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NISHIMORI MakotoGraduate School of Medicine / Faculty of Medical SciencesAssistant Professor
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■ Paper- BACKGROUND: ATP citrate lyase (ACLY) is a key enzyme in de novo lipogenesis that generates acetyl-CoA from citrate. Although fatty acids are required for energy production and biomass synthesis in the heart, the regulatory mechanisms of ACLY-mediated de novo lipogenesis in pathological cardiac fibroblasts remain unknown. The aim of this study was to investigate the biological role of ACLY in cardiac remodeling. METHODS: Adeno-associated virus serotype 9-mediated shRNA targeting Acly was intravenously injected into C57BL/6J male mice. The mice were subsequently continuously infused with a mixture of angiotensin II and phenylephrine. Cardiac phenotypes were evaluated via histological staining. Cell proliferation assays, stable isotope tracing with 13C-labeled glucose, and chromatin immunoprecipitation assays were performed using human cardiac fibroblasts. RESULTS: ACLY expression was upregulated in the heart sections of mice treated with angiotensin II/phenylephrine, in particular in fibrotic areas. Masson trichrome staining revealed that Acly gene silencing significantly reduced cardiac fibrosis in these mice. Both siRNA-mediated ACLY knockdown and pharmacological ACLY inhibition suppressed the proliferation and expression of fibrous proteins in cultured human cardiac fibroblasts stimulated with transforming growth factor-β. Mechanistically, ACLY inhibition reduced de novo lipogenesis, limiting the fatty acid supply essential for cellular growth and proliferation. It also decreased H3K9 and H3K27 acetylation, in addition to the presence of acetylated H3K9 and H3K27 at the promoter regions of fibrotic genes. CONCLUSIONS: Our findings demonstrate that ACLY plays an important role in maladaptive cardiac fibrosis. ACLY could be a novel therapeutic target to prevent the development of heart failure.Ovid Technologies (Wolters Kluwer Health), Mar. 2025, Hypertension, English, International magazineScientific journal
- AIMS: Optical coherence tomography (OCT) can identify high-risk plaques indicative of worsening prognosis in patients with acute coronary syndrome (ACS). However, manual OCT analysis has several limitations. In this study, we aim to construct a deep-learning model capable of automatically predicting ACS prognosis from patient OCT images following percutaneous coronary intervention (PCI). METHODS AND RESULTS: Post-PCI OCT images from 418 patients with ACS were input into a deep-learning model comprising a convolutional neural network (CNN) and transformer. The primary endpoint was target vessel failure (TVF). Model performances were evaluated using Harrell's C-index and compared against conventional models based on human observation of quantitative (minimum lumen area, minimum stent area, average reference lumen area, stent expansion ratio, and lesion length) and qualitative (irregular protrusion, stent thrombus, malapposition, major stent edge dissection, and thin-cap fibroatheroma) factors. GradCAM activation maps were created after extracting attention layers by using the transformer architecture. A total of 60 patients experienced TVF during follow-up (median 961 days). The C-index for predicting TVF was 0.796 in the deep-learning model, which was significantly higher than that of the conventional model comprising only quantitative factors (C-index: 0.640) and comparable to that of the conventional model, including both quantitative and qualitative factors (C-index: 0.789). GradCAM heat maps revealed high activation corresponding to well-known high-risk OCT features. CONCLUSION: The CNN and transformer-based deep-learning model enabled fully automatic prognostic prediction in patients with ACS, with a predictive ability comparable to a conventional survival model using manual human analysis. CLINICAL TRIAL REGISTRATION: The study was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN000049237).Nov. 2024, European heart journal. Digital health, 5(6) (6), 692 - 701, English, International magazineScientific journal
- AIMS: Several algorithms can differentiate inferior axis premature ventricular contractions (PVCs) originating from the right side and left side on 12-lead electrocardiograms (ECGs). However, it is unclear whether distinguishing the origin should rely solely on PVC or incorporate sinus rhythm (SR). We compared the dual-rhythm model (incorporating both SR and PVC) to the PVC model (using PVC alone) and quantified the contribution of each ECG lead in predicting the PVC origin for each cardiac rotation. METHODS AND RESULTS: This multicentre study enrolled 593 patients from 11 centres-493 from Japan and Germany, and 100 from Belgium, which were used as the external validation data set. Using a hybrid approach combining a Resnet50-based convolutional neural network and a transformer model, we developed two variants-the PVC and dual-rhythm models-to predict PVC origin. In the external validation data set, the dual-rhythm model outperformed the PVC model in accuracy (0.84 vs. 0.74, respectively; P < 0.01), precision (0.73 vs. 0.55, respectively; P < 0.01), specificity (0.87 vs. 0.68, respectively; P < 0.01), area under the receiver operating characteristic curve (0.91 vs. 0.86, respectively; P = 0.03), and F1-score (0.77 vs. 0.68, respectively; P = 0.03). The contributions to PVC origin prediction were 77.3% for PVC and 22.7% for the SR. However, in patients with counterclockwise rotation, SR had a greater contribution in predicting the origin of right-sided PVC. CONCLUSION: Our deep learning-based model, incorporating both PVC and SR morphologies, resulted in a higher prediction accuracy for PVC origin, considering SR is particularly important for predicting right-sided origin in patients with counterclockwise rotation.Oct. 2024, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 26(10) (10), English, International magazineScientific journal
- Sep. 2024, SCIENTIFIC REPORTS, 14(1) (1), 20508 - 20508, English, International magazineScientific journal
- Anterior Atlas Fracture After C1 Laminectomy Which Was Successfully Treated by Brace Therapy: A Case Report.CASE: We report a case of a 67-year-old male patient who underwent a C1 laminectomy with laminoplasty at C2-3 because of cervical ossification of the posterior longitudinal ligament. At 6 weeks after surgery, neck pain occurred after minor trauma without neurological deterioration. Computed tomography (CT) demonstrated C1 anterior atlas fracture with a 3-mm gap. After a 3-month brace therapy using a Philadelphia collar, the patient's neck pain disappeared with complete bone union according to the CT. CONCLUSION: Among 14 cases that were reported previously, none of the adult patients achieved bone union by brace therapy. Therefore, this is the only case report in which bone union could be achieved by brace therapy.Jul. 2021, JBJS case connector, 11(3) (3), English, International magazineScientific journal
- INTRODUCTION: Surgeons need precise information about motor deterioration risk during surgery for intramedullary spinal cord tumors (IMSCTs). However, the conventional TcMsEP alarm criterion provides limited information with a less than or a more than single alarm criterion without any grades in between, resulting in false-negative and false-positive outcomes. Therefore, we developed a "seven-color TcMsEP grading system" for neuromonitoring to provide more graded information. This study investigates the system's efficacy. METHODS: This study included 60 patients that underwent resection surgeries for IMSCTs. TcMsEP outcomes were classified into seven grades: Grade "D-0 Green" includes a wave amplitude decrease of 0%-50% compared with the baseline amplitude. Grade "D-1 Lime" includes a 50%-70% decrease. Grade "D-2 Yellow" includes a 70%-90% decrease. Grade "D-3 Orange" includes a more than 90% decrease with a clearly visible waveform. Grade "D-4 Red" includes a minimal and abnormally shaped wave. The severest, grade "D-5 Black," includes a wave that has completely disappeared. The additional grade "D-X Gray" includes cases in which the baseline wave is undetectable. Postoperative motor deterioration was evaluated in the upper limbs (PUMD) and lower limbs (PLMD) individually. RESULTS: PLMD only occurred in cases with more than a 90% wave amplitude decrease (from D-3 to D-5) and with the undetectable baseline wave (D-X). The PLMD rate increased according to the severity of the amplitude decreases (29% in D-3, 67% in D-4, 80% in D-5). Most PUMD occurred in cases with more than a 90% decrease, but one case with grade D1 had PUMD. CONCLUSIONS: The seven-color graded alarm criterion supports surgeons' decisions on how to treat the wave amplitude decrease during surgery. It provides motor deterioration risk in each grade without false negatives. Moreover, the corresponding colors enable quick comprehension of the risks.2021, Spine surgery and related research, 5(4) (4), 238 - 243, English, Domestic magazineScientific journal
- OBJECTIVE: Sub-Saharan Africa remains the region most heavily affected by HIV infection. This study aimed to evaluate the knowledge, attitudes, and practices of Congolese students of risk behaviors for sexual transmission of HIV in comparison with their Japanese counterparts. METHODS: Of the 1,747 undergraduate students who participated in the survey, there were 1,326 respondents (752 Japanese, 574 Congolese) who voluntarily and fully filled out the auto-administered questionnaire. RESULTS: The proportion of Congolese respondents who do not always use condoms with an occasional sex partner was significantly higher, 57%, as compared with their Japanese counterparts (15%; p < 0.001). Fewer than 40% (9.9-39.7%) of Congolese respondents had accurate knowledge about multiple sex partnership (MSP), men sex with men (MSM), precocious sex, and commercial sex work (CSW) being high-risk behaviors (p < 0.001) for the sexual transmission of HIV infection. However, the proportion of Congolese tested or willing to get tested for HIV was significantly higher (97.2%) than that in the Japanese group (72.4%, p < 0.001). In Congolese students, we observed an absence of adherence to preventive measures such as condom use with an occasional sex partner, and a greater proportion of students having inaccurate knowledge of major risk behaviors such as MSM, precocious sex, and MSP, compared with their Japanese counterparts. CONCLUSIONS: This study showed that, though sexual contact remains the main mode of HIV transmission in the region, Congolese students tend to have inaccurate knowledge of risk behaviors that expose people to the sexual transmission of HIV. This suggests that continuous education targeting those risk behaviors is of great importance to reduce the spread of the HIV epidemic.Mar. 2012, Environmental health and preventive medicine, 17(2) (2), 139 - 46, English, Domestic magazineScientific journal
- BACKGROUND: Although low high-density lipoprotein cholesterol (HDL-C) levels are a common metabolic abnormality associated with insulin resistance, their role in cardiovascular risk stratification remains controversial. Recently, we developed a simple, high-throughput, cell-free assay system to evaluate the "cholesterol uptake capacity (CUC)" as a novel concept for HDL functionality. In this study, we assessed the CUC in patients with hypertriglyceridemia and diabetes mellitus. METHODS: The CUC was measured using cryopreserved serum samples from 285 patients who underwent coronary angiography or percutaneous coronary intervention between December 2014 and May 2019 at Kobe University Hospital. RESULTS: The CUC was significantly lower in diabetic patients (n = 125) than in nondiabetic patients (93.0 vs 100.7 arbitrary units (A.U.), P = 0.002). Patients with serum triglyceride (TG) levels >150 mg/dL (n = 94) also had a significantly lower CUC (91.8 vs 100.0 A.U., P = 0.004). Furthermore, the CUC showed a significant inverse correlation with TG, hemoglobin A1c (Hb A1c), homeostasis model assessment of insulin resistance (HOMA-IR), and body mass index (BMI). Finally, the HDL-C/Apolipoprotein A1 (ApoA1) ratio, calculated as a surrogate index of HDL particle size, was significantly positively correlated with the CUC (r2 = 0.49, P < 0.001), but inversely correlated with TG levels (r2 = -0.30, P < 0.001). CONCLUSIONS: The CUC decreased in patients with hypertriglyceridemia and diabetes mellitus, and HDL particle size was a factor defining the CUC and inversely correlated with TG levels, suggesting that impaired CUC in insulin-resistant states was partially due to the shift in HDL towards smaller particles. These findings provide a better understanding of the mechanisms underlying impaired HDL functionality.01 Jul. 2024, The journal of applied laboratory medicine, 9(4) (4), 728 - 740, English, International magazine
- Background: Left ventricular (LV) longitudinal myocardial function is associated with the outcomes of heart failure (HF) patients. HF with improved ejection fraction (EF), known as HFimpEF, which is defined as current LVEF >40% but any previously documented LVEF ≤40%, has favorable outcomes compared with HF with preserved EF (HFpEF). However, LV longitudinal myocardial function in patients with previously reduced LVEF (<50%) but improved LVEF to within the normal range (≥50%) (HFnorEF) and its association with cardiovascular events remain unclear. Methods and Results: We studied 70 patients with HFpEF and 65 with HFnorEF. LV longitudinal myocardial function was assessed as global longitudinal strain (GLS). The primary endpoint was defined as cardiovascular death or HF hospitalization during follow-up of 5.6±3.1 years. The GLS of HFpEF patients was significantly lower than that of HFnorEF patients (13.6±3.5% vs. 14.8±2.2%, P=0.02) even when the LVEF was similar. Multivariate Cox proportional hazards analysis showed that GLS was independently associated with cardiovascular events. Furthermore, of the entire study population, patients with GLS >15.0% had fewer cardiovascular events than those without (log-rank P=0.014) among all the patients. Conclusions: LV longitudinal myocardial dysfunction was more frequently observed in patients with HFpEF than in those with HFnorEF, even when LVEF was similar, and was independently associated with cardiovascular events for HF patients with current LVEF ≥50%.10 May 2024, Circulation reports, 6(5) (5), 161 - 167, English, Domestic magazine
- BACKGROUND: Detection of left ventricular (LV) abnormalities is essential for patients with preclinical heart failure (HF) to delay progression to clinical HF. Global longitudinal strain (GLS) is a sensitive marker for the early occurrence of subtle abnormalities in LV function, but not all echocardiographic instruments can measure GLS.Methods and Results: We studied 853 preclinical HF patients to devise a scoring system for predicting low GLS (<16%). The associations of medical history and echocardiographic parameters with low GLS were evaluated using Cox proportional hazards analysis. Model 1 of the system consisted of medical history; for Model 2, conventional echocardiographic parameters were added to Model 1. For Model 1, a score ≥5 points meant prediction of low GLS with 90.2% sensitivity and 62.9% specificity (male=1 point, hypertension=4 points, dyslipidemia=1 point, atrial fibrillation=2 points, history of cardiac surgery=2 points). For Model 2, a score ≥4 points denotes prediction of low GLS with 80.3% sensitivity and 76.5% specificity (male=1 point, hypertension=2 points, atrial fibrillation=2 points, LV mass index >116 g/m2[male] or >96 g/m2[female]=1 point, LV ejection fraction <59%=2 points, E/e' >14=1 point). CONCLUSIONS: Our scoring system provides an easy-to-use evaluation of LV longitudinal myocardial dysfunction, and may prove useful for risk stratification of patients with preclinical HF.25 Apr. 2024, Circulation journal : official journal of the Japanese Circulation Society, 88(5) (5), 703 - 710, English, Domestic magazine
- Stress has garnered significant attention as a prominent risk factor for inflammation-related diseases, particularly cardiovascular diseases (CVDs). However, the precise mechanisms underlying stress-driven CVDs remain elusive, thereby impeding the development of preventive and therapeutic strategies. To explore the correlation between plasma lipid metabolites and human depressive states, liquid chromatography-mass spectrometry (LC/MS) based analysis of plasma and the self-rating depression (SDS) scale questionnaire were employed. We also used a mouse model with restraint stress to study its effects on plasma lipid metabolites and stenotic vascular remodeling following carotid ligation. In vitro functional and mechanistic studies were performed using macrophages, endothelial cells, and neutrophil cells. We revealed a significant association between depressive state and reduced plasma levels of 4-oxoDHA, a specific omega-3 fatty acid metabolite biosynthesized by 5-lipoxygenase (LO), mainly in neutrophils. In mice, restraint stress decreased plasma 4-oxoDHA levels and exacerbated stenotic vascular remodeling, ameliorated by 4-oxoDHA supplementation. 4-oxoDHA enhanced Nrf2-HO-1 pathways, exerting anti-inflammatory effects on endothelial cells and macrophages. One of the stress hormones, noradrenaline, reduced 4-oxoDHA and the degraded 5-LO in neutrophils through the proteasome system, facilitated by dopamine D2-like receptor activation. Our study proposed circulating 4-oxoDHA levels as a stress biomarker and supplementation of 4-oxoDHA as a novel therapeutic approach for controlling stress-related vascular inflammation.20 Feb. 2024, Scientific reports, 14(1) (1), 4178 - 4178, English, International magazine
- Sacubitril/valsartan has become an important first-line drug for symptomatic heart failure (HF) patients, especially with left ventricular (LV) ejection fraction (LVEF) < 50%. However, the impact of sacubitril/valsartan on cardiovascular outcomes, especially LV reverse remodeling for such patients with low blood pressure, remains uncertain. We retrospectively studied 164 HF patients with LVEF < 50% who were treated with sacubitril/valsartan from two institutions. Echocardiography was performed before and 9.5 ± 5.1 months after initiation of maximum tolerated dose of sacubitril/valsartan. The maximum tolerated dose of sacubitril/valsartan was lower for the low blood pressure group (≤ 100 mmHg in systole) than for the non-low blood pressure group (> 100 mmHg in systole) (165 ± 106 mg vs. 238 ± 124 mg, P = 0.017). As expected, significant LV reverse remodeling was observed in the non-low blood pressure group after initiation of sacubitril/valsartan. It was noteworthy that significant LV reverse remodeling was also observed in the low blood pressure group after initiation of sacubitril/valsartan (LV end-diastolic volume: 177.3 ± 66.0 mL vs. 137.7 ± 56.1 mL, P < 0.001, LV end-systolic volume: 131.6 ± 60.3 mL vs. 94.6 ± 55.7 mL, P < 0.001, LVEF: 26.8 ± 10.3% vs. 33.8 ± 13.6%, P = 0.015). Relative changes in LV volumes and LVEF after initiation of sacubitril/valsartan were similar for the two groups. In conclusion, significant LV reverse remodeling occurred after initiation of sacubitril/valsartan, even in HF patients with LVEF < 50% and systolic blood pressure ≤ 100 mmHg.Feb. 2024, Heart and vessels, 39(2) (2), 95 - 104, English, Domestic magazine
- 26 Jan. 2024, Scientific reports, 14(1) (1), 2233 - 2233, English, International magazine
- BACKGROUND: Diabetes increases the risk of heart failure (HF). 3-Hydroxyisobutyric acid (3-HIB) is a muscle-derived metabolite reflecting systemic insulin resistance. In this study, we investigated the prognostic impact of 3-HIB in patients with chronic HF.Methods and Results: The KUNIUMI Registry chronic cohort is a community-based cohort study of chronic HF in Awaji Island, Japan. We analyzed the association between serum 3-HIB concentrations and adverse cardiovascular (CV) events in 784 patients from this cohort. Serum 3-HIB concentrations were significantly higher in patients with than without diabetes (P=0.0229) and were positively correlated with several metabolic parameters. According to Kaplan-Meier analysis, rates of CV death and HF hospitalization at 2 years were significantly higher among HF patients without diabetes in the high 3-HIB group (3-HIB concentrations above the median; i.e., >11.30 μmol/L) than in the low 3-HIB group (log-rank P=0.0151 and P=0.0344, respectively). Multivariable Cox proportional hazard models adjusted for established risk factors for HF revealed high 3-HIB as an independent predictor of CV death (hazard ratio [HR] 1.82; 95% confidence interval [CI] 1.16-2.85; P=0.009) and HF hospitalization (HR 1.72; 95% CI 1.17-2.53, P=0.006) in HF patients without diabetes, whereas no such trend was seen in subjects with diabetes. CONCLUSIONS: In a community cohort, circulating 3-HIB concentrations were associated with prognosis in chronic HF patients without diabetes.25 Dec. 2023, Circulation journal : official journal of the Japanese Circulation Society, 88(1) (1), 110 - 116, English, Domestic magazine
- Elevated circulating homocysteine (Hcy) is a well-known risk factor for cardiovascular diseases (CVDs), including coronary artery disease (CAD) and heart failure (HF). It remains unclear how Hcy and its derivatives relate to left ventricular (LV) diastolic function. The aim of the present study was to investigate the relationship between plasma Hcy-related metabolites and diastolic dysfunction (DD) in patients with heart disease (HD). A total of 62 HD patients with preserved LV ejection fraction (LVEF ≥ 50%) were enrolled. Plasma Hcy and its derivatives were measured by liquid chromatography‒mass spectrometry (LC-MS/MS). Spearman's correlation test and multiple linear regression models were used to analyze the associations between metabolite levels and LV diastolic function. The cystine/methionine (CySS/Met) ratio was positively correlated with LV diastolic function, which was defined from the ratio of mitral inflow E and mitral e' annular velocities (E/e') (Spearman's r = 0.43, p < 0.001). When the subjects were categorized into two groups by E/e', the high-E/e' group had a significantly higher CySS/Met ratio than the low-E/e' group (p = 0.002). Multiple linear regression models revealed that the CySS/Met ratio was independently associated with E/e' after adjustment for age, sex, body mass index (BMI), diabetes mellitus, hypertension, chronic kidney disease (CKD), hemoglobin, and lipid peroxide (LPO) {standardized β (95% CI); 0.14 (0.04-0.23); p = 0.005}. Hcy, CySS, and Met did not show a significant association with E/e' in the same models. A high plasma CySS/Met ratio reflected DD in patients with HD.Dec. 2023, Heart and vessels, 38(12) (12), 1422 - 1430, English, Domestic magazine
- "Preprocessing" is the first step required in brain image analysis that improves the overall quality and reliability of the results. However, it is computationally demanding and time-consuming, particularly to handle and parcellate complicatedly folded cortical ribbons of the human brain. In this study, we aimed to shorten the analysis time for data preprocessing of 1410 brain images simultaneously on one of the world's highest-performing supercomputers, "Fugaku." The FreeSurfer was used as a benchmark preprocessing software for cortical surface reconstruction. All the brain images were processed simultaneously and successfully analyzed in a calculation time of 17.33 h. This result indicates that using a supercomputer for brain image preprocessing allows big data analysis to be completed shortly and flexibly, thus suggesting the possibility of supercomputers being used for expanding large data analysis and parameter optimization of preprocessing in the future.14 Nov. 2023, Scientific reports, 13(1) (1), 19901 - 19901, English, International magazine
- Left atrial (LA) enlargement frequently occurs in atrial fibrillation (AF) patients, and this enlargement is associated with the development of heart failure, thromboembolism, or atrial functional mitral regurgitation (AFMR). AF patients can develop LA enlargement over time, but its progression depends on the individual. So far, the factors that cause progressive LA enlargement in AF patients have thus not been elucidated, so that the aim of this study was to identify the factors associated with the progression of LA enlargement in AF patients. We studied 100 patients with persistent or permanent AF (aged: 67 ± 2 years, 40 females). Echocardiography was performed at baseline and 12 (5-30) months after follow-up. LA size was evaluated as the LA volume index which was calculated with the biplane modified Simpson's method from apical four-and two-chamber views, and then normalized to the body surface area (LAVI). The deterioration of AFMR after follow-up was defined as a deterioration in severity of mitral regurgitation (MR) by a grade of 1 or more. Multivariate regression analysis demonstrated that hypertension (p = .03) was an independently associated parameter of progressive LA enlargement, as was baseline LAVI. In addition, the Kaplan-Meier curve indicated that patients with hypertension tended to show greater deterioration of AFMR after follow-up than those without hypertension (log-rank p = .08). Hypertension proved to be strongly associated with progression of LA enlargement over time in patients with AF. Our findings provide new insights for better management of patients with AF to prevent the development of AFMR.Sep. 2023, Echocardiography (Mount Kisco, N.Y.), 40(9) (9), 976 - 982, English, International magazine
- This study determined the predictive accuracy of optical frequency domain imaging (OFDI) on debulking effects of rotational atherectomy (RA) and compared the predictive accuracy of OFDI catheter-based with Rota wire-based prediction methods. This prospective, single-center, observational study included 55 consecutive patients who underwent OFDI-guided RA. On pre-RA OFDI images, a circle, identical to the Rota burr was drawn at the center of the OFDI catheter (OFDI catheter-based prediction method) or wire (wire-based prediction method). The area overlapping the vessel wall was defined as the predicted ablation area (P-area). The actual ablated area (A-area) was measured by superimposing the OFDI images before and after RA. The overlapping P-area and A-area were defined as overlapped ablation area (O-area), and the predictive accuracy was evaluated by %Correct area (O-area/P-area) and %Error area (A-area - O-area/A-area). The median %Correct and %Error areas were 47.8% and 41.6%, respectively. Irrelevant ablation (low %Correct-/high % Error areas) and over ablation (high %Correct-/high % Error areas) were related to deep vessel injury and intimal flap outside the P-area. The predictive accuracy was better in the OFDI catheter-based prediction method than the wire-based prediction method in the cross sections where the OFDI catheter and wire came in contact. However, it was better in the latter than the former where the OFDI catheter and wire were not in contact. OFDI-based simulation of the RA effect is feasible though accuracy may be affected by the OFDI catheter and wire position. OFDI-based simulation of RA effect might reduce peri-procedural complications during RA.Jul. 2023, Cardiovascular intervention and therapeutics, 38(3) (3), 316 - 326, English, Domestic magazine
- BACKGROUND: Evidence of prognostic factors for stent failure after drug-eluting stent implantation for calcified nodules (CNs) is limited. AIMS: We aimed to clarify the prognostic risk factors associated with stent failure among patients who underwent drug-eluting stent implantation for CN lesions using optical coherence tomography (OCT). METHODS: This retrospective, multicentre, observational study included 108 consecutive patients with CNs who underwent OCT-guided percutaneous coronary intervention (PCI). To evaluate the quality of CNs, we measured their signal intensity and analysed the degree of signal attenuation. All CN lesions were divided into dark or bright CNs according to the half width of signal attenuation, greater or lower than 332, respectively. RESULTS: During the median follow-up period of 523 days, 25 patients (23.1%) experienced target lesion revascularisation (TLR). The 5-year cumulative incidence of TLR was 32.6%. Multivariable Cox regression analysis revealed that younger age, haemodialysis, eruptive CNs, dark CNs assessed by pre-PCI OCT, disrupted fibrous tissue protrusions, and irregular protrusions assessed by post-PCI OCT were independently associated with TLR. The prevalence of in-stent CNs (IS-CNs) observed at follow-up OCT was significantly higher in the TLR group than in the non-TLR group. CONCLUSIONS: Factors such as younger age, haemodialysis, eruptive CNs, dark CNs, disrupted fibrous tissue, or irregular protrusions were independently related to TLR in patients with CNs. The high prevalence of IS-CNs might indicate that the main cause of stent failure implanted in CN lesions could be the recurrence of CN progression in the stented segment.05 Jun. 2023, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology, 19(2) (2), e123-e133, English, International magazine
- AIMS: Accessory pathway (AP) ablation is a standard procedure for the treatment of Wolff-Parkinson-White syndrome (WPW). Twelve-lead electrocardiogram (ECG)-based delta wave analysis is essential for predicting ablation sites. Previous algorithms have shown to be complex, time-consuming, and unprecise. We aimed to retrospectively develop and prospectively validate a new, simple ECG-based algorithm considering the patients' heart axis allowing for exact localization of APs in patients undergoing ablation for WPW. METHODS AND RESULTS: Our multicentre study included 211 patients undergoing ablation of a single manifest AP due to WPW between 2013 and 2021. The algorithm was developed retrospectively and validated prospectively by comparing its efficacy to two established ones (Pambrun and Arruda). All patients (32 ± 19 years old, 47% female) underwent successful pathway ablation. Prediction of AP-localization was correct in 197 patients (93%) (sensitivity 92%, specificity 99%, PPV 96%, and NPV 99%). Our algorithm was particularly useful in correctly localizing antero-septal/-lateral (sensitivity and specificity 100%) and posteroseptal (sensitivity 98%, specificity 92%) AP in proximity to the tricuspid valve. The accuracy of EASY-WPW was superior compared to the Pambrun (93% vs. 84%, P = 0.003*) and the Arruda algorithm (94% vs. 75%, P < 0.001*). A subgroup analysis of children (n = 58, 12 ± 4 years old, 55% female) revealed superiority to the Arruda algorithm (P < 0.001*). The reproducibility of our algorithm was excellent (ϰ>0.8; P < 0.001*). CONCLUSION: The novel EASY-WPW algorithm provides reliable and accurate pre-interventional ablation site determination in WPW patients. Only two steps are necessary to locate left-sided AP, and three steps to determine right-sided AP.16 Feb. 2023, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 25(2) (2), 600 - 609, English, International magazine
- BACKGROUND: Several algorithms have been proposed for differentiating the right and left outflow tracts (RVOT/LVOT) arrhythmia origins from 12-lead electrocardiograms (ECGs); however, the procedure is complicated. A deep learning (DL) model, a form of artificial intelligence, can directly use ECGs and depict the importance of the leads and waveforms. This study aimed to create a visualized DL model that could classify arrhythmia origins more accurately.Methods and Results: This study enrolled 80 patients who underwent catheter ablation. A convolutional neural network-based model that could classify arrhythmia origins with 12-lead ECGs and visualize the leads that contributed to the diagnosis using a gradient-weighted class activation mapping method was developed. The average prediction results of the origins by the DL model were 89.4% (88.2-90.6) for accuracy and 95.2% (94.3-96.2) for recall, which were significantly better than when a conventional algorithm is used. The ratio of the contribution to the prediction differed between RVOT and LVOT origins. Although leads V1 to V3 and the limb leads had a focused balance in the LVOT group, the contribution ratio of leads aVR, aVL, and aVF was higher in the RVOT group. CONCLUSIONS: This study diagnosed the arrhythmia origins more accurately than the conventional algorithm, and clarified which part of the 12-lead waveforms contributed to the diagnosis. The visualized DL model was convincing and may play a role in understanding the pathogenesis of arrhythmias.25 Jul. 2022, Circulation journal : official journal of the Japanese Circulation Society, 86(8) (8), 1273 - 1280, English, Domestic magazine
- Alterations in cardiac metabolism are strongly associated with the pathogenesis of heart failure (HF). We recently reported that glutamine-dependent anaplerosis, termed glutaminolysis, was activated by H2O2 stimulation in rat cardiomyocytes, which seemed to be an adaptive response by which cardiomyocytes survive acute stress. However, the molecular mechanisms and fundamental roles of glutaminolysis in the pathophysiology of the failing heart are still unknown. Here, we treated wild-type mice (C57BL/6J) and rat neonatal cardiomyocytes (RNCMs) and fibroblasts (RNCFs) with angiotensin II (ANG II) to induce pathological cardiac remodeling. Glutaminase 1 (GLS1), a rate-limiting glutaminolysis enzyme, was significantly increased in ANG II-induced mouse hearts, RNCMs and RNCFs. Unexpectedly, a GLS1 inhibitor attenuated ANG II-induced left ventricular hypertrophy and fibrosis in the mice, and gene knockdown and pharmacological perturbation of GLS1 suppressed hypertrophy and the proliferation of RNCMs and RNCFs, respectively. Using mass spectrometry (MS)-based stable isotope tracing with 13C-labeled glutamine, we observed glutamine metabolic flux in ANG II-treated RNCMs and RNCFs. The incorporation of 13C atoms into tricarboxylic acid (TCA) cycle intermediates and their derivatives was markedly enhanced in both cell types, indicating the activation of glutaminolysis in hypertrophied hearts. Notably, GLS1 inhibition reduced the production of glutamine-derived aspartate and citrate, which are required for the biosynthesis of nucleic acids and lipids, possibly contributing to the suppression of cardiac hypertrophy and fibrosis. The findings of the present study reveal that GLS1-mediated upregulation of glutaminolysis leads to maladaptive cardiac remodeling. Inhibition of this anaplerotic pathway could be a novel therapeutic approach for HF.NEW & NOTEWORTHY To our knowledge, this study is the first to demonstrate that increased GLS1 expression and subsequent activation of glutaminolysis are associated with exacerbation of cardiac hypertrophy and fibrosis. Inhibiting GLS1 antagonized the adverse cardiac remodeling in vitro and in vivo, partly due to reduction of glutamine-derived metabolites, which are necessary for cellular growth and proliferation. Increased glutamine utilization for anabolic reactions in cardiac cells may be related to the pathogenesis and development of HF.01 May 2022, American journal of physiology. Heart and circulatory physiology, 322(5) (5), H749-H761, English, International magazine
- In-home monitoring systems have been used to detect cognitive decline in older adults by allowing continuous monitoring of routine activities. In this study, we investigated whether unobtrusive in-house power monitoring technologies could be used to predict cognitive impairment. A total of 94 older adults aged ≥65 years were enrolled in this study. Generalized linear mixed models with subject-specific random intercepts were used to evaluate differences in the usage time of home appliances between people with and without cognitive impairment. Three independent power monitoring parameters representing activity behavior were found to be associated with cognitive impairment. Representative values of mean differences between those with cognitive impairment relative to those without were -13.5 min for induction heating in the spring, -1.80 min for microwave oven in the winter, and -0.82 h for air conditioner in the winter. We developed two prediction models for cognitive impairment, one with power monitoring data and the other without, and found that the former had better predictive ability (accuracy, 0.82; sensitivity, 0.48; specificity, 0.96) compared to the latter (accuracy, 0.76; sensitivity, 0.30; specificity, 0.95). In summary, in-house power monitoring technologies can be used to detect cognitive impairment.17 Sep. 2021, Sensors (Basel, Switzerland), 21(18) (18), English, International magazine
- Recently we established a cell-free assay to evaluate "cholesterol uptake capacity (CUC)" as a novel concept for high-density lipoprotein (HDL) functionality and demonstrated the feasibility of CUC for coronary risk stratification, although its regulatory mechanism remains unclear. HDL fluidity affects cholesterol efflux, and trans fatty acids (TFA) reduce lipid membrane fluidity when incorporated into phospholipids (PL). This study aimed to clarify the effect of TFA in HDL-PL on CUC. Serum was collected from 264 patients after coronary angiography or percutaneous coronary intervention to measure CUC and elaidic acid levels in HDL-PL, and in vitro analysis using reconstituted HDL (rHDL) was used to determine the HDL-PL mechanism affecting CUC. CUC was positively associated with HDL-PL levels but negatively associated with the proportion of elaidic acid in HDL-PL (elaidic acid in HDL-PL/HDL-PL ratio). Increased elaidic acid-phosphatidylcholine (PC) content in rHDL exhibited no change in particle size or CUC compared to rHDL containing oleic acid in PC. Recombinant human lecithin-cholesterol acyltransferase (LCAT) enhanced CUC, and LCAT-dependent enhancement of CUC and LCAT-dependent cholesterol esterification were suppressed in rHDL containing elaidic acid in PC. Therefore, CUC is affected by HDL-PL concentration, HDL-PL acyl group composition, and LCAT-dependent cholesterol esterification. Elaidic acid precipitated an inhibition of cholesterol uptake and maturation of HDL; therefore, modulation of HDL-PL acyl groups could improve CUC.04 Sep. 2021, Nutrients, 13(9) (9), English, International magazine
- Cardiac accessory pathways (APs) in Wolff-Parkinson-White (WPW) syndrome are conventionally diagnosed with decision tree algorithms; however, there are problems with clinical usage. We assessed the efficacy of the artificial intelligence model using electrocardiography (ECG) and chest X-rays to identify the location of APs. We retrospectively used ECG and chest X-rays to analyse 206 patients with WPW syndrome. Each AP location was defined by an electrophysiological study and divided into four classifications. We developed a deep learning model to classify AP locations and compared the accuracy with that of conventional algorithms. Moreover, 1519 chest X-ray samples from other datasets were used for prior learning, and the combined chest X-ray image and ECG data were put into the previous model to evaluate whether the accuracy improved. The convolutional neural network (CNN) model using ECG data was significantly more accurate than the conventional tree algorithm. In the multimodal model, which implemented input from the combined ECG and chest X-ray data, the accuracy was significantly improved. Deep learning with a combination of ECG and chest X-ray data could effectively identify the AP location, which may be a novel deep learning model for a multimodal model.13 Apr. 2021, Scientific reports, 11(1) (1), 8045 - 8045, English, International magazine
- This work established a new murine venous thromboembolism (VTE) model. This model has multiple novel features representing clinical VTE that include the following: 1) deep venous thrombosis (DVT) was formed and extended in the long axis of femoral/saphenous vein; 2) thrombus was formed in a venous valve pocket; 3) deligation of suture-induced spontaneous pulmonary emboli of fibrin-rich DVT; and 4) cardiac motion-free femoral/saphenous vein allowed high-resolution intravital microscopic imaging of fibrin-rich DVT. This new model requires only commercially available epifluorescence microscopy. Therefore, this model has significant potential for better understanding of VTE pathophysiology.Apr. 2020, JACC. Basic to translational science, 5(4) (4), 344 - 356, English, International magazine
- May 2019, ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 39, EnglishEstablishment of Femoral Vein Ligation Model: a New DVT Imaging ModelSummary international conference
- 06 Nov. 2018, CIRCULATION, 138, EnglishEstablishment of Novel Deep Venous Thrombosis Model Suitable for In Vivo Imaging.Summary international conference
- Sep. 2018, HeartRhythm case reports, 4(9) (9), 389 - 392, English, International magazine
- Although acute pulmonary edema (APE) is common in patients with heart failure (HF) with preserved ejection fraction (EF), its pathogenesis in patients with HF with reduced EF (HFrEF) is not completely understood. The purpose of our study was to explore the contributions of left ventricular (LV) geometry to understand the difference between HFrEF patients with or without APE. We studied 122 consecutive acute decompensated HF patients with HFrEF (≤40%). APE was defined as acute-onset dyspnea and radiographic alveolar edema requiring immediate airway intervention. LV geometry was determined from a combination of the LV mass index and relative wall thickness (RWT). Long-term unfavorable outcome events were tracked during a follow-up of a median of 21 months (interquartile range, 10-28 months), during which APE was observed in 29 patients (24%). Compared to those without APE, hospitalized patients with APE had a higher systolic blood pressure, RWT, and LVEF and lower end-diastolic dimension. Among echocardiographic variables, a multivariate logistic regression analysis identified RWT as the only independent determinant of APE (hazard ratio: 2.46, p < 0.001). Those with concentric geometry (n = 25; RWT > 0.42) had a higher incidence of APE relative to those with non-concentric geometry. Furthermore, among patients with APE, mortality was significantly higher among those with concentric geometry (log-rank, p = 0.008). Compared with non-concentric geometry, concentric geometry (increased RWT, not LV mass) was strongly associated with APE onset and a poorer outcome among APE patients. An easily obtained echocardiographic RWT index may facilitate the risk stratification of patients.Feb. 2018, The international journal of cardiovascular imaging, 34(2) (2), 185 - 192, English, International magazine
- Pulmonary arterial hypertension (PAH) is a rare complication of dasatinib that was approved as a first-line therapy for chronic myelocytic leukemia (CML). A 24-year-old man presenting dyspnea at rest and leg edema was admitted to our hospital. He had been diagnosed with CML and prescribed dasatinib for 4 years. Chest X-ray showed significant bilateral pleural effusion and heart enlargement. Echocardiography revealed interventricular septal compression and elevated peak tricuspid regurgitation pressure gradient of 66.7 mmHg indicating severe pulmonary hypertension. After the other specific diseases to provoke PAH were excluded, he was diagnosed with dasatinib-induced PAH. Despite discontinuation of dasatinib and intravenous administration of diuretic for two weeks, World Health Organization (WHO) functional class was still II and mean pulmonary arterial pressure (PAP) was high at 37 mmHg. Therefore, we administered sildenafil and bosentan together as an upfront combination therapy three weeks after dasatinib discontinuation. Six months later, his symptoms improved to WHO functional class I and mean PAP was decreased to 31 mmHg. Although PAH is a rare complication of dasatinib, symptomatic patients prescribed with dasatinib should have an echocardiogram for PAH screening. Moreover, the upfront combination therapy would be a useful option for symptomatic patients after discontinuation of dasatinib.2018, Case reports in cardiology, 2018, 3895197 - 3895197, English, International magazine
- A 47-year-old woman with marked thrombocytosis of 1,650 × 10(9)/L was diagnosed with chronic eosinophilic pneumonia (CEP) based on imaging of the lung and abundant eosinophils in bronchoalveolar lavage fluid. Known gene abnormalities that cause eosinophilia were not detected in bone marrow cells. Treatment with oral prednisolone at 20 mg/day relieved the CEP and resolved the laboratory abnormalities, including eosinophilia and thrombocytosis. Serum concentrations of interleukin (IL)-5 and IL-6 were elevated to 9.6 and 14.0 pg/mL, respectively. The megakaryocyte-potentiating activity of IL-6 and possibly, that of IL-1β, which is known to be secreted by activated eosinophils, may have caused the marked thrombocytosis in this patient.2015, Journal of clinical and experimental hematopathology : JCEH, 55(2) (2), 97 - 102, English, Domestic magazine
- Scedosporium prolificans (S. prolificans) is a type of mold, which rarely affects immunocompromised people. We treated a 71-year-old woman with acute myeloid leukemia (AML-M5a) with low-dose cytarabine, acralubicin, and filgrastim as the induction therapy. On day 7 after the initiation of chemotherapy, she became febrile and agranulocytic, and developed anal pain ; therefore, we discontinued the chemotherapy on day 8. Broad-spectrum antibiotics, micafungin, and then liposomal amphotericin B were ineffective. The serum concentration of β-D-glucan was 525 pg/mL. She died of multiple organ failure on day 17. S. prolificans was detected from the blood culture on day 13. Physicians should consider Scedosporium spp. infection when principal antifungal agents are ineffective and fungal infection is strongly suspected.2014, Medical mycology journal, 55(4) (4), E63-70, English, Domestic magazine