Background: Nodular calcification (NC) detected via intracoronary imaging is associated with adverse cardiovascular events after percutaneous coronary intervention (PCI). However, the impact of NC detected on pre-PCI non-contrast computed tomography (CT) on clinical outcomes has not been fully investigated.

Methods and Results: We retrospectively included 267 consecutive patients with chronic coronary syndrome who underwent electrocardiography-gated non-contrast CT before PCI for severely calcified lesions. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, stroke, non-fatal myocardial infarction, and target lesion revascularization (TLR). Fifty-eight patients had NC detected on non-contrast CT in target lesions. The MACCE-free survival rate was significantly lower in patients with than without NC (P<0.001). All-cause death, cardiac death, and TLR-free survival rates were significantly lower among patients with than without NC. Multivariate Cox regression analysis revealed that hemodialysis (hazard ratio [HR] 3.00; P=0.003), peripheral artery disease (HR 2.65; P=0.01), and the presence of NC (HR 5.25; P<0.001) were independently associated with MACCE. Adding NC to traditional cardiovascular risk factors, peripheral artery disease, and hemodialysis can provide discriminatory and reclassification abilities in predicting MACCE.

Conclusions: NC detected on non-contrast CT was independently associated with MACCE. Therefore, evaluating NC using preprocedural non-contrast CT may be useful in predicting future clinical outcomes after PCI.

Background: Initially regarded as a benign acute cardiomyopathy, recent insights have shown that takotsubo syndrome (TTS) carries a prognosis comparable to that of acute coronary syndrome, with a notable impact of inflammatory burden. Given the seasonal variation seen in air pollution, inflammation, and coronary events, we investigated whether chronobiology and inflammation contribute to adverse outcomes.

Methods and Results: Between 2008 and 2020, all consecutive TTS patients were retrospectively included in a multicenter registry. We analyzed the impact of seasonal variation and inflammation on in-hospital events, including acute cardiac failure, cardiogenic shock, and death, as well as 30-day mortality. In-hospital events were identified in 238 (42.6%) patients. Higher rates of in-hospital events and 30-day mortality were observed during winter and spring than in summer and autumn. Multivariate analysis identified the presence of dyspnea on admission (odds ratio [OR] 4.02; 95% confidence interval [CI] 2.61–6.17; P<0.001), a neurological trigger (OR 2.58; 95% CI 1.21–5.50; P=0.014), hyperleukocytosis (OR 1.04; 95% CI 1.02–1.17; P=0.002), and left ventricular ejection fraction at admission (OR 0.98; 95% CI 0.96–1.00; P=0.011) as independent predictors of adverse outcomes.

Conclusions: In TTS, higher rates of in-hospital events and 30-day mortality were observed during winter and spring. Inflammatory burden and neurological disorders emerged as independent predictors of poor prognosis.

Background: Lipid-lowering therapy with high-intensity statins has not been widely implemented in Japan for patients with coronary artery disease who undergo percutaneous coronary intervention (PCI). We examined the efficacy and safety of high-intensity statin therapy in a real-world setting.

Methods and Results: We used the Clinical Deep Data Accumulation System (CLIDAS) to accumulate multimodal data from the electronic medical records of 7 cardiovascular centers. We analyzed 9,690 patients who underwent PCI between 2013 and 2019 and completed a median 2.5-year follow-up (CLIDAS-PCI database). The risk of developing major adverse cardiac and cerebrovascular events (MACCE) was significantly greater in patients with acute (ACS) than chronic (CCS) coronary syndrome. High-intensity statins were prescribed to 49% of ACS patients and 33% of CCS patients within the first 30 days after the index PCI. After propensity score matching, MACCE event rates were similar between the high- and moderate-intensity statin groups. Importantly, among ACS patients, Cox proportional hazard analysis revealed that the rate of myocardial infarction was lower (adjusted hazard ratio [aHR] 0.65; 95% confidence interval [CI] 0.44–0.97) and the rate of stroke was greater (aHR 1.71; 95% CI 1.12–2.62) in the high-intensity statin group, driven mostly by intracranial hemorrhage.

Conclusions: The CLIDAS-PCI database provides real-world evidence for the efficacy and safety of high-intensity statins in Japanese ACS patients who have undergone PCI.

Background: The SAPIEN 3 Ultra RESILIA (S3UR) is the latest balloon-expandable valve used in transcatheter aortic valve implantation (TAVI). However, hemolysis is a potential concern with the S3UR. This Japanese single-center retrospective study evaluated the prevalence and associated factors of subclinical hemolysis in the S3UR compared with the SAPIEN 3 (S3).

Methods and Results: We analyzed data for 339 patients who underwent TAVI for severe aortic stenosis and completed a 1-month follow-up (S3UR, n=69; S3, n=270). Subclinical hemolysis was defined as an increase lactate dehydrogenase >2.5-fold from baseline. The prevalence of subclinical hemolysis at 1 month was significantly higher in the S3UR than S3 group (14.5% vs. 2.7%; P<0.001). Notably, subclinical hemolysis was more frequently observed in the S3UR group when mild paravalvular leak (PVL) remained at 1 month. Univariate analysis revealed that mild or greater PVL at 1 month, decreasing annular oversizing, and increasing the difference between the mean diameter of the sinus of Valsalva (SOV) and transcatheter heart valve (THV) size were associated with subclinical hemolysis in the S3UR group.

Conclusions: Remaining mild or greater PVL and using an undersized THV relative to the annulus and SOV were associated with subclinical hemolysis in the S3UR. These findings highlight the importance of selecting a THV size that appropriately matches the aortic valve complex and ensuring adequate THV expansion to prevent subclinical hemolysis.

Background: The prognosis for survivors of acute coronary syndrome (ACS) remains substantially worse compared with the general population. In Japan, regional clinical alliance paths (RCAPs) have been promoted to support the secondary prevention of ACS within community settings. However, the implementation of RCAPs is currently low, and their clinical efficacy has not been established. This study evaluated the impact of RCAP implementation on secondary prevention outcomes in ACS patients.

Methods and Results: Of 405 patients admitted to Tottori University Hospital for ACS between May 2020 and April 2023, 136 who underwent primary percutaneous coronary intervention (PCI) and received follow-up care at primary care clinics were included in the study. Sixty-five (47.8%) patients received care under an RCAP, whereas 71 received standard care. RCAP implementation was associated with a higher proportion of patients achieving low-density lipoprotein cholesterol (LDL-C) levels below 70 mg/dL and with greater reductions in LDL-C levels overall. Propensity score-weighted analysis confirmed that the RCAP group achieved significantly better LDL-C control after adjustment for baseline characteristics using inverse probability weighting.

Conclusions: RCAP implementation improved the rate of LDL-C target achievement and the degree of LDL-C reduction in post-ACS patients receiving follow-up care from family physicians. RCAP implementation is an effective strategy for the secondary prevention of ACS, particularly by enhancing adherence to established pharmacological therapies.

Background: B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-pro-BNP) are key biomarkers used for heart failure (HF) management. Although traditional auscultation lacks objective evaluation, the SSS01-series phonocardiogram enables rapid recording of heart sounds and ECG. We developed a deep-learning model to estimate plasma BNP levels from these non-invasive dynamic physiological signals, with the aim of validating the model’s performance with an external validation dataset and assessing its feasibility for clinical application.

Methods and Results: This multicenter study evaluated the estimated BNP (eBNP) model for predicting plasma BNP levels ≥100 pg/mL using 8 s of heart sound and ECG data. Validation was performed on an external validation dataset of 140 patients, achieving an area under the receiver operating characteristic curve (AUROC) of 0.895, with sensitivity and specificity of 84.3% and 82.9%, respectively. Subgroup analysis of patients with body mass index of 18.5–25 (n=127) showed more substantial predictive capability, with an AUROC of 0.959, sensitivity of 92.5%, and specificity of 84.8%.

Conclusions: The eBNP model demonstrated strong potential for non-invasive and rapid HF screening. Its simplicity and objectivity make it ideally suited for point-of-care testing, offering a promising approach for early HF diagnosis and detection monitoring of HF exacerbations. These findings, validated on datasets independent of training, highlight the model’s robustness across diverse clinical populations.

Background: In addition to the J-HeartMate Risk Score (J-HMRS) and HeartMate 3 Risk Score (HM3RS), the J-MACS Risk Score (J-MACS-RS) was developed to predict death after left ventricular assist device (LVAD) implantation in Japanese patients with heart failure (HF). However, the correlation between these scores, the characteristics of high-risk patients as per these scores, and the mortality stratification of these scores in HF patients regardless of LVAD implantation are still not fully understood.

Methods and Results: Hospitalized patients with HF who underwent echocardiography and right heart catheterization were included (n=269). Patients at low or medium risk per the J-HMRS or HM3RS and at high risk per the J-MACS-RS (LM_J-HMH_J-MACS and LM_HM3H_J-MACS, respectively) were compared with those at low or medium risk per both scores (LM_J-HMLM_J-MACSand LM_HM3LM_J-MACS, respectively). The J-MACS-RS was well associated with the J-HMRS (r=0.66) and HM3RS (r=0.65). Patients with LM_J-HMH_J-MACS were older and showed a higher prevalence of ischemic etiology and history of cardiac surgery than those with LM_J-HMLM_J-MACS. LM_J-HMH_J-MACS and LM_HM3H_J-MACSshowed higher serum creatinine levels and central venous pressure-to-pulmonary artery wedge pressure ratios than LM_J-HMLM_J-MACSand LM_HM3LM_J-MACS, respectively. All scores stratified the 3-year mortality in patients with HF.

Conclusions: The J-MACS-RS correlated well with the J-HMRS and HM3RS. These scores may predict 3-year mortality, even in Japanese HF patients, regardless of LVAD implantation.

Background: The Amplatzer^TMPFO Occluder was approved for marketing in Japan in May 2019, and the Amplatzer PFO Occluder Japan Post-Marketing Surveillance (PFO Japan PMS) study started in December 2019. This analysis presents clinical outcomes of study patients through 1 year of follow-up.

Methods and Results: PFO Japan PMS is a prospective single-arm multicenter clinical study. Eligible patients were indicated for patent foramen ovale (PFO) closure and underwent an implant attempt with the Amplatzer^TMPFO Occluder, with no age restrictions. PFO closure was evaluated at 1 year via a bubble study, and patients will be followed for 3 years. From December 2019 to July 2021, 500 patients were enrolled across 53 sites. The mean (±SD) patient age was 52.7±15.4 years, with 29.8% of patients aged >60 years. Low adverse event rates were observed through 1 year of follow-up, including atrial fibrillation (2.4%; predominantly transient and within the first 30 days) and ischemic stroke (0.6%). Among patients in whom a 1-year bubble study was performed, a high rate (91.5%) of clinically relevant PFO closure (<20 bubbles) was achieved.

Conclusions: Through 1 year of follow-up in this real-world Japanese study with 30% of patients aged >60 years, a high degree of closure was achieved with the Amplatzer^TMPFO Occluder, along with low rates of atrial fibrillation, ischemic stroke, and overall adverse events.

Iron is an essential requirement for normal cellular function and oxygen transport. Deficiency of iron, due to suboptimal intake, blood loss, malabsorption or maldistribution is the most common nutrient deficiency worldwide. Iron deficiency (ID) has traditionally been ignored until anemia develops. Amongst patients with cardiovascular (CV) disease, ID is common and is associated with worse symptoms, poorer quality of life, and a worse prognosis. However, the criteria used to define ID in studies and international guidelines are inconsistent and lack universal acceptance. Accordingly, we review the various criteria used to define ID in patients with CV disease, discuss how these might have influenced the results of observational studies and randomized trials and suggest areas for future research.

Background: Intracoronary acetylcholine (ACh) provocation testing is a guideline-recommended invasive standard for diagnosing vasospastic angina (VSA)/coronary spastic angina. A positive ACh test is usually defined as significant epicardial vasospasm accompanied by signs of ischemia, namely chest symptoms and/or electrocardiographic (ECG) changes. However, the differential impact of diagnostic ACh test criteria on clinical characteristics and outcomes is unclear.

Methods and Results: From 2012 to 2024, 973 patients underwent ACh provocation testing for VSA diagnosis. Patients were divided into 3 groups: negative ACh test; and positive ACh test (2 groups), defined as significant epicardial vasospasm with either narrow (both chest symptoms and ECG changes) or broad (chest symptoms or ECG changes) definitions of signs of ischemia. Clinical characteristics and adverse outcomes during ACh testing and follow-up were compared among the 3 groups. In all, 356 (36.6%), 166 (17.1%), and 451 (46.4%) had positive ACh tests with narrow and broad definitions of ischemia and negative ACh tests, respectively. Among patients with positive ACh tests, there were no significant differences in baseline characteristics and adverse outcomes between those with narrow and broad definitions of ischemia.

Conclusions: In patients undergoing ACh provocation testing, there were no significant differences in clinical characteristics and outcomes between those diagnosed as having VSA using narrow and broad definitions of signs of ischemia, suggesting that either sign can be used as a criterion of ischemia.

Background: Relative hyperglycemia, as defined by the stress hyperglycemia ratio (SHR), is linked to death and ischemic events in patients with acute coronary syndrome (ACS). As a modifiable factor, the association between SHR and bleeding risk after percutaneous coronary intervention (PCI) across different glycemic status remains unexplored.

Methods and Results: In this study, ACS patients treated with PCI were extracted from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) registry and the Tianjin Health and Medical Data Platform (THMDP). SHR was derived from admission fasting blood glucose and hemoglobin A1c. Patients were classified as having diabetes mellitus, pre-diabetes mellitus (Pre-DM), or normal glucose regulation. The primary outcome was in-hospital major bleeding. Among the 33,265 patients in the CCC-ACS cohort, major bleeding was recorded for 437. A high SHR (>1.0) independently predicted major bleeding in the total cohort (adjusted odds ratio [aOR] 1.51; 95% confidence interval [CI] 1.24–1.83), with the highest risk in the Pre-DM group (aOR 1.98; 95% CI 1.34–2.92). These findings were externally validated among 23,423 patients with myocardial infarction in the THMDP cohort. Early guideline-directed medical therapy mitigated the bleeding risk associated with a high SHR.

Conclusions: In this study, a high SHR was an independent risk factor for in-hospital major bleeding after PCI, particularly in patients with Pre-DM. Further clinical trials are needed to explore SHR-targeted therapies in Pre-DM.

Background: This study evaluated the utility of myocardial strain analysis on computed tomography (CT) using state-of-the-art image analysis software to predict the prognosis of patients who underwent transcatheter aortic valve replacement (TAVR).

Methods and Results: We included 126 patients with severe aortic valve stenosis (AS) who underwent preoperative CT. Major adverse cardiovascular events (MACE) were defined as a composite of cardiac death (including unknown death based on medical records), hospitalization due to heart failure, and fatal arrhythmia. Twenty-four (19%) patients experienced MACE. Global longitudinal strain (GLS), circumferential strain (GCS), radial strain (GRS) of the left ventricular (LV) myocardium (LVM), LV ejection fraction on CT, and the percentage of patients administered aspirin or statins was significantly lower among patients with than without MACE (all P<0.05). The percentage of patients with AF, a history of congestive heart failure, and tolvaptan or oral anticoagulants administration was significantly higher among patients with than without MACE (all P<0.05). In multivariate survival analysis using a Cox proportional hazard model, LV-GLS ≥−9.92% on CT (hazard ratio [HR] 4.45; 95% confidence interval [CI] 1.89–10.48; P=0.0007) and aspirin (HR 0.27; 95% CI 0.10–0.70; P=0.0074) or statin (HR 0.33; 95% CI 0.13–0.84; P=0.02) administration were significant predictors of prognosis after TAVR.

Conclusions: Our findings indicate that LV-GLS on CT is a sensitive predictor of prognosis after TAVR.

Background: Several cross-sectional studies have implicated gut dysbiosis caused by an abundance of oral commensals in stroke, but the effect on long-term prognosis is still unknown. Therefore, we longitudinally investigated oral pathobionts in the gut and their clinical relevance to stroke.

Methods and Results: We analyzed the salivary and gut microbiomes collected from 189 acute stroke and 55 non-stroke subjects, and found that Streptococcus anginosus was significantly more abundant in both the saliva (median [IQR], 0.01 [0.00–0.14] vs. 0.00 [0.00–0.03], P=0.02) and gut (0.09 [0.00–0.28] vs. 0.00 [0.00–0.02], P<0.001) of the stroke patients compared with their non-stroke counterparts. Network analysis revealed S. anginosus as a central hub in gut dysbiosis. After adjusting for vascular risks, S. anginosus (odds ratio 1.20, 95% confidence interval 1.06–1.36, P<0.01), Anaerostipes hadrus (0.82, [0.73–0.93], P<0.01), and Bacteroides plebeius (0.86, [0.86–0.93], P=0.01) in the gut were independent predictors of stroke. Longitudinally, S. anginosus in the gut was significantly associated with increased rates of death and major cardiovascular events (P=0.04; log-rank test), whereas A. hadrus and B. plebeius were not (P=0.45 and P=0.19). After adjusting for vascular risks, S. anginosus in the gut was a residual risk for increased rates of death and major cardiovascular events (hazard ratio 4.78, 95% confidence interval 1.08–21.18, P=0.04)

Conclusions: S. anginosus in the gut may increase the risk of stroke and a poor prognosis.

Background: Coronary artery disease (CAD) is a major cause of mortality worldwide. Serum carboxyl-terminal telopeptide of type I collagen (CITP), a marker of collagen degradation in the heart and blood vessels, is associated with plaque vulnerability and cardiac remodeling in patients with acute myocardial infarction. However, the effect of CITP on the clinical outcomes of patients with CAD has not yet been elucidated.

Methods and Results: Serum CITP concentrations were measured in 621 consecutive patients with CAD. All patients were prospectively followed up for a median period of 1,554 days. The primary endpoint was a composite of hospitalization for heart failure or cardiovascular death; the secondary endpoints were all-cause death and heart failure rehospitalization. B-Type natriuretic peptide and the left ventricular mass index were higher in the highest CITP tertile group. Kaplan-Meier analysis demonstrated that the CAD patients in the highest CITP tertile group had the greatest risk of both primary and secondary endpoints, independent of acute or chronic coronary syndrome. Multivariate Cox proportional hazard regression analysis demonstrated that CITP was an independent predictor of both primary and secondary endpoints after adjusting for confounding risk factors, regardless of acute or chronic coronary syndrome.

Conclusions: The serum CITP concentration could be a feasible marker for clinical outcomes in patients with CAD.

Myocarditis is a heterogeneous disease with diverse etiologies and clinical trajectories. Traditionally, its diagnosis has been guided by the Dallas criteria, which focus on histopathological features. Clinically, myocarditis is categorized as acute or chronic based on the duration since symptom onset. However, recent expert consensus, particularly in Western countries, has redefined myocarditis as either acute myocarditis or chronic inflammatory cardiomyopathy, including inflammatory dilated cardiomyopathy, reflecting advancements in viral genome analysis and histopathology. In 2023, the Japanese Circulation Society proposed the concept of chronic active myocarditis, a high-risk phenotype characterized by persistent inflammation and ongoing cardiomyocyte injury. The transition from acute myocarditis to its chronic phase involves complex immune mechanisms, with sustained myocardial inflammation driving ventricular remodeling and progression to heart failure. Cardiac magnetic resonance imaging and endomyocardial biopsy remain pivotal diagnostic modalities, though their diagnostic yield varies according to disease phase. Management strategies focus on heart failure treatment, arrhythmia control, and, in select cases, immunosuppressive therapy, particularly for virus-negative inflammatory cardiomyopathy. Although antiviral therapy has shown promise, its clinical efficacy remains uncertain. Given the evolving understanding of the chronic phase of myocarditis, further research is warranted to refine the diagnostic criteria and optimize personalized therapeutic strategies. This review gives a comprehensive overview of the pathophysiology, classification, and management of chronic myocarditis, with an emphasis on emerging disease concepts and their clinical implications.

Background: Although body mass index (BMI) is a simple marker of in-hospital cardiac arrest (IHCA) in patients with cerebro- and cardiovascular disease, the association between BMI on admission and the incidence of IHCA is still controversial. In this study, Japanese patients with cerebro- and cardiovascular disease were investigated for the association between BMI on admission and the incidence of IHCA.

Methods and Results: This was a retrospective study from the Japanese Registry Of All cardiac and vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC), a large-scale nationwide claims-based database, using data from between 2012 and 2021. From among all 10,923,676 cases, 7,571,826 patients who were hospitalized for cerebro- or cardiovascular disease were investigated. BMI was classified as underweight (<18.5 kg/m²), normal and under ideal (18.5–22 kg/m²), normal and over ideal (22–25 kg/m²), or obese (≥25.0 kg/m²). The average age, ratio of males, and average BMI were 71.6±12.8 years, 63.4%, and 23.3±3.7 kg/m², respectively. IHCA occurred in 270,380 cases (3.57%). In a Cox regression analysis according to BMI group, the underweight group showed significantly higher hazard risk for the incidence of IHCA after adjusting cofounding factors, both in all patients and a subgroup analysis according to the patient’s age generation.

Conclusions: Underweight, rather than obesity, might be a risk factor for IHCA in an aging society.

Background: The aim of this study was to retrain our existing deep learning-based fully automated aortic valve leaflets/root measurement algorithm, using computed tomography (CT) data for root dilatation (RD), and assess its clinical feasibility.

Methods and Results: 67 ECG-gated cardiac CT scans were retrospectively collected from 40 patients with RD to retrain the algorithm. An additional 100 patients’ CT data with aortic stenosis (AS, n=50) and aortic regurgitation (AR) with/without RD (n=50) were collected to evaluate the algorithm. 45 AR patients had RD. The algorithm provided patient-specific 3-dimensional aortic valve/root visualization. The measurements of 100 cases automatically obtained by the algorithm were compared with an expert’s manual measurements. Overall, there was a moderate-to-high correlation, with differences of 6.1–13.4 mm²for the virtual basal ring area, 1.1–2.6 mm for sinus diameter, 0.1–0.6 mm for coronary artery height, 0.2–0.5 mm for geometric height, and 0.9 mm for effective height, except for the sinotubular junction of the AR cases (10.3 mm) with an indefinite borderline over the dilated sinuses, compared with 2.1 mm in AS cases. The measurement time (122 s) per case by the algorithm was significantly shorter than those of the experts (618–1,126 s).

Conclusions: This fully automated algorithm can assist in evaluating aortic valve/root anatomy for planning surgical and transcatheter treatments while saving time and minimizing workload.

Background: Despite active research into the pathophysiology of Brugada syndrome (BrS), the mechanisms of the genesis of changes in the characteristic electrocardiogram (ECG) are still controversial.

Methods and Results: Using multiscale computer simulation of ECGs, we compared 3 hypotheses to identify the mechanisms of the BrS-type ECG caused by a mutation in cardiac sodium channels. In addition to the dominant repolarization disorder and depolarization disorder hypotheses, we tested a new hypothesis assuming the combination of a slow conduction property, upregulation of transient outward potassium current channels, and reduced expression levels of sodium channels in the right ventricular outflow tract (embryonic phenotype model). We found that only the embryonic phenotype model reproduced the clinically observed BrS-type ECG by strongly inhibiting sodium current selectively in the right ventricular outflow tract. We also simulated a ventricular wedge experiment and confirmed that strong inhibition of the sodium current was the prerequisite for a change in the ECG.

Conclusions: Strong selective inhibition of the sodium current in the right ventricular outflow tract generates the characteristic BrS-type ECG in the precordial leads without affecting the waveforms in other lead positions. This change can only be achieved using the embryonic phenotype model in which reduced expression levels of sodium channels play an essential role.

Background: In Japan, the implantation of implantable cardioverter defibrillators (ICD) for the primary prevention of sudden cardiac death (SCD) is not covered by insurance reimbursement, and the underuse of ICDs has been noted. Therefore, this study analyzed the medical costs incurred due to a lack of primary prevention ICD therapy for SCD.

Methods and Results: This retrospective cohort study analyzed data from 4 advanced critical care centers between January 2020 and December 2024. From a database of 3,606 cases of cardiac arrest, there were 348 patients with a documented rhythm at the time of arrest that could have been treated with an ICD. Of these patients, 43 (12.4%) had documented evidence of heart failure treatment and were eligible for ICD implantation before experiencing a cardiac arrest. The total mean (±SD) medical cost for these patients was US $11,679±14,666 (¥1,775,150±2,229,272).

Conclusions: In this multicenter retrospective analysis, we identified a subset of patients who were eligible for primary prevention ICD therapy but did not receive it prior to experiencing sudden cardiac arrest. These cases were associated with substantial post-arrest medical costs. Our findings highlight the potential clinical and economic impact of the underutilization of ICDs in Japan and suggest that broader implementation of guideline-directed ICD therapy for primary prevention may reduce both mortality and healthcare expenditure.

Background: The prognostic significance of the 6-minute walk distance (6MWD) in patients with severe aortic stenosis (AS) has not been thoroughly investigated.

Methods and Results: This study evaluated 998 patients with severe AS who underwent a 6-min walk test as part of a large multicenter prospective cohort. Patients were categorized as either fast walkers (6MWD ≥300 m; n=515) or slow walkers (6MWD <300 m; n=483). During a median follow-up of 2.3 years, 861 (86.3%) patients underwent surgical or transcatheter aortic valve replacement (AVR; 87.0% of fast walkers vs. 85.5% of slow walkers). The cumulative 3-year incidence of death was significantly lower among fast walkers than slow walkers (10.9% vs. 31.7%; P<0.001). After adjusting for confounders, slow walkers had a significantly higher risk of all-cause mortality than fast walkers (hazard ratio 2.36; 95% confidence interval 1.55–3.58; P<0.001). Stratified analysis by initial treatment strategy revealed that the cumulative 3-year incidence of all-cause death was consistently lower among fast walkers than slow walkers (initial AVR strategy: 10.1% vs. 28.1% [P<0.001]; conservative strategy: 13.4% vs. 46.7% [P<0.001]). Among asymptomatic patients managed conservatively, fast walkers demonstrated a remarkably low cumulative 3-year incidence of all-cause death (8.1%).

Conclusions: The 6MWD is a reliable prognostic marker for patients with severe AS, regardless of initial treatment strategy.

Background: Acute coronary syndrome (ACS) requires prompt diagnosis and treatment. Although “OPQRST” (Onset, Provocation, Quality, Region/Radiation, Symptoms, and Time) is commonly used, the evidence linking emergency department (ED) chest pain characteristics to ACS remains inconclusive. This study evaluated detailed symptoms in ED patients with and without ACS using a broad chest pain registry with symptom data.

Methods and Results: This single-center prospective study was conducted at Rakuwakai-Otowa Hospital in Kyoto, Japan, as a pilot study for a multicenter registry. We enrolled 420 consecutive adult patients presenting with chest pain at the ED from June 2022 to May 2023. Baseline characteristics (including symptoms) and outcomes were recorded. Of the 420 patients, 65 (15.5%) were diagnosed with ACS. Patients with and without ACS differed in the proportion with sudden onset (58.5% vs. 27.6%, respectively), radiation to the tooth (9.2% vs. 0.6%, respectively), and cold sweat (diaphoresis; 44.6% vs. 16.9%, respectively). In the overall population, positive likelihood ratios were 2.12 (95% confidence interval [CI] 1.63–2.76) for sudden onset, 16.38 (95% CI 3.38–79.41) for radiation to the tooth, and 2.64 (95% CI 1.85–3.77) for diaphoresis.

Conclusions: This study in a suburban area of Japan (one of the most super-aged societies) identified key chest pain characteristics in a broad chest pain cohort (i.e., sudden onset, radiation to the tooth, and diaphoresis) that may help with the rapid triage and diagnosis of ACS.

Background: The antiplatelet effect of prasugrel for acute ischemic stroke or transient ischemic attack (TIA) remains unclear. This study compared platelet reactivity between prasugrel and clopidogrel, considering cytochrome P450 family 2 subfamily C member 19 (CYP2C19) gene polymorphisms (extensive metabolizers [EM], intermediate metabolizers [IM], and poor metabolizers [PM]), in patients with acute large artery atherosclerosis (LAA) or high-risk TIA.

Methods and Results: In this multicenter open-label randomized controlled study, patients with acute LAA or high-risk TIA received prasugrel or clopidogrel with aspirin. The primary endpoint was platelet reaction units (PRU) 5 days after the start of drug administration, stratified according to CYP2C19 polymorphism. In all, 176 patients participated (88 in each group). Compared with the clopidogrel group, PRU on Day 5 in the prasugrel group were significantly lower in the overall population (adjusted mean 136.0 vs. 169.9; estimated difference −33.9; 95% confidence interval [CI] −49.0, −18.8), EM group (118.5 vs. 144.8; estimated difference −26.2; 95% CI −48.0, −4.4), and IM group (140.3 vs. 173.1; estimated difference −32.8; 95% CI −56.6, −9.0), and tended to be lower in the PM group (164.7 vs. 196.2; estimated difference −31.6; 95% CI −68.3, 5.1). The prevalence of new infarct lesions was comparable between the prasugrel and clopidogrel groups, as was the incidence of adverse events (30.7% vs. 26.1%, respectively) and bleeding events up to Day 5 of administration.

Conclusions: In patients with acute LAA or high-risk TIA, prasugrel resulted in stable inhibition of platelet aggregation 5 days after starting drug administration compared with clopidogrel, regardless of CYP2C19 polymorphisms.

Background: This study examined the association between Life’s Essential 8 (LE8) and the Korean population’s risk of all-cause and cardiovascular disease (CVD) mortality.

Methods and Results: This study included 21,482 adults aged ≥19 years who were enrolled in the Korea National Health and Nutrition Examination Survey. Cardiovascular health (CVH) was assessed using the LE8 score, which comprises the following 8 components: diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. The LE8 score ranges from 0 to 100 and was categorized as low (0–49), middle (50–79), high (≥80), with higher scores indicating better CVH. A Cox proportional hazards model was used to estimate hazard ratios, and the population attributable fraction (PAF) was used to determine individual risks associated with each CVH metric. During a median follow-up of 6.3 years, there were 709 all-cause and 122 CVD-related deaths. In the fully adjusted model, compared with low scores, middle and high LE8 scores were associated with 34% and 42% lower risks of all-cause mortality, respectively. A similar reduction in CVD mortality was observed with higher LE8 scores. Physical activity showed the highest PAF, contributing 37% for all-cause mortality and 51% for CVD mortality.

Conclusions: Higher LE8 scores were significantly associated with lower all-cause and CVD mortality. Physical activity had the greatest impact on PAF for mortality.

Background: This study evaluated the efficacy of dual antiplatelet therapy (DAPT) on the long-term prognosis of coronary artery bypass grafting (CABG) patients with high inflammatory risk.

Methods and Results: We analyzed 2,409 patients who underwent isolated CABG between January 2001 and December 2017 and had baseline high-sensitivity C-reactive protein (hs-CRP) levels >2.0 mg/L. Patients were divided into 2 groups: those on DAPT for ≥12 months (n=545) and those on single antiplatelet therapy (SAPT; n=1,864). The primary outcome was all-cause death or myocardial infarction (MI) after CABG. Propensity score (PS) matching was used to minimize confounding factors and selection bias. During follow-up, the ≥12-month DAPT group had a significantly lower risk of the primary outcome than the SAPT group (7.5% vs. 13.3%; hazard ratio [HR] 0.42; 95% confidence interval [CI] 0.24–0.72; P=0.002). After PS matching, the incidence of the primary outcome remained lower in the DAPT group (HR 0.36; 95% CI 0.19–0.71; P=0.003). The benefit of prolonged DAPT was consistent across subgroups.

Conclusions: In CABG patients with high inflammatory risk, prolonged DAPT (≥12 months) was associated with significantly lower rates of all-cause death or MI compared with SAPT.

Background: This study compared procedural complications, patency, and adverse events between a stent strategy and drug-coated balloon (DCB) treatment after using the JETSTREAM atherectomy device for severely calcified femoropopliteal (FP) lesions.

Methods and Results: We retrospectively analyzed multicenter data from 588 patients who underwent endovascular therapy for severely calcified de novo FP lesions between April 2018 and December 2023 at 8 centers in Japan. Patients were categorized into 2 groups based on the revascularization method: stent strategy and DCB after JETSTREAM atherectomy. Propensity score matching (PSM) was performed to compare primary patency, clinically driven target lesion revascularization (CD-TLR), and the occurrence of acute limb ischemia (ALI)/major amputation at 1 year. After PSM, 82 matched pairs of patients were identified, with no significant intergroup differences in baseline characteristics. The rates of primary patency, CD-TLR, ALI, and major amputation were similar between the 2 groups. However, the rate of distal embolization was significantly higher in the DCB after JETSTREAM group. (18.3% vs. 1.2%; P<0.001) Baseline characteristics had no interaction effects on the association between the 2 strategies and the 1-year restenosis risk.

Conclusions: DCB after JETSTREAM atherectomy demonstrated comparable safety, except for distal embolization, and high efficacy in patients with severely calcified FP lesions, suggesting that it may be an alternative revascularization method to the stent strategy.

Background: HMGB2 is reported to be strongly associated with cardiovascular diseases, but its relationship with coronary collateralization is unclear.

Methods and Results: We determined the serum HMGB2 levels in 322 patients with type 2 diabetes and coronary chronic total occlusion (CTO), and evaluated the degree of coronary collaterals by Rentrop classification (poor collaterals: Rentrop score 0 or 1; good collaterals: Rentrop score 2 or 3). Anti-HMGB2 neutralizing antibody was administered in a diabetic ischemic hindlimb mouse model, followed by laser Doppler perfusion imaging and histological examinations. Human umbilical vein endothelial cells (HUVECs) were treated with HMGB2 to assess the potential mechanisms. Serum HMGB2 decreased stepwise across Rentrop score 0 to 3 (P<0.001), with significantly higher levels in patients with poor collaterals than in those with good collaterals (P<0.001). After adjustment for various confounders, HMGB2 remained an independent factor for poor coronary collateralization (adjusted odds ratio, 1.234; 95% confidence interval, 1.136–1.340; P<0.001). In diabetic mice with hindlimb ischemia, administration of anti-HMGB2 neutralizing antibody increased blood flow restoration. HMGB2 inhibited migration and tube formation of HUVECs in a dose-dependent manner under high-glucose and hypoxic conditions, and promoted NLRP3-mediated pyroptosis.

Conclusions: Elevated circulating HMGB2 was associated with poor coronary collateralization in CTO patients with diabetes. HMGB2 impaired angiogenesis and collateral vessel growth in diabetic mice. Such effects are mediated by NLRP3.

Calcific aortic valve disease (CAVD) is one of the most prevalent heart valve diseases and is characterized by progressive stiffening and calcification of the aortic valve. For decades, CAVD has been treated with surgical intervention. In recent years, some progress has been made in understanding the pathogenesis of CAVD and the exploration of novel therapeutic strategies, leading to the identification of potential therapeutic targets and innovative treatment approaches. This review systematically outlines the pathophysiological advances in CAVD over the past 5 years, proposing a 3-stage model for disease progression: inflammatory, fibrotic, and calcification stages. In addition, recent clinical trials investigating pharmacological therapies, such as those targeting lipid metabolism, vitamin K pathways, and calcium-phosphorus balance, are summarized and discussed. These developments hold promise for improving patient outcomes and revolutionizing the management of CAVD.

Short QT syndrome (SQTS) is a very rare inherited arrhythmia characterized by extremely short QT intervals on electrocardiograms and sudden cardiac death in young patients. Among the genotypes of SQTS, gain-of-function variants in the potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene are accountable for SQTS type 2 (SQT2). Pathogenic variants for SQT2 are rare and, among them, the p.Val141Met is relatively prevalent. This review summarizes findings for 5 SQTS patients harboring p.Val141Met we recently encountered and compares them to another 14 patients reported in the literature.

Background: The Friedewald equation, commonly used to calculate low-density lipoprotein cholesterol (LDL-C), occasionally yields inaccurate estimations for very-low-density lipoprotein cholesterol, suggesting the need for an alternative method such as the Martin equation. In this study, we aimed to evaluate the discrepancies between the Friedewald and Martin equations, particularly in the context of pathogenic variants associated with familial hypercholesterolemia (FH).

Methods and Results: We evaluated the discrepancies between LDL-C levels calculated using the Friedewald and Martin equations, and for the presence of pathogenic variants of FH in 53 children with hypercholesterolemia detected through universal lipid screening. Genetic testing revealed pathogenic variants of FH in 24 of the 53 children. Chi-squared tests indicated a significant difference in the presence of pathogenic variants of FH between the “Friedewald ≥ Martin” and “Friedewald < Martin” groups (χ²=11.348, P<0.001). Even in 37 children with LDL-C <180 mg/dL, discrepancies between the equations were still associated with the presence of pathogenic FH variants (Fisher’s exact test, P=0.028).

Conclusions: Discrepancies in LDL-C levels measured by the Friedewald and Martin equations might serve as a useful predictive marker for identifying pathogenic variants of FH, especially in cases of LDL-C <180 mg/dL, which are often challenging to diagnose.

Background: This study aimed to elucidate the age trends among non-surgical patients requiring intensive care over a 10-year period and the prognostic impact of aging in relation to their underlying etiologies.

Methods and Results: In all, 4,279 non-surgical patients requiring intensive care from 2012 to 2021 were enrolled in the study. Patient backgrounds and prognoses were compared among age 4 groups: Group A, age <60 years (n=910); Group B, age 60–69 years (n=1,062); Group C, age 70–79 years (n=1,355); and Group D, age ≥80 years (n=952). During the study period, the number of patients aged 60–69 years decreased significantly with time, whereas the number aged over 80 years increased significantly. A multivariate Cox regression model identified Group D as an independent predictor of 365-day all-cause mortality (hazard ratio [HR] 2.070; 95% confidence interval [CI] 1.619–2.646) relative to Group A. Multivariate logistic regression analysis indicated that the presence of sepsis was independently associated with 365-day mortality, especially in the cohort aged ≥80 years (HR 1.878; 95% CI 1.270–2.777; P=0.002).

Conclusions: The mean age of patients requiring non-surgical intensive care is increasing annually, and greater age was identified as a significant factor associated with a higher 365-day mortality rate. The presence of sepsis was linked to increased 365-day mortality among older individuals.

Background: Abdominal aortic aneurysm (AAA) is a vascular disease strongly associated with immune dysregulation and metabolic disturbances. Although lactate metabolism and its associated process, lactylation, have been implicated in various diseases, their specific role in AAA pathogenesis remains poorly understood.

Methods and Results: In this study, we used a multi-faceted approach, integrating single-cell and bulk RNA data analyses, with the objective of elucidating the interrelationship between lactylation and immune response in AAA patients. The result revealed significant heterogeneity in lactylation levels across different immune cell types. Cells with higher lactylation activity exhibited markedly elevated immune response scores. Differential expression and correlation analyses identified 65 lactylation-associated genes, which were further evaluated in the bulk RNA sequencing data to assess their relationship with the immune microenvironment in patients with AAA. Using 113 combinations of machine-learning algorithms, we identified 8 lactylation-related hub genes. The immune infiltration analysis demonstrated that these genes were linked to a multitude of immune cells. The animal experiments corroborated that Tnfsf8, Hist1 h2ag, Cd79b, Cd69, and Bank1 were upregulated in the AAA group, while Rpl36a and Rps29 were downregulated in the AAA group.

Conclusions: This study highlighted a potentially critical link between lactylation and immune dysregulation in AAA, thereby advancing our comprehension of the function of lactylation in AAA.

Background: Statins can effectively reduce low-density lipoprotein cholesterol (LDL-C), but additional options are needed for inadequate responses to statins or statin intolerance. Bempedoic acid is a small-molecule oral LDL-C-lowering drug that inhibits ATP citrate lyase, an enzyme 2 steps upstream of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the metabolic pathway for cholesterol synthesis.

Methods and Results: The CLEAR-J trial evaluated bempedoic acid 180 mg/day for 12 weeks in Japanese patients with inadequately controlled LDL-C. Percentage changes in LDL-C between baseline and Week 12 (primary endpoint) were −25.25% and −3.46% in the bempedoic acid and placebo groups, respectively, with a significant between-group difference (−21.78%; 95% confidence interval [CI] –26.71%, –16.85%; P<0.001). Changes in secondary endpoints in the bempedoic acid and placebo groups were as follows: non-high-density lipoprotein cholesterol, −20.33% and −2.76%, respectively (between-group difference −17.57%; 95% CI −22.03%, −13.12%); total cholesterol −16.36% and −2.23%, respectively (between-group difference –14.13%; 95% CI −17.79%, −10.47%); and apolipoprotein B −18.10% and −0.67%, respectively (between-group difference −17.43%; 95% CI –21.97%, −12.89%). At 12 weeks, 62.5% of the bempedoic acid group had achieved target LDL-C values. Treatment-emergent adverse events appeared in 3 patients taking bempedoic acid and 2 patients taking placebo.

Conclusions: This study confirmed the safety and efficacy of bempedoic acid after 12 weeks treatment in Japanese patients with high LDL-C who had inadequate response to statins or statin intolerance.

Background: The efficacy of exercise-based cardiac rehabilitation (CR) in patients with angina and non-obstructive coronary artery disease (ANOCA) remains unclear. This study investigated whether a multidisciplinary CR program improves myocardial flow reserve (MFR), symptom status, and exercise capacity in patients with ANOCA.

Methods and Results: Myocardial blood flow at rest and during ATP-induced hyperemia was quantified using ¹³N-ammonia positron emission tomography (PET) in 29 patients diagnosed with ANOCA and impaired MFR (<2.5). Overall, 16 patients completed the 5-month CR program (complete CR group) and 13 did not (non-complete CR group). At baseline and the 5-month follow-up PET, symptom status and exercise capacity were assessed using the Seattle Angina Questionnaire (SAQ)-7 and cardiopulmonary exercise testing, respectively. The MFR in the complete CR group increased significantly (P=0.001) from a median of 1.60 (interquartile range [IQR] 1.43–1.98) to 2.09 (IQR 1.83–2.48). Significant improvements were also seen in the median SAQ-7 total score (from 16 [IQR 11–20] to 11 [IQR 8–14]; P=0.008) and peak oxygen consumption (V̇O₂; from 14.2 [IQR 12.4–15.8] to 15.3 [13.0–17.9] mL/kg/min; P=0.02). In contrast, there were no improvements in MFR (P=0.83) or peak V̇O₂(P=0.27) in the non-complete CR group.

Conclusions: The 5-month exercise-based CR significantly improved MFR, symptom status, and exercise capacity in patients with ANOCA and impaired MFR.

Background: Preoperative risk assessment is very important to ensure surgical safety and predict postoperative complications. However, no large-scale studies have evaluated the risk of perioperative cardiovascular events in Japan. This study evaluated perioperative cardiovascular events using real-world data. In addition, the applicability of machine learning to risk stratification was examined to develop a predictive model for perioperative cardiovascular events.

Methods and Results: This was an observational cohort study using the Japan Medical Data Center database, which includes claim and health examination data in Japan, between January 2005 and April 2021. In all, 133,634 gastrointestinal surgeries were included in the analysis. The primary outcome was 30-day risk of major adverse cardiovascular events (MACE). The 30-day MACE incidence rate following surgery was 3.8%. Machine learning was used to perform a binary classification task to predict MACE occurrence within 30 days after surgery. A clustering algorithm was developed based on the Shapley additive explanation values obtained from training data, and generalizability was evaluated using test data. Of the variables, age, history of ischemic heart disease or heart failure, history of stroke, diabetes, hypertension, atrial fibrillation, cases of malignancy, and pancreatic biliary surgery were identified as factors associated with MACE occurrence.

Conclusions: A machine learning model built from basic clinical information, comorbidities, and surgical information demonstrated the capacity to stratify MACE risk in patients undergoing gastrointestinal surgery.

Background: This study compared postoperative outcomes in patients with a preoperative left ventricular ejection fraction (LVEF) of ≤35% who underwent multiple (MAG) or single (SAG) arterial grafting during off-pump isolated coronary artery bypass grafting.

Methods and Results: Of 1,627 patients who underwent isolated coronary artery bypass grafting at Shiga University of Medical Science between 2002 and 2023, 176 with a preoperative LVEF ≤35% underwent MAG (n=115) or SAG (n=61). Baseline patient characteristics were comparable in the MAG and SAG groups after adjustment using inverse probability of treatment weighting. The study’s mean (±SD) follow-up duration was 4.8±4.7 years. In the MAG and SAG groups, the adjusted estimated 5-year rates of freedom from all-cause death were 71.5% and 69.1%, respectively, while those of cardiac death were 94.1% and 89.5%, respectively. Kaplan-Meier curves showed significant differences in all-cause death (P=0.013) and cardiac death (P=0.001) favoring the MAG group. In a multivariable Cox hazards model, MAG was a predictor of all-cause death (hazard ratio 0.568; P=0.034) and cardiac death (hazard ratio 0.276; P=0.008).

Conclusions: Compared with SAG, MAG was associated with significantly lower rates of all-cause death and cardiac death.

Background: Hospital-associated disability (HAD), characterized by a worsening of activities of daily living and physical function following hospitalization, is a common complication in older adults during the course of acute care hospitalization. HAD is a significant concern affecting older adults undergoing transcatheter aortic valve implantation (TAVI).

Methods and Results: This retrospective study investigated 243 consecutive patients who underwent elective transfemoral TAVI between January 2016 and April 2022. HAD was defined as a decrease of at least 1 point in the Short Physical Performance Battery (SPPB) assessed before discharge compared with before TAVI. Logistic regression identified the first ambulation day after TAVI as an independent predictor of HAD incidence (odds ratio 1.500; 95% confidence interval [CI] 1.115–2.008; P=0.007). Patients with HAD had significantly lower body mass index, hemoglobin, and albumin, and higher serum creatinine. All-cause mortality was significantly higher in patients with than without HAD (log-rank P<0.001). Kaplan-Meier analysis confirmed poorer survival in patients with HAD, regardless of the degree of decline in SPPB. Multivariate Cox analysis regression identified HAD as a predictor of all-cause death (hazard ratio 4.249; 95% CI 1.798–10.04; P<0.001).

Conclusions: The timing of the first ambulation was associated with the incidence of HAD. Promoting early mobilization may reduce the risk of HAD after TAVI.

Background: Although tricuspid regurgitation (TR) is no longer considered a negligible disease, its detailed status in real-world heart failure (HF) patients remains unknown.

Methods and Results: From the KUNIUMI registry, we evaluated data for 1,646 consecutive HF patients. The primary endpoint was all-cause mortality over a median follow-up period of 3.0 years (interquartile range 1.4–3.0 years). Of the 1,646 HF patients, 369 (22.4%) had moderate or greater TR; the mean (±SD) age of these patients was 82.0±8.5 years. Atrial functional TR was the most common etiology of TR in HF patients with moderate or greater TR (70.7%), and was more common in HF patients with severe than moderate TR (75.5% vs. 65.3%; P=0.032). The mortality rate was high in HF patients with severe and moderate TR (27.1% and 17.0%, respectively). During follow-up, 33.1% of HF patients with moderate TR progressed to severe TR, and showed unfavorable all-cause mortality compared with those with unchanged TR. Atrial functional TR was a more common etiology in HF patients with moderate TR and worsened TR than in those with unchanged TR (84.6% vs. 59.5%; P=0.004). Right atrial enlargement was independently correlated with worsened TR.

Conclusions: Moderate or greater TR was prevalent in 22.4% of the real-world super-aged HF population. Even HF patients with moderate TR had poor outcomes, with right atrial remodeling a key factor for worsened TR.

Background: There are few studies regarding the predictors of stent underexpansion (SUE) in post-debulking calcified lesions. We investigated predictors of SUE in severely calcified lesions after debulking using optical coherence tomography-guided rotational atherectomy (RA) or orbital atherectomy (OA).

Methods and Results: As a post hoc analysis of the DIRO trial, we compared various parameters, including calcium and lipid parameters (lipid-rich plaque, thin cap fibroatheroma [TCFA], maximum lipid arc, mean lipid arc, lipid length, and lipid volume index), between groups with adequate stent expansion (ASE) and SUE. To find predictors of SUE, multivariable analysis was performed using significant factors from the univariable analysis. We also evaluated adverse events 8 months after the procedure. The SUE group consisted of 57 (65.5%) patients. After suitable debulking of severely calcified lesions using RA or OA, there was no correlation between calcium parameters and SUE; however, the lipid parameters of maximum lipid arc ≥224° and TCFA were significantly and independently correlated with SUE Approximately 45% of severely calcified lesions contained lipid-rich plaques. Adverse events occurred more frequently in the SUE than ASE group.

Conclusions: The role of calcium parameters in predicting SUE in severely calcified lesions after suitable debulking using RA or OA is weak; however, maximum lipid arc and TCFA are important predictors of SUE.

Background: The long-term effects of cumulative resting heart rate (cumRHR) on the incidence of cardiovascular events and all-cause mortality in older (age ≥60 years) hypertensive populations remain unclear. Therefore, the aim of this study was to investigate the association between cumRHR and cardiovascular events and all-cause mortality.

Methods and Results: This post hoc analysis used data from the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial of 7,517 patients in whom resting heart rate (RHR) was measured at 0, 3, 6, 9, and 12 months. “cumRHR” refers to the weighted mean of the RHR for each time interval. Participants were divided into quartiles (Q1–Q4) based on cumRHR. After adjustment for potential confounders and using Q3 (72.19–75.88 [beats/min] × year) as the reference, patients in Q4 (75.94–109.44 [beats/min] × year) had higher risks of the primary outcome (a composite of stroke, acute coronary syndrome, acute decompensated heart failure, coronary revascularization, atrial fibrillation, and death from any cardiovascular cause) (hazard ratio [HR] 2.21; 95% confidence interval [CI] 1.42–3.43; P<0.001), major adverse cardiovascular events (HR 1.93; 95% CI 1.18–3.16; P=0.009), and stroke (HR 3.55; 95% CI 1.42–8.86; P=0.007) and those in Q1 (44.50–68.44 [beats/min] × year) had an increased risk of the primary outcome (HR 1.71; 95% CI 1.08–2.71; P=0.02). No such trends were observed for all-cause mortality. A U-shaped relationship was observed with the primary outcome, with higher risk for both very low or very high cumRHR levels compared with midrange values.

Conclusions: Both low and high cumRHR levels were associated with higher risk of cardiovascular events in older patients with hypertension.

Background: Cardiovascular emergencies often require intensive care unit (ICU) management, but there is limited data comparing outcomes based on the admission ward.

Methods and Results: We analyzed data from the Japanese Registry of All Cardiac and Vascular Diseases Diagnosis Procedure Combination (JROAD-DPC) database (2016–2020) for 715,054 patients (mean age, 75.4±14.2 years, 58.4% male) admitted with acute myocardial infarction (N=175,974), unstable angina (N=45,308), acute heart failure (N=179,871), acute aortic dissection (N=58,597), pulmonary embolism (N=17,009), or post-cardiac arrest (N=184,701). Patients were categorized into 4 groups: intensive care add-ons 1/2, 3/4 (ICU 1/2, 3/4), high-care unit (HCU), and general wards. Comparisons included patient characteristics, hospitalization duration, mortality rates, and rates of defibrillation or cardiopulmonary resuscitation (CPR) defined by chest compression. General ward patients were the oldest and with shortest hospitalization durations. Additionally, mortality rates were the highest in general wards for acute heart failure, myocardial infarction, and aortic dissection. Defibrillation rates were 7.0%, 5.6%, 3.1%, and 4.3%, for ICU 1/2, 3/4, HCU, and general ward, respectively, with corresponding mortality rates of 40.4%, 44.1%, 44.6%, and 79.3%. CPR rates were 10.1%, 9.5%, 6.2%, and 30.8%, with mortality rates of 71.0%, 73.9%, 78.4%, and 97.7%, respectively.

Conclusions: High mortality rates in general wards highlight the importance of ICU management, particularly for acute myocardial infarction and aortic emergencies. These findings support prioritizing ICU admission for these critical conditions.

Background: With aging of the population, atherosclerotic diseases have increased in Japan, with acute coronary syndrome (ACS) a significant cause of morbidity and mortality. In Kagoshima Prefecture, ACS mortality rates exceed the national average, reflecting challenges in lipid management and access to care.

Methods and Results: The Optimal Therapy for All Kagoshima Acute Coronary Syndrome (OK-ACS) Registry, initiated in April 2022, enrolled 2,328 ACS patients across Kagoshima. This study evaluated the impact of a standardized lipid management pathway, the “Kagoshima Style,” on low-density lipoprotein cholesterol (LDL-C) control and guideline adherence, as well as the regional profile of ACS in Kagoshima. The pathway was implemented at all percutaneous coronary intervention facilities to optimize lipid management and secondary prevention. LDL-C levels decreased significantly (P<0.0001) from admission to discharge and at 3 months (113.3±39.9, 74.6±28.0, and 69.2±25.9 mg/dL, respectively), with no difference according to place of residence. The proportion of patients with LDL-C <70 mg/dL increased from 12% at admission to 59% at 3 months. Maximum tolerated doses of high-intensity statin use increased from 7% at baseline to 9.3% after pathway implementation. Geographic disparities were evident, with patients from isolated islands experiencing delayed treatment access.

Conclusions: The Kagoshima Style pathway improved lipid management, reducing LDL-C and enhancing guideline adherence. This interim analysis provides insights into lipid management and regional disparities in patients with ACS across Kagoshima prefecture.

Background: Anthracyclines are widely used in cancer treatment, yet their potential for anthracycline-induced cardiotoxicity (AIC) limits their clinical utility. Despite the significant anatomical relevance of pericardial adipose tissue (PeAT) to cardiovascular disease, its response to anthracycline exposure remains poorly understood.

Methods and Results: Male New Zealand White rabbits (n=17) received weekly doxorubicin injections and underwent magnetic resonance imaging (MRI) scans biweekly for 10 weeks. PeAT volumes (total, left paraventricular, right paraventricular) were measured together with ventricular function. Histopathological evaluations were also conducted. A mixed linear model identified the earliest timeframe for detectable changes in PeAT volume and left ventricular function. Total PeAT volume decreased from the 6th week (1.17±0.06, P<0.05) and continued to decrease until the 8th week (0.96±0.06, P<0.05) and left paraventricular adipose tissue volume decreased significantly, but no changes were observed in right paraventricular adipose tissue volume. The volume of PeAT exhibited a positive correlation with left ventricular ejection fraction (LVEF) (r=0.43, P<0.05), which declined below 50% by the 8th week, and a negative correlation with myocardial cell injury scores (r=−0.595, P<0.05).

Conclusions: Anthracycline administration led to an early reduction in PeAT volume, particularly in the left paraventricular region, detectable by MRI as early as the 6th week. Changes in PeAT volume preceded alterations in LVEF and were associated with declines in cardiac function and myocardial cell damage.

Background: Both underweight and overweight are recognized as important factors influencing outcomes in patients undergoing cardiovascular surgery. This study investigated the effects of body mass index (BMI) on hospital-associated disability (HAD) and hospitalization costs in patients undergoing elective cardiovascular surgery (coronary artery bypass grafting, valve surgery, aortic surgery) by analyzing data from the Japanese Registry of All Cardiac and Vascular Diseases – Diagnosis Procedure Combination (JROAD-DPC) database.

Methods and Results: All patients in the JROAD-DPC database were categorized into 5 groups according to the World Health Organization BMI criteria for Asians. HAD was defined as a decrease of ≥5 points in the Barthel Index from admission to discharge. The primary outcome was the prevalence of HAD, and the secondary outcome was hospitalization costs. Among the 228,891 patients included in the study, the median BMI was 23.2 kg/m². The prevalence of HAD was 8.7%, with a U-shaped relationship between BMI and HAD, indicating that both extremely low and high BMIs were associated with a higher incidence of HAD. Hospitalization costs also showed a U-shape relationship with BMI, with higher costs for patients with HAD.

Conclusions: Low BMI in any age group was associated with HAD, and older people with a BMI considered too high also had HAD. BMI could be an important risk stratification tool for functional outcomes and economic burden in patients undergoing elective cardiovascular surgery.

Background: We previously reported that a high level of small dense low-density lipoprotein cholesterol (sdLDL-C) calculated by the Sampson equation was independently associated with the development of ischemic heart disease (IHD), but it remains unclear whether the effect depends on the level of low-density lipoprotein cholesterol (LDL-C).

Methods and Results: We investigated the associations of new onset of IHD with categorized groups of high (H-) and low (L-) levels of estimated sdLDL-C and LDL-C using 25^thpercentile levels of sdLDL-C level (25.2 mg/dL) and LDL-C (100 mg/dL) as cutoff values in 17,963 Japanese individuals (men/women: 11,508/6,455, mean age: 48 years) who underwent annual health checkups. During a 10-year follow-up period, 570 subjects (men/women: 449/121) had new development of IHD. Multivariable Cox proportional hazard analyses after adjustment of age, sex, smoking habit, hypertension and diabetes mellitus at baseline showed that the hazard ratio (HR) [95% confidence interval (CI)] for new onset of IHD was significantly higher in subjects with H-sdLDL-C/H-LDL-C (1.49 [1.06–2.08]) and subjects with H-sdLDL-C/L-LDL-C (1.49 [1.00–2.22]) than in subjects with L-sdLDL-C/L-LDL-C as the reference.

Conclusions: A high level of sdLDL-C estimated by the Sampson equation was a predominant predictor for the development of IHD, regardless of the level of LDL-C, in a general Japanese population.