記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/OBJECTIVES: This study aimed to investigate the prevalence of liver damage and its associated non-invasive markers and echocardiographic risk factors in patients who underwent surgery for congenital heart disease. METHODS: This retrospective observational study was conducted at a single tertiary-care university hospital in Niigata, Japan. Of 142 patients (ventricular septal defect [VSD] n = 47, tetralogy of Fallot [TOF] n = 67, Fontan n = 28), 52.8% were male [median age: 22.7 years; VSD (24.3 years), TOF (24.0 years), and Fontan (12.5 years)]. Pediatric patients with liver diseases unrelated to congestive liver disease, such as viral hepatitis and alcoholic liver disease, were excluded. We compared non-invasive liver fibrosis age-invariant biomarkers, such as the aspartate aminotransferase-to-platelet ratio index (APRI), and various serum markers and echocardiographic parameters to assess the prevalence and predictors of hepatic fibrosis. RESULTS: The Fontan circulation group had the highest APRI, followed by the TOF group, while the VSD group had a low risk of APRI elevation. Postoperative TOF patients required monitoring for cirrhosis progression. Inferior vena cava mobility was associated with echocardiographic parameters and fibrosis severity, along with a loss of respiratory variability. The limitations of other cardiac assessments were highlighted by poor anatomical measurements. Gamma-glutamyl transpeptidase (γ-GTP) demonstrated strong discriminatory ability. The optimal cutoff value was 53.0 U/L, suggesting its use as a clinical marker. CONCLUSIONS: Assessing fibrosis is crucial in CHD patients, especially those with late post-TOF repair findings. Non-invasive markers (APRI, γ-GTP, and B-type natriuretic peptide), along with echocardiographic findings, may help detect fibrosis early, enabling timely intervention and improving long-term outcomes. CLINICAL TRIAL REGISTRATION: 2020-0199.

DOI： 10.3390/children12091131

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: The number of patients with heart failure with disability and the use of Long-Term Care Insurance (LTCI) has been increasing in the Japanese aging society. This study investigated the main causes of LTCI demands for better care management. METHODS: We carried out a retrospective study including patients with heart failure with reduced ejection fraction in seven hospitals in Niigata City from 2011 to 2016. Data related to LTCI introduction, such as the main cause and degree of impairments, were collected from official documents for LTCI registration based on the doctor's opinion. Of 3738 patients, 312 were newly eligible for LTCI. RESULTS: LTCI was introduced due to cardiac and non-cardiac diseases in 49.4% and 50.6% of patients, respectively. Physical impairment was milder in the cardiac group than major non-cardiac groups (Kruskal-Wallis test; P < 0.001, Steel test; cardiac vs cancer: P = 0.027 vs stroke: P < 0.001 vs orthopedic: P = 0.002 vs others: P = 0.041). Only the cancer group had a poorer prognosis than the cardiac group (log-rank test with Bonferroni correction; cardiac vs cancer: P < 0.001 vs stroke: P = 0.282 vs orthopedic disease: P = 0.866 vs others: P = 0.476). CONCLUSION: Half of the LTCI users were introduced due to non-cardiac diseases in heart failure patients. The cause of LTCI indicating the degree of the patient's disability and prognosis is valuable information to provide favorable care. Geriatr Gerontol Int 2025; 25: 871-878.

DOI： 10.1111/ggi.70052

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Polypharmacy, driven by guideline-directed medical therapy (GDMT) and medications for comorbidities, including potentially inappropriate medications (PIMs), is common in older adults with heart failure (HF). Although medication profiles affect survival, the effects of frailty and disability status remain underexplored. METHODS AND RESULTS: This retrospective study assessed polypharmacy (≥5 medications), the use of GDMT, and PIMs based on the Beers Criteria. Frailty and disability status were determined using Japan's Long-term Care Insurance (LTCI) certification. Patients were stratified according to LTCI, and the prognostic impact of medication profiles was analyzed. The total medication count was correlated with both GDMT and PIM use. Among 1,264 patients, those with LTCI were older, had more severe comorbidities, higher polypharmacy and PIM use, and lower use of GDMT medications. In multivariate Cox regression analysis, regardless of LTCI, GDMT medication use was associated with a favorable prognosis (LTCI: odds ratio [OR] 0.47, 95% confidence interval [CI] 0.258-0.866, P=0.015; no LTCI: OR 0.57, 95% CI 0.400-0.799, P=0.001). PIM use was associated with a poor prognosis only in the no-LTCI group (OR 1.51; 95% CI 1.040-2.203; P=0.030). CONCLUSIONS: Polypharmacy may have both beneficial and harmful effects, with prognostic implications potentially influenced by frailty and disability status. Although GDMT medications were consistently associated with favorable outcomes, the impact of PIMs appeared to differ depending on LTCI.

DOI： 10.1253/circj.CJ-25-0200

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Catheter ablation (CA) is a standard treatment for atrial fibrillation (AF); however, some patients experience worsening heart failure (WHF) afterward. The H2FPEF and HFA-PEFF scores are validated tools for HFpEF risk stratification, but their predictive value for WHF after CA in patients with preclinical heart failure (HF) remains unclear. METHOD: This retrospective, single-center observational study included 257 AF patients with preserved left ventricular ejection fraction (LVEF) ≥50% and no history or symptoms of HF who underwent first-time CA between February 2017 and September 2022. Patients were classified as high HFpEF score group if they had H2FPEF score ≥6 or HFA-PEFF score ≥5. The primary endpoint was WHF: HF hospitalization, initiation of oral diuretics, or intravenous administration of diuretics. RESULTS: Among 257 patients, 54 (21.01%) were classified as high HFpEF score group. WHF incidence was significantly higher in the high HFpEF score group than in the low HFpEF score group (log-rank p < 0.001), while AF recurrence did not differ significantly (log-rank p = 0.546). In Firth's penalized logistic regression analysis, high HFA-PEFF score (HR 6.52, 95% CI 1.54-23.21, p = 0.014) and AF recurrence (HR 8.18, 95% CI 1.80-77.60, p = 0.005) appeared to be potential independent predictors of WHF. CONCLUSIONS: In this exploratory analysis, the HFA-PEFF score potentially represent an independent predictor of WHF after CA in AF patients with preclinical HF and preserved LVEF.

DOI： 10.3389/fcvm.2025.1704164

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cell-free eosinophil granules, harmful to the heart, are stained red by haematoxylin-eosin (HE); however, they can be overlooked in cardiac tissues. Direct fast scarlet (DFS) and Congo red (CR), known for staining amyloids, may offer clearer detection of eosinophil granules; however, no firm evidence exists. This study aimed to confirm that DFS and CR stain eosinophil granules and evaluate their advantages over HE.Paraffin-embedded endomyocardial biopsy samples from 6 patients with eosinophil-infiltrating cardiac disorders and 6 with lymphocytic myocarditis were stained.The distributions of red granules stained with DFS and CR resembled those stained with HE in serial sections. Eosinophil granules, identified by major basic protein (MBP), were detected in intact eosinophils, identified by galectin-10, using immunofluorescence pre-scanning and were subsequently stained red by HE, DFS, and CR. MBP-positive granules surrounding galectin-10-negative cells with degenerated nuclei, indicative of cytolytic degranulation (ETosis), were also stained by HE, DFS, and CR. Non-granular MBP-positive interstitial areas were not visualised by HE, DFS, or CR, suggesting that they did not detect the deposition of granule proteins released from disrupted granules. Eosinophil granules were identified by extracting the red colour using ImageJ software in DFS-stained images, more specifically than in CR-stained or HE-stained images. Cardiologists counted more eosinophils in DFS-stained sections than in HE-stained serial sections within a certain time without miscounting.DFS staining effectively identifies eosinophils and their cell-free granules in cardiac tissues, outperforming HE and CR. DFS may advance the diagnosis and management of eosinophil-related heart diseases.

DOI： 10.1536/ihj.25-317

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Brown adipose tissue (BAT) plays an important role in energy metabolism because it uses fatty acids for thermogenesis during cold exposure. Preclinical studies found that boysenberry anthocyanins (BoyACs) activate BAT. Therefore, the aim of this preliminary study was to evaluate how BoyAC intake affects BAT in humans. We performed an open-label single-arm nonrandomized study in healthy volunteers. Before and after 4 weeks of daily consumption of 100 ml boysenberry juice (BoyJ) containing 61 mg of BoyACs, participants were assessed at 24 °C and then after 1 h of mild cold exposure (18 °C). An infrared thermography camera was used to measure skin surface temperatures in the supraclavicular BAT region (Tscv) and the non-BAT region of the upper chest (Tch). Energy metabolism was measured by indirect calorimetry. For each endpoint, we calculated Δ as the difference between values before and after cold exposure and compared the values before and after BoyJ intake. 10 volunteers participated (age: 36.1 ± 4.1, body mass index (BMI): 20.9 ± 0.6). After BoyJ intake, ΔTscv-ch was significantly higher (p = 0.029), but Δ energy expenditure, Δ fat oxidation, and Δ carbohydrate oxidation were not significantly different. We found a significant positive correlation between BMI and Δfat oxidation with BoyJ intake. The results indicate that 4 weeks of BoyJ intake activates cold-induced thermogenesis in the scv-BAT but does not have a significant effect on energy metabolism. BoyJ intake may increase fat oxidation during cold exposure in individuals with higher BMI.Trial registry number: UMIN000043476, 05/03/2021.

DOI： 10.1038/s41598-024-76452-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Circulation Society  

BACKGROUND: The ONCO DVT study demonstrated potential benefits of extended edoxaban treatment in patients with isolated distal deep vein thrombosis in terms of thrombotic risk. However, the risk-benefit balance in patients with anemia remains unclear. METHODS AND RESULTS: This prespecified subgroup analysis included 601 patients, divided into anemia (n=402) and no-anemia (n=199) groups. The primary endpoint was symptomatic recurrent venous thromboembolism (VTE) or VTE-related death. Anemia was defined as hemoglobin <12 g/dL for women and <13 g/dL for men. In the anemia subgroup, the primary endpoint occurred in 3 (1.5%) and 17 (8.4%) patients in the 12- and 3-month edoxaban treatment groups, respectively (odds ratio [OR] 0.17; 95% confidence interval [CI] 0.05-0.58), compared with 0 and 5 (4.9%) patients, respectively, in the no-anemia subgroup (P interaction=0.997). Major bleeding occurred in 26 (13.1%) and 17 (8.4%) patients with anemia in the 12- and 3-month edoxaban treatment groups, respectively (OR 1.64; 95% CI 0.86-3.14), compared with 2 (2.1%) and 5 (4.9%) patients without anemia (OR 0.67; 95% CI 0.26-1.73; P interaction=0.13). CONCLUSIONS: Regardless of the presence of anemia, edoxaban treatment for 12 months was superior to treatment for 3 months in reducing thrombotic events, whereas the risk of major bleeding did not differ significantly between the 2 treatment groups.

DOI： 10.1253/circj.cj-24-0571

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Lowering mean pulmonary arterial pressure (mPAP) without reducing cardiac output is essential in treating pulmonary hypertension (PH). Isosorbide dinitrate (ISDN) potentially achieves this in post-capillary PH but can decrease cardiac output and blood pressure (BP), especially in pre-capillary PH. However, post-capillary PH and pre-capillary PH can overlap, and their clear discrimination is difficult. The aim of the study was to examine to what extent bolus ISDN injection reduces mPAP and BP, and changes mixed venous oxygen saturation (SvO2), an indicator of cardiac output in PH with various cardiopulmonary comorbidities in the context of treatment modifications. We retrospectively examined the hemodynamic effects of bolus ISDN injection in patients with PH who underwent right heart catheterization and their subsequent treatment modification. Our sample comprised 13 PH patients. In seven with pre-capillary PH, ISDN significantly lowered mPAP from the median 34 (interquartile range 32-39) to 28 (28-30) mmHg and the mean BP (mBP) from 90 (79-92) to 72 (68-87) mmHg. In six with post-capillary PH, ISDN lowered mPAP from 40 (29-44) to 27 (23-31) mmHg and mBP from 91 (87-110) to 87 (82-104) mmHg. There was a significant decrease in SvO2 from 69.8% (64.9%-78.1%) to 63.9% (60.5%-71.5%) in pre-capillary PH, but not in post-capillary PH including combined post- and pre-capillary PH and some patients showed a large increase in SvO2. In all patients showing an SvO2 increase, diuretics or hemodialysis were up-titrated or continued. Bolus ISDN injection lowered mPAP. However, in pre-capillary PH, it caused a significant decrease in SvO2 and a notable reduction in blood pressure. In post-capillary PH, including combined post- and pre-capillary PH, it clarified whether systemic preload and afterload reduction increased or decreased SvO2 in each patient, which may aid in treatment modification.

DOI： 10.1007/s00380-024-02451-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Trastuzumab has improved breast cancer (BC) prognosis and reduced anthracycline use. However, the characteristic changes of anthracycline-related cardiomyopathy (ARCM) in patients with BC remain unclear. We aimed to update our understanding of ARCM in the trastuzumab era. METHODS: This retrospective observational cohort study included 2959 patients with BC treated with anthracyclines at three regional cancer centers in Niigata City between 1990 and 2020. Seventy-five patients (2.5%) developed ARCM and were categorized into two groups: pre- 2007 (early phase) and post-2007 (late phase), corresponding to before and during the trastuzumab era in Japan. RESULTS: ARCM incidence peaked at 6% in the 1990s, then decreased and stabilized at 2% until the 2010s. Survivors of anthracycline-treated BC increased more rapidly in the late phase, with four times as many patients with ARCM compared to the end of the early phase (26 and six, respectively). Although the rate of change in accumulation from the early phase to the late phase was slight in the anthracycline-treated BC group, it was more pronounced in the ARCM group (P < 0.001). Mean anthracycline use in the late phase was significantly lower than in the early phase (307 vs. 525 mg/m2, P < 0.001). Five-year survival rates in the late phase tended to be higher than early phase (45% and 28%, respectively. P = 0.058). Human epidermal growth factor receptor type 2 (HER2) positivity with trastuzumab therapy in the late phase was an independent predictor for mortality within 10 years (hazard ratio = 0.24, 95% confidence interval: 0.10-0.56; P = 0.001). CONCLUSIONS: HER2-positive patients with ARCM receiving trastuzumab therapy had a better prognosis than HER2-positive and HER2-negative patients with ARCM not receiving trastuzumab therapy, and this trend has been increasing in the trastuzumab era. These findings highlight the importance of HER2-targeted treatments in improving prognosis for BC patients with ARCM.

DOI： 10.1007/s12282-024-01623-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The coagulation response during vascular injury with uninterrupted administration of direct oral anticoagulants has not been elucidated. OBJECTIVE: Our aim was to evaluate differences in coagulation responses after vascular injury between uninterrupted direct thrombin inhibitor and direct factor Xa inhibitor recipients. METHODS: Patients scheduled for catheter ablation for atrial fibrillation were randomly assigned to receive dabigatran or apixaban in this prospective, randomized, comparative, parallel-group study. Venous blood was collected 3 times: 180 minutes after taking the anticoagulant on the day before the procedure, before vascular punctures of the ablation procedure, and 10-15 minutes after the start of vascular punctures. RESULTS: Forty-two patients were enrolled. The prothrombin fragment 1+2 level, the primary end point, was much larger after vascular puncture in the uninterrupted dabigatran recipients (median, 83 pmol/L; interquartile range, 56-133 pmol/L) than in the uninterrupted apixaban recipients (median, 1 pmol/L; interquartile range, -3 to 19 pmol/L; P < .001). Antithrombin levels decreased after vascular puncture in dabigatran recipients, and both protein C and antithrombin levels decreased after vascular puncture in apixaban recipients. CONCLUSION: Unlike uninterrupted apixaban, uninterrupted dabigatran does not inhibit thrombin generation in response to vascular injury.

DOI： 10.1016/j.hrthm.2024.07.017

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death with type 2 diabetes; however, their effect on arrhythmias is unclear. The purpose of this study was to investigate the effects of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes. METHODS: A total of 150 patients with type 2 diabetes who were treated with an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator (ICD/CRT-D) were randomized to once-daily empagliflozin or placebo for 24 weeks. The primary endpoint was the change in the number of ventricular arrhythmias from the 24 weeks before to the 24 weeks during treatment. Secondary endpoints included the change in the number of appropriate device discharges and other values. RESULTS: In the empagliflozin group, the number of ventricular arrhythmias recorded by ICD/CRT-D decreased by 1.69 during treatment compared to before treatment, while in the placebo group, the number increased by 1.79. The coefficient for the between-group difference was - 1.07 (95% confidence interval [CI] - 1.29 to - 0.86; P < 0.001). The change in the number of appropriate device discharges during and before treatment was 0.06 in the empagliflozin group and 0.27 in the placebo group, with no significant difference between the groups (P = 0.204). Empagliflozin was associated with an increase in blood ketones and hematocrit and a decrease in blood brain natriuretic peptide and body weight. CONCLUSIONS: In patients with type 2 diabetes treated with ICD/CRT-D, empagliflozin reduces the number of ventricular arrhythmias compared with placebo. Trial registration jRCTs031180120.

DOI： 10.1186/s12933-024-02309-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

It has been reported that accumulation of senescent cells in various tissues contributes to pathological aging and that elimination of senescent cells (senolysis) improves age-associated pathologies. Here, we demonstrate that inhibition of sodium-glucose co-transporter 2 (SGLT2) enhances clearance of senescent cells, thereby ameliorating age-associated phenotypic changes. In a mouse model of dietary obesity, short-term treatment with the SGLT2 inhibitor canagliflozin reduced the senescence load in visceral adipose tissue and improved adipose tissue inflammation and metabolic dysfunction, but normalization of plasma glucose by insulin treatment had no effect on senescent cells. Canagliflozin extended the lifespan of mice with premature aging even when treatment was started in middle age. Metabolomic analyses revealed that short-term treatment with canagliflozin upregulated 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, enhancing immune-mediated clearance of senescent cells by downregulating expression of programmed cell death-ligand 1. These findings suggest that inhibition of SGLT2 has an indirect senolytic effect by enhancing endogenous immunosurveillance of senescent cells.

DOI： 10.1038/s43587-024-00642-y

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記述言語：英語  

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/FJC.0000000000001430

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective Spontaneous mechanical alternans (MA), or pulsus alternans, has been observed in heart failure patients with hypertension or tachycardia for 150 years and is considered a sign of a poor prognosis. However, in some dilated cardiomyopathy (DCM) patients with MA, optimal medical therapy (OMT) brings left ventricular reverse remodeling (LVRR), a preferable prognostic indicator. This study examined the probability of LVRR in DCM patients with spontaneous MA and whether or not LVRR can be predicted by the baseline blood pressure or heart rate. Methods We conducted a single-center, retrospective observational study of newly diagnosed DCM patients from January 2017 to December 2020. Results Thirty-three newly diagnosed DCM patients were retrospectively examined. Spontaneous MA was observed during diagnostic cardiac catheterization in at least 1 of the pressure waveforms of the aorta, left ventricle, pulmonary artery, or right ventricle in 10 patients (30%) (MA-group). LVRR after OMT was achieved roughly equally in the MA group (6 of 10, 60%) and the non-MA group (12 of 23, 52%). In the MA group, those who achieved LVRR had a significantly higher baseline systolic aortic pressure (more than 120 mmHg in all 6 patients) than those who did not, although the baseline heart rate did not show a significant correlation with LVRR. In contrast, in the non-MA group, LVRR was unrelated to the baseline aortic pressure or heart rate. Conclusion The probability of LVRR in newly-diagnosed DCM patients with spontaneous MA was similar to that in those without spontaneous MA. Spontaneous MA may not necessarily be a sign of a poor prognosis if observed in patients with a preserved blood pressure.

DOI： 10.2169/internalmedicine.0711-22

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

UNLABELLED: A 45-year-old woman with no medical history underwent pacemaker implantation for a symptomatic complete atrioventricular block. On day 6, she noticed diplopia and then fever, general malaise, and elevation of serum creatinine kinase (CK). She was transferred to our hospital on day 21. Serum CK was elevated to 4543 IU/L, and echocardiography revealed a left ventricular ejection fraction of 43 %. We diagnosed her with giant cell myocarditis (GCM) via an emergent myocardial biopsy that revealed a proliferation of lymphocytes, eosinophils, and giant cells without granulomas. Initial treatment with high doses of intravenous methylprednisolone and immunoglobulin improved her symptoms in a few days, and prednisolone was given as follow-up treatment. CK was normalized in a week and a thinning of the interventricular septum mimicking cardiac sarcoidosis (CS) occurred. On day 38, we added a calcineurin inhibitor, tacrolimus, and maintained her with a combination of prednisolone and tacrolimus at a target dose of 10-15 ng/mL. Six months after the onset, there were no signs of relapse despite the persistent mild elevation of troponin I levels. We present a case of GCM mimicking CS successfully maintained by a combination of two immunosuppressive agents. LEARNING OBJECTIVE: Recommended treatment for giant cell myocarditis (GCM), a potentially fatal disease, is a combination of three immunosuppressive agents. However, GCM shares many characteristics with cardiac sarcoidosis (CS), which is treated using prednisolone alone in many cases. Recent studies on GCM and CS suggest they are different spectrums of a common entity. Although they can clinically overlap, they have different progressive speeds and severities. We present a case of GCM mimicking CS successfully treated with a combination of two immunosuppressive agents.

DOI： 10.1016/j.jccase.2023.01.009

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Immunosuppressive therapy with prednisolone (PSL) is the first-line treatment for cardiac sarcoidosis (CS), and 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) is used to evaluate its efficacy to guide treatment. However, the appropriate timing of FDG-PET in CS remains unknown. This single-center, retrospective, observational study included 15 consecutive CS patients who underwent 3 serial FDG-PET scans (at baseline, in the early phase [1-2 months after PSL introduction], and in the late phase [≥ 5 months after PSL introduction with a maintenance dose of PSL]). We adhered to the PSL tapering protocol by the Japanese Circulation Society even when early FDG-PET showed positive results (SUVmax ≥ 4.0). No patient died during the 908 (644-1600) days of observation. Negative results in the late phase were observed in 3 of 6 early-positive patients, and 3 of 9 early-negative patients showed positive results in the late phase. Changes in echocardiographic parameters from baseline to the late phase were significantly better in late-negative patients than in late-positive patients (left ventricular end-diastolic diameter: -0.7 (-9.3-[-0.5]) mm versus +3.5 (0.8-7.5) mm, P = 0.039; left ventricular end-systolic diameter: -4.2 (-6.9-[-0.1]) mm versus +5.1 (0.5-7.0) mm, P = 0.015; left ventricular ejection fraction: +4.7% (-1.0-9.0%) versus -1.5% (-11.3-1.5%), P = 0.045) ), although early FDG-PET did not predict those consequent changes. An interval of ≥ 5 months after introducing the PSL with a maintenance dose of PSL is long enough for FDG-PET to reflect consequent left ventricular functions, while an interval of 1-2 months can be too short.

DOI： 10.1536/ihj.22-406

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although guideline-directed medical therapy (GDMT), including β-blockers, angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs), improves survival and quality of life, most patients with heart failure with reduced (HFrEF) and mildly reduced (HFmrEF) ejection fraction are treated with inadequate medications. We investigated the prescription patterns of GDMT in elderly patients with HFrEF and HFmrEF and their characteristics, including the certification of long-term care insurance (LTCI), which represents frailty and disability.Methods and Results: This retrospective cross-sectional study analyzed 1,296 elderly patients with symptomatic HFrEF and HFmrEF with diuretic use (median age 78 years; 63.8% male; median left ventricular ejection fraction 40%). Prescription rates of GDMT were inadequate (ACEi, ARBs, β-blockers, and MRAs: 27.0%, 30.1%, 54.1%, and 41.9%, respectively). LTCI certification was independently associated with reduced prescription of all medications (ACEi/ARB: odds ratio [OR] 0.591, 95% confidence interval [CI] 0.449-0.778, P=0.001; β-blockers: OR 0.698, 95% CI 0.529-0.920, P<0.001; MRAs: OR 0.743, 95% CI 0.560-0.985, P=0.052). Patients with LTCI certification also had a high prevalence of polypharmacy and prescription of diuretics. CONCLUSIONS: Vulnerable patients with LTCI may be an explanation for the challenges in implementing GDMT, and communicating is required for favorable heart failure care in this population.

DOI： 10.1253/circj.CJ-22-0830

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記述言語：英語  

J-GLOBAL

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語  

J-GLOBAL

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Vascular Ehlers-Danlos syndrome (vEDS) is a hereditary connective tissue disorder (HCTD) characterized by arterial dissection/aneurysm/rupture, sigmoid colon rupture, or uterine rupture. Diagnosis is confirmed by detecting heterozygous variants in COL3A1. This is the largest Asian case series and the first to apply an amplification-based next-generation sequencing through custom panels of causative genes for HCTDs, including a specific method of evaluating copy number variations. Among 429 patients with suspected HCTDs analyzed, 101 were suspected to have vEDS, and 33 of them (32.4%) were found to have COL3A1 variants. Two patients with a clinical diagnosis of Loeys-Dietz syndrome and/or familial thoracic aortic aneurysm and dissection were also found to have COL3A1 variants. Twenty cases (57.1%) had missense variants leading to glycine (Gly) substitutions in the triple helical domain, one (2.9%) had a missense variant leading to non-Gly substitution in this domain, eight (22.9%) had splice site alterations, three (8.6%) had nonsense variants, two (5.7%) had in-frame deletions, and one (2.9%) had a multi-exon deletion, including two deceased patients analyzed with formalin-fixed and paraffin-embedded samples. This is a clinically useful system to detect a wide spectrum of variants from various types of samples.

DOI： 10.1002/ajmg.a.62982

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本門脈圧亢進症学会  

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記述言語：日本語   出版者・発行元：(一社)日本門脈圧亢進症学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

Brown adipose tissue (BAT) has a role in maintaining systemic metabolic health in rodents and humans. Here, we show that metabolic stress induces BAT to produce coagulation factors, which then-together with molecules derived from the circulation-promote BAT dysfunction and systemic glucose intolerance. When mice were fed a high-fat diet (HFD), the levels of tissue factor, coagulation Factor VII (FVII), activated coagulation Factor X (FXa), and protease-activated receptor 1 (PAR1) expression increased significantly in BAT. Genetic or pharmacological suppression of coagulation factor-PAR1 signaling in BAT ameliorated its whitening and improved thermogenic response and systemic glucose intolerance in mice with dietary obesity. Conversely, the activation of coagulation factor-PAR1 signaling in BAT caused mitochondrial dysfunction in brown adipocytes and systemic glucose intolerance in mice fed normal chow. These results indicate that BAT produces endogenous coagulation factors that mediate pleiotropic effects via PAR1 signaling under metabolic stress.

DOI： 10.1016/j.isci.2022.104547

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: In patients with chronic heart failure (CHF) and type 2 diabetes (T2D), sodium-glucose cotransporter-2 (SGLT2) inhibition improves cardiorenal outcomes, but details of the effects on distinct subsets of body fluid volume remain incomplete. METHODS: This was a post hoc analysis of patients with CHF and T2D in the CANDLE trial (UMIN000017669), an investigator-initiated, multi-center, randomized open-label trial that compared the effect of canagliflozin (100 mg, n = 113) with glimepiride (starting dose: 0.5 mg, n = 120) on changes in N-terminal pro-brain natriuretic peptide. The estimated plasma volume (ePV, calculated with the Straus formula) and estimated extracellular volume (eEV, determined by the body surface area) were compared between treatment groups at weeks 4, 12, and 24. RESULTS: Among 233 patients analyzed, 166 (71.2%) had an ejection fraction (EF) > 50%. Reductions in ePV and eEV were observed only in the canagliflozin group until week 12 (change from baseline at week 12, ePV; - 7.63%; 95% confidence interval [CI], - 10.71 to - 4.55%, p < 0.001, eEV; - 123.15 mL; 95% CI, - 190.38 to - 55.92 mL, p < 0.001). While ePV stopped falling after week 12, eEV continued to fall until week 24 ([change from baseline at week 24] - [change from baseline at week 12], ePV; 1.01%; 95%CI, - 2.30-4.32%, p = 0.549, eEV; - 125.15 mL; 95% CI, - 184.35 to - 65.95 mL, p < 0.001). CONCLUSIONS: Maintenance of a modest reduction in ePV and continuous removal of eEV via chronic SGLT2 inhibition suggests that favorable body fluid regulation contributes to the cardiorenal benefits of SGLT2 inhibitors in patients with CHF, irrespective of EF. TRIAL REGISTRATION: UMIN000017669.

DOI： 10.1007/s00392-022-02049-4

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本循環器病予防学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

J-GLOBAL

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Since permanent inferior vena cava (IVC) filters increase deep vein thrombosis (DVT), filter retrieval should be performed as possible. Despite the guideline recommendation, IVC filters are not always retrieved in clinical practice. To date, many patients with not-retrieval IVC filters have been prescribed anticoagulant therapy, but the long-term prognosis, including venous thromboembolism (VTE) and bleeding events, remains unknown. In this study, 195 patients who underwent IVC filter implantation between 2006 and 2017 at 3 institutions in Niigata City have been investigated about their deaths, VTE recurrence, and bleeding events. After peaking 2009, the number of IVC filter implantation gradually decreased. During observational period, there were 158 patients with not-retrieval IVC filters (the overall retrieval rate of 19.0%). The not-retrieval group included significantly older and more patients with cancer compared to the retrieval group. Anticoagulation therapy was continued in 88% of the not-retrieval group. During a mean follow-up of 5.0 years, 6 symptomatic DVT events associated with inadequate control of anticoagulation and 13 bleeding events were observed. A total of 52 patients died and only the presence of cancer was prognostic risk factor. Although long-term anticoagulation therapy may be associated with bleeding events, there were few recurrent VTE under optimal anticoagulation. It is anticipated that even if the IVC filter cannot be retrieved, appropriate anticoagulation is useful for prevention of DVT recurrence despite the risk of bleeding.

DOI： 10.1536/ihj.21-814

PubMed

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1253/circj.cj-21-0580

Web of Science

PubMed

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background Frailty is a multifactorial physiological syndrome most often associated with age but which has received increasing recognition as a component of chronic illnesses such as heart failure. Patients with heart failure are likely to be frail, irrespective of their age. Adipokine dysregulation, which is associated with frailty, occurs in patients with heart failure. In this study, we tested the hypothesis that adipokines are associated with frailty in patients with heart failure. Methods Thirty-five patients with heart failure (age, 67 ± 14 years; 25 males; left ventricular ejection fraction, 45 ± 19%) were included. Serum adipokine levels, physical performance, and body composition were measured. Results Adiponectin and leptin were inversely correlated with grip strength. Adiponectin was inversely correlated with bone mineral density. Leptin was positively correlated with fat mass. Adipokines were not correlated with skeletal muscle mass. Conclusions Adipokines were associated with frailty in patients with heart failure. Adipokine dysregulation may play a role in the development of frailty in heart failure.

DOI： 10.23750/abm.v92i3.9228

PubMed

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s13300-020-00924-9

Web of Science

PubMed

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その他リンク： http://link.springer.com/article/10.1007/s13300-020-00924-9/fulltext.html

記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語  

Web of Science

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1536/ihj.15-374

Web of Science

PubMed

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記述言語：英語  

DOI： 10.1016/j.cardfail.2015.08.120

Web of Science

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記述言語：英語  

DOI： 10.1016/j.cardfail.2014.07.428

Web of Science

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記述言語：英語  

DOI： 10.1016/j.cardfail.2013.08.442

Web of Science

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A protein crystal lattice consists of surface contact regions, where the interactions of specific groups play a key role in stabilizing the regular arrangement of the protein molecules. In an attempt to control protein incorporation in a crystal lattice, a leucine zipper-like hydrophobic interface (comprising four leucine residues) was introduced into a helical region (helix 2) of the human pancreatic ribonuclease 1 (RNase 1) that was predicted to form a suitable crystallization interface. Although crystallization of wild-type RNase 1 has not yet been reported, the RNase 1 mutant having four leucines (4L-RNase 1) was successfully crystallized under several different conditions. The crystal structures were subsequently determined by X-ray crystallography by molecular replacement using the structure of bovine RNase A. The overall structure of 4L-RNase 1 is quite similar to that of the bovine RNase A, and the introduced leucine residues formed the designed crystal interface. To characterize the role of the introduced leucine residues in crystallization of RNase 1 further, the number of leucines was reduced to three or two (3L- and 2L-RNase 1, respectively). Both mutants crystallized and a similar hydrophobic interface as in 4L-RNase 1 was observed. A related approach to engineer crystal contacts at helix 3 of RNase 1 (N4L-RNase 1) was also evaluated. N4L-RNase 1 also successfully crystallized and formed the expected hydrophobic packing interface. These results suggest that appropriate introduction of a leucine zipper-like hydrophobic interface can promote intermolecular symmetry for more efficient protein crystallization in crystal lattice engineering efforts.

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本循環器学会  

J-GLOBAL

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記述言語：英語  

J-GLOBAL

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記述言語：英語  

J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本在宅医療連合学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：株式会社 医学書院  

DOI： 10.11477/mf.1438200693

CiNii Books

J-GLOBAL

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記述言語：英語  

J-GLOBAL

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語  

J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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J-GLOBAL

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J-GLOBAL

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本抗加齢医学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：日本語   出版者・発行元：メディカルレビュー社  

CiNii Article

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その他リンク： http://search.jamas.or.jp/link/ui/2020297787

記述言語：日本語   出版者・発行元：科学評論社  

CiNii Article

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2020230859

記述言語：日本語   出版者・発行元：(一社)日本病態栄養学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：日本語   出版者・発行元：(一社)日本病態栄養学会  

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記述言語：日本語   出版者・発行元：(一社)日本肥満学会  

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記述言語：日本語   出版者・発行元：(一社)日本肥満学会  

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記述言語：日本語   出版者・発行元：(公財)日本心臓財団  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00679&link_issn=&doc_id=20170420180017&doc_link_id=%2Fah2sinzd%2F2017%2F004904%2F019%2F0405-0410%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fah2sinzd%2F2017%2F004904%2F019%2F0405-0410%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：新潟医学会  

CiNii Article

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その他リンク： https://niigata-u.repo.nii.ac.jp/records/8337

記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本循環器病予防学会  

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記述言語：日本語   出版者・発行元：(一社)日本循環器病予防学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

CiNii Article

CiNii Books

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その他リンク： https://niigata-u.repo.nii.ac.jp/records/8554

記述言語：日本語   出版者・発行元：新潟医学会  

CiNii Article

CiNii Books

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その他リンク： https://niigata-u.repo.nii.ac.jp/records/8560

記述言語：日本語   出版者・発行元：(一社)日本集中治療医学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

CiNii Article

CiNii Books

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その他リンク： https://niigata-u.repo.nii.ac.jp/records/9708

会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

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会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

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会議種別：シンポジウム・ワークショップ パネル（公募）  

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会議種別：シンポジウム・ワークショップ パネル（指名）  

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