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Nitrogen doped hydrogenated amorphous carbon films grown using radio frequency plasma-enhanced chemical vapor deposition were studied for spectroscopic characteristics.

Aim: It remains unknown whether sodium-glucose cotransporter 2 inhibitors (SGLT2i) could be associated with incident cancer., Methods: We analyzed individuals having diabetes and newly prescribed SGLT2i or dipeptidyl peptidase 4 inhibitors (DPP4i) in a large-scale epidemiological database. The primary outcome was the incidence of cancer. A propensity score matching algorithm was employed to compare the subsequent development of cancer between the SGLT2i and DPP4i groups., Results: After 1:2 propensity score matching, 26,823 individuals (8,941 SGLT2i, 17,882 DPP4i) were analyzed. During the mean follow-up duration of 2.0 ± 1.6 years, 1,076 individuals developed cancer. SGLT2i administration was associated with a reduced risk of cancer (HR 0.80, 95% CI 0.70-0.91). Particularly, SGLT2i administration was related to a lower risk of colorectal cancer (HR 0.71, 95% CI 0.50-0.998). Our primary findings remained consistent across various sensitivity analyses, including overlap weighting analysis (HR 0.79, 95% CI 0.66-0.94), inverse probability of treatment weighting 0.75 (95% CI 0.65-0.86), and induction period settings 0.78 (95% CI 0.65-0.93). The risk of developing cancer was comparable among individual SGLT2is (P-value of 0.1738)., Conclusion: Our investigation using nationwide real-world data demonstrated the potential advantage of SGLT2i over DPP4i in reducing the development of cancer in individuals with diabetes., Competing Interests: Declaration of competing interest Research funding and scholarship funds (Hidehiro Kaneko and Katsuhito Fujiu) from Medtronic Japan CO., LTD, Boston Scientific Japan CO., LTD, Biotronik Japan, Simplex QUANTUM CO., LTD, and Fukuda Denshi, Central Tokyo CO., LTD. Hidehiro Kaneko owns stocks of PrevMed Co. Issei Komuro received remuneration for a lecture from AstraZeneca K.K, MSD K.K, Otsuka Pharmaceutical Co. Ltd., ONO PHARMACEUTICAL CO. LTD., DAIICHI SANKYO COMPANY LIMITED., Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., BAYER YAKUHIN, LTD., Novo Nordisk Pharma Ltd., Pfizer Japan Inc and trust research/joint research funds from ONO PHARMACEUTICAL CO. LTD. and scholarship fund from Idorsia Pharmaceuticals Japan Ltd., MSD K.K., ONO PHARMACEUTICAL CO. LTD., Sanofi K. K., DAIICHI SANKYO COMPANY LIMITED., Dainippon Sumitomo Pharma Co. Ltd., Takeda Pharmaceutical Company Limited., Mitsubishi Tanabe Pharma Corporation, TEIJIN PHARMA LIMITED, TOA EIYO LTD.., (Copyright © 2024. Published by Elsevier Masson SAS.)

Competing Interests: Conflict of interest: Research funding and scholarship funds (H.K. and K.F.) from Medtronic Japan Co., Ltd., Abbott Medical Japan Co., Ltd., Boston Scientific Japan Co., Ltd., and Fukuda Denshi, Central Tokyo Co., Ltd. Other authors have no conflicts of interest to declare.

Aim: To investigate the clinical significance of body weight changes on kidney outcomes among individuals with diabetes using sodium-glucose cotransporter-2 (SGLT2) inhibitors., Materials and Methods: This is a retrospective cohort study using a nationwide epidemiological database, and we conducted an analysis involving 11 569 individuals with diabetes who were newly prescribed SGLT2 inhibitors. The main outcome was the rate of decline in estimated glomerular filtration rate (eGFR), determined through a linear mixed-effects model with an unstructured covariance structure., Results: The median age of the patients was 52 (Q1-Q3: 47-58) years, and the median fasting plasma glucose and glycated haemoglobin (HbA1c) levels were 144 (Q1-Q3: 124-175) mg/dL and 7.4 (Q1-Q3: 6.8-8.3)%, respectively. The median estimated eGFR was 77.7 (Q1-Q3: 67.2-89.1) mL/min/1.73 m 2 . The median follow-up period was 1.7 (Q1-Q3: 1.0-2.6) years. Participants were stratified into three groups based on the body mass index change rate tertiles between baseline and 1 year after (tertile 1: <-4.55%, tertile 2: -4.55% to -1.43%, tertile 3: >-1.43%). The annual change in eGFR was -0.78 (-0.94 to -0.63) mL/min/1.73 m 2 in tertile 1, -0.95 (-1.09 to -0.81) mL/min/1.73 m 2 in tertile 2, and -1.65 mL/min/1.73 m 2 (-1.84 to -1.47) in tertile 3 (p interaction  < 0.001). A variety of sensitivity analyses confirmed the relationship between the 1-year body mass index decrease and favourable kidney outcomes after SGLT2 inhibitor administration., Conclusions: Our analysis of a nationwide epidemiological cohort revealed that kidney outcomes following the initiation of SGLT2 inhibitors would be more favourable, with greater body weight loss observed after the initiation of SGLT2 inhibitors., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Competing Interests: Conflict of interest: H.K. and K.F. received research funding and scholarship funds from Medtronic Japan Co., Ltd; Abbott Medical Japan Co., Ltd; Boston Scientific Japan Co., Ltd; and Fukuda Denshi, Central Tokyo Co., Ltd. Other authors have no conflicts of interest to declare.

Although clonal hematopoiesis of indeterminate potential (CHIP) is an adverse prognostic factor for atherosclerotic disease, its impact on nonischemic dilated cardiomyopathy (DCM) is elusive. The authors performed whole-exome sequencing and deep target sequencing among 198 patients with DCM and detected germline mutations in cardiomyopathy-related genes and somatic mutations in CHIP driver genes. Twenty-five CHIP driver mutations were detected in 22 patients with DCM. Ninety-two patients had cardiomyopathy-related pathogenic mutations. Multivariable analysis revealed that CHIP was an independent risk factor of left ventricular reverse remodeling, irrespective of known prognostic factors. CHIP exacerbated cardiac systolic dysfunction and fibrosis in a DCM murine model. The identification of germline and somatic mutations in patients with DCM predicts clinical prognosis., Competing Interests: This work was supported by grants from the SENSHIN Medical Research Foundation (to Dr Nomura), the Japan Foundation for Applied Enzymology (to Drs Ko, Nomura, and Dai), the Kanae Foundation for the Promotion of Medical Science (to Dr Nomura), the MSD Life Science Foundation (to Dr Nomura), the Sakakibara Heart Foundation Cardiovascular Research Program 2023 (to Dr Ko), the Tokyo Biomedical Research Foundation (to Dr Nomura), the Astellas Foundation for Research on Metabolic Disorders (to Dr Nomura), the Novartis Foundation (Japan) for the Promotion of Science (to Dr Nomura), the Japanese Circulation Society (to Drs Ko and Nomura), the Takeda Science Foundation (to Drs Ko and Nomura), the Cell Science Research Foundation (to Dr Nomura), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (to Dr Nomura), the Japan Heart Foundation (to Dr Ko), and the Daiichi-Sankyo Foundation of Life Science (to Dr Nomura); a Grant-in-Aid for Scientific Research (A) (to Dr Nomura); a Grant-in-Aid for Scientific Research (S) (to Dr Komuro); the UTEC-UTokyo FSI Research Grant Program (to Dr Nomura); the JST FOREST Program (grant JPMJFR210U) (to Dr Nomura); a Japan Society for the Promotion of Science Grant-in-Aid for Japan Society for the Promotion of Science fellow (23KJ0434) (to Dr Dai) and AMED JP23ek0109600h0002 (to Dr Ko); and JP20ek0109487, JP18km0405209, JP21ek0109543, JP21tm0724601, JP22ama121016, JP22ek0210172, JP22ek0210167, JP22bm1123011, JP23tm0724607, JP23gm4010020, JP23tm0524009, JP23tm0524004, JP23jf0126003, and JP24ek0109755 (to Drs Nomura and Komuro). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Backgrounds: Remote cardiac rehabilitation has proven useful in patients with cardiovascular disease; however, the methodology had not been fully validated. This study aimed to investigate the efficacy and safety of remote cardiac rehabilitation (RCR) with real-time monitoring and an ergometer using a bidirectional communication tool during the recovery phase of cardiovascular diseases., Methods: This multicenter, nonrandomized, interventional study was conducted at 29 institutions across Japan and enrolled patients with cardiovascular diseases who met indications for cardiac rehabilitation (CR) after receiving in-hospital treatment. The RCR group exercised at home using an ergometer and was monitored in real-time using interactive video and monitoring tools for 2-3 months. Educational instructions were provided concurrently through e-learning approaches. The safety of the RCR protocol and the improvement in peak oxygen consumption (VO2) were compared with those of the historical control group that participated in center-based CR., Results: Fifty-three patients from the RCR group were compared with 103 historical controls having similar background characteristics. No patients in RCR experienced significant cardiovascular complications while engaging in exercise sessions. After 2-3 months of RCR, the peak VO2 improved significantly, and the increases in the RCR group did not exhibit any significant differences compared to those in the historical controls. During follow-up, the proportion of patients whose exercise capacity increased by 10% or more was also evaluated; this finding did not indicate a statistically significant distinction between the groups., Conclusions: RCR during the recovery phase of cardiovascular diseases proved equally efficient and safe as center-based CR., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eisuke Amiya belongs to the Department, endowed by NIPRO-Corp, Terumo-Corp., Senko-Medical-Instrument-Mfg., Century-Medical, Inc., ONO-pharmaceutical-Co., Ltd. Medtronic-JAPAN Co., Ltd, Nippon-Shinyaku Co., Ltd, Mochida Pharmaceutical Co.; Boehringer Ingelheim Pharmaceuticals Inc., Abiomed-Inc, AQuA-Inc, Fukuda-Denshi Co., Ltd, and Sun-Medical-Technology-Research Corp. Eisuke Amiya received research funding from Bristol-Myers Squibb Co. The authors declare that the research was conducted in the absence of commercial or financial relationships that could be construed as potential conflicts of interest., (© 2024 The Author(s).)

Background: Climate is known to influence the incidence of cardiovascular events. However, their prediction with traditional statistical models remains imprecise., Methods and Results: We analyzed 27,799 acute heart failure (AHF) admissions within the Tokyo CCU Network Database from January 2014 to December 2019. High-risk AHF (HR-AHF) day was defined as a day with the upper 10th percentile of AHF admission volume. Deep neural network (DNN) and traditional regression models were developed using the admissions in 2014-2018 and tested in 2019. Explanatory variables included 17 meteorological parameters. Shapley additive explanations were used to evaluate their importance. The median number of incidences of AHF was 12 (9-16) per day in 2014-2018 and 11 (9-15) per day in 2019. The predicted AHF admissions correlated well with the observed numbers (DNN: R 2  = 0.413, linear regression: R 2  = 0.387). The DNN model was superior in predicting HR-AHF days compared with the logistic regression model [c-statistics: 0.888 (95% CI: 0.818-0.958) vs 0.827 (95% CI: 0.745-0.910): P = .0013]. Notably, the strongest predictive variable was the 7-day moving average of the lowest ambient temperatures., Conclusions: The DNN model had good prediction ability for incident AHF using climate information. Forecasting AHF admissions could be useful for the effective management of AHF., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: Evidence on the association between ambient temperature and the onset of acute heart failure (AHF) is scarce and mixed. We sought to investigate the incidence of AHF admissions based on ambient temperature change, with particular interest in detecting the difference between AHF with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF)., Methods and Results: Individualized AHF admission data from January 2015 to December 2016 were obtained from a multicentre registry (Tokyo CCU Network Database). The primary event was the daily number of admissions. A linear regression model, using the lowest ambient temperature as the explanatory variable, was selected for the best-estimate model. We also applied the cubic spline model using five knots according to the percentiles of the distribution of the lowest ambient temperature. We divided the entire population into HFpEF + HFmrEF and HFrEF for comparison. In addition, the in-hospital treatment and mortality rates were obtained according to the interquartile ranges (IQRs) of the lowest ambient temperature (IQR1 <5.5°C; IQR25.5-13.3°C; IQR3 13.3-19.7°C; and IQR4 >19.7°C). The number of admissions for HFpEF, HFmrEF and HFrEF were 2736 (36%), 1539 (20%), and 3354 (44%), respectively. The lowest ambient temperature on the admission day was inversely correlated with the admission frequency for both HFpEF + HFmrEF and HFrEF patients, with a stronger correlation in patients with HFpEF + HFmrEF (R 2  = 0.25 vs. 0.05, P < 0.001). In the sensitivity analysis, the decrease in the ambient temperature was associated with the greatest incremental increases in HFpEF, followed by HFmrEF and HFrEF patients (3.5% vs. 2.8% vs. 1.5% per -1°C, P < 0.001), with marked increase in admissions of hypertensive patients (systolic blood pressure >140 mmHg vs. 140-100 mmHg vs. <100 mmHg, 3.0% vs. 2.0% vs. 0.8% per -1°C, P for interaction <0.001). A mediator analysis indicated the presence of the mediator effect of systolic blood pressure. The in-hospital mortality rate (7.5%) did not significantly change according to ambient temperature (P = 0.62)., Conclusions: Lower ambient temperature was associated with higher frequency of AHF admissions, and the effect was more pronounced in HFpEF and HFmrEF patients than in those with HFrEF., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

With the widespread use of implantable left ventricular assist device (LVAD), right ventricular failure (RVF) has become a serious problem that becomes apparent several weeks or later after LVAD implantation. However, there are no marked preoperative signs of RVF. This is called late-onset RVF and is currently a major problem leading to long-term complications following implantable LVAD use. Pathogenically, this could be the result of left ventricular suction by LVAD that causes the septum shift to the left ventricular side. This causes a change in morphology of the right ventricle, resulting in impaired right ventricular function. Aortic insufficiency and ventricular arrhythmia, which are also important as long-term complications after LVAD implantation, are considered to be closely involved in the onset and progression of RVF. Once late-onset RVF develops, exercise capacity declines and inotrope administration may be required. Late-onset RVF was also reported to be significantly associated with increased mortality. Several predictors of RVF have been proposed such as preoperative left ventricular diastolic dimension <64 mm, tricuspid valve annulus diameter ≥41 mm, and so on. However, some reports identified no predictors. The basic treatment strategy for late-onset RVF is to optimize volume status by administering diuretics and ensuring inotrope as needed. β-blockers and antiarrhythmic agents often need to be reduced in terms of dosage or even discontinued because these might reduce right ventricular function. Although their efficacy is unclear, pulmonary vasodilators may be used to reduce right ventricular afterload. It is better to decrease the rotation speed of LVAD to minimize the displacement of the septum; however, this is often difficult because the required flow rate cannot be secured. Progress in the prevention and management of late-onset RVF is required because the number of patients who require longer-term LVAD support will increase with the spread of LVAD use as destination therapy., (Copyright © 2021. Published by Elsevier Ltd.)

Onco-cardiology is the emerging field, and the concept of shared risk factor holds an important position in this field. The increasing prevalence of colorectal cancer (CRC) in young adults is a critical epidemiological issue. Although metabolic syndrome, which is a major risk factor for cardiovascular disease, is known to be associated with CRC incidence in middle-aged and elderly individuals, it is unclear whether this association is present in young adults. We assessed whether metabolic syndrome was associated with CRC events in young adults (aged <50 years), and whether the association differed by the definition of metabolic syndrome. We retrospectively analyzed 902,599 adults (20 to 49 years of age) enrolled in the JMDC Claims Database which is a nationwide epidemiological database in Japan between January 2005 and August 2018. Participants who had a history of CRC, colorectal polyps, or inflammatory bowel disease were excluded. Study participants were categorized into 2 groups according to the presence of metabolic syndrome, defined using the Japanese criteria (waist circumference ≥85 cm for men and ≥90 cm for women, and ≥2 metabolic parameters including elevated blood pressure, elevated triglycerides, reduced high-density lipoprotein cholesterol, or elevated fasting plasma glucose). Clinical outcomes were collected between January 2005 and August 2018. The primary outcome was CRC of any stage. Median (interquartile range) age was 41 (37 to 45), and 55.4% were men. Over a median follow-up of 1,008 (429 to 1,833) days, there were 1,884 incidences of CRC. After multivariable adjustment, the hazard ratio (HR) of metabolic syndrome for CRC events was 1.26 (95% confidence interval [CI] = 1.07 to 1.49). Cox regression analysis after multiple imputation for missing values showed that metabolic syndrome was associated with CRC incidence (HR = 1.35, 95% CI = 1.17 to 1.56). Metabolic syndrome was also associated with a higher incidence of CRC in individuals with a follow-up period of ≥365 days (HR = 1.33, 95% CI = 1.10 to 1.60). This association was observed when metabolic syndrome was defined according to the International Diabetes Federation criteria (HR = 1.30, 95% CI = 1.09 to 1.55) and the National Cholesterol Education Program Adult Treatment Panel III criteria (HR = 1.39, 95% CI = 1.12 to 1.72). In conclusion, metabolic syndrome was associated with a higher incidence of CRC among individuals aged <50 years. These results could be informative for risk stratification of subsequent CRC among young adults., Competing Interests: Disclosures Research funding and scholarship funds (Hidehiro Kaneko and Katsuhito Fujiu) from Medtronic Japan CO., LTD; Biotronik Japan; SIMPLEX QUANTUM CO., LTD; Boston Scientific Japan CO., LTD; and Fukuda Denshi, Central Tokyo CO., LTD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Stent edge-related restenosis (SER) remains a potential limitation of drug-eluting stent (DES). Hinge motion at the stent edge could lead to mechanical stress and contribute to incidents of SER. We investigated the effect of hinge motion on SER after implantation of current-generation DES in the right coronary artery (RCA), where excessive vessel movement is commonly observed., Methods and results: Of 647 consecutive lesions in the RCA treated with second-generation or later DESs, 426 with follow-up angiography were included in this study. Intravascular imaging analysis was performed for 584 stent edges and reference segments. Binary restenosis occurred in 42 lesions (9.9%), and 55% were SERs. The hinge angle was significantly larger in the SER group than in the other restenosis or the no-restenosis group (17.9° vs. 11.6° and 10.6°, respectively; P<0.001). Lesions with an excessive hinge angle (>11.5°) had an increased rate of target lesion revascularization (19.1% vs. 7.2%; P<0.001) during the median follow-up period of 1,578 days. In per-edge analysis, hinge angle and residual plaque burden were independent predictors of SER. The coexistence of excessive hinge motion and residual plaque burden had a synergistic effect on stenotic progression in quantitative angiographic analysis (P interaction <0.001) at follow-up angiography., Conclusions: Substantial stress determined by angulation at a stent edge and its interaction with residual plaque can be considered as one plausible mechanism for SER.

The effects of empagliflozin, a sodium-glucose co-transporter 2 inhibitor, on neointimal response after drug-eluting-stent (DES) implantation remains unknown. Insufficiently controlled diabetes patients with coronary artery disease planned for DES stenting were consecutively enrolled. The patients were assigned to receive empagliflozin in addition to standard therapy or intensive therapy using other glucose-lowering drugs (oGLD). The primary endpoint was thickness of neointimal hyperplasia (NIH) 12 months after stenting assessed by optical coherence tomography (OCT). A total of 28 patients were analyzed (n = 15 in the empagliflozin group, n = 13 in the oGLD group). The levels of glucose profile were not significantly different between both groups at follow-up [HbA1c; 7.2 ± 0.8 vs 7.3 ± 0.9%, p = 0.46]. In OCT analysis, neointima was significantly less in the empagliflozin group than the oGLD group [mean NIH thickness: 137 ± 32 vs 168 ± 39 μm, p = 0.02]. Changes of systolic and diastolic blood pressure (BP), changes of body mass index, and changes of hematocrit after additional treatment were significantly associated with NIH attenuation, whereas no correlation was observed in changes in blood glucose parameters. Multivariate logistic regression analysis revealed that changes in systolic BP was the strongest predictor for NIH attenuation, followed by changes in diastolic BP. In patients with type 2 diabetes, standard plus empagliflozin attenuated neointimal progression as compared with intensive standard therapy after DES implantation. Our data possibly support a beneficial effect of empagliflozin in type 2 diabetes required for coronary revascularization therapy.

Background: The absence of high quality, large-scale data that indicates definitive mortality benefits does not allow for firm conclusions on the role of intravenous vasodilators in acute heart failure. We aimed to investigate the associations between intravenous vasodilators and clinical outcomes in acute heart failure patients, with a specific focus on patient profiles and type of vasodilators., Methods: Data of 26,212 consecutive patients urgently hospitalised for a primary diagnosis of acute heart failure between 2009 and 2015 were extracted from a government-funded multicentre data registration system. Propensity scores were calculated with multiple imputations and 1:1 matching performed between patients with and without vasodilator use. The primary endpoint was inhospital mortality., Results: On direct comparison of the vasodilator and non-vasodilator groups after propensity score matching, there were no significant differences in the inhospital mortality rates (7.5% vs. 8.8%, respectively; P =0.098) or length of intensive/cardiovascular care unit stay and hospital stay between the two groups. However, there was a substantial difference in baseline systolic blood pressure by vasodilator type; favourable impacts of vasodilator use on inhospital mortality were observed among patients who had higher systolic blood pressures and those who had no atrial fibrillation on admission. Furthermore, when compared to nitrates, the use of carperitide (natriuretic peptide agent) was significantly associated with worse outcomes, especially in patients with intermediate systolic blood pressures., Conclusions: In acute heart failure patients, vasodilator use was not universally associated with improved inhospital outcomes; rather, its effect depended on individual clinical presentation: patients with higher systolic blood pressure and no atrial fibrillation seemed to benefit maximally from vasodilators., Trial Registration: UMIN-CTR identifier, UMIN000013128.