Tsujino Ichizo

Faculty of MedicineSpecially Appointed Professor
Last Updated :2025/06/10

■Researcher basic information

Researchmap personal page

Research Keyword

  • sarcoidosis
  • pulmonary hypertension
  • 呼吸器病学
  • 循環器病学

Research Field

  • Life sciences, Metabolism and endocrinology
  • Life sciences, Cardiology

■Career

Career

  • Sep. 2021 - Present
    Hokkaido University, Hokkaido University Hospital, 医師, 特任教授

■Research activity information

Papers

  • Cancer as an independent mortality risk in chronic thromboembolic pulmonary hypertension.
    Junichi Nakamura, Ichizo Tsujino, Kohei Masaki, Kazuya Hosokawa, Kouta Funakoshi, Yu Taniguchi, Shiro Adachi, Takumi Inami, Jun Yamashita, Hitoshi Ogino, Masaru Hatano, Nobuhiro Yaoita, Nobutaka Ikeda, Hiroto Shimokawahara, Nobuhiro Tanabe, Kayoko Kubota, Ayako Shigeta, Yoshito Ogihara, Koshin Horimoto, Yoshihiro Dohi, Takashi Kawakami, Yuichi Tamura, Koichiro Tatsumi, Kohtaro Abe
    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 44, 3, 339, 348, Mar. 2025, [International Magazine]
    English, Scientific journal, BACKGROUND: The management of chronic thromboembolic pulmonary hypertension (CTEPH) has advanced significantly in recent years, thereby improving patient prognosis. However, the impact of cancer on the outcomes of patients with CTEPH under current treatment remains unclear. This study aimed to investigate the prevalence of cancer in patients with CTEPH and determine how comorbid cancer affects their prognosis and clinical course. METHODS: Data from an ongoing Japanese prospective cohort study were analyzed. Prevalence and primary cancer sites were evaluated. The association of a history of cancer with a composite endpoint, including all-cause death, lung transplantation, and worsening of CTEPH, as well as venous thromboembolism and bleeding events, was assessed. RESULTS: Of the 1,270 patients in the cohort, 134 (10.6%) had a history of cancer, with the most common primary sites being the breast in women and the prostate in men. The incidence of composite outcome and all-cause death was higher in those with a history of cancer (p < 0.001, log-rank test). In the Cox proportional hazard model, age- and sex-adjusted hazard ratios for the composite outcome and all-cause death were 2.69 (95% confidence interval, 1.48-4.89, p = 0.001) and 4.25 (95% confidence interval, 1.98-9.10, p < 0.001), respectively, for patients with a history of cancer. No significant differences in venous thromboembolism and bleeding events were observed between patients with and those without a history of cancer. CONCLUSIONS: A history of cancer, with a prevalence of 10.6%, is an independent risk factor for mortality in patients with CTEPH undergoing the currently recommended treatment.
  • Prevalence, incidence, and clinical features of cardiac involvement in patients with pulmonary sarcoidosis.
    Junichi Nakamura, Takahiro Sato, Hiroshi Ohira, Shuhei Yoshikawa, Takeshi Hattori, Osamu Manabe, Noriko Oyama-Manabe, Satonori Tsuneta, Hirokazu Kimura, Sakae Takenaka, Toshiyuki Nagai, Toshihisa Anzai, Masaharu Nishimura, Isao Yokota, Ichizo Tsujino, Satoshi Konnno
    Respiratory medicine, 238, 107954, 107954, Mar. 2025, [International Magazine]
    English, Scientific journal, BACKGROUND: The epidemiology and characteristics of cardiac involvement in patients with pulmonary sarcoidosis remain unclear. We aimed to determine the prevalence, incidence, and clinical features of cardiac sarcoidosis in patients with pulmonary sarcoidosis. METHODS: The characteristics of patients with biopsy-proven pulmonary sarcoidosis were retrospectively evaluated. Cardiac sarcoidosis was diagnosed via evaluations, including 18F-fluorodeoxyglucose positron emission tomography at the time of diagnosis of pulmonary sarcoidosis and during follow-up. Characteristics of patients with and without cardiac complications were compared. RESULTS: In total, 438 patients with pulmonary sarcoidosis were included, of which 40 (9.1 %) were diagnosed with cardiac sarcoidosis at the time of diagnosis of pulmonary sarcoidosis. During the follow-up period, 14 patients (4 %) developed cardiac complications (0.0075/person-years). Electrocardiographic abnormalities were the most common findings leading to the diagnosis of cardiac sarcoidosis (85 %). Compared to patients without cardiac involvement, those with cardiac sarcoidosis had lower serum angiotensin converting enzyme concentration [19.9 (15.5-25.1) vs. 17.4 (12.6-23.8) U/L)], higher rates of kidney complications (3 vs. 13 %), fewer ocular complications (78 vs. 17 %), and lower lymphocyte levels [35.8 (18.6-53) vs. 25.1 (14.2-38.2)%] and CD4/CD8 ratios [4.8 (3.1-7.5)% vs. 3.9 (1.8-6)%] in bronchoalveolar lavage fluid analysis. CONCLUSION: At the time of diagnosis of pulmonary sarcoidosis, cardiac complications occurred in approximately 10 % of the patients and developed in 0.0075/person-year during follow-up. Low serum angiotensin converting enzyme concentration, lymphocyte level and CD4/CD8 ratio in the bronchoalveolar lavage fluid may be unique features of patients with cardiac sarcoidosis.
  • Insights into balloon pulmonary angioplasty and the WHO functional class of chronic thromboembolic pulmonary hypertension patients: findings from the CTEPH AC registry.
    Nobutaka Ikeda, Kohei Masaki, Kazuya Hosokawa, Kouta Funakoshi, Yu Taniguchi, Shiro Adachi, Takumi Inami, Jun Yamashita, Hitoshi Ogino, Ichizo Tsujino, Masaru Hatano, Nobuhiro Yaoita, Hiroto Shimokawahara, Nobuhiro Tanabe, Kayoko Kubota, Ayako Shigeta, Yoshito Ogihara, Koshin Horimoto, Yoshihiro Dohi, Takashi Kawakami, Yuichi Tamura, Koichiro Tatsumi, Kohtaro Abe
    Cardiovascular intervention and therapeutics, 22 Jan. 2025, [Domestic magazines]
    English, Scientific journal, Advances in chronic thromboembolic pulmonary hypertension (CTEPH) treatment have improved prognosis, shifting focus towards symptom management. This study aimed to identify factors influencing the World Health Organization functional class (WHO-FC) in CTEPH patients. The CTEPH AC registry is a prospective, multicenter database from 35 Japanese institutions, analyzing data from August 2018 to July 2023. We examined factors associated with achieving WHO-FC I and WHO-FC changes over time in 1,270 patients. Significant factors for WHO-FC I achievement included male sex (odds ratio: 1.86, p = 0.019), age (0.98, p = 0.007), pulmonary vasodilator use (0.51, p = 0.001), post-balloon pulmonary angioplasty (BPA) (1.93, p = 0.010), lower mean pulmonary arterial pressure (0.94, p = 0.004), and lower pulmonary vascular resistance (PVR) (0.78, p = 0.006). Multivariate analysis showed that WHO-FC improvement correlated with male sex, baseline PVR, and BPA during follow-up. WHO-FC deterioration was associated with cancer, history of pulmonary endarterectomy and/or BPA at registration, bleeding risks, and thyroid disease or hormone therapy. BPA implementation is closely linked to symptomatic improvement and achieving WHO-FC I, while symptom worsening is often associated with patient-specific, difficult-to-control conditions.
  • Prevalence and clinical impact of asthma-COPD overlap in severe asthma.
    Miho Wakazono, Hirokazu Kimura, Ichizo Tsujino, Nobuyasu Wakazono, Michiko Takimoto-Sato, Munehiro Matsumoto, Kaoruko Shimizu, Houman Goudarzi, Hironi Makita, Masaharu Nishimura, Satoshi Konno
    Allergology international : official journal of the Japanese Society of Allergology, 11 Dec. 2024, [International Magazine]
    English, Scientific journal, BACKGROUND: Patients with asthma-COPD overlap (ACO) have a greater symptom burden, worse respiratory function, and more frequent exacerbations than those with asthma alone. However, only a few studies have investigated the prevalence and clinical course of ACO in severe asthma. This study aimed to examine the comorbid rate of ACO and its clinical impact on severe asthma. METHODS: We prospectively enrolled 127 patients with severe asthma from 30 hospitals and clinics. Favorable treatment adherence was ensured, and the prevalence of ACO was assessed using the Japanese Respiratory Society ACO criteria. Patients were categorized into two groups, ACO and non-ACO, and their clinical characteristics were compared. The exacerbation rates with a 3-year follow-up and the annual change in FEV1 with a 5-year follow-up of 105 individuals were evaluated. The exacerbation-free rate was analyzed using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: The prevalence of ACO in severe asthma was 31.5 %. Patients with ACO were older, more frequently male, and had a longer duration of asthma than those without. No significant difference was observed in exacerbation rates between the ACO and non-ACO groups (62.2 % vs. 63.2 %, P = 0.91) or the annual change in FEV1 (-39.2 mL/year vs. -31.2 mL/year, P = 0.11). CONCLUSIONS: The prevalence of ACO in our multicenter cohort study on severe asthma was approximately 30 %. The presence of ACO was not an independent risk for exacerbations or decline in FEV1.
  • Development and Validation of Quality Indicators for Pulmonary Arterial Hypertension Management in Japan: A Modified Delphi Consensus Study.
    Yuichi Tamura, Kazuya Hosokawa, Koshin Horimoto, Satoshi Ikeda, Takumi Inami, Kayoko Kubota, Naohiko Nakanishi, Yuichiro Shirai, Nobuhiro Tanabe, Ichizo Tsujino, Hiromi Matsubara
    Diagnostics (Basel, Switzerland), 14, 23, 25 Nov. 2024, [International Magazine]
    English, Scientific journal, BACKGROUND: Quality indicators (QIs) are used to standardize care and improve outcomes in patients with pulmonary arterial hypertension (PAH). It is important that QIs are validated within specific healthcare contexts. Therefore, this study aimed to validate QIs for PAH management in Japan using a modified Delphi consensus method. METHODS: QI candidates were identified from published European QIs and clinical practice guidelines. An expert panel of 11 PAH specialists from diverse Japanese institutions anonymously rated the 36 initial QI candidates in two rounds using a nine-point appropriateness scale. RESULTS: In the first round, 35 QIs received a median score of ≥7 points. A panel discussion was held between rounds to address the single low-scored QI, biomarker modifications, and invasive examinations, resulting in 36 modified QIs. In the second round, all modified QIs received median scores of ≥7 points and were judged to be valid as the final Japanese set of QIs. CONCLUSIONS: The findings of this study validated a set of QIs for PAH management tailored to the Japanese healthcare context. These QIs can be used to standardize care, identify areas for improvement, and ultimately enhance outcomes for Japanese patients with PAH.
  • 肺サルコイドーシス組織診断例における心病変合併例の割合および臨床的特徴
    吉川 修平, 佐藤 隆博, 辻野 一三, 中村 順一, 永井 利幸, 木村 孔一, 今野 哲
    日本サルコイドーシス/肉芽腫性疾患学会雑誌, 44, サプリメント号, 58, 58, 日本サルコイドーシス, Oct. 2024
    Japanese
  • Outcomes of Chronic Thromboembolic Pulmonary Hypertension After Balloon Pulmonary Angioplasty and Pulmonary Endarterectomy.
    Kohei Masaki, Kazuya Hosokawa, Kouta Funakoshi, Yu Taniguchi, Shiro Adachi, Takumi Inami, Jun Yamashita, Hitoshi Ogino, Ichizo Tsujino, Masaru Hatano, Nobuhiro Yaoita, Nobutaka Ikeda, Hiroto Shimokawahara, Nobuhiro Tanabe, Kayoko Kubota, Ayako Shigeta, Yoshito Ogihara, Koshin Horimoto, Yoshihiro Dohi, Takashi Kawakami, Yuichi Tamura, Koichiro Tatsumi, Kohtaro Abe
    JACC. Asia, 4, 8, 577, 589, Aug. 2024, [International Magazine]
    English, Scientific journal, BACKGROUND: The contemporary outcome of balloon pulmonary angioplasty (BPA) and pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) are unclear. OBJECTIVES: This study aimed to clarify the characteristics and outcomes of CTEPH patients treated with BPA and PEA in Japan. METHODS: Among 1,270 participants enrolled between 2018 and 2023 in the CTEPH AC (Chronic Thromboembolic Pulmonary Hypertension Anticoagulant) registry, a Japanese nationwide CTEPH registry, 369 treatment-naive patients (BPA strategy: n = 313; PEA strategy: n = 56) and 690 on-treatment patients (BPA strategy: n = 561; PEA strategy: n = 129) were classified according to the presence of prior reperfusion therapy. Morbidity and mortality events (all-cause death, rescue mechanical reperfusion therapy, and/or initiation of parenteral pulmonary vasodilators), pulmonary hemodynamics, exercise tolerance, and relevant laboratory test results were evaluated. RESULTS: The BPA strategy was chosen in older patients than the PEA strategy (mean age, BPA vs PEA: 66.5 ± 12.6 years vs 62.5 ± 11.8 years; P = 0.028). Median follow-up period was 615 (Q1-Q3: 311-997) days in treatment-naive patients and 1,136 (Q1-Q3: 684-1,300) days in on-treatment patients. BPA strategy had as acceptable morbidity and mortality as PEA strategy (5-year morbidity and mortality event rate, BPA vs PEA: 10.2% [95% CI: 5.2%-19.5%] vs 16.1% [95% CI: 4.3%-50.6%] in treatment-naive patients; 9.7% [95% CI: 6.7%-13.8%] vs 6.9% [95% CI: 2.7%-17.3%] in on-treatment patients), with greater improvement of renal function; glomerular filtration rate in propensity score-matched population (difference between change: 4.9 [95% CI: 0.5-9.3] mL/min/1.73 m2; P = 0.030). CONCLUSIONS: BPA strategy was more frequently chosen in older patients compared with PEA strategy and showed acceptable outcomes for efficacy with greater advantage for improvement in renal function. (Multicenter registry of chronic thromboembolic pulmonary hypertension in Japan; UMIN000033784).
  • Pulmonary Hypertension With Interstitial Pneumonia: Initial Treatment Effectiveness and Severity in a Japan Registry.
    Nobuhiro Tanabe, Hiraku Kumamaru, Yuichi Tamura, Yasuhiro Kondoh, Kazuhiko Nakayama, Naoko Kinukawa, Tomoki Kimura, Osamu Nishiyama, Ichizo Tsujino, Ayako Shigeta, Yoshiteru Morio, Yoshikazu Inoue, Hiroshi Kuraishi, Ken-Ichi Hirata, Kensuke Tanaka, Masataka Kuwana, Tetsutaro Nagaoka, Tomohiro Handa, Koichiro Sugimura, Fumio Sakamaki, Akira Naito, Yu Taniguchi, Hiromi Matsubara, Masayuki Hanaoka, Takumi Inami, Naoki Hayama, Yoshihiro Nishimura, Hiroshi Kimura, Hiroaki Miyata, Koichiro Tatsumi
    JACC. Asia, 4, 5, 403, 417, May 2024, [International Magazine]
    English, Scientific journal, BACKGROUND: Recent guidelines discourage the use of pulmonary arterial hypertension (PAH)-targeted therapies in patients with pulmonary hypertension (PH) associated with respiratory diseases. Therefore, stratifications of the effectiveness of PAH-targeted therapies are important for this group. OBJECTIVES: The authors aimed to identify phenotypes that might benefit from initial PAH-targeted therapies in patients with PH associated with interstitial pneumonia and combined pulmonary fibrosis and emphysema. METHODS: We categorized 270 patients with precapillary PH (192 interstitial pneumonia, 78 combined pulmonary fibrosis and emphysema) into severe and mild PH using a pulmonary vascular resistance of 5 WU. We investigated the prognostic factors and compared the prognoses of initial (within 2 months after diagnosis) and noninitial treatment groups, as well as responders (improvements in World Health Organization functional class, pulmonary vascular resistance, and 6-minute walk distance) and nonresponders. RESULTS: Among 239 treatment-naive patients, 46.0% had severe PH, 51.8% had mild ventilatory impairment (VI), and 40.6% received initial treatment. In the severe PH with mild VI subgroup, the initial treatment group had a favorable prognosis compared with the noninitial treatment group. The response rate in this group was significantly higher than the others (48.2% vs 21.8%, ratio 2.21 [95% CI: 1.17-4.16]). In multivariate analysis, initial treatment was a better prognostic factor for severe PH but not for mild PH. Within the severe PH subgroup, responders had a favorable prognosis. CONCLUSIONS: This study demonstrated an increased number of responders to initial PAH-targeted therapy, with a favorable prognosis in severe PH cases with mild VI. A survival benefit was not observed in mild PH cases. (Multi-institutional Prospective Registry in Pulmonary Hypertension associated with Respiratory Disease; UMIN000011541).
  • Switching from Beraprost to Selexipag in the Treatment of Pulmonary Arterial Hypertension: Insights from a Phase IV Study of the Japanese Registry (The EXCEL Study: EXChange from bEraprost to seLexipag Study).
    Yuichi Tamura, Hiraku Kumamaru, Ichizo Tsujino, Rika Suda, Kohtaro Abe, Takumi Inami, Koshin Horimoto, Shiro Adachi, Satoshi Yasuda, Fusako Sera, Yu Taniguchi, Masataka Kuwana, Koichiro Tatsumi
    Pharmaceuticals (Basel, Switzerland), 17, 5, 26 Apr. 2024, [International Magazine]
    English, Scientific journal, Pulmonary arterial hypertension (PAH) remains a significant challenge in cardiology, necessitating advancements in treatment strategies. This study explores the safety and efficacy of transitioning patients from beraprost to selexipag, a novel selective prostacyclin receptor agonist, within a Japanese cohort. Employing a multicenter, open-label, prospective design, 25 PAH patients inadequately managed on beraprost were switched to selexipag. Key inclusion criteria included ongoing beraprost therapy for ≥3 months, a diagnosis of PAH confirmed by mean pulmonary artery pressure (mPAP) ≥ 25 mmHg, and current treatment with endothelin receptor antagonists and/or phosphodiesterase type 5 inhibitors. Outcomes assessed were changes in hemodynamic parameters (mPAP, cardiac index, pulmonary vascular resistance) and the 6 min walk distance (6-MWD) over 3-6 months. The study found no statistically significant changes in these parameters post-switch. However, a subset of patients, defined as responders, demonstrated improvements in all measured hemodynamic parameters, suggesting a potential benefit in carefully selected patients. The transition was generally well-tolerated with no serious adverse events reported. This investigation underscores the importance of personalized treatment strategies in PAH, highlighting that certain patients may benefit from switching to selexipag, particularly those previously on higher doses of beraprost. Further research is needed to elucidate the predictors of positive response to selexipag and optimize treatment regimens for this complex condition.
  • Exploratory analysis of the accuracy of echocardiographic parameters for the assessment of right ventricular function and right ventricular-pulmonary artery coupling.
    Hideki Shima, Ichizo Tsujino, Junichi Nakamura, Toshitaka Nakaya, Ayako Sugimoto, Takahiro Sato, Taku Watanabe, Hiroshi Ohira, Masaru Suzuki, Satonori Tsuneta, Yasuyuki Chiba, Michito Murayama, Isao Yokota, Satoshi Konno
    Pulmonary circulation, 14, 2, e12368, Apr. 2024, [International Magazine]
    English, Scientific journal, Echocardiography is a widely used modality for the assessment of right ventricular (RV) function; however, few studies have comprehensively compared the accuracy of echocardiographic parameters using invasively obtained reference values. Therefore, this exploratory study aimed to compare the accuracy of echocardiographic parameters of RV function and RV-pulmonary artery (PA) coupling. We calculated four indices of RV function (end-systolic elastance [Ees] for systolic function [contractility], τ for relaxation, and β and end-diastolic elastance [Eed] for stiffness), and an index of RV-PA coupling (Ees/arterial elastance [Ea]), using pressure catheterization, cardiac magnetic resonance imaging, and a single-beat method. We then compared the correlations of RV indices with echocardiographic parameters. In 63 participants (54 with pulmonary hypertension (PH) and nine without PH), Ees and τ correlated with several echocardiographic parameters, such as RV diameter and area, but the correlations were moderate (|correlation coefficients (ρ)| < 0.5 for all parameters). The correlations of β and Eed with echocardiographic parameters were weak, with |ρ| < 0.4. In contrast, Ees/Ea closely correlated with RV free wall longitudinal strain (RVFW-LS)/estimated systolic PA pressure (eSPAP) (ρ = -0.72). Ees/Ea also correlated with tricuspid annular plane systolic excursion/eSPAP, RV diameter, and RV end-systolic area, with |ρ | >0.65. In addition, RVFW-LS/eSPAP yielded high sensitivity (0.84) and specificity (0.75) for detecting reduced Ees/Ea. The present study indicated a limited accuracy of echocardiographic parameters in assessing RV systolic and diastolic function. In contrast to RV function, they showed high accuracy for assessing RV-PA coupling, with RVFW-LS/eSPAP exhibiting the highest accuracy.
  • Deep learning to assess right ventricular ejection fraction from two-dimensional echocardiograms in precapillary pulmonary hypertension.
    Michito Murayama, Hiroyuki Sugimori, Takaaki Yoshimura, Sanae Kaga, Hideki Shima, Satonori Tsuneta, Aoi Mukai, Yui Nagai, Shinobu Yokoyama, Hisao Nishino, Junichi Nakamura, Takahiro Sato, Ichizo Tsujino
    Echocardiography (Mount Kisco, N.Y.), 41, 4, e15812, Apr. 2024, [International Magazine]
    English, Scientific journal, BACKGROUND: Precapillary pulmonary hypertension (PH) is characterized by a sustained increase in right ventricular (RV) afterload, impairing systolic function. Two-dimensional (2D) echocardiography is the most performed cardiac imaging tool to assess RV systolic function; however, an accurate evaluation requires expertise. We aimed to develop a fully automated deep learning (DL)-based tool to estimate the RV ejection fraction (RVEF) from 2D echocardiographic videos of apical four-chamber views in patients with precapillary PH. METHODS: We identified 85 patients with suspected precapillary PH who underwent cardiac magnetic resonance imaging (MRI) and echocardiography. The data was divided into training (80%) and testing (20%) datasets, and a regression model was constructed using 3D-ResNet50. Accuracy was assessed using five-fold cross validation. RESULTS: The DL model predicted the cardiac MRI-derived RVEF with a mean absolute error of 7.67%. The DL model identified severe RV systolic dysfunction (defined as cardiac MRI-derived RVEF < 37%) with an area under the curve (AUC) of .84, which was comparable to the AUC of RV fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE) measured by experienced sonographers (.87 and .72, respectively). To detect mild RV systolic dysfunction (defined as RVEF ≤ 45%), the AUC from the DL-predicted RVEF also demonstrated a high discriminatory power of .87, comparable to that of FAC (.90), and significantly higher than that of TAPSE (.67). CONCLUSION: The fully automated DL-based tool using 2D echocardiography could accurately estimate RVEF and exhibited a diagnostic performance for RV systolic dysfunction comparable to that of human readers.
  • Echocardiographic estimation of right ventricular diastolic stiffness based on pulmonary regurgitant velocity waveform analysis in precapillary pulmonary hypertension.
    Yui Nagai, Michito Murayama, Sanae Kaga, Hideki Shima, Satonori Tsuneta, Shinobu Yokoyama, Hisao Nishino, Mana Goto, Yukino Suzuki, Yusuke Yanagi, Suguru Ishizaka, Hiroyuki Iwano, Junichi Nakamura, Takahiro Sato, Ichizo Tsujino
    The international journal of cardiovascular imaging, 27 Mar. 2024, [International Magazine]
    English, Scientific journal, Right ventricular (RV) diastolic stiffness is an independent predictor of survival and is strongly associated with disease severity in patients with precapillary pulmonary hypertension (PH). Therefore, a fully validated echocardiographic method for assessing RV diastolic stiffness needs to be established. This study aimed to compare echocardiography-derived RV diastolic stiffness and invasively measured pressure-volume loop-derived RV diastolic stiffness in patients with precapillary PH. We studied 50 consecutive patients with suspected or confirmed precapillary PH who underwent cardiac catheterization, magnetic resonance imaging, and echocardiography within a 1-week interval. Single-beat RV pressure-volume analysis was performed to determine the gold standard for RV diastolic stiffness. Elevated RV end-diastolic pressure (RVEDP) was defined as RVEDP ≥ 8 mmHg. Using continuous-wave Doppler and M-mode echocardiography, an echocardiographic index of RV diastolic stiffness was calculated as the ratio of the atrial-systolic descent of the pulmonary artery-RV pressure gradient derived from pulmonary regurgitant velocity (PRPGDAC) to the tricuspid annular plane movement during atrial contraction (TAPMAC). PRPGDAC/TAPMAC showed significant correlation with β (r = 0.54, p < 0.001) and RVEDP (r = 0.61, p < 0.001). A cut-off value of 0.74 mmHg/mm for PRPGDAC/TAPMAC showed 83% sensitivity and 93% specificity for identifying elevated RVEDP. Multivariate analyses indicated that PRPGDAC/TAPMAC was independently associated with disease severity in patients with precapillary PH, including substantial PH symptoms, stroke volume index, right atrial size, and pressure. PRPGDAC/TAPMAC, based on pulmonary regurgitation velocity waveform analysis, is useful for the noninvasive assessment of RV diastolic stiffness and is associated with prognostic risk factors in precapillary PH.
  • Prognostic Value of Combined Assessments of Late Gadolinium Enhancement and Fluorodeoxyglucose Uptake in Cardiac Sarcoidosis.
    Sho Kazui, Sakae Takenaka, Toshiyuki Nagai, Satonori Tsuneta, Kenji Hirata, Yoshiya Kato, Hirokazu Komoriyama, Yuta Kobayashi, Akinori Takahashi, Kiwamu Kamiya, Taro Temma, Takuma Sato, Atsushi Tada, Yutaro Yasui, Michikazu Nakai, Takahiro Sato, Ichizo Tsujino, Kohsuke Kudo, Satoshi Konno, Toshihisa Anzai
    JACC. Cardiovascular imaging, 11 Mar. 2024, [International Magazine]
    English
  • Insulin resistance assessed by short insulin tolerance test and its association with obesity and insulin resistance-related parameters in humans: A pilot randomized trial.
    Akiko Hayashishita, Taku Watanabe, Naoko Suzuki, Toshitaka Nakaya, Ayako Sugimoto, Isao Yokota, Hiroshi Ohira, Masaharu Nishimura, Ichizo Tsujino
    PloS one, 19, 6, e0297718, 2024, [International Magazine]
    English, Scientific journal, The aim of this study was to examine the association of insulin resistance (evaluated by the short insulin tolerance test [SITT]) with parameters related to obesity and insulin resistance. We prospectively recruited controls and patients with type 2 diabetes mellitus (T2DM), subjected them to the SITT, and calculated the K indices of the intravenous insulin tolerance test (KITT(iv)) and the subcutaneous insulin tolerance test (KITT(sc)). We compared KITT(iv) results between the volunteers and patients and examined its correlation with KITT(sc). We also examined the association of KITT(iv) with obesity, insulin resistance-related parameters, and the insulin dose required for glycemic control. A total of 24 participants (seven controls and 17 patients with T2DM) were studied. The mean KITT(iv) was significantly lower in patients with T2DM than in the controls (2.5%±2.1% vs. 4.5%±1.8%). In all participants, KITT(iv) was significantly correlated with the homeostasis model assessment for insulin resistance (HOMA-IR) values (r = -0.601, p<0.05) but not with KITT(sc) (p = 0.62). KITT(iv) was correlated positively with the serum adiponectin concentration, but negatively with the visceral fat area and serum concentrations of tumor necrosis factor-α and branched-chain amino acids. In patients with T2DM, KITT(iv) and HOMA-IR values were significantly correlated with the total insulin dose required for glycemic control. Insulin resistance evaluated using KITT(iv) was correlated with the HOMA-IR values, but not with the resistance evaluated using KITT(sc). The degree of insulin resistance was associated with biomarkers, such as adiponectin, tumor necrosis factor-α, branched-chain amino acids, the visceral fat area, and the dose of insulin required for glycemic control.
  • Adult-onset idiopathic peripheral pulmonary artery stenosis
    Yudai Tamura, Yuichi Tamura, Ayako Shigeta, Kazuya Hosokawa, Yu Taniguchi, Takumi Inami, Shiro Adachi, Ichizo Tsujino, Naohiko Nakanishi, Kimi Sato, Jiro Sakamoto, Nobuhiro Tanabe, Noriaki Takama, Kazuto Nakamura, Kayoko Kubota, Naohiro Komura, Shigehiko Kato, Jun Yamashita, Makoto Takei, Shuji Joho, Shunsuke Ishii, Ryo Takemura, Koichiro Sugimura, Koichiro Tatsumi
    European Respiratory Journal, 2300763, 2300763, European Respiratory Society (ERS), 07 Dec. 2023
    Scientific journal, Background

    Peripheral pulmonary artery stenosis (PPS) refers to the stenosis of the pulmonary artery from the trunk to the peripheral arteries. Although pediatric PPS is well described, the clinical characteristics of adult-onset idiopathic PPS have not been established.

    Objectives

    We characterized the disease profile of adult-onset PPS.

    Methods

    We collected data in Japanese centers. This cohort included patients underwent pulmonary angiography (PAG) and excluded patients with chronic thromboembolic pulmonary hypertension or Takayasu arteritis. Patient backgrounds, right heart catheterization findings, imaging findings, and treatment profiles were collected.

    Results

    Forty-four patients (median age: 39 years [Q1–Q3:29–57]; 29 females [65.9%]) with PPS were enrolled from 20 centers. In PAG, stenosis of segmental and peripheral pulmonary arteries was observed in 41 (93.2%) and 36 patients (81.8%), respectively. Thirty-five patients (79.5%) received medications approved for pulmonary arterial hypertension (PAH-drugs) and 22 patients (50.0%) received combination therapy. Twenty-five patients (56.8%) underwent transcatheter pulmonary angioplasty. Right heart catheterization data showed improvements in both the mean pulmonary artery pressure (44versus40 mmHg; p<0.001) and pulmonary vascular resistance (760versus514 dyn·s·cm−5; p<0.001) from baseline to the final follow-up. The 3-, 5-, and 10-year survival rates of patients with PPS were 97.5% (95% confidence interval [CI]:83.5–99.6), 89.0% [95% CI:68.9–96.4), and 67.0% (95% CI:41.4–83.3), respectively.

    Conclusions

    In this study, the patients with adult-onset idiopathic PPS presented with segmental and peripheral pulmonary artery stenosis. Although patients had severe pulmonary hypertension at baseline, they showed a favorable treatment response to the PAH-drugs combined with transcatheter pulmonary angioplasty.
  • A Multicenter, Single-Blind, Randomized, Warfarin-Controlled Trial of Edoxaban in Patients With Chronic Thromboembolic Pulmonary Hypertension: KABUKI Trial
    Kazuya Hosokawa, Hiroko Watanabe, Yu Taniguchi, Nobutaka Ikeda, Takumi Inami, Satoshi Yasuda, Toyoaki Murohara, Masaru Hatano, Yuichi Tamura, Jun Yamashita, Koichiro Tatsumi, Ichizo Tsujino, Yuko Kobayakawa, Shiro Adachi, Nobuhiro Yaoita, Shun Minatsuki, Koji Todaka, Keiichi Fukuda, Hiroyuki Tsutsui, Kohtaro Abe
    Circulation, Ovid Technologies (Wolters Kluwer Health), 13 Nov. 2023
    Scientific journal
  • 心臓サルコイドーシス患者の免疫抑制療法開始後における心筋トロポニン値経時的評価の予後的意義               
    數井 翔, 竹中 秀, 永井 利幸, 加藤 喜哉, 小森山 弘和, 小林 雄太, 高橋 昌寛, 神谷 究, 佐藤 琢真, 多田 篤司, 安井 悠太郎, 中井 陸運, 佐藤 隆博, 辻野 一三, 今野 哲, 安斉 俊久
    日本サルコイドーシス/肉芽腫性疾患学会雑誌, 43, サプリメント号, 64, 64, 日本サルコイドーシス, Oct. 2023
    Japanese
  • The chest CT signs for pulmonary veno-occlusive disease correlate with pulmonary haemodynamics in systemic sclerosis.
    Haruka Moriya, Masaru Kato, Ryo Hisada, Keita Ninagawa, Maria Tada, Kodai Sakiyama, Mitsutaka Yasuda, Michihito Kono, Yuichiro Fujieda, Olga Amengual, Yasuka Kikuchi, Ichizo Tsujino, Takahiro Sato, Tatsuya Atsumi
    Rheumatology (Oxford, England), 15 Sep. 2023, [International Magazine]
    English, Scientific journal, OBJECTIVE: Pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc) sometimes accompanies pulmonary veno-occlusive disease (PVOD). We aimed to reveal the relation between clinical signs of PVOD and severing of pulmonary vasculopathy in SSc. METHODS: This study comprised 52 consecutive SSc patients who had pulmonary haemodynamic abnormalities (mPAP > 20 mmHg, PVR > 2 W.U. or PAWP > 15 mmHg). The chest CT scan was evaluated in all patients. Patients were divided into two groups, the 0-1 group and the 2-3 group, according to the number of chest CT signs for PVOD, including 1) mediastinal lymph node enlargement, 2) thickened interlobular septal wall, and 3) ground glass opacity. Pulmonary haemodynamics, echocardiography and MRI-based cardiac function, pulmonary function, and serum biomarkers were compared between the two groups. RESULTS: Mediastinal lymph node enlargement, thickened interlobular septal wall, and ground glass opacity were observed in 11 (21%), 32 (62%), and 11 (21%) patients, respectively. The 2-3 group (n = 15) had higher mPAP (p= 0.02) while lower DLco/VA (p= 0.02) compared with the 0-1 group (n = 37). Other parameters, including PAWP, cardiac output, left ventricular ejection fraction, left atrial diameter, forced vital capacity, brain natriuretic peptide, and Krebs von den Lunge-6 were not different between the two groups. CONCLUSION: The CT signs for PVOD had positive correlation with mPAP but negative correlation with DLco in SSc patients, indicating that PAH-SSc may reflect a spectrum of pulmonary vascular disease that ranges from the pulmonary artery to the vein.
  • Impact of cancer on the prevalence, management, and outcome of patients with chronic thromboembolic pulmonary hypertension.
    Junichi Nakamura, Ichizo Tsujino, Hideki Shima, Toshitaka Nakaya, Ayako Sugimoto, Takahiro Sato, Taku Watanabe, Hiroshi Ohira, Masaru Suzuki, Isao Yokota, Satoshi Konno
    Journal of thrombosis and thrombolysis, 24 Aug. 2023, [International Magazine]
    English, Scientific journal, INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) results from unresolved thrombotic obstruction of the pulmonary vasculature. Cancer is a known risk factor for CTEPH. This study aimed to determine the impact of cancer on the prevalence, management, and outcomes of patients with CTEPH. MATERIALS AND METHODS: In this retrospective study involving 99 patients sequentially diagnosed with CTEPH in our hospital, the prevalence of 10 comorbid conditions including a past history of cancer at the time of CTEPH diagnosis were calculated. RESULTS: Among the 99 patients, 17 (17%) had a history of cancer. Breast cancer (n = 6) was the most common cancer type, followed by gastrointestinal cancer (n = 3), uterine cancer (n = 2), and malignant lymphoma (n = 2). Between patients with and without cancer, there were no differences in the demographics, severity of CTEPH, and management; however, the 5-year survival rate was lower for patients with cancer (65%) than for those without (89%). In addition, patients with cancer had significantly worse survival than those without (p = 0.03 by log-rank test). During follow-up, nine patients developed cancer after the diagnosis of CTEPH. Among the 99 patients, 13 died during follow-up, 6 (46%) of whom died of cancer. CONCLUSIONS: 17% of our patients with CETPH were diagnosed with cancer, with breast and gastrointestinal tract cancers being the most common. Cancer comorbidity was associated with a poor prognosis and contributed to death in 46% of deceased patients. The impact of cancer on CTEPH should be further evaluated in the future.
  • Association of longitudinal cardiac troponin trajectory with adverse events in patients with cardiac sarcoidosis.
    Sho Kazui, Sakae Takenaka, Toshiyuki Nagai, Yoshiya Kato, Hirokazu Komoriyama, Yuta Kobayashi, Akinori Takahashi, Kiwamu Kamiya, Takuma Sato, Atsushi Tada, Yutaro Yasui, Michikazu Nakai, Takahiro Sato, Ichizo Tsujino, Satoshi Konno, Toshihisa Anzai
    International journal of cardiology, 389, 131268, 131268, 15 Aug. 2023, [International Magazine]
    English, Scientific journal, BACKGROUND: Although high-sensitivity cardiac troponins may be sensitive and easily repeatable markers of disease activity in patients with cardiac sarcoidosis (CS), the association between longitudinal cardiac troponin trajectory and adverse events remains unclear. This study aimed to clarify whether longitudinal cardiac troponin levels were associated with adverse events in patients with CS. METHODS: We examined 63 consecutive CS-initiated prednisolone (PSL) patients with available longitudinal high-sensitivity cardiac troponin T (cTnT) data between December 2013 and March 2023. The area under the cTnT trajectory, which reflected cumulative cTnT release, was calculated to assess the association between longitudinal cTnT levels and adverse events. Patients were divided into two groups according to the median area under the cTnT trajectory per month. The primary outcome was a composite of sustained ventricular tachycardia or fibrillation, worsening heart failure, and sudden cardiac death (SCD). RESULTS: In total, 463 cTnT measurements were collected over a median follow-up period of 30.4 (interquartile range [IQR] 15.6-34.2) months. The primary outcome was observed in 12 (19%) patients. A higher area under the cTnT trajectory was significantly associated with an increased incidence of the primary outcome (P = 0.027), while cTnT levels before and one month after initiation of PSL, and these changes were not related to adverse events (P = 0.179, 0.096, and 0.95, respectively). CONCLUSIONS: Longitudinal cTnT trajectory following PSL initiation was associated with adverse cardiac events in patients with CS, suggesting that longitudinal measurement of cTnT would be useful for the early identification of high-risk patients.
  • Initial Triple Combination Therapy Including Intravenous Prostaglandin I<sub>2</sub> for the Treatment of Patients with Severe Pulmonary Arterial Hypertension
    Yuichi Tamura, Hiraku Kumamaru, Shiori Nishimura, Yasuo Nakajima, Hiromi Matsubara, Yu Taniguchi, Ichizo Tsujino, Ayako Shigeta, Koichiro Kinugawa, Kazuhiro Kimura, Koichiro Tatsumi
    International Heart Journal, 64, 4, 684, 692, International Heart Journal (Japanese Heart Journal), 29 Jul. 2023
    Scientific journal
  • Long-term outcome of chronic thromboembolic pulmonary hypertension using direct oral anticoagulants and warfarin: a Japanese prospective cohort study.
    Kazuya Hosokawa, Kohtaro Abe, Kouta Funakoshi, Yuichi Tamura, Naoki Nakashima, Koji Todaka, Yu Taniguchi, Takumi Inami, Shiro Adachi, Ichizo Tsujino, Jun Yamashita, Shun Minatsuki, Nobutaka Ikeda, Hiroto Shimokawahara, Takashi Kawakami, Takeshi Ogo, Masaru Hatano, Hitoshi Ogino, Yoshihiro Fukumoto, Nobuhiro Tanabe, Hiromi Matsubara, Keiichi Fukuda, Koichiro Tatsumi, Hiroyuki Tsutsui
    Journal of thrombosis and haemostasis : JTH, 10 Apr. 2023, [International Magazine]
    English, Scientific journal, BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) requires lifelong anticoagulation. Long-term outcomes of CTEPH under current anticoagulants are unclear. OBJECTIVES: The CTEPH AC registry is a prospective, nationwide cohort study comparing the safety and effectiveness of direct oral anticoagulants (DOACs) and warfarin for CTEPH. PATIENTS/METHODS: Patients with CTEPH, both tre atment-naïve and on treatment, were eligible for the registry. Inclusion criteria were patients aged ≥20 years and those who were diagnosed with CTEPH according to standard guidelines. Exclusion criteria were not specified. The primary efficacy outcome was a composite morbidity, and mortality outcome comprised all-cause death, rescue reperfusion therapy, initiation of parenteral pulmonary vasodilators, and worsened 6-minute walk distance and WHO functional class. The safety outcome was clinically relevant bleeding, including major bleeding. RESULTS: Nine hundred twenty-seven patients on oral anticoagulants at baseline were analyzed: 481 (52%) used DOACs and 446 (48%) used warfarin. The 1-, 2-, and 3-year rates of composite morbidity and mortality outcome were comparable between the DOAC and warfarin groups (2.6%, 3.1%, and 4.2% vs 3.0%, 4.8%, and 5.9%, respectively; P = .52). The 1-, 2-, and 3-year rates of clinically relevant bleeding were significantly lower in DOACs than in the warfarin group (0.8%, 2.4%, and 2.4% vs 2.5%, 4.8%, and 6.4%, respectively; P = 0.036). Multivariable Cox proportional-hazards regression models revealed lower risk of clinically relevant bleeding in the DOAC group than the warfarin group (hazard ratio: 0.35; 95% CI: 0.13-0.91; P = .032). CONCLUSION: This registry demonstrated that under current standard of care, morbidity and mortality events were effectively prevented regardless of anticoagulants, while the clinically relevant bleeding rate was lower when using DOACs compared with warfarin.
  • SATISFY-JP, a phase II multicenter open-label study on Satralizumab, an anti-IL-6 receptor antibody, use for the treatment of pulmonary arterial hypertension in patients with an immune-responsive-phenotype: Study protocol.
    Yuichi Tamura, Rika Takeyasu, Tomohiro Takata, Naoki Miyazaki, Ryo Takemura, Michihiko Wada, Yudai Tamura, Kohtaro Abe, Ayako Shigeta, Yu Taniguchi, Shiro Adachi, Takumi Inami, Ichizo Tsujino, Nobuhiro Tahara, Masataka Kuwana
    Pulmonary circulation, 13, 2, e12251, Apr. 2023, [International Magazine]
    English, Scientific journal, Pulmonary arterial hypertension (PAH), an intractable disease with a poor prognosis, is commonly treated using pulmonary vasodilators modulating the endothelin, cGMP, and prostacyclin pathway. Since the 2010s, drugs for treating pulmonary hypertension based on mechanisms other than pulmonary vasodilation have been actively developed. However, precision medicine is based on tailoring disease treatment to particular phenotypes by molecular-targeted drugs. Since interleukin-6 (IL-6) is involved in the development of PAH in animal models, and some patients with PAH have elevated IL-6 levels, the cytokine is expected to obtain potentials for therapeutic targeting. Accordingly, we identified a phenotype with elevated cytokine activity of the IL-6 family in the PAH population by combining case data extracted from the Japan Pulmonary Hypertension Registry with a comprehensive analysis of 48 cytokines using artificial intelligence clustering techniques. Including an IL-6 threshold ≥2.73 pg/mL as inclusion criteria for reducing the risk of insufficient efficacy, an investigator-initiated clinical study using satralizumab, a recycling anti-IL6 receptor monoclonal antibody, for patients with an immune-responsive phenotype is underway. This study is intended to test whether use of patient biomarker profile can identify a phenotype responsive to anti-IL6 therapy.
  • Clinical and Hemodynamic Responses to Imatinib in Pulmonary Veno-Occlusive Disease/Pulmonary Capillary Hemangiomatosis: A Retrospective Pilot Study of Five Cases and Review of the Literature
    Junichi Nakamura, Ichizo Tsujino, Hideki Shima, Toshitaka Nakaya, Ayako Sugimoto, Takahiro Sato, Taku Watanabe, Hiroshi Ohira, Masaru Suzuki, Satonori Tsuneta, Ryo Hisada, Masaru Kato, Satoshi Konno
    American Journal of Cardiovascular Drugs, 23, 3, 329, 338, Springer Science and Business Media LLC, 30 Mar. 2023
    Scientific journal
  • Risk Factors and Impact on Outcomes of Thrombosis in Patients with COVID-19 in Japan: From the CLOT-COVID Study.
    Sen Yachi, Makoto Takeyama, Yuji Nishimoto, Ichizo Tsujino, Junichi Nakamura, Naoto Yamamoto, Hiroko Nakata, Satoshi Ikeda, Michihisa Umetsu, Shizu Aikawa, Hiroya Hayashi, Hirono Satokawa, Yoshinori Okuno, Eriko Iwata, Yoshito Ogihara, Nobutaka Ikeda, Akane Kondo, Takehisa Iwai, Norikazu Yamada, Tomohiro Ogawa, Takao Kobayashi, Makoto Mo, Yugo Yamashita, On Behalf Of The Clot-Covid Study Investigators
    Annals of vascular diseases, 16, 1, 31, 37, 25 Mar. 2023, [Domestic magazines]
    English, Scientific journal, Objectives: The relationship between the thrombotic event and prognosis in patients with coronavirus disease 2019 (COVID-19) has not yet been fully investigated in Japan. Our study aimed to investigate the clinical outcomes and risk factors for thrombosis in hospitalized patients with COVID-19 in Japan. Materials and Methods: We compared the patient characteristics and clinical outcomes among patients with thrombosis (N=55) and those without thrombosis (N=2839) by using a large-scale data of CLOT-COVID study (thrombosis and antiCoaguLatiOn Therapy in patients with COVID-19 in Japan Study: UMIN000045800). Thrombosis included venous thromboembolism, ischemic stroke, myocardial infarction, and systemic arterial thromboembolism. Results: Higher rates of mortality and bleeding events were shown in hospitalized patients with COVID-19 with thrombosis compared to those without thrombosis (all-cause mortality, 23.6% vs. 5.1%, P<0.001; major bleeding, 23.6% vs. 1.6%, P<0.001). Multivariable analysis revealed that the independent risk factors of thrombosis were male sex, D-dimer level on admission>1.0 µg/mL, and moderate and severe COVID-19 status on admission. Conclusions: The development of thrombosis in hospitalized patients with COVID-19 was related to higher mortality and major bleeding, and several independent risk factors for thrombosis could help determine the patient-appropriate treatment for COVID-19.
  • 呼吸と循環のCross road:肺高血圧症の臨床と基礎の最前線 間質性肺疾患に伴う肺高血圧症の剖検例における肺血管病変の病理学的解析
    杉本 絢子, 辻野 一三, 中村 順一, 佐藤 隆博, 鈴木 雅, 高村 圭, 岩崎 沙理, 種井 善一, 谷口 浩二, 田中 伸哉, 今野 哲
    日本呼吸器学会誌, 12, 増刊, 44, 44, (一社)日本呼吸器学会, Mar. 2023
    Japanese
  • Prophylactic Anticoagulation and Thrombosis in Hospitalized Patients with Clinically Stable COVID-19 at Admission: From the Practice-Based Observational Study
    Yugo Yamashita, Sen Yachi, Makoto Takeyama, Yuji Nishimoto, Ichizo Tsujino, Junichi Nakamura, Naoto Yamamoto, Hiroko Nakata, Satoshi Ikeda, Michihisa Umetsu, Shizu Aikawa, Hiroya Hayashi, Hirono Satokawa, Yoshinori Okuno, Eriko Iwata, Yoshito Ogihara, Nobutaka Ikeda, Akane Kondo, Takehisa Iwai, Norikazu Yamada, Tomohiro Ogawa, Takao Kobayashi, Makoto Mo, on behalf of the Clot-COVID Study Investigators
    Annals of Vascular Diseases, 2023
    English, Scientific journal
  • Pulmonary arterial hypertension in an 80-year-old man with long-term use of cyclophosphamide.
    Takatoshi Suzuki, Ichizo Tsujino, Wataru Harabayashi, Hideki Shima, Junichi Nakamura, Takahiro Sato, Masaru Suzuki, Yukari Takeda, Satohi Konno
    Respiratory medicine case reports, 44, 101867, 101867, 2023, [International Magazine]
    English, An 80-year-old man diagnosed with primary macroglobulinemia 7 years earlier had been treated with cyclophosphamide, following which he developed dyspnea on exertion. Cyclophosphamide was discontinued. The patient's dyspnea, however, failed to improve. Right heart catheterization (RHC) revealed precapillary pulmonary hypertension (PH). He was transferred to our institution for further examination. Prior use of cyclophosphamide was the patient's only risk factor for PH, and cyclophosphamide use was considered as a possible cause of PH in this case. He was treated with tadalafil and dyspnea gradually improved. A follow-up RHC exhibited improvement in mean pulmonary arterial pressure and pulmonary vascular resistance.
  • Validation of Echocardiographic Estimation of Right Atrial Pressure: Reconsideration of Guideline-Based Secondary Indices
    Murayama Michito, Kaga Sanae, Onoda Airi, Okada Kazunori, Nakabachi Masahiro, Yokoyama Shinobu, Nishino Hisao, Aoyagi Hiroyuki, Tamaki Yoji, Motoi Ko, Ishizaka Suguru, Iwano Hiroyuki, Nagai Toshiyuki, Tsujino Ichizo, Anzai Toshihisa
    Japanese Journal of Medical Ultrasound Technology, advpub, Japanese Society of Sonographers, 2023
    Japanese, Purpose: Sonographic measurements of the inferior vena cava parameters are common noninvasive methods for estimating right atrial pressure. In intermediate cases in which the inferior vena cava parameters showed indeterminate value, the current guidelines of the American Society of Echocardiography recommended using secondary indices, which include restrictive right-sided diastolic filling pattern, the ratio of early-diastolic transtricuspid flow velocity to tricuspid annular velocity, and the hepatic venous systolic filling fraction. We aimed to clarify whether the above secondary indices improve the diagnostic ability of elevated right atrial pressure using inferior vena cava parameters and to test the incremental predictive value of right atrial area measurement.

    Subjects and Methods: In 128 consecutive patients with various cardiac diseases referred for cardiac catheterization, the elevated right atrial pressure was defined as greater than or equal to 8 mmHg. Based on the inferior vena cava morphology, the estimated right atrial pressure was determined as 3, 8, and 15 mmHg (model 1). Additionally, the restrictive filling pattern, the ratio of early-diastolic transtricuspid flow velocity to tricuspid annular velocity, and the systolic filling fraction were evaluated to reclassify the intermediate value of 8 mmHg (model 2). The right atrial minimum and maximum area and volume were measured at ventricular end diastole and end systole, respectively, and the expansion indices were calculated.

    Results: Elevated right atrial pressure was observed in 29 patients. Logistic regression analysis showed that estimated right atrial pressure based on the inferior vena cava indices and systolic filling fraction were significantly associated with elevated right atrial pressure (p<0.05). Restrictive filling pattern was not observed in any of the patients, and the ratio of early-diastolic transtricuspid flow velocity to tricuspid annular velocity was not associated with elevated right atrial pressure. Right atrial morphological and functional parameters were significantly associated with elevated right atrial pressure (p<0.05). Notably, the minimum right atrial area demonstrated the strongest association with right atrial pressure elevation (odds ratio adjusted for right ventricular systolic function: 10.64, p<0.01). The predictive ability of model 2 was comparable to that of model 1 (global χ2 value=9 for model 1, 11 for model 2; p=0.28). In contrast, incorporated with systolic filling fraction and minimal right atrial area as secondary indices, the predictive ability of the new model was improved compared to that of model 1 (global χ2 value=9 for model 1, 25 for the new model; p<0.01).

    Conclusion: Reclassification using guideline-recommended secondary indices failed to improve the predictive ability of elevated right atrial pressure. In contrast, a combination of systolic filling fraction and minimal right atrial area with inferior vena cava indices improved the predictive ability of elevated right atrial pressure.
  • Clinical Features Comparing Arterial Thrombosis and Venous Thromboembolism in Hospitalized Patients with COVID-19: Result from the CLOT-COVID Study
    Michihisa Umetsu, Hajime Kanamori, Koji Murakami, Takuya Shiga, Sen Yachi, Makoto Takeyama, Yuji Nishimoto, Ichizo Tsujino, Junichi Nakamura, Naoto Yamamoto, Hiroko Nakata, Satoshi Ikeda, Shizu Aikawa, Hiroya Hayashi, Hirono Satokawa, Yoshinori Okuno, Eriko Iwata, Yoshito Ogihara, Nobutaka Ikeda, Akane Kondo, Takehisa Iwai, Norikazu Yamada, Tomohiro Ogawa, Takao Kobayashi, Makoto Mo, Yugo Yamashita
    Annals of Vascular Diseases, The Editorial Committee of Annals of Vascular Diseases, 2023
    Scientific journal
  • Efficacy, safety, and pharmacokinetics of inhaled treprostinil in Japanese patients with pulmonary arterial hypertension
    Masataka Kuwana, Kohtaro Abe, Hideyuki Kinoshita, Hiromi Matsubara, Shun Minatsuki, Toyoaki Murohara, Seiichiro Sakao, Yuichiro Shirai, Nobuhiro Tahara, Ichizo Tsujino, Kenta Takahashi, Shingo Kanda, Takeshi Ogo
    Pulmonary Circulation, 13, 1, Wiley, Jan. 2023
    Scientific journal
  • Real-World Management of Pharmacological Thromboprophylactic Strategies for COVID-19 Patients in Japan: From the CLOT-COVID Study.
    Hiroya Hayashi, Yasuhiro Izumiya, Daiju Fukuda, Fumiaki Wakita, Yasumitsu Mizobata, Hiromichi Fujii, Sen Yachi, Makoto Takeyama, Yuji Nishimoto, Ichizo Tsujino, Junichi Nakamura, Naoto Yamamoto, Hiroko Nakata, Satoshi Ikeda, Michihisa Umetsu, Shizu Aikawa, Hirono Satokawa, Yoshinori Okuno, Eriko Iwata, Yoshito Ogihara, Nobutaka Ikeda, Akane Kondo, Takehisa Iwai, Norikazu Yamada, Tomohiro Ogawa, Takao Kobayashi, Makoto Mo, Yugo Yamashita
    JACC. Asia, 2, 7, 897, 907, Dec. 2022, [International Magazine]
    English, Scientific journal, BACKGROUND: Data on prophylactic anticoagulation are important in understanding the current issues, unmet needs, and optimal management of Japanese COVID-19 patients. OBJECTIVES: This study aimed to investigate the clinical management strategies for prophylactic anticoagulation of COVID-19 patients in Japan. METHODS: The CLOT-COVID study was a multicenter observational study that enrolled 2,894 consecutive hospitalized patients with COVID-19. The study population consisted of 2,889 patients (after excluding 5 patients with missing data); it was divided into 2 groups: patients with pharmacological thromboprophylaxis (n = 1,240) and those without (n = 1,649). Furthermore, we evaluated the 1,233 patients who received prophylactic anticoagulation-excluding 7 patients who could not be classified based on the intensity of their anticoagulants-who were then divided into 2 groups: patients receiving prophylactic anticoagulant doses (n = 889) and therapeutic anticoagulant doses (n = 344). RESULTS: The most common pharmacological thromboprophylaxis anticoagulant was unfractionated heparin (68.2%). The severity of COVID-19 at admission was a predictor of the implementation of pharmacological thromboprophylaxis in the multivariable analysis (moderate vs mild: OR: 16.6; 95% CI:13.2-21.0; P < 0.001, severe vs mild: OR: 342.6, 95% CI: 107.7-1090.2; P < 0.001). It was also a predictor of the usage of anticoagulants of therapeutic doses in the multivariable analysis (moderate vs mild: OR: 2.10; 95% CI: 1.46-3.02; P < 0.001, severe vs mild: OR: 5.96; 95% CI: 3.91-9.09; P < 0.001). CONCLUSIONS: In the current real-world Japanese registry, pharmacological thromboprophylaxis, especially anticoagulants at therapeutic doses, was selectively implemented in COVID-19 patients with comorbidities and severe COVID-19 status at admission.
  • Risk of bleeding associated with transbronchial biopsy using flexible bronchoscopy in patients with echocardiographic or chest CT evidence of pulmonary hypertension.
    Yuta Takashima, Naofumi Shinagawa, Daisuke Morinaga, Junichi Nakamura, Megumi Furuta, Tetsuaki Shoji, Hajime Asahina, Eiki Kikuchi, Junko Kikuchi, Jun Sakakibara-Konishi, Ichizo Tsujino, Satoshi Konno
    BMC pulmonary medicine, 22, 1, 449, 449, 28 Nov. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: Endobronchial ultrasound (EBUS)-guided transbronchial biopsy (TBB) facilitates the diagnosis of various respiratory diseases. The safety of performing EBUS-guided TBB in patients with a finding of pulmonary hypertension (PH) is controversial. Little is known about the relationship between the risk of bleeding associated with EBUS-guided TBB in the presence of PH suspected on echocardiography or chest CT. METHODS: To assess the risk of bleeding associated with EBUS-guided TBB in patients with presumed PH per echocardiography or chest CT, we retrospectively reviewed the medical records of 314 consecutive patients who underwent EBUS-guided TBB using a guide sheath (GS), as well as echocardiography and chest CT. Bleeding complication was defined as over one minute of suctioning; repeated wedging of the bronchoscope; instillation of cold saline, diluted vasoactive substances, or thrombin due to persistent bleeding. Findings of suspected PH were defined as peak tricuspid regurgitation velocity (TRV) > 2.8 m/s on echocardiography or pulmonary artery to aorta ratio (PA:A ratio) > 0.9 on chest CT. RESULTS: In total, 35 (11.1%) patients developed bleeding, and all cases were managed safely. Furthermore, 17 (5.4%) and 59 (18.8%) patients were suspected to have PH based on echocardiography and chest CT, respectively. Among the patients suspected to have PH on echocardiography, five (5/17 = 29.4%) patients developed bleeding. Among the patients suspected to have PH on chest CT, 11 (11/59 = 18.6%) patients developed bleeding. Univariate analysis revealed that long diameter (≥ 30 mm) of the lesion, lesion location (the biopsy site was inner than the segmental bronchus), bronchoscopic diagnosis of malignancy, and additional biopsy were potential predictive factors for bleeding. The finding of suspected PH on echocardiography correlated significantly with bleeding (p = 0.03). On multivariate analysis, long diameter (≥ 30 mm) of the lesion (p = .021) and findings of suspected PH on echocardiography (p = .049) were significantly associated with bleeding. CONCLUSION: All cases of bleeding in the present study were managed safely. The risk of bleeding is moderately elevated when PH is suspected by echocardiography in patients undergoing EBUS-guided TBB using a GS.
  • Mortality-Associated Risk Factors in Hospitalized COVID-19 Patients in Japan: Findings of the CLOT-COVID Study.
    Makoto Takeyama, Sen Yachi, Yuji Nishimoto, Ichizo Tsujino, Junichi Nakamura, Naoto Yamamoto, Hiroko Nakata, Satoshi Ikeda, Michihisa Umetsu, Shizu Aikawa, Hiroya Hayashi, Hirono Satokawa, Yoshinori Okuno, Eriko Iwata, Yoshito Ogihara, Nobutaka Ikeda, Akane Kondo, Takehisa Iwai, Norikazu Yamada, Tomohiro Ogawa, Takao Kobayashi, Makoto Mo, Yugo Yamashita
    Journal of epidemiology, 33, 3, 150, 157, 12 Nov. 2022, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, BACKGROUND: Reports of mortality-associated risk factors in patients with coronavirus disease (COVID-19) are limited. METHODS: We evaluated the clinical features that were associated with mortality among patients who died during hospitalization (N=158) and those who were alive at discharge (N=2,736) from the large-scale, multicenter, retrospective, observational cohort CLOT-COVID study enrolled consecutively hospitalized COVID-19 patients from 16 centers in Japan from April to September 2021. Data from 2,894 hospitalized COVID-19 participants of the CLOT-COVID study were analyzed in this study. RESULTS: Patients who died were older (71.1 years versus 51.6 years, P<0.001), had higher median D-dimer values on admission (1.7 μg/mL versus 0.8 μg/mL, P<0.001), and had more comorbidities. On admission, the patients who died had more severe COVID-19 than did those who survived (mild: 16% versus 63%, moderate: 47% versus 31%, and severe: 37% versus 6.2%, P<0.001). In patients who died, the incidence of thrombosis and major bleeding during hospitalization was significantly higher than that in those who survived (thrombosis: 8.2% vs. 1.5%, P<0.001; major bleeding: 12.7% vs. 1.4%, P<0.001). Multivariable logistic regression analysis revealed that age >70 years, high D-dimer values on admission, heart disease, active cancer, higher COVID-19 severity on admission, and development of major bleeding during hospitalization were independently associated with a higher mortality risk. CONCLUSIONS: This large-scale observational study in Japan identified several independent risk factors for mortality in hospitalized patients with COVID-19 that could facilitate appropriate risk stratification of patients with COVID-19.
  • Clinical Management and Outcomes of Patients With Portopulmonary Hypertension Enrolled in the Japanese Multicenter Registry.
    Yudai Tamura, Yuichi Tamura, Yu Taniguchi, Ichizo Tsujino, Takumi Inami, Hiromi Matsubara, Ayako Shigeta, Yoichi Sugiyama, Shiro Adachi, Kohtaro Abe, Yuichi Baba, Masaru Hatano, Satoshi Ikeda, Kenya Kusunose, Koichiro Sugimura, Soichiro Usui, Yasuchika Takeishi, Kaoru Dohi, Saki Hasegawa-Tamba, Koshin Horimoto, Noriko Kikuchi, Hiraku Kumamaru, Koichiro Tatsumi
    Circulation reports, 4, 11, 542, 549, 10 Nov. 2022, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, Background: Portopulmonary hypertension (PoPH) is one of the major underlying causes of pulmonary arterial hypertension (PAH). However, PoPH, especially treatment strategies, has been poorly studied. Therefore, this study evaluated current treatments for PoPH, their efficacy, and clinical outcomes of patients with PoPH. Methods and Results: Clinical data were collected for patients with PoPH who were enrolled in the Japan Pulmonary Hypertension Registry between 2008 and 2021. Hemodynamic changes, functional class, and clinical outcomes were compared between patients with PoPH treated with monotherapy and those treated with combination therapies. Clinical data were analyzed for 62 patients with PoPH, including 25 treatment-naïve patients, from 21 centers in Japan. In more than half the patients, PAH-specific therapy improved the New York Heart Association functional class by at least one class. The 3- and 5-year survival rates of these patients were 88.5% (95% confidence interval [CI] 76.0-94.7) and 80.2% (95% CI 64.8-89.3), respectively. Forty-one (66.1%) patients received combination therapy. Compared with patients who had received monotherapy, the mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac index were significantly improved in patients who had undergone combination therapies. Conclusions: Combination therapy was commonly used in patients with PoPH with a favorable prognosis. Combination therapies resulted in significant hemodynamic improvement without an increased risk of side effects.
  • Efficacy and safety of oral pulmonary vasodilators in pulmonary veno‐occlusive disease
    Junichi Nakamura, Ichizo Tsujino, Hideki Shima, Toshitaka Nakaya, Ayako Sugimoto, Takahiro Sato, Taku Watanabe, Hiroshi Ohira, Masaru Suzuki, Satonori Tsuneta, Ryo Hisada, Masaru Kato, Satoshi Konno
    Pulmonary Circulation, 12, 4, Wiley, Oct. 2022
    Scientific journal
  • 脈管疾患における抗凝固療法の進歩 COVID-19と抗凝固療法 日本での新型コロナウイルス感染症と静脈血栓塞栓症 タスクフォース実態調査報告を含めて               
    孟 真, 山下 侑吾, 小林 隆夫, 小川 智弘, 山田 典一, 中田 弘子, 佐戸川 弘之, 池田 聡司, 山本 尚人, 谷地 繊, 竹山 誠, 西本 裕二, 林 浩也, 中村 順一, 辻野 一三, 梅津 道久, 荻原 義人, 池田 長生, 相川 志都, 岩田 英理子
    脈管学, 62, Suppl., S106, S106, (一社)日本脈管学会, Oct. 2022
    Japanese
  • Incidence, risk factors, and clinical impact of major bleeding in hospitalized patients with COVID-19: a sub-analysis of the CLOT-COVID Study.
    Junichi Nakamura, Ichizo Tsujino, Sen Yachi, Makoto Takeyama, Yuji Nishimoto, Satoshi Konno, Naoto Yamamoto, Hiroko Nakata, Satoshi Ikeda, Michihisa Umetsu, Shizu Aikawa, Hiroya Hayashi, Hirono Satokawa, Yoshinori Okuno, Eriko Iwata, Yoshito Ogihara, Nobutaka Ikeda, Akane Kondo, Takehisa Iwai, Norikazu Yamada, Tomohiro Ogawa, Takao Kobayashi, Makoto Mo, Yugo Yamashita
    Thrombosis journal, 20, 1, 53, 53, 20 Sep. 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, BACKGROUND: The coronavirus disease 2019 (COVID-19) causes extensive coagulopathy and a potential benefit of anticoagulation therapy has been documented for prevention of thromboembolic events. Bleeding events has also been reported as a notable complication; whereas, the incidence, risks, and clinical impact of bleeding remain unclear. METHOD: The CLOT-COVID Study was a nationwide, retrospective, multicenter cohort study on consecutive hospitalized patients with COVID-19 in Japan between April 2021 and September 2021. In this sub-analysis, we compared the characteristics of patients with and without major bleeding; moreover, we examined the risk factors for and clinical impact of bleeding events. RESULTS: Among 2882 patients with COVID-19, 57 (2.0%) had major bleeding. The incidence of major bleeding increased with COVID-19 severity as follows: 0.5%, 2.3%, and 12.3% in patients with mild, moderate, and severe COVID-19, respectively. COVID-19 severity, history of major bleeding, and anticoagulant type/dose were independently and additively associated with the bleeding incidence. Compared with patients without major bleeding, those with major bleeding exhibited a longer duration of hospitalization (9 [6-14] vs 28 [19-43] days, P < 0.001) and higher mortality during hospitalization (4.9% vs. 35.1%, P < 0.001). CONCLUSIONS: In the real-world clinical practice, the incidence of major bleeding was not uncommon, especially in patients with severe COVID-19. Independent risk factors for major bleeding included history of major bleeding, COVID-19 severity, and anticoagulant use, which could be associated with poor clinical outcomes including higher mortality. Precise recognition of the risks for bleeding may be helpful for an optimal use of anticoagulants and for better outcomes in patients with COVID-19.
  • Predicting the response to pulmonary vasodilator therapy in systemic sclerosis with pulmonary hypertension by using quantitative chest CT.
    Keita Ninagawa, Masaru Kato, Yasuka Kikuchi, Hiroyuki Sugimori, Michihito Kono, Yuichiro Fujieda, Ichizo Tsujino, Tatsuya Atsumi
    Modern rheumatology, 33, 4, 758, 767, 02 Sep. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, OBJECTIVE: Systemic sclerosis (SSc) is associated with pulmonary vascular disease (PVD) and interstitial lung disease (ILD), making it difficult to differentiate pulmonary arterial hypertension and pulmonary hypertension (PH) due to lung diseases and/or hypoxia and to decide treatments. We aimed to predict the response to pulmonary vasodilators in patients with SSc and PH. METHODS: 84 SSc patients were included with 47 having PH. Chest CT was evaluated using a software to calculate abnormal lung volume (ALV). To define the response to vasodilators, Δ mean pulmonary artery pressure (mPAP)/basal mPAP was used (cut-off value: 10%). The predictive value was evaluated by using receiver operating characteristic curve. RESULTS: The mean (±SD) value of ALV was 26.8 (±32.2) %. A weak correlation was observed between ALV and forced vital capacity (FVC) (R = -0.46). The predictive value of ALV (area under curve; AUC = 0.74) was superior to that of FVC (AUC = 0.62) for the response to vasodilators. No hemodynamic parameters differed between patients with high and low ALV, whereas survival was worse in high ALV. CONCLUSION: Quantitative chest CT well predicted the response to vasodilators in patients with SSc and PH. Our results suggest its utility in differentiating the dominance of PVD or ILD.
  • Various factors contribute to death in patients with different types of pulmonary hypertension: A retrospective pilot study from a single tertiary center.
    Junichi Nakamura, Ichizo Tsujino, Hiroshi Ohira, Toshitaka Nakaya, Ayako Sugimoto, Takahiro Sato, Taku Watanabe, Masaru Suzuki, Masaru Kato, Isao Yokota, Satoshi Konno
    Respiratory investigation, 60, 5, 647, 657, Sep. 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, BACKGROUND: A few studies have focused on the cause of death from different types of pulmonary hypertension (PH). This study aimed to systematically analyze the primary and secondary causes of death and compare the profiles between different PH groups. METHODS: The contribution of PH to death was assessed in precapillary PH (i.e., group 1 [pulmonary arterial hypertension], group 3 [PH associated with lung disease], and group 4 [chronic thromboembolic PH]) using specific criteria; death was classified into three categories: PH death (death due to PH only), PH-related death, and PH-unrelated death. Disorders other than PH that contributed to death were analyzed, and mortality profiles were compared between groups. RESULTS: Eighty deceased patients with PH were examined (group 1, n = 28; group 3, n = 39; and group 4, n = 13). The contribution of PH to death was significantly different between the three groups. "PH death" was most common in group 1 (61%), "PH-related death" in group 3 (56%), and "PH-related death" and "PH-unrelated death" in group 4 (38% for both). The highest contributing factor to death other than PH was respiratory failure in group 3 and malignant disease in group 4. CONCLUSIONS: Significant variations in the causes of death were observed in groups 1, 3, and 4 PH patients. In addition to PH, respiratory failure and malignant disease significantly contributed to death in group 3 and group 4 PH, respectively. Understanding the precise death cause may be important in achieving better outcomes in PH patients.
  • Influence of obesity on incidence of thrombosis and disease severity in patients with COVID-19: From the CLOT-COVID study.
    Yoshito Ogihara, Sen Yachi, Makoto Takeyama, Yuji Nishimoto, Ichizo Tsujino, Junichi Nakamura, Naoto Yamamoto, Hiroko Nakata, Satoshi Ikeda, Michihisa Umetsu, Shizu Aikawa, Hiroya Hayashi, Hirono Satokawa, Yoshinori Okuno, Eriko Iwata, Nobutaka Ikeda, Akane Kondo, Takehisa Iwai, Norikazu Yamada, Tomohiro Ogawa, Takao Kobayashi, Makoto Mo, Yugo Yamashita
    Journal of cardiology, 81, 1, 105, 110, 29 Aug. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: The influence of obesity on the development of thrombosis and severity of coronavirus disease 2019 (COVID-19) remains unclear. METHOD: The CLOT-COVID study was a retrospective multicenter cohort study enrolling 2894 consecutive hospitalized patients with COVID-19 between April 2021 and September 2021 among 16 centers in Japan. The present study consisted of 2690 patients aged over 18 years with available body mass index (BMI), who were divided into an obesity group (BMI ≥30) (N = 457) and a non-obesity group (BMI <30) (N = 2233). RESULTS: The obesity group showed more severe status of COVID-19 at admission compared with the non-obesity group. The incidence of thrombosis was not significantly different between the groups (obesity group: 2.6 % versus non-obesity group: 1.9 %, p = 0.39), while the incidence of a composite outcome of all-cause death, or requirement of mechanical ventilation or extracorporeal membrane oxygenation during hospitalization was significantly higher in the obesity group (20.1 % versus 15.0 %, p < 0.01). After adjusting confounders in the multivariable logistic regression model, the risk of obesity relative to non-obesity for thrombosis was not significant (adjusted OR, 1.39; 95 % CI, 0.68-2.84, p = 0.37), while the adjusted risk of obesity relative to non-obesity for the composite outcome was significant (adjusted OR, 1.85; 95 % CI, 1.39-2.47, p < 0.001). CONCLUSIONS: In the present large-scale observational study, obesity was not significantly associated with the development of thrombosis during hospitalization; however, it was associated with severity of COVID-19.
  • Significant Impact of Age on Mortality and Non-significant Impact of Age on Thrombosis and Major Bleeding in Patients with COVID-19: From the CLOT-COVID Study.
    Yugo Yamashita, Sen Yachi, Makoto Takeyama, Yuji Nishimoto, Ichizo Tsujino, Junichi Nakamura, Naoto Yamamoto, Hiroko Nakata, Satoshi Ikeda, Michihisa Umetsu, Shizu Aikawa, Hiroya Hayashi, Hirono Satokawa, Yoshinori Okuno, Eriko Iwata, Yoshito Ogihara, Nobutaka Ikeda, Akane Kondo, Takehisa Iwai, Norikazu Yamada, Tomohiro Ogawa, Takao Kobayashi, Makoto Mo
    Journal of atherosclerosis and thrombosis, 30, 6, 624, 635, 29 Jul. 2022, [Domestic magazines]
    English, Scientific journal, AIM: There is scarce data on the impact of age on clinical outcomes in patients with coronavirus disease 2019 (COVID-19). METHOD: The CLOT-COVID Study was a retrospective, multicenter cohort study enrolling 2894 consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021. We divided the entire cohort into five groups according to age strata; -19, 20-39, 40-59, 60-79, and 80- years. RESULTS: Most patients under 19 had mild COVID-19 on admission (99%), while older patients had more severe COVID-19. The incidence rates of clinical outcomes during hospitalization in patients aged ≤ 19, 20-39, 40-59, 60-79, and 80 ≥ years were 0.0%, 0.5%, 2.2%, 2.7%, and 1.5% for thrombosis; 0.0%, 1.2%, 1.5%, 3.4%, and 2.0% for major bleeding; and 0.0%, 0.4%, 2.0%, 12.1%, and 16.8% for all-cause death, respectively. In the stratified analysis according to COVID-19 severity on admission, the incidences of thrombosis were generally higher among patients with more severe status, although those were not significantly different among age strata in all sub-types of COVID-19 severity. However, the incidences of all-cause death were significantly higher with increasing age in all sub-types of COVID-19 severity. CONCLUSIONS: In the current large observational study of patients with COVID-19, the risk of mortality became markedly higher with increased age. However, the risks of thrombosis and major bleeding did not necessarily increase as age increases, which seemed to be consistent irrespective of COVID-19 severity on admission.
  • An Adult Case of Unilateral Left Pulmonary Artery Agenesis Presenting with Hemoptysis.
    Yuriko Ishida, Masaru Suzuki, Hiroshi Horii, Junichi Nakamura, Munehiro Matsumoto, Sho Nakakubo, Takahiro Sato, Ichizo Tsujino, Ryo Morita, Daisuke Abo, Satoshi Konno
    Internal medicine (Tokyo, Japan), 62, 5, 763, 767, 22 Jul. 2022, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, Pulmonary artery agenesis (PAA) is a rare congenital vascular anomaly usually diagnosed during infancy. We herein report a 67-year-old man with PAA manifesting as massive hemoptysis. Contrast-enhanced computed tomography of the chest revealed the diagnosis of PAA, which we speculated to have resulted in the present event. Detailed angiography provided more accurate information on the pulmonary vasculature and collateral circulation, which helped us plan tailored treatment. Although very rare, we must consider the possibility of PAA in adults with unexplained hemoptysis.
  • Association Between the Development of Thrombosis and Worsening of Disease Severity in Patients With Moderate COVID-19 on Admission - From the CLOT-COVID Study.
    Satoshi Ikeda, Yuki Ueno, Koji Maemura, Sen Yachi, Makoto Takeyama, Yuji Nishimoto, Ichizo Tsujino, Junichi Nakamura, Naoto Yamamoto, Hiroko Nakata, Michihisa Umetsu, Shizu Aikawa, Hiroya Hayashi, Hirono Satokawa, Yoshinori Okuno, Eriko Iwata, Yoshito Ogihara, Nobutaka Ikeda, Akane Kondo, Takehisa Iwai, Norikazu Yamada, Tomohiro Ogawa, Takao Kobayashi, Makoto Mo, Yugo Yamashita
    Circulation journal : official journal of the Japanese Circulation Society, 87, 3, 448, 455, 01 Jul. 2022, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, BACKGROUND: The worsening of coronavirus disease 2019 (COVID-19) severity is a critical issue in current clinical settings and may be associated with the development of thrombosis.Methods and Results: This study used patient data obtained in the CLOT-COVID study, a retrospective multicenter cohort study. The demographics of patients with moderate COVID-19 on admission with and without worsened severity during hospitalization were compared and predictors were identified. Of 927 patients with moderate COVID-19 on admission, 182 (19.6%) had worsened severity during hospitalization. Patients with worsening of severity were older, more likely to have hypertension, diabetes, heart disease, and active cancer, and more likely to use pharmacological thromboprophylaxis. Patients with worsening of severity had higher D-dimer levels on admission and were more likely to develop thrombosis and major bleeding during hospitalization than those without worsening. Increased age (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01-1.03, P=0.005), diabetes (OR: 1.63, 95% CI: 1.11-2.33, P=0.012), D-dimer levels >1.0 μg/mL on admission (OR: 2.10, 95% CI: 1.45-3.03, P<0.001), and thrombosis (OR: 6.28, 95% CI: 2.72-14.53, P<0.001) were independently associated with worsening of COVID-19 severity. CONCLUSIONS: Approximately 20% of patients with moderate COVID-19 had worsened severity during hospitalization. Increased age, diabetes, D-dimer levels >1.0 μg/mL on admission, and the development of thrombosis during hospitalization were significantly associated with worsened COVID-19 severity.
  • Effects of obesity on CC16 and their potential role in overweight/obese asthma.
    Houman Goudarzi, Hirokazu Kimura, Hiroki Kimura, Hironi Makita, Munehiro Matsumoto, Nozomu Takei, Kaoruko Shimizu, Masaru Suzuki, Taku Watanabe, Eiki Kikuchi, Hiroshi Ohira, Ichizo Tsujino, Jun Sakakibara-Konishi, Naofumi Shinagawa, Noriharu Shijubo, Hirokazu Sato, Katsunori Shigehara, Kichizo Kaga, Yasuhiro Hida, Soichi Murakami, Yuma Ebihara, Akinobu Nakamura, Hideaki Miyoshi, Satoshi Hirano, Nobuyuki Hizawa, Tatsuya Atsumi, Shau-Ku Huang, Yoichi M Ito, Masaharu Nishimura, Satoshi Konno
    Respiratory research, 23, 1, 174, 174, 29 Jun. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, INTRODUCTION: Club cell secretory protein-16 (CC16) is a major anti-inflammatory protein expressed in the airway; however, the potential role of CC16 on overweight/obese asthma has not been assessed. In this study, we examined whether obesity reduces airway/circulatory CC16 levels using experimental and epidemiological studies. Then, we explored the mediatory role of CC16 in the relationship of overweight/obesity with clinical asthma measures. METHODS: Circulating CC16 levels were assessed by ELISA in three independent human populations, including two groups of healthy and general populations and asthma patients. The percentage of cells expressing club markers in obese vs. non-obese mice and human airways was determined by immunohistochemistry. A causal mediation analysis was conducted to determine whether circulatory CC16 acted as a mediator between overweight/obesity and clinical asthma measures. RESULTS: BMI was significantly and monotonously associated with reduced circulating CC16 levels in all populations. The percentage of CC16-expressing cells was reduced in the small airways of both mice and humans with obesity. Finally, mediation analysis revealed significant contributions of circulatory CC16 in the association between BMI and clinical asthma measures; 21.8% of its total effect in BMI's association with airway hyperresponsiveness of healthy subjects (p = 0.09), 26.4% with asthma severity (p = 0.030), and 23% with the required dose of inhaled corticosteroid (p = 0.042). In logistic regression analysis, 1-SD decrease in serum CC16 levels of asthma patients was associated with 87% increased odds for high dose ICS requirement (p < 0.001). CONCLUSIONS: We demonstrate that airway/circulating CC16, which is inversely associated with BMI, may mediate development and severity in overweight/obese asthma.
  • Therapeutic-Dose vs. Prophylactic-Dose Anticoagulation Therapy for Critically Ill Patients With COVID-19 in a Practice-Based Observational Study.
    Yugo Yamashita, Sen Yachi, Makoto Takeyama, Yuji Nishimoto, Ichizo Tsujino, Junichi Nakamura, Naoto Yamamoto, Hiroko Nakata, Satoshi Ikeda, Michihisa Umetsu, Shizu Aikawa, Hiroya Hayashi, Hirono Satokawa, Yoshinori Okuno, Eriko Iwata, Yoshito Ogihara, Nobutaka Ikeda, Akane Kondo, Takehisa Iwai, Norikazu Yamada, Tomohiro Ogawa, Takao Kobayashi, Makoto Mo
    Circulation journal : official journal of the Japanese Circulation Society, 86, 7, 1137, 1142, 03 Jun. 2022, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, BACKGROUND: The potential benefit of therapeutic-dose anticoagulation for critically ill patients with coronavirus disease 2019 (COVID-19) is still controversial.Methods and Results: In the CLOT-COVID study, 225 patients with severe COVID-19 on admission requiring mechanical ventilation or extracorporeal membrane oxygenation were divided into patients with therapeutic-dose anticoagulation (N=110) and those with prophylactic-dose anticoagulation (N=115). There was no significant difference in the incidence of thrombosis between the groups (9.1% vs. 7.8%, P=0.73). CONCLUSIONS: Among a cohort of critically ill patients with COVID-19, approximately half received therapeutic-dose anticoagulation, although it did not show a potential benefit compared with prophylactic-dose anticoagulation.
  • COVID-19と血栓症 総論、海外と我が国のデータ               
    谷地 繊, 竹山 誠, 山下 侑吾, 西本 裕二, 辻野 一三, 中村 順一, 山本 尚人, 中田 弘子, 池田 聡司, 梅津 道久, 相川 志都, 林 浩也, 佐戸川 弘, 奥野 善教, 岩田 英理子, 荻原 義人, 池田 長生, 近藤 朱音, 岩井 武尚, 山田 典一, 小川 智弘, 小林 隆夫, 孟 真
    静脈学, 33, 2, 144, 144, (一社)日本静脈学会, Jun. 2022
    Japanese
  • 静脈および動脈血栓症の分析 CLOT-COVID Studyより               
    梅津 道久, 山下 侑吾, 谷地 繊, 竹山 誠, 西本 裕二, 辻野 一三, 中村 順一, 山本 尚人, 中田 弘子, 池田 聡司, 相川 志都, 林 浩也, 佐戸川 弘之, 奥野 善教, 岩田 英理子, 荻原 義人, 池田 長生, 近藤 朱音, 岩井 武尚, 山田 典一, 小川 智弘, 小林 隆夫, 孟 真
    静脈学, 33, 2, 147, 147, (一社)日本静脈学会, Jun. 2022
    Japanese
  • COVID-19患者における入院時D-ダイマーの重要性               
    池田 長生, 谷地 繊, 竹山 誠, 西本 裕二, 辻野 一三, 中村 順一, 山本 尚人, 中田 弘子, 池田 聡司, 梅津 道久, 相川 志都, 林 浩也, 佐戸川 弘, 奥野 善教, 岩田 英理子, 荻原 義人, 近藤 朱音, 岩井 武尚, 山田 典一, 小川 智弘, 小林 隆夫, 孟 真, 山下 侑吾
    静脈学, 33, 2, 148, 148, (一社)日本静脈学会, Jun. 2022
    Japanese
  • Changes in the Characteristics and Initial Treatments of Pulmonary Hypertension Between 2008 and 2020 in Japan
    Yuichi Tamura, Hiraku Kumamaru, Takumi Inami, Hiromi Matsubara, Ken-ichi Hirata, Ichizo Tsujino, Rika Suda, Hiroaki Miyata, Shiori Nishimura, Byron Sigel, Masashi Takano, Koichiro Tatsumi
    JACC: Asia, 2, 3, 273, 284, Elsevier BV, Jun. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare, progressive disease. The treatment landscape for PAH in Japan has evolved considerably in recent years, but there is limited knowledge of the changes in treatment practices or patient characteristics. OBJECTIVES: The aim of this study was to evaluate the changes in characteristics and initial treatments for PAH in Japan over time. METHODS: This study used data from the Japan Pulmonary Hypertension Registry (JAPHR) to compare patient characteristics and treatment practices between 2008-2015 (n = 316) and 2016-2020 (n = 315). RESULTS: The mean ± standard deviation age at diagnosis increased from 47.9 ± 16.7 years in 2008-2015 to 52.7 ± 16.9 years in 2016-2020. The mean pulmonary arterial pressure decreased from 45.4 ± 15.0 to 38.6 ± 13.1 mm Hg. Idiopathic/hereditary PAH was the most common etiology in both periods (50.0% and 51.1%, respectively). The proportion of patients prescribed oral/inhaled combination therapies increased from 47.8% to 57.5%. Oral/inhaled combination therapies were frequently prescribed to patients with congenital heart disease-related PAH (81.8%). There was no significant trend in prescribing practices based on French low-risk criteria: among patients with 0, 1, 2, 3, or 4 criteria, 53.8%, 68.8%, 52.8%, 66.7%, and 39.4% were prescribed oral/inhaled combination therapies, and 0%, 16.7%, 27.0%, 17.3%, and 15.2% were prescribed oral/inhaled monotherapies. Macitentan, tadalafil, selexipag, and epoprostenol were the most frequently prescribed drugs. CONCLUSIONS: The severity of PAH decreased over time in Japan. Oral/inhaled combination therapies were generally preferred. Physicians generally prescribed therapies after considering the patients' hemodynamics and clinical severity. (Japan Pulmonary Hypertension Registry [JAPHR]; UMIN000026680).
  • D-Dimer Values and Venous Thromboembolism in Patients With COVID-19 in Japan - From the CLOT-COVID Study.
    Nobutaka Ikeda, Sen Yachi, Makoto Takeyama, Yuji Nishimoto, Ichizo Tsujino, Junichi Nakamura, Naoto Yamamoto, Hiroko Nakata, Satoshi Ikeda, Michihisa Umetsu, Shizu Aikawa, Hiroya Hayashi, Hirono Satokawa, Yoshinori Okuno, Eriko Iwata, Yoshito Ogihara, Akane Kondo, Takehisa Iwai, Norikazu Yamada, Tomohiro Ogawa, Takao Kobayashi, Makoto Mo, Yugo Yamashita
    Circulation reports, 4, 5, 215, 221, 10 May 2022, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, Background: To date, there are no large-scale data on the association between D-dimer levels at admission and the occurrence of venous thromboembolism (VTE) in Japanese patients with coronavirus disease 2019 (COVID-19). Methods and Results: The CLOT-COVID study was a retrospective, multicenter cohort study enrolling consecutive hospitalized patients with COVID-19 across 16 centers in Japan from April 2021 to September 2021. Among 2,894 enrolled patients, 2,771 (96%) had D-dimer levels measured at admission. Patients were divided into 3 groups based on tertiles of D-dimer levels at admission (1st tertile, D-dimer ≤0.5 μg/mL, n=949; 2nd tertile, D-dimer 0.51-1.09 μg/mL, n=894; 3rd tertile, D-dimer ≥1.1 μg/mL, n=928). The higher the tertile group, the more severe the COVID-19 status at admission. The incidence of VTE during hospitalization was highest in the 3rd tertile group (1st tertile, 0.3%; 2nd tertile, 0.3%; 3rd tertile, 3.6%; P<0.001). Even after adjusting for confounders in the multivariable logistic regression model, the higher D-dimer levels in the 3rd tertile (≥1.1 μg/mL) were independently associated with a higher risk of VTE during hospitalization (adjusted odds ratio 4.83 [95% confidence interval 1.93-12.11; P<0.001]; reference=1st tertile). Conclusions: Higher D-dimer levels at admission were associated with a higher risk of VTE events during hospitalization in Japanese patients with COVID-19. This could be helpful in determining patient-specific anticoagulation management strategies for COVID-19 in Japan.
  • A cardiac arrest case due to left coronary artery compression in congenital heart disease-associated pulmonary arterial hypertension
    Ayako Chida-Nagai, Ichizo Tsujino, Satoshi Yakuwa, Hiroyuki Akagawa, Takao Tsujioka, Kota Taniguchi, Osamu Sasaki, Gaku Izumi, Hirokuni Yamazawa, Atsuhito Takeda
    CJC Pediatric and Congenital Heart Disease, Elsevier BV, May 2022
    Scientific journal
  • The current status of thrombosis and anticoagulation therapy in patients with COVID-19 in Japan: From the CLOT-COVID study.
    Yuji Nishimoto, Sen Yachi, Makoto Takeyama, Ichizo Tsujino, Junichi Nakamura, Naoto Yamamoto, Hiroko Nakata, Satoshi Ikeda, Michihisa Umetsu, Shizu Aikawa, Hiroya Hayashi, Hirono Satokawa, Yoshinori Okuno, Eriko Iwata, Yoshito Ogihara, Nobutaka Ikeda, Akane Kondo, Takehisa Iwai, Norikazu Yamada, Tomohiro Ogawa, Takao Kobayashi, Makoto Mo, Yugo Yamashita
    Journal of cardiology, 80, 4, 285, 291, 05 Apr. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: Data on thrombosis and current real-world management strategies for anticoagulation therapy are scarce but important for understanding current issues and unmet needs of an optimal management of patients with coronavirus disease 2019 (COVID-19). METHOD: The CLOT-COVID Study (thrombosis and antiCoaguLatiOn Therapy in patients with COVID-19 in Japan Study: UMIN000045800) was a retrospective, multicenter cohort study enrolling consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021, and we tried to capture the status of the patients in the fourth and fifth waves of the COVID-19 infections in Japan. We enrolled consecutive hospitalized patients who were diagnosed with COVID-19 and had a positive polymerase chain reaction test obtained from the hospital databases. RESULTS: Among 2894 patients with COVID-19, 1245 (43%) received pharmacological thromboprophylaxis. The proportion of pharmacological thromboprophylaxis increased according to the severity of the COVID-19 in 9.8% with mild COVID-19, 61% with moderate COVID-19, and 97% with severe COVID-19. The types and doses of anticoagulants varied widely across the participating centers. During the hospitalization, 38 patients (1.3%) and 126 (4.4%) underwent ultrasound examinations for the lower extremities and contrast-enhanced computed tomography examinations, respectively, and 55 (1.9%) developed thrombosis, mostly venous thromboembolism (71%). The incidence of thrombosis increased according to the severity of the COVID-19 in 0.2% with mild COVID-19, 1.4% with moderate COVID-19, and 9.5% with severe COVID-19. Major bleeding occurred in 57 patients (2.0%) and 158 (5.5%) died, and 81% of them were due to respiratory failure from COVID-19 pneumonia. CONCLUSIONS: In the present large-scale observational study, pharmacological thromboprophylaxis for hospitalized patients with COVID-19 was common especially in patients with severe COVID-19, and management strategies varied widely across the participating centers. The overall incidence of thrombosis was substantially low with an increased incidence according to the severity of the COVID-19.
  • 前毛細管性肺高血圧症における心筋遅延造影像と左室収縮障害との関連               
    新川 未緒, 加賀 早苗, 岩野 弘幸, 千葉 泰之, 宮本 知佳, 岡田 一範, 村山 迪史, 中鉢 雅大, 常田 慧徳, 辻野 一三
    超音波医学, 49, Suppl., S706, S706, (公社)日本超音波医学会, Apr. 2022
    Japanese
  • Underdiagnosis of cardiac sarcoidosis by ECG and echocardiography in cases of extracardiac sarcoidosis.
    Hiroshi Ohira, Takahiro Sato, Osamu Manabe, Noriko Oyama-Manabe, Akiko Hayashishita, Toshitaka Nakaya, Junichi Nakamura, Naoko Suzuki, Ayako Sugimoto, Sho Furuya, Satonori Tsuneta, Taku Watanabe, Ichizo Tsujino, Satoshi Konno
    ERJ open research, 8, 2, Apr. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Background: Although screening with 12-lead electrocardiography and transthoracic echocardiography for cardiac involvement has been recommended for patients with biopsy-proven extracardiac sarcoidosis, cardiac sarcoidosis has been reported even in patients with normal electrocardiography and echocardiography findings. We investigated the prevalence and characteristics of these patient cohorts. Methods: We studied 112 consecutive patients (age, 55±17 years, 64% females) with biopsy-proven extracardiac sarcoidosis who had undergone 18F-fluorodeoxyglucose positron emission tomography and cardiac magnetic resonance imaging for cardiac sarcoidosis evaluation. The patients were categorised as those showing normal findings both in electrocardiography and transthoracic echocardiography (normal group) and those showing abnormal findings in one or both examinations (abnormal group). Results: 33 (29%) and 79 (71%) patients were categorised into the normal and abnormal groups, respectively, of which 6 (18%) and 43 (54%) patients, respectively, were diagnosed with cardiac sarcoidosis (p<0.01). Of these six patients in the normal group, two with multiple-organ sarcoidosis showed clinical deterioration of cardiac involvement and required steroid therapy; three with small cardiac involvement showed natural remission over follow-up assessments; and one underwent steroid therapy and showed an improvement in the left ventricular ejection fraction to within normal limits. Conclusions: The prevalence of cardiac sarcoidosis in patients with biopsy-proven extracardiac sarcoidosis and normal electrocardiography and transthoracic echocardiography findings was ∼20%. Electrocardiography and transthoracic echocardiography may not detect cardiac sarcoidosis in patients without conduction and morphological abnormalities. However, some of these patients may subsequently show clinically manifested cardiac sarcoidosis. Physicians should be mindful of this population.
  • Accuracy of Swan‒Ganz catheterization-based assessment of right ventricular function: Validation study using high-fidelity micromanometry-derived values as reference.
    Hideki Shima, Toshitaka Nakaya, Ichizo Tsujino, Junichi Nakamura, Ayako Sugimoto, Takahiro Sato, Taku Watanabe, Hiroshi Ohira, Masaru Suzuki, Masaru Kato, Isao Yokota, Satoshi Konno
    Pulmonary circulation, 12, 2, e12078, Apr. 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Right ventricular (RV) function critically affects the outcomes of patients with pulmonary hypertension (PH). Pressure wave analysis using Swan‒Ganz catheterization (SG-cath) allows for the calculation of indices of RV function. However, the accuracy of these indices has not been validated. In the present study, we calculated indices of systolic and diastolic RV functions using SG-cath-derived pressure recordings in patients with suspected or confirmed PH. We analyzed and validated the accuracies of three RV indices having proven prognostic values, that is, end-systolic elastance (Ees)/arterial elastance (Ea), β (stiffness constant), and end-diastolic elastance (Eed), using high-fidelity micromanometry-derived data as reference. We analyzed 73 participants who underwent SG-cath for the diagnosis or evaluation of PH. In this study, Ees/Ea was calculated via the single-beat pressure method using [1.65 × (mean pulmonary arterial pressure) - 7.79] as end-systolic pressure. SG-cath-derived Ees/Ea, β, and Eed were 0.89 ± 0.69 (mean ± standard deviation), 0.027 ± 0.002, and 0.16 ± 0.02 mmHg/ml, respectively. The mean differences (limits of agreement) between SG-cath and micromanometry-derived data were 0.13 (0.99, -0.72), 0.002 (0.020, -0.013), and 0.04 (0.20, -0.12) for Ees/Ea, β, and Eed, respectively. The intraclass correlation coefficients of the indices derived from the two catheterizations were 0.76, 0.71, and 0.57 for Ees/Ea, β, and Eed, respectively. In patients with confirmed or suspected PH, SG-cath-derived RV indices, especially Ees/Ea and β, exhibited a good correlation with micromanometry-derived reference values.
  • Phorbol 12-myristate 13-acetate stimulation under hypoxia induces nuclear swelling with DNA outflow but not extracellular trap formation of neutrophils.
    Sakiko Masuda, Kurumi Kato, Misato Ishibashi, Yuka Nishibata, Ayako Sugimoto, Daigo Nakazawa, Satoshi Tanaka, Utano Tomaru, Ichizo Tsujino, Akihiro Ishizu
    Experimental and molecular pathology, 125, 104754, 104754, Apr. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Neutrophils stand sentinel over infection and possess diverse antimicrobial weapons, including neutrophil extracellular traps (NETs). NETs are composed of web-like extracellular DNA decorated with antimicrobial substances and can trap and eliminate invading microorganisms. Although phorbol 12-myristate 13-acetate (PMA) is a potent NET inducer, previous studies have demonstrated that not all neutrophils exhibit NET formation even if stimulated by PMA at high concentrations. This study first showed that some neutrophils stimulated by PMA displayed a swollen nucleus but not NET formation and that hypoxic environments suppressed the NET release. Next, characterization of PMA-stimulated neutrophils with a swollen nucleus was accomplished by differentiating between suicidal-type NETosis and apoptosis. Furthermore, the significance of the phenomenon was examined using formalin-fixed, paraffin-embedded human lung disease tissues with and without pneumonia. As a result, histone H3 citrullination, DNA outflow, propidium iodide labeling, resistance to DNase I, and suspended actin rearrangement were characteristics of PMA-stimulated neutrophils with a swollen nucleus distinct from neutrophils that underwent either suicidal-type NETosis or apoptosis. Neutrophils stimulated by PMA under hypoxic conditions secreted matrix metalloproteinase-9 cytotoxic to human lung-derived fibroblasts. Further, deposition of neutrophil-derived citrullinated histone H3+ chromatin substances in pulmonary lesions was greater in patients with pneumonia than in patients without pneumonia and positively correlated with hypoxia-inducible factor-1α expression. The collective findings suggested that neutrophils activated under hypoxic conditions could be putative modulators of hypoxia-related disease manifestations.
  • Influence of sex on development of thrombosis in patients with COVID-19: From the CLOT-COVID study.
    Yugo Yamashita, Sen Yachi, Makoto Takeyama, Yuji Nishimoto, Ichizo Tsujino, Junichi Nakamura, Naoto Yamamoto, Hiroko Nakata, Satoshi Ikeda, Michihisa Umetsu, Shizu Aikawa, Hiroya Hayashi, Hirono Satokawa, Yoshinori Okuno, Eriko Iwata, Yoshito Ogihara, Nobutaka Ikeda, Akane Kondo, Takehisa Iwai, Norikazu Yamada, Tomohiro Ogawa, Takao Kobayashi, Makoto Mo
    Thrombosis research, 213, 173, 178, 31 Mar. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, INTRODUCTION: There has been limited data on the influence of sex on development of thrombosis in patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: The CLOT-COVID Study was a retrospective, multicenter cohort study enrolling 2894 consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021. We divided the entire cohort into the men (N = 1885) and women (N = 1009) groups. RESULTS: There were no significant differences in D-dimer levels at admission between men and women. Men had more severe status of the COVID-19 at admission compared with women (Mild: 57% versus 66%, Moderate: 34% versus 29%, and Severe: 9.1% versus 5.7%, P < 0.001). Men more often received pharmacological thromboprophylaxis than women (47% versus 35%, P < 0.001). During the hospitalization, men more often developed thrombosis than women (2.5% [95%CI, 1.9-3.3%] versus 0.8% [95%CI, 0.4-1.6%], P = 0.001). Men had numerically higher incidences of thrombosis than women in all subgroups of the worst severity of COVID-19 during the hospitalization (Mild: 0.3% versus 0.0%, Moderate: 1.6% versus 1.0%, and Severe: 11.1% versus 4.3%). Even after adjusting confounders in the multivariable logistic regression model, the excess risk of men relative to women remained significant for thrombosis (adjusted OR, 2.51; 95%CI, 1.16-5.43, P = 0.02). CONCLUSIONS: In the current large observational study of patients with COVID-19, men had more severe status of the COVID-19 than women, and the risk of development of thrombosis was higher in men compared with women, which could be helpful in determining the patient-specific optimal management strategies for COVID-19.
  • Determinants of altered left ventricular suction in pre-capillary pulmonary hypertension.
    Yasuyuki Chiba, Hiroyuki Iwano, Satonori Tsuneta, Shingo Tsujinaga, Brett Meyers, Pavlos Vlachos, Suguru Ishizaka, Ko Motoi, Hiroyuki Aoyagi, Yoji Tamaki, Asuka Tanemura, Michito Murayama, Shinobu Yokoyama, Masahiro Nakabachi, Hisao Nishino, Sanae Kaga, Kiwamu Kamiya, Hiroshi Ohira, Ichizo Tsujino, Toshihisa Anzai
    European heart journal. Cardiovascular Imaging, 23, 10, 1399, 1406, 10 Jan. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, AIMS: Although the left ventricular (LV) dysfunction in pre-capillary pulmonary hypertension (PH) has been recently recognized, the mechanism of LV dysfunction in this entity is not completely understood. We thus aimed to elucidate the determinants of intraventricular pressure difference (IVPD), a measure of LV suction, in pre-capillary PH. METHODS AND RESULTS: Right heart catheterization and echocardiography were performed in 86 consecutive patients with pre-capillary PH (57 ± 18 years, 85% female). IVPD was determined using colour M-mode Doppler to integrate the Euler equation. In overall, IVPD was reduced compared to previously reported value in normal subjects. In univariable analyses, QRS duration (P = 0.028), LV ejection fraction (P = 0.006), right ventricular (RV) end-diastolic area (P < 0.001), tricuspid annular plane systolic excursion (P = 0.004), and LV early-diastolic eccentricity index (P = 0.009) were associated with IVPD. In the multivariable analyses, RV end-diastolic area and LV eccentricity index independently determined the IVPD. CONCLUSION: Aberrant ventricular interdependence caused by RV enlargement could impair the LV suction. This study first applied echocardiographic IVPD, a reliable marker of LV diastolic suction, to investigate the mechanism of LV diastolic dysfunction in pre-capillary PH.
  • Selexipag for the treatment of chronic thromboembolic pulmonary hypertension.
    Takeshi Ogo, Hiroto Shimokawahara, Hideyuki Kinoshita, Seiichiro Sakao, Kohtaro Abe, Satoaki Matoba, Hirohiko Motoki, Noriaki Takama, Junya Ako, Yasuhiro Ikeda, Shuji Joho, Hisataka Maki, Takahiro Saeki, Teruyasu Sugano, Ichizo Tsujino, Koichiro Yoshioka, Naoki Shiota, Shinichi Tanaka, Chieko Yamamoto, Nobuhiro Tanabe, Koichiro Tatsumi
    The European respiratory journal, 60, 1, 25 Nov. 2021, [International Magazine]
    English, Scientific journal, Treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) remain limited. Selexipag, an oral selective IP prostacyclin-receptor agonist approved for pulmonary arterial hypertension, is a potential treatment option for CTEPH.In this multicentre, randomised, double-blind, placebo-controlled study, 78 Japanese patients with inoperable CTEPH or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy and/or balloon pulmonary angioplasty were randomly assigned to receive placebo or selexipag. The primary endpoint was the change in pulmonary vascular resistance (PVR) from baseline to week 20. The secondary endpoints were changes in other haemodynamic parameters, 6-min walk distance (6 WMD), Borg Dyspnoea Scale score, World Health Organisation (WHO) functional class, EuroQol 5 dimensions 5-level and N-terminal pro-brain natriuretic peptide.The change in PVR was -98.2±111.3 dyn·s·cm-5 and -4.6±163.6 dyn·s·cm-5 in the selexipag and placebo groups, respectively (mean difference, -93.5 dyn·s·cm-5; 95% confidence interval, -156.8, -30.3; p=0.006). The changes in cardiac index (p<0.001) and Borg Dyspnoea Scale score (p=0.036) were also significantly improved over placebo. 6WMD and WHO functional class were not significantly improved. The common adverse events in the selexipag group were corresponded to those generally observed following a prostacyclin analogue is administered.Selexipag significantly improved PVR and other haemodynamic variables in patients with CTEPH, although exercise capacity remained unchanged. Further large-scale investigation is necessary to prove the role of selexipag in CTEPH.
  • 肺動脈圧の上昇が疑われる症例でのEBUS-GS-TBBに伴う出血に関する検討
    高島 雄太, 品川 尚文, 山本 岳, 森永 大亮, 古田 恵, 庄司 哲明, 朝比奈 肇, 菊地 英毅, 菊地 順子, 榊原 純, 中村 順一, 辻野 一三, 今野 哲
    気管支学, 43, 6, 690, 690, (一社)日本呼吸器内視鏡学会, Nov. 2021
    Japanese
  • 肺動脈圧の上昇が疑われる症例でのEBUS-GS-TBBに伴う出血に関する検討
    高島 雄太, 品川 尚文, 山本 岳, 森永 大亮, 古田 恵, 庄司 哲明, 朝比奈 肇, 菊地 英毅, 菊地 順子, 榊原 純, 中村 順一, 辻野 一三, 今野 哲
    気管支学, 43, 6, 690, 690, (NPO)日本呼吸器内視鏡学会, Nov. 2021
    Japanese
  • Right ventricular function as assessed by cardiac magnetic resonance imaging-derived strain parameters compared to high-fidelity micromanometer catheter measurements
    Takahiro Sato, Bharath Ambale-Venkatesh, Stefan L. Zimmerman, Ryan J. Tedford, Steven Hsu, Ela Chamera, Tomoki Fujii, Christopher J. Mullin, Valentina Mercurio, Rubina Khair, Celia P. Corona-Villalobos, Catherine E. Simpson, Rachel L. Damico, Todd M. Kolb, Stephen C. Mathai, Joao A.C. Lima, David A. Kass, Ichizo Tsujino, Paul M. Hassoun
    Pulmonary Circulation, 11, 4, 204589402110325, 204589402110325, SAGE Publications, Oct. 2021, [Peer-reviewed]
    Scientific journal, Right ventricular function has prognostic significance in patients with pulmonary hypertension. We evaluated whether cardiac magnetic resonance-derived strain and strain rate parameters could reliably reflect right ventricular systolic and diastolic function in precapillary pulmonary hypertension. End-systolic elastance and the time constant of right ventricular relaxation tau, both derived from invasive high-fidelity micromanometer catheter measurements, were used as gold standards for assessing systolic and diastolic right ventricular function, respectively. Nineteen consecutive precapillary pulmonary hypertension patients underwent cardiac magnetic resonance and right heart catheterization prospectively. Cardiac magnetic resonance data were compared with those of 19 control subjects. In pulmonary hypertension patients, associations between strain- and strain rate-related parameters and invasive hemodynamic parameters were evaluated. Longitudinal peak systolic strain, strain rate, and early diastolic strain rate were lower in PAH patients than in controls; peak atrial-diastolic strain rate was higher in pulmonary hypertension patients. Similarly, circumferential peak systolic strain rate was lower and peak atrial-diastolic strain rate was higher in pulmonary hypertension. In pulmonary hypertension, no correlations existed between cardiac magnetic resonance-derived and hemodynamically derived measures of systolic right ventricular function. Regarding diastolic parameters, tau was significantly correlated with peak longitudinal atrial-diastolic strain rate ( r = −0.61), deceleration time ( r = 0.75), longitudinal systolic to diastolic time ratio ( r = 0.59), early diastolic strain rate ( r = −0.5), circumferential peak atrial-diastolic strain rate ( r = −0.52), and deceleration time ( r = 0.62). Strain analysis of the right ventricular diastolic phase is a reliable non-invasive method for detecting right ventricular diastolic dysfunction in PAH.
  • Incidence and Clinical Features of Venous Thromboembolism in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) in Japan.
    Yugo Yamashita, Yuuki Maruyama, Hirono Satokawa, Yuji Nishimoto, Ichizo Tsujino, Hideki Sakashita, Hiroko Nakata, Yoshinori Okuno, Yoshito Ogihara, Sen Yachi, Naoki Toya, Masami Shingaki, Satoshi Ikeda, Naoto Yamamoto, Shizu Aikawa, Nobutaka Ikeda, Hiroya Hayashi, Shingo Ishiguro, Eriko Iwata, Michihisa Umetsu, Akane Kondo, Takehisa Iwai, Takao Kobayashi, Makoto Mo, Norikazu Yamada
    Circulation journal : official journal of the Japanese Circulation Society, 85, 12, 2208, 2214, 20 May 2021, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, BACKGROUND: Coronavirus disease 2019 (COVID-19) reportedly causes venous thromboembolism (VTE), but the status of this complication in Japan was unclear.Methods and Results:The VTE and COVID-19 in Japan Study is a retrospective, multicenter cohort study enrolling hospitalized patients with COVID-19 who were evaluated with contrast-enhanced computed tomography (CT) examination at 22 centers in Japan between March 2020 and October 2020. Among 1,236 patients with COVID-19, 45 (3.6%) were evaluated with contrast-enhanced CT examination. VTE events occurred in 10 patients (22.2%), and the incidence of VTE in mild, moderate, and severe COVID-19 was 0%, 11.8%, and 40.0%, respectively. COVID-19 patients with VTE showed a higher body weight (81.6 vs. 64.0 kg, P=0.005) and body mass index (26.9 vs. 23.2 kg/m2, P=0.04), and a higher proportion had a severe status for COVID-19 compared with those without. There was no significant difference in the proportion of patients alive at discharge between patients with and without VTE (80.0% vs. 88.6%, P=0.48). Among 8 pulmonary embolism (PE) patients, all were low-risk PE. CONCLUSIONS: Among a relatively small number of patients undergoing contrast-enhanced CT examination in Japanese real-world clinical practice, there were no VTE patients among those with mild COVID-19, but the incidence of VTE seemed to be relatively high among severe COVID-19 patients, although all PE events were low-risk without significant effect on mortality risk.
  • The assessment of left heart disease in patients with systemic sclerosis and pulmonary hypertension.
    Keita Ninagawa, Masaru Kato, Hiroshi Ohira, Satonori Tsuneta, Hiroyuki Iwano, Michihito Kono, Yuichiro Fujieda, Kenji Oku, Ichizo Tsujino, Tatsuya Atsumi
    Clinical and experimental rheumatology, 12 May 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, OBJECTIVES: Systemic sclerosis associated pulmonary arterial hypertension (SSc-PAH) is of clinical significance owing to its poor outcome. One of the explanations for the outcome is the co-presence of left heart disease (LHD). The aim of this study is to assess LHD phenotype in patients with SSc and pulmonary hypertension (PH). METHODS: This study included consecutive patients with SSc who underwent right heart catheterisation to diagnose PAH. Heart failure with preserved ejection fraction (HFpEF) was evaluated according to the recommendation of 6th WSPH and to the Framingham criteria. RESULTS: In total, 76 patients were enrolled in this study. Of them, 42 had PH (mPAP >20 mmHg) with a normal left ventricle ejection fraction (≥50%). Among the 42 patients, four and three patients were classified "HFpEF not excluded" and "HFpEF confirmed" whereas 10 had a clinical diagnosis of HFpEF according to 6th WSPH and Framingham criteria, respectively. These differences were due mainly to relatively low PAWP (<13 mmHg). By a combination of ROC curve and logistic regression analyses, left atrial dimension and left ventricular end-diastolic volume index assessed with echocardiography and cardiac MRI, respectively, had significantly higher predictive values for detecting the complication of HFpEF rather than PAWP. CONCLUSIONS: Morphological evaluation using echocardiography and cardiac MRI, compared with haemodynamic evaluation by PAWP, may better reflect the copresence of LHD phenotype in patients with SSc and PH. Our data would also indicate a limited elevation of PAWP in patients with SSc, PH and HFpEF.
  • 胸部CTでの定量的手法による1群又は3群強皮症性肺高血圧症の評価               
    蜷川 慶太, 加藤 将, 河野 通仁, 藤枝 雄一郎, 大平 洋, 奥 健志, 杉森 博行, 辻野 一三, 渥美 達也
    日本肺高血圧・肺循環学会学術集会・日本小児肺循環研究会プログラム・抄録集, 6回・27回, 41, 41, 日本肺高血圧・肺循環学会・日本小児肺循環研究会, May 2021
    Japanese
  • Right ventricular pressure-volume loop produced with simultaneous application of three-dimensional echocardiography and high-fidelity micromanometry in a patient with pulmonary arterial hypertension.
    Toshitaka Nakaya, Ichizo Tsujino, Junichi Nakamura, Yasuyuki Chiba, Hiroyuki Iwano
    Echocardiography (Mount Kisco, N.Y.), 38, 5, 805, 807, May 2021, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Accurate assessment of right ventricular (RV) function has received a growing attention. Pressure-volume (PV) loop analysis is the gold standard method for evaluating RV function; however, it is not widely employed because of its invasive nature and complexity. The present report is the first to have drawn a RV PV loop in a patient with pulmonary hypertension, with a simultaneous recording of RV pressure and volume using high-fidelity micromanometry and three-dimensional echocardiography. This allows for less invasive and simple assessment of RV function, potentially promoting better understanding and management of pulmonary hypertension and other cardiovascular diseases.
  • Multi-Institutional Prospective Cohort Study of Patients With Pulmonary Hypertension Associated With Respiratory Diseases.
    Nobuhiro Tanabe, Hiraku Kumamaru, Yuichi Tamura, Hiroyuki Taniguchi, Noriaki Emoto, Yoshihito Yamada, Osamu Nishiyama, Ichizo Tsujino, Hiroshi Kuraishi, Yoshihiro Nishimura, Hiroshi Kimura, Yoshikazu Inoue, Yoshiteru Morio, Yasuto Nakatsumi, Toru Satoh, Masayuki Hanaoka, Kei Kusaka, Mitsuhiro Sumitani, Tomohiro Handa, Seiicihiro Sakao, Tomoki Kimura, Yasuhiro Kondoh, Kazuhiko Nakayama, Kensuke Tanaka, Hiroshi Ohira, Masaharu Nishimura, Hiroaki Miyata, Koichiro Tatsumi
    Circulation journal : official journal of the Japanese Circulation Society, 85, 4, 333, 342, 25 Mar. 2021, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, BACKGROUND: There is limited evidence for pulmonary arterial hypertension (PAH)-targeted therapy in patients with pulmonary hypertension associated with respiratory disease (R-PH). Therefore, we conducted a multicenter prospective study of patients with R-PH to examine real-world characteristics of responders by evaluating demographics, treatment backgrounds, and prognosis.Methods and Results:Among the 281 patients with R-PH included in this study, there was a treatment-naïve cohort of 183 patients with normal pulmonary arterial wedge pressure and 1 of 4 major diseases (chronic obstructive pulmonary diseases, interstitial pneumonia [IP], IP with connective tissue disease, or combined pulmonary fibrosis with emphysema); 43% of patients had mild ventilatory impairment (MVI), whereas 52% had a severe form of PH. 68% received PAH-targeted therapies (mainly phosphodiesterase-5 inhibitors). Among patients with MVI, those treated initially (i.e., within 2 months of the first right heart catheterization) had better survival than patients not treated initially (3-year survival 70.6% vs. 34.2%; P=0.01); there was no significant difference in survival in the group with severe ventilatory impairment (49.6% vs. 32.1%; P=0.38). Responders to PAH-targeted therapy were more prevalent in the group with MVI. CONCLUSIONS: This first Japanese registry of R-PH showed that a high proportion of patients with MVI (PAH phenotype) had better survival if they received initial treatment with PAH-targeted therapies. Responders were predominant in the group with MVI.
  • Improvements in French risk stratification score were correlated with reductions in mean pulmonary artery pressure in pulmonary arterial hypertension: a subanalysis of the Japan Pulmonary Hypertension Registry (JAPHR).
    Yuichi Tamura, Hiraku Kumamaru, Kohtaro Abe, Toru Satoh, Hiroaki Miyata, Aiko Ogawa, Nobuhiro Tanabe, Masaru Hatano, Atsushi Yao, Ichizo Tsujino, Keiichi Fukuda, Hiroshi Kimura, Masataka Kuwana, Hiromi Matsubara, Koichiro Tatsumi
    BMC pulmonary medicine, 21, 1, 28, 28, 14 Jan. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: Since there was no previous report, we analyzed the relationship between French Risk Stratification parameters in pulmonary arterial hypertension (PAH) and mean pulmonary arterial pressures (mPAP) using Japan PH Registry (JAPHR) national-wide cohort. METHODS: We enrolled 108 patients with PAH from JAPHR from previous reported cohort and analyzed the relations between French Risk Stratification scores and hemodynamic improvements. RESULTS: The ratio meeting 0 to 4 French Risk Stratification score was 21.3%, 31.5%, 32.4%, 13.0%, and 1.9% at baseline, and 6.5%, 23.2%, 33.3%, 23.2%, 13.9% at follow-up, respectively. The improvements in the number of criteria met were associated both with mPAP at follow-up (p = 0.03) and with the improvements in mPAP (p < 0.001). CONCLUSION: The improvements in French Risk Stratification may become a marker of improved hemodynamics including mPAP.
  • 目でみる肺高血圧症 右心評価におけるMRI
    常田 慧徳, 佐藤 隆博, 大平 洋, 辻野 一三
    Pulmonary Hypertension Update, 6, 2, 76, 80, (株)メディカルレビュー社, Nov. 2020
    Japanese
  • Selexipag for Chronic Thromboembolic Pulmonary Hypertension in Japanese Patients - A Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase II Study.
    Nobuhiro Tanabe, Keiichi Fukuda, Hiromi Matsubara, Norifumi Nakanishi, Nobuhiro Tahara, Satoshi Ikeda, Takuya Kishi, Toru Satoh, Ken-Ichi Hirata, Teruo Inoue, Hiroshi Kimura, Yoshiaki Okano, Osamu Okazaki, Masataka Sata, Ichizo Tsujino, Shuichi Ueno, Norikazu Yamada, Atsushi Yao, Takayuki Kuriyama
    Circulation journal : official journal of the Japanese Circulation Society, 84, 10, 1866, 1874, 25 Sep. 2020, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, BACKGROUND: Selexipag is an oral prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. This study examined its efficacy and safety in Japanese patients with non-operated or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH).Methods and Results:This Phase II study was a randomized, double-blind, placebo-controlled parallel-group comparison. The primary endpoint was a change in pulmonary vascular resistance (PVR) from baseline to week 17. The main analysis involved a per-protocol set group of 28 subjects. The change in PVR (mean±SD) after 17 weeks of treatment in the selexipag group was -104±191 dyn·s/cm5, whereas that in the placebo group was 26±180 dyn·s/cm5. Thus, the treatment effect after 17 weeks of selexipag treatment was calculated as -130±189 dyn·s/cm5(P=0.1553). Although the primary endpoint was not met, for the group not concomitantly using a pulmonary vasodilator the PVR in the selexipag group was significantly decreased compared with placebo group (P=0.0364). The selexipag group also showed improvement in total pulmonary resistance and cardiac index. CONCLUSIONS: Selexipag treatment improved pulmonary hemodynamics in Japanese patients with CTEPH, but PVR did not show a significant difference between the selexipag and placebo groups. (Trial registration: JAPIC Clinical Trials Information [JapicCTI-111667]).
  • 2型糖尿病患者におけるイプラグリフロジンと高用量メトホルミンの有効性の比較検討               
    中谷 資隆, 渡部 拓, 長谷川 敦, 吉村 治彦, 池田 大輔, 坂上 慎二, 一宮 由紀子, 本多 敏朗, 藤原 豊, 高階 知紗, 合田 晶, 佐藤 文彦, 藤本 晶子, 広川 淳一, 鈴木 奈緒子, 中村 順一, 杉本 絢子, 林下 晶子, 大平 洋, 辻野 一三, 西村 正治, 今野 哲
    糖尿病, 63, Suppl.1, S, 132, (一社)日本糖尿病学会, Aug. 2020
    Japanese
  • Right ventriculo–pulmonary arterial uncoupling and poor outcomes in pulmonary arterial hypertension
    Toshitaka Nakaya, Hiroshi Ohira, Takahiro Sato, Taku Watanabe, Masaharu Nishimura, Noriko Oyama-Manabe, Masaru Kato, Yoichi M. Ito, Ichizo Tsujino
    Pulmonary Circulation, 10, 3, 204589402095722, 204589402095722, SAGE Publications, Jul. 2020, [Peer-reviewed]
    Scientific journal, Right ventricular function critically affects the prognosis of patients with pulmonary arterial hypertension. We aimed to analyze the prognostic value of right ventricular indices calculated using magnetic resonance imaging and right heart catheterization metrics in pulmonary arterial hypertension. We retrospectively collected data from 57 Japanese patients with pulmonary arterial hypertension and 18 controls and calculated six indices of right ventricular function: two indices of contractility (end-systolic elastance calculated with right ventricular maximum pressure and with magnetic resonance imaging metrics); two indices of right ventricular–pulmonary arterial coupling (end-systolic elastance/arterial elastance calculated with the pressure method (end-systolic elastance/arterial elastance (P)) and with the volume method (end-systolic elastance/arterial elastance (V)); and two indices of right ventricular diastolic function (stiffness (β) and end-diastolic elastance). We compared the indices between controls and patients with pulmonary arterial hypertension and examined their prognostic role. In patients with pulmonary arterial hypertension, end-systolic elastance (right ventricular maximum pressure) was higher (pulmonary arterial hypertension 0.94 (median) vs control 0.42 (mmHg/mL), p < 0.001), end-systolic elastance/arterial elastance (V) was lower (pulmonary arterial hypertension 0.72 vs control 1.69, p < 0.001), and β and end-diastolic elastance were significantly higher than those in the controls. According to the log-rank test, end-systolic elastance/arterial elastance (P) and end-diastolic elastance were significantly associated with the composite event rate. According to the multivariate Cox regression analysis, decreased end-systolic elastance/arterial elastance (P) was associated with a higher composite event rate (hazard ratio 11.510, 95% confidence interval: 1.954–67.808). In conclusion, an increased right ventricular contractility, diastolic dysfunction, and a trend of impaired right ventricular–pulmonary arterial coupling were observed in our pulmonary arterial hypertension cohort. According to the multivariate outcome analysis, a decreased end-systolic elastance/arterial elastance (P), suggestive of impaired right ventricular–pulmonary arterial coupling, best predicted the pulmonary arterial hypertension-related event.
  • Psychometric Validation of a Japanese Version of the emPHasis-10 Questionnaire, a Patient-Reported Outcome Measure for Pulmonary Hypertension - Multicenter Study in Japan.
    Rika Takeyasu, Yuichi Tamura, Kohtaro Abe, Ayumi Goda, Toru Satoh, Rika Suda, Nobuhiro Tanabe, Ichizo Tsujino, Tsutomu Yamazaki, Koichiro Tatsumi
    Circulation reports, 2, 4, 255, 259, 20 Mar. 2020, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, Background: The emPHasis-10 questionnaire is a disease-specific patient-reported outcome assessment of quality of life (QOL) in pulmonary hypertension (PH). The aim of this study was to psychometrically validate a linguistically validated Japanese version of the emPHasis-10. Methods and Results: Japanese patients with PH (age ≥18 years) and no change in functional status, or initiation or change in PH-specific treatment during the past 3 months were recruited from 5 institutions from August 2018 to July 2019. A set of questionnaires was administered twice. The validity and reliability of the emPHasis-10 were assessed using the data of 76 patients. On concurrent validity analysis, a moderate-to-strong correlation was seen with the total score of all 5 external criteria (the Minnesota Living with Heart Failure modified for PH [MLHFQ-PH], Hospital Anxiety and Depression Scale, Dyspnea-12 questionnaire, European Quality of Life-5 Dimensions questionnaire [EQ-5D], and 6-min walk test), with a notably strong correlation with the MLHFQ-PH (0.77) and EQ-5D (-0.64). On known-group validity, a linear increasing trend of the emPHasis-10 score was observed across 4 World Health Organization functional status groups (Jonckheere-Terpstra test, 1-sided, P<0.001). Intraclass correlation coefficient for test-retest reliability was 0.86, and the Cronbach's α for internal consistency was 0.89. Conclusions: The Japanese emPHasis-10 questionnaire is psychometrically valid to evaluate QOL in Japanese PH patients in a clinical setting.
  • Right ventricular dimension index by cardiac magnetic resonance for prognostication in connective tissue diseases and pulmonary hypertension.
    Nobuya Abe, Masaru Kato, Michihito Kono, Yuichiro Fujieda, Hiroshi Ohira, Ichizo Tsujino, Noriko Oyama-Manabe, Kenji Oku, Toshiyuki Bohgaki, Shinsuke Yasuda, Tatsuya Atsumi
    Rheumatology (Oxford, England), 59, 3, 622, 633, 01 Mar. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, OBJECTIVES: Pulmonary hypertension (PH) in patients with CTD is a heterogeneous condition affected by left heart disease, chronic lung disease and thromboembolism as well as pulmonary vascular disease. Recent studies using cardiac magnetic resonance (CMR) have shown that right ventricular dysfunction is predictive for mortality in patients with PH, but limited to pulmonary arterial hypertension. This study aimed to analyse prognostic factors in PH-CTD. METHODS: This retrospective analysis comprised 84 CTD patients, including SSc, who underwent both CMR and right heart catheterization from 2008 to 2018. Demographics, laboratory findings, and haemodynamic and morphological parameters were extracted. The prognostic value of each parameter was evaluated by multivariate analysis using covariables derived from propensity score to control confounding factors. RESULTS: Of 84 patients, 65 had right heart catheterization-confirmed PH (54 pulmonary arterial hypertension, 11 non-pulmonary arterial hypertension). Nine out of these PH patients died during a median follow-up period of 25 months. In 65 patients with PH, right ventricular end-diastolic dimension index (RVEDDI) evaluated by CMR was independently associated with mortality (hazard ratio 1.24; 95% CI: 1.08-1.46; P = 0.003). In a receiver operating characteristic analysis, RVEDDI highly predicted mortality, with area under the curve of 0.87. The 0.5-2-year follow-up data revealed that RVEDDI in both survivors and non-survivors did not significantly change over the clinical course, leading to the possibility that an early determination of RVEDDI could predict the prognosis. CONCLUSION: RVEDDI simply evaluated by CMR could serve as a significant predictor of mortality in PH-CTD. A further validation cohort study is needed to confirm its usability.
  • 肺基礎疾患を有する肺炎患者における分解抵抗性好中球細胞外トラップの形成               
    益田 紗季子, 石橋 美郷, 加藤 くるみ, 西端 友香, 田中 敏, 外丸 詩野, 辻野 一三, 石津 明洋
    日本病理学会会誌, 109, 1, 308, 308, (一社)日本病理学会, Mar. 2020
    Japanese
  • Prognostic Value of 18F-FDG PET Using Texture Analysis in Cardiac Sarcoidosis.
    Osamu Manabe, Kazuhiro Koyanagawa, Kenji Hirata, Noriko Oyama-Manabe, Hiroshi Ohira, Tadao Aikawa, Sho Furuya, Masanao Naya, Ichizo Tsujino, Yuuki Tomiyama, Yuka Otaki, Toshihisa Anzai, Nagara Tamaki
    JACC. Cardiovascular imaging, 13, 4, 1096, 1097, 09 Jan. 2020, [Peer-reviewed], [International Magazine]
    English
  • Pulmonary capillary hemangiomatosis-predominant vasculopathy in a patient with rheumatoid arthritis-associated interstitial lung disease: An autopsy report.
    Junichi Nakamura, Ichizo Tsujino, Gaku Yamamoto, Toshitaka Nakaya, Kei Takahashi, Hirokazu Kimura, Takahiro Sato, Taku Watanabe, Shimpei Nakagawa, Noriyuki Otsuka, Hiroshi Ohira, Satoshi Konno
    Respiratory medicine case reports, 31, 101215, 101215, 2020, [Corresponding author], [International Magazine]
    English, Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary hypertension (PH) associated with poor prognosis. Clinically, it is characterized by severe hypoxemia, centrilobular ground-glass opacities on computed tomography, and pulmonary congestion triggered by pulmonary vasodilating therapy. In some cases, PCH has been reported to develop with other disorders including connective tissue disease; however, to date, no reports have described PCH in a patient with rheumatoid arthritis. We report a case of a 59-year-old male PCH patient with rheumatoid arthritis and associated pulmonary fibrosis. He was initially diagnosed with severe group 3 PH and received sildenafil, which generated a favorable hemodynamic response. However, 5 years later, his pulmonary hemodynamics deteriorated, and he died at the age of 67. An autopsy was performed, and thickening of alveolar septa and capillary proliferation, pathological features of PCH, were extensively observed in both lungs. We discuss when PCH developed, how sildenafil improved his hemodynamics, and how PCH could be clinically detected by noninvasive evaluations.
  • A histopathological report of a 16-year-old male with peripheral pulmonary artery stenosis and Moyamoya disease with a homozygous RNF213 mutation.
    Kei Takahashi, Junichi Nakamura, Shinya Sakiyama, Toshitaka Nakaya, Takahiro Sato, Taku Watanabe, Hiroshi Ohira, Keishi Makita, Utano Tomaru, Akihiro Ishizu, Ichizo Tsujino
    Respiratory medicine case reports, 29, 100977, 100977, 2020, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Peripheral pulmonary artery stenosis (PPAS) is a rare pulmonary vasculopathy characterized by multiple stenoses and obstructions in the peripheral pulmonary arteries. PPAS often develops in children with congenital diseases such as Williams syndrome and Alagille syndrome; however, recent studies have reported PPAS cases in adults with Moyamoya disease (MMD). Recent genetic studies have demonstrated that ring finger protein 213 (RNF213) is a susceptibility gene for MMD. However, the pathophysiology of combined PPAS and MMD and the relationship between the two diseases remain largely unknown. Here we report a case of PPAS in a 16-year-old male, with a history of MMD, who died suddenly at 24. An autopsy was performed, and remarkable pathological changes were identified in the pulmonary arteries and in other arteries. Furthermore, genetic analysis revealed that the patient had a homozygous c.14576G > A (p.R4859K) mutation in RNF213. This is the first report to demonstrate the histopathology of systemic arteriopathy in a case with MMD and PPAS with a confirmed homozygous RNF213 mutation. We also review immunohistochemical data from the case and discuss how RNF213 mutation could have resulted in the observed vascular abnormalities.
  • 18F-FMISO PET/CT detects hypoxic lesions of cardiac and extra-cardiac involvement in patients with sarcoidosis.
    Sho Furuya, Masanao Naya, Osamu Manabe, Kenji Hirata, Hiroshi Ohira, Tadao Aikawa, Kazuhiro Koyanagawa, Keiichi Magota, Ichizo Tsujino, Toshihisa Anzai, Yuji Kuge, Noriko Oyama-Manabe, Kohsuke Kudo, Tohru Shiga, Nagara Tamaki
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology, 28, 5, 2141, 2148, 09 Dec. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: 18F-fluoromisonidazole (FMISO) is a hypoxia positron emission tomography (PET) tracer. Here, we evaluated cardiac and extra-cardiac sarcoidosis using both FMISO and 18F-fluorodeoxyglucose (FDG) PET/CT in a prospective cohort of patients with sarcoidosis. METHODS: Ten consecutive sarcoidosis patients with suspected cardiac involvement were prospectively enrolled. Each patient fasted overnight (for ≥ 18 hours) preceded by a low-carbohydrate diet before FDG PET/CT but not given special dietary instructions before the FMISO PET/CT scan. We visually and semiquantitatively assessed the uptakes of FMISO and FDG using the maximal standardized uptake value (SUVmax). The metabolic volume (MV) of FDG was calculated as the volume within the boundary determined by the threshold (mean SUV of blood pool × 1.5). RESULTS: Nine patients showed focal FDG uptake in the myocardium and were diagnosed with cardiac sarcoidosis. Among the patients with extra-cardiac lesions, FDG uptake was seen in 8 lymph nodes and 3 lung lesions. FMISO uptake was seen in the 7 cardiac (77.8%) and 6 extra-cardiac (54.5%) lesions. None of the patients showed physiological FMISO uptake in the myocardium. The SUVmax values of the lesions with FMISO uptake were higher than those of the lesions without FMISO uptake in both the cardiac (SUVmax: 9.9, IQR: 8.4-10.0 vs 7.3, IQR: 6.3-8.2) and non-cardiac lesions (SUVmax: 17.6, IQR: 14.5-19.3 vs 6.1, IQR: 5.9-6.2; P = 0.006). The MV values of the lesions with FMISO uptake were significantly higher than those of the lesions without FMISO uptake (111.3, IQR: 78.3-135.7 vs 6.4, IQR: 1.9-23.3; P = 0.0009). CONCLUSIONS: FMISO showed no physiological myocardial uptake and did not require special preparation. FMISO PET has the potential to detect hypoxic lesions in patients with sarcoidosis.
  • The rate of myocardial perfusion recovery after steroid therapy and its implication for cardiac events in cardiac sarcoidosis and primarily preserved left ventricular ejection fraction.
    Kazuhiro Koyanagawa, Masanao Naya, Tadao Aikawa, Osamu Manabe, Sho Furuya, Masato Kuzume, Noriko Oyama-Manabe, Hiroshi Ohira, Ichizo Tsujino, Toshihisa Anzai
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology, 28, 4, 1745, 1756, 11 Oct. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: Sarcoidosis is a multisystemic disorder of unknown cause characterized by immune granuloma formation in the involved organs. Few studies have reported on the myocardial perfusion changes by immunosuppression therapy in cardiac sarcoidosis (CS). Additionally, the relationship between myocardial perfusion changes and prognosis is unknown. Therefore, this study aimed to clarify myocardial perfusion recovery after steroid therapy and its prognostic value for major adverse cardiac events (MACE) in patients with CS. METHODS AND RESULTS: Thirty-eight consecutive patients with CS {median age, 63 [interquartile range (IQR) 51-68] years; 10 men} underwent both 18F-fluorodeoxyglucose positron emission tomography/computed tomography (CT) and electrocardiography-gated single-photon emission CT (SPECT) pre- and post-steroid therapy. Patients with improved or preserved myocardial perfusion after post-therapy were defined as the recovery group and those with worsened myocardial perfusion as the non-recovery group. Twenty-six patients (68%) were categorized as the recovery group. MACE occurred in eight patients. The Kaplan-Meier curves revealed a significantly higher rate of MACE in the non-recovery group (17.4%/y vs 2.9%/y, P = 0.007). CONCLUSIONS: Myocardial perfusion was recovered by steroid therapy in 61% and preserved in 8% of patients. Myocardial perfusion recovery after steroid therapy was significantly associated with a low incidence of MACE.
  • FDG PETのテクスチャ解析を用いた心臓サルコイドーシスの予後検討               
    真鍋 治, 平田 健司, 真鍋 徳子, 古家 翔, 小梁川 和宏, 大平 洋, 相川 忠夫, 納谷 昌直, 辻野 一三, 玉木 長良, 志賀 哲
    核医学, 56, Suppl., S137, S137, (一社)日本核医学会, Oct. 2019, [Peer-reviewed], [Domestic magazines]
    English
  • 心筋サルコイドーシスにおける心筋血流の改善から予想される心イベントの減少化(Improvement in myocardial perfusion predicts fewer cardiac events in cardiac sarcoidosis)               
    小梁川 和宏, 納谷 昌直, 相川 忠夫, 真鍋 治, 古家 翔, 葛目 将人, 真鍋 徳子, 大平 洋, 辻野 一三, 安斉 俊久
    核医学, 56, Suppl., S137, S137, (一社)日本核医学会, Oct. 2019, [Peer-reviewed], [Domestic magazines]
    English
  • 心臓サルコイドーシス評価のFDG-PET/CT撮像にヘパリン注射は必要か?               
    古家 翔, 真鍋 治, 大平 洋, 納谷 昌直, 相川 忠夫, 小梁川 和宏, 辻野 一三, 真鍋 徳子[大山], 平田 健司, 志賀 哲
    核医学, 56, Suppl., S137, S137, (一社)日本核医学会, Oct. 2019, [Peer-reviewed], [Domestic magazines]
    Japanese
  • Reduced diffusing capacity for carbon monoxide predicts borderline pulmonary arterial pressure in patients with systemic sclerosis.
    Ninagawa K, Kato M, Nakamura H, Abe N, Kono M, Fujieda Y, Oku K, Yasuda S, Ohira H, Tsujino I, Atsumi T
    Rheumatology international, 39, 11, 1883, 1887, Jul. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Early intervention in pulmonary arterial hypertension associated with systemic sclerosis (SSc) may improve its prognosis. We aimed to establish an algorithm to detect mean pulmonary artery pressure (mPAP) > 20 mmHg using non-invasive examinations in SSc patients by modifying the DETECT algorithm. This study included SSc patients who underwent right heart catheterization (RHC) in our hospital during 2010-2018. Following variables were assessed for performance to predict mPAP ≥ 25 mmHg or > 20 mmHg; anti-centromere or U1-RNP antibody, plasma BNP level, serum urate level, right axis deviation, forced vital capacity (FVC)/diffusing capacity for carbon monoxide (DLCO) ratio, and tricuspid regurgitation velocity. Of 58 patients enrolled in this study, 24 had mPAP of ≥ 25 mmHg and 9 had mPAP of 21-24 mmHg. Among variables tested, only FVC/DLCO elevated similarly in patients with mPAP of ≥ 25 mmHg (median 2.5) and those with mPAP of 21-24 mmHg (median 2.5) compared to those with mPAP of ≤ 20 mmHg (median 1.5). Given the particularly good correlation between DLCO and mPAP of > 20 mmHg, each variable was weighted according to its odds ratio and the total weighted score was calculated. The total weighted score exhibited a good predictive performance for mPAP of > 20 mmHg with its sensitivity of 87.5% and specificity of 92%. Among conventional risk factors for PAH, decreased DLCO may predict mPAP > 20 mmHg with priority in SSc patients. Weighting DLCO may improve the performance of screening algorithm for early SSc-PAH.
  • 【肺高血圧症-診断・治療の最新動向-】肺高血圧症の診断 胸部画像検査による右心・肺循環系機能評価
    佐藤 隆博, 大平 洋, 真鍋 徳子, 辻野 一三
    日本臨床, 77, 7, 1102, 1107, (株)日本臨床社, Jul. 2019
    Japanese
  • Use of 18F-FDG PET/CT texture analysis to diagnose cardiac sarcoidosis.
    Osamu Manabe, Hiroshi Ohira, Kenji Hirata, Souichiro Hayashi, Masanao Naya, Ichizo Tsujino, Tadao Aikawa, Kazuhiro Koyanagawa, Noriko Oyama-Manabe, Yuuki Tomiyama, Keiichi Magota, Keiichiro Yoshinaga, Nagara Tamaki
    European journal of nuclear medicine and molecular imaging, 46, 6, 1240, 1247, Jun. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, PURPOSE: 18F-fluorodeoxyglocose positron emission tomography (FDG PET) plays a significant role in the diagnosis of cardiac sarcoidosis (CS). Texture analysis is a group of computational methods for evaluating the inhomogeneity among adjacent pixels or voxels. We investigated whether texture analysis applied to myocardial FDG uptake has diagnostic value in patients with CS. METHODS: Thirty-seven CS patients (CS group), and 52 patients who underwent FDG PET/CT to detect malignant tumors with any FDG cardiac uptake (non-CS group) were studied. A total of 36 texture features from the histogram, gray-level co-occurrence matrix (GLCM), gray-level run length matrix (GLRLM), gray-level zone size matrix (GLZSM) and neighborhood gray-level difference matrix (NGLDM), were computed using polar map images. First, the inter-operator and inter-scan reproducibility of the texture features of the CS group were evaluated. Then, texture features of the patients with CS were compared to those without CS lesions. RESULTS: Twenty-eight of the 36 texture features showed high inter-operator reproducibility with intraclass correlation coefficients (ICCs) over 0.80. In addition, 17 of the 36 showed high inter-scan reproducibility with ICCs over 0.80. The SUVmax showed no difference between the CS and non-CS group [7.36 ± 2.77 vs. 8.78 ± 4.65, p = 0.45, area under the curve (AUC) = 0.60]. By contrast, 16 of the 36 texture features could distinguish CS from non-CS grsoup with AUC > 0.80. Multivariate logistic regression analysis after hierarchical clustering concluded that long-run emphasis (LRE; P = 0.0004) and short-run low gray-level emphasis (SRLGE; P = 0.016) were significant independent factors that could distinguish between the CS and non-CS groups. Specifically, LRE was significantly higher in CS than in non-CS (30.1 ± 25.4 vs. 11.4 ± 4.6, P < 0.0001), with high diagnostic ability (AUC = 0.91), and had high inter-operator reproducibility (ICC = 0.98). CONCLUSIONS: The texture analysis had high inter-operator and high inter-scan reproducibility. Some of texture features showed higher diagnostic value than SUVmax for CS diagnosis. Therefore, texture analysis may have a role in semi-automated systems for diagnosing CS.
  • 心臓サルコイドーシスにおけるステロイド治療後の心筋血流改善は心血管イベントの低発症率を予測する               
    小梁川 和宏, 納谷 昌直, 相川 忠夫, 真鍋 治, 真鍋 徳子, 古家 翔, 辻野 一三, 大平 洋
    日本心臓核医学会ニュースレター, 21, 2, 124, 124, 日本心臓核医学会, Jun. 2019, [Peer-reviewed], [Domestic magazines]
    Japanese
  • Guidelines for the Treatment of Pulmonary Hypertension (JCS 2017/JPCPHS 2017).
    Fukuda K, Date H, Doi S, Fukumoto Y, Fukushima N, Hatano M, Ito H, Kuwana M, Matsubara H, Momomura SI, Nishimura M, Ogino H, Satoh T, Shimokawa H, Yamauchi-Takihara K, Tatsumi K, Ishibashi-Ueda H, Yamada N, Yoshida S, Abe K, Ogawa A, Ogo T, Kasai T, Kataoka M, Kawakami T, Kogaki S, Nakamura M, Nakayama T, Nishizaki M, Sugimura K, Tanabe N, Tsujino I, Yao A, Akasaka T, Ando M, Kimura T, Kuriyama T, Nakanishi N, Nakanishi T, Tsutsui H, Japanese Circulation Society, the Japanese Pulmonary Circulation, Pulmonary Hypertension, Society Joint, Working Group
    Circulation journal : official journal of the Japanese Circulation Society, 83, 4, 842, 945, Mar. 2019, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal
  • Prognostic value of phase analysis on gated single photon emission computed tomography in patients with cardiac sarcoidosis.
    Kazuhiro Koyanagawa, Masanao Naya, Tadao Aikawa, Osamu Manabe, Masato Kuzume, Hiroshi Ohira, Ichizo Tsujino, Nagara Tamaki, Toshihisa Anzai
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology, 28, 1, 128, 136, 27 Feb. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: We aimed to determine the correlation between phase analysis, reflecting the heterogeneity of perfusion defects, and the dyssynchrony of the left ventricle wall motion, and adverse cardiac events in cardiac sarcoidosis (CS) patients. METHODS: Fifty-seven consecutive patients with diagnosed CS (64 [IQR 55-71] years old, 14 males), who underwent 18F-FDG PET/CT and ECG-gated SPECT, were studied. FDG PET was analysed to measure cardiac metabolic volume (CMV), and total lesion glycolysis (TLG). The SPECT findings, such as LVEF, Summed Rest Score (SRS), bandwidth (BW) were evaluated. RESULTS: The median of BW was 56° (IQR 40-95). BW showed a strong inverse correlation with LVEF (r = - 0.60, P < 0.0001), and positive correlation with SRS (r = 0.82, P < 0.0001). However, there were no significant correlations between BW and CMV or TLG. The Kaplan-Meier curves revealed a significantly higher rate of MACE in the high BW group (BW > 56°) than the low BW group (BW ≤ 56°) (15.1%/years vs. 4.4%/years, P = 0.025). In multivariable analysis, BW was a significant independent predictor of MACE (P = 0.015). CONCLUSION: Phase analysis on gated SPECT was a significant and independent predictor of MACE in patients with CS.
  • Cardiac sarcoidosis classification with deep convolutional neural network-based features using polar maps.
    Ren Togo, Kenji Hirata, Osamu Manabe, Hiroshi Ohira, Ichizo Tsujino, Keiichi Magota, Takahiro Ogawa, Miki Haseyama, Tohru Shiga
    Computers in biology and medicine, 104, 81, 86, Jan. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, AIMS: The aim of this study was to determine whether deep convolutional neural network (DCNN)-based features can represent the difference between cardiac sarcoidosis (CS) and non-CS using polar maps. METHODS: A total of 85 patients (33 CS patients and 52 non-CS patients) were analyzed as our study subjects. One radiologist reviewed PET/CT images and defined the left ventricle region for the construction of polar maps. We extracted high-level features from the polar maps through the Inception-v3 network and evaluated their effectiveness by applying them to a CS classification task. Then we introduced the ReliefF algorithm in our method. The standardized uptake value (SUV)-based classification method and the coefficient of variance (CoV)-based classification method were used as comparative methods. RESULTS: Sensitivity, specificity and the harmonic mean of sensitivity and specificity of our method with the ReliefF algorithm were 0.839, 0.870 and 0.854, respectively. Those of the SUVmax-based classification method were 0.468, 0.710 and 0.564, respectively, and those of the CoV-based classification method were 0.655, 0.750 and 0.699, respectively. CONCLUSION: The DCNN-based high-level features may be more effective than low-level features used in conventional quantitative analysis methods for CS classification.
  • Chinese herbal medicine Qing-Dai-induced pulmonary arterial hypertension in a patient with ulcerative colitis: A case report and experimental investigation.
    Sato K, Ohira H, Horinouchi T, Nakaya T, Mazaki Y, Sugimoto A, Watanabe T, Tsujino I, Nishimura M
    Respiratory medicine case reports, 26, 265, 269, 2019, [Peer-reviewed], [International Magazine]
    English, A recent case report described a case of pulmonary arterial hypertension (PAH) associated with use of the Chinese herbal medicine Qing-Dai; however, the clinical course and possible mechanisms have not been characterized. We present the case of a man with ulcerative colitis who was diagnosed with idiopathic PAH. After initiating oral beraprost therapy, the patient showed significant hemodynamic improvements and an unusual course of clinical recovery. In 2016, the Japanese Ministry of Health, Labour, and Welfare issued a warning regarding the possible side effects of Qing-Dai. We learned that our patient had been taking self-purchased Qing-Dai for 2 years. Therefore, we performed an experimental study and determined that Qing-Dai may cause PAH through a mechanism involving nitric oxide synthase inhibition and pulmonary artery endothelial dysfunction.
  • 正常耐糖能日本人男性における体幹部脂肪分布パターンとインスリン抵抗性の関連               
    高階 知紗, 辻野 一三, 坂上 慎二, 渡部 拓, 池田 大輔, 山田 安寿香, 佐藤 隆博, 大平 洋, 大塚 吉則, 大山 徳子[真鍋], 西村 正治
    Diabetes Frontier Online, 5, np25, np25, (株)メディカルレビュー社, Dec. 2018
    Japanese
  • Which is the proper reference tissue for measuring the change in FDG PET metabolic volume of cardiac sarcoidosis before and after steroid therapy?
    Sho Furuya, Osamu Manabe, Hiroshi Ohira, Kenji Hirata, Tadao Aikawa, Masanao Naya, Ichizo Tsujino, Kazuhiro Koyanagawa, Toshihisa Anzai, Noriko Oyama-Manabe, Tohru Shiga
    EJNMMI research, 8, 1, 94, 94, 05 Oct. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: Cardiac sarcoidosis (CS) is a rare but potentially life-threatening disease that causes conduction disturbance, systolic dysfunction, and, most notably, sudden cardiac death. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) plays important roles not only in diagnosing CS but also in evaluating the effects of anti-inflammatory therapy. A volume-based analysis of parameters measured by FDG PET, so-called cardiac metabolic volume (CMV), has emerged as a new assessment tool. CMV is measured as the volume within the boundary determined by a reference tissue such as the liver and the blood pool uptake. However, there is a possibility that oral steroid therapy could lead to variations of the liver and the blood pool uptake. Here, we attempted to evaluate the steroid effects on the liver and the blood pool uptake. A total of 38 CS patients who underwent FDG PET/CT before and during steroid therapy were retrospectively enrolled. Volumes of interest (VOIs) were placed in the right lobe of the liver and descending aorta (DA). The maximum standardized uptake value (SUVmax), SUVmean, and SUVpeak of the liver and DA were compared between time points before and during steroid therapy. RESULTS: The SUVmax, SUVmean, and SUVpeak of the liver during steroid therapy significantly increased from the time point before the therapy (SUVmax 3.5 ± 0.4 vs. 3.8 ± 0.6, p = 0.014; SUVmean 2.7 ± 0.3 vs. 3.0 ± 0.5, p = 0.0065; SUVpeak 3.0 ± 0.4 vs. 3.4 ± 0.6, p = 0.006). However, the SUVmax, SUVmean, and SUVpeak in the DA did not significantly change (SUVmax 2.2 ± 0.3 vs. 2.2 ± 0.4, p = 0.46; SUVmean 1.9 ± 0.3 vs. 2.0 ± 0.4, p = 0.56; SUVpeak 2.0 ± 0.3 vs. 2.0 ± 0.3, p = 0.70). CONCLUSIONS: We measured FDG uptake in the liver and blood pool before and during steroid therapy. Steroid therapy increased the liver uptake but not the blood pool uptake. Our findings suggested that the DA uptake is a more suitable threshold than liver uptake to evaluate therapeutic effects using volume-based analysis of cardiac FDG PET.
  • 【右室・肺循環の最前線】右室機能の画像評価 心臓MRI
    佐藤 隆博, 辻野 一三, 真鍋 徳子
    循環器内科, 84, 2, 165, 170, (有)科学評論社, Aug. 2018
    Japanese
  • Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension: A systematic review.
    Tanabe N, Kawakami T, Satoh T, Matsubara H, Nakanishi N, Ogino H, Tamura Y, Tsujino I, Ogawa A, Sakao S, Nishizaki M, Ishida K, Ichimura Y, Yoshida M, Tatsumi K
    Respiratory investigation, 56, 4, 332, 341, Jul. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: Balloon pulmonary angioplasty (BPA) has been performed for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or residual pulmonary hypertension after pulmonary endarterectomy (PEA). We performed a systematic review to assess the efficacy and safety of BPA, especially compared to medical treatment or PEA. METHODS: We reviewed all studies investigating pre- and post-treatment pulmonary hemodynamics, mortality, or complications from three electronic databases (PubMed, Cochrane Library, Japan Medical Abstracts Society) prior to February 2017. From 26 studies retrieved, we selected 13 studies (493 patients): the 10 most recent ones including complete data from each institution, one study of residual pulmonary hypertension, and two studies comparing BPA with medical treatment or PEA. RESULTS: No randomized controlled or prospective controlled studies comparing BPA with medical treatment or PEA were reported. The early mortality of BPA ranged from 0% to 14.3%; lung injury occurred in 7.0% to 31.4% (average sessions, 2.5-6.6). Mean pulmonary arterial pressure decreased from 39.4-56 to 20.9-36 mm Hg, and the 6-min walk distance increased from 191-405 to 359-501 m. The 2-year mortality of 80 patients undergoing BPA was significantly lower compared to 68 patients receiving medical treatment (1.3% vs. 13.2%); the risk ratio was 0.14 (95% confidence interval: 0.03-0.76). No significant difference was observed in the 2-year mortality between BPA (n=97) and PEA (n=63) patients. CONCLUSIONS: This systematic review suggests that BPA improves hemodynamics, has acceptable early mortality, and may improve long-term survival compared with medical treatment in inoperable CTEPH patients.
  • Successful Application of Edoxaban in the Treatment of Venous Thromboembolism Recurrence in a Patient with Non-small Cell Lung Cancer after Tumor Shrinkage.
    Tetsuaki Shoji, Hidenori Mizugaki, Yasuyuki Ikezawa, Megumi Furuta, Yuta Takashima, Hajime Kikuchi, Houman Goudarzi, Hajime Asahina, Junko Kikuchi, Eiki Kikuchi, Jun Sakakibara-Konishi, Naofumi Shinagawa, Ichizo Tsujino, Masaharu Nishimura
    Internal medicine (Tokyo, Japan), 57, 12, 1769, 1772, 15 Jun. 2018, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, This report describes the case of a 66-year-old man with non-small cell lung cancer and venous thromboembolism (VTE). Unfractionated heparin (UFH) was initially used to control VTE before chemotherapy. However, switching UFH to warfarin or edoxaban, a novel oral anticoagulant (NOAC), failed. Chemotherapy was then administered to control the tumor which was thought to have been the main cause of VTE, which had been treated by UFH. After tumor shrinkage was achieved by chemotherapy, we were able to successfully switch from UFH to edoxaban. Controlling the tumor size and activity enabled the use of edoxaban as maintenance therapy for VTE.
  • Use of deep convolutional neural network-based features for detection of cardiac sarcoidosis from polar map               
    Ren Togo, Kenji Hirata, Osamu Manabe, Hiroshi Ohira, Ichizo Tsujino, Takahiro Ogawa, Miki Haseyama, Tohru Shiga
    Society of Nuclear Medicine and Molecular Imaging Annual Meeting (SNMMI), Jun. 2018, [Peer-reviewed], [International Magazine]
    English, International conference proceedings
  • Amelioration of right ventricular systolic function and stiffness in a patient with idiopathic pulmonary arterial hypertension treated with oral triple combination therapy.
    Nakaya T, Tsujino I, Ohira H, Sato T, Watanabe T, Oyama-Manabe N, Nishimura M
    Pulmonary circulation, 8, 2, 2045894018765350, 204589401876535, SAGE Publications, Apr. 2018, [Peer-reviewed], [Corresponding author], [International Magazine]
    Scientific journal, Right ventricular (RV) function is an important determinant of the prognosis in patients with pulmonary arterial hypertension (PAH). In the context of recent therapeutic progress, there is an increasing need for better monitoring of RV function for management of PAH. We present the case of a 42-year-old woman with idiopathic PAH who was treated with three oral pulmonary vasodilators, i.e. tadalafil, ambrisentan, and beraprost. At the baseline assessment, the mean pulmonary arterial pressure (mPAP) was 45 mmHg, cardiac index (CI) was 1.36 L/min/m2, and pulmonary vascular resistance (PVR) was elevated to 21.3 Wood units (WU). However, three months after the start of combination treatment, mPAP and PVR decreased to 42 mmHg and 7.5 WU, respectively, and conventional indices of RV function, such as CI, right atrial area, and right atrial pressure also improved. Beyond three months, however, there were no further improvements in mPAP, PVR, or indices of RV function. In addition, we calculated three recently introduced indices of intrinsic RV function: end-systolic elastance (Ees; an index of RV contractility), Ees/arterial elastance ratio (Ees/Ea; an index of RV/pulmonary arterial coupling), and β (an index of RV stiffness) using cardiac magnetic resonance imaging and Swan-Ganz catheterization measurements. Notably, in contrast to conventional parameters, Ees, Ees/Ea, and β showed persistent improvement during the entire two-year follow-up. The application of Ees, Ees/Ea, and β may play an additional role in a comprehensive assessment of RV function in PAH.
  • Successful treatment of tocilizumab-resistant large vessel pulmonary arteritis with infliximab.
    Tanimura S, Kato M, Abe N, Ohira H, Tsujino I, Atsumi T
    Immunological medicine, 41, 1, 39, 42, Mar. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Pulmonary hypertension associated with large vessel pulmonary arteritis (LVPA) has been reported in the course of Takayasu arteritis (TAK). Biologic therapies targeting inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin-6, have recently been successful to treat refractory TAK. Infliximab (IFX), an anti-TNF-α antibody and tocilizumab (TCZ), an anti-IL-6 receptor antibody may have similar efficacy and safety profile in the treatment of TAK. However, some cases are refractory to TNF inhibitors but respond to TCZ, and vice versa. Here, we report a severe case of LVPA, who was successfully treated with IFX but was refractory to TCZ and presented a discrepancy between serum C-reactive protein levels and fluorodeoxyglucose vascular positivity. This case would indicate heterogeneity of pathogenic mechanisms in LVPA and TAK.
  • Efficient detection of pulmonary arterial hypertension using serum haptoglobin level and cardiac MRI in patients with connective tissue diseases: A pilot study
    H. Nakamura, Masaru Kato, A. Noguchi, H. Ohira, I. Tsujino, T. Atsumi
    Clinical and Experimental Rheumatology, 36, 2, 345, 346, Clinical and Experimental Rheumatology S.A.S., 2018, [Peer-reviewed], [International Magazine]
    English
  • 先天性門脈体循環シャントによる門脈肺高血圧症疑いに対しAMPLATZER Vascular Plug IIで塞栓術を施行した1例               
    曽山 武士, 阿保 大介, 森田 亮, 作原 祐介, 工藤 與亮, 辻野 一三, 中谷 資隆
    IVR: Interventional Radiology, 32, 4, 324, 325, (一社)日本インターベンショナルラジオロジー学会, Jan. 2018
    Japanese
  • Effectiveness and outcome of pulmonary arterial hypertension-specific therapy in japanese patients with pulmonary arterial hypertension
    Yuichi Tamura, Hiraku Kumamaru, Toru Satoh, Hiroaki Miyata, Aiko Ogawa, Nobuhiro Tanabe, Masaru Hatano, Atsushi Yao, Kohtaro Abe, Ichizo Tsujino, Keiichi Fukuda, Hiroshi Kimura, Masataka Kuwana, Hiromi Matsubara, Koichiro Tatsumi, on behalf of the Japan PH Registry (JAPHR) Network
    Circulation Journal, 82, 1, 275, 282, Japanese Circulation Society, 2018, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal
  • Performance of computed tomography-derived pulmonary vasculature metrics in the diagnosis and haemodynamic assessment of pulmonary arterial hypertension
    Kaoruko Shimizu, Ichizo Tsujino, Takahiro Sato, Ayako Sugimoto, Toshitaka Nakaya, Taku Watanabe, Hiroshi Ohira, Yoichi M. Ito, Masaharu Nishimura
    EUROPEAN JOURNAL OF RADIOLOGY, 96, 31, 38, Nov. 2017, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal
  • Accuracy of echocardiographic indices for serial monitoring of right ventricular systolic function in patients with precapillary pulmonary hypertension
    Takahiro Sato, Ichizo Tsujino, Hiroshi Ohira, Noriko Oyama-Manabe, Yoichi M. Ito, Chisa Takashina, Taku Watanabe, Masaharu Nishimura
    PLOS ONE, 12, 11, e0187806, Nov. 2017, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal
  • Decreased haptoglobin levels inversely correlated with pulmonary artery pressure in patients with pulmonary arterial hypertension: A cross-sectional study
    Hiroyuki Nakamura, Masaru Kato, Toshitaka Nakaya, Michihiro Kono, Shun Tanimura, Takahiro Sato, Yuichiro Fujieda, Kenji Oku, Hiroshi Ohira, Toshiyuki Bohgaki, Shinsuke Yasuda, Ichizo Tsujino, Masaharu Nishimura, Tatsuya Atsumi
    MEDICINE, 96, 43, e8349, Oct. 2017, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Delayed contrast-enhanced computed tomography in patients with known or suspected cardiac sarcoidosis: A feasibility study.
    Tadao Aikawa, Noriko Oyama-Manabe, Masanao Naya, Hiroshi Ohira, Ayako Sugimoto, Ichizo Tsujino, Masahiko Obara, Osamu Manabe, Kohsuke Kudo, Hiroyuki Tsutsui, Nagara Tamaki
    European radiology, 27, 10, 4054, 4063, Oct. 2017, [Peer-reviewed], [International Magazine]
    English, Scientific journal, OBJECTIVES: To evaluate the diagnostic value of delayed contrast-enhanced computed tomography (DE-CT) for cardiac sarcoidosis (CS) in patients with or without implantable devices, including a quantitative comparison with late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). METHODS: Twenty-four patients (mean age, 64 ± 9 years; 17 women) with known or suspected CS underwent retrospective electrocardiogram-gated DE-CT at 80 kV with knowledge-based iterative model reconstruction. Fourteen patients without implantable devices also underwent LGE-CMR, while ten with pacemakers or implantable cardioverter-defibrillators did not. The presence of hyperenhanced myocardium was assessed visually and quantitatively using a 5-standard deviation threshold above the mean of remote myocardium. RESULTS: Inter-observer agreement for visual detection of hyperenhanced segments on DE-CT was excellent in patients with implantable devices and in those without (κ = 0.91 and κ = 0.94, respectively). Comparisons of the percent area of hyperenhanced myocardium between DE-CT and LGE-CMR on both per-patient and per-segment analyses showed good correlations (r = 0.96 and r = 0.83, respectively; p < 0.001). The sensitivity and specificity of DE-CT for the diagnosis of CS were 94% and 33%. CONCLUSIONS: The extent of hyperenhanced lesion with DE-CT showed good agreement with LGE-CMR results. DE-CT showed high sensitivity for detecting CS and may be useful particularly in patients with contraindications to CMR. KEY POINTS: • Delayed contrast-enhanced CT (DE-CT) can be applied to patients with implantable devices. • DE-CT can detect cardiac sarcoidosis (CS) lesions similarly to cardiac MRI. • DE-CT shows high sensitivity for detecting CS. • DE-CT may be useful particularly in patients with contraindications to cardiac MRI.
  • Replacement myocardial fibrosis at the site of late gadolinium enhancement on magnetic resonance imaging in a patient with diffuse cutaneous systemic sclerosis: An autopsy report.
    Atsushi Noguchi, Ichizo Tsujino, Noriko Oyama-Manabe, Mishie Tanino
    Journal of cardiology cases, 16, 2, 48, 51, Aug. 2017, [Peer-reviewed], [Corresponding author], [Domestic magazines]
    English, Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a well-known finding indicative of cardiac involvement in systemic sclerosis (SSc heart). However, few studies have reported the precise histopathology at the site of LGE. We present an autopsy report of a 51-year-old man diagnosed with diffuse cutaneous SSc according to a systematic diagnostic workup, including skin biopsy. CMR indicated left ventricular (LV) dilatation and broadly distributed subendocardial LGE in the LV walls. The patient was treated with methylprednisolone pulse therapy because of multiple episodes of ventricular tachycardia, whereas he subsequently died of left heart failure. An autopsy study revealed broad subendocardial replacement fibrosis, concomitant with the distribution of LGE on CMR, without inflammatory or edematous changes. Notably, myocardial fibrosis was evident around the intramural coronary arteries, although the arteries themselves were intact. These findings demonstrated that broad subendocardial LGE on CMR reflected replacement myocardial fibrosis in a patient with diffuse cutaneous SSc. These clinicopathological observations suggested that spasms in the intramyocardial arteries or the cardiac Raynaud's phenomenon may have provoked broad subendocardial fibrosis of the LV walls. .
  • Representative chest auscultation findings in pulmonary hypertension: Phonocardiograms and sound clips
    Takahiro Sato, Hiroshi Ohira, Ichizo Tsujino
    Annals of the American Thoracic Society, 14, 5, e1, e3, 01 May 2017, [Peer-reviewed], [Corresponding author], [International Magazine]
    English
  • 先天性門脈体循環シャントによる門脈肺高血圧症に対しAMPLATZER Vascular Plug2で塞栓術を施行した1例               
    曽山 武士, 阿保 大介, 森田 亮, 加藤 大貴, 作原 祐介, 工藤 與亮, 辻野 一三, 中谷 資隆
    IVR: Interventional Radiology, 32, Suppl., 231, 231, (一社)日本インターベンショナルラジオロジー学会, Apr. 2017
    Japanese
  • Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension results of a multicenter registry
    Aiko Ogawa, Toru Satoh, Tetsuya Fukuda, Koichiro Sugimura, Yoshihiro Fukumoto, Noriaki Emoto, Norikazu Yamada, Atsushi Yao, Motomi Ando, Hitoshi Ogino, Nobuhiro Tanabe, Ichizo Tsujino, Masayuki Hanaoka, Kenji Minatoya, Hiroshi Ito, Hiromi Matsubara
    Circulation: Cardiovascular Quality and Outcomes, 10, 11, Lippincott Williams and Wilkins, 2017, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Clinical Application of 18F-fluorodeoxyglucose PET and LGE CMR in Cardiac Sarcoidosis
    Ohira Hiroshi, Yoshinaga Keiichiro, Manabe Osamu, Oyama-Manabe Noriko, Tsujino Ichizo, Nishimura Masaharu, Tamaki Nagara
    Annals of Nuclear Cardiology, 3, 1, 125, 130, Japanese Society of Nuclear Cardiology, 2017
    English, Sarcoidosis is a multisystem granulomatous disease of unknown etiology that is characterized by the formation of non-caseating granulomas at various sites in the body. Cardiac sarcoidosis (CS) has been underdiagnosed in the past due to a lack of imaging modalities with high sensitivity. CS may cause various symptoms including conduction disturbance, ventricular arrhythmias, cardiac dysfunction and sudden cardiac death, which account for an increased mortality rate in these patients. 18F-fluorodeoxyglucose positron emission tomography (FDG PET) and late gadolinium-enhanced cardiac magnetic resonance imaging (LGE CMR) have played important roles in the recent guidelines for the diagnosis of CS. Each one possesses its own unique abilities and can contribute to early disease detection, assessment of disease activity, response to treatment, and risk stratification.
    However, further studies are necessary in order to establish the standard methods for clinical application of FDG PET and CMR.
  • Bi-ventricular interplay in patients with systemic sclerosis-associated pulmonary arterial hypertension: Detection by cardiac magnetic resonance
    Atsushi Noguchi, Masaru Kato, Michihito Kono, Kazumasa Ohmura, Hiroshi Ohira, Ichizo Tsujino, Noriko Oyama-Manabe, Kenji Oku, Toshiyuki Bohgaki, Tetsuya Horita, Shinsuke Yasuda, Masaharu Nishimura, Tatsuya Atsumi
    MODERN RHEUMATOLOGY, 27, 3, 481, 488, 2017, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • The effects of pulmonary vasodilating agents on right ventricular parameters in severe group 3 pulmonary hypertension: a pilot study
    Takahiro Sato, Ichizo Tsujino, Ayako Sugimoto, Toshitaka Nakaya, Taku Watanabe, Hiroshi Ohira, Masaru Suzuki, Satoshi Konno, Noriko Oyama-Manabe, Masaharu Nishimura
    Pulmonary Circulation, 6, 4, 524, 531, Dec. 2016, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal
  • C-11 Hydroxyephedrine PET/CTを用いた心交感神経機能検出による心サルコイドーシス診断の有用性               
    吉永 恵一郎, 真鍋 治, 大平 洋, 辻野 一三, 佐藤 隆博, 加藤 千恵次, 西村 正治, 玉木 長良
    核医学, 53, Suppl., S305, S305, (一社)日本核医学会, Oct. 2016
    Japanese
  • MRI計測による肺循環時間は肺高血圧重症度と相関するか               
    真鍋 徳子[大山], 佐藤 隆博, 大平 洋, 辻野 一三, 中谷 資隆, 加藤 扶美, 工藤 與亮, 玉木 長良
    日独医報, 61, 1, 133, 133, バイエル薬品(株), Sep. 2016
    Japanese
  • 肺高血圧症の病態と治療2016Up to Date 肺高血圧症における右心形態・機能および代謝異常
    中谷資隆, 大平洋, 辻野一三
    呼吸と循環, 64, 6, 543‐547, 542, 医学書院, 15 Jun. 2016, [Corresponding author], [Domestic magazines]
    Japanese
  • Right heart morphology, function and metabolism in pulmonary hypertension               
    Toshitaka Nakaya, Hiroshi Ohira, Ichizo Tsujino
    Respiration and Circulation, 64, 6, 543, 547, Igaku-Shoin Ltd, 01 Jun. 2016
    Japanese, Scientific journal
  • Japan PH Registryによる本邦のPAHの予後解析               
    田村 雄一, 宮田 裕章, 佐藤 徹, 松原 広己, 巽 浩一郎, 田邉 信宏, 八尾 厚史, 阿部 弘太郎, 辻野 一三, 木村 弘, JAPHR investigators
    呼吸と循環, 64, 5, S24, S24, (株)医学書院, May 2016
    Japanese
  • 肺高血圧症における右室stiffnessに関する検討               
    中谷 資隆, 辻野 一三, 佐藤 隆博, 渡部 拓, 大平 洋, 真鍋 徳子, 西村 正治
    呼吸と循環, 64, 5, S37, S37, (株)医学書院, May 2016
    Japanese
  • 重症3群肺高血圧症の右室形態と収縮能への肺血管拡張療法の効果               
    杉本 絢子, 辻野 一三, 中村 順一, 佐藤 隆博, 大平 洋, 渡部 拓, 鈴木 雅, 今野 哲, 西村 正治
    呼吸と循環, 64, 5, S38, S38, (株)医学書院, May 2016
    Japanese
  • The regional evaluation of cardiac sympathetic nervous system dysfunction and inflammatory lesion for sarcoidosis patients
    Manabe Osamu, Yoshinaga Keiichiro, Ohira Hiroshi, Tsujino Ichizo, Oyama-Manabe Noriko, Nishimura Masaharu, Tamaki Nagara
    JOURNAL OF NUCLEAR MEDICINE, 57, 01 May 2016, [Peer-reviewed], [International Magazine]
  • Assessment of reduction in quantitative pulmonary blood flow using O-15-labeled water PET in patients with chronic thromboembolic pulmonary hypertension
    Yoshinaga Keiichiro, Tomiyama Yuuki, Hiroshi Ohira, Manabe Osamu, Tsujino Ichizo, Katoh Chietsugu, Masaharu Nishimura, Tamaki Nagara
    JOURNAL OF NUCLEAR MEDICINE, 57, 01 May 2016, [Peer-reviewed], [International Magazine]
  • Steroid therapy affects the cardiac metabolic shift and requires the careful attention in evaluation of the cardiac sarcoidosis with FDG PET/CT
    Manabe Osamu, Yoshinaga Keiichiro, Ohira Hiroshi, Oyama-Manabe Noriko, Tsujino Ichizo, Hirata Kenji, Kikuchi Hisaya, Nishimura Masaharu, Tamaki Nagara
    JOURNAL OF NUCLEAR MEDICINE, 57, 01 May 2016, [Peer-reviewed], [International Magazine]
  • The effects of 18-h fasting with low-carbohydrate diet preparation on suppressed physiological myocardial (18)F-fluorodeoxyglucose (FDG) uptake and possible minimal effects of unfractionated heparin use in patients with suspected cardiac involvement sarcoidosis.
    Osamu Manabe, Keiichiro Yoshinaga, Hiroshi Ohira, Atsuro Masuda, Takahiro Sato, Ichizo Tsujino, Asuka Yamada, Noriko Oyama-Manabe, Kenji Hirata, Masaharu Nishimura, Nagara Tamaki
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology, 23, 2, 244, 52, Apr. 2016, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: (18)F-fluorodeoxyglucose (FDG) PET plays an important role in the detection of cardiac involvement sarcoidosis (CS). However, diffuse left ventricle (LV) wall uptake sometimes makes it difficult to distinguish between positive uptake and physiological uptake. The aims of this study were to evaluate the effects of 18-h fasting with low-carbohydrate diet (LCD) vs a minimum of 6-h fasting preparations on diffuse LV FDG uptake and free fatty acid (FFA) levels in patients with suspected CS. METHODS: Eighty-two patients with suspected CS were divided into 2 preparation protocols: one with a minimum 6-h fast without LCD preparation (group A, n = 58) and the other with a minimum 18-h fast with LCD preparation (group B, n = 24). All patients also received intravenous unfractionated heparin (UFH; 50 IU/kg) before the injection of FDG. RESULTS: Group A showed a higher percentage of diffuse LV uptake than did group B (27.6 vs 0.0%, P = .0041). Group B showed higher FFA levels (1159.1  ±  393.0, 650.5  ±  310.9 μEq/L, P < .0001) than did group A. Patients with diffuse LV uptake (n = 16) showed lower FFA levels than did other patients (n = 66) (432.1  ±  296.1, 888.4  ±  381.4 μEq/L, P < .0001). UFH administration significantly increased FFAs in both groups, even in the patients with diffuse LV FDG uptake. CONCLUSIONS: The 18-h fast with LCD preparation significantly reduced diffuse LV uptake and increased FFA levels. In particular, the FFA level was significantly lower in patients with LV diffuse uptake than in patients without LV diffuse uptake. Acutely increasing plasma FFA through the use of UFH may not have a significant role in reducing physiological LV FDG uptake.
  • Association between Smoking Status and Obesity in a Nationwide Survey of Japanese Adults
    Taku Watanabe, Ichizo Tsujino, Satoshi Konno, Yoichi M. Ito, Chisa Takashina, Takahiro Sato, Akira Isada, Hiroshi Ohira, Yoshinori Ohtsuka, Yuma Fukutomi, Hiroyuki Nakamura, Yukio Kawagishi, Chiharu Okada, Nobuyuki Hizawa, Masami Taniguchi, Akira Akasawa, Masaharu Nishimura
    PLOS ONE, 11, 3, e0148926, Mar. 2016, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Comparison of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) and cardiac magnetic resonance (CMR) in corticosteroid-naive patients with conduction system disease due to cardiac sarcoidosis.
    Hiroshi Ohira, David H Birnie, Elena Pena, Jordan Bernick, Brian Mc Ardle, Eugene Leung, George A Wells, Keiichiro Yoshinaga, Ichizo Tsujino, Takahiro Sato, Osamu Manabe, Noriko Oyama-Manabe, Masaharu Nishimura, Nagara Tamaki, Alexander Dick, Carole Dennie, Ran Klein, Jennifer Renaud, Robert A deKemp, Terrence D Ruddy, Benjamin J W Chow, Ross Davies, Renee Hessian, Peter Liu, Rob S B Beanlands, Pablo B Nery
    European journal of nuclear medicine and molecular imaging, 43, 2, 259, 269, Feb. 2016, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English, Scientific journal, PURPOSE: Cardiac sarcoidosis (CS) is a cause of conduction system disease (CSD). (18)F-Fluorodeoxyglucose-positron emission tomography (FDG PET) and cardiac magnetic resonance (CMR) are used for detection of CS. The relative diagnostic value of these has not been well studied. The aim was to compare these imaging modalities in this population. METHODS: We recruited steroid-naive patients with newly diagnosed CSD due to CS. All CS patients underwent both imaging studies within 12 weeks of each other. Patients were classified into two groups: group A with chronic mild CSD (right bundle branch block and/or axis deviation), and group B with new-onset atrioventricular block (AVB, Mobitz type II or third-degree AVB). RESULTS: Thirty patients were included. Positive findings on both imaging studies were seen in 72 % of patients (13/18) in group A and in 58 % of patients (7/12) in group B. The remainder (28 %) of the patients in group A were positive only on CMR. Of the patients in group B, 8 % were positive only on CMR and 33 % were positive only on FDG PET. Patients in group A were more likely to be positive only on CMR, and patients in group B were more likely to be positive only on FDG PET (p = 0.02). Patients in group B positive only on FDG PET underwent CMR earlier relative to their symptomatology than patients positive only on CMR (median 7.0, IQR 1.5 - 34.3, vs. 72.0, IQR 25.0 - 79.5 days; p = 0.03). CONCLUSION: The number of positive FDG PET and CMR studies was different in patients with CSD depending on their clinical presentation. This study demonstrated that CMR can adequately detect cardiac involvement associated with chronic mild CSD. In patients presenting with new-onset AVB and a negative CMR study, FDG PET may be useful for detecting cardiac involvement due to CS.
  • Associations among the plasma amino acid profile, obesity, and glucose metabolism in Japanese adults with normal glucose tolerance
    Chisa Takashina, Ichizo Tsujino, Taku Watanabe, Shinji Sakaue, Daisuke Ikeda, Asuka Yamada, Takahiro Sato, Hiroshi Ohira, Yoshinori Otsuka, Noriko Oyama-Manabe, Yoichi M. Ito, Masaharu Nishimura
    NUTRITION & METABOLISM, 13, 5, 5, Jan. 2016, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal
  • 日本人における肥満と禁煙の関連について               
    渡部 拓, 今野 哲, 辻野 一三, 伊藤 陽一, 高階 知紗, 佐藤 隆博, 谷口 正実, 秋山 一男, 赤澤 晃, 西村 正治
    糖尿病, 58, 9, 721, 721, (一社)日本糖尿病学会, Sep. 2015
    Japanese
  • 慢性血栓性肺高血圧症における両側肺血流量の低下 酸素15標識水ポジトロン断層撮像による定量的検出               
    吉永 恵一郎, 富山 勇輝, 大平 洋, 辻野 一三, 佐藤 隆博, 真鍋 治, 加藤 千恵次, 西村 正治, 玉木 長良
    核医学, 52, 3, 257, 257, (一社)日本核医学会, Sep. 2015
    Japanese
  • 膠原病 心臓MRIは強皮症性肺高血圧症の予後予測に有用である               
    野口 淳史, 保田 晋助, 河野 通仁, 加藤 将, 真鍋 徳子, 佐藤 隆博, 辻野 一三, 西村 正治, 渥美 達也
    呼吸と循環, 63, 8, S34, S34, (株)医学書院, Aug. 2015
    Japanese
  • 重症3群肺高血圧症9例に対する肺血管拡張剤の治療経験               
    佐藤 隆博, 辻野 一三, 中谷 資隆, 板谷 利, 渡部 拓, 大平 洋, 西村 正治
    呼吸と循環, 63, 8, S56, S57, (株)医学書院, Aug. 2015
    Japanese
  • Multi-institutional retrospective cohort study of patients with severe pulmonary hypertension associated with respiratory diseases
    Nobuhiro Tanabe, Hiroyuki Taniguchi, Ichizo Tsujino, Fumio Sakamaki, Noriaki Emoto, Hiroshi Kimura, Kei Takamura, Masayuki Hanaoka, Masaharu Nishimura, Koichiro Tatsumi
    RESPIROLOGY, 20, 5, 805, 812, Jul. 2015, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Reduced Sympathetic Nervous Function is Useful Marker to Detect Cardiac Sarcoidosis among Patients with Extracardiac Sarcoidosis and Suspected Cardiac Involvement using C-11 Hydroxyephedrine PET/CT
    Yoshinaga Keiichiro, Manabe Osamu, Tomiyama Yuuki, Ohira Hiroshi, Tsujino Ichizo, Sato Takahiro, Nishijima Ken-ichi, Nishimura Masaharu, Tamaki Nagara
    JOURNAL OF NUCLEAR MEDICINE, 56, 3, 01 May 2015, [Peer-reviewed], [International Magazine]
  • Reduced Absolute Bilateral Pulmonary Blood Flow using O-15 labeled water PET in Patients with Chronic Thromboembolic Pulmonary Hypertension
    Yoshinaga Keiichiro, Tomiyama Yuuki, Tsujino Ichizo, Ohira Hiroshi, Manabe Osamu, Katoh Chietsugu, Nishimura Masaharu, Tamaki Nagara
    JOURNAL OF NUCLEAR MEDICINE, 56, 3, 01 May 2015, [Peer-reviewed], [International Magazine]
  • Right atrial volume and reservoir function are novel independent predictors of clinical worsening in patients with pulmonary hypertension
    Takahiro Sato, Ichizo Tsujino, Hiroshi Ohira, Noriko Oyama-Manabe, Yoichi M. Ito, Asuka Yamada, Daisuke Ikeda, Taku Watanabe, Masaharu Nishimura
    JOURNAL OF HEART AND LUNG TRANSPLANTATION, 34, 3, 414, 423, Mar. 2015, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal
  • 肺高血圧症における血管病変の形態学的・免疫組織学的変化               
    谷野 美智枝, 辻野 一三, 石田 雄介, 加藤 容崇, 王 磊, 木村 太一, 西原 広史, 田中 伸哉
    日本病理学会会誌, 104, 1, 311, 311, (一社)日本病理学会, Mar. 2015
    Japanese
  • 呼吸不全に関する調査研究 酢酸PETによる肺高血圧症患者の右室エネルギー代謝に関する研究
    西村正治, 吉永恵一郎, 大平洋, 辻野一三, 真鍋徳子, MIELNICZUK L, BEANLANDS R S B, 加藤千恵次, 葛西克彦, 真鍋治, 佐藤隆博, 藤井聡, 伊藤陽一, 富山勇輝, 玉木長良
    呼吸不全に関する調査研究 平成26年度 総括・分担研究報告書, 257‐259, 2015, [Domestic magazines]
    Japanese
  • Hemodynamic effects of ambrisentan-tadalafil combination therapy on progressive portopulmonary hypertension.
    Yu Yamashita, Ichizo Tsujino, Takahiro Sato, Asuka Yamada, Taku Watanabe, Hiroshi Ohira, Masaharu Nishimura
    World journal of hepatology, 6, 11, 825, 9, 27 Nov. 2014, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Intravenous epoprostenol is recommended for World Health Organization functional class (WHO-FC) IV patients with pulmonary arterial hypertension (PAH) in the latest guidelines. However, in portopulmonary hypertension (PoPH) patients, advanced liver dysfunction and/or thrombocytopenia often makes the use of intravenous epoprostenol challenging. Here we report the cases of two WHO-FC IV PoPH patients who were successfully treated with a combination of two oral vasodilators used to treat PAH: ambrisentan and tadalafil. Oral vasodilator therapy using a combination of ambrisentan and tadalafil may be a safe and effective therapeutic option for WHO-FC IV PoPH patients and should be considered for selected patients with severe and rapidly progressing PoPH.
  • 日本人における肥満と喫煙状態の関連について
    渡部 拓, 今野 哲, 辻野 一三, 伊藤 陽一, 中谷 資隆, 高階 知紗, 佐藤 隆博, 谷口 正実, 秋山 一男, 赤澤 晃, 西村 正治
    肥満研究, 20, Suppl., 180, 180, (一社)日本肥満学会, Oct. 2014
    Japanese
  • 自殺企図にてグラルギン300単位を自己注射したミトコンドリア病合併糖尿病の1例
    辻野 一三, 林下 晶子, 渡部 拓, 山田 安寿香, 佐藤 隆博, 板谷 利, 高階 知紗, 大塚 吉則, 清水 祐輔, 西村 正治
    糖尿病, 57, 9, 722, 728, (一社)日本糖尿病学会, Sep. 2014
    Japanese
  • 酸素15標識水ポジトロン断層撮像による慢性血栓性肺高血圧症における肺血流量の低下の定量的検出               
    吉永 恵一郎, 富山 勇輝, 辻野 一三, 佐藤 隆博, 真鍋 治, 加藤 千恵次, 大平 洋, 西村 正治, 玉木 長良
    核医学, 51, 3, 332, 332, (一社)日本核医学会, Sep. 2014
    Japanese
  • Right ventricular (18)F-FDG uptake is an important indicator for cardiac involvement in patients with suspected cardiac sarcoidosis.
    Osamu Manabe, Keiichiro Yoshinaga, Hiroshi Ohira, Takahiro Sato, Ichizo Tsujino, Asuka Yamada, Noriko Oyama-Manabe, Atsuro Masuda, Keiichi Magota, Masaharu Nishimura, Nagara Tamaki
    Annals of nuclear medicine, 28, 7, 656, 63, Aug. 2014, [Peer-reviewed], [International Magazine]
    English, Scientific journal, PURPOSE: Cardiac sarcoidosis is most commonly found in the left ventricular (LV) free wall. Presence in the right ventricle (RV) is less common but might be useful for detecting cardiac involvement of sarcoidosis. (18)F-fluorodeoxyglucose ((18)F-FDG) PET has been used to detect LV regions with cardiac sarcoidosis. However, the same has not been done for RV involvement. The aims of the current study were to evaluate RV (18)F-FDG uptake and its relationship to the distribution of LV wall (18)F-FDG-positive segments in the LV, and to evaluate whether patients with positive RV (18)F-FDG uptake met the 1993 diagnostic criteria of the Japanese Ministry of Health and Welfare (JMHW) guidelines regarding sarcoidosis with suspected cardiac involvement. METHOD: Fifty-nine biopsy-proven extra-cardiac sarcoidosis patients (age 56.1 ± 14.7 years) with suspected cardiac involvement based on abnormal electrocardiography or echocardiography findings underwent fasting (18)F-FDG PET or PET/CT. The LV wall was divided into 17 segments and RV uptake was also evaluated. RESULT: Among 59 patients, 35 (59.3%) showed some abnormal (18)F-FDG uptake in the RV and/or LV wall. With respect to the RV wall, 13 (22.0%) showed abnormal (18)F-FDG uptake. The number of LV-involved segments was 4.8 ± 2.4 in the patients with RV (18)F-FDG uptake, which was significantly higher than in the patients without RV uptake, 1.8 ± 2.2 (P < 0.0001). Patients with RV uptake more frequently met the diagnostic criteria of the 1993 JMHW guidelines (n = 27), than did those without RV uptake (84.6 vs. 34.8%, P = 0.0033). CONCLUSION: (18)F-FDG PET identified RV involvement less frequently than LV involvement in this study population. However, patients who had RV uptake showed a greater number of LV-involved segments and met the JMHW diagnostic criteria more frequently. Although RV uptake is less frequent, (18)F-FDG RV uptake may be useful in diagnosing cardiac involvement in sarcoidosis. CLINICAL TRIAL REGISTRATION: UMIN000006533.
  • Attenuated right ventricular energetics evaluated using ¹¹C-acetate PET in patients with pulmonary hypertension.
    Keiichiro Yoshinaga, Hiroshi Ohira, Ichizo Tsujino, Noriko Oyama-Manabe, Lisa Mielniczuk, Rob S B Beanlands, Chietsugu Katoh, Katsuhiko Kasai, Osamu Manabe, Takahiro Sato, Satoshi Fujii, Yoichi M Ito, Yuuki Tomiyama, Masaharu Nishimura, Nagara Tamaki
    European journal of nuclear medicine and molecular imaging, 41, 6, 1240, 50, Jun. 2014, [Peer-reviewed], [International Magazine]
    English, Scientific journal, PURPOSE: The right ventricle (RV) has a high capacity to adapt to pressure or volume overload before failing. However, the mechanisms of RV adaptation, in particular RV energetics, in patients with pulmonary hypertension (PH) are still not well understood. We aimed to evaluate RV energetics including RV oxidative metabolism, power and efficiency to adapt to increasing pressure overload in patients with PH using (11)C-acetate PET. METHODS: In this prospective study, 27 patients with WHO functional class II/III PH (mean pulmonary arterial pressure 39.8 ± 13.5 mmHg) and 9 healthy individuals underwent (11)C-acetate PET. (11)C-acetate PET was used to simultaneously measure oxidative metabolism (k mono) for the left ventricle (LV) and RV. LV and RV efficiency were also calculated. RESULTS: The RV ejection fraction in PH patients was lower than in controls (p = 0.0054). There was no statistically significant difference in LV k mono (p = 0.09). In contrast, PH patients showed higher RV k mono than did controls (0.050 ± 0.009 min(-1) vs. 0.030 ± 0.006 min(-1), p < 0.0001). PH patients exhibited significantly increased RV power (p < 0.001) and hence increased RV efficiency compared to controls (0.40 ± 0.14 vs. 0.017 ± 0.12 mmHg·mL·min/g, p = 0.001). CONCLUSION: The RV oxidative metabolic rate was increased in patients with PH. Patients with WHO functional class II/III PH also had increased RV power and efficiency. These findings may indicate a myocardial energetics adaptation response to increasing pulmonary arterial pressure.
  • Increased left ventricular F-18 fluorodeoxyglucose uptake associated with cardiac sympathetic nervous dysfunction using C-11 hydroxyephedine PET/CT in patients with cardiac sarcoidosis
    Yoshinaga Keiichiro, Tsujino Ichizo, Sato Takahiro, Yamada Aska, Tomiyama Yuuki, Ohira Hiroshi, Manabe Osamu, Nishijima Ken-ichi, Nishimura Masaharu, Tamaki Nagara
    JOURNAL OF NUCLEAR MEDICINE, 55, May 2014, [Peer-reviewed], [International Magazine]
  • The effects of the 18 hours fasting preparation on plasma free fatty acid and physiological myocardial F-18-FDG uptake in patients of suspected cardiac involvement sarcoidosis
    Manabe Osamu, Yoshinaga Keiichiro, Ohira Hiroshi, Masuda Atsuro, Sato Takahiro, Tsujino Ichizo, Yamada Asuka, Oyama-Manabe Noriko, Nishimura Masaharu, Tamaki Nagara
    JOURNAL OF NUCLEAR MEDICINE, 55, May 2014, [Peer-reviewed], [International Magazine]
  • Reduced pulmonary blood flow using O-15 labeled water PET in patients with chronic thromboembolic pulmonary hypertension
    Yoshinaga Keiichiro, Tomiyama Yuuki, Tsujino Ichizo, Sato Takahiro, Manabe Osamu, Katoh Chietsugu, Ohira Hiroshi, Nishimura Masaharu, Tamaki Nagara
    JOURNAL OF NUCLEAR MEDICINE, 55, May 2014, [Peer-reviewed], [International Magazine]
  • 日本人における肥満と喫煙状態の関連について               
    中谷 資隆, 渡部 拓, 辻野 一三, 今野 哲, 伊藤 陽一, 板谷 利, 高階 知紗, 佐藤 隆博, 山田 安寿香, 大塚 吉則, 谷口 正実, 秋山 一男, 赤澤 晃, 西村 正治
    糖尿病, 57, Suppl.1, S, 287, (一社)日本糖尿病学会, Apr. 2014
    Japanese
  • LEFT VENTRICULAR F-18 FLUORODEOXYGLUCOSE UPTAKE ASSOCIATED WITH MYOCARDIAL AUT ONOMIC DYSFUNCTION IN PATIENTS SUSPECTED WITH CARDIAC SARCOIDOSIS
    Yoshinaga Keiichiro, Ohira Hiroshi, Tsujino Ichizo, Katoh Chietsugu, Kasai Katsuhiko, Tomiyama Yuuki, Sato Takahiro, Oyama-Manabe Noriko, Nishimura Masaharu, Tamaki Nagara
    JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 63, 12, A1018, 01 Apr. 2014, [Peer-reviewed], [International Magazine]
  • 胃切後ダンピング症状及び高血糖がシタグリプチンにより改善した2症例               
    渡部 拓, 山田 安寿香, 板谷 利, 林下 晶子, 高階 知紗, 佐藤 隆博, 辻野 一三, 大塚 吉則, 西村 正治
    糖尿病, 57, 3, 220, 220, (一社)日本糖尿病学会, Mar. 2014
    Japanese
  • 自殺企図にてグラルギン300単位を自己注射したミトコンドリア糖尿病の1例               
    井口 大暢, 辻野 一三, 林下 晶子, 山田 安寿香, 板谷 利, 高階 知紗, 佐藤 隆博, 渡部 拓, 大塚 吉則, 西村 正治
    糖尿病, 57, 3, 222, 222, (一社)日本糖尿病学会, Mar. 2014
    Japanese
  • Current trends in the management of pulmonary hypertension associated with respiratory disease in institutions approved by the Japanese Respiratory Society
    Nobuhiro Tanabe, Hiroyuki Taniguchi, Ichizo Tsujino, Fumio Sakamaki, Noriaki Emoto, Hiroshi Kimura, Katsumasa Miyaji, Kei Takamura, Shinichi Hayashi, Masayuki Hanaoka, Koichiro Tatsumi
    Respiratory Investigation, 52, 3, 167, 172, Elsevier, 2014, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Severe Pulmonary Hypertension in Adult Pulmonary Langerhans Cell Histiocytosis: The Effect of Sildenafil as a Bridge to Lung Transplantation
    Takayuki Yoshida, Satoshi Konno, Ichizo Tsujino, Takahiro Sato, Hiroshi Ohira, Fengshi Chen, Hiroshi Date, Akihiro Ishizu, Hironori Haga, Mishie Tanino, Masaharu Nishimura
    INTERNAL MEDICINE, 53, 17, 1985, 1990, 2014, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal
  • Subcutaneous injection of 300 IU of glargine during a suicide attempt in a man with mitochondrial diabetes               
    Ichizo Tsujino, Akiko Hayashishita, Taku Watanabe, Asuka Yamada, Takahiro Sato, Satoshi Itaya, Chisa Takashina, Yoshinori Otsuka, Yusuke Shimizu, Masaharu Nishimura
    Journal of the Japan Diabetes Society, 57, 9, 722, 728, Japan Diabetes Society, 2014
    Japanese, Scientific journal
  • 呼吸不全に関する調査研究 肺高血圧症における右心形態および機能評価
    辻野一三, 佐藤隆博, 大平洋, 池田大輔, 山田安寿香, 渡部拓, 西村正治
    呼吸不全に関する調査研究 平成25年度 総括・分担研究報告書(1/2冊), 329, 332, 2014, [Lead author], [Domestic magazines]
    Japanese
  • Simple prediction of right ventricular ejection fraction using tricuspid annular plane systolic excursion in pulmonary hypertension
    Takahiro Sato, Ichizo Tsujino, Noriko Oyama-Manabe, Hiroshi Ohira, Yoichi M. Ito, Hiroyuki Sugimori, Asuka Yamada, Chisa Takashina, Taku Watanabe, Masaharu Nishimura
    INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING, 29, 8, 1799, 1805, Dec. 2013, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal
  • Pulmonary veno-occlusive disease(PVOD)の一剖検例               
    山田 洋介, 大塚 紀幸, 大平 洋, 辻野 一三, 深谷 進司, 外丸 詩野, 石津 明洋
    脈管学, 53, December, 242, 243, (一社)日本脈管学会, Dec. 2013, [Peer-reviewed], [Domestic magazines]
    Japanese
  • Effects of Metabolic Syndrome on Arterial Responses to Drug-Eluting Stents: Obesity Paradox and Sex-Associated Differences
    Sakamoto Kenji, Waseda Katsuhisa, Kitahara Hideki, Yamaria Ryotaro, Huang Ching-Chang, Shimohama Takao, Yamasaki Masao, Tsujino Ichizo, Miyazawa Akiyoshi, Nakatani Daisaku, Sakata Kenji, Kawarada Osami, Yock Paul G, Sudhir Krishnankutty, Fitzgerald Peter J, Honda Yasuhiro
    CIRCULATION, 128, 22, 26 Nov. 2013, [Peer-reviewed], [Internationally co-authored], [International Magazine]
  • Right Atrial Volume and Reservoir Function are Novel Predictors of Clinical Worsening in Pulmonary Hypertension
    Sato Takahiro, Tsujino Ichizo, Ohira Hiroshi, Oyama-Manabe Noriko, Ito Yoichi M, Nishimura Masaharu
    CIRCULATION, 128, 22, 26 Nov. 2013, [Peer-reviewed], [International Magazine]
  • Low Agreement of 18F-Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) and Cardiac Magnetic Resonance (CMR) in Patients With Conduction Disease Due to Cardiac Sarcoidosis
    Ohira Hiroshi, Birnie David, Mc Ardle Brian, Leung Eugene, Yoshinaga Keiichiro, Tsujino Ichizo, Sato Takahiro, Bernick Jordan, Manabe Osamu, Nishimura Masaharu, Tamaki Nagara, Davies Ross, Klein Ran, Guo Ann, Garrard Linda, Ruddy Terrence, Chow Benjamin, Hessian Renee, Kingsbury Kori, Beanlands Rob S, Nery Pablo
    CIRCULATION, 128, 22, 26 Nov. 2013, [Peer-reviewed], [Internationally co-authored], [International Magazine]
  • FAVORABLE EFFECT OF ORAL COMBINATION VASODILATOR THERAPY FOR TWO CASES WITH SEVERE PORTOPULMONARY HYPERTENSION
    Yamashita Yu, Sato Takahiro, Tsujino Ichizo, Satoshi Itaya, Hayashishita Akiko, Yamada Asuka, Watanabe Taku, Ohira Hiroshi, Nishimura Masaharu
    RESPIROLOGY, 18, 21, Nov. 2013, [Peer-reviewed], [Corresponding author], [International Magazine]
  • SIMPLE PREDICTION OF RIGHT VENTRICULAR EJECTION FRACTION USING TRICUSPID ANNULAR PLANE SYSTOLIC EXCURSION IN PULMONARY HYPERTENSION
    Sato Takahiro, Tsujino Ichizo, Oyama-Manabe Noriko, Ohira Hiroshi, Ito Yoichi. M, Sugimori Hiroyuki, Yamada Asuka, Takashina Chisa, Watanabe Taku, Nishimura Masaharu
    RESPIROLOGY, 18, 20, Nov. 2013, [Peer-reviewed], [International Magazine]
  • FIVE CASES WITH OUT-OF-PROPORTION GROUP 3 PULMONARY HYPERTENSION WITH FAVORABLE HEMODYNAMIC RESPONSE TO VASODILATORS
    Kuroki Akane, Sato Takahiro, Tsujino Ichizo, Igarashi Ayako, Ohira Hiroshi, Yamada Asuka, Watanabe Taku, Suzuki Masaru, Konno Satoshi, Nishimura Masaharu
    RESPIROLOGY, 18, 172, Nov. 2013, [Peer-reviewed], [International Magazine]
  • Elevated (18)F-fluorodeoxyglucose uptake in the interventricular septum is associated with atrioventricular block in patients with suspected cardiac involvement sarcoidosis.
    Osamu Manabe, Hiroshi Ohira, Keiichiro Yoshinaga, Takahiro Sato, Alisa Klaipetch, Noriko Oyama-Manabe, Yoichi M Ito, Ichizo Tsujino, Masaharu Nishimura, Nagara Tamaki
    European journal of nuclear medicine and molecular imaging, 40, 10, 1558, 66, Oct. 2013, [Peer-reviewed], [International Magazine]
    English, Scientific journal, PURPOSE: Cardiac involvement in sarcoidosis is one of the leading causes of death associated with abnormalities of the conduction system. (18)F-FDG PET is useful for detecting inflammatory lesions in cardiac sarcoidosis. However, the relationship between ECG abnormalities and focal (18)F-FDG uptake has not been studied. The aim of this study was to evaluate the relationship between electrocardiogram (ECG) abnormalities and the location of elevated myocardial (18)F-FDG uptake in patients with sarcoidosis. METHODS: Included in the study were 50 patients (56.3 ± 14.9 years old) with histologically proven sarcoidosis with suspected cardiac involvement based on ECG or echocardiography. All patients had fasted for at least 6 h and were given unfractionated heparin (50 IU/kg) intravenously to reduce the physiological (18)F-FDG uptake in the myocardium. The left ventricle (LV) wall was divided into 17 segments by visual analysis. Obvious accumulation in each segment was defined as positive. RESULTS: Of the 50 patients, 33 showed some ECG abnormalities, including atrioventricular (AV) block in 13. Patients with abnormal ECG findings had a higher number of regions with (18)F-FDG uptake than patients without ECG abnormality (3.48 ± 2.73 vs. 1.41 ± 2.09 regions, p = 0.0051). Among ECG abnormalities, the predictor for interventricular septum wall (18)F-FDG involvement was AV block (p = 0.0025). CONCLUSION: Patients with ECG abnormalities showed a higher number of abnormal (18)F-FDG myocardial uptake regions than patients without ECG abnormalities. In particular, focal (18)F-FDG uptake in the interventricular septum in cardiac sarcoidosis was associated with AV block. Therefore, determination of regional (18)F-FDG distribution might contribute to patient management in cardiac sarcoidosis.
  • Right atrial volume and phasic function in pulmonary hypertension
    Takahiro Sato, Ichizo Tsujino, Noriko Oyama-Manabe, Hiroshi Ohira, Yoichi M. Ito, Asuka Yamada, Daisuke Ikeda, Taku Watanabe, Masaharu Nishimura
    INTERNATIONAL JOURNAL OF CARDIOLOGY, 168, 1, 420, 426, Sep. 2013, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal
  • Incidence, clinical manifestations and prognosis of cardiac sarcoidosis in patients with pulmonary sarcoidosis
    Abe Tomoe, Sato Takahiro, Tsujino Ichizo, Ohira Hiroshi, Yoshinaga Keiichiro, Oyama-Manabe Noriko, Hattori Takeshi, Konno Satoshi, Nishimura Masaharu, Karino Tomoe
    EUROPEAN RESPIRATORY JOURNAL, 42, 01 Sep. 2013, [Peer-reviewed], [International Magazine]
  • Accurate monitoring of the right ventricular ejection fraction by echocardiography in pulmonary hypertension
    Sato Takahiro, Tsujino Ichizo, Oyama-Manabe Noriko, Ohira Hiroshi, Watanabe Taku, Nishimura Masaharu
    EUROPEAN RESPIRATORY JOURNAL, 42, 01 Sep. 2013, [Peer-reviewed], [International Magazine]
  • 【肺高血圧症制圧のための完全ガイド】診る 肺高血圧症はどうやって診断する
    佐藤 隆博, 辻野 一三
    Heart View, 17, 7, 692, 699, (株)メジカルビュー社, Jul. 2013
    Japanese
  • Paradoxical Interventricular Septal Motion as a Major Determinant of Late Gadolinium Enhancement in Ventricular Insertion Points in Pulmonary Hypertension
    Takahiro Sato, Ichizo Tsujino, Hiroshi Ohira, Noriko Oyama-Manabe, Yoichi M. Ito, Teruo Noguchi, Asuka Yamada, Daisuke Ikeda, Taku Watanabe, Masaharu Nishimura
    PLOS ONE, 8, 6, e66724, Jun. 2013, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal
  • 日本人における肥満と喫煙状態の関連について               
    渡部 拓, 今野 哲, 辻野 一三, 高階 知紗, 佐藤 隆博, 山田 安寿香, 伊佐田 朗, 谷口 正実, 秋山 一男, 赤澤 晃, 西村 正治
    糖尿病, 56, Suppl.1, S, 362, (一社)日本糖尿病学会, Apr. 2013
    Japanese
  • EFFECTS OF INTENSIFIED PULMONARY HYPERTENSION SPECIFIC VASODILATOR THERAPY ON MYOCARDIAL OXIDATIVE METABOLISM AASSESSED USING C-11 ACETATE PET IN PATIENTS WITH PULMONARY HYPERTENSION
    Yoshinaga Keiichiro, Ohira Hiroshi, Tsujino Ichizo, Manabe Osamu, Sato Takahiro, Katoh Chietsugu, Kasai Katsuhiko, Tomiyama Yuuki, Oyama-Manabe Noriko, Nishimura Masaharu, Tamaki Nagara
    JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 61, 10, E1002, 12 Mar. 2013, [Peer-reviewed], [International Magazine]
  • 脳死肺移植を施行した重症の肺高血圧を伴う肺ランゲルハンス細胞組織球症の一例
    吉田 貴之, 佐藤 隆博, 大平 洋, 長井 桂, 今野 哲, 辻野 一三, 西村 正治, 谷野 美智枝, 陳 豊史, 伊達 洋至
    日本呼吸器学会誌, 2, 増刊, 160, 160, (一社)日本呼吸器学会, Mar. 2013
    Japanese
  • 呼吸器疾患に伴う肺高血圧症に対する経口肺高血圧症治療薬の効果
    五十嵐 絢子, 鈴木 雅, 佐藤 隆博, 辻野 一三, 大平 洋, 山田 安寿香, 高階 知紗, 渡部 拓, 吉田 貴之, 清水 健一, 長井 桂, 今野 哲, 西村 正治
    日本呼吸器学会誌, 2, 増刊, 179, 179, (一社)日本呼吸器学会, Mar. 2013
    Japanese
  • The strain-encoded (SENC) MR imaging for detection of global right ventricular dysfunction in pulmonary hypertension.
    Noriko Oyama-Manabe, Takahiro Sato, Ichizo Tsujino, Kohsuke Kudo, Osamu Manabe, Fumi Kato, Nael F Osman, Satoshi Terae
    The international journal of cardiovascular imaging, 29, 2, 371, 8, Feb. 2013, [Peer-reviewed], [International Magazine]
    English, Scientific journal, The aim of this study was to explore whether the regional peak longitudinal (LS) and circumferential strains (CS) at the right ventricular (RV) free wall could be used to identify global RV dysfunction in relation to RV ejection fraction (RVEF) and plasma concentration of brain natriuretic peptide (BNP) in pulmonary hypertension (PH). A total of 37 consecutive patients diagnosed with PH and 13 healthy control subjects were included. Fast strain encoded and routine cine MRI was performed. The LS and CS at three RV levels were quantified and their relations with RVEF and BNP were investigated. Receiver operating characteristic (ROC) analysis was employed to assess the diagnostic utility of strain encoded MRI for the detection of low RVEF. Significant correlations with LS were observed for RVEF and BNP. Compared to CS, LS showed better correlation with RVEF. The mid-ventricular level of RV was the most sensitive site for evaluation of RV dysfunction. According to our ROC analysis, LS showed higher sensitivity and specificity to detect low RVEF. Compared to CS, LS showed stronger correlations with RVEF and BNP and could be a good detector of RV dysfunction in PH.
  • F-18-FDG PETを用いたサルコイドーシス患者における心病変と他臓器病変との関係の検討(Relationship between the cardiac involvements and the other organ involvements in patients with sarcoidosis using F-18-FDG PET)               
    真鍋 治, 吉永 恵一郎, 大平 洋, 真鍋 徳子, 辻野 一三, 佐藤 隆博, 納谷 昌直, 孫田 恵一, 西村 正治, 玉木 長良
    日本医学放射線学会学術集会抄録集, 72回, S365, S365, (公社)日本医学放射線学会, Feb. 2013
    English
  • Four cases with group 3 out-of-proportion pulmonary hypertension with a favorable response to vasodilators
    Ayako Igarashi, Takahiro Sato, Ichizo Tsujino, Hiroshi Ohira, Asuka Yamada, Taku Watanabe, Masaru Suzuki, Satoshi Konno, Masaharu Nishimura
    Respiratory Medicine Case Reports, 9, 1, 4, 7, 2013, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal
  • Broad and heterogeneous vasculopathy in pulmonary fibrosis and emphysema with pulmonary hypertension
    Takahiro Sato, Ichizo Tsujino, Mishie Tanino, Hiroshi Ohira, Masaharu Nishimura
    Respirology Case Reports, 1, 1, 10, 13, Wiley-Blackwell Publishing Ltd, 2013, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal
  • 高用量のインスリンからエキセナチドへの切り替えが成功した2型糖尿病の1例               
    老田 真佑子, 渡部 拓, 高階 知紗, 佐藤 隆博, 山田 安寿香, 大塚 吉則, 辻野 一三, 西村 正治
    糖尿病, 56, 1, 52, 52, (一社)日本糖尿病学会, Jan. 2013
    Japanese
  • Comparison of vascular response to the everolimus-eluting stent versus the paclitaxel-eluting stent: intravascular ultrasound results from the SPIRIT III trial
    Masao Yamasaki, Ichizo Tsujino, Moyses O. Lima-Filho, Junya Ako, Takao Shimohama, Takao Hasegawa, Ryota Sakurai, Krishnankutty Sudhir, Gregg W. Stone, Katsuhisa Waseda, Yasuhiro Honda, Peter J. Fitzgerald
    EUROINTERVENTION, 8, 6, 724, 731, Oct. 2012, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English, Scientific journal
  • インスリン治療からエキセナチドに切り替えた2症例               
    後藤 知紗, 大平 洋, 佐藤 隆博, 山田 安寿香, 渡部 拓, 大平 恵, 辻野 一三, 大塚 吉則, 西村 正治
    糖尿病, 55, 10, 828, 828, (一社)日本糖尿病学会, Oct. 2012
    Japanese
  • 肺高血圧症患者の右室収縮能の心エコー指標の正確性の検討
    佐藤 隆博, 辻野 一三, 大平 洋, 西村 正治
    Therapeutic Research, 33, 10, 1469, 1471, ライフサイエンス出版(株), Oct. 2012
    Japanese
  • Paradoxical motion of the interventricular septum as a primary mechanism of late gadolinium enhancement at ventricular insertion points
    Takahiro Sato, Ichizo Tsujino, Hiroshi Ohira, Noriko Oyama-Manabe, Masaharu Nishimura
    INTERNATIONAL JOURNAL OF CARDIOLOGY, 158, 1, 156, 157, Jun. 2012, [Peer-reviewed], [Corresponding author], [International Magazine]
    English
  • Regional F-18-FDG uptake in relation to ECG abnormalities in patients with cardiac sarcoidosis
    Manabe Osamu, Yoshinaga Keiichiro, Ohira Hiroshi, Klaipetch Alisa, Oyama-Manabe Noriko, Tsujino Ichizo, Sato Takahiro, Magota Keiichi, Nishimura Masaharu, Tamaki Nagara
    JOURNAL OF NUCLEAR MEDICINE, 53, 01 May 2012, [Peer-reviewed], [International Magazine]
  • Relationship between the cardiac lesion and the other organ involvements of sarcoidosis using F-18-FDG PET
    Manabe Osamu, Yoshinaga Keiichiro, Ohira Hiroshi, Klaipetch Alisa, Oyama-Manabe Noriko, Tsujino Ichizo, Sato Takahiro, Magota Keiichi, Nishimura Masaharu, Tamaki Nagara
    JOURNAL OF NUCLEAR MEDICINE, 53, 01 May 2012, [Peer-reviewed], [International Magazine]
  • Abnormal interventricular septal displacement reflects increased oxidative metabolism in right ventricular free wall but not interventricular septum in patients with pulmonary hypertension using C-11 acetate PET
    Yoshinaga Keiichiro, Sato Takahiro, Ohira Hiroshi, Tsujino Ichizo, Manabe Osamu, Katoh Chietsuim, Kasai Katsuhiko, Nishimura Masaharu, Tamaki Nagara
    JOURNAL OF NUCLEAR MEDICINE, 53, 01 May 2012, [Peer-reviewed], [International Magazine]
  • 中高用量インスリン治療からエキセナチドへの切り替えに成功した2症例               
    後藤 知紗, 大平 洋, 佐藤 隆博, 山田 安寿香, 渡部 拓, 大塚 吉則, 辻野 一三, 西村 正治
    糖尿病, 55, Suppl.1, S, 258, (一社)日本糖尿病学会, Apr. 2012
    Japanese
  • Validation Study on the Accuracy of Echocardiographic Measurements of Right Ventricular Systolic Function in Pulmonary Hypertension
    Takahiro Sato, Ichizo Tsujino, Hiroshi Ohira, Noriko Oyama-Manabe, Asuka Yamada, Yoichi M. Ito, Chisa Goto, Taku Watanabe, Shinji Sakaue, Masaharu Nishimura
    JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY, 25, 3, 280, 286, Mar. 2012, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal
  • Intravascular ultrasound insights from the Cobalt Chromium Stent With Antiproliferative for Restenosis II (COSTAR II) trial comparing CoStar and Taxus paclitaxel-eluting stents.
    Tsujino I, Koizumi T, Shimohama T, Ako J, Waseda K, Krucoff M, Honda Y, Fitzgerald PJ
    Cardiovascular revascularization medicine : including molecular interventions, 13, 2, 111, 118, Mar. 2012, [Peer-reviewed], [Lead author], [Internationally co-authored], [International Magazine]
  • Right Atrial Late Gadolinium Enhancement on Cardiac Magnetic Resonance Imaging in Pulmonary Hypertension
    Takahiro Sato, Ichizo Tsujino, Hiroshi Ohira, Noriko Oyama-Manabe, Yosuke Yamada, Noriyuki Otsuka, Masaharu Nishimura
    CIRCULATION JOURNAL, 76, 1, 238, 239, Jan. 2012, [Peer-reviewed], [Corresponding author], [Domestic magazines]
    English, Scientific journal
  • Intravascular Ultrasound Assessment of Postprocedural Incomplete Stent Apposition
    Teruyoshi Kume, Katsuhisa Waseda, Junya Ako, Kenji Sakata, Masao Yamasaki, Takao Shimohama, Ichizo Tsujino, Takao Hasegawa, Peter J. Fitzgerald, Yasuhiro Honda
    JOURNAL OF INVASIVE CARDIOLOGY, 24, 1, 13, 16, Jan. 2012, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English, Scientific journal
  • Chronological Change in Pulmonary Vascular Response to Hypoxia in Hepatopulmonary Syndrome
    Yoshinori Tanino, Hironi Makita, Ichizo Tsujino, Hideki Shinano, Masaharu Nishimura
    RESPIRATION, 84, 3, 242, 245, 2012, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Elevated Right Ventricular Oxidative Metabolism in Patients with Chronic Thromboembolic Pulmonary Hypertension (CTEPH) or Pulmonary Arterial Hypertension (PAH) Using C-11 Acetate PET
    Yoshinaga Keiichiro, Ohira Hiroshi, Tsujino Ichizo, Manabe Osamu, Katoh Chietsugu, Kasai Katsuhiko, Satoh Takahiro, Oyama-Manabe Noriko, Nishimura Masaharu, Tamaki Nagara
    CIRCULATION, 124, 21, 22 Nov. 2011, [Peer-reviewed], [International Magazine]
  • Paradoxical Interventricular Septal Motion Predisposes to Late Gadolinium Enhancement of Ventricular Insertion Points in Pulmonary Hypertension
    Sato Takahiro, Tsujino Ichizo, Ohira Hiroshi, Oyama-Manabe Noriko, Yamada Asuka, Nishimura Masaharu
    CIRCULATION, 124, 21, 22 Nov. 2011, [Peer-reviewed], [International Magazine]
  • 門脈肺高血圧症の急性増悪にAmbrisentanとTadalafilのCombination Therapyが著効した1例
    佐藤 隆博, 辻野 一三, 大平 洋, 山田 安寿香, 後藤 知紗, 渡部 拓, 西村 正治
    Therapeutic Research, 32, 10, 1214, 1216, ライフサイエンス出版(株), Oct. 2011
    Japanese
  • The short-term role of corticosteroid therapy for pulmonary arterial hypertension associated with connective tissue diseases: Report of five cases and a literature review
    M. Kato, H. Kataoka, T. Odani, Y. Fujieda, K. Otomo, K. Oku, T. Horita, S. Yasuda, T. Atsumi, H. Ohira, I. Tsujino, M. Nishimura, T. Koike
    Lupus, 20, 1047, 1056, 01 Oct. 2011, [International Magazine]
  • 18F-fluoro-2-deoxyglucose positron emission tomography in cardiac sarcoidosis
    Hiroshi Ohira, Ichizo Tsujino, Keiichiro Yoshinaga
    European Journal of Nuclear Medicine and Molecular Imaging, 38, 9, 1773, 1783, Sep. 2011, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • ELEVATED RIGHT VENTRICULAR OXIDATIVE METABOLISM USING C-11 ACETATE PET IN PATIENTS WITH PULMONARY HYPERTENSION
    Yoshinaga Keiichiro, Ohira Hiroshi, Tsujino Ichizo, Manabe Osamu, Katoh Chietsugu, Kasai Katsuhiko, Satoh Takahiro, Oyama Noriko, Nishimura Masaharu, Tamaki Nagara
    JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 57, 14, E845, 05 Apr. 2011, [Peer-reviewed], [International Magazine]
  • An autopsy case of pulmonary veno-occlusive disease refractory to imatinib
    H. Koiwa, I. Tsujino, D. Ikeda, H. Ohira, M. Tanino, M. Nishimura
    European Respiratory Journal, 37, 968, 970, 01 Apr. 2011, [Corresponding author], [International Magazine]
  • グリシン血中濃度とメタボリックシンドロームとの関係について               
    佐藤 隆博, 坂上 慎二, 池田 大輔, 山田 安寿香, 大平 洋, 後藤 知紗, 渡部 拓, 大平 恵, 辻野 一三, 大塚 吉則, 西村 正治
    糖尿病, 54, 2, 143, 143, (一社)日本糖尿病学会, Feb. 2011
    Japanese
  • Early detection of cardiac sarcoid lesions with (18)F-fluoro-2-deoxyglucose positron emission tomography.
    Hiroshi Ohira, Ichizo Tsujino, Takahiro Sato, Keiichiro Yoshinaga, Osamu Manabe, Noriko Oyama, Masaharu Nishimura
    Internal medicine (Tokyo, Japan), 50, 11, 1207, 9, 2011, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, In April 2005, a 72-year-old woman with pulmonary sarcoidosis exhibited focal (18)F-fluoro-2-deoxyglucose ((18)F-FDG) uptake in her heart on (18)F-FDG positron emission tomography (PET). Although Japanese guidelines for diagnosing cardiac sarcoidosis were not met at this point, electrocardiography, echocardiography, and magnetic resonance imaging became diagnostic for cardiac sarcoidosis 1 year later. In the present case report, the potential of (18)F-FDG PET in the early recognition of cardiac sarcoidosis in comparison with other imaging modalities is discussed.
  • Incidence of diffuse and focal chronic stent recoil after implantation of current generation bare-metal and drug-eluting stents
    Bon-Kwon Koo, Katsuhisa Waseda, Junya Ako, Takao Hasegawa, Takao Shimohama, Daisaku Nakatani, Hiromasa Otake, Masao Yamasaki, Ryota Sakurai, Ichizo Tsujino, Yasuhiro Honda, Peter J. Fitzgerald
    INTERNATIONAL JOURNAL OF CARDIOLOGY, 144, 1, 132, 134, Sep. 2010, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English
  • Imaging of Cardiac Sarcoid Lesions Using Fasting Cardiac F-18-Fluorodeoxyglucose Positron Emission Tomography: An Autopsy Case
    Hiroaki Koiwa, Ichizo Tsujino, Hiroshi Ohira, Keiichiro Yoshinaga, Noriyuki Otsuka, Masaharu Nishimura
    CIRCULATION, 122, 5, 535, 536, Aug. 2010, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Comparison of Everolimus- Versus Paclitaxel-Eluting Stents Implanted in Patients With Diabetes Mellitus as Evaluated by Three-Dimensional Intravascular Ultrasound Analysis
    Hiromasa Otake, Junya Ako, Masao Yamasaki, Ichizo Tsujino, Takao Shimohama, Takao Hasegawa, Ryota Sakurai, Katsuhisa Waseda, Yasuhiro Honda, Poornima Sood, Krishnankutty Sudhir, Gregg W. Stone, Peter J. Fitzgerald
    AMERICAN JOURNAL OF CARDIOLOGY, 106, 4, 492, 497, Aug. 2010, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English, Scientific journal
  • SPIRIT III JAPAN Versus SPIRIT III USA: A Comparative Intravascular Ultrasound Analysis of the Everolimus-Eluting Stent
    Takao Shimohama, Junya Ako, Masao Yamasaki, Hiromasa Otake, Ichizo Tsujino, Takao Hasegawa, Daisaku Nakatani, Ryota Sakurai, Hyeonsoo Chang, Hajime Kusano, Katsuhisa Waseda, Yasuhiro Honda, Gregg W. Stone, Shigeru Saito, Peter J. Fitzgerald, Krishnankutty Sudhir
    AMERICAN JOURNAL OF CARDIOLOGY, 106, 1, 13, 17, Jul. 2010, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English, Scientific journal
  • Relationship between Serum Glycine Levels and Visceral Obesity
    Ikeda Daisuke, Sakaue Shinji, Watanabe Asuka, Ohyama Noriko, Goto Chisa, Ohira Hiroshi, Tsujino Ichizo, Ohtsuka Yoshinori, Nishimura Masaharu
    DIABETES, 59, A494, Jun. 2010, [Peer-reviewed], [International Magazine]
  • Relationship between Insulin Sensitivity and Abdominal Fat Distribution in Healthy Japanese Adults
    Watanabe Asuka, Sakaue Shinji, Ikeda Daisuke, Ohyama Noriko, Gotoh Chisa, Ohira Hiroshi, Tsujino Ichizo, Ohtsuka Yoshinori, Nishimura Masaharu
    DIABETES, 59, A688, Jun. 2010, [Peer-reviewed], [International Magazine]
  • Vascular Response to Overlapping Everolimus-Eluting Stents - Comparison With Paclitaxel-Eluting Stents
    Hiromasa Otake, Yasuhiro Honda, Masao Yamasaki, Ichizo Tsujino, Takao Shimohama, Ryota Sakurai, Takao Hasegawa, Katsuhisa Waseda, Junya Ako, Peter J. Fitzgerald
    CIRCULATION JOURNAL, 74, 5, 1023, 1025, May 2010, [Peer-reviewed], [Internationally co-authored], [Domestic magazines]
    English, Scientific journal
  • Enhanced computed tomography unveiling the underlying cause of pulmonary hypertension
    Naofumi Ito, Ichizo Tsujino, Masaharu Nishimura
    INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING, 26, 3, 257, 258, Mar. 2010, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal
  • Preprocedural Inflammation Does Not Affect Neointimal Hyperplasia following Everolimus-Eluting Stent Implantation
    Daisaku Nakatani, Junya Ako, Masao Yamasaki, Takao Shimohama, Takao Hasegawa, Hiromasa Otake, Katsuhisa Waseda, Ichizo Tsujino, Ryota Sakurai, Bon-Kwon Koo, Hyeonsoo Chang, Paul G. Yock, Krishnankutty Sudhir, Wesley Pierson, Gregg W. Stone, Shigeru Saito, Yasuhiro Honda, Peter J. Fitzgerald
    JOURNAL OF INVASIVE CARDIOLOGY, 21, 12, 613, 617, Dec. 2009, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English, Scientific journal
  • Relationship Between Glucose Lowering Effect and Circulating Bile Acid Level Following Colestimide Administration in Patients with Type 2 Diabetes
    大平恵, 坂上慎二, 大平洋, 渡邊安寿香, 池田大輔, 吉田和博, 山口佳奈, 村井毅, 黒澤隆夫, 辻野一三, 大塚吉則, 西村正治
    Prog Med, 29, 8, 2043, 2048, ライフ・サイエンス, 10 Aug. 2009, [Domestic magazines]
    Japanese
  • Intravascular Ultrasound Results From the ENDEAVOR IV Trial Randomized Comparison Between Zotarolimus- and Paclitaxel-Eluting Stents in Patients With Coronary Artery Disease
    Katsuhisa Waseda, Akiyoshi Miyazawa, Junya Ako, Takao Hasegawa, Ichizo Tsujino, Ryota Sakurai, Paul G. Yock, Yasuhiro Honda, David E. Kandzari, Martin B. Leon, Peter J. Fitzgerald
    JACC-CARDIOVASCULAR INTERVENTIONS, 2, 8, 779, 784, Aug. 2009, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English, Scientific journal
  • Knockdown of Macrophage Migration Inhibitory Factor Disrupts Adipogenesis in 3T3-L1 Cells
    Daisuke Ikeda, Shinji Sakaue, Mitsunori Kamigaki, Hiroshi Ohira, Naofumi Itoh, Yoshinori Ohtsuka, Ichizo Tsujino, Masaharu Nishimura
    ENDOCRINOLOGY, 149, 12, 6037, 6042, Dec. 2008, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • SPIRIT III Japan: Eight-Month IVUS Analysis of Everolimus-Elurting Stent Compared to the US Arm
    Shimohama Takao, Otake Hiromasa, Ako Junya, Yamasaki Masao, Tsujino Ichizo, Waseda Katsuhisa, Hasegawa Takao, Sakurai Ryota, Nakatani Daisaku, Chang Hyaonsoo, Yock Paul G, Honda Yasuhiro, Kusano Hajime, Sudhir Krishnankutty, Saito Shigeru, Stone Gregg W, Fitzgerald Peter J
    CIRCULATION, 118, 18, S1044, 28 Oct. 2008, [Peer-reviewed], [Internationally co-authored], [International Magazine]
  • IVUS Analysis in the SPIRIT III Japan Treated with XIENCE (TM) V Everolimus-Eluting Stent Compared to the SPIRIT III US Arm
    Shimohama Takao, Otake Hiromasa, Ako Junya, Yamasaki Masao, Tsujino Ichizo, Waseda Katsuhisa, Hasegawa Takao, Sakurai Ryota, Nakatani Daisaku, Chang Hyeonsoo, Yock Paul G, Honda Yasuhiro, Kusano Hajime, Sudhir Krishnankutty, Saito Shigeru, Stone Gregg W, Fitzgerald Peter J
    AMERICAN JOURNAL OF CARDIOLOGY, 102, 8A, 138I, 12 Oct. 2008, [Peer-reviewed], [Internationally co-authored], [International Magazine]
  • Impact of Pre-procedural C-reactive Protein on Intravascular Ultrasound Parameters following Everolimus-eluting Stent Implantation: Results from the SPIRIT III Trial
    Daisaku Nakatani, Junya Ake, Masao Yamasaki, Takao Shimohama, Hiromasa Otake, Ichizo Tsujino, Bon-Kwon Koo, Katsuhisa Waseda, Hyeonsoo Chang, Ryota Sakurai, Paul G. Yock, Yasuhiro Honda, Wesley Pierson, Krishnankutty Sudhir, Peter J. Fitzgerald
    CIRCULATION, 118, 18, S1051, S1051, Oct. 2008, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English
  • Two-Year Intravascular Ultrasound Observations in Diabetic Patients Treated with Single and Double Dose Sirolimus-Eluting Stents: Results of the Double Dose Diabetes (3D) Study
    Seung-Ho Hur, Junya Ako, Yoshihisa Shimada, Ichizo Tsujino, Ali H. M. Hassan, Alexandre Abizaid, Avinoam Shiran, Basil S. Lewis, Giulio Guagliumi, Sidney A. Cohen, Yasuhiro Honda, Peter J. Fitzgerald, J. Eduardo Sousa
    JOURNAL OF INVASIVE CARDIOLOGY, 20, 8, 411, 416, Aug. 2008, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English, Scientific journal
  • Clinical and Angiographic Outcomes in Diabetic Patients following Single or Multivessel Stenting in the COSTAR II Randomized Trial
    Dean J. Kereiakes, John L. Petersen, Wayne B. Batchelor, Peter J. Fitzgerald, Roxana Mehran, Alexandra Lansky, Ichizo Tsujino, Joachim Schofer, Christophe Dubois, Stefan Verheye, Ecaterina Cristea, Jyotsna Garg, William Wijns, Mitchell W. Krucoff
    JOURNAL OF INVASIVE CARDIOLOGY, 20, 7, 335, 341, Jul. 2008, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English, Scientific journal
  • Comprehensive analysis of N-glycans in serum glycoproteins of subjects with high fasting glucose levels
    Ohira Hiroshi, Sakaue Shinji, Itoh Naofumi, Furukawa Jun-Ichi, Miura Yoshiaki, Tsujino Ichizo, Nishimura Shin-Ichiro, Nishimura Masaharu
    DIABETES, 57, A704, Jun. 2008, [Peer-reviewed], [International Magazine]
  • Myocardial imaging with F-18-fluoro-2-deoxyglucose positron emission tomography and magnetic resonance imaging in sarcoidosis
    Hiroshi Ohira, Ichizo Tsujino, Shinji Ishimaru, Noriko Oyama, Toshiki Takei, Eriko Tsukamoto, Masatake Miura, Shinji Sakaue, Nagara Tamaki, Masaharu Nishimura
    EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 35, 5, 933, 941, May 2008, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal
  • Comparison of vascular response to zotarolimus-eluting stent versus sirolimus-eluting stent: Intravascular ultrasound results from ENDEAVOR III
    Akiyoshi Miyazawa, Junya Ako, Yoichiro Hongo, Seung-Ho Hur, Ichizo Tsujino, Brian K. Courtney, Ali H. M. Hassan, David E. Kandzari, Yasuhiro Honda, Peter J. Fitzgerald
    AMERICAN HEART JOURNAL, 155, 1, 108, 113, Jan. 2008, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English, Scientific journal
  • A case of tuberculous pericarditis with significant improvements by corticosteroids with antituberculosis
    Watanabe Takeshi, Kamigaki Mitsunori, Itoh Naofumi, Yokota Miki, Watanabe Asuka, Ikeda Daisuke, Sakaue Shinji, Tsujino Ichizo, Tokuhara Satoshi, Okamoto Hiroshi, Tsutsui Hiroyuki, Nishimura Masaharu
    Shinzo, 40, 11, 983, 988, Japan Heart Foundation, 2008
    Japanese, 症例は55歳,男性.2006年9月上旬から発熱と咳が出現.倦怠感と労作時息切れも認め近医入院.心膜液の貯留も認め各種精査を行うも原因疾患不明であり,精査目的に当院循環器内科に転院.CTにて著明な心膜肥厚と心膜液貯留所見を認め,心膜生検施行し結核性心膜炎の診断となる.病理学的には肉芽腫性乾酪化とフィブリンや膠原線維により心膜肥厚をきたす第3期であった.加療目的に当科(第一内科)転科.転科当日より抗結核薬4剤併用を開始.右心カテーテル・心エコーにて心拍出量低下と拡張障害を示唆する所見を認めた.予後改善と病態進行阻止目的に,3週目より抗結核薬に加えステロイドの併用療法を開始した.ステロイド開始後,症状改善,心膜肥厚改善,心膜液減少を認めた.発症1年後にも再発を認めていない.
  • Characterization of late incomplete stent apposition: a comparison among bare-metal stents, intracoronary radiation and sirolimus-eluting stents.
    Miyazawa A, Tsujino I, Ako J, Shimada Y, Courtney BK, Sakurai R, Nakamura M, Okura H, Waseda K, Honda Y, Fitzgerald PJ
    The Journal of invasive cardiology, 19, 12, 515, 518, Dec. 2007, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English, Scientific journal, BACKGROUND: Late incomplete stent apposition (LISA) develops following implantation of conventional bare-metal stents (BMS) or drug-eluting stents, or after adjunctive intracoronary radiation (IR). However, no study has systematically compared the morphology of LISA seen with various treatment modalities. PURPOSE: To compare the morphometric features of LISA accompanying BMS, IR or sirolimus-eluting stents (SES) using serial intravascular ultrasound (IVUS). METHODS: A query of Stanford University's IVUS database of the Cardiovascular Core Analysis Laboratory was performed to identify LISA cases. Dedicated software programs were used for volumetric IVUS analyses. RESULTS: In 30 LISA cases (12 BMS, 6 IR and 12 SES), there was no intertreatment difference in the degree of LISA (lumen area minus stent area at follow up). Serial analyses of LISA segments showed that vessel area of SES and IR showed significant increase at follow up as compared with post procedure, while there was no significant change in plaque area. In contrast, the BMS group showed no increase in vessel area, whereas plaque area revealed significant reduction. Eight of 12 BMS cases were treated by directional atherectomy before stenting; however, there was no difference in the area change between patients with or without pre-stent atherectomy. Post-procedure plaque thickness beneath the stent struts of LISA was thinner for SES as compared with BMS. CONCLUSIONS: Plaque reduction primarily contributes to LISA after BMS, whereas vessel expansion is the predominant factor in LISA development for IR and SES. Thus, the mechanism of LISA may vary among different interventional treatments.
  • Pilot study of short-term effects of a novel long-acting oral beraprost in patients with pulmonary arterial hypertension
    Daisuke Ikeda, Ichizo Tsujino, Shinji Sakaue, Hiroshi Ohira, Naofumi Itoh, Mitsunori Kamigaki, Shinji Ishimaru, Tatsuya Atsumi, Masaharu Nishimura
    CIRCULATION JOURNAL, 71, 11, 1829, 1831, Nov. 2007, [Peer-reviewed], [Corresponding author], [Domestic magazines]
    English, Scientific journal
  • Drug delivery via nano-, micro and macroporous coronary stent surfaces
    Ichizo Tsujino, Junya Ako, Yasuhiro Honda, Peter J. Fitzgerald
    EXPERT OPINION ON DRUG DELIVERY, 4, 3, 287, 295, May 2007, [Peer-reviewed], [Lead author], [Internationally co-authored], [International Magazine]
    English, Scientific journal
  • Comparison of vessel response following sirolimus-eluting stent implantation as assessed by serial 3-D intravascular ultrasound study.
    Waseda K, Ako J, Shimada Y, Morino Y, Tsujino I, Hongo Y, Sudhir K, Yock PG, Fitzgerald PJ, Honda Y
    The Journal of invasive cardiology, 19, 4, 171, 173, Apr. 2007, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English, Scientific journal, Recent sirolimus-eluting stent (SES) studies have suggested higher rates of restenosis in non-left anterior descending (LAD) artery lesions. The aim of this study was to evaluate differential vessel response (LAD versus non-LAD) to SES implantation using serial intravascular ultrasound (IVUS). A total of 94 patients who underwent SES implantation and serial (post-PCI and 8 months) 3-dimensional IVUS were enrolled from our database. Volumetric analysis was performed throughout the stent as well as the adjacent reference segment (up to 5 mm). Volume index (volume/length) was calculated for vessel (VVI), lumen (LVI), and plaque (PVI). Cross-sectional narrowing (CSN) was defined as neointimal area divided by stent area (%). With respect to the in-stent segment, VVI, PVI, and LVI at post-PCI were not significantly different between the LAD (n = 41) and non-LAD (n = 53) lesions. At follow up, however, maximum CSN was significantly greater in the non-LAD lesions (18.3 +/- 15.2% versus 12.2 +/- 10.0%; p = 0.029). At the proximal reference segment, the non-LAD lesions showed a significantly greater LVI decrease than the LAD lesions (p <0.05), primarily due to mild vessel shrinkage observed in the non-LAD lesions. There were no significant differences at the distal reference segment between the LAD and non-LAD lesions. This detailed IVUS analysis suggests that there are minimal differences in the vessel responses following SES implantation. These findings may have potential implications for mechanical and pharmacokinetic properties of next-generation drug-eluting stent technology.
  • Trousseau's syndrome associated with tissue factor produced by pulmonary adenocarcinoma
    T. Sato, I. Tsujino, D. Ikeda, M. Ieko, M. Nishimura
    THORAX, 61, 11, 1009, 1010, Nov. 2006, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal
  • Recovery of protein-losing enteropathy after living-donor lobar lung transplantation in primary pulmonary hypertension
    H Ohira, Tsujino, I, S Sakaue, D Ikeda, N Itoh, M Kamigaki, S Ishimaru, H Date, Y Sano, N Shimizu, M Nishimura
    JOURNAL OF HEART AND LUNG TRANSPLANTATION, 25, 4, 486, 488, Apr. 2006, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal
  • Oxidative stress provokes atherogenic changes in adipokine gene expression in 3T3-L1 adipocytes
    M Kamigaki, S Sakaue, Tsujino, I, H Ohira, D Ikeda, N Itoh, S Ishimaru, Y Ohtsuka, M Nishimura
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 339, 2, 624, 632, Jan. 2006, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Promoter polymorphism in the macrophage migration inhibitory factor gene is associated with obesity.               
    Sakaue, S, Ishimaru, S, Hizawa, N, Ohtsuka, Y, Tsujino, I, Honda, T, Suzuki, J, Kawakami, Y, Nishihara, J, Nishimura, M
    Int. J. Obes., 30, 238, 242, 2006, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Combination of F-18-fluoro-2-deoxyglucose positron emission tomography and magnetic resonance imaging in assessing cardiac sarcoidosis
    S Ishimaru, Tsujino, I, S Sakaue, N Oyama, T Takei, E Tsukamoto, N Tamaki, M Nishimura
    SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES, 22, 3, 234, 235, Oct. 2005, [Peer-reviewed], [Corresponding author], [International Magazine]
    English
  • Focal uptake on F-18-fluoro-2-deoxyglucose positron emission tomography images indicates cardiac involvement of sarcoidosis
    S Ishimaru, Tsujino, I, T Takei, E Tsukamoto, S Sakaue, M Kamigaki, N Ito, H Ohira, D Ikeda, N Tamaki, M Nishimura
    EUROPEAN HEART JOURNAL, 26, 15, 1538, 1543, Aug. 2005, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal
  • Comparative simulation of gas transport in airway models of rat, dog, and human
    Tsujino, I, Y Kawakami, A Kaneko
    INHALATION TOXICOLOGY, 17, 9, 475, 485, Aug. 2005, [Peer-reviewed], [Lead author], [International Magazine]
    English, Scientific journal
  • Small cell carcinoma of the lung exclusively localized within the left descending pulmonary artery
    M Kamigaki, K Yamazaki, Tsujino, I, M Suga, S Sakaue, H Dosaka-Akita, M Nishimura
    CHEST, 127, 6, 2273, 2276, Jun. 2005, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Addition of oral sildenafil to beraprost is a safe and effective therapeutic option for patients with pulmonary hypertension
    D Ikeda, Tsujino, I, H Ohira, N Itoh, M Kamigaki, S Ishimaru, S Sakaue, M Nishimura
    JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 45, 4, 286, 289, Apr. 2005, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal
  • 肺高血圧症例におけるBeraprost単独とBeraprost・Sildenafil併用の急性効果の比較
    池田大輔, 辻野一三, 大平洋, 伊東直史, 神垣光徳, 石丸伸司, 坂上慎二, 西村正治
    Ther Res, 25, 10, 1987, 1990, ライフサイエンス出版(株), 20 Oct. 2004, [Corresponding author], [Domestic magazines]
    Japanese
  • 〈第10回〉肺塞栓症研究会・学術集会 症例報告 7 複数部位の再発性静脈血栓症の発症後に診断された原発性肺癌の若年男性症例
    佐藤隆博, 池田大輔, 大平洋, 辻野一三, 西村正治, 家子正裕
    Ther Res, 25, 6, 1236, 1239, ライフサイエンス出版(株), 20 Jun. 2004, [Domestic magazines]
    Japanese
  • beraprost(ドルナー)に対するSildenafil(バイアグラ)の相加効果を確認した慢性肺血栓塞栓性肺高血圧症の一例
    佐藤 隆博, 池田 大輔, 大平 洋, 神垣 光徳, 石丸 伸司, 吉村 治彦, 坂上 慎二, 辻野 一三, 西村 正治, 工藤 敏行
    Circulation Journal, 68, Suppl.II, 756, 756, (一社)日本循環器学会, Apr. 2004
    Japanese
  • 当科における肺高血圧症5例に対する静注PGI2製剤(エポプロステノール)による治療経験
    池田大輔, 大平洋, 神垣光徳, 石丸伸司, 古谷純吾, 吉村治彦, 坂上慎二, 辻野一三, 西村正治
    Ther Res, 24, 9, 1809, 1811, 20 Sep. 2003, [Domestic magazines]
    Japanese
  • Tissue hypoxia in sleep apnea syndrome assessed by uric acid and adenosine
    H Saito, M Nishimura, E Shibuya, H Makita, Tsujino, I, K Miyamoto, Y Kawakami
    CHEST, 122, 5, 1686, 1694, Nov. 2002, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • A case of idiopathic constrictive bronchiolitis in a middle-aged male smoker
    Ichizo Tsujino, Masaharu Nishimura, Kouji Ohira, Haruhiko Yoshimura, Yuh Fukuda
    Respirology, 5, 3, 305, 307, 2000, [Peer-reviewed], [Lead author], [International Magazine]
    English, Scientific journal
  • Plasma concentration of adenosine during normoxia and moderate hypoxia in humans
    H Saito, M Nishimura, H Shinano, H Makita, Tsujino, I, E Shibuya, F Sato, K Miyamoto, Y Kawakami
    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 159, 3, 1014, 1018, Mar. 1999, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Effects of inhaled bronchodilators on pulmonary hemodynamics at rest and during exercise in patients with COPD
    S Saito, K Miyamoto, M Nishimura, A Aida, H Saito, Tsujino, I, Y Kawakami
    CHEST, 115, 2, 376, 382, Feb. 1999, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Measurement of exhaled nitric oxide concentration using nasal continuous negative pressure
    Ichizo Tsujino, Kenji Miyamoto, Masaharu Nishimura, Hideki Shinano, Yoshikazu Kawakami
    Respirology, 4, 2, 155, 159, 1999, [Peer-reviewed], [Lead author], [International Magazine]
    English, Scientific journal
  • Production of nitric oxide (NO) in intrathoracic airways of normal humans
    Tsujino, I, K Miyamoto, M Nishimura, H Shinano, H Makita, S Saito, T Nakano, Y Kawakami
    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 154, 5, 1370, 1374, Nov. 1996, [Peer-reviewed], [Lead author], [International Magazine]
    English, Scientific journal
  • Morphological observation of the rat lungs after nitric oxide inhalation               
    I. Tsujino, T. Nakano, K. Miyamoto, S. Saito, A. Aida, M. Nishimura, Y. Kawakami
    Respiration and Circulation, 44, 4, 397, 401, 1996
    Japanese, Scientific journal
  • A Case of Inflammatory Esophagogastric Polyp
    Ichizo Tsujino, Hideyuki Seki, Syuuichi Kitahama, Hirohide Hamamoto, Tetsunobu Kanai, Tomoaki Adachi, Junichi Suzuki, Yoshikazu Kawakami, Ken Itou
    Gastroenterological Endoscopy, 38, 11, 2620, 2624, 1996, [Peer-reviewed], [Lead author], [Domestic magazines]
    English, Scientific journal
  • Effects of inhaled oxitropium bromide, an anticholinergic drug, on pulmonary hemodynamics in patients with chronic obstructive pulmonary diseases
    S. Saito, K. Miyamoto, A. Aida, H. Saito, F. Sato, I. Tsujino, T. Nakano, M. Nishimura, Y. Kawakami
    Japanese Journal of Thoracic Diseases, 33, 9, 924, 929, 1995, [Peer-reviewed], [Domestic magazines]
    Japanese, Scientific journal

Other Activities and Achievements

Lectures, oral presentations, etc.

  • 今後も肺高血圧症と付き合っていく中で、一番心配なことは何ですか?               
    辻野一三
    肺高血圧症患者さんと医師による座談会2022, 15 Jul. 2022
  • 特別企画2 CLOT-COVID Study における大出血例の検討               
    中村 順一, 辻野, 一三, 児島, 裕一, 島 秀起, 中久保, 祥, 今野 哲 COVID, とVTEの実態調査タスクフォース
    第42回日本静脈学会総会, 07 Jul. 2022
  • 右室収縮/拡張能の評価に 最も適切な心エコー指標は何か?               
    島 秀起, 辻野一三, 中谷資隆, 三浦 瞬, 堀井洋志, 中村順一, 佐藤隆博, 大平 洋, 千葉泰之, 今野 哲
    第7回日本肺高血圧・肺循環学会学術集会, 02 Jul. 2022
  • 北海道大学病院における PVOD/PCH症例の検討               
    中村 順一, 辻野, 一三 島, 秀起, 中谷, 資隆, 杉本 絢子, 佐藤 隆博, 渡部, 拓, 鈴木, 雅, 大平, 洋, 常田, 慧徳, 今野 哲
    第7回日本肺高血圧・肺循環学会学術集会, 02 Jul. 2022
  • 肺高血圧合併間質性肺疾患における 肺血管病変の病理学的解析               
    杉本 絢子, 辻野 一三, 大塚 紀幸, 中村 順一, 佐藤 隆博, 大平 洋, 鈴木 雅, 高村 圭, 石田 雄介, 田中 伸哉, 今野 哲
    第7回日本肺高血圧・肺循環学会学術集会, 02 Jul. 2022
  • Nottingham型の不安定ヘモグロビン症に 合併した肺高血圧症の一例               
    三浦 瞬, 佐藤 隆博, 島 秀紀, 中村 順一, 中谷 資隆, 渡部 拓, 大平 洋, 辻野 一三, 橋本 大吾, 今野 哲
    第7回日本肺高血圧・肺循環学会学術集会, 02 Jul. 2022
  • ランチョンセミナー3 CTD-PAHにおける連携診療 呼吸器・循環器内科の立場から考える 連携のポイント               
    辻野一三
    第7回肺高血圧・肺循環学会学術集会, 02 Jul. 2022
  • 慢性血栓塞栓性肺高血圧症診療 up-to-date~治療編               
    佐藤隆博
    第127回日本循環器学会 北海道地方会, 25 Jun. 2022
  • 教育講演II 慢性血栓塞栓性肺高血圧症診療 up-to-date~診断編~               
    辻野一三
    第127回日本循環器学会北海道地方会, 25 Jun. 2022
  • 慢性血栓塞栓性肺高血圧症と悪性腫瘍合併に関する疫学的検討               
    辻野一三
    令和4年度(2022年度)難治性疾患政策研究事業 難治性呼吸器疾患・肺高血圧症に関する調査研究 第一回班会議, 17 Jun. 2022
  • 医学部生は肺高血圧症の何をどう学んでいる?そこで足りないものは?               
    辻野一三
    NPO法人PAHの会 北海道支部オンラインセミナー, 15 May 2022
  • 間質性肺疾患への肺高血圧症合併における 肺小血管リモデリングの寄与               
    杉本 絢子, 辻野 一三, 大塚 紀幸, 石田 雄介, 中村 順一, 中谷 資隆, 佐藤 隆博, 大平 洋, 鈴木 雅, 高村 圭, 田中 伸哉, 今野 哲
    第62回日本呼吸器学会学術講演会, 22 Apr. 2022
  • その「息切れ」気のせい/歳のせいにしていませんか?               
    辻野一三
    web市民公開講座, 17 Apr. 2022
  • 肺高血圧症の精査で診断がついた乳癌による肺腫瘍血栓性微小血管症の一例               
    島秀起, 佐藤隆博, 堀井洋志, 中村順一, 辻野一三, 渡邊健一, 橋本大和, 安孫子光春, 清水亜衣, 今野哲
    第294回日本内科学会北海道地方会, 12 Feb. 2022
  • 肺高血圧症 病気のキホンから最新治療まで               
    辻野一三
    薬剤師 生涯教育講座(ビデオ収録), 27 Jan. 2022, Public discourse
  • Pulmonary vasculopathy in pulmonary hypertension with interstitial lung disease:a morphometric study of autopsy cases               
    Ayako Sugimoto, Ichizo Tsujino, Noriyuki Otsuka, Yusuke Ishida, Junichi Nakamura, Toshitaka Nakaya, Takahiro Sato, Hiroshi Ohira, Masaru Suzuki, Shinya Tanaka, Satoshi Konno
    The 25th Congress of the Asian Pacific Society of Respirology APSR 2021, 20 Nov. 2021
  • バルーン肺動脈形成術により在宅酸素・血管拡張薬を中止できた慢性血栓塞栓性肺高血圧症の一例               
    島 秀起, 佐藤 隆博, 千葉 葵, 三田 明音, 高木 統一郎, 堀井 洋, 森永 大亮, 中村 順一, 松本 宗大, 中久保 祥, 鈴木 雅, 辻野 一三, 今野 哲
    第126回日本循環器学会北海道地方会, 17 Nov. 2021
  • 心臓サルコイドーシスとの鑑別を要した抗ミトコン ドリア抗体陽性筋炎の一例               
    佐藤 一紀, 高木 統一郎, 堀井 洋志, 中村 順一, 中久保 祥, 鎌田 啓佑, 鈴木 雅, 大平 洋, 辻野 一三, 今野 哲
    第292回日本内科学会北海道地方会, 03 Jul. 2021
  • プレッシャーカテーテルを用いた肺高血圧症症例の右室機能解析~第2報~               
    辻野一三
    難治性呼吸器疾患・肺高血圧症に関する調査研究班会議, 02 Jul. 2021
  • 今後も肺高血圧症と付き合っていく中で、一番心配なことは何ですか?               
    辻野一三
    Meet The Doctor - ZOOMで専門医と語ろう!NPO法人PAHの会北海道支部 2021年度患者会 オンラインセミナー, 27 Jun. 2021
  • 北海道大学病院における肺高血圧症診療~スクリーニングから最新治療まで~               
    辻野一三
    第125回日本循環器学会北海道地方会, 26 Jun. 2021
  • 肺高血圧症~キホン事項と知っておきたい治療の進歩               
    辻野一三
    第57回日本肝臓学会総会, 18 Jun. 2021
  • 胸部CTにおける定量的手法を用いた1群または3群強皮症性肺高血圧症の優位性の評価               
    蜷川 慶太, 加藤 将, 河野 通仁, 藤枝 雄一郎, 大平 洋, 奥 健志, 杉森 博行, 辻野 一三, 渥美 達也
    第6回 日本肺高血圧・肺循環学会学術集会, 06 May 2021
  • 北海道大学病院における肺高血圧症の 臨床分類と生存率の報告               
    大平 洋, 中村 順一, 杉本 絢子, 中谷 資隆, 鈴木 雅, 加藤 将, 佐藤 隆博, 辻野 一三, 今野 哲
    第6回 日本肺高血圧・肺循環学会学術集会, 06 May 2021
  • 間質性肺疾患合併肺高血圧症の 肺血管形態に関する病理学的検討               
    杉本 絢子, 辻野 一三, 中村 順一, 中谷 資隆, 佐藤 隆博, 渡部 拓, 大平 洋, 鈴木 雅, 今野 哲
    第6回 日本肺高血圧・肺循環学会学術集会, 06 May 2021
  • 肺高血圧症の死因解析~各群の特徴を実臨床でどう活かすか~               
    中村 順一, 辻野 一三, 杉本 絢子, 佐藤 隆博, 鈴木 雅, 渡部 拓, 大平 洋, 今野 哲
    第6回日本肺高血圧・肺循環学会学術集会, 06 May 2021
  • 神経線維腫症Ⅰ型(NF1)に合併した肺高血圧症の一例               
    若園 順康, 中村 順一, 嘉島 相裕, 佐藤 一紀, 山下 優, 鎌田 啓佑, 中久保 祥, 鈴木 雅, 大平 洋, 辻野 一三, 今野 哲
    第 121 回 日本呼吸器学会北海道支部学術集会, 27 Mar. 2021
  • Underestimation of E/e to Predict Elevated Left Ventricular Filling Pressure in Patients with Non-cardiac Pulmonary Hypertension               
    Yasuyuki Chiba, Hiroyuki Iwano, Sanae Kaga, Mio Shinkawa, Michito Murayama, Hiroshi Ohira, Ko Motoi, Suguru Ishizaka, Shingo Tsujinaga, MD, PhD, Asuka Tanemura, Shinobu Yokoyama, Masahiro Nakabachi, Hisao Nishino, Kazunori Okada, Kiwamu Kamiya, Toshiyuki Nagai, Ichizo Tsujino, Toshihisa Anzai
    第85回日本循環器学会学術集会, 26 Mar. 2021
  • 集学的治療により救命し得た慢性血栓塞栓性肺高血圧症の一例               
    西村弘基, 中村順一, 嘉島相裕, 若園順康, 中久保祥, 鎌田啓佑, 鈴木雅, 大平洋, 辻野一三, 今野哲
    第291回 日本内科学会北海道地方会, 13 Feb. 2021
  • 肺高血圧症の死因解析 ~各群の特性の認識と今後の診療・研究に向けた提言~               
    辻野一三
    難治性疾患政策研究 「難治性呼吸器疾患・肺高血圧症に関する調査研究班」, 18 Dec. 2020
  • 慢性骨髄性白血病治療中に認めた 薬剤性肺動脈性肺高血圧症の1例               
    児島裕一, 大平洋, 堀井洋志, 中村順一, 鎌田啓佑, 中久保祥, 渡部拓, 鈴木雅, 辻野一三, 今野哲
    第290回北海道内科学会地方会, 28 Nov. 2020
  • 3群肺高血圧症における右室機能障害および予後との関連               
    島 秀起, 辻野一三, 中谷資隆, 中村順一, 杉本絢子, 渡部 拓, 大平 洋, 佐藤隆博, 今野 哲
    第5回日本肺高血圧・肺循環学会, 26 Sep. 2020
  • PH50例のPRO調査~ 「あなたの今後一番心配なことは何ですか?」               
    辻野一三
    第5回日本肺高血圧・肺循環学会学術集会, 26 Sep. 2020
  • シンポジウム9 病態から考える肺高血圧症:最新の病態にせまる 右心不全               
    辻野一三
    第60回 日本呼吸器学会, 20 Sep. 2020, Nominated symposium
  • 慢性骨髄性白血病治療中に認めた薬剤性肺動脈性肺高血圧症の1例               
    島秀起, 大平洋, 中谷資隆, 中村順一, 杉本絢子, 渡部拓, 辻野一三, 今野哲
    第125回日本循環器学会北海道地方会, 05 Sep. 2020
  • 当科における肺高血圧症の臨床分類と生存率について               
    大平 洋, 中村順一, 中谷資隆, 杉本絢子, 渡部 拓, 佐藤隆博, 辻野一三
    第123回日本循環器学会北海道地方会, 05 Sep. 2020

Affiliated academic society

  • European Respiratory Society               
  • THE JAPAN DIABETES SOCIETY               
  • Japanese Pulmonary Circulation and Pulmonary Hypertension Society               
  • THE JAPANESE SOCIETY OF INTERNAL MEDICINE               
  • THE JAPANESE RESPIRATORY SOCIETY               
  • 日本循環器学会               

Research Themes

  • 慢性肺血栓塞栓性肺高血圧症の呼吸困難に関する検討
    科学研究費助成事業
    01 Apr. 2023 - 31 Mar. 2026
    佐藤 隆博, 辻野 一三, 平田 健司, 清水 薫子
    慢性肺血栓塞栓性肺高血圧症(Chronic thromboembolic pulmonary hypertension (CTEPH))における治療後残存息切れの原因を明らかにし、息切れと関連する指標、適切な対処方法を確立することを目的に研究をしている。下記(A)~(C)の指標との関連を検討することを目的としている。
    (A)心臓の形態・機能異常の評価系の確立。これは、従来、PH症例の心臓形態・機能の評価は血中脳性ナトリウム利尿ペプチド濃度、心エコー、心臓カテーテル検査などで行われてきた。これらの指標は治療の適正化や予後予測の上で有用である。しかし、従来の指標は負荷依存性であり心臓固有の機能を反映しないという問題があった。その中で近年、心臓MRIと右心カテーテル指標を組み合わせることで右室固有の収縮・拡張能を算出している。
    (B)呼吸機能と肺容積の評価系の確立。CTEPH症例では、拘束性障害や閉塞性障害を認めることが報告されているが、治療前後の変化については報告がない。本研究では治療前後の呼吸機能を呼吸機能検査(含肺拡散能力)と肺CTを用いて比較する。CTでは肺容積をAVIEWTMを用いて算出し解析する。これらと治療前後の息切れの程度・質、運動耐用能(6分間歩行距離およびボルグ指数、最大酸素摂取量)との関連を解析する。
    (C)肺循環動態の安静時、運動負荷時の定量的評価を確立。15OでラベリングしたH20(水)をトレーサーとして用いたPET検査にて肺内血流量測定を行い息切れとの関連を検討する。
    現在、CTEPH症例のカテーテル治療後の症例が10例ほど蓄積されてきており、次年度はこれらの結果を学会発表、論文発表していく予定とされている。
    日本学術振興会, 基盤研究(C), 北海道大学, 23K07593
  • Comprehensive evaluation with CT for cardiac sarcoidosis
    Grants-in-Aid for Scientific Research
    01 Apr. 2017 - 31 Mar. 2020
    Oyama-Manabe Noriko
    The usefulness of cardiac magnetic resonance (CMR) for the assessment of cardiac sarcoidosis (CS) has been reported. Late gadolinium enhancement (LGE) on CMR is an effective technique for the diagnosis of CS. CMR has high diagnostic accuracy and prognostic value. While LGE-CMR can evaluate only myocardium, contrast-enhanced CT could comprehensively evaluate the whole-body and myocardium on delayed phase. We have demonstrated that delayed enhanced CT (DE-CT) has the potential to detect myocardial fibrosis due to CS as part of evaluation for systemic sarcoidosis. DE-CT had sufficient image quality to allow the assessment of hyperenhanced myocardium in patients with or without implantable devices. DE-CT delineated the extent of CS with accuracy comparable to that of LGE-CMR. DE-CT had high sensitivity for the diagnosis of CS, suggesting that DE-CT may be appropriate for screening and monitoring of CS, particularly in patients with contraindications to CMR.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 17K10349
  • Analysis of microenvironment and exploration of new biomarker for pulmonary arterial hypertention
    Grants-in-Aid for Scientific Research
    01 Apr. 2015 - 31 Mar. 2018
    Tanino Mishie
    (1)Immunohistochemisty for FGFR1, VEGFR2, EGFR in the lungs of pulmonary venous obstructive hypertension(PVOD) showed higher expression of FGFR compared to VEGFR and EGFR in PVOD lungs. FGF-FGFR may pathway contribute the pathogenesis of PVOD. (2)Therapy related proteins such as PDE5、ER-A/B、PGI2、sGCα/βexpressed higher in pulmonary hypertension(PH) compared to controls, however there were no difference between Group 1-PH and Group 3-PH. These drugs contribute to dilate vessel wall in both types of PH. (3) Systemic sclerosis (Ssc) related PH showed denser fibrosis compared to SLE related PH and replacement myocardial fibrosis was demonstrated at the site of late gadolinium enchancement of MRI in Ssc patient.(4) FoxF1 mutation was detected in Alveolar capillary dysplasia related PH children and Heterozygous mutations in OAS1 were detected in infantile-onset pulmonary alveolar proteinosis with hypogammaglobulinemia. These genetic background relate to secondary PH.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 15K08359
  • Clinicopathological study on the pulmonary vasculopathy and right heart morphology/function in lung disease-associated pulmonary hypertension
    Grants-in-Aid for Scientific Research
    01 Apr. 2014 - 31 Mar. 2017
    TSUJINO Ichizo
    We studied cases with lung disease-associated pulmonary hypertension and demonstrated remodeling of the pulmonary vasculature as well as the expression of target proteins of pulmonary vasodilators. The expression was also shown in myocardial tissue, suggesting favorable effects of pulmonary vasodilating treatment. In the clinical study, we showed significant improvement in the pulmonary vascular resistance and right heart morphology/function (published in the journal Pulmonary Circulation, 2017). We also notably shown elevations of blood insulin level, index of insulin resistance, and plasma concentration of BDNF, one of the myokines, in pulmonary hypertension patients. Lastly, in our study, clinical relevance of chest computed tomography-derived indices of pulmonary vascular system was examined and we found their usefulness in the diagnosis and hemodynamic evaluation of pulmonary hypertension.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 26461150
  • Development of new diagnosis approaches for detecting cardiovascular dysfunction in patients with respiratory disease using positron emission tomography
    Grants-in-Aid for Scientific Research
    01 Apr. 2011 - 31 Mar. 2014
    YOSHINAGA Keiichiro, KATOH Chietsugu, TSUJINO Ichizo, MANABE Noriko
    Right ventricular (RV) oxidative metabolism increased in patients with PH in association with prognostic markers such as mean PAP, PVR, and BNP.. Patients with WHO functional class II to III PH also had increased RV power and efficiency. These findings may indicate a myocardial energetics adaptation response to increasing PAP. Intensive PH treatments reduced RV oxidative metabolism and improved RV volume/oxygen consumption index. In this project, we developed possible new prognostic markers and useful treatment monitor markers in patients with PH.
    F-18 flucorodeoxyglucose (FDG) has been considered to be a diagnostic marker of cardiac involvement sarcoidosis (CS). We reported the association between the ECG abnormalities and positive F-18 FDG uptake in LV. This indicates active inflammation is associated with rhythm abnormalities. We also reported the reduced cardiac sympathetic nervous function in CS. These findings may contribute the understanding the disease mechanisms.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 23390294
  • 冠動脈疾患、肺循環疾患               
    Competitive research funding
  • 肺疾患合併肺高血圧症における心筋および骨格筋評価系の確立と臨床応用               
    科学研究費助成事業 基盤C
    辻野 一三
    文部科学省および日本学術振興会, Principal investigator, Competitive research funding