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Abstract The introduction of the “da Vinci S HD Surgical System” marked a significant shift towards robotic surgeries in Japan. However, initial high costs and lack of efficacy data posed barriers to its widespread adoption. By 2023, more than 570 da Vinci units were operational in Japan, highlighting the growing acceptance of robotic surgery despite these challenges. This study aimed to investigate the prevalence and regional disparities in the adoption of robot-assisted laparoscopic prostatectomy (RALP) across Japan using diagnosis procedure combination data. This retrospective observational study analyzed data from 2857 urban and 4184 regional hospitals across 47 prefectures in Japan. The study focused on the number of RALP procedures, da Vinci systems, and certified urological surgery proctors. Multiple regression analysis was performed to identify significant factors influencing RALP adoption. Urban areas demonstrated a higher prevalence of RALP procedures and more da Vinci systems compared to regional areas, with urban hospitals performing an average of 937 RALP procedures compared to 195.5 in regional hospitals. The number of certified urological surgeons also showed significant urban-regional disparities, contributing to the overall imbalance. Our findings highlight substantial regional disparities in access to robot-assisted surgery in Japan, with urban areas benefiting from better access to advanced medical technologies and specialist training. Addressing these disparities will require targeted policies to improve the dissemination of robotic surgery systems and enhance training opportunities in regional cities.

Abstract Patients with atrial fibrillation (AF) often develop acute coronary syndrome and undergo percutaneous coronary intervention (PCI), and vice versa. Acute coronary syndrome and PCI mandate the use of dual antiplatelet therapy, while oral anticoagulation is recommended in patients with AF to mitigate thromboembolic risks. Clinical evidence concerning antithrombotic treatment in patients with AF and PCI has been accumulated, but when combined, the therapeutic strategy becomes complex. Although triple therapy, a combination of oral anticoagulation with dual antiplatelet therapy, has been used for patients with AF undergoing PCI as an initial antithrombotic strategy, less intensive regimens may be associated with a lower rate of bleeding without an increased risk in thrombotic events. This narrative review article summarizes currently available evidence of antithrombotic therapy in patients with AF undergoing PCI.

Abstract Background Left ventricular enlargement (LVE) is a common manifestation of cardiac remodeling that is closely associated with cardiac dysfunction, heart failure (HF), and arrhythmias. This study aimed to propose a machine learning (ML)-based strategy to identify LVE in HF patients by means of pulse wave signals. Method We constructed two high-quality pulse wave datasets comprising a non-LVE group and an LVE group based on the 264 HF patients. Fourier series calculations were employed to determine if significant frequency differences existed between the two datasets, thereby ensuring their validity. Then, the ML-based identification was undertaken by means of classification and regression models: a weighted random forest model was employed for binary classification of the datasets, and a densely connected convolutional network was utilized to directly estimate the left ventricular diastolic diameter index (LVDdI) through regression. Finally, the accuracy of the two models was validated by comparing their results with clinical measurements, using accuracy and the area under the receiver operating characteristic curve (AUC-ROC) to assess their capability for identifying LVE patients. Results The classification model exhibited superior performance with an accuracy of 0.91 and an AUC-ROC of 0.93. The regression model achieved an accuracy of 0.88 and an AUC-ROC of 0.89, indicating that both models can quickly and accurately identify LVE in HF patients. Conclusion The proposed ML methods are verified to achieve effective classification and regression with good performance for identifying LVE in HF patients based on pulse wave signals. This study thus demonstrates the feasibility and potential of the ML-based strategy for clinical practice while offering an effective and robust tool for diagnosing and intervening ventricular remodeling.

Abstract Giant cell myocarditis (GCM) is a rare but fatal disease that can lead to cardiac failure. Survival with a cardiac standstill requires mechanical circulatory support or a biventricular assist device (BiVAD) and prolonged survival is extremely rare. Drug‐induced hypersensitivity syndrome (DIHS) is a severe cutaneous adverse reaction. Some cases of DIHS are reportedly associated with the onset of GCM. We present a case of a 28‐year‐old woman who developed GCM during steroid tapering after DIHS. She went into continuous cardiac standstill but survived for 74 days under BiVAD support. Our case is noteworthy because the histopathologic specimens obtained on three occasions contributed to the diagnosis of this particular condition over time. We also reviewed previous literature on concomitant cases of GCM and DIHS. We found that two are potentially associated and most cases of GCM occur within 3 months of DIHS during steroid tapering.

Abstract Background We aimed to evaluate the length of hospital stay following total knee arthroplasty to determine the impact of relevant factors using data from the Diagnosis Procedure Combination database. Methods This was a retrospective observational study. The study cohort included 5,831 patients who had osteoarthritis of the knee and had undergone total knee replacement between February 2018 and October 2022 at 38 hospitals. Results Multivariate analysis showed that the factors influencing the length of stay included: age (p

Abstract Pulse wave, as a message carrier in the cardiovascular system (CVS), enables inferring CVS conditions while diagnosing cardiovascular diseases (CVDs). Heart failure (HF) is a major CVD, typically requiring expensive and time-consuming treatments for health monitoring and disease deterioration; it would be an effective and patient-friendly tool to facilitate rapid and precise non-invasive evaluation of the heart’s blood-supply capability by means of powerful feature-abstraction capability of machine learning (ML) based on pulse wave, which remains untouched yet. Here we present an ML-based methodology, which is verified to accurately evaluate the blood-supply capability of patients with HF based on clinical data of 237 patients, enabling fast prediction of five representative cardiovascular function parameters comprising left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVDd), left ventricular end-systolic diameter (LVDs), left atrial dimension (LAD), and peripheral oxygen saturation (SpO2). Two ML networks were employed and optimized based on high-quality pulse wave datasets, and they were validated consistently through statistical analysis based on the summary independent-samples t-test (p > 0.05), the Bland–Altman analysis with clinical measurements, and the error-function analysis. It is proven that evaluation of the SpO2, LAD, and LVDd performance can be achieved with the maximum error

Abstract Background/objective Few reports have directly compared the outcomes of patients with acute ischemic stroke (AIS) who are managed in a stroke care unit (SCU) with those who are managed in an intensive care units (ICU). This large database study in Japan aimed to compare in-hospital mortality between patients with AIS admitted into SCU and those admitted into ICU. Methods Patients with AIS who were admitted between April 1, 2014, and March 31, 2019, were selected from the administrative database and divided into the SCU and ICU groups. We calculated the propensity score to match groups for which the admission unit assignment was independent of confounding factors, including the modified Rankin scale (mRS) score. The primary outcome was in-hospital mortality, and secondary outcomes were the mRS score at discharge, length of stay (LOS), and total hospitalization cost. Results Overall, 8,683 patients were included, and 960 pairs were matched. After matching, the in-hospital mortality rates of the SCU and ICU groups were not significantly different (5.9% vs. 7.9%, P = 0.106). LOS was significantly shorter (SCU = 20.9 vs. ICU = 26.2 days, P

Abstract Background Autoantibodies develop in autoimmune diseases, cancer, diabetes mellitus (DM), and atherosclerosis-related diseases. However, autoantibody biomarkers have not been successfully examined for diagnosis and therapy. Methods Serological identification of antigens through recombinant cDNA expression cloning (SEREX) was used for primary screening of antigens. The cDNA product was expressed in bacteria and purified. Amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) was used to evaluate antibody levels in serum samples. Results Phosphoenolpyruvate carboxykinase 1 (PCK1) was recognized as an antigen by serum IgG antibodies in the sera of patients with atherosclerosis. AlphaLISA showed significantly higher serum antibody levels against recombinant PCK1 protein in patients with DM and cardiovascular disease than in healthy donors, but not in those with acute ischemic stroke, transient ischemic attack, or obstructive sleep apnea syndrome. The area under the receiver operating characteristic curve for anti-PCK1 antibodies was 0.7024 for DM. The serum anti-PCK1 antibody levels were associated with age, platelet count, and blood pressure. Anti-PCK1-antibody-positive patients showed significantly lower overall survival than the negative patients. Conclusions Serum anti-PCK1 antibody levels were found to be associated with DM. The anti-PCK1 antibody marker is useful for predicting the overall survival of patients with DM.

Abstract The effect of prehospital factors on favorable neurological outcomes remains unclear in patients with witnessed out-of-hospital cardiac arrest (OHCA) and a shockable rhythm. We developed a decision tree model for these patients by using prehospital factors. Using a nationwide OHCA registry database between 2005 and 2020, we retrospectively analyzed a cohort of 1,930,273 patients, of whom 86,495 with witnessed OHCA and an initial shockable rhythm were included. The primary endpoint was defined as favorable neurological survival (cerebral performance category score of 1 or 2 at 1 month). A decision tree model was developed from randomly selected 77,845 patients (development cohort) and validated in 8650 patients (validation cohort). In the development cohort, the presence of prehospital return of spontaneous circulation was the best predictor of favorable neurological survival, followed by the absence of adrenaline administration and age. The patients were categorized into 9 groups with probabilities of favorable neurological survival ranging from 5.7 to 70.8% (areas under the receiver operating characteristic curve of 0.851 and 0.844 in the development and validation cohorts, respectively). Our model is potentially helpful in stratifying the probability of favorable neurological survival in patients with witnessed OHCA and an initial shockable rhythm.

Although patients with hyperuricemia and gout often have dyslipidemia, the effects of febuxostat, a xanthine oxidase inhibitor, on their lipid profiles are unclear. Thus, we performed a sub-analysis of the randomized PRIZE study in which the effects of febuxostat on carotid atherosclerosis were investigated in patients with hyperuricemia. The participants were randomized to the febuxostat or control group. The primary endpoint of this sub-analysis was changes in the patients’ non-high-density lipoprotein cholesterol (HDL-C) levels from baseline to 6-month follow-up. Correlations between the changes in lipid profiles and cardiometabolic parameters were also evaluated. In total, 456 patients were included. From baseline to 6 months, non-HDL-C levels were significantly reduced in the febuxostat group (−5.9 mg/dL, 95% confidence interval [CI]: −9.1 to −2.8 mg/dL, p < 0.001), but not in the control group (−1.3 mg/dL, 95% CI: −4.4 to 1.8, p = 0.348). The reduction in non-HDL-C levels was more pronounced in women and correlated with changes in serum uric acid and estimated glomerular filtration rate levels only in the febuxostat group. In patients with hyperuricemia, febuxostat treatment was associated with reduced non-HDL-C levels from baseline to the 6-month follow-up compared to the control treatment, suggesting that the lipid-lowering effect of febuxostat should be considered when targeting dyslipidemia.

Abstract Hyperuricemia is reportedly associated with the progression of carotid intima-media thickness (IMT), a surrogate of cardiovascular risks and events. However, factors associated with carotid IMT progression in patients with asymptomatic hyperuricemia are largely unknown. In this post-hoc analysis of the multicenter, randomized PRIZE study, we analyzed data from a total of 326 patients who underwent carotid ultrasonography in a blind manner at baseline and 24 months to evaluate carotid IMT. Mean and maximum IMT at the common carotid artery (CCA) were measured at a central core laboratory. Factors related to the absolute change in mean and maximum IMT from baseline to 24 months were explored. Overall, the adjusted mean [0.0032 (− 0.0214 to 0.0278) mm] and maximum [0.0011 (− 0.0327 to 0.0351) mm] CCA-IMT increased numerically from baseline to 24 months. Multivariable analysis identified higher body mass index, history of atherosclerotic cardiovascular disease (ASCVD), and lower mean CCA-IMT at baseline as significant factors associated with the increase in mean CCA-IMT. In addition, older age and lower mean CCA-IMT at baseline were significant factors for an increased absolute change in the maximum CCA-IMT at 24 months. The present sub-analysis of the PRIZE study showed higher body mass index, history of ASCVD, and older age as significant factors associated with CCA-IMT progression in patients with asymptomatic hyperuricemia. These factors may be considered when identifying the possible risk of atherosclerotic progression in this specific patient population of hyperuricemia. Trial registration: UMIN000012911 and UMIN000041322.

Background: Although guidelines recommend intracoronary acetylcholine (ACh) and ergonovine (ER) provocation testing for diagnosis of vasospastic angina, the feasibility and safety of sequential (combined) use of both pharmacological agents during the same catheterization session remain unclear. Objectives: In this study, we investigated the feasibility and safety of sequential intracoronary ACh and ER administration for coronary spasm provocation testing. Methods: The study included 235 patients who showed positive results on ACh and ER provocation testing. Initial intracoronary ACh administration was followed by ER administration for left coronary artery (LCA) spasm provocation testing. Subsequently, the right coronary artery (RCA) was subjected to sequential ACh and ER administration for provocation testing. The primary outcome of the study was the safety of sequential intracoronary ACh and ER provocation testing, which was assessed based on a composite of all-cause death, sustained ventricular tachycardia and fibrillation, and cardiogenic shock. Results: Even in patients with negative results on sequential intracoronary ACh and ER provocation testing in the LCA and only ACh administration into the RCA, additional administration of ER into the RCA showed a positive provocation test result in 33 of 235 (14.0%) patients; three (1.3%) patients developed adverse effects (cardiogenic shock occurred in all cases) during LCA provocation testing. We observed no deaths attributable to spasm provocation testing. Conclusion: Sequential administration of intracoronary ACh and ER was associated with a relatively low major complication rate and may be safe and potentially useful for diagnosis of vasospastic angina.

One of the severe complications of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is myocarditis. However, the characteristics of fulminant myocarditis with SARS-CoV-2 infection are still unclear. We systematically reviewed the previously reported cases of fulminant myocarditis associated with SARS-CoV-2 infection from January 2020 to December 2022, identifying 108 cases. Of those, 67 were male and 41 female. The average age was 34.8 years; 30 patients (27.8%) were ≤20 years old, whereas 10 (9.3%) were ≥60. Major comorbidities included hypertension, obesity, diabetes mellitus, asthma, heart disease, gynecologic disease, hyperlipidemia, and connective tissue disorders. Regarding left ventricular ejection fraction (LVEF) at admission, 93% of the patients with fulminant myocarditis were classified as having heart failure with reduced ejection fraction (LVEF ≤ 40%). Most of the cases were administered catecholamines (97.8%), and mechanical circulatory support (MCS) was required in 67 cases (62.0%). The type of MCS was extracorporeal membrane oxygenation (n = 56, 83.6%), percutaneous ventricular assist device (Impella®) (n = 19, 28.4%), intra-aortic balloon pumping (n = 12, 12.9%), or right ventricular assist device (n = 2, 3.0%); combination of these devices occurred in 20 cases (29.9%). The average duration of MCS was 7.7 ± 3.8 days. Of the 76 surviving patients whose cardiac function was available for follow-up, 65 (85.5%) recovered normally. The overall mortality rate was 22.4%, and the recovery rate was 77.6% (alive: 83 patients, dead: 24 patients; outcome not described: 1 patient).

Inflammation is closely associated with cerebrovascular diseases, cardiovascular diseases, diabetes, and cancers, and it is accompanied by the development of autoantibodies in the early stage of inflammation-related diseases. Hence, it is meaningful to discover novel antibody biomarkers targeting inflammation-related diseases. In this study, Jumonji C-domain-containing 6 (JMJD6) was identified by the serological identification of antigens through recombinant cDNA expression cloning. In particular, JMJD6 is an antigen recognized in serum IgG from patients with unstable angina pectoris (a cardiovascular disease). Then, the serum antibody levels were examined using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay and a purified recombinant JMJD6 protein as an antigen. We observed elevated levels of serum anti-JMJD6 antibodies (s-JMJD6-Abs) in patients with inflammation-related diseases such as ischemic stroke, acute myocardial infarction (AMI), diabetes mellitus (DM), and cancers (including esophageal cancer, EC; gastric cancer; lung cancer; and mammary cancer), compared with the levels in healthy donors. The s-JMJD6-Ab levels were closely associated with some inflammation indicators, such as C-reactive protein and intima–media thickness (an atherosclerosis index). A better postoperative survival status of patients with EC was observed in the JMJD6-Ab-positive group than in the negative group. An immunohistochemical analysis showed that JMJD6 was highly expressed in the inflamed mucosa of esophageal tissues, esophageal carcinoma tissues, and atherosclerotic plaques. Hence, JMJD6 autoantibodies may reflect inflammation, thereby serving as a potential biomarker for diagnosing specific inflammation-related diseases, including stroke, AMI, DM, and cancers, and for prediction of the prognosis in patients with EC.

Objectives We aimed to investigate the regional variations in the number of interventions and surgeries for peripheral artery disease (PAD) and explore the major determinants of the variations.Design Cross-sectional study.Setting The Japanese Ministry of Health, Labour and Welfare National Database and Diagnostic Procedure Combination database in 2018.Data The rates of endovascular treatment (EVT), bypass surgery per 100 000 individuals in the population were calculated for all 47 prefectures in Japan. The total annual changes in the rates of EVT and bypass surgery in Japan from 2012 to 2019 were calculated.Analysis A linear regression model was developed with rates of EVT and bypass surgery as dependent variables and regional medical supply in each prefecture as explanatory variables. These regional factors included the rate of percutaneous coronary intervention (PCI) for angina, the numbers of cardiovascular specialists, specialists in cardiac surgery, interventional radiology (IVR) training facilities and cardiovascular surgery training facilities, per 100 000, respectively.Results There was a 5.7-fold difference (143 and 25 per 100 000 individuals aged ≥40 years) in the highest and lowest EVT rates. The highest and lowest rates of bypass surgery were 34 and

Key Clinical Message Right‐sided heart failure, including tricuspid regurgitation (TR), can cause cardiac cirrhosis. The pathophysiology is reduced arterial perfusion and passive congestion secondary to increased systemic venous pressure. However, hepatic encephalopathy due to cardiac cirrhosis is rare. This is the first case of hepatic encephalopathy with cardiac cirrhosis caused by persistent TR.

Key Clinical Message May‐Thurner syndrome (MTS) can be caused by abdominal aortic aneurysm (AAA) compressing the left common iliac vein against the lumbar vertebra. We reported a rare case of MTS due to AAA Compression successfully treated with anticoagulation.

Background In patients with cardiogenic shock (CS), acute myocardial infarction (AMI) is the most common cause, and a percutaneous microaxial ventricular assist device (Impella, Abiomed, Danvers, MA) is a choice for temporary mechanical circulatory support. However, data are limited on complications and outcomes of Impella treatment in patients with CS with and without AMI. Methods and Results Using nationwide prospective registry data in Japan, we included a total of 2047 patients with CS in whom the Impella devices were successfully placed between February 2020 and December 2021. Patients were divided into 2 groups according to the primary indication for the Impella use: AMI versus non‐AMI. The primary end point was a composite of in‐hospital all‐cause death and major complications. Of the 2047 patients, the Impella was indicated for AMI in 1337 (65.3%). In the group without AMI, myocarditis was the leading cause of CS. Patients with AMI‐CS were older and more likely to have cardiovascular risk factors than those with non‐AMI‐CS. The rates of in‐hospital mortality (46.0% versus 43.9%, P=0.38) and major complications (35.2% versus 34.7%, P=0.85) were similar between the 2 groups. Overall, multivariable analysis identified older age, higher body mass index, previous transient ischemic attack or stroke, out‐of‐hospital cardiac arrest, and the Impella 5.0 as factors significantly associated with the primary end point. Conclusions The use of Impella in patients with and without AMI was related to similar clinical outcomes with high mortality and complication rates. Further studies are needed to identify patients who may benefit from the Impella devices in CS. Registration URL: https://www.umin.ac.jp/english. Identifier: UMIN000033603.

Although coronary artery perforation can be a fatal complication during percutaneous coronary intervention, it is rarely observed in in-stent restenotic lesions. We present a case with coronary artery perforation after balloon dilatation for a recurrent in-stent restenotic lesion with calcified nodule inside the double-layered stents that were previously implanted. (Level of Difficulty: Advanced.)

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by insufficient activity of α-galactosidase A (α-Gal A) encoded by GLA. The enzymatic defect causes the progressive accumulation of sphingolipids in various tissues and body fluids, causing systemic disorders. We report a rare familial case of inherited cardiac FD associated with a novel double mutation in the GLA gene: W24R and N419D.A young man with severe obesity was admitted for heart failure (HF) with the diagnosis of dilated cardiomyopathy. Left ventricular hypertrophy was suspected during HF treatment after discharge, and in association with his mother's family history of cardiac diseases and sudden death, the etiology of the hypertrophy was re-examined. Very low α-Gal A activity confirmed the diagnosis of FD. Gene mutation analysis of GLA demonstrated a double mutation: W24R and N419D. Proband analysis revealed the same double mutation in his mother. Although she had no signs or symptoms of FD, we detected mild accumulation of globotriaosylsphingosine. The good laboratory practice-validated assay using HEK293 cells showed that the double mutation was amenable to migalastat, a pharmacological chaperone stabilizing α-Gal A.This case highlights a novel double gene mutation in GLA (W24R and N419D) identified in a family with FD. Although clinical significance of each mutation remains unknown, its combination might work synergistically to attain or augment pathogenicity.

The role of the incomplete form of Kawasaki disease in future cardiovascular risk is unknown. The present case demonstrates that even a healthy young man with only a history of incomplete Kawasaki disease can develop endothelial dysfunction and suffer myocardial infarction. We did not obtain ethical/institutional review board approval for our submission because this is not a clinical study, but the patient gave written informed consent to publish the case. (Level of Difficulty: Advanced.)

Background and Objectives: An interventional diagnostic procedure (IDP), including intracoronary acetylcholine (ACh) provocation and coronary physiological testing, is recommended as an invasive diagnostic standard for patients suspected of ischemia with no obstructive coronary arteries (INOCA). Recent guidelines suggest Thrombolysis In Myocardial Infarction frame count (TFC) as an alternative to wire-based coronary physiological indices for diagnosing coronary microvascular dysfunction. We evaluated trajectories of TFC during IDP and the impact of ACh provocation on TFC. Materials and Methods: This was a single-center, retrospective study. Patients who underwent IDP to diagnose INOCA were included and divided into two groups according to the positive or negative ACh provocation test. Wire-based invasive physiological assessment was preceded by ACh provocation tests and intracoronary isosorbide dinitrate (ISDN). We evaluated TFC at three different time points during IDP; pre-ACh, post-ISDN, and post-hyperemia. Results: Of 104 patients, 58 (55.8%) had positive ACh provocation test. In the positive ACh group, resting mean transit time (Tmn) and baseline resistance index were significantly higher than in the negative ACh group. Post-ISDN TFC was significantly correlated with resting Tmn (r = 0.31, p = 0.002). Absolute TFC values were highest at pre-ACh, followed by post-ISDN and post-hyperemia in both groups. All between-time point differences in TFC were statistically significant in both groups, except for the change from pre-ACh to post-ISDN in the positive ACh group. Conclusions: In patients suspected of INOCA, TFC was modestly correlated with Tmn, a surrogate of coronary blood flow. The positive ACh provocation test influenced coronary blood flow assessment during IDP.

Abstract Rapid and precise prehospital recognition of acute coronary syndrome (ACS) is key to improving clinical outcomes. The aim of this study was to investigate a predictive power for predicting ACS using the machine learning-based prehospital algorithm. We conducted a multicenter observational prospective study that included 10 participating facilities in an urban area of Japan. The data from consecutive adult patients, identified by emergency medical service personnel with suspected ACS, were analyzed. In this study, we used nested cross-validation to evaluate the predictive performance of the model. The primary outcomes were binary classification models for ACS prediction based on the nine machine learning algorithms. The voting classifier model for ACS using 43 features had the highest area under the receiver operating curve (AUC) (0.861 [95% CI 0.775–0.832]) in the test score. After validating the accuracy of the model using the external cohort, we repeated the analysis with a limited number of selected features. The performance of the algorithms using 17 features remained high AUC (voting classifier, 0.864 [95% CI 0.830–0.898], support vector machine (radial basis function), 0.864 [95% CI 0.829–0.887]) in the test score. We found that the machine learning-based prehospital algorithms showed a high predictive power for predicting ACS.

Platelet activation in the hemodialysis (HD) circuit often causes thrombocytopenia. However, its clinical and pathophysiological significance has rarely been explored. Herein, we investigated the predictive value of thrombocytopenia for cardiovascular events (CVE) in maintenance HD patients and attempted to explore its mechanistic background considering recent knowledge of platelet dynamics. We conducted a retrospective cohort study on HD patients with the composite primary endpoint of predicting CVE, i.e., myocardial infarction, ischemic stroke, and cardiovascular death. Baseline clinical data were analyzed and explored. Multivariate Cox regression analysis showed that platelet decrease was independently associated with CVE. Thrombocytopenia was correlated with the disuse of antiplatelet therapy (APT) and macrocytosis. These findings are possibly associated with platelet activation and senescent hematopoiesis. The prognostic significance of thrombocytopenia was more prominent in patients undergoing APT, implying the presence of APT-resistant platelets in such patients. To fully explain these results, we hypothesized that HD-activated platelets induce the biological aging of hematopoiesis, which is presumably extramedullary in the lung, where activated platelets could deliver massive amounts of inflammatory cytokines and reactive oxidative species. This results in the production of qualitatively altered and hyper-reactive platelets, a process that could form a vicious cycle that induces CVE-associated thrombocytopenia. Further investigations focusing on the dynamics of the biological aging of platelets in HD patients are warranted.

Many studies have explored cardiac progenitor cell (CPC) therapy for heart disease. However, optimal scaffolds are needed to ensure the engraftment of transplanted cells. We produced a three-dimensional hydrogel scaffold (CPC-PRGmx) in which high-viability CPCs were cultured for up to 8 weeks. CPC-PRGmx contained an RGD peptide-conjugated self-assembling peptide with insulin-like growth factor-1 (IGF-1). Immediately after creating myocardial infarction (MI), we transplanted CPC-PRGmx into the pericardial space on to the surface of the MI area. Four weeks after transplantation, red fluorescent protein-expressing CPCs and in situ hybridization analysis in sex-mismatched transplantations revealed the engraftment of CPCs in the transplanted scaffold (which was cellularized with host cells). The average scar area of the CPC-PRGmx-treated group was significantly smaller than that of the non-treated group (CPC-PRGmx-treated group = 46 ± 5.1%, non-treated MI group = 59 ± 4.5%; p < 0.05). Echocardiography showed that the transplantation of CPC-PRGmx improved cardiac function and attenuated cardiac remodeling after MI. The transplantation of CPCs-PRGmx promoted angiogenesis and inhibited apoptosis, compared to the untreated MI group. CPCs-PRGmx secreted more vascular endothelial growth factor than CPCs cultured on two-dimensional dishes. Genetic fate mapping revealed that CPC-PRGmx-treated mice had more regenerated cardiomyocytes than non-treated mice in the MI area (CPC-PRGmx-treated group = 0.98 ± 0.25%, non-treated MI group = 0.25 ± 0.04%; p < 0.05). Our findings reveal the therapeutic potential of epicardial-transplanted CPC-PRGmx. Its beneficial effects may be mediated by sustainable cell viability, paracrine function, and the enhancement of de novo cardiomyogenesis.

In this study, we aim to develop gold-coated Fe3O4 nanoparticles (Fe3O4@Au NPs) as theranostic agents for magnetic hyperthermia and CT imaging applications. The Fe3O4 NPs were synthesized via thermal decomposition method, and the gold was then deposited onto the surface of Fe3O4 NPs by reducing gold acetate at 190 °C. The average sizes of Fe3O4 and Fe3O4@Au NPs were 5.2 nm and 6.1 nm, respectively, which are effectively removed by the kidneys. The magnetization of Fe3O4@Au NPs (9.7 emu/g-Fe3O4) at 300 K was much smaller than that of Fe3O4 NPs (52.4 emu/g-Fe3O4). The heating efficiency of Fe3O4@Au NPs in water was sufficient to treat the tumor at 43–45 °C, and their high CT value of 851 HU was obtained. The synthesized ultrasmall Fe3O4@Au NPs showed great promise as a potential theranostic agent for magnetic hyperthermia and CT imaging applications.

Background: Cardiobacterium hominis is a member of the HACEK group, which causes infective endocarditis (IE) but is rarely associated with other infections. It is difficult to biologically identify C. hominis because of its slow growth in culture. However, the clinical features of C. hominis IE remain unclear. Method: We searched the PubMed database for all articles of C. hominis IE published between January 2000 and July 2022. Results: The major clinical features of 44 previously reported cases of C. hominis IE were as follows: the median age was 59 years, of which 36 were men; the initial presenting symptoms were chest discomfort (30 %), followed by fever (27 %), night sweats (20 %), fatigability (18 %), weight loss (16 %), and dyspnea (16 %). Almost half of the patients were febrile upon admission. The major predisposing factors were postsurgical valve treatment (57 %), dental treatment or caries (20 %), and congenital valve abnormality (5 %). The median time to identify C. hominis in the blood culture was 4 days, but the longest time was 42 days. The most commonly infected valve was the aortic valve, and the most common complication was systemic embolism. Surgical treatment was performed in 23 (52 %) patients. The most frequent initial treatment regimen was cephem antibiotics, with a median treatment duration of 6 weeks. The overall mortality and recovery rates of C. hominis IE were 9 % and 91 %, respectively. Conclusion: If C. hominis infection is confirmed, physicians should check for the presence of vegetations of the heart valves and understand these characteristics.

[This corrects the article DOI: 10.1371/journal.pone.0272140.].

BackgroundChronic systemic inflammatory diseases (CSIDs) such as rheumatoid arthritis (RA) are reportedly associated with an increased risk of ischemic cardiovascular events including acute myocardial infarction (MI). However, data are limited on clinical characteristics and ischemic and bleeding outcomes after acute MI in patients with CSIDs.MethodsThis bi-center registry included a total of 1001 patients with acute MI undergoing percutaneous coronary intervention. CSIDs included inflammatory rheumatological conditions (RA, systemic lupus erythematosus, vasculitis, etc.) and organ-specific diseases (chronic hepatitis, psoriasis, inflammatory bowel disease, etc.). The primary endpoint was net adverse clinical events (NACE), a composite of ischemic (all-cause death, MI, and ischemic stroke) and major bleeding (Bleeding Academic Research Consortium type 3 or 5) events, during hospitalization and after discharge.ResultsOf the 1001 patients, 58 (5.8%) had CSIDs. The proportion of women was higher in patients with CSIDs than those without (37.9% vs. 22.1%, p = 0.009). During the hospitalization, no significant differences in the primary endpoint of NACE were observed between patients with and without CSIDs (10.3% vs. 12.7%, p = 0.84). During the median follow-up of 42.6 months after discharge, patients with CSIDs had a higher risk of NACE (22.5% vs. 10.1%, p = 0.01) than those without, mainly driven by an increased risk of ischemic events (18.4% vs. 8.4%, p = 0.03).ConclusionsA small but significant proportion of patients with acute MI (5.8%) had CSIDs. While the incidence of in-hospital events was similar, patients with CSIDs had worse outcomes after discharge, suggesting that further clinical investigations and therapeutic approaches are needed in this patient subset.

Abstract The patients after heart transplantation usually present resting tachycardia, a slower increase in heart rate (HR) at the onset of exercise, a blunted chronotropic response to exercise in general, maximal HR being attained in the recovery period rather than at peak exercise, and a slower decline in HR after exercise.

Abstract Roof‐dependent atrial flutter (AFL) is a major tachyarrhythmia rotating in the left atrium (LA). Here, we describe a case of roof‐dependent AFL during atrial fibrillation ablation. LA posterior wall (LAPW) debulking ablation was performed before the induction. Atrial tachycardia (AT) was induced by burst pacing, and the 3D mappings showed a focal pattern from the LA inferior area. The post‐pacing interval from the roof and bottom line corresponded to the AT cycle length. The LAPW debulking ablation masked roof‐dependent AFL due to the lack of endocardium potentials in the LAPW. We report that roof‐dependent AFL connected by epicardium fibers.

Abstract The present work proposes a method for fabricating metallic Al particles in aqueous solution. An aqueous colloidal solution was prepared from an aqueous aluminum nitrate nonahydrate solution by electrolysis using metallic Al plates as the anode and cathode under ultrasonic irradiation in water at 25–45 °C. The sizes of the particles in the colloidal solutions prepared at 25, 35, and 45 °C were 76.3, 77.0, and 84.7 nm, respectively. The powder obtained from the colloidal solution prepared at 25 °C was not crystalline. By contrast, the powders obtained from the colloidal solutions prepared at 35 and 45 °C had a crystal structure of cubic Al and crystal sizes of 55.7 and 59.3 nm, respectively. Thus, elevated temperatures promoted both particle growth and crystal growth, which was explained by higher temperatures increasing the frequency and energy of particle collisions. The metallic Al particles were chemically stable in both an aqueous solution and the ambient atmosphere. The chemically stable metallic Al particles are expected to be used as sources for fabricating materials related to fuels, energy storage, and pigments.

Abstract Fulminant myocarditis is an inflammatory disease of the cardiac muscle that severely deteriorates cardiac function and often causes haemodynamic collapse in a manner similar to acute coronary syndrome. In rare cases, the myocardium of the right ventricle is dominantly damaged. In cases of lymphocytic myocarditis, a common type of fulminant myocarditis, cardiac function is often recovered after peak myocardial inflammation subsides; however, some cases show irreversible myocardial damage. Herein, we report the case of a 43‐year‐old woman with irreversible, right‐side dominant ventricular myocardial damage; she presented with various cardiopulmonary conditions including complete atrioventricular block, ventricular tachycardia, right heart failure, right ventricular thrombosis, and pulmonary embolism. The patient was successfully treated with medications and a cardiac resynchronization therapy‐defibrillator device.

Abstract Aims Little is known regarding factors that predict the occurrence of lethal ventricular arrhythmias (VAs) occurring after acute myocardial infarction (AMI). This observational cohort study aimed to identify factors that predicted lethal VAs during the late phase after AMI in patients with reduced left ventricular ejection fraction (LVEF). Methods and results Data were collected from our AMI database regarding consecutive patients with an LVEF of ≤40% after AMI (January 2012 to July 2018). The ‘late phase’ was defined as ≥7 days after AMI onset, and the primary endpoint was defined as lethal VAs in the late phase. The study included 136 patients (82% men; mean age: 66 ± 13 years). The average LVEF at admission was 32.7 ± 8.2%. During a mean follow‐up period of 20.7 months, 14 patients (10%) experienced lethal VAs, including ventricular fibrillation (n = 8) and sustained ventricular tachycardia (n = 10). Univariate analyses revealed that lethal VAs were predicted by age and LVEF at admission. Receiver operating characteristic curve analysis indicated that the optimal cut‐off value was 23% for using the LVEF at admission to predict the primary endpoint (area under the curve: 0.77, P

Aim: The impact of in-hospital and ambulatory glucose variability (GV) on lipid core plaques (LCP) is unclear. We evaluated the relation of GV during hospitalization and after discharge to LCPs. Methods: A total of 35 patients undergoing percutaneous coronary intervention (PCI) under near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) guidance for acute myocardial infarction (MI) and stable coronary artery disease were prospectively included. LCP was evaluated with a lipid core burden index (LCBI) and a maximum LCBI in 4 mm (max LCBI4mm) in the non-target vessel using NIRS-IVUS. GV was measured by a flush glucose monitoring system. Results: In-hospital mean amplitude of glucose excursion (MAGE) was significantly higher than that after discharge (73.4±26.8 vs. 66.0±22.8 mg/dl, p=0.03). In the entire study population, LCBI and maxLCBI4mm in the non-target vessel were correlated with MAGE after discharge (r=0.51, p=0.002 and r=0.39, p=0.02), but not significantly correlated with in-hospital MAGE. The relations of MAGE to higher LCBI and maxLCBI4mm were more evident in patients with acute MI. Conclusions: GV was greater during hospitalization than after discharge in patients undergoing PCI. Greater GV after discharge was significantly associated with higher LCBI and maxLCBI4mm, suggesting that ambulatory GV may be closely link to coronary atherosclerosis.

Objectives Although uric acid lowering therapies, including xanthine oxidase (XO) inhibition, may reduce the absolute level of blood pressure (BP), the effect of XO inhibition on BP variability is largely unknown. The aim of the present analysis was to evaluate the impact of febuxostat, an XO inhibitor, on BP variability in a randomised trial setting.Methods This was a subanalysis of the PRIZE Study, a randomised trial to evaluate the potential effect of febuxostat on carotid intima–media thickness progression. Patients with hyperuricemia and carotid plaques were randomly assigned to the febuxostat or control group. During a 24-month period, office BP and pulse rate (PR) were measured ≥3 times. BP and PR variabilities were assessed with SD and coefficient of variation (CV). The effect of febuxostat on BP and PR variabilities was adjusted with age, sex and baseline BP or PR, expressed with 95% CIs.Results A total of 472 patients were included into the present subanalysis. During the 24-month follow-up period, the febuxostat group had a significantly lower adjusted mean systolic BP (128.4 (126.8–130.0) vs 130.7 (129.1–132.2) mm Hg, p=0.04) and CV of systolic BP (7.4 (6.7–8.0) vs 8.2 (7.6–8.8), p=0.04) than the control group. Adjusted SD of PR was also lower in the febuxostat group than their counterpart (5.95 (4.93–6.97) vs 7.33 (6.32–8.33), p=0.04).Conclusion XO inhibition with febuxostat was associated with reduced visit-to-visit BP variability as well as reduced PR variability in patients with hyperuricemia and carotid plaques.Trial registration numbers University Hospital Medical Information Network Clinical Trial Registry (UMIN000012911 and UMIN000041322).

Abstract Background Acute ischemic stroke (AIS) is a serious cause of mortality and disability. AIS is a serious cause of mortality and disability. Early diagnosis of atherosclerosis, which is the major cause of AIS, allows therapeutic intervention before the onset, leading to prevention of AIS. Methods Serological identification by cDNA expression cDNA libraries and the protein array method were used for the screening of antigens recognized by serum IgG antibodies in patients with atherosclerosis. Recombinant proteins or synthetic peptides derived from candidate antigens were used as antigens to compare serum IgG levels between healthy donors (HDs) and patients with atherosclerosis-related disease using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay. Results The first screening using the protein array method identified death-inducer obliterator 1 (DIDO1), forkhead box J2 (FOXJ2), and cleavage and polyadenylation specificity factor (CPSF2) as the target antigens of serum IgG antibodies in patients with AIS. Then, we prepared various antigens including glutathione S-transferase-fused DIDO1 protein as well as peptides of the amino acids 297–311 of DIDO1, 426–440 of FOXJ2, and 607–621 of CPSF2 to examine serum antibody levels. Compared with HDs, a significant increase in antibody levels of the DIDO1 protein and peptide in patients with AIS, transient ischemic attack (TIA), and chronic kidney disease (CKD) but not in those with acute myocardial infarction and diabetes mellitus (DM). Serum anti-FOXJ2 antibody levels were elevated in most patients with atherosclerosis-related diseases, whereas serum anti-CPSF2 antibody levels were associated with AIS, TIA, and DM. Receiver operating characteristic curves showed that serum DIDO1 antibody levels were highly associated with CKD, and correlation analysis revealed that serum anti-FOXJ2 antibody levels were associated with hypertension. A prospective case–control study on ischemic stroke verified that the serum antibody levels of the DIDO1 protein and DIDO1, FOXJ2, and CPSF2 peptides showed significantly higher odds ratios with a risk of AIS in patients with the highest quartile than in those with the lowest quartile, indicating that these antibody markers are useful as risk factors for AIS. Conclusions Serum antibody levels of DIDO1, FOXJ2, and CPSF2 are useful in predicting the onset of atherosclerosis-related AIS caused by kidney failure, hypertension, and DM, respectively.

Abstract Aims Acute pulmonary disorders are known physical triggers of takotsubo syndrome (TTS). This study aimed to investigate prevalence of acute pulmonary triggers in patients with TTS and their impact on outcomes. Methods and results Patients with TTS were enrolled from the International Takotsubo Registry and screened for triggering factors and comorbidities. Patients were categorized into three groups (acute pulmonary trigger, chronic lung disease, and no lung disease) to compare clinical characteristics and outcomes. Of the 1670 included patients with TTS, 123 (7%) were identified with an acute pulmonary trigger, and 194 (12%) had a known history of chronic lung disease. The incidence of cardiogenic shock was highest in patients with an acute pulmonary trigger compared with those with chronic lung disease or without lung disease (17% vs. 10% vs. 9%, P = 0.017). In‐hospital mortality was also higher in patients with an acute pulmonary trigger than in the other two groups, although not significantly (5.7% vs. 1.5% vs. 4.2%, P = 0.13). Survival analysis demonstrated that patients with an acute pulmonary trigger had the worst long‐term outcome (P = 0.002). The presence of an acute pulmonary trigger was independently associated with worse long‐term mortality (hazard ratio 2.12, 95% confidence interval 1.33–3.38; P = 0.002). Conclusions The present study demonstrates that TTS is related to acute pulmonary triggers in 7% of all TTS patients, which accounts for 21% of patients with physical triggers. The presence of acute pulmonary trigger is associated with a severe in‐hospital course and a worse long‐term outcome.

Abstract Atherosclerosis has been considered as the main cause of morbidity, mortality, and disability worldwide. The first screening for antigen markers was conducted using the serological identification of antigens by recombinant cDNA expression cloning, which has identified adaptor-related protein complex 3 subunit delta 1 (AP3D1) as an antigen recognized by serum IgG antibodies of patients with atherosclerosis. Serum antibody levels were examined using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) using a recombinant protein as an antigen. It was determined that the serum antibody levels against AP3D1 were higher in patients with acute ischemic stroke (AIS), transient ischemic attack, diabetes mellitus (DM), cardiovascular disease, chronic kidney disease (CKD), esophageal squamous cell carcinoma (ESCC), and colorectal carcinoma than those in the healthy donors. The area under the curve values of DM, nephrosclerosis type of CKD, and ESCC calculated using receiver operating characteristic curve analysis were higher than those of other diseases. Correlation analysis showed that the anti-AP3D1 antibody levels were highly associated with maximum intima-media thickness, which indicates that this marker reflected the development of atherosclerosis. The results of the Japan Public Health Center-based Prospective Study indicated that this antibody marker is deemed useful as risk factors for AIS.

Abstract Corrigan’s pulse is characterized by the abrupt distension and quick collapse of carotid arteries in aortic regurgitation, whereas water hammer pulse is the characteristic pulse observed in peripheral arteries.

Coronary microvascular dysfunction (CMD) is described as an important subset of ischemia with no obstructive coronary artery disease. Resistive reserve ratio (RRR) and microvascular resistance reserve (MRR) have been proposed as novel physiological indices evaluating coronary microvascular dilation function. The aim of this study was to explore factors associated with impaired RRR and MRR. Coronary physiological indices were invasively evaluated in the left anterior descending coronary artery using the thermodilution method in patients suspected of CMD. CMD was defined as a coronary flow reserve p < 0.001) and MRR (3.4 ± 1.9 vs. 6.9 ± 3.5, p < 0.001) were lower in the CMD group. In the receiver operating characteristic curve analysis, RRR (area under the curve 0.84, p < 0.001) and MRR (area under the curve 0.85, p < 0.001) were both predictive of the presence of CMD. In the multivariable analysis, previous myocardial infarction, lower hemoglobin, higher brain natriuretic peptide levels, and intracoronary nicorandil were identified as factors associated with lower RRR and MRR. In conclusion, the presence of previous myocardial infarction, anemia, and heart failure was associated with impaired coronary microvascular dilation function. RRR and MRR may be useful to identify patients with CMD.

Background Clinical outcomes of acute myocardial infarction complicated by cardiogenic shock remain poor with high in‐hospital mortality. Veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) has been widely used for patients with acute myocardial infarction complicated by cardiogenic shock refractory to conservative therapy, which is likely fatal without mechanical circulatory support. However, whether additional intra‐aortic balloon pumping (IABP) use during VA‐ECMO support improves clinical outcomes remains controversial. This study sought to investigate prognostic impact of the combined VA‐ECMO plus IABP treatment compared with VA‐ECMO alone. Methods and Results From the nationwide Japanese administrative case‐mix Diagnostic Procedure Combination (DPC), the JROAD (Japanese Registry of All Cardiac and Vascular Diseases)–DPC, we identified 3815 patients with acute myocardial infarction complicated by cardiogenic shock who underwent primary percutaneous coronary intervention and managed with VA‐ECMO. Of these, 2964 patients (77.7%) were managed with IABP (VA‐ECMO plus IABP), whereas 851 (22.3%) were managed without IABP (VA‐ECMO alone). We compared in‐hospital, 7‐day, and 30‐day mortality between the VA‐ECMO plus IABP versus the VA‐ECMO alone support. Patients managed with VA‐ECMO plus IABP demonstrated significantly lower in‐hospital, 7‐day, and 30‐day mortality than those managed with VA‐ECMO alone (adjusted odds ratios [95% CI] of 0.47 [95% CI, 0.38–0.59], 0.41 [95% CI, 0.33–0.51], and 0.30 [95% CI, 0.25–0.37], respectively). The findings were consistent in the propensity matching and inverse probability of treatment‐weighting models. Conclusions This large‐scale, nationwide study demonstrated that the combination of VA‐ECMO plus IABP support was associated with significantly lower mortality compared with VA‐ECMO support alone in patients presenting with acute myocardial infarction complicated by cardiogenic shock who underwent primary percutaneous coronary intervention.

Background Lower primary percutaneous coronary intervention (PCI) volume is known to be associated with worse outcomes in patients with acute myocardial infarction (MI) at hospital level. The present study aimed to evaluate the relations of primary, elective, and total PCI volume and primary/total PCI volume ratio per hospital to in‐hospital mortality in patients with acute MI undergoing primary PCI. Methods and Results Using a large nationwide administrative database, we included a total of 83 076 patients from 154 hospitals in Japan undergoing PCI for either acute MI or elective cases. Relations of annual procedural volumes for primary, elective, and total PCI to in‐hospital mortality after acute MI at hospital level were evaluated. The ratio of primary to total PCI volume per hospital was also assessed. The primary end point was the ratio of observed to predicted mortality. Of 83 076 patients, 26 913 (32.4%) underwent primary PCI for acute MI, among whom 1561 (5.8%) died during hospitalization. Overall, observed in‐hospital mortality after acute MI and observed/predicted mortality ratio were higher in hospitals with lower primary, elective, and total PCI volumes. Observed/predicted in‐hospital mortality ratio was higher in hospitals with low primary/total PCI volume ratio, even in those with high total PCI volume. Conclusions Primary, elective, and total PCI volume at hospitals were inversely associated with in‐hospital mortality in patients with acute MI undergoing primary PCI. Lower ratio of primary to total PCI volume were related to higher in‐hospital mortality, suggesting primary/total PCI volume ratio as an institutional indicator of quality of care for acute MI.

We report the case of a 70-year-old woman with hypertrophic obstructive cardiomyopathy, who was admitted because of severe heart failure and cardiogenic shock and mechanical support requiring extracorporeal membrane oxygenation. She recovered well by percutaneous transluminal septal myocardial ablation under the extracorporeal membrane oxygenation support and was discharged without complications. (Level of Difficulty: Advanced.)