas from saline-treated mice and mice treated with angiotensin (Ang: 1,000 ng/kg/min) II via subcutaneously implanted mini-osmotic pumps for 14 or 28 days showed that nuclear factor (NF)-κB signaling contributes to the phenotypic switch and inflammation, and identified Nfkb1 as a potential key gene in vascular smooth muscle cells (VSMCs) for AAA development. Andrographolide (an NF-κB1 inhibitor) was administered via intraperitoneal injection at a dose of 20 mg/kg/day to pre-treat vascular lesions before AAA formation, and transcriptomic and functional studies were performed to explore the underlying mechanisms. In AngII-treated mice, andrographolide significantly attenuated vascular lesions at the early stage (day 14) and reduced AAA formation at later stages of the disease (day 28). Andrographolide also reduced aortic macrophage infiltration, decreased neutrophil recruitment, and suppressed cytokines. Although detailed mechanistic analyses focused on VSMCs due to their structural predominance in early lesions, chromatin immunoprecipitation (ChIP) further demonstrated that NF-κB1 regulates its direct target Krüppel-like factor 4 to induce VSMC dedifferentiation and tumor necrosis factor (TNF)-α to drive inflammation, indicating that NF-κB1 exacerbates inflammation via TNF-α signaling.

Conclusions: Our results demonstrate a previously unrecognized role of vascular lesions in AAA development and progression. Andrographolide pretreatment may be a novel therapeutic approach for AAA.

Background: Because vascular regeneration of diabetic lower limb ischemia (LLI) and prevention of disease progression is a major problem, we explored the molecular mechanism of E2F transcription factor 5 (E2F5) in regulating autophagy to promote angiogenesis in diabetic HLI.

Methods and Results: The streptozotocin-induced diabetic mice model, hindlimb ischemia (HLI) model and high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs) were constructed for in vivo and in vitro assays. Autophagy inhibitor, 3-methyladenine, reversed the effects of E2F5 overexpression on microtubule-associated protein 1 light chain 3B (LC3B) expression, cell proliferation, migration and tube formation, supporting the involvement of autophagy in E2F5-mediated HUVEC restoration. In vivo injection of E2F5 overexpressed lentivirus also promoted angiogenesis in diabetic HLI mice, concomitant with autophagy activation. Phosphorylated yes-associated protein (pYAP) expression in HUVECs was upregulated after HG treatment and E2F5 overexpression reversed this change. pYAP colocalized with CD31, and pYAP expression was decreased after E2F5 overexpression. Treatment with Ki16425 increased pYAP expression and affected the influence of E2F5 on the proliferation, migration and tubule formation of HUVECs, and LC3B expression.

Conclusions: E2F5 promoted angiogenesis by downregulating pYAP, which is associated with autophagy activation. These findings provide a novel therapeutic strategy for diabetic LLI.

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: 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: 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: 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: 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.