Researcher Profile and Settings

Master

Affiliation (Master)

• Faculty of Medicine

Affiliation (Master)

• Faculty of Medicine

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Profile and Settings

Affiliation

• Hokkaido University, Hokkaido University Hospital, 特任教授

Profile and Settings

• Name (Japanese)

  Tsujino

• Name (Kana)

  Ichizo

• Name

  200901017997610243

Affiliation

• Hokkaido University, Hokkaido University Hospital, 特任教授

Achievement

Research Interests

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

Research Areas

• Life sciences / Metabolism and endocrinology
• Life sciences / Cardiology

Research Experience

• 2021/09 - Today Hokkaido University Hokkaido University Hospital

Published Papers

• 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 2024/08 

  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 2024/05 

  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) 2024/04/26 

  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  2024/04 

  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  2024/04 

  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 2024/03/27 

  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 2024/03/11
• 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 

  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 0903-1936 2023/12/07 

  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 0009-7322 2023/11/13
• 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) 2023/09/15 

  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 2023/08/24 

  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 2023/08/15 

  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 I₂ 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 1349-2365 2023/07/29
• 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 2023/04/10 

  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  2023/04 

  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 1175-3277 2023/03/30
• 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 2023/03/25 

  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 (一社)日本呼吸器学会 12 (増刊) 44 - 44 2186-5876 2023/03
• 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 1881-641X 2023
• 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 

  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 一般社団法人 日本超音波検査学会 advpub 1881-4506 2023 

  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 1881-641X 2023
• 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) 2045-8940 2023/01
• 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 2022/12 

  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 2022/11/28 [Refereed]
   

  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 2022/11/12 [Refereed]
   

  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 2022/11/10 [Refereed]
   

  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) 2045-8940 2022/10
• 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 (一社)日本脈管学会 62 (Suppl.) S106 - S106 0387-1126 2022/10
• 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 2022/09/20 [Refereed][Not invited]
   

  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 2022/09/02 [Refereed]
   

  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 2022/09 [Refereed]
   

  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 2022/08/29 [Refereed]
   

  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 2022/07/29 

  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 2022/07/22 [Refereed]
   

  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 2022/07/01 [Refereed]
   

  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 2022/06/29 [Refereed]
   

  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 2022/06/03 [Refereed]
   

  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 (一社)日本静脈学会 33 (2) 144 - 144 0915-7395 2022/06
• 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 (一社)日本静脈学会 33 (2) 147 - 147 0915-7395 2022/06
• 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 (一社)日本静脈学会 33 (2) 148 - 148 0915-7395 2022/06
• 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 2772-3747 2022/06 [Refereed]
   

  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 2022/05/10 [Refereed]
   

  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.
• 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 2022/04/05 [Refereed]
   

  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 (公社)日本超音波医学会 49 (Suppl.) S706 - S706 1346-1176 2022/04
• 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) 2022/04 [Refereed]
   

  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  2022/04 [Refereed]
   

  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 2022/04 [Refereed]
   

  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 2022/03/31 [Refereed]
   

  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 2022/01/10 [Refereed]
   

  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) 2021/11/25 

  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 (一社)日本呼吸器内視鏡学会 43 (6) 690 - 690 0287-2137 2021/11
• 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 (NPO)日本呼吸器内視鏡学会 43 (6) 690 - 690 0287-2137 2021/11
• 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 2045-8940 2021/10 [Refereed]
   

  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 2021/05/20 [Refereed]
   

  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 0392-856X 2021/05/12 [Refereed]
   

  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 日本肺高血圧・肺循環学会・日本小児肺循環研究会 6回・27回 41 - 41 2021/05
• 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 2021/05 [Refereed]
   

  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 2021/03/25 [Refereed]
   

  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 2021/01/14 [Refereed]
   

  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 (株)メディカルレビュー社 6 (2) 76 - 80 2189-4434 2020/11
• 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 2020/09/25 [Refereed]
   

  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 (一社)日本糖尿病学会 63 (Suppl.1) S - 132 0021-437X 2020/08
• 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 2045-8940 2020/07 [Refereed]
   

  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 2020/03/20 [Refereed]
   

  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 1462-0324 2020/03/01 [Refereed][Not invited]
   

  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 (一社)日本病理学会 109 (1) 308 - 308 0300-9181 2020/03
• 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 2020/01/09 [Refereed][Not invited]
  
• 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 

  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 [Refereed][Not invited]
   

  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 2019/12/09 [Refereed][Not invited]
   

  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.
• 【肺高血圧症 ガイドラインとニース会議提言を紐解く】肺高血圧症の定義の変更,病態,診断を紐解く 肺動脈性肺高血圧症の右心機能とその病態

  佐藤 隆博, 大平 洋, 辻野 一三

  呼吸器ジャーナル (株)医学書院 67 (4) 574 - 578 2432-3268 2019/11 

  ＜文献概要＞Point ・右心機能は右房機能,右室機能に大別され,後者の右室機能はさらに収縮能・拡張能,右室・肺動脈カップリングなどに分類される.・肺動脈性肺高血圧症では一般に右室収縮能は代償的に亢進し,拡張能,右室・肺動脈カップリングは低下していることが多い.・肺動脈性肺高血圧症の病態の理解や予後改善の観点から右心機能の正確な評価の重要性は今後さらに増すと思われる.
• 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 2019/10/11 [Refereed][Not invited]
   

  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 0022-7854 2019/10 [Refereed][Not invited]
  
• 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 0022-7854 2019/10 [Refereed][Not invited]
  
• 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 (一社)日本核医学会 56 (Suppl.) S137 - S137 0022-7854 2019/10 [Refereed][Not invited]
  
• 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 0172-8172 2019/07 [Refereed][Not invited]
   

  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 (株)日本臨床社 77 (7) 1102 - 1107 0047-1852 2019/07
• 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 1619-7070 2019/06 [Refereed][Not invited]
   

  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 日本心臓核医学会 21 (2) 124 - 124 1346-2733 2019/06 [Refereed][Not invited]
  
• 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 1346-9843 2019/03 [Refereed][Not invited]
  
• 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 1071-3581 2019/02/27 [Refereed][Not invited]
   

  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 0010-4825 2019/01 [Refereed][Not invited]
   

  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 [Refereed][Not invited]
   

  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 (株)メディカルレビュー社 5 np25 - np25 2018/12
• 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 2018/10/05 [Refereed][Not invited]
   

  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 (有)科学評論社 84 (2) 165 - 170 1884-2909 2018/08
• 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 2212-5345 2018/07 [Refereed][Not invited]
   

  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 0918-2918 2018/06/15 [Refereed][Not invited]
   

  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) 2018/06 [Refereed][Not invited]
  
• 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 2045-8932 2018/04 [Refereed][Not invited]
   

  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 2018/03 [Refereed][Not invited]
   

  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 1593-098X 2018 [Refereed][Not invited]
  
• 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 (一社)日本インターベンショナルラジオロジー学会 32 (4) 324 - 325 1340-4520 2018/01
• 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 1347-4820 2018 [Refereed][Not invited]
   

  Background: The trend of the initial treatment strategy for pulmonary arterial hypertension (PAH) has changed from monotherapies to upfront combination therapies. This study analyzed treatments and outcomes in Japanese patients with PAH, using data from the Japan PH Registry (JAPHR), which is the first organized multicenter registry for PAH in Japan. Methods and Results: We studied 189 consecutive patients (108 treatment-naïve and 81 background therapy patients) with PAH in 8 pulmonary hypertension (PH) centers enrolled from April 2008 to March 2013. We performed retrospective survival analyses and analyzed the association between upfront combination and hemodynamic improvement, adjusting for baseline NYHA classification status. Among the 189 patients, 1-, 2-, and 3-year survival rates were 97.0% (95% CI: 92.1–98.4), 92.6% (95% CI: 87.0–95.9), and 88.2% (95% CI: 81.3–92.7), respectively. In the treatment-naïve cohort, 33% of the patients received upfront combination therapy. In this cohort, 1-, 2-, and 3-year survival rates were 97.6% (95% CI: 90.6–99.4), 97.6% (95% CI: 90.6–99.4), and 95.7% (95% CI: 86.9–98.6), respectively. Patients on upfront combination therapy were 5.27-fold more likely to show hemodynamic improvement at the first follow-up compared with monotherapy (95% CI: 2.68–10.36). Conclusions: According to JAPHR data, initial upfront combination therapy is associated with improvement in hemodynamic status.
• 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 0720-048X 2017/11 [Refereed][Not invited]
   

  Background: Few studies have addressed the value of combining computed tomography-derived pulmonary vasculature metrics for the diagnosis and haemodynamic evaluation of pulmonary arterial hypertension (PAH). Materials and methods: We measured three computed tomography parameters for the pulmonary artery, peripheral vessels, and pulmonary veins: the ratio of the diameter of the pulmonary artery to the aorta (PA/Ao), the cross-sectional area of small pulmonary vessels < 5 mm(2) as a percentage of total lung area (%CSA(<5)), and the diameter of the right inferior pulmonary vein (PVD). The measured quantities were compared between patients with PAH (n = 45) and control subjects (n = 56), and their diagnostic performance and associations with PAH-related clinical indices, including right heart catheterization measurements, were examined. Results: PA/Ao and %CSA(< 5) were significantly higher in patients with PAH than in controls. Receiver-operating characteristic curve analysis for ability to diagnose PAH showed a high area under the curve (AUC) for PA/Ao (0.95) and modest AUC5 for %CSA(< 5) (0.75) and PVD (0.56). PA/Ao correlated positively with mean pulmonary arterial pressure and PVD correlated negatively with pulmonary vascular resistance. The %CSA(<5) correlated negatively with mean pulmonary arterial pressure and pulmonary vascular resistance and positively with cardiac index. Notably, the PA/Ao and PVD values divided by %CSA(< 5) correlated better with right heart catheterization indices than the non-divided values. Conclusion: PA/Ao, %CSA(< 5), and PVD are useful non-invasive pulmonary vasculature metrics, both alone and in combination, for diagnosis and haemodynamic assessment of PAH.
• 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  1932-6203 2017/11 [Refereed][Not invited]
   

  Background Serial assessment of right ventricular ejection fraction (RVEF) predicts the clinical outcome of patients with pulmonary hypertension (PH). Cardiac magnetic resonance imaging (CMRI) enables RVEF monitoring, but its applicability is limited in clinical practice. This study aimed to examine the correlation between changes in CMRI-derived RVEF with those in echocardiographic indices in patients with precapillary PH. Methods CMRI and echocardiographic indices of RV systolic function were evaluated at baseline and follow-up in 54 consecutive patients with precapillary PH (pulmonary arterial hypertension (PAH), n = 23; non-PAH, n = 31). During follow-up, medical treatment was optimized according to the guidelines for PH. Using CMRI-derived RVEF as the gold standard, we examined the accuracy of five echocardiographic indices by correlation analysis and receiver operating characteristic (ROC) analysis and by calculating sensitivity, specificity, and positive and negative predictive values. Results After an average period of 9.5 months, CMRI-derived RVEF improved from 30.2% +/- 10.6% at baseline to 41.4% +/- 11.3% at follow-up. These changes significantly correlated with those in the five echocardiographic indices, i.e., % RV fractional shortening (r = 0.27), % RV area change (r = 0.46), tricuspid annular plane systolic excursion (TAPSE) (r = 0.84), RV myocardial performance index (RVMPI) (r = -0.72), and systolic lateral tricuspid annular motion velocity (TVlat) (r = 0.66). Of these indices, % RV area change, TAPSE, and TVlat significantly correlated with those of CMRI-derived RVEF in both PAH and non-PAH subgroups. ROC analysis showed that improvement in echocardiographic indices predicted a prespecified improvement in CMRI-derived RVEF (>2.9%), with TAPSE and TVlat showing better accuracy over the other three indices. Conclusions Echocardiographic indices modestly correlate with the changes in CMRI-derived RVEF in precapillary PH patients. Comparison among the five echocardiographic indices revealed that TAPSE and TVlat provide better accuracy than % RV fractional shortening, % RV area change, and RVMPI.
• 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  0025-7974 2017/10 [Refereed][Not invited]
   

  We investigated the serum haptoglobin levels in patients with pulmonary arterial hypertension (PAH) based on the hypothesis that haptoglobin levels would reflect subclinical hemolysis due to microangiopathy in pulmonary arterioles.This cross-sectional study included 3 groups of patients attending Hokkaido University Hospital: PAH, chronic thromboembolic pulmonary hypertension (CTEPH), and connective tissue diseases (CTD) without PAH (CTD-non-PAH) group. Serum haptoglobin levels were measured by standardized turbidimetric immunoassay in all patients. Demographic data, laboratory results, right heart catheter, and echocardiographic findings were extracted from the medical records. Decreased haptoglobin levels were defined as below 19mg/dL based on the 95th percentile of healthy controls.Thirty-five patients in PAH group including 11 with idiopathic PAH (IPAH) and 24 with CTD-associated PAH (CTD-PAH), 27 in CTEPH group, and 32 in CTD-non-PAH group were analyzed. Serum haptoglobin levels in PAH group (median 66mg/dL) were significantly lower than those in CTEPH group (median 94mg/dL, P=.03) and CTD-non-PAH group (median 79mg/dL, P=.03). The prevalence of decreased haptoglobin levels was 26% in PAH group, 15% in CTEPH group, and 6% in CTD-non-PAH group. Serum haptoglobin levels had a significant negative correlation (r=-0.66, P<.001) with mean pulmonary artery pressure in PAH group, particularly in CTD-PAH subgroup (r=-0.74, P<.001), but no correlation in IPAH subgroup (r=-0.52, P=.13) and in CTEPH group (r=-0.17, P=.41). Follow-up cases of CTD-PAH showed lowering pulmonary artery pressure led to normalizing serum haptoglobin levels.Serum haptoglobin levels decreased in PAH patients and inversely correlated with pulmonary artery pressure in CTD-PAH patients, suggesting their potential as a surrogate marker for CTD-PAH.
• 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 0938-7994 2017/10 [Refereed][Not invited]
   

  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 2017/08 [Refereed][Not invited]
   

  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 2325-6621 2017/05/01 [Refereed][Not invited]
  
• 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 (一社)日本インターベンショナルラジオロジー学会 32 (Suppl.) 231 - 231 1340-4520 2017/04
• 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) 1941-7705 2017 [Refereed][Not invited]
   

  Background-Balloon pulmonary angioplasty (BPA) is an alternative therapy for patients with chronic thromboembolic pulmonary hypertension who are ineligible for pulmonary endarterectomy-the standard therapy. Currently, most reported results of BPA are from relatively small cohorts treated at single centers. The present study evaluated the safety and efficacy of BPA for chronic thromboembolic pulmonary hypertension based on a multicenter registry. Methods and Results-A total of 308 patients (62 men and 246 women mean age, 61 years) underwent 1408 procedures at 7 institutions in Japan. Data were retrospectively reviewed to evaluate clinical outcome and complications. Hemodynamics were significantly improved in 249 patients in whom BPA was terminated, most often because of improvement in mean pulmonary arterial pressure or symptomatic improvement after 1154 procedures. In 196 patients who underwent followup right heart catheterization, improvement of hemodynamic parameters was maintained. Mean pulmonary arterial pressure decreased from 43.2±11.0 to 24.3±6.4 mm Hg after final BPA and 22.5±5.4 mm Hg at follow-up, with significant reduction of concomitant use of pulmonary hypertension-targeted therapy and oxygen supplementation. Complications occurred in 511 (36.3%), including pulmonary injury (17.8%), hemoptysis (14.0%), and pulmonary artery perforation (2.9%). Twelve patients (3.9%) died during follow-up, including 8 patients who died within 30 days after BPA. The leading causes of death were right heart failure, multiorgan failure, and sepsis. Overall survival was 96.8% (95% confidence interval, 93.7%-98.4%) at 1 and 2 years and 94.5% (95% confidence interval, 89.3%-97.3%) at 3 years, respectively, after the initial BPA procedure for all 308 patients. Conclusions-This multicenter registry suggested improved hemodynamic results after BPA. Complication rates were high, but overall survival was comparable with pulmonary endarterectomy. BPA may be an important therapeutic option in patients with chronic thromboembolic pulmonary hypertension.
• 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 日本心臓核医学会 3 (1) 125 - 130 2017 

  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 1439-7595 2017 [Refereed][Not invited]
   

  Objectives: Pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc) has a poor prognosis compared to PAH associated with other connective tissue diseases (CTD). The objective of this study was to examine the difference in hemodynamic state between SSc-PAH and other CTD-PAH by performing cardiac magnetic resonance (CMR) imaging.Methods: A single center retrospective analysis was conducted comprising 40 consecutive CTD patients who underwent right heart catheterization and CMR at the same period from January 2010 to October 2015.Results: Thirty-two patients had pre-capillary pulmonary hypertension. Of these, 15 had SSc and 17 had other CTD. CMR measurements, particularly the ratio of right to left end-diastolic volume (RVEDV/LVEDV), correlated well with mean pulmonary arterial pressure (mPAP). Conversely, RVEDV/LVEDV and mPAP correlated differently in SSc and non-SSc patients. In SSc patients, the ratio of RVEDV/LVEDV to mPAP was significantly higher compared to non-SSc patients. In the follow-up study, 2 SSc patients exhibited increased RVEDV/LVEDV in spite of decreased mPAP following treatment. Kaplan-Meier analysis revealed poor prognosis of patients with increased RVEDV/LVEDV following treatment.Conclusions: Our data indicated that altered bi-ventricular interplay detected at CMR may represent SSc-related cardiac involvement and reflect poor prognosis of SSc-PAH.
• 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 2045-8932 2016/12 [Refereed][Not invited]
   

  Pulmonary arterial hypertension (PAH)-approved vasodilators improve right ventricular (RV) function in patients with PAH. However, whether PAH-approved drugs ameliorate RV morphology and function in lung disease-associated pulmonary hypertension (lung-PH) remains unclear. We aimed to prospectively evaluate the changes in RV volume and ejection fraction (RVEF) in 14 consecutive severe lung-PH patients treated with PAH-approved vasodilators. Severe lung-PH was defined as a mean pulmonary arterial pressure (MPAP) of >= 35 mmHg or an MPAP of >= 25 mmHg with a cardiac index (L/min/m(2)) of <2. Right heart catheterization and cardiac magnetic resonance (CMR) imaging were performed at baseline and at 3 months after starting sildenafil with or without other PAH-approved drugs. Follow-up was conducted at 3 months in 11 participants; compared with baseline values, MPAP and pulmonary vascular resistance (PVR) decreased by 18% and 37%, respectively. Baseline CMR imaging revealed an elevated RV end-diastolic volume index (RVEDVI; mL/m(2)) of 117.5 +/- 35.9 and a below-average RVEF of 25.2% +/- 7.2%; after 3 months, RVEDVI decreased by 23.7% (P = 0.0061) and RVEF increased by 32.9% (P = 0.0165). Among the 11 patients, 3 were thought to be a stable and homogenous subset in terms of background lung disease and medical management administered. These 3 patients exhibited similar ameliorations in PVR and RVEF, compared with the other 8 patients. PAH-approved drug treatment may improve RV dilatation and systolic function among patients with severe lung-PH.
• 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 (一社)日本核医学会 53 (Suppl.) S305 - S305 0022-7854 2016/10
• 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 バイエル薬品(株) 61 (1) 133 - 133 0912-0351 2016/09
• 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 医学書院 64 (6) 543‐547 - 542 0452-3458 2016/06/15 [Not refereed][Not invited]
  
• Right heart morphology, function and metabolism in pulmonary hypertension

  Toshitaka Nakaya, Hiroshi Ohira, Ichizo Tsujino

  Respiration and Circulation 64 (6) 543 - 547 0452-3458 2016/06/01
• 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 (株)医学書院 64 (5) S37 - S37 0452-3458 2016/05
• 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 (株)医学書院 64 (5) S38 - S38 0452-3458 2016/05
• 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 0161-5505 2016/05/01 [Refereed][Not invited]
  
• 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 0161-5505 2016/05/01 [Refereed][Not invited]
  
• 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 0161-5505 2016/05/01 [Refereed][Not invited]
  
• 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 1071-3581 2016/04 [Refereed][Not invited]
   

  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  1932-6203 2016/03 [Refereed][Not invited]
   

  Objective A positive association between the number of cigarettes smoked per day and obesity has been reported, whereas how other smoking-related indices, such as pack-years and duration of smoking, are related with obesity has been less investigated. We analyzed the age-adjusted cross-sectional association between smoking and obesity in a general Japanese population. Methods We used data from a nationwide epidemiological study of Japanese adults (N = 23,106). We compared the prevalence of obesity (defined as body mass index >= 25kg/m(2)) among groups classified by smoking behavior, pack-years, number of cigarettes per day, duration of smoking, and duration and time of smoking cessation. Results In men, current smokers had a lower odds ratio (OR) for obesity of 0.80 (95% confidence interval (CI): 0.72-0.88) compared to non-smokers, whereas past smokers had a higher OR of 1.23 (95% CI: 1.09-1.37) compared to current smokers. In women, there were no differences in obesity between the three groups classified by smoking behavior. However, in both sexes, the prevalence of obesity tended to increase with pack-years and the number of cigarettes per day, but not with duration of smoking in current and past smokers. Further, in male smokers, the risks for obesity were markedly higher in short-term heavy smokers compared with long-term light smokers, even with the same number of pack-years. Regarding the impact of smoking cessation, female past smokers who quit smoking at an age > 55-years had an elevated OR of 1.60 (95% CI: 1.05-2.38) for obesity. Conclusions In a general Japanese population, obesity is progressively associated with pack-years and number of cigarettes per day, but not with the duration of smoking. When investigating the association between obesity and cigarette smoking, the daily smoking burden and the duration of smoking require to be independently considered.
• 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 1619-7070 2016/02 [Refereed][Not invited]
   

  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 1743-7075 2016/01 [Refereed][Not invited]
   

  Background: Amino acids (AAs) are emerging as a new class of effective molecules in the etiology of obesity and diabetes mellitus. However, most investigations have focused on subjects with obesity and/or impaired glucose regulation; the possible involvement of AAs in the initial phase of glucose dysregulation remains poorly understood. Furthermore, little attention has been given to possible associations between the pattern/degree of fat deposition and the plasma AA profile. Our objective was therefore to determine the relationships between plasma AA concentrations and the type/degree of obesity and glucose regulation in Japanese adults with normal glucose tolerance. Methods: Eighty-three subjects with normal glucose tolerance were classified as obese or nonobese and as visceral obesity or nonvisceral obesity. Correlations between the plasma levels of 23 AAs and somatometric measurements, visceral fat area (VFA), subcutaneous fat area (SFA), and 75-g oral glucose tolerance test results were analyzed. Results: Obesity or visceral obesity was associated with higher levels of branched-chain AAs (isoleucine, leucine, and valine), lysine, tryptophan, cystine, and glutamate but lower levels of asparagine, citrulline, glutamine, glycine, and serine (p < 0.04). Age-and gender-adjusted analyses indicated that VFA was positively correlated with tryptophan and glutamate levels, whereas VFA and SFA were negatively correlated with citrulline, glutamine, and glycine levels (p < 0.05). The fasting and 2-h plasma glucose levels or the homeostasis model assessment of insulin resistance were positively correlated with valine, glutamate, and tyrosine levels but negatively correlated with citrulline, glutamine, and glycine levels. The homeostasis model assessment for the beta-cell function index was positively correlated with leucine, tryptophan, valine, and glutamate levels but negatively correlated with citrulline, glutamine, glycine, and serine levels (p < 0.05). Conclusions: The present study identified specific associations between 10 AAs and the type/degree of obesity, and indices of glucose/insulin regulation, in Japanese adults with preserved glucose metabolism. With the growing concern about the increasing prevalence of obesity and diabetes, the possible roles of these AAs as early markers and/or precursors warrant further investigation.
• 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 (一社)日本糖尿病学会 58 (9) 721 - 721 0021-437X 2015/09
• 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 (一社)日本核医学会 52 (3) 257 - 257 0022-7854 2015/09
• 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 (株)医学書院 63 (8) S34 - S34 0452-3458 2015/08
• 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 (株)医学書院 63 (8) S56 - S57 0452-3458 2015/08
• 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 1323-7799 2015/07 [Refereed][Not invited]
   

  Background and objectivePulmonary hypertension (PH) is often associated with respiratory diseases, but only a small number of patients present with severe PH defined as mean pulmonary arterial pressure35mmHg. We here conducted a multicenter, retrospective study of patients with severe PH associated with respiratory diseases (R-PH) to reveal their demographics, treatment, prognosis and determinants of prognosis. MethodsFrom 101 patients with severe R-PH collected by postal survey at the first stage, 70 patients with four major diseases (chronic obstructive pulmonary disease (COPD), combined pulmonary fibrosis with emphysema (CPFE), interstitial pneumonia associated with connective tissue disease (CTD-IP), interstitial pneumonia (IP)) and normal pulmonary arterial wedge pressure were studied for clinical characteristics, treatment and prognosis. ResultsThree-year survival rates were 50% for COPD (n=18), 35.7% for IP (n=19) and 68.1% for CTD-IP (n=20), and the 2-year survival rate for CPFE (n=13) was only 22.6%. Eighty-onepercent of patients had been treated with pharmacotherapy specific for pulmonary arterial hypertension. Those patients who had received phosphodiesterase-5 inhibitors (PDE-5I) displayed significantly better survival from the date of diagnosis than those who had not (3-year survival: 61.8% vs 20.0% P<0.0001), especially in the IP, CTD-IP and CPFE groups. Multivariate analysis also revealed that treatment with PDE-5I was a positive prognostic factor. ConclusionsWe here demonstrated the dismal prognosis of patients with severe R-PH. The remarkably better survival in those patients who had received PDE-5I warrants and facilitates future prospective randomized studies in this particular population.
• 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) 0161-5505 2015/05/01 [Refereed][Not invited]
  
• 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) 0161-5505 2015/05/01 [Refereed][Not invited]
  
• 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 1053-2498 2015/03 [Refereed][Not invited]
   

  BACKGROUND: Symptoms and signs and indices of right heart function are predictors of clinical outcomes in patients with pulmonary hypertension (PH). However, the significance of right atrial (RA) indices has not been sufficiently investigated. We investigated whether RA parameters predict outcomes in patients with pre-capillary PH. METHODS: Study subjects were 68 patients with pre-capillary PH. RA size and function (systolic, reservoir, and conduit functions) were evaluated by cardiac magnetic resonance imaging. RESULTS: During the mean follow-up period of 24 months, 16 of 68 patients experienced clinical worsening (CW), defined as hospitalization because of right heart failure, lung transplantation, or PHrelated death. Kaplan-Meier and log-rank test showed that World Health Organization functional class, pericardial effusion, increased brain natriuretic peptide concentration, reduced right ventricular ejection fraction (RVEF), increased minimum RA volume index, and decreased RA reservoir volume were associated with CW-free survival. The combination of RVEF and RA reservoir function was a better predictor of CW-free survival. In univariate Cox hazard proportional analysis, CW was associated with the RA reservoir volume index (hazard ratio [HR] = 0.80). In multivariate analysis, CW was associated with World Health Organization functional class (HR = 4.3), RA minimum volume index (HR = 1.07), and RA reServoir volume index (HR = 0.73). CONCLUSIONS: RA volume and reservoir function and their combined use with RVEF are novel predictors of CW in patients with pre-capillary PH. (C) 2015 International Society for Heart and Lung Transplantation. All rights reserved.
• 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 (一社)日本病理学会 104 (1) 311 - 311 0300-9181 2015/03
• 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 [Not refereed][Not invited]
  
• 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 2014/11/27 [Refereed][Not invited]
   

  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 (一社)日本肥満学会 20 (Suppl.) 180 - 180 1343-229X 2014/10
• 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 (一社)日本糖尿病学会 57 (9) 722 - 728 0021-437X 2014/09 

  症例は35歳、男性。糖尿病、うつ病にて当院通院中の平成25年5月、自殺企図にてインスリングラルギン300単位を皮下注したところを家族に発見され、当科へ救急搬送となった。血糖値の頻回モニタリングと経口および静脈内グルコース投与にて、皮下注射から約50時間の経過で重篤な合併症や後遺症なく低血糖状態から脱した。入院中の精査にてミトコンドリア病の診断基準を満たし、うつ病および糖尿病は同疾患によるものと考えた。うつ病と糖尿病の合併は臨床的に重要な問題であり、本報告ではうつ病合併糖尿病の診療上の問題点、インスリン大量投与時の対処と病態、さらにミトコンドリア病の本症例における関与について若干の文献的考察を加え報告する。(著者抄録)
• 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 (一社)日本核医学会 51 (3) 332 - 332 0022-7854 2014/09
• 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 0914-7187 2014/08 [Refereed][Not invited]
   

  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 1619-7070 2014/06 [Refereed][Not invited]
   

  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 0161-5505 2014/05 [Refereed][Not invited]
  
• 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 0161-5505 2014/05 [Refereed][Not invited]
  
• 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 0161-5505 2014/05 [Refereed][Not invited]
  
• 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 (一社)日本糖尿病学会 57 (Suppl.1) S - 287 0021-437X 2014/04
• 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  0735-1097 2014/04/01 [Refereed][Not invited]
  
• 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 (一社)日本糖尿病学会 57 (3) 220 - 220 0021-437X 2014/03
• 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 (一社)日本糖尿病学会 57 (3) 222 - 222 0021-437X 2014/03
• 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 2212-5353 2014 [Refereed][Not invited]
   

  Background: Pulmonary hypertension (PH) often correlates with respiratory disease severity. Right heart catheterization (RHC) is recommended for the definitive diagnosis of PH associated with respiratory disease (R-PH). However, no previous studies have evaluated the perceived necessity for pulmonologists to use RHC for R-PH diagnosis, or the management of R-PH in Japan. Methods: Questionnaires were mailed to 855 institutions, approved by the Japanese Respiratory Society. Questions included the prevalence and necessity of RHC and other methods in R-PH diagnosis, and current trends in the treatment of R-PH. Results: Questionnaires were returned from 289 institutions (34%). Patients with R-PH were examined by pulmonologists in 89% of institutions some pulmonologists performed echocardiography (15%) and some RHC (13%). Echocardiography was used to diagnose R-PH in 99% of institutions and RHC was used in 36%. RHC was considered in cases of suspected PH in 49% of institutions and prior to initiation of pulmonary arterial hypertension (PAH)-specific therapy in 57%. Of patients diagnosed with R-PH, 47% were treated with ambulatory oxygen therapy. Furthermore, 98 of 145 institutions used PAH-specific therapy to treat R-PH. Of the 1355 patients who underwent RHC as a part of PH evaluation, 29% were confirmed to have PH, and 8% had severe PH with a mean pulmonary arterial pressure of ≥35. mmHg. Conclusions: The current diagnostic and treatment modalities for R-PH in Japan were evaluated. Although few pulmonologists perform RHC for R-PH diagnosis in Japan, more than half consider using RHC for patients before initiating PAH-specific therapy. © 2013 The Japanese Respiratory Society.
• 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 0918-2918 2014 [Refereed][Not invited]
   

  Severe pulmonary hypertension (PH) often develops in patients with pulmonary Langerhans cell histiocytosis (PLCH). Supplemental oxygen treatment is often used, whereas pulmonary arterial hypertension-specific vasodilators are generally considered hazardous because of the possible development of pulmonary edema and deterioration of hypoxia. In the present report, we herein describe a PLCH patient with severe PH in whom sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, substantially improved the pulmonary hemodynamics before lung transplantation. An immunohistochemical study of the resected lung revealed positive staining for PDE5 on the diseased pulmonary arteries. These observations suggest that sildenafil can be a promising therapeutic option for PH in patients with PLCH.
• 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 0021-437X 2014 

  A 35-year-old man with depression and diabetes mellitus was admitted to our department following a suicide attempt in which he subcutaneously injected himself with 300 IU of insulin glargine. We closely monitored the patient's glucose level and administered oral/intravenous glucose as needed, and he subsequently recovered from hypoglycemia approximately 50 hours after admission. He was also found to have hearing loss, hypertrophic cardiomyopathy and a mutation in the mitochondrial DNA at nucleotide position 3243, thereby fulfilling the diagnostic criteria for mitochondrial disease. Clinically, both the patient's diabetes mellitus and depression were considered to be caused by this underlying disease. In the present report, we discuss the possible role of mitochondrial disease in the present case as well as the appropriate management of insulin overdoses and issues regarding concurrent depression in diabetic patients.
• 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 [Not refereed][Not invited]
  
• 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 1569-5794 2013/12 [Refereed][Not invited]
   

  The present study examined whether tricuspid annular plane systolic excursion (TAPSE) can simply predict right ventricular ejection fraction (RVEF) in patients with pulmonary hypertension (PH). The TAPSE cut-off value to predict reduced RVEF was also evaluated. The association between TAPSE and cardiac magnetic resonance imaging (CMRI)-derived RVEF was examined in 53 PH patients. The accuracy of the prediction equation to calculate RVEF using TAPSE was also evaluated. In PH patients, TAPSE was strongly correlated with CMRI-derived RVEF in PH patients (r = 0.86, p < 0.0001). We then examined the accuracy of the two equations: the original regression equation (RVEF = 2.01 x TAPSE + 0.6) and the simplified prediction equation (RVEF = 2 x TAPSE). Bland-Altman plot showed that the mean difference +/- A limits of agreement was 0.0 +/- A 10.6 for the original equation and -0.6 +/- A 10.6 for the simplified equation. Intraclass correlation coefficient was 0.84 for the original and 0.82 for the simplified equation. Normal RVEF was considered to be a parts per thousand yen40 % based on the data from 53 matched controls, and the best TAPSE cut-off value to determine reduced RVEF (< 40 %) was calculated to be 19.7 mm (sensitivity 88.9 %, specificity 84.6 %). A simple equation of RVEF = 2 x TAPSE enables easy prediction of RVEF using TAPSE, an easily measurable M-mode index of echocardiography. TAPSE of 19.7 mm predicts reduced RVEF in PH patients with clinically acceptable sensitivity and specificity.
• 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 (一社)日本脈管学会 53 (December) 242 - 243 0387-1126 2013/12 [Refereed][Not invited]
  
• 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) 0009-7322 2013/11/26 [Refereed][Not invited]
  
• 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) 0009-7322 2013/11/26 [Refereed][Not invited]
  
• 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) 0009-7322 2013/11/26 [Refereed][Not invited]
  
• 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  1323-7799 2013/11 [Refereed][Not invited]
  
• 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  1323-7799 2013/11 [Refereed][Not invited]
  
• 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  1323-7799 2013/11 [Refereed][Not invited]
  
• 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 1619-7070 2013/10 [Refereed][Not invited]
   

  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 0167-5273 2013/09 [Refereed][Not invited]
   

  Background: Few studies have focused on right atrial (RA) structure and function in pulmonary hypertension (PH). We sought to evaluate RA volume and phasic function using cardiac magnetic resonance (CMR), and to examine their clinical relevance in PH. Methods: We prospectively studied 50 PH patients and 21 control subjects. RA volume and indices of phasic function (reservoir volume, ejection fraction [EF], and conduit volume) were evaluated by CMR. Results: Maximum RA volume index was significantly higher in PH patients (56 [44-70] ml/m(2)) than in controls (40 [30-48] ml/m(2)) (p<0.001). Reservoir volume index was significantly lower in PH than in controls (p<0.001), but conduit volume index was higher in PH than in controls (p=0.008). RA EF was similar when comparing the two groups (p=0.925). Interestingly, RA EF was increased in PH patients with WHO functional class III patients as compared with controls (p<0.001) but was reduced in advanced PH patients with WHO functional class IV (p<0.01). Maximum RA volume and RA EF significantly correlated with pulmonary hemodynamic indices, atrial and brain natriuretic hormone levels, and CMR-derived right ventricular indices. By contrast, RA reservoir volume correlated with cardiac index and 6-minute walk distance. Conclusions: PH is associated with increased size, decreased reservoir function, and increased conduit function of the right atrium. RA systolic function indicated by RA EF increases in patients with mild to moderate PH but decreases in patients with advanced PH. Varying associations between RA indices and conventional PH indices suggest their unique role in the management of PH. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
• 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 0903-1936 2013/09/01 [Refereed][Not invited]
  
• 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 0903-1936 2013/09/01 [Refereed][Not invited]
  
• 【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 (株)メジカルビュー社 17 (7) 692 - 699 1342-6591 2013/07
• 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  1932-6203 2013/06 [Refereed][Not invited]
   

  Background: This study investigated the major clinical determinants of late gadolinium enhancement (LGE) at ventricular insertion points (VIPs) commonly seen in patients with pulmonary hypertension (PH). Methods: Forty-six consecutive PH patients (mean pulmonary artery pressure >= 25 mmHg at rest) and 21 matched controls were examined. Right ventricular (RV) morphology, function and LGE mass volume at VIPs were assessed by cardiac magnetic resonance (CMR). Radial motion of the left ventricular (LV) wall and interventricular septum (IVS) was assessed by speckle-tracking echocardiography. Paradoxical IVS motion index was then calculated. Univariate and multivariate regression analysis were conducted to characterize the relationship between LGE volume at VIPs and PH-related clinical indices, including the paradoxical IVS motion index. Results: Mean pulmonary arterial pressure (MPAP) of PH patients was 3869 mmHg. LGE at VIPs was observed in 42 of 46 PH patients, and the LGE volume was 2.02 mL (0.47-2.99 mL). Significant correlations with LGE volume at VIPs were observed for MPAP (r = 0.50) and CMR-derived parameters [RV mass index (r = 0.53), RV end-diastolic volume index (r = 0.53), RV ejection fraction (r = -0.56), and paradoxical IVS motion index (r = 0.77)]. In multiple regression analysis, paradoxical IVS motion index alone significantly predicted LGE volume at VIPs (p<0.001). Conclusions: LGE at VIPs seen in patients with PH appears to reflect altered IVS motion rather than elevated RV pressure or remodeling. Long-term studies would be of benefit to characterize the clinical relevance of LGE at VIPs.
• 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 (一社)日本糖尿病学会 56 (Suppl.1) S - 362 0021-437X 2013/04
• 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  0735-1097 2013/03/12 [Refereed][Not invited]
  
• 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 (一社)日本呼吸器学会 2 (増刊) 160 - 160 2186-5876 2013/03
• 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 (一社)日本呼吸器学会 2 (増刊) 179 - 179 2186-5876 2013/03
• 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 1569-5794 2013/02 [Refereed][Not invited]
   

  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 0048-0428 2013/02
• 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 2213-0071 2013 [Refereed][Not invited]
   

  Some patients with group 3 pulmonary hypertension (PH) (PH due to lung disease and/or hypoxia) exhibit disproportionately advanced or " out-of-proportion" PH. In the present case series, we document four consecutive patients with progressive out-of-proportion group 3 PH. All patients exhibited progressive dyspnea or peripheral edema and were treated by pulmonary artery hypertension (PAH)-specific vasodilator(s). At the follow-up assessment 3-4 months later, symptoms/signs and pulmonary hemodynamic measurements improved in all four patients (45 ± 8% decrease in pulmonary vascular resistance). Pulmonary oxygenation deteriorated in one patient but improved or did not significantly change in the remaining three cases. Importantly, the background lung parenchymal disease (early-onset chronic obstructive pulmonary disease, rheumatoid arthritis-associated interstitial pneumonia, and combined pulmonary fibrosis and emphysema) was stable upon progression of the right heart failure symptoms/signs, and also during the 3-4-month follow-up period in all cases. We herein describe the clinical features of the four cases and discuss the potential benefits and risks of PAH-specific treatment in this emerging population. © 2013 Elsevier Ltd.
• 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 2051-3380 2013 [Refereed][Not invited]
   

  A 69-year-old man with progressive dyspnea was referred to our hospital in Oct 2010. The patient was clinically diagnosed with combined pulmonary fibrosis and emphysema (CPFE) and pulmonary hypertension (PH). Sildenafil and bosentan were used for the treatment of progressive PH, and dyspnea and pulmonary hemodynamics improved at 3 months follow-up. However, the patient died of respiratory failure 1 year later. Autopsy identified marked intimal and medial thickening of the pulmonary arteries/arterioles, and modest but broad fibrous obstruction of the veins/venules and capillary multiplication. Also, immunohistochemical study showed positive staining for the target proteins of the PH-specific vasodilators, sildenafil and bosentan, on the diseased vessels. The present autopsy report is the first to pathologically document the diseased pulmonary vasculature and how PH-vasodilators can ameliorate pulmonary hemodynamics in a patient with CPFE and PH.
• 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 (一社)日本糖尿病学会 56 (1) 52 - 52 0021-437X 2013/01
• 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 1774-024X 2012/10 [Refereed][Not invited]
   

  Aims: The purpose of this study was to investigate the vascular response of the everolimus-eluting stent (EES) compared with the paclitaxel-eluting stent (PES) using serial intravascular ultrasound (IVUS). Methods and results: Data were obtained from the SPIRIT III trial, a multicentre, 2:1 randomised, controlled study comparing EES and PES in de novo native coronary artery lesions. IVUS images were eligible for volumetric analysis at eight-month follow-up in 158 lesions (EES: 113, PES: 45). At eight months, EES had a smaller neointimal volume index (VI: mm(3)/mm) (EES: 0.4 +/- 0.4 vs. PES: 0.8 0.8 mm(3)/mm, p=0.002) and also a smaller % neointimal obstruction (EES: 7.1 +/- 6.7% vs. PES: 11.1 +/- 10.5%, p=0.005) compared with PES. While there was no significant change in vessel VI with EES, there was a significant increase in vessel VI in PES during eight-month follow-up (EES: 0.1 +/- 1.2 vs. PES: 1.2 0.8 mm(3)/mm, p=0.001). There were no statistical differences in the frequency of edge dissection or incomplete stent apposition between the two groups. Conclusions: Detailed IVUS analysis confirmed significantly less neointimal hyperplasia with EES compared with PES. While there was no increase in vessel volume with EES during the eight-month follow-up period, vessel enlargement was seen at the stented segment in PES.
• 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 (一社)日本糖尿病学会 55 (10) 828 - 828 0021-437X 2012/10
• 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 ライフサイエンス出版(株) 33 (10) 1469 - 1471 0289-8020 2012/10 

  心臓MRIの右室駆出率(RVEF)をgold standardとして、肺高血圧患者のRVEFを最もよく表す心エコー指標を検討した。肺高血圧症評価のために入院した37例を対象とした。5つの心エコー指標はすべて心MRIのRVEFと有意に相関し、五つの心エコー指標のなかで、TAPSEが最も相関係数が高値であり、重回帰分析ではTAPSEのみが有意に心MRIによるRVEFを予測する因子であった。サブグループ解析でも同様の結果で、TAPSEが心MRIのRVEFとの相関係数が最も高値であった。
• 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 0167-5273 2012/06 [Refereed][Not invited]
  
• 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 0161-5505 2012/05/01 [Refereed][Not invited]
  
• 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 0161-5505 2012/05/01 [Refereed][Not invited]
  
• 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 0161-5505 2012/05/01 [Refereed][Not invited]
  
• 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 (一社)日本糖尿病学会 55 (Suppl.1) S - 258 0021-437X 2012/04
• 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 0894-7317 2012/03 [Refereed][Not invited]
   

  Background: The accuracy of echocardiographic parameters of right ventricular (RV) function has not been sufficiently validated in patients with pulmonary hypertension (PH). The aim of this study was to evaluate whether echocardiographic measurements reliably reflect RV systolic function in PH using cardiac magnetic resonance imaging (CMRI)-derived RV ejection fraction (RVEF) as a gold standard. Methods: A total of 37 consecutive patients with PH, 20 with pulmonary arterial hypertension, 12 with chronic thromboembolic PH, and five others, were prospectively studied. All patients underwent echocardiography, CMRI, and right-heart catheterization within a 1-week interval. Associations between five echocardiography-derived parameters of RV systolic function and CMRI-derived RVEF were evaluated. Results: All five echocardiography-derived parameters were significantly correlated with CMRI-derived RVEF (percentage RV fractional shortening: r = 0.48, P = .0011; percentage RV area change: r = 0.40, P = .0083; tricuspid annular plane systolic excursion [TAPSE]: r = 0.86, P < .0001; RV myocardial performance index: r = -0.59, P < .0001; and systolic lateral tricuspid annular motion velocity: r = 0.63, P < .0001). Compared with the other indices, TAPSE exhibited the highest correlation coefficient. Of the five echocardiographic measurements, only TAPSE significantly predicted CMRI-derived RVEF in multiple regression analysis (P < .0001). Intraobserver and interobserver reproducibility was favorable for all five indices and was particularly high for TAPSE and systolic lateral tricuspid annular motion velocity. Conclusions: Echocardiographic measurements are promising noninvasive indices of RV systolic function in patients with PH. In particular, TAPSE is superior to other indices in accuracy. (J Am Soc Echocardiogr 2012;25:280-6.)
• 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 1553-8389 2012/03 [Refereed][Not invited]
  
• 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 1346-9843 2012/01 [Refereed][Not invited]
  
• 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 1042-3931 2012/01 [Refereed][Not invited]
   

  Background. There has been no detailed intravascular ultrasound (IVUS) analysis to evaluate the degree to which stent underexpansion or reference vessel/stent size mismatch contributes to the occurrence of post-procedural incomplete stent apposition (post-ISA). Methods. We evaluated 238 lesions treated with everolimus-eluting stents (n = 110) or paclitaxel-eluting stents (n = 128). Reference lumen/stent area ratio was defined as the ratio of lumen area adjacent to the stent edge in the reference segment to stent area at the stent edge or at stent body ISA site. Results. Post-ISA was observed in 36 of the 238 cases (15%) at the proximal stent edge, 15 of the 238 cases (6%) at the distal stent edge and 14 of the 238 cases (6%) at stent body. Reference lumen/stent area ratio was significantly greater in the ISA group compared with non-ISA in proximal edge (127 +/- 20 vs 99 +/- 10%; P<.001), and greater reference lumen/stent area ratio (118 +/- 18 vs 94 +/- 11%; P<.001) and higher presence of calcification (60 vs 29%; P<0.001) were observed in distal edge ISA group compared with non-ISA. At the stent body, presence of calcification was more frequently observed in the ISA compared with the non-ISA group (86 vs 42%; P=.002). Conclusions. Post-ISA at the stent edge was significantly associated with vessel/stent mismatch rather than stent underexpansion. IVUS-guided appropriate stent or balloon sizing might be useful to prevent post-ISA and optimize initial stent deployment. J INVASIVE CARDIOL 2012;24(1):13-16
• 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 0025-7931 2012 [Refereed][Not invited]
   

  Here we present a case of hepatopulmonary syndrome (HPS) where spontaneous resolution of severe hypoxaemia occurred with the development of pulmonary hypertension over several years after the initial diagnosis of HPS. The pulmonary vascular responses to hypoxia examined before and after the spontaneous resolution of HPS confirmed that the pathogenesis of HPS could be functional and reversible in nature. To the best of our knowledge, this is the first report demonstrating a remarkable change in the pulmonary vascular response to hypoxia before and after the spontaneous resolution of hypoxaemia in HPS. Copyright (c) 2012 S. Karger AG, Basel
• 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) 0009-7322 2011/11/22 [Refereed][Not invited]
  
• 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) 0009-7322 2011/11/22 [Refereed][Not invited]
  
• 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 ライフサイエンス出版(株) 32 (10) 1214 - 1216 0289-8020 2011/10 

  53歳男。30年前にB型慢性肝炎と診断され、15年前から当院に通院していた。14年前に食道静脈瘤が出現し、4ヵ月前に食道静脈瘤再発のため入院、心電図で肺高血圧症が疑われ、当科に紹介された。精査により門脈肺高血圧症と診断、その症状は急速に増悪し、3ヵ月間でWHO FC I→IVとなった。治療薬は初めepoprostenolを考えたが、血小板減少を認め、鼻出血もあることから使用は困難と判断、ambrisentanとtadalafilで治療し、改善が得られた。
• 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 0961-2033 2011/10/01 [Not refereed][Not invited]
   

  Pulmonary arterial hypertension (PAH) is a life-threatening complication in connective tissue diseases (CTD). It remains controversial whether immunosuppressive therapy is useful for PAH associated with CTD (PAH-CTD). The Dana Point algorithm does not refer such treatments in patients with PAH-CTD due to the lack of evidence. However, some case reports have shown the potential efficacy of immunosuppression for PAH-CTD. Here we report five cases of PAH-CTD treated with corticosteroids and discuss the current management of PAH-CTD with immunosuppressive agents. Our cases consisted of three active systemic lupus erythematosus (SLE), a quiescent SLE and an active polymyositis. WHO functional classes at baseline were class III in three cases and class II in two. Median follow-up period was 44 (28-92) weeks. PAH was diagnosed by right heart catheterization in all cases (median pulmonary arterial pressure was 45 (29-49) mmHg). All patients received 1 mg/kg of prednisolone (PSL) for 2-4 weeks, followed by appropriate dose reduction. Methylprednisolone pulse therapy was performed in patients resistant to the high dosage of PSL. Four patients received vasodilators in combination. The therapy as above improved WHO functional class 4 weeks after the initiation of PSL in all the patients. Two patients required dose increase or additional administration of vasodilators due to the dose reduction of PSL. Corticosteroid therapy may be effective for PAH-CTD at least in the short term, even in low general activity of CTD or moderate PAH. Our experience suggests that corticosteroid therapy, by itself or in conjunction with standard vasodilators, is effective for PAH-CTD patients. © The Author(s), 2011. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav.
• 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 1619-7070 2011/09 [Refereed][Not invited]
   

  Cardiac sarcoidosis (CS) is a rare and potentially life-threatening disease that causes conduction disturbance, systolic dysfunction, and most notably sudden cardiac death. Accurate diagnosis of CS is thus mandatory however, a reliable approach that enables diagnosis of CS with high sensitivity and specificity has yet to be established. Recent studies have demonstrated the promising potential of 18F-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET) in the diagnosis and assessment of CS. Indeed, 18F-FDG PET provides a wide variety of advantages over previous imaging modalities however, there are pitfalls and limitations that should be recognized. In this review article, (1) the rationale for 18F-FDG PET application in CS, (2) suitable pretest preparations, and (3) evaluation protocols for the 18F-FDG PET images obtained will be addressed. In particular, sufficient suppression of physiological 18F-FDG uptake in the heart is essential for accurate assessment of CS. Also, (4) recent studies addressing the diagnostic role of 18F-FDG PET and (5) the clinically important differences between 18F-FDG PET and other imaging technologies will be reviewed. For example, active sarcoid lesions and their response to steroid treatment will be better detected by 18F-FDG PET, whereas fibrotic lesions might be shown more clearly by magnetic resonance imaging or other nuclear myocardial perfusion imaging. In the last decade, 18F-FDG PET has substantially enhanced detection of CS however, CS would be better evaluated by a combination of multiple modalities. In the future, advances in 18F-FDG PET and other emerging imaging modalities are expected to enable better management of patients with sarcoidosis. © Springer-Verlag 2011.
• 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  0735-1097 2011/04/05 [Refereed][Not invited]
  
• 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 0903-1936 2011/04/01 [Not refereed][Not invited]
  
• 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 (一社)日本糖尿病学会 54 (2) 143 - 143 0021-437X 2011/02
• 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 0918-2918 2011 [Refereed][Not invited]
   

  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 0167-5273 2010/09 [Refereed][Not invited]
  
• 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 0009-7322 2010/08 [Refereed][Not invited]
  
• 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 0002-9149 2010/08 [Refereed][Not invited]
   

  Previous reports have shown the advantage of paclitaxel compared to limus-derivative drugs for the treatment of diabetics. A total of 109 diabetics (115 lesions) treated with everolimus-eluting stents (EESs, n = 58) or paclitaxel-eluting stents (PESs, n = 55) undergoing 8 to 9 months of follow-up 3-dimensional intravascular ultrasound examinations were enrolled. In addition to the standard intravascular ultrasound parameters, the percentage of neointimal volume (neointimal volume/stent volume) and maximum percentage of cross-sectional narrowing (neointimal area/stent area) was calculated. EESs showed a lower percentage of neointimal volume (7.2 +/- 7.1% vs 11.7 +/- 11.0%; p = 0.01) and maximum percentage of cross-sectional narrowing (22.5 +/- 16.3% vs 29.4 +/- 19.2%; p = 0.04) than PESs. One case of severe narrowing (lesions with maximum percentage of cross-sectional narrowing >60%) in the EES group developed and 6 cases in the PESs group (p = 0.05). The EESs showed no serial changes for vessel or peri-stent plaque during the follow-up period, and PESs showed significant increases in vessel and peri-stent plaque. PESs showed significantly greater peri-stent plaque increase, with a tendency toward greater vessel enlargement than EESs. Late acquired incomplete stent apposition was observed in 2 PES cases. The major adverse cardiac event rate was comparable <= 2 years. In conclusion, EESs showed greater neointimal suppression without significant vessel expansion than PESs in diabetic patients. In this small cohort, no significant differences were observed in the major adverse cardiac event rate <= 2 years. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;106:492-497)
• 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 0002-9149 2010/07 [Refereed][Not invited]
   

  The aim of this study was to evaluate the vascular response after everolimus-eluting stent (EES) implantation in the SPIRIT III Japan Registry (JAPAN) compared to EES implantation in the SPIRIT III United States (USA) trial using serial intravascular ultrasound (IVUS) analysis. Data were obtained from the JAPAN and the randomized EES arm of the USA trial. Serial (postprocedure and 8-month follow-up) IVUS analysis was available in 199 lesions (JAPAN 82, USA 117) of 183 patients (JAPAN 73, USA 110). Although no difference was observed in vessel size in the reference segment between the 2 groups, postprocedure minimum lumen area and stent volume index were significantly greater in the JAPAN arm (minimum lumen area 5.8 +/- 2.2 vs 5.1 +/- 1.5 mm(2), p = 0.03; stent volume index 7.0 +/- 2.4 vs 6.3 +/- 1.7 mm(3)/mm, p = 0.03). Postprocedure incomplete stent apposition (ISA) was less frequently observed in the JAPAN arm (15.9% vs 33.3%, p = 0.006), possibly related to higher maximum balloon pressure and/or more postdilatation without excess tissue prolapse or edge dissection. In the JAPAN arm, percent neointimal obstruction and maximum percent cross-sectional narrowing were significantly lower at 8-month follow-up (percent neointimal obstruction 3.5 +/- 4.2% vs 6.8 +/- 6.4%, p = 0.0004). Late acquired ISA was infrequent in the 2 arms. In conclusion, comparative IVUS analysis between the JAPAN and USA arms showed more optimal stent deployment in the JAPAN arm as evidenced by the lower incidence of postprocedure ISA and larger minimum lumen area after the procedure. Moreover, there was less neointimal hyperplasia in patients with EES implants from the JAPAN arm compared to the USA arm. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;106:13-17)
• 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  0012-1797 2010/06 [Refereed][Not invited]
  
• 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  0012-1797 2010/06 [Refereed][Not invited]
  
• 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 1346-9843 2010/05 [Refereed][Not invited]
   

  Background: Overlapping drug-eluting stents might be associated with an adverse vessel response because of increased drug/polymer toxicity and lesion rigidity. Methods and Results: Lesions treated with overlapping everolimus- (EES=36) or paclitaxel-eluting stents (PES=38) were analyzed for 8-9-months by 3-dimensional intravascular ultrasound. EES were associated with significantly greater neointimal suppression in the single-strut regions than PES, with a similar trend in the overlap region. PES had significant vessel expansion in all regions, whereas there were no changes with EES. Neither stent fracture nor late incomplete stent apposition (LISA) in the overlap region was observed. Conclusions: Overlapping EES appears to be effective without vessel expansion, stent fracture or LISA for up to 8-9 months. (Circ J 2010; 74: 1023-1025)
• 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 1569-5794 2010/03 [Refereed][Not invited]
   

  A 45-year-old man, who had been diagnosed with primary pulmonary hypertension (PPH) 8 years before, was referred to our hospital because of short breath and lower-limb edema. Findings of chest X-ray, electrocardiogram, and cardiac ultrasound showed right atrial and ventricular dilatation/hypertrophy that were compatible with advanced PPH. Chest enhanced computed tomography (CT), however, unexpectedly showed that contrast in the main pulmonary artery was diluted by blood flow from the descending aorta. On electrocardiography-synchronized CT, the arterial duct connecting the main pulmonary artery and descending aorta was clearly delineated. As a result, the long-standing diagnosis of PPH was corrected to secondary pulmonary arterial hypertension caused by patent ductus arteriosus, thanks to the "reverse" enhancement on CT.
• 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 1042-3931 2009/12 [Refereed][Not invited]
   

  Background. Preprocedual C-reactive protein (CRP) has been reported to correlate with in-stent restenosis following bare-metal stem implantation. The aim of this study was to investigate the impact of preprocedural inflammation on neointimal hyperplasia assessed by intravascular ultrasound (IVUS) following everolimus-eluting stern (EES) implantation. Methods. We identified 134 patients meeting the following criteria: 1) patients treated with EES; 2) those with stable or unstable angina; and 3) patients available for high-sensitivity (hs)-CRP before the procedure and volumetric IVUS analysis at follow up. We divided the patients into two groups on the basis of hs-CRP levels (<3 or a >= 3 mg/L) before the procedure and compared IVUS parameters. Volume index (volume/length) was calculated for vessel (VVI), plaque (PVI), neointima (NIV), stem (SVI), and lumen (LVI). Percent neointimal volume (%NIV) was calculated as (NIV/SVI) x 100. Cross-sectional narrowing (CSN) was defined as neointimal area divided by stem area (%). Results. There was no significant difference in VVI, PVI, or LVI at either baseline or 8-month follow up between the two groups. At 8-month follow up, there was also no significant difference in %NIV (4.93 +/- 5.66% vs. 4.98 +/- 5.25 %;p = 0.959) and maximum %CSN (16.81 +/- 13.62% vs. 18.14 +/- 13.91 %; p = 0.608) as well as VVI, PVI, and LVI between the two groups. Furthermore, hs-CRP did not correlate with %NIV (r = 0.044; p = 0.610) and maximum %CSN (r = 0.086, p = 0.321) at follow up. There was no significant difference in incidence of late-acquired incomplete stern apposition between the two groups (1.2% vs. 0%; p = 0.512). Conclusion. Our results suggest that preprocedural inflammation does not affect neointimal hyperplasia following EES implantation.
• 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 ライフ・サイエンス 29 (8) 2043 - 2048 0287-3648 2009/08/10 [Not refereed][Not invited]
   

  近年、胆汁酸吸着レジンであるコレスチミドには、血中コレステロール値を低下させるだけでなく、血糖値を低下させる作用を併せ持つことが報告されている。胆汁酸とエネルギー代謝との関連が明らかになってきており、コレスチミドの血糖降下作用のメカニズムにも胆汁酸分画の変化が関与している可能性もある。われわれは、外来通院中で高LDLコレステロール血症を伴う2型糖尿病患者19例に対しコレスチミドを12週間投与し、血中胆汁酸分画の変化と血糖降下作用との関連を検討した。投与後、血中LDLコレステロール値の低下とともに、臍周囲径、空腹時血糖値、HbA1c、HOMA-Rの有意な低下を認めた。しかし、血中総胆汁酸濃度とその分画の濃度には変化を認めず、HbA1cや臍周囲径の変化との相関関係も認められなかった。コレスチミドによる血糖降下作用は、血中胆汁酸分画の変化とは関連せず、他の機序が関与していることが示唆された。(著者抄録)
• 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 1936-8798 2009/08 [Refereed][Not invited]
   

  Objectives The aim of this study was to compare the vessel response between zotarolimus-eluting stents (ZES) and paclitaxel-eluting stents (PES) using intravascular ultrasound. Background The ENDEAVOR IV (Randomized Comparison of Zotarolimus- and Paclitaxel-Eluting Stents in Patients With Coronary Artery Disease) trial was a randomized controlled study of zotarolimus-eluting, phosphorylcholine-coated, cobalt-alloy stents for the treatment of de novo coronary lesions compared with using PES for the same treatment. Methods Data were obtained from patients with serial (baseline and 8-months follow-up) intravascular ultrasound analysis available (n = 198). Volumetric analysis was performed for vessel, lumen, plaque, stent, and neointima. Cross-sectional narrowing (given as percentage) was defined as neointimal area divided by stent area. Neointima-free frame ratio was calculated as the number of frames without intravascular ultrasound-detectable neointima divided by the total number of frames within the stent. Subsegment analysis was performed at every matched 1-mm subsegment throughout the stent. Results At follow-up, the ZES group showed significantly greater percentage of neointimal obstruction (16.6 +/- 12.0% vs. 9.9 +/- 8.9%, p < 0.01) and maximum cross-sectional narrowing (31.8 +/- 16.1% vs. 25.2 +/- 14.9%, p < 0.01) with smaller minimum lumen area than the PES group did. However, the incidence of maximum cross-sectional narrowing >50% was similar in the 2 groups. Neointima-free frame ratio was significantly lower in the ZES group. In overall analysis, whereas the PES group showed positive remodeling during follow-up (13.7 +/- 4.2 mm(3)/mm to 14.3 +/- 4.3 mm(3)/mm), the ZES group showed no significant difference (12.7 +/- 3.6 mm(3)/mm to 12.9 +/- 3.5 mm(3)/mm). In subsegment analysis, significant focal positive vessel remodeling was observed in 5% of ZES and 25% of PES cases (p < 0.05). Conclusions There were different global and focal vessel responses for ZES and PES. Both drug-eluting stents showed a similar incidence of lesions with severe narrowing despite ZES having a moderate increase in neointimal hyperplasia compared with neointimal hyperplasia in PES. There was a relatively lower neointima-free frame ratio in ZES, suggesting a greater extent of neointimal coverage. (The ENDEAVOR IV Clinical Trial: A Trial of a Coronary Stent System in Coronary Artery Lesions; NCT00217269) (J Am Coll Cardiol Intv 2009;2:779-84) (C) 2009 by the American College of Cardiology Foundation
• 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 0013-7227 2008/12 [Refereed][Not invited]
   

  Obesity is a condition in which adipose tissue mass is expanded. Increases in both adipocyte size and number contribute to enlargement of adipose tissue. The increase in cell number is thought to be caused by proliferation and differentiation of preadipocytes. Macrophage migration inhibitory factor (MIF) is expressed in adipocytes, and intracellular MIF content is increased during adipogenesis. Therefore, we hypothesized that MIF is associated with adipocyte biology during adipogenesis and focused on the influence of MIF on adipogenesis. To examine the effects of MIF on adipocytes, MIF expression in 3T3-L1 preadipocytes was inhibited by RNA interference, and cell differentiation was induced by standard procedures. The triglyceride content of MIF small interfering RNA (siRNA)-transfected 3T3-L1 cells was smaller than that of nonspecific siRNA-transfected cells. In addition, MIF knockdown apparently abrogated increases in adiponectin mRNA levels during differentiation. Gene expression of peroxisome proliferator-activated receptor (PPAR)gamma, CCAAT/enhancer binding protein (C/EBP)alpha, and C/EBP delta decreased with MIF siRNA transfection, butC/EBP beta expression increased. Cell number and incorporation of 5-bromo-2-deoxyuridine into cells decreased from 1-3 d and from 14-20 h, respectively, after induction of differentiation in MIF siRNA-transfected cells, thus suggesting that MIF siRNA inhibits mitotic clonal expansion. Taken together, these results indicated that MIF regulates differentiation of 3T3-L1 preadipocytes, at least partially, through inhibition of mitotic clonal expansion and/or C/EBP delta expression. (Endocrinology 149: 6037-6042, 2008)
• 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  0009-7322 2008/10/28 [Refereed][Not invited]
  
• 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  0002-9149 2008/10/12 [Refereed][Not invited]
  
• 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 0009-7322 2008/10 [Refereed][Not invited]
  
• 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 1042-3931 2008/08 [Refereed][Not invited]
   

  Background. Diabetes has been reported as an independent predictor of restenosis after drug-eluting stern implantation. The purpose of this study was to assess the long-term impact of increased drug dose in sirolimus-eluting stems (SES) on neointimal hyperplasia (NIH) in diabetic patients using volumetric intravascular ultrasound analysis. Methods. The 3D trial is a multicenter, prospective, randomized, feasibility study of double-dose (280 mu g/cm(2)) or conventional single-dose (140 mu g/cm(2)!) SES for the treatment of de nova coronary lesions in diabetic patients. To evaluate long-term efficacy, complete serial volumetric analyses (baseline, 6-month and 2-year follow up) were performed in 39 diabetic patients (17 single-dose, 22 double-dose). Each volume was divided by scent length to acquire volume index, expressed as mm(3)/mm. Percent neointimal volume was calculated as (neointimal volume/stent volume) x 100 at follow up. Results. Volumetric analysis showed similar results over time between the 2 scent groups (p = NS for all). At 2-year follow up, minimal increases in NIH area and percent NIH were observed in both groups, which translated into a decrease in lumen volume index compared to baseline (p < 0.05 for all). No late-acquired incomplete scent apposition was observed in either group. Conclusions. The current single dose of sirolimus in SES is effective in inhibiting NIH in diabetic patients up to 2 years. In this patient subset, double-dose SES did not confer additional NIH suppression at 2-year follow up compared to conventional single-dose SES.
• 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 1042-3931 2008/07 [Refereed][Not invited]
   

  Background. Percutaneous coronary intervention (PCI) is associated with increased clinical and angiographic restenosis in diabetic patients. Stent-based elution of paclitaxel from a biostable polymer reduces restenosis and major adverse cardiovascular events (MACE) when compared with bare-metal Milt deployment. The safety and efficacy of paclitaxel elution from a bioresorbable polymer has not been studied in diabetic patients. Methods. Patients (n = 1700) with single- or multivessel coronary disease were randomized (3:2) to receive the CoStar (R) or Taxus (R) stent. All patients had glycolated hemoglobin (HbA1c) obtained at enrollment. Results. Medically-treated diabetes was present in 469 patients (117 insulin-treated) and 77 patients had elevated HbA1c > 6.5% in the absence of previously diagnosed diabetes. MACE were increased in diabetics and were greatest in those requiring insulin. Elevated HbA1c, in the absence of diagnosed diabetes, was not associated with adverse outcomes. MACE (8 months) in the diabetic cohort trended lower with Taxus versus CoStar (10.9 vs. 14.4%, respectively; p = 0.271) due to a reduction in target vessel revascularization. Late lumen loss in-segment (9 months) was reduced by Taxus compared to CoStar (0.20 vs. 0.52 mm, respectively; p < 0.05). Conclusion. Diabetes is associated with adverse outcomes following scent deployment. Taxus stents improved angiographic outcomes with a trend toward improved clinical outcomes when compared with CoStar stents following PCI in diabetic patients. As a measure of preprocedural glycemic control, the HbA1c level was weakly correlated with outcomes.
• 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  0012-1797 2008/06 [Refereed][Not invited]
  
• 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 1619-7070 2008/05 [Refereed][Not invited]
   

  Despite accumulating reports on the clinical value of F-18-fluoro-2-deoxyglucose positron emission tomography (F-18-FDG PET) and magnetic resonance imaging (MRI) in the assessment of cardiac sarcoidosis, no studies have systematically compared the images of these modalities. Twenty-one consecutive patients with suspected cardiac sarcoidosis underwent cardiac examinations that included F-18-FDG PET and MRI. The association of F-18-FDG PET and MRI findings with blood sampling data such as serum angiotensin converting enzyme levels was also evaluated. Eight of 21 patients were diagnosed as having cardiac sarcoidosis according to the Japanese Ministry of Health and Welfare Guidelines for Diagnosing Cardiac Sarcoidosis. Sensitivity and specificity for diagnosing cardiac sarcoidosis were 87.5 and 38.5%, respectively, for F-18-FDG PET, and 75 and 76.9%, respectively, for MRI. When the F-18-FDG PET and MRI images were compared, 16 of 21 patients showed positive findings in one (n=8) or both (n=8) of the two modalities. In eight patients with positive findings on both images, the distribution of the findings differed among all eight cases. The presence of positive findings on F-18-FDG PET was associated with elevated serum angiotensin-converting enzyme levels; this association was not demonstrated on MRI. Both F-18-FDG PET and MRI provided high sensitivity for diagnosing cardiac sarcoidosis in patients with suspected cardiac involvement, but the specificity of F-18-FDG PET was not as high as previously reported. The different distributions of the findings in the two modalities suggest the potential of F-18-FDG PET and MRI in detecting different pathological processes in the heart.
• 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 0002-8703 2008/01 [Refereed][Not invited]
   

  Background The purpose of this study was to investigate the vascular response of zotarolimus-eluting stent (ZES) and sirolimus-eluting stent (SES) using serial intravascular ultrasound (IVUS). Methods Data were obtained from the Endeavor Drug-Eluting Coronary Stent System Versus the Center Siromlimus-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions (ENDEAVOR) III trial, a randomized study comparing ZES and SES for the treatment of de novo native coronary artery lesions. Serial (baseline and 8-month follow-up) IVUS was available in 258 patients (190 ZES, 68 SES). Results At 8 months, ZES had greater percentage of neointimal volume index (ZES 1.1 +/- 0.8 mm(3)/mm vs SES 0.2 +/- 0.1 mm(3)/mm, P <.01), resulting in smaller lumen volume index (6.0 +/- 2.0 mm(3)/mm vs 7.0 +/- 2.1 mm(3)/mm, P <.05). Zotarolimus-eluting stents showed larger IVUS-detectable neointimal coverage over stent surface (50.2% vs 10.5%, P <.01) and greater mean neointimal thickness (0.19 +/- 0.07 mm vs 0.10 +/- 0.06 mm, P <.01). Zotarolimus-eluting stents had a significantly lower incidence of late-acquired incomplete stent apposition. Conclusions Zotarolimus-eluting stent is associated with a significantly greater amount of neointimal hyperplasia compared with SES. This amount of hyperplasia in ZES is distributed throughout the stent at 8-month follow-up.
• 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 公益財団法人 日本心臓財団 40 (11) 983 - 988 0586-4488 2008 

  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 1042-3931 2007/12 [Refereed][Not invited]
   

  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 1346-9843 2007/11 [Refereed][Not invited]
   

  Background Oral prostacyclin analogs can improve the prognosis of patients with mild to moderate pulmonary arterial hypertension (PAH), but because they often provoke adverse effects, such as flushing and dizziness, administering the optimal dose can be difficult. Methods and Results In the present study, a novel long-acting oral beraprost (TRK-100STP: 0-360 mu g/day for 12 weeks) was administered to 4 patients with mild to moderate PAH. The patients tolerated the drug well with mild adverse manifestations and negligible effects on the systemic circulation. In contrast, pulmonary vascular resistance decreased by 27+/-12% and the 6-min walk test distance increased by 11+/-11%. Conclusions TRK-100STP is a novel option in the medical management of patients with PAH.
• 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 1742-5247 2007/05 [Refereed][Not invited]
   

  Drug-eluting stents (DESs) have revolutionized the treatment of occlusive coronary artery disease via marked reduction of in-stent restenosis. One critical feature for successful DESs is the sustained release of drugs, which is achieved using a polymer coating in the present generation of DESs. However, recent studies have raised a concern that polymers may trigger allergic reactions and/or prolonged inflammation in some patients. These untoward reactions may eventually lead to undesirable clinical events, including stent thrombosis and sudden cardiac death. A new drug delivery technology, using a porous stent surface, may offer desirable drug elution properties without the use of polymers, and may translate into an improved safety profile for the next-generation DESs.
• 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 1042-3931 2007/04 [Refereed][Not invited]
   

  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 0040-6376 2006/11 [Refereed][Not invited]
   

  The case history is presented of a patient with Trousseau's syndrome in which tissue factor originating from lung cancer appeared responsible for recurrent DVT/PE. This is thought to be the first such case to be reported.
• 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 1053-2498 2006/04 [Refereed][Not invited]
   

  The patient investigated was a 43-year-old woman with primary pulmonary hypertension (PPH) and refractory protein-losing enteropathy (PLE). She underwent living-donor lobar lung transplantation (LDLLT), which led to remarkable improvement in both pulmonary hypertension and PLE. Although there have been no reports, to our knowledge, that have demonstrated PLE as a complication of PPH, the present case clearly shows how PLE could complicate PPH. In addition, and more importantly, hypo-proteinemia due to PLE should not necessarily be an exclusion criterion for lung transplantation when PPH is involved, because it could markedly improve after transplantation.
• 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 0006-291X 2006/01 [Refereed][Not invited]
   

  Increased oxidative stress has been associated with obesity-related disorders. In this study, we investigated how oxidative stress, in different ways of exposure, regulates gene expression of various adipokines in 3T3-L1 adipocytes. Exposure to 100-500 mu M H2O2 for 10 min, as well as exposure to 5-25 mU/ml glucose oxidase for 18 h, similarly decreased adiponectin, leptin, and resistin mRNAs, and increased plasminogen activator inhibitor-1 mRNA. Secretion levels of adipokines were also changed by oxidative stress in parallel with mRNA expression levels. Although a peak increase in plasminogen activator. inhibitor- I mRNA was achieved between 4 and 8 h after exposure to H2O2 for 10 min, significant decreases in adiponectin and resistin mRNA were observed after 16 It, while leptin mRNA was decreased earlier. Our results suggest that oxidative stress, even of short duration, has a significant impact on the regulation of various adipokine gene expressions favoring atherosclerosis. (c) 2005 Elsevier Inc. All rights reserved.
• 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 [Refereed][Not invited]
  
• 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 1124-0490 2005/10 [Refereed][Not invited]
  
• 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 0195-668X 2005/08 [Refereed][Not invited]
   

  Aims To evaluate the value of F-18-fluoro-2-deoxyglucose positron emission tomography (F-18-FDG PET) in detecting cardiac sarcoidosis. Methods and results Thirty-two patients with sarcoidosis and thirty controls were recruited. All subjects underwent cardiac F-18-FDG PET after a 6 h fasting period, and subjects with sarcoidosis underwent blood testing, ECG, echocardiography, and Ga-67 and Tc-99m-sestamibi (MIBI) scintigraphy. We classified F-18-FDG PET images into four patterns ('none', 'diffuse', 'focal', and 'focal on diffuse') and found that all the control subjects exhibited either none (n=16) or diffuse (n=14) pattern. In contrast, fifteen subjects with sarcoidosis exhibited none, seven exhibited diffuse, eight exhibited focal, and two exhibited focal on diffuse patterns, with the prevalence of the focal and focal on diffuse patterns being significantly higher in the sarcoidosis group when compared with the control group (P=0.001), None of the 32 subjects with sarcoidosis exhibited abnormal findings on Ga-67 scintigraphy, and 4 exhibited abnormal findings on Tc-99m-MIBI scintigraphy. Conclusion Focal uptake of the heart on F-18-FDG PET images is a characteristic feature of patients with sarcoidosis. Furthermore, F-18-FDG PET has the potential to detect cardiac sarcoidosis that cannot be diagnosed by Ga-67 or Tc-99m-MIBI scintigraphy.
• 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 0895-8378 2005/08 [Refereed][Not invited]
   

  Although a number of animal studies have been conducted to investigate the toxic effects of gaseous pollutants on human airways, the anatomical and physiological differences between animals and humans represent a challenge in extrapolating the animal data to humans. The aim of this study was to examine how interspecies anatomical and physiological differences influence the transport of the inhaled gases throughout the airways and alveoli. We designed mathematical airway models of three mammalian species, rats, dogs, and humans, in which interspecies differences in airway dimensions and respiratory patterns were taken into account. We then simulated the bulk flow of three gases (ozone [O-3], nitrogen dioxide [NO2], and sulfur dioxide [SO2]) and obtained the intra-airway concentrations of the gases and the amount absorbed using these models. For all three gases, both real-time and mean concentrations in the upper and lower airways were higher in humans when compared with rats and dogs. For example, the mean concentration of O-3 in the 5th bronchi of humans was 3 and 12 times higher than in rats and dogs, respectively. Similarly, the amount of absorbed gases corrected for airway surface area was again higher in the upper and lower airways of humans than the other two species. Sensitivity analysis indicated that tidal volume, respiratory rate, and surface area of the upper and lower airways had significant impact on the results. In conclusion, kinetics of inhaled gaseous substances vary substantially among animals and humans, and such variations are, at least partially, the result of anatomical and physiological differences in their airways.
• 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 0012-3692 2005/06 [Refereed][Not invited]
   

  We encountered a 69-year-old woman displaying a filling defect within the left descending pulmonary artery (PA) on a chest CT scan and pulmonary angiography. A subsequent 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scan demonstrated focal uptake in the left hilum. A cytologic examination of transbronchial needle aspiration specimens revealed small cell carcinoma. The patient underwent concurrent radiation therapy and chemotherapy with cisplatin and etoposide, resulting in tumor shrinkage and recanalization of the involved PA. This is the first case of small cell carcinoma localized exclusively within the PA, and positive findings on FDG-PET facilitated the unexpected diagnosis.
• 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 0160-2446 2005/04 [Refereed][Not invited]
   

  Although sildenafil, an oral phosphodiesterase type-5 inhibitor, may offer benefits in the pharmacological management of pulmonary hypertension (PH), safety and effectiveness have not been studied during coadministration with beraprost, an oral prostacyclin analogue. To address this issue, we administered oral beraprost (40 mu g) on day 1 and beraprost (40 mu g) plus sildenafil (25 mg) on days 2 to 6 patients with moderate to severe PH. Although sildenatil plus beraprost produced transient flushing in 2 of 6 patients, systemic hemodynamics and arterial and venous gas analyses were similar in comparisons between the 2 treatment groups. In contrast, sildenafil plus beraprost therapy resulted in a 2.2-fold greater reduction in mean pulmonary arterial pressure and a 1.6-fold greater reduction in pulmonary vascular resistance compared with beraprost alone, and reductions in these parameters persisted longer with combination therapy than with beraprost alone. Addition of oral sildenafil to beraprost appears to represent a safe and effective therapeutic option, at least in the acute phase, for patients with pulmonary hypertension.
• 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 ライフサイエンス出版(株) 25 (10) 1987 - 1990 0289-8020 2004/10/20 [Not refereed][Not invited]
   

  Beraprostにsidenafilを追加した場合の安全性,急性効果について検討した.対象は,血栓塞栓症性肺高血圧症4例,抗原病性肺高血圧症1例,ASDによるEisenmenger症候群1例であった.副作用は,beraprost単独群,両薬剤併用群共に頭痛を1例ずつ,顔面ほてりを併用群で2例に認めたが,いずれも軽度であった.脈拍,平均体血圧,体血管抵抗は両群で明らかな差はなかったが,平均肺動脈圧は単独群に比し併用群で有意に良好な改善効果を認めた.単独群では30〜120分で有意な低下を認めたのに対し,併用群では15〜240分にいたるまで有意に低下した.併用群では肺血管抵抗の改善も有意に強く認められた
• 〈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 ライフサイエンス出版(株) 25 (6) 1236 - 1239 0289-8020 2004/06/20 [Not refereed][Not invited]
   

  31歳男.右足に倦怠感を自覚し,右下肢深部静脈血栓症(DVT),肺血栓塞栓症と診断された.warfarin治療をを行ったが,左下肢DVT,左上肢DVTを発症した.種々の凝固線溶系の精査を行ったが,原因は不明であった.呼吸困難が出現し,再入院した.胸部X線写真では右肺は中肺野に達する胸水像を認め,左中肺野には結節影と心陰影に重なる径3cmの腫瘤影を認めた.左主気管支の狭小化を認めた.右胸水の性状は血性,浸出性で,細胞診では悪性,特に腺癌を示唆する細胞集塊を一つのみ認めた.生検でadenocarcinomaとの病理学的確定診断を得た.よって,左S8原発の肺腺癌,肺血栓塞栓症,再発性の深部静脈血栓症と考えた
• 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 (一社)日本循環器学会 68 (Suppl.II) 756 - 756 1346-9843 2004/04
• 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 0289-8020 2003/09/20 [Not refereed][Not invited]
  
• 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 0012-3692 2002/11 [Refereed][Not invited]
   

  Study objective: Although the overnight increase in urinary uric acid/creatinine ratio (DeltaUA/Cr) is considered by some to be a marker of tissue hypoxia in patients with obstructive sleep apnea-hypopnea syndrome (OSAS), this index is not universally accepted. The purpose of this study was to confirm the validity of DeltaUA/Cr as a marker of tissue hypoxia by measuring the plasma level of adenosine during sleep, and also to test the hypothesis that the heart rate (HR) response to apnea is a determinant of tissue hypoxia. Design: Intergroup comparative study. Setting: A university hospital, Sapporo, Japan. Patients; Eighteen patients with OSAS who had apnea-associated, moderate-to-severe arterial desaturation. The patients were classified into two groups: the DeltaUA/Cr-positive group, who were considered to have tissue hypoxia, and the DeltaUA/Cr-normal group, who were not. Measurements and results: Although there were no significant differences between two groups of the patients in either arterial desaturation parameters or the apnea-hypopnea index, the plasma level of adenosine during sleep was significantly higher in the DeltaUA/Cr-positive group than in the DeltaUA/Cr-normal group. Successful treatment with nasal continuous positive airway pressure significantly decreased both DeltaUA/Cr and the plasma level of adenosine only in the DeltaUA/Crpositive group. The magnitude of the HR increase after the termination of apnea was significantly smaller in the DeltaUA/Cr-positive group. Conclusions; DeltaUA/Cr is a marker of tissue hypoxia, which does not necessarily parallel arterial desaturation indexes in OSAS. Intersubject variability in the HR response to apnea may explain the discrepancy between tissue hypoxia and arterial desaturation indexes.
• 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 1323-7799 2000 [Refereed][Not invited]
   

  When one sees a middle-aged male smoker who presents with progressive exertional dyspnoea and irreversible airflow obstruction, the most likely clinical diagnosis is pulmonary emphysema or chronic obstructive pulmonary disease (COPD). We report a 45-year-old male smoker who was initially suspected to have such a disease but was eventually diagnosed as having idiopathic constrictive bronchiolitis by lung biopsy, clinical history, and laboratory findings. A finding on lung computed tomography of diffuse hyperinflation but few low attenuation areas and relatively well-preserved diffusing capacity of carbon monoxide seems to be the key for suspecting this rare clinical entity. The pathological difference between this bronchiolitis and small airway disease observed in COPD will be also discussed.
• 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 1073-449X 1999/03 [Refereed][Not invited]
   

  Adenosine, a purine nucleoside, plays a variety of roles In cardiovascular and ventilatory control, and may be a marker of tissue hypoxia. There is, however, no direct evidence of an increase In plasma or in tissue levels of adenosine during moderate hypoxia in humans. We measured the plasma concentrations of adenosine in an artery and the median cubital vein simultaneously in 12 normal volunteers, and also in the internal jugular vein in seven of them during normoxia and moderate hypoxia (Sa(o2) = 80%, 20 min) with or without dipyridamole (0.6 mg/kg) pretreatment. Dipyridamole was expected to block reuptake of adenosine by red blood cells and vascular endothelial cells so that the plasma level of adenosine would more likely reflect the tissue level. Blood was sampled with an appropriate stopping solution, and adenosine was measured with a high-pressure liquid chromatographic (HPLC)-fluorometric technique. The plasma concentration of adenosine did not rise either in the artery or in the vein at any phase of hypoxia without the dipyridamole pretreatment. However, when subjects were pretreated with dipyridamole, the plasma concentration of adenosine increased significantly and markedly in a time-dependent manner during hypoxia in the vein, but not in the artery. The adenosine level rose from 20.7 +/- 2.5 nM (mean +/- SE) during normoxia to 50/7 +/- 10.7 nM at 20 min of hypoxia, and returned to the baseline level in the recovery phase. The plasma concentration of adenosine In the jugular vein did not change during hypoxia either with or without dipyridamole pretreatment. These data provide evidence that in humans, the local production of adenosine Increases during moderate hypoxia in forearm tissue, although this is not reflected in plasma unless the subject is pretreated with dipyridamole.
• 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 0012-3692 1999/02 [Refereed][Not invited]
   

  Introduction: Inhaled anticholinergic drugs are often recommended for use as a first-line therapy for patients with COPD because they provide similar or more effective bronchodilating actions, as well as fewer side effects. It is not known, however, which class of bronchodilators is more advantageous for pulmonary hemodynamics, particularly during exercise. Objectives: To compare the effects of oxitropium and fenoterol on pulmonary hemodynamics in patients with COPD at rest and during exercise. Patients: The study participants consisted of 20 consecutive male patients with stable COPD, a mean (+/- SD) age of 68 +/- 8 years old, and an FEV1/FVC ratio of 47.5 +/- 10.%, Methods: Eleven patients inhaled two puffs of oxitropium, and nine patients inhaled two puffs of fenoterol, Seven members of each group performed incremental exercise using a cycle ergometer, The hemodynamic measurements with right heart catheterization were performed by taking the average of three consecutive respiratory cycles before and after the administration of inhaled bronchodilators at rest and during exercise. Results: At rest, despite a similar improvement of spirometric data with the two drugs, fenoterol, not oxtropium, caused significant increases in heart rate and cardiac output, a decrease in pulmonary vascular resistance, and a deteriorated Pao(2). During exercise, however, both drugs similarly attenuated elevations in the mean pulmonary arterial pressure (40 +/-2 to 38 +/- mm Hg by oxitropium, and 41 +/- to 36 +/- mm Ng by fenoterol), the mean pulmonary capillary wedge pressure, and the mean right atrial pressure. Conclusion: Our findings indicate that both classes of bronchodilators are equally beneficial in the attenuation of right heart afterload during exercise in patients with COPD.
• 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 1323-7799 1999 [Refereed][Not invited]
   

  Contamination of nasal nitric oxide (NO) is a major obstacle when one needs to sample exhaled NO originating only from the lungs. To eliminate nasal NO, we used the nasal continuous negative pressure (nasal CNP) technique which, we verified, caused closure of the vellum. Exhaled gas was sampled from six healthy volunteers into fraction 1 (initially exhaled 200 mL) and fraction 2 (remainder of the gas) under three conditions while subjects were wearing a noseclip, using nasal CNP at -5, -10 and -20 cmH2O, and under endotracheal intubation. Exhaled NO concentration ([NO]) obtained with nasal CNP was significantly lower, regardless of the pressure applied, than that measured with a noseclip, and was similar to and closely correlated to that obtained under intubation (F1, r= 0.90 F2, r= 0.88 P< 0.05). Real- time recorded [NO] obtained with nasal CNP of-5 cmH2O was again lower than that measured with a noseclip at any expiratory flow rate examined, indicating nasal NO contamination was eliminated irrespective of the flow rate. In conclusion, because a nasal CNP of -5 cmH2O was easily tolerated without any discomfort, this technique is a simple, easy and effective technique to eliminate nasal NO which should be widely applicable for the measurement of exhaled [NO].
• 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 1073-449X 1996/11 [Refereed][Not invited]
   

  To gain insight into the source of exhaled nitric oxide (NO) in normal humans, we examined the effects of respiratory pattern on the concentration of NO in exhaled air while subjects were wearing a noseclip and then under endotracheal intubation, using a specially designed gas sampling system to separate exhaled air into two fractions: the initially exhaled 200 ml (Fraction 1; F-1), and the remainder (Fraction 2; F-2) We also examined the effect of hypoxic gas inhalation (FIo2 = 0.1, 3 min) on the concentration of exhaled NO. The concentration of exhaled NO measured with a chemiluminescence NO analyzer was significantly lower with intubation, by 59.2 +/- 10.6% (mean +/- SD) (F-1) and 54.4 +/- 8.0% (F-2), than without intubation. The concentration of NO in F-1 was consistently higher than that in F-2 with or without intubation. With breath holding, the concentration of NO increased markedly only in F-1. In contrast, prolongation of the expiratory phase slightly but significantly increased the concentration of NO only in F-2. Inhalation of hypoxic gas did not cause any significant change in NO concentration in either fraction. These data indicate that in normal humans wearing a noseclip, about 40 to 45% of NO in exhaled air originates from the lungs, particularly from intrathoracic airways. The concentration of exhaled NO collected from subjects wearing a noseclip is not affected by hypoxic gas inhalation.
• 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 0452-3458 1996 

  Although inhalation of nitric oxide (NO) has come to be used as a new therapeutic modality for primary pulmonary hypertension and adult respiratory distress syndrome, little attention has been paid to its toxicity to the lungs. In this study, we morphologically investigated the effects of a two-hour inhalation of 100 ppm NO on rat lungs. Microscopic examinations were performed in the lungs immediately and 22 hours after the inhalation of NO. There was no evidence of infiltration with inflammatory cells in the alveolar wall or fluid flooding in the alveoli. Observations by an electron microscopy showed no morphological changes in the alveolar epithelium, cilia and clara cells. We thus conclude that a 2-hour inhalation of 100 ppm of NO has morphologically no harmful effect on rat lungs.
• 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 0387-1207 1996 [Refereed][Not invited]
   

  A 34-year-old man came to our hospital with a complaint of epigastric discomfort. Upper gastrointestinal endoscopy revealed a sessile polyp of about 1.5 cm in diameter just proximal to esophagogastric mucosal junction. Polypectomy was performed and histological examination showed granulation tissue with irregular epithelial hyperplasia and inflammatory cell invasion. Inflammatory esophagogastric polyp is rare among benign tumors of esophagus, but it must be noted as one of the important diseases in differential diagnosis of elevated lesion of esophagus. © 1996, Japan Gastroenterological Endoscopy Society. All rights reserved.
• 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 0301-1542 1995 [Refereed][Not invited]
   

  We studied the effects of the inhaled anticholinergic agent oxitropium bromide (Ox) on pulmonary hemodynamics in eleven patients with chronic obstructive pulmonary disease. All the patients underwent right heart catheterization and seven of them underwent all incremental ergometer exercise test while in the supine position. Pulmonary hemodynamics and arterial blood gases were measured at rest and during maximal exercise, before and 30 minutes after inhalation of 2 puffs (200 μg) of Ox. Inhalation of Ox did not significantly change pulmonary hemodynamics at rest. The mean pulmonary arterial pressure and the mean pulmonary capillary wedge pressure during exercise decreased significantly (from 40.3 ± 4.6 to 37.7 ± 3.9 mmHg, and from 20.4 ± 3.5 to 17.1 ± 2.7 mmHg, respectively, mean ± SE). However, neither cardiac output nor pulmonary vascular resistance changed with inhalation of the drug, at rest or during exercise. We therefore conclude that this commonly used dose of Ox does not directly affect the pulmonary vascular system. The small but significant decreases in pulmonary arterial pressure and pulmonary capillary wedge pressure with Ox may have been indirect effects, caused by bronchodilation.

MISC

• 心臓サルコイドーシス患者におけるガドリニウム遅延造影心臓MRIとFDG-PETを用いた複合的画像評価の予後的意義

  數井 翔, 竹中 秀, 永井 利幸, 常田 慧徳, 加藤 喜哉, 小森山 弘和, 小林 雄太, 高橋 昌寛, 神谷 究, 天満 太郎, 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, 工藤 與亮, 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)  65  -65  2023/10
• Association between myocardial late gadolinium enhancement and left ventricular systolic dysfunction in pre-capillary pulmonary hypertension

  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, 村山迪史, 中鉢雅大, 常田慧徳, 辻野一三  超音波医学 Supplement  49-  2022
• Effects of hypoxia on neutrophil extracellular trap formation

  益田紗季子, 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  110-  (1)  2021
• 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, 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, 辻野一三, 西村正治, 今野哲  糖尿病(Web)  63-  (Suppl)  2020
• 左室拡張機能の評価は臨床で役に立っているのか? 肺動脈性肺高血圧症における左室充満圧推定の問題点

  岩野 弘幸, 辻野 一三, 安斉 俊久  超音波医学  46-  (Suppl.)  S262  -S262  2019/04  [Not refereed][Not invited]
  
• 北海道胆振東部地震に伴う大規模停電時の在宅酸素療法患者への対応の後方視的検討

  佐藤 峰嘉, 鈴木 雅, 松本 宗大, 武井 望, 山下 優, 木村 孔一, 木村 裕樹, 長岡 健太郎, 清水 薫子, 水柿 秀紀, 大平 洋, 品川 尚文, 辻野 一三, 南須原 康行, 今野 哲  日本呼吸器学会誌  8-  (増刊)  309  -309  2019/03  [Not refereed][Not invited]
  
• 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(Web)  56-  (Supplement)  2019
• 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(大山)徳子, 平田健司, 志賀哲  核医学(Web)  56-  (Supplement)  2019
• 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(Web)  56-  (Supplement)  2019
• 心臓サルコイドーシス患者における心電図同期心筋血流イメージングを用いた位相解析による予後評価

  小梁川 和宏, 納谷 昌直, 葛目 将人, 相川 忠夫, 真鍋 治, 大平 洋, 辻野 一三, 真鍋 徳子, 志賀 晢, 安斉 俊久  核医学  55-  (Suppl.)  S175  -S175  2018/11  [Not refereed][Not invited]
  
• 心臓サルコイドーシス患者において心筋血流イメージング位相解析は心事故を予測する

  小梁川和宏, 納谷昌直, 葛目将人, 相川忠夫, 古家翔, 真鍋治, 大平洋, 辻野一三, 真鍋徳子, 安斉俊久  日本サルコイドーシス/肉芽腫性疾患学会雑誌  38-  (サプリメント号)  64  -64  2018/10/05  [Not refereed][Not invited]
  
• 心臓サルコイドーシス患者における心電図同期心筋血流イメージングを用いた位相解析による予後評価

  小梁川和宏, 納谷昌直, 葛目将人, 相川忠夫, 真鍋治, 大平洋, 辻野一三, 真鍋徳子, 志賀哲, 安斉俊久  核医学(Web)  55-  (Supplement)  2018
• 化学療法による腫瘍縮小後にエドキサバンが奏功した肺癌合併静脈血栓塞栓症の1例

  庄司 哲明, 水柿 秀紀, 池澤 靖元, 古田 恵, 高島 雄太, 菊池 創, Goudarzi Houman, 朝比奈 肇, 菊地 順子, 菊地 英毅, 榊原 純, 品川 尚文, 辻野 一三, 西村 正治  肺癌  57-  (7)  914  -914  2017/12  [Not refereed][Not invited]
  
• Diagnosis and evaluation of cardiac sarcoidosis with FDG PET/CT and MRI

  真鍋 治, 真鍋 徳子, 大平 洋, 辻野 一三, 納谷 昌直, 相川 忠雄, 小原 雅彦, 吉永 恵一郎, 玉木 長良  臨床放射線  62-  (1)  133  -144  2017/01/10  [Not refereed][Not invited]
  
• 多施設におけるイプラグリフロジンの2年間のHbA1c,体重に対する影響の検討

  鈴木奈緒子, 渡部拓, 長谷川敦, 坂上慎二, 吉村治彦, 池田大輔, 中谷資隆, 杉本絢子, 林下晶子, 高階知紗, 大平洋, 辻野一三, 大塚吉則, 西村正治  糖尿病(Web)  60-  (Suppl)  2017
• 化学療法による腫瘍縮小後にエドキサバンが奏功した肺癌合併静脈血栓塞栓症の1例

  庄司哲明, 水柿秀紀, 池澤靖元, 古田恵, 高島雄太, 菊池創, GOUDARZI Houman, 朝比奈肇, 菊地順子, 菊地英毅, 榊原純, 品川尚文, 辻野一三, 西村正治  肺癌(Web)  57-  (7)  914(J‐STAGE)  2017  [Not refereed][Not invited]
  
• CARDIAC MAGNETIC RESONANCE IMAGING DETECTS DISEASE-SPECIFIC BIVENTRICULAR INVOLVEMENT IN PATIENTS WITH SYSTEMIC SCLEROSIS-ASSOCIATED PULMONARY ARTERIAL HYPERTENSION

  A. Noguchi, S. Yasuda, M. Kono, M. Kato, K. Oku, T. Bohgaki, O. Amengual, T. Horita, T. Sato, I. Tsujino, M. Nishimura, T. Atsumi  ANNALS OF THE RHEUMATIC DISEASES  74-  1124  -1124  2015/06  [Not refereed][Not invited]
  
• An Analysis of Anticoagulation Treatment for Cancer Patients with Newly Diagnosed VTE

  Ikezawa Yasuyuki, Nishimura Masaharu, Sakakibara Jun, Shoji Tetsuaki, Takashima Yuta, Morimoto Megumi, Kikuchi Hajime, Takashina Taichi, Oizumi Satoshi, Tsujino Ichizo  Haigan  55-  (6)  1001  -1007  2015  [Not refereed][Not invited]
   

  <b><i>Objective. </i></b>Patients with lung cancer have a higher risk for venous thromboembolism (VTE). Anticoagulation treatment for VTE is important in addition to the treatment for lung cancer. Warfarin is one of the anticoagulation treatments for VTE, however, recurrence of VTE is often problematic during warfarin treatment. In January 2012, the subcutaneous injection of heparin calcium at home was covered by health insurance in Japan, which may be added to potential anticoagulation treatment for VTE. <b><i>Methods. </i></b>We conducted a retrospective analysis of 29 patients who received initial anticoagulation treatment, including a heparin injection into the vein, and were subsequently treated with warfarin among 39 lung cancer patients with newly diagnosed VTE in the First Department of Medicine, Hokkaido University Hospital, between October 2006 and April 2014. <b><i>Results. </i></b>Eleven patients had recurrence of VTE. Of these, 9 patients received a subcutaneous injection of heparin calcium and 1 patient received fondaparinux sodium and responded. Although all 9 patients ultimately died of cancer, the subcutaneous injection of heparin calcium enabled 2 patients to continue to receive chemotherapy and ambulatory treatments for VTE without recurrence of VTE. <b><i>Conclusions. </i></b>This study demonstrates that patients with recurrence of VTE can continue to receive regular ambulatory chemotherapy for cancers in combination with the subcutaneous injection of heparin calcium at home.
• 心サルコイドーシス診断におけるFDG PET検査前の遊離脂肪酸値とFDG心筋生理的集積の関連

  MANABE OSAMU, YOSHINAGA KEIICHIRO, OHIRA HIROSHI, SATO TAKAHIRO, TSUJINO ICHIZO, MASUDA ATSURO, WATANABE TAKU, MANABE TOKUKO, NISHIMURA MASAHARU, TAMAKI NAGARA  核医学  51-  (3)  322  -322  2014/09/30  [Not refereed][Not invited]
  
• 心サルコイドーシスにおける心筋炎症と心交感神経異常の関連

  吉永 恵一郎, 辻野 一三, 佐藤 隆博, 山田 安寿香, 富山 勇輝, 真鍋 治, 大平 洋, 西嶋 剣一, 西村 正治, 玉木 長良  日本心臓病学会学術集会抄録  62回-  O  -366  2014/09  [Not refereed][Not invited]
  
• Acute Right Heart Failure Associated with Respiratory Diseases

  辻野 一三  最新医学  69-  (7)  1336  -1342  2014/07
• 心サルコイドーシス疑い患者に対する長時間絶食及び低炭水化物食がもたらす生理的なFDG心筋集積抑制効果

  MASUDA ATSUO, MANABE OSAMU, YOSHINAGA KEIICHIRO, OHIRA HIROSHI, SATO TAKAHIRO, TSUJINO ICHIZO, WATANABE TAKU, MANABE NORIKO, NISHIMURA MASAHARU, TAMAKI NAGARA  心臓核医学  16-  (2)  91  -91  2014/06/20  [Not refereed][Not invited]
  
• 心サルコイドーシスにおける心筋炎症は左室全体の交感神経機能異常と関連する

  吉永 恵一郎, 辻野 一三, 佐藤 隆博, 富山 勇輝, 真鍋 治, 益田 淳朗, 大平 洋, 西嶋 剣一, 西村 正治, 玉木 長良  日本心臓核医学会ニュースレター  16-  (2)  91  -91  2014/06  [Not refereed][Not invited]
  
• 日本人高齢者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, 佐藤 隆博, 谷口 正実, 秋山 一男, 赤澤 晃, 大塚 吉則, 西村 正治  日本老年医学会雑誌  51-  (3)  277  -278  2014/05  [Not refereed][Not invited]
  
• Effects of Intensified Pulmonary Hypertension (PH) Therapy on Myocardial Energetics Assessed by C-11 Acetate PET in Patients with PH

  YOSHINAGA KEIICHIRO, OHHIRA HIROSHI, TSUJINO ICHIZO, MANABE OSAMU, KATOH CHIETSUGU, KASAI KATSUHIKO, TOMIYAMA YUUKI, SATOH TAKAHIRO, OYAMA-MANABE NORIKO, NISHIMURA MASAHARU, TAMAKI NAGARA  Circ J  78-  (Supplement 1(CD-ROM))  ROMBUNNO.PJ-098  2014/02/20  [Not refereed][Not invited]
  
• Incidence, Clinical Manifestations and Prognosis of Cardiac Sarcoidosis in Patients with Pulmonary Sarcoidosis

  SATO TAKAHIRO, TSUJINO ICHIZO, ABE TOMOE, OHHIRA HIROSHI, YOSHINAGA KEIICHIRO, MANABE-OYAMA NORIKO, HATTORI TAKESHI, KONNO SATOSHI, NISHIMURA MASAHARU  Circ J  78-  (Supplement 1(CD-ROM))  ROMBUNNO.FRS-022  2014/02/20  [Not refereed][Not invited]
  
• Left Ventricular Inflammation Associated with Myocardial Autonomic Dysfunction in Patients Suspected with Cardiac Sarcoidosis

  YOSHINAGA KEIICHIRO, OHHIRA HIROSHI, YAMADA ASUKA, KASAI KATSUHIKO, TOMIYAMA YUUKI, MANABE OSAMU, TSUJINO ICHIZO, SATOH TAKAHIRO, NISHIJIMA KEN-ICHI, NISHIMURA MASAHARU, TAMAKI NAGARA  Circ J  78-  (Supplement 1(CD-ROM))  ROMBUNNO.OJ-286  2014/02/20  [Not refereed][Not invited]
  
• Recent progress on the diagnosis and the treatment of cardiac sarcoidosis

  辻野 一三  臨床放射線  59-  (1)  70  -75  2014/01
• Pulmonary Hypertension due to Lung Diseases

  辻野 一三  呼吸と循環  61-  (12)  1110  -1116  2013/12
• Pulmonary hypertension due to lung diseases and/or hypoxia

  辻野 一三  循環器内科  74-  (6)  584  -590  2013/12
• Pulmonary Hypertension due to Lung Disease - Increasing need for the Early Diagnosis and Future Treatment Strategies

  Ichizo Tsujino  JOURNAL OF CARDIAC FAILURE  19-  (10)  S124  -S124  2013/10  [Not refereed][Not invited]
  
• DIFFERENT CHARACTERISTICS OF DISEASE DETECTION BETWEEN 18F-FLUORODEOXYGLUCOSE-POSITRON EMISSION TOMOGRAPHY (FDG-PET) AND CARDIAC MAGNETIC RESONANCE (CMR) IN PATIENTS WITH CONDUCTION DISEASE DUE TO CARDIAC SARCOIDOSIS

  H. Ohira, D. Birnie, B. Mc Ardle, E. Leung, K. Yoshinaga, I. Tsujino, T. Sato, J. Bernick, G. Wells, R. Klein, A. Guo, L. Garrard, T. Ruddy, B. Chow, R. Davies, R. Hessian, K. Kingsbury, R. S. Beanlands, P. B. Nery  CANADIAN JOURNAL OF CARDIOLOGY  29-  (10)  S273  -S273  2013/10  [Not refereed][Not invited]
  
• 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, 今野 哲, 辻野 一三, 佐藤 隆博, 大平 洋, 長井 桂, 谷野 美智枝, 羽賀 博典, 石津 明洋, 陳 豊史, 伊達 洋至, 西村 正治  日本サルコイドーシス/肉芽腫性疾患学会雑誌  33-  (サプリメント号)  52  -52  2013/10  [Not refereed][Not invited]
  
• 肺高血圧患者における右心室酸素代謝亢進は右心室容量の増加よりも肺血管抵抗の上昇と強く関連する

  YOSHINAGA KEIICHIRO, ITO YOICHI, OHIRA HIROSHI, TSUJINO ICHIZO, MANABE OSAMU, KATO CHIETSUGU, SATO TAKAHIRO, MANABE TOKUKO, FUJII SATOSHI, NISHIMURA MASAHARU, TAMAKI NAGARA  核医学  50-  (3)  214  -S204  2013/09/30  [Not refereed][Not invited]
  
• 右室心筋へのF‐18 fluorodeoxyglucose(FDG)PETの集積は心サルコイドーシス疑い患者において広範な左室FDG集積と関連する

  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  日本心臓病学会誌  8-  (Supplement 1)  262  -262  2013/09/09  [Not refereed][Not invited]
  
• An autopsy case of portopulmonary hypertension associated with idiopathic portal hypertension

  Megumi Furuta, Takahiro Sato, Ichizo Tsujino, Mishie Tanino, Taku Watanabe, Masaharu Nishimura  EUROPEAN RESPIRATORY JOURNAL  42-  2013/09  [Not refereed][Not invited]
  
• 心サルコイドーシスが疑われた患者における心電図異常と半定量解析による局所心筋FDG PET集積の関連

  MANABE OSAMU, YOSHINAGA KEIICHIRO, OHIRA HIROSHI, TSUJINO ICHIZO, SATO TAKAHIRO, MANABE NORIKO, NISHIMURA MASAHARU, TAMAKI NAGARA  心臓核医学  15-  (2)  70  2013/06/10  [Not refereed][Not invited]
  
• Recent progress in the diagnosis and treatment of pulmonary hypertension due to chronic obstructive pulmonary disease

  辻野 一三  呼吸器内科  23-  (6)  590  -595  2013/06
• サルコイドーシス患者における¹⁸F‐FDG心筋集積と心電図異常の関連性の検討

  真鍋治, 吉永恵一郎, 大平洋, 辻野一三, 佐藤隆博, 真鍋徳子, 西村正治, 玉木長良  核医学  49-  (3)  295  -S275  2012/08/31  [Not refereed][Not invited]
  
• 心電図同期¹¹C‐hydroxyephedrine PETを用いた左心駆出率測定における収集時間の最適化

  孫田惠一, 服部直也, 潟端純也, 川鍋和美, 納谷昌直, 西嶋剣一, 辻野一三, 吉永恵一郎, 玉木長良  核医学  49-  (3)  282  2012/08/31  [Not refereed][Not invited]
  
• 肺高血圧症における心室中隔の左方圧排による扁平化は右心室の心筋酸素代謝亢進と関連する

  吉永恵一郎, 佐藤隆博, 大平洋, 辻野一三, 真鍋治, 加藤千恵次, 葛西克彦, 西村正治, 玉木長良  日本心臓病学会誌  7-  (Supplement 1)  339  -339  2012/08/06  [Not refereed][Not invited]
  
• 肺高血圧患者におけるMRI右心機能評価

  大山徳子, 杉森博行, 佐藤隆博, 大平洋, 辻野一三, 後藤大祐, 玉木長良, 寺江聡  日独医報  56-  (2)  260  -260  2011/12/20  [Not refereed][Not invited]
  
• Relationship between Serum n-3 and n-6 Fatty Acid Levels and Insulin Secretion

  Shinji Sakaue, Asuka Watanabe, Daisuke Ikeda, Ichizo Tsujino, Yoshinori Ohtsuka, Masaharu Nishimura  DIABETES  59-  A657  -A658  2010/06  [Not refereed][Not invited]
  
• Comparison of Sirolimus-Eluting NEVO (TM) Stents With Paclitaxel-eluting CoStar (TM) Stents and Paclitaxel-eluting Taxus Liberte (TM) Stents: Insights From Intravascular Ultrasound Analysis of the Res-elution I and Costar II Trials

  Hiromasa Otake, Takao Shimohama, Ichizo Tsujino, Junya Ako, Katsuhisa Waseda, Paul G. Yock, Yasuhiro Honda, Dean J. Kereiakes, Mitch W. Krucoff, Christian Spaulding, John Ormiston, Alexandre Abizaid, Peter J. Fitzgerald  CIRCULATION  120-  (18)  S915  -S915  2009/11  [Not refereed][Not invited]
  
• Impact of Lumen Narrowing Within Everolimus-Eluting Stents on Downstream Vessel Segments

  Kenji Sakata, Junya Ako, Katsuhisa Waseda, Masao Yamasaki, Ichizo Tsujino, Takao Shimohama, Hiromasa Otake, Takao Hasegawa, Ryota Sakurai, Paul G. Yock, Krishnankulty Sudhir, Hajime Kusano, Gregg W. Stone, Peter J. Fitzgerald, Yasuhiro Honda  AMERICAN JOURNAL OF CARDIOLOGY  104-  (6A)  18D  -18D  2009/09  [Not refereed][Not invited]
  
• Dipeptidyl peptidase 4 expression and activity in rodent models of type 1 and 2 diabetes

  D. Ikeda, S. Sakaue, I. Tsujino, Y. Ohtsuka, M. Nishimura  DIABETOLOGIA  52-  S315  -S315  2009/09  [Not refereed][Not invited]
  
• Monitoring cardiac sarcoid lesions using F-18-FDG PET

  H. Ohira, I. Tsujino, D. Ikeda, S. Sakaue, K. Yoshinaga, N. Tamaki, M. Nishimura  EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING  36-  S162  -S163  2009/09  [Not refereed][Not invited]
  
• 循環器画像診断 心サルコイドーシスの遅延造影MRIとFDG‐PET所見の比較

  大山徳子, 大平洋, 辻野一三, 玉木長良, 寺江聡, 白土博樹  映像情報Medical  41-  (10)  1053-1057  2009/09/01  [Not refereed][Not invited]
  
• PJ-102 Monitoring Cardiac Involvement of Sarcoidosis Using 18F-FDG PET(PJ017,Nuclear Cardiology (PET) (I),Poster Session (Japanese),The 73rd Annual Scientific Meeting of The Japanese Circulation Society)

  Ohira Hiroshi, Tsujino Ichizo, Koiwa Hiroaki, Ikeda Daisuke, Sakaue Shinji, Yoshinaga Keiichirou, Tamaki Nagara, Nishimura Masaharu  Circulation journal : official journal of the Japanese Circulation Society  73-  571  -571  2009/03/01
• FRS-098 SPIRIT III Japan vs. SPIRIT III US : Eight-Month IVUS Analysis of Everolimus-Eluting Stent(FRS20,Clinical Evidence of DES Era (2) (IHD),Featured Research Session (English),The 73rd Annual Scientific Meeting of The Japanese Circulation Society)

  Shimohama Takao, Yamasaki Masao, Ako Junya, Tsujino Ichizo, Ohtake Hiromasa, Hasegawa Takao, Nakatani Daisaku, Sakurai Ryota, Waseda Katsuhisa, Stone Gregg, Honda Yasuhiro, Saito Shigeru, Fitzgerald Peter  Circulation journal : official journal of the Japanese Circulation Society  73-  163  -163  2009/03/01
• Comparison of Vessel Response Between Zotarolimus- and Paclitaxel-eluting Stents: Global and Focal Vessel Responses as Assessed by Serial Intravascular Ultrasound

  Katsuhisa Waseda, Akiyoshi Miyazawa, Takao Hasegawa, Ichizo Tsujino, Ryota Sakurai, Junya Ako, Paul G. Yock, David E. Kandzari, Martin B. Leon, Peter J. Fitzgerald, Yasuhiro Honda  JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY  53-  (10)  A12  -A12  2009/03  [Not refereed][Not invited]
  
• 心サルコイドーシスの遅延造影MRIとFDG‐PET所見の比較

  大山徳子, 大平洋, 辻野一三, 玉木長良, 寺江聡, 白土博樹  日本医学放射線学会総会抄録集  68th-  S361  2009/02/28  [Not refereed][Not invited]
  
• 27 Cases of Cardiac Sarcoidosis : Distribution and Pattern of Delayed-Enhancement in Cardiac Magnetic Resonance Imaging

  OYAMA Noriko, OHIRA Hiroshi, TSUJINO Ichizo, TERAE Satoshi, SHIRATO Hiroki  日本磁気共鳴医学会雑誌  29-  (1)  45  -47  2009/02/15  [Not refereed][Not invited]
  
• 27) 動脈管開存症による成人肺高血圧症の1例(第99回日本循環器学会北海道地方会)

  伊東 直史, 渡辺 武史, 辻野 一三, 神垣 光徳, 小岩 弘明, 大平 洋, 大平 恵, 池田 大輔, 坂上 慎二, 石井 勝久, 西村 正治  Circulation journal : official journal of the Japanese Circulation Society  72-  1074  -1074  2008/10/20
• Vascular Response to Overlapping Everolimus-eluting stents: Comparison with Paclitaxel-eluting Stents

  Hiromasa Otake, Junys Ako, Masao Yamasaki, Ichizo Tsujino, Takao Shimohama, Takato Hasegawa, Ryota Sakurai, Katsuhisa Waseda, Paul G. Yock, Yasuhiro Honda, Krishnankutty Sudhir, Gregg W. Stone, Peter J. Fitzgerald  AMERICAN JOURNAL OF CARDIOLOGY  102-  (8A)  170I  -170I  2008/10  [Not refereed][Not invited]
  
• Efficacy Of The Everolimus-eluting Stent in Diabetic Patients: Comparison With The Paclitaxel-eluting Stent

  Hiromasa Otake, Junya Ako, Masao Yamasaki, Ichizo Tsujino, Takao Shimohama, Takao Hasegawa, Ryota Sakurai, Katsuhisa Waseda, Paul G. Yock, Yasuhiro Honda, Poornima Sood, Krishnankutty Sudhir, Gregg W. Stone, Peter J. Fitzgerald  CIRCULATION  118-  (18)  S1042  -S1042  2008/10  [Not refereed][Not invited]
  
• Six-Month IVUS Analysis of Pimecrolimus and Dual Pimecrolimus/Paclitaxel Eluting Stents: Results of the GENESIS Trial

  Takao Shimohama, Ichizo Tsujino, Junya Ako, Takao Hasegawa, Hyeonsoo Chang, Paul G. Yock, Yasuhiro Honda, Keith D. Dawkins, Stefan Verheye, Peter J. Fitzgerald  AMERICAN JOURNAL OF CARDIOLOGY  102-  (8A)  139I  -140I  2008/10  [Not refereed][Not invited]
  
• Characteristics of Late Incomplete Stent Apposition: A Comparison with Sirolimus-, Paclitaxel- and Zotarolimus-Eluting Stents

  Katsuhisa Waseda, Junya Ako, Ichizo Tsujino, Masao Yamasaki, Tomomi Koizumi, Akiyoshi Miyazawa, Paul G. Yock, Ian Meredith, Peter J. Fitzgerald, Yasuhiro Honda  CIRCULATION  118-  (18)  S1045  -S1045  2008/10  [Not refereed][Not invited]
  
• Arterial Responses at Proximal and Distal Edges of Everolimus-Eluting Stents: Insights from the Spirit III Randomized Controlled Trial

  Hiromasa Otake, Junya Ako, Masao Yamasaki, Ichizo Tsujino, Takao Shimohama, Takao Hasegawa, Ryota Sakurai, Katsuhisa Waseda, Yasuhiro Honda, Paul G. Yock, Wai-Fung Cheong, Krishnankutty Sudhir, Gregg W. Stone, Peter J. Fitzgerald  CIRCULATION  118-  (18)  S1045  -S1045  2008/10  [Not refereed][Not invited]
  
• Comparison of Vascular Response to Zotarolimus-Eluting Stent Versus Paclitaxel-Eluting Stent Implantation: IVUS Results From the ENDEAVOR IV Trial

  Katsuhisa Waseda, Akiyoshi Miyazawa, Takao Hasegawa, Ichizo Tsujino, Ryota Sakurai, Junyo Ako, Paul G. Yock, Yasuhiro Honda, David E. Kandzari, Martin B. Leon, Peter J. Fitzgerald  AMERICAN JOURNAL OF CARDIOLOGY  102-  (8A)  146I  -146I  2008/10  [Not refereed][Not invited]
  
• Comparison of Vascular Response to Everolimus-Eluting Stent versus Paclitaxel-Eluting Stent: IVUS Analysis from SPIRIT III

  Takao Shimohama, Hiromasa Otake, Junya Ako, Masao Yamasaki, Ichizo Tsujino, Yasuhiro Honda, Shigeru Saito, Gregg W. Stone, Peter J. Fitzgerald  JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY  45-  S29  -S29  2008/10  [Not refereed][Not invited]
  
• FRS-067 Comparison of Neointimal Hyperplasia Pattern in Drug-Eluting Stents : Second versus First Generation Drug-Eluting Stents(Pioneers in Intravascular Imagings(I),Featured Research Session,The 72nd Annual Scientific Meeting of the Japanese Circulation Society)

  Sakurai Ryota, Courtney Brian, Yamasaki Masao, Tsujino Ichizo, Waseda Katsuhisa, Hasegawa Takao, Shimohama Takao, Ako Junya, Hongo Yoichiro, Morino Yoshihiro, Miyazawa Akiyoshi, Hur Seung-Ho, Koizumi Tomomi, Honda Yasuhiro, Yock Paul, Lansky Alexandra, Sudhir Krishnankutty, Stone Gregg, Fitzgerald Peter  Circulation journal : official journal of the Japanese Circulation Society  72-  160  -160  2008/03/01
• PE-564 Pilot study of short-term effects of a novel long-acting oral beraprost in patients with pulmonary arterial hypertension(Pulmonary circulation(02)(H),Poster Session(English),The 72nd Annual Scientific Meeting of the Japanese Circulation Society)

  Ikeda Daisuke, Tsujino Ichizo, Sakaue Shinji, Ohhira Megumu, Ohira Hiroshi, Itoh Naofumi, Kamigaki Mitsunori, Ishimaru Shinji, Atsumi Tatsuya, Nishimura Masaharu  Circulation journal : official journal of the Japanese Circulation Society  72-  501  -501  2008/03/01
• PJ-546 Myocardial Imaging with 18F-Fluoro-2-Deoxyglucose Positron Emission Tomography and Magnetic Resonance Imaging in Sarcoidosis(Nuclear cardiology(09)(I),Poster Session(Japanese),The 72nd Annual Scientific Meeting of the Japanese Circulation Society)

  Ohira Hiroshi, Tsujino Ichizo, Ishimaru Shinji, Oyama Noriko, Igarashi Tadashi, Ikeda Daisuke, Itoh Naofumi, Kamigaki Mitsunori, Miura Masatake, Sakaue Shinji, Tamaki Nagara, Nishimura Masaharu  Circulation journal : official journal of the Japanese Circulation Society  72-  649  -649  2008/03/01
• Eight-month volumetric IVUS analysis in DIM and non-DM patients treated with XIENCE V everolimus-eluting coronary stent

  Takao Shimohama, Junya Ake, Masao Yamasalki, Ichizo Tsujino, Ali H. M. Hassan, Takao Hasegawa, Ryota Sakurai, Katsuhisa Waseca, Paul G. Yock, Yasuhiro Honda, Krishnankutty Suchir, Gregg W. Stone, Peter J. Fitzgerald  JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY  51-  (10)  B43  -B43  2008/03  [Not refereed][Not invited]
  
• Overlapping drug-eluting stents: Intravascular ultrasound insights from cobalt chromium stent with antiproliferative for restenosis II (COSTAR II) trial

  Junya Ako, Ichizo Tsujino, Tomomi Koizumi, Katsuhisa Waseda, Yesuhiro Honda, Paul G. Yock, Dean J. Kereiakes, Mitchell W. Krucoff, Peter J. Fitzgerald  JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY  51-  (10)  B41  -B41  2008/03  [Not refereed][Not invited]
  
• Characteristics of late incomplete stent apposition: A comparison between sirolimus- and zotarblimds-eluting stents

  Katsuhisa Waseda, Junya Ako, Ichizo Tsujino, Masao Yamasaki, Tomomi Koizumi, Akiyoshi Miyazawa, Yoshihisa Shimada, Paul G. Yock, Ian Meredith, Peter J. Fitzgerald, Yasuhiro Honda  CIRCULATION  116-  (16)  468  -468  2007/10  [Not refereed][Not invited]
  
• Comparison of everolimus-eluting Stents with paclitaxel-eluting Stents in de novo native coronary artery lesions: Intravascular ultrasound results from the SPIRIT III trial

  Masao Yamasaki, Ichizo Tsujino, Ryota Sakurai, Katsuhisa Waseda, Takao Hasegawa, Takao Shimohama, Junya Ako, Yasuhiro Honda, Poomima Sood, Alexandra J. Lansky, Krishnankutty Sudhirr, Gregg W. Stone, Peter J. Fitzgerald  CIRCULATION  116-  (16)  615  -615  2007/10  [Not refereed][Not invited]
  
• Post-procedural incomplete stent apposition after implantation of everolimus-eluting or paclitaxel-eluting stents: Insights from the randomized SPIRIT III trial

  Masao Yamasaki, Junya Ako, Ichizo Tsujino, Ryota Sakurai, Katsuhisa Waseca, Takao Hasegawa, Takao Shimohama, Yasuhro Honda, Alexandra J. Lansky, Krishnankutty Suchir, Gregg W. Stone, Peter J. Fitzgerald  CIRCULATION  116-  (16)  361  -361  2007/10  [Not refereed][Not invited]
  
• Neointimal hyperplasia patterns among 3 drug-eluting stents: A comparative intravascular ultrasound analysis of everolimus-, sirolimus-, and paclitaxel-eluting stents

  Ryota Sakurai, Brian K. Courtney, Masao Yamasaki, Ichizo Tsujino, Katsuhisa Waseda, Takao Hasegawa, Takao Shimohama, Junya Ako, Yoichim Hongo, Yoshihiro Morino, Akiyoshi Miyazawa, Seung-Ho Hur, Tomomi Koizumi, Yasuhiro Honda, Paul G. Yock, Alexandra J. Lansky, Krismankutty Sudhir, Gregg W. Stone, Peter J. Fitzgerald  CIRCULATION  116-  (16)  615  -615  2007/10  [Not refereed][Not invited]
  
• 18FDG-PET陽性所見が心電図異常に先行した心サルコイドーシスの一例

  五十嵐 正, 神垣 光徳, 木村 孔一, 長谷川 幸生, 渡邊 安寿香, 横田 美紀, 池田 大輔, 大平 洋, 伊東 直史, 坂上 慎二, 辻野 一三, 西村 正治, 石丸 伸司  Circulation Journal  71-  (Suppl.II)  826  -826  2007/04  [Not refereed][Not invited]
  
• 28)心サルコイドーシス診断における^<18>F-FDG PETとMRI併用の有用性(第95回日本循環器学会北海道地方会)

  大平 洋, 辻野 一三, 渡部 拓, 五十嵐 正, 池田 大輔, 伊東 直史, 神垣 光徳, 坂上 慎二, 西村 正治, 石丸 伸司, 三浦 真健, 大山 徳子, 玉木 長良  Circulation journal : official journal of the Japanese Circulation Society  70-  (0)  1187  -1187  2006/10/20  [Not refereed][Not invited]
  
• Influence of intra-luminal tissue on myocardial injury after stent implantation with intravascular ultrasound observation

  Akiyoshi Miyazawa, Junya Ako, Yoichiro Hongo, Seung-Ho Hur, Katsuhisa Waseda, Ichizo Tsujino, Ali H. M. Hassan, Yasuhiro Honda, Martine B. Leon, David E. Kandzari, Peter J. Fitzgerald  AMERICAN JOURNAL OF CARDIOLOGY  98-  (8A)  100M  -100M  2006/10  [Not refereed][Not invited]
  
• Intravascular ultrasound observation of "Black hole" appearance: Porcine carotid artery model with artificial focal stenosis

  Akiyoshi Miyazawa, Junya Ako, Fumiaki Ikeno, Katsuhisa Waseda, Ichizo Tsujino, Ali H. M. Hassan, Yasuhiro Honda, Peter J. Fitzgerald  AMERICAN JOURNAL OF CARDIOLOGY  98-  (8A)  100M  -100M  2006/10  [Not refereed][Not invited]
  
• 11)ベラプロストナトリウム徐放性製剤の肺動脈性肺高血圧症に対する治療経験(第94回 日本循環器学会北海道地方会)

  池田 大輔, 辻野 一三, 渡部 拓, 大平 恵, 大平 洋, 伊東 直史, 神垣 光徳, 石丸 伸司, 坂上 慎二, 西村 正治  Circulation journal : official journal of the Japanese Circulation Society  70-  1016  -1016  2006/04/20
• 下肢深部静脈血栓症を有する若年者に発症した慢性血栓塞栓性肺高血圧症に対する血栓内膜摘除術の1例 道内最初の施行例

  大岡 智学, 国原 孝, 村下 十志文, 辻野 一三, 安藤 太三, 安田 慶秀  北海道外科雑誌  50-  (2)  121  -126  2005/12  [Not refereed][Not invited]
   

  26歳男.患者は呼吸困難,胸痛,血痰を主訴とした.22歳時,重症筋無力症と診断され,ステロイド内服中であった.突然の主訴により急性肺血栓塞栓症が疑われ,入院時,肺血管抵抗696dyn・sec・cm -5,平均肺動脈圧は44mmHgで,肺血流シンチグラムでは右中下葉と左上葉領域のみ血流分布を認めた.抗凝結療法,血栓溶解療法を施行して改善を認めたが自覚症状が残存し,慢性血栓塞栓性肺高血圧の急性増悪と考えられた.腹部CT,下肢静脈造影で左総腸骨静脈閉塞を認め,下肢深部静脈血栓症と考えられた.ステロイド漸減中でもあり,抗凝結療法の効果を経過観察することとしたが,肺動脈内血栓は縮小せず,約2年半後,肺血栓内膜摘除術を施行した.計42分の超低体温間欠的循環停止を要したが,再灌流性肺障害は軽度であり,術後18時間で抜管できた.平均肺動脈圧,肺血管抵抗,自覚症状は著明に改善し,術後約15ヵ月現在,再発徴候は認められていない
• 17) 慢性肺血栓塞栓症に対する血栓内膜摘除術の一例(第91回日本循環器学会北海道地方会)

  国原 孝, 大岡 智学, 村下 十志文, 安田 慶秀, 池田 大輔, 伊東 直史, 辻野 一三  Circulation journal : official journal of the Japanese Circulation Society  68-  865  -865  2004/10/20
• 18) 原発性肺高血圧症に伴う蛋白漏出性胃腸症が生体肺移植後に軽快した1例(第91回日本循環器学会北海道地方会)

  大平 洋, 辻野 一三, 池田 大輔, 神垣 光徳, 石丸 伸司, 坂上 慎二, 西村 正治, 伊達 洋至, 佐野 由文, 清水 信義  Circulation journal : official journal of the Japanese Circulation Society  68-  865  -865  2004/10/20
• 症例 経カテーテル的血栓溶解療法および吸引療法にても救命しえなかった急性広範性肺血栓塞栓症の1剖検例

  福家 聡, 辻野 一三, 石丸 伸司  ICUとCCU  28-  (8)  607  -614  2004/08
• OJ-315 ^<18>F-Fluoro-2-Deoxyglucose-Positron Emission Tomography : A Novel Tool for Detecting Cardiac Involvement of Sarcoidosis(Nuclear Cardiology 7 (I) : OJ38)(Oral Presentation (Japanese))

  Ishimaru Shinji, Tsujino Ichizo, Ikeda Daisuke, Ohira Hiroshi, Ito Naofumi, Kamigaki Mitsunori, Yoshimura Haruhiko, Sakaue Shinji, Takei Tosiki, Tsukamoto Eriko, Tamaki Nagara, Nishimura Masaharu  Circulation journal : official journal of the Japanese Circulation Society  68-  306  -306  2004/03/01
• 当科における肺高血圧症5例に対するepo-prostenol(フローラン)持続静注療法の治療経験(第89回日本循環器学会北海道地方会)

  池田 大輔, 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  Circulation journal : official journal of the Japanese Circulation Society  67-  887  -887  2003/10/20
• 進行性の右側大量胸水を来した特発注収縮性心膜炎の一例(第89回日本循環器学会北海道地方会)

  神垣 光徳, 山本 潤, 坂下 智博, 池田 大輔, 石丸 伸司, 吉村 治彦, 坂上 慎二, 辻野 一三, 村下 十志文  Circulation journal : official journal of the Japanese Circulation Society  67-  (0)  888  -888  2003/10/20  [Not refereed][Not invited]
  
• <18>^F-FDG PETを用いたサルコイドーシスの心病変評価(第89回日本循環器学会北海道地方会)

  石丸 伸司, 辻野 一三, 池田 大輔, 神垣 光徳, 吉村 治彦, 坂上 慎二, 西村 正治, 竹井 俊樹, 塚本 江利子, 玉木 長良  Circulation journal : official journal of the Japanese Circulation Society  67-  (0)  884  -884  2003/10/20  [Not refereed][Not invited]
  
• 48)Sildenafil citrate投与で改善を認めた肺高血圧症の1例

  池田 大輔, 伊東 直史, 石丸 伸司, 神垣 光徳, 吉村 治彦, 坂上 慎二, 辻野 一三, 西村 正治  Circulation journal : official journal of the Japanese Circulation Society  67-  762  -762  2003/04/20
• 31) 再発乳癌切除後に難治性の肺血栓塞栓症を発症した一剖検例

  福家 聡, 大泉 聡史, 辻野 一三, 檜澤 伸之, 山口 悦郎, 西村 正治, 田中 伸哉  Circulation journal : official journal of the Japanese Circulation Society  66-  1004  -1004  2002/10/20
• 循環器病の診断と治療に関するガイドライン(1999-2000年度合同研究班報告)肺高血圧症治療ガイドライン

  中野 赳, 青柳 成明, 川合 明彦, 栗山 喬之, 小林 正, 佐地 勉, 清水 信義, 鳥飼 勝隆, 中西 宣文, 西村 正治, 藤岡 博文, 増田 政久, 百村 伸一, 八巻 重雄, 押領司 篤茂, 岡田 修, 国枝 武義, 塩見 利明, 伊達 洋至, 谷川 高士, 辻野 一三, 深谷 修作, 山田 典一, 矢津 卓宏, 川上 義和, 近藤 啓文, 白土 邦男, 高本 眞一, 門間 和夫  日本呼吸器学会雑誌 = The journal of the Japanese Respiratory Society  40-  (5)  413  -454  2002/05/10
• 48)プロスタサイクリン持続静注療法を導入し自覚状の改善を得たportopulmonary hypertensionの1例(日本循環器学会 第86回北海道地方会)

  鈴木 誉也, 神垣 光徳, 白井 真也, 石丸 伸司, 谷野 功典, 辻野 一三, 西村 正治  Circulation journal : official journal of the Japanese Circulation Society  66-  886  -886  2002/04/20
• 肺高血圧症治療ガイドライン

  中野 赳, 青柳 成明, 川合 明彦, 栗山 喬之, 小林 正, 佐地 勉, 清水 信義, 鳥飼 勝隆, 中西 宣文, 西村 正治, 藤岡 博文, 増田 政久, 百村 伸一, 八巻 重雄, 押領司 篤茂, 岡田 修, 国枝 武義, 塩見 利明, 伊達 洋至, 谷川 高士, 辻野 一三, 深谷 修作, 山田 典一, 矢津 卓宏, 川上 義和, 近藤 啓文, 白土 邦男, 高本 眞一, 門間 和夫  Japanese circulation journal  65-  1077  -1118  2001/11/25
• 13) PGl_2持続静注療法で9ヶ月間経過を観察した原発性肺高血圧症の一例(日本循環器学会 第85回北海道地方会)

  白井 真也, 辻野 一三, 神垣 光徳, 石丸 伸司, 古谷 純吾, 谷野 功典, 西村 正治  Japanese circulation journal  65-  700  -700  2001/10/20
• III-1 原発性肺高血圧症 循環器病の診断と治療に関するガイドライン (1999-2000年度合同班研究報告) 肺高血圧症治療ガイドライン

  中野赳, 青柳 成明, 川合 明彦, 栗山 喬之, 小林 正, 佐地 勉, 清水 信義, 鳥飼 勝隆, 中西 宣文, 西村 正治, 藤岡 博文, 増田 政久, 百村 伸一, 八巻 重雄, 押領司 篤茂, 岡田 修, 国枝 武義, 塩見 利明, 伊達 洋至, 谷川 高士, 辻野 一三, 深谷 修作, 山田 典一, 矢津 卓宏, 川上 義和, 近藤 啓文, 白土 邦男, 高本 眞一, 門間 和夫  Jpn Circ J  65-  1085  -1090  2001
• Exhaled nitric oxide - Is it really a good marker of airway inflammation in bronchial asthma?

  Tsujino, I, M Nishimura, A Kamachi, H Makita, M Munakata, K Miyamoto, Y Kawakami  RESPIRATION  67-  (6)  645  -651  2000/11  [Not refereed][Not invited]
   

  Background: The concentration of exhaled nitric oxide ([NO]) has been reported to reflect the inflammatory process of airways in patients with bronchial asthma, particularly when they are steroid naive. However, it is not fully understood whether it equally reflects the degree of airway inflammation in patients receiving inhaled corticosteroids, but whose symptoms are not necessarily well controlled. Objective: To examine whether the exhaled [NO] really reflects airway inflammation in patients with bronchial asthma, regardless of treatment with inhaled steroids. Methods: Exhaled [NO] was measured in patients with bronchial asthma (43 steroid treated and 32 steroid naive), chronic obstructive pulmonary disease (COPD) (n = 36), bronchiectasis (n = 10) and in control subjects (n = 26). We examined in each asthmatic group whether the exhaled [NO] correlated with parameters reflecting airway inflammation. Results: Exhaled [NO] was significantly correlated with symptom score, clinical severity, circulating eosinophil count, and the percentage of eosinophils in induced sputum in the steroid-naive asthmatics, but not in the steroid-treated asthmatics, although airway inflammation in this group was not well controlled, as evidenced by clinical symptoms and the higher percentage of eosinophils in induced sputum. Exhaled [NO] from the patients with COPD (6.2 +/- 0.7 ppb) or bronchiectasis (5.4 +/- 1.3 ppb) was not significantly increased compared with the controls (6.0 +/- 1.0 ppb), and was significantly lower than in the asthmatic patients as a whole (19.0 +/- 2.0 ppb). Conclusions: Although exhaled [NO] is a useful marker of airway inflammation for differential diagnosis and evaluation of severity in steroid-naive patients with bronchial asthma, it may not be as useful in steroid-treated patients. Copyright (C) 2000 S. Karger AG, Basel.
• 32) 虚血性心疾患との鑑別を要した心サルコイドーシスの一例

  小川 浩司, 澁谷 英二, 辻野 一三, 斉藤 俊一, 西村 正治, 川上 義和, 望月 孝司, 塚本 江利子, 玉木 長良  Japanese circulation journal  63-  (3)  820  -820  1999/10/20  [Not refereed][Not invited]
  
• Chronic Pulmonary Thromboembolism Diagnosed on the Basis of Characteristic Mosaic Patterns on Lung Computed Tomograms

  TANINO Michie, HONDA Toshirou, SHINANO Hideki, TANINO Yoshinori, TSUJINO Ichizou, SAITO Shunichi, NISHIMURA Masaharu, MIYAMOTO Kenji, KAWAKAMI Yoshikazu  日本呼吸器学会雑誌 = The journal of the Japanese Respiratory Society  37-  (7)  594  -599  1999/07/10  [Not refereed][Not invited]
  
• Can exhaled nitric oxide really be a good marker of eosinophilic airway inflammation in bronchial asthma?

  Tsujino, I, A Kamachi, R Sato, M Munakata, K Miyamoto, M Nishimura, Y Kawakami  AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  159-  (3)  A101  -A101  1999/03  [Not refereed][Not invited]
  
• Non-invasive Evaluation of Pulmonary Hemodynamics by pulsed Doppler Echocardiography in Patients with Chronic Obstructive Pulmonary Disease

  MIYAMOTO Kenji, AIDA Akira, SAITO Shunichi, TSUJINO Ichizo, MAKITA Hirohito, NAKANO Tsuyoshi, NISHIMURA Masaharu, KAWAKAMI Yoshikazu  日本胸部疾患学会雑誌 = The Japanese journal of thoracic diseases  33-  155  -158  1995/12/25
• 34)睡眠時無呼吸症候群に合併した異型狭心症の一例(日本循環器学会 第71回北海道地方会)

  斎藤 俊一, 辻野 一三, 佐藤 文彦, 合田 晶, 宮本 顕二, 川上 義和  Japanese circulation journal  59-  585  -585  1995/06/20

Presentations

• 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  2022/07
• 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  2022/07
• 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  2022/07
• 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  2022/07
• 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  2022/07
• 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  2022/07
• 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  2022/07
• 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  2022/06
• 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  2022/06
• 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  2022/06
• 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  2022/05
• 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  2022/04
• 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  2022/04
• 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  2022/02
• 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）  2022/01
• 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  2021/11
• 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  2021/11
• 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  2021/07
• 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  2021/07
• 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  2021/06
• 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  2021/06
• 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  2021/06
• 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  2021/05
• 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  2021/05
• 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  2021/05
• 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  2021/05
• 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  2021/03
• 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  2021/03
• 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  2021/02
• 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」  2020/12
• 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  2020/11
• 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  2020/09
• 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  2020/09
• 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  2020/09
• 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  2020/09
• 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  2020/09

Association Memberships

• 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 Projects

• Comprehensive evaluation with CT for cardiac sarcoidosis

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2017/04 -2020/03 

  Author : 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.
• Analysis of microenvironment and exploration of new biomarker for pulmonary arterial hypertention

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2015/04 -2018/03 

  Author : 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.
• Clinicopathological study on the pulmonary vasculopathy and right heart morphology/function in lung disease-associated pulmonary hypertension

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2014/04 -2017/03 

  Author : 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.
• Development of new diagnosis approaches for detecting cardiovascular dysfunction in patients with respiratory disease using positron emission tomography

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2011/04 -2014/03 

  Author : 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.
• 冠動脈疾患、肺循環疾患
• 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

  文部科学省および日本学術振興会：科学研究費助成事業 基盤C

  Author : 辻野 一三