Jul. 2022, 日本肺高血圧・肺循環学会, 学会奨励賞　　　　　　　　　　　　　　　

Right Ventricular Dysfunction in Lung Disease/Hypoxia-Associated Pulmonary Hypertension.
Hideki Shima, Ichizo Tsujino, Toshitaka Nakaya, Junichi Nakamura, Ayako Igarashi-Sugimoto, Takahiro Sato, Taku Watanabe, Hiroshi Ohira, Ryo Hisada, Masaru Kato, Satonori Tsuneta, Isao Yokota, Satoshi Konno
Journal of the American Heart Association, e042186, 12 Aug. 2025, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Limited data exist on right ventricular (RV) function in lung disease/hypoxia-associated pulmonary hypertension (PH). We aimed to clarify the presence, characteristics, and clinical significance of RV dysfunction in patients with lung disease/hypoxia-associated PH. METHODS: We analyzed data from 3 groups of patients: those with lung disease/hypoxia-associated PH, those without PH, and those with pulmonary arterial hypertension (PAH). RV volume was assessed using cardiac magnetic resonance imaging, and RV pressure data were obtained by right heart catheterization and analyzed using dedicated software and a single-beat method. We then evaluated RV contractility by end-systolic elastance (Ees), diastolic function by β and end-diastolic elastance, and RV-pulmonary artery coupling by Ees/arterial elastance. RESULTS: We studied 68 patients with lung disease/hypoxia-associated PH, 40 without PH, and 93 with PAH. In the lung disease/hypoxia-associated PH group, Ees was sustained (0.46 [95% CI, 0.26-0.75] mm Hg/mL), whereas β (0.035 [95% CI, 0.022-0.049]) and end-diastolic elastance (0.19 [95% CI, 0.11-0.38] mm Hg/mL) were higher, and Ees/arterial elastance was lower (0.59 [95% CI, 0.27-0.79]) compared with the no-PH group. There were no differences in these values between the groups with lung disease/hypoxia-associated PH and PAH. Ees/arterial elastance was significantly correlated with the 6-minute walk distance and associated with mortality (hazard ratio, 0.18 [95% CI, 0.04-0.79]) in the group with PAH, but it was not in the group with lung disease/hypoxia-associated PH. Similarly, whereas the group with PAH showed improvement in β and Ees/arterial elastance with pulmonary vasodilator therapy, such improvement was not observed in the group with lung disease/hypoxia-associated PH. CONCLUSIONS: In lung disease/hypoxia-associated PH, RV contractility is preserved, whereas diastolic function and RV-pulmonary artery coupling are impaired. Further investigation is needed to elucidate the distinct clinical relevance of RV dysfunction in lung disease/hypoxia-associated PH.

Two cases of bronchial artery aneurysms in patients with long-standing precapillary pulmonary hypertension.
Taku Komori, Takahiro Sato, Ichizo Tsujino, Daisuke Tamatsuki, Shuhei Yoshikawa, Hideki Shima, Junichi Nakamura, Ryo Morita, Daisuke Abo, Satoshi Konno
Respiratory investigation, 63, 4, 521, 523, Jul. 2025, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, Bronchial artery aneurysm (BAA) is a rare but increasingly recognized condition due to advances in imaging. We report two cases of BAA in patients with long-standing pulmonary hypertension. Case 1 is a 30-year-old man with idiopathic peripheral pulmonary artery stenosis diagnosed at age 23. He developed a slightly dilated bronchial artery, which later enlarged, leading to bronchial artery embolization. Case 2 is a 30-year-old woman with pulmonary arterial hypertension diagnosed at age 3. Multiple BAAs were identified at age 24, and progressive enlargement was observed at age 28. Due to lesion complexity, she remains under careful observation.

Reduced hemoglobin-corrected diffusing capacity in pulmonary arterial hypertension with preserved pulmonary function and morphology.
Ayako Igarashi-Sugimoto, Ichizo Tsujino, Hideki Shima, Junichi Nakamura, Toshitaka Nakaya, Takahiro Sato, Taku Watanabe, Hiroshi Ohira, Kaoruko Shimizu, Takashi Yokota, Sari Iwasaki, Satonori Tsuneta, Isao Yokota, Satoshi Konno
Respiratory investigation, 63, 4, 600, 607, Jul. 2025, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: The diffusing capacity and the transfer coefficient of the lung for carbon monoxide (DLCO and KCO, respectively) are reduced in pulmonary arterial hypertension; however, the effect of pulmonary arterial hypertension alone on these parameters and their clinical impact remain unclear. We aimed to elucidate the exclusive impact of pulmonary arterial hypertension on these two parameters and examine their association with other parameters. METHODS: We retrospectively selected patients with pulmonary arterial hypertension with normal pulmonary function upon pulmonary function testing and with normal lung parenchyma upon chest computed tomography. We calculated the hemoglobin-corrected DLCO (DLCO-Hbc) and KCO (KCO-Hbc) and examined their association with established pulmonary hypertension-related parameters. An exploratory analysis of pulmonary vasculopathy was performed in an autopsy case. RESULTS: We included 50 patients with pulmonary arterial hypertension for analysis. Their median %DLCO-Hbc and %KCO-Hbc were 62 % and 70 %, respectively. The DLCO-Hbc was associated with functional class, 6-min walk distance, alveolar-arterial oxygen tension difference, cardiac output, and pulmonary arterial hypertension-related death. The DLCO-Hbc and KCO-Hbc were also correlated with the lowest minute ventilation/carbon dioxide production ratio (ρ = -0.84 and -0.49, respectively), an index that represents ventilation-perfusion mismatch. The autopsy revealed pulmonary arterial hypertension-specific arteriopathy that was heterogeneously distributed in the lungs. CONCLUSIONS: The DLCO-Hbc and KCO-Hbc were reduced to 60 %-70 % in patients with pulmonary arterial hypertension even when their pulmonary function and morphology were preserved. The decreases were associated with pulmonary hypertension-related clinical parameters and survival and may be caused by heterogeneous vasculopathy and subsequent ventilation-perfusion mismatch.

Prevalence, incidence, and clinical features of cardiac involvement in patients with pulmonary sarcoidosis.
Junichi Nakamura, Takahiro Sato, Hiroshi Ohira, Shuhei Yoshikawa, Takeshi Hattori, Osamu Manabe, Noriko Oyama-Manabe, Satonori Tsuneta, Hirokazu Kimura, Sakae Takenaka, Toshiyuki Nagai, Toshihisa Anzai, Masaharu Nishimura, Isao Yokota, Ichizo Tsujino, Satoshi Konnno
Respiratory medicine, 238, 107954, 107954, Mar. 2025, [Peer-reviewed], [Invited], [Corresponding author], [International Magazine]
English, Scientific journal, BACKGROUND: The epidemiology and characteristics of cardiac involvement in patients with pulmonary sarcoidosis remain unclear. We aimed to determine the prevalence, incidence, and clinical features of cardiac sarcoidosis in patients with pulmonary sarcoidosis. METHODS: The characteristics of patients with biopsy-proven pulmonary sarcoidosis were retrospectively evaluated. Cardiac sarcoidosis was diagnosed via evaluations, including 18F-fluorodeoxyglucose positron emission tomography at the time of diagnosis of pulmonary sarcoidosis and during follow-up. Characteristics of patients with and without cardiac complications were compared. RESULTS: In total, 438 patients with pulmonary sarcoidosis were included, of which 40 (9.1 %) were diagnosed with cardiac sarcoidosis at the time of diagnosis of pulmonary sarcoidosis. During the follow-up period, 14 patients (4 %) developed cardiac complications (0.0075/person-years). Electrocardiographic abnormalities were the most common findings leading to the diagnosis of cardiac sarcoidosis (85 %). Compared to patients without cardiac involvement, those with cardiac sarcoidosis had lower serum angiotensin converting enzyme concentration [19.9 (15.5-25.1) vs. 17.4 (12.6-23.8) U/L)], higher rates of kidney complications (3 vs. 13 %), fewer ocular complications (78 vs. 17 %), and lower lymphocyte levels [35.8 (18.6-53) vs. 25.1 (14.2-38.2)%] and CD4/CD8 ratios [4.8 (3.1-7.5)% vs. 3.9 (1.8-6)%] in bronchoalveolar lavage fluid analysis. CONCLUSION: At the time of diagnosis of pulmonary sarcoidosis, cardiac complications occurred in approximately 10 % of the patients and developed in 0.0075/person-year during follow-up. Low serum angiotensin converting enzyme concentration, lymphocyte level and CD4/CD8 ratio in the bronchoalveolar lavage fluid may be unique features of patients with cardiac sarcoidosis.

肺サルコイドーシス組織診断例における心病変合併例の割合および臨床的特徴
吉川 修平, 佐藤 隆博, 辻野 一三, 中村 順一, 永井 利幸, 木村 孔一, 今野 哲
日本サルコイドーシス/肉芽腫性疾患学会雑誌, 44, サプリメント号, 58, 58, 日本サルコイドーシス, Oct. 2024
Japanese

Exploratory analysis of the accuracy of echocardiographic parameters for the assessment of right ventricular function and right ventricular-pulmonary artery coupling.
Hideki Shima, Ichizo Tsujino, Junichi Nakamura, Toshitaka Nakaya, Ayako Sugimoto, Takahiro Sato, Taku Watanabe, Hiroshi Ohira, Masaru Suzuki, Satonori Tsuneta, Yasuyuki Chiba, Michito Murayama, Isao Yokota, Satoshi Konno
Pulmonary circulation, 14, 2, e12368, Apr. 2024, [Peer-reviewed], [International Magazine]
English, Scientific journal, Echocardiography is a widely used modality for the assessment of right ventricular (RV) function; however, few studies have comprehensively compared the accuracy of echocardiographic parameters using invasively obtained reference values. Therefore, this exploratory study aimed to compare the accuracy of echocardiographic parameters of RV function and RV-pulmonary artery (PA) coupling. We calculated four indices of RV function (end-systolic elastance [Ees] for systolic function [contractility], τ for relaxation, and β and end-diastolic elastance [Eed] for stiffness), and an index of RV-PA coupling (Ees/arterial elastance [Ea]), using pressure catheterization, cardiac magnetic resonance imaging, and a single-beat method. We then compared the correlations of RV indices with echocardiographic parameters. In 63 participants (54 with pulmonary hypertension (PH) and nine without PH), Ees and τ correlated with several echocardiographic parameters, such as RV diameter and area, but the correlations were moderate (|correlation coefficients (ρ)| < 0.5 for all parameters). The correlations of β and Eed with echocardiographic parameters were weak, with |ρ| < 0.4. In contrast, Ees/Ea closely correlated with RV free wall longitudinal strain (RVFW-LS)/estimated systolic PA pressure (eSPAP) (ρ = -0.72). Ees/Ea also correlated with tricuspid annular plane systolic excursion/eSPAP, RV diameter, and RV end-systolic area, with |ρ | >0.65. In addition, RVFW-LS/eSPAP yielded high sensitivity (0.84) and specificity (0.75) for detecting reduced Ees/Ea. The present study indicated a limited accuracy of echocardiographic parameters in assessing RV systolic and diastolic function. In contrast to RV function, they showed high accuracy for assessing RV-PA coupling, with RVFW-LS/eSPAP exhibiting the highest accuracy.

Deep learning to assess right ventricular ejection fraction from two-dimensional echocardiograms in precapillary pulmonary hypertension.
Michito Murayama, Hiroyuki Sugimori, Takaaki Yoshimura, Sanae Kaga, Hideki Shima, Satonori Tsuneta, Aoi Mukai, Yui Nagai, Shinobu Yokoyama, Hisao Nishino, Junichi Nakamura, Takahiro Sato, Ichizo Tsujino
Echocardiography (Mount Kisco, N.Y.), 41, 4, e15812, Apr. 2024, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Precapillary pulmonary hypertension (PH) is characterized by a sustained increase in right ventricular (RV) afterload, impairing systolic function. Two-dimensional (2D) echocardiography is the most performed cardiac imaging tool to assess RV systolic function; however, an accurate evaluation requires expertise. We aimed to develop a fully automated deep learning (DL)-based tool to estimate the RV ejection fraction (RVEF) from 2D echocardiographic videos of apical four-chamber views in patients with precapillary PH. METHODS: We identified 85 patients with suspected precapillary PH who underwent cardiac magnetic resonance imaging (MRI) and echocardiography. The data was divided into training (80%) and testing (20%) datasets, and a regression model was constructed using 3D-ResNet50. Accuracy was assessed using five-fold cross validation. RESULTS: The DL model predicted the cardiac MRI-derived RVEF with a mean absolute error of 7.67%. The DL model identified severe RV systolic dysfunction (defined as cardiac MRI-derived RVEF < 37%) with an area under the curve (AUC) of .84, which was comparable to the AUC of RV fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE) measured by experienced sonographers (.87 and .72, respectively). To detect mild RV systolic dysfunction (defined as RVEF ≤ 45%), the AUC from the DL-predicted RVEF also demonstrated a high discriminatory power of .87, comparable to that of FAC (.90), and significantly higher than that of TAPSE (.67). CONCLUSION: The fully automated DL-based tool using 2D echocardiography could accurately estimate RVEF and exhibited a diagnostic performance for RV systolic dysfunction comparable to that of human readers.

Echocardiographic estimation of right ventricular diastolic stiffness based on pulmonary regurgitant velocity waveform analysis in precapillary pulmonary hypertension.
Yui Nagai, Michito Murayama, Sanae Kaga, Hideki Shima, Satonori Tsuneta, Shinobu Yokoyama, Hisao Nishino, Mana Goto, Yukino Suzuki, Yusuke Yanagi, Suguru Ishizaka, Hiroyuki Iwano, Junichi Nakamura, Takahiro Sato, Ichizo Tsujino
The international journal of cardiovascular imaging, 27 Mar. 2024, [Peer-reviewed], [International Magazine]
English, Scientific journal, Right ventricular (RV) diastolic stiffness is an independent predictor of survival and is strongly associated with disease severity in patients with precapillary pulmonary hypertension (PH). Therefore, a fully validated echocardiographic method for assessing RV diastolic stiffness needs to be established. This study aimed to compare echocardiography-derived RV diastolic stiffness and invasively measured pressure-volume loop-derived RV diastolic stiffness in patients with precapillary PH. We studied 50 consecutive patients with suspected or confirmed precapillary PH who underwent cardiac catheterization, magnetic resonance imaging, and echocardiography within a 1-week interval. Single-beat RV pressure-volume analysis was performed to determine the gold standard for RV diastolic stiffness. Elevated RV end-diastolic pressure (RVEDP) was defined as RVEDP ≥ 8 mmHg. Using continuous-wave Doppler and M-mode echocardiography, an echocardiographic index of RV diastolic stiffness was calculated as the ratio of the atrial-systolic descent of the pulmonary artery-RV pressure gradient derived from pulmonary regurgitant velocity (PRPGDAC) to the tricuspid annular plane movement during atrial contraction (TAPMAC). PRPGDAC/TAPMAC showed significant correlation with β (r = 0.54, p < 0.001) and RVEDP (r = 0.61, p < 0.001). A cut-off value of 0.74 mmHg/mm for PRPGDAC/TAPMAC showed 83% sensitivity and 93% specificity for identifying elevated RVEDP. Multivariate analyses indicated that PRPGDAC/TAPMAC was independently associated with disease severity in patients with precapillary PH, including substantial PH symptoms, stroke volume index, right atrial size, and pressure. PRPGDAC/TAPMAC, based on pulmonary regurgitation velocity waveform analysis, is useful for the noninvasive assessment of RV diastolic stiffness and is associated with prognostic risk factors in precapillary PH.

Prognostic Value of Combined Assessments of Late Gadolinium Enhancement and Fluorodeoxyglucose Uptake in Cardiac Sarcoidosis.
Sho Kazui, Sakae Takenaka, Toshiyuki Nagai, Satonori Tsuneta, Kenji Hirata, Yoshiya Kato, Hirokazu Komoriyama, Yuta Kobayashi, Akinori Takahashi, Kiwamu Kamiya, Taro Temma, Takuma Sato, Atsushi Tada, Yutaro Yasui, Michikazu Nakai, Takahiro Sato, Ichizo Tsujino, Kohsuke Kudo, Satoshi Konno, Toshihisa Anzai
JACC. Cardiovascular imaging, 11 Mar. 2024, [Peer-reviewed], [International Magazine]
English

心臓サルコイドーシス患者の免疫抑制療法開始後における心筋トロポニン値経時的評価の予後的意義
數井 翔, 竹中 秀, 永井 利幸, 加藤 喜哉, 小森山 弘和, 小林 雄太, 高橋 昌寛, 神谷 究, 佐藤 琢真, 多田 篤司, 安井 悠太郎, 中井 陸運, 佐藤 隆博, 辻野 一三, 今野 哲, 安斉 俊久
日本サルコイドーシス/肉芽腫性疾患学会雑誌, 43, サプリメント号, 64, 64, 日本サルコイドーシス, Oct. 2023
Japanese

The chest CT signs for pulmonary veno-occlusive disease correlate with pulmonary haemodynamics in systemic sclerosis.
Haruka Moriya, Masaru Kato, Ryo Hisada, Keita Ninagawa, Maria Tada, Kodai Sakiyama, Mitsutaka Yasuda, Michihito Kono, Yuichiro Fujieda, Olga Amengual, Yasuka Kikuchi, Ichizo Tsujino, Takahiro Sato, Tatsuya Atsumi
Rheumatology (Oxford, England), 15 Sep. 2023, [Peer-reviewed], [International Magazine]
English, Scientific journal, OBJECTIVE: Pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc) sometimes accompanies pulmonary veno-occlusive disease (PVOD). We aimed to reveal the relation between clinical signs of PVOD and severing of pulmonary vasculopathy in SSc. METHODS: This study comprised 52 consecutive SSc patients who had pulmonary haemodynamic abnormalities (mPAP > 20 mmHg, PVR > 2 W.U. or PAWP > 15 mmHg). The chest CT scan was evaluated in all patients. Patients were divided into two groups, the 0-1 group and the 2-3 group, according to the number of chest CT signs for PVOD, including 1) mediastinal lymph node enlargement, 2) thickened interlobular septal wall, and 3) ground glass opacity. Pulmonary haemodynamics, echocardiography and MRI-based cardiac function, pulmonary function, and serum biomarkers were compared between the two groups. RESULTS: Mediastinal lymph node enlargement, thickened interlobular septal wall, and ground glass opacity were observed in 11 (21%), 32 (62%), and 11 (21%) patients, respectively. The 2-3 group (n = 15) had higher mPAP (p= 0.02) while lower DLco/VA (p= 0.02) compared with the 0-1 group (n = 37). Other parameters, including PAWP, cardiac output, left ventricular ejection fraction, left atrial diameter, forced vital capacity, brain natriuretic peptide, and Krebs von den Lunge-6 were not different between the two groups. CONCLUSION: The CT signs for PVOD had positive correlation with mPAP but negative correlation with DLco in SSc patients, indicating that PAH-SSc may reflect a spectrum of pulmonary vascular disease that ranges from the pulmonary artery to the vein.

Impact of cancer on the prevalence, management, and outcome of patients with chronic thromboembolic pulmonary hypertension.
Junichi Nakamura, Ichizo Tsujino, Hideki Shima, Toshitaka Nakaya, Ayako Sugimoto, Takahiro Sato, Taku Watanabe, Hiroshi Ohira, Masaru Suzuki, Isao Yokota, Satoshi Konno
Journal of thrombosis and thrombolysis, 9th (CD-ROM), 24 Aug. 2023, [Peer-reviewed], [International Magazine]
English, INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) results from unresolved thrombotic obstruction of the pulmonary vasculature. Cancer is a known risk factor for CTEPH. This study aimed to determine the impact of cancer on the prevalence, management, and outcomes of patients with CTEPH. MATERIALS AND METHODS: In this retrospective study involving 99 patients sequentially diagnosed with CTEPH in our hospital, the prevalence of 10 comorbid conditions including a past history of cancer at the time of CTEPH diagnosis were calculated. RESULTS: Among the 99 patients, 17 (17%) had a history of cancer. Breast cancer (n = 6) was the most common cancer type, followed by gastrointestinal cancer (n = 3), uterine cancer (n = 2), and malignant lymphoma (n = 2). Between patients with and without cancer, there were no differences in the demographics, severity of CTEPH, and management; however, the 5-year survival rate was lower for patients with cancer (65%) than for those without (89%). In addition, patients with cancer had significantly worse survival than those without (p = 0.03 by log-rank test). During follow-up, nine patients developed cancer after the diagnosis of CTEPH. Among the 99 patients, 13 died during follow-up, 6 (46%) of whom died of cancer. CONCLUSIONS: 17% of our patients with CETPH were diagnosed with cancer, with breast and gastrointestinal tract cancers being the most common. Cancer comorbidity was associated with a poor prognosis and contributed to death in 46% of deceased patients. The impact of cancer on CTEPH should be further evaluated in the future.

Association of longitudinal cardiac troponin trajectory with adverse events in patients with cardiac sarcoidosis.
Sho Kazui, Sakae Takenaka, Toshiyuki Nagai, Yoshiya Kato, Hirokazu Komoriyama, Yuta Kobayashi, Akinori Takahashi, Kiwamu Kamiya, Takuma Sato, Atsushi Tada, Yutaro Yasui, Michikazu Nakai, Takahiro Sato, Ichizo Tsujino, Satoshi Konno, Toshihisa Anzai
International journal of cardiology, 389, 131268, 131268, 15 Aug. 2023, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Although high-sensitivity cardiac troponins may be sensitive and easily repeatable markers of disease activity in patients with cardiac sarcoidosis (CS), the association between longitudinal cardiac troponin trajectory and adverse events remains unclear. This study aimed to clarify whether longitudinal cardiac troponin levels were associated with adverse events in patients with CS. METHODS: We examined 63 consecutive CS-initiated prednisolone (PSL) patients with available longitudinal high-sensitivity cardiac troponin T (cTnT) data between December 2013 and March 2023. The area under the cTnT trajectory, which reflected cumulative cTnT release, was calculated to assess the association between longitudinal cTnT levels and adverse events. Patients were divided into two groups according to the median area under the cTnT trajectory per month. The primary outcome was a composite of sustained ventricular tachycardia or fibrillation, worsening heart failure, and sudden cardiac death (SCD). RESULTS: In total, 463 cTnT measurements were collected over a median follow-up period of 30.4 (interquartile range [IQR] 15.6-34.2) months. The primary outcome was observed in 12 (19%) patients. A higher area under the cTnT trajectory was significantly associated with an increased incidence of the primary outcome (P = 0.027), while cTnT levels before and one month after initiation of PSL, and these changes were not related to adverse events (P = 0.179, 0.096, and 0.95, respectively). CONCLUSIONS: Longitudinal cTnT trajectory following PSL initiation was associated with adverse cardiac events in patients with CS, suggesting that longitudinal measurement of cTnT would be useful for the early identification of high-risk patients.

Clinical and Hemodynamic Responses to Imatinib in Pulmonary Veno-Occlusive Disease/Pulmonary Capillary Hemangiomatosis: A Retrospective Pilot Study of Five Cases and Review of the Literature
Junichi Nakamura, Ichizo Tsujino, Hideki Shima, Toshitaka Nakaya, Ayako Sugimoto, Takahiro Sato, Taku Watanabe, Hiroshi Ohira, Masaru Suzuki, Satonori Tsuneta, Ryo Hisada, Masaru Kato, Satoshi Konno
American Journal of Cardiovascular Drugs, 23, 3, 329, 338, Springer Science and Business Media LLC, 30 Mar. 2023, [Peer-reviewed]
Scientific journal

呼吸と循環のCross road:肺高血圧症の臨床と基礎の最前線 間質性肺疾患に伴う肺高血圧症の剖検例における肺血管病変の病理学的解析
杉本 絢子, 辻野 一三, 中村 順一, 佐藤 隆博, 鈴木 雅, 高村 圭, 岩崎 沙理, 種井 善一, 谷口 浩二, 田中 伸哉, 今野 哲
日本呼吸器学会誌, 12, 増刊, 44, 44, (一社)日本呼吸器学会, Mar. 2023
Japanese

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, [Peer-reviewed], [International Magazine]
English, An 80-year-old man diagnosed with primary macroglobulinemia 7 years earlier had been treated with cyclophosphamide, following which he developed dyspnea on exertion. Cyclophosphamide was discontinued. The patient's dyspnea, however, failed to improve. Right heart catheterization (RHC) revealed precapillary pulmonary hypertension (PH). He was transferred to our institution for further examination. Prior use of cyclophosphamide was the patient's only risk factor for PH, and cyclophosphamide use was considered as a possible cause of PH in this case. He was treated with tadalafil and dyspnea gradually improved. A follow-up RHC exhibited improvement in mean pulmonary arterial pressure and pulmonary vascular resistance.

Efficacy and safety of oral pulmonary vasodilators in pulmonary veno‐occlusive disease
Junichi Nakamura, Ichizo Tsujino, Hideki Shima, Toshitaka Nakaya, Ayako Sugimoto, Takahiro Sato, Taku Watanabe, Hiroshi Ohira, Masaru Suzuki, Satonori Tsuneta, Ryo Hisada, Masaru Kato, Satoshi Konno
Pulmonary Circulation, 12, 4, Wiley, Oct. 2022, [Peer-reviewed]
Scientific journal

Various factors contribute to death in patients with different types of pulmonary hypertension: A retrospective pilot study from a single tertiary center.
Junichi Nakamura, Ichizo Tsujino, Hiroshi Ohira, Toshitaka Nakaya, Ayako Sugimoto, Takahiro Sato, Taku Watanabe, Masaru Suzuki, Masaru Kato, Isao Yokota, Satoshi Konno
Respiratory investigation, 60, 5, 647, 657, Sep. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: A few studies have focused on the cause of death from different types of pulmonary hypertension (PH). This study aimed to systematically analyze the primary and secondary causes of death and compare the profiles between different PH groups. METHODS: The contribution of PH to death was assessed in precapillary PH (i.e., group 1 [pulmonary arterial hypertension], group 3 [PH associated with lung disease], and group 4 [chronic thromboembolic PH]) using specific criteria; death was classified into three categories: PH death (death due to PH only), PH-related death, and PH-unrelated death. Disorders other than PH that contributed to death were analyzed, and mortality profiles were compared between groups. RESULTS: Eighty deceased patients with PH were examined (group 1, n = 28; group 3, n = 39; and group 4, n = 13). The contribution of PH to death was significantly different between the three groups. "PH death" was most common in group 1 (61%), "PH-related death" in group 3 (56%), and "PH-related death" and "PH-unrelated death" in group 4 (38% for both). The highest contributing factor to death other than PH was respiratory failure in group 3 and malignant disease in group 4. CONCLUSIONS: Significant variations in the causes of death were observed in groups 1, 3, and 4 PH patients. In addition to PH, respiratory failure and malignant disease significantly contributed to death in group 3 and group 4 PH, respectively. Understanding the precise death cause may be important in achieving better outcomes in PH patients.

An Adult Case of Unilateral Left Pulmonary Artery Agenesis Presenting with Hemoptysis.
Yuriko Ishida, Masaru Suzuki, Hiroshi Horii, Junichi Nakamura, Munehiro Matsumoto, Sho Nakakubo, Takahiro Sato, Ichizo Tsujino, Ryo Morita, Daisuke Abo, Satoshi Konno
Internal medicine (Tokyo, Japan), 62, 5, 763, 767, 22 Jul. 2022, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Pulmonary artery agenesis (PAA) is a rare congenital vascular anomaly usually diagnosed during infancy. We herein report a 67-year-old man with PAA manifesting as massive hemoptysis. Contrast-enhanced computed tomography of the chest revealed the diagnosis of PAA, which we speculated to have resulted in the present event. Detailed angiography provided more accurate information on the pulmonary vasculature and collateral circulation, which helped us plan tailored treatment. Although very rare, we must consider the possibility of PAA in adults with unexplained hemoptysis.

Underdiagnosis of cardiac sarcoidosis by ECG and echocardiography in cases of extracardiac sarcoidosis.
Hiroshi Ohira, Takahiro Sato, Osamu Manabe, Noriko Oyama-Manabe, Akiko Hayashishita, Toshitaka Nakaya, Junichi Nakamura, Naoko Suzuki, Ayako Sugimoto, Sho Furuya, Satonori Tsuneta, Taku Watanabe, Ichizo Tsujino, Satoshi Konno
ERJ open research, 8, 2, Apr. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, Background: Although screening with 12-lead electrocardiography and transthoracic echocardiography for cardiac involvement has been recommended for patients with biopsy-proven extracardiac sarcoidosis, cardiac sarcoidosis has been reported even in patients with normal electrocardiography and echocardiography findings. We investigated the prevalence and characteristics of these patient cohorts. Methods: We studied 112 consecutive patients (age, 55±17 years, 64% females) with biopsy-proven extracardiac sarcoidosis who had undergone 18F-fluorodeoxyglucose positron emission tomography and cardiac magnetic resonance imaging for cardiac sarcoidosis evaluation. The patients were categorised as those showing normal findings both in electrocardiography and transthoracic echocardiography (normal group) and those showing abnormal findings in one or both examinations (abnormal group). Results: 33 (29%) and 79 (71%) patients were categorised into the normal and abnormal groups, respectively, of which 6 (18%) and 43 (54%) patients, respectively, were diagnosed with cardiac sarcoidosis (p<0.01). Of these six patients in the normal group, two with multiple-organ sarcoidosis showed clinical deterioration of cardiac involvement and required steroid therapy; three with small cardiac involvement showed natural remission over follow-up assessments; and one underwent steroid therapy and showed an improvement in the left ventricular ejection fraction to within normal limits. Conclusions: The prevalence of cardiac sarcoidosis in patients with biopsy-proven extracardiac sarcoidosis and normal electrocardiography and transthoracic echocardiography findings was ∼20%. Electrocardiography and transthoracic echocardiography may not detect cardiac sarcoidosis in patients without conduction and morphological abnormalities. However, some of these patients may subsequently show clinically manifested cardiac sarcoidosis. Physicians should be mindful of this population.

Accuracy of Swan‒Ganz catheterization-based assessment of right ventricular function: Validation study using high-fidelity micromanometry-derived values as reference.
Hideki Shima, Toshitaka Nakaya, Ichizo Tsujino, Junichi Nakamura, Ayako Sugimoto, Takahiro Sato, Taku Watanabe, Hiroshi Ohira, Masaru Suzuki, Masaru Kato, Isao Yokota, Satoshi Konno
Pulmonary circulation, 12, 2, e12078, Apr. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, Right ventricular (RV) function critically affects the outcomes of patients with pulmonary hypertension (PH). Pressure wave analysis using Swan‒Ganz catheterization (SG-cath) allows for the calculation of indices of RV function. However, the accuracy of these indices has not been validated. In the present study, we calculated indices of systolic and diastolic RV functions using SG-cath-derived pressure recordings in patients with suspected or confirmed PH. We analyzed and validated the accuracies of three RV indices having proven prognostic values, that is, end-systolic elastance (Ees)/arterial elastance (Ea), β (stiffness constant), and end-diastolic elastance (Eed), using high-fidelity micromanometry-derived data as reference. We analyzed 73 participants who underwent SG-cath for the diagnosis or evaluation of PH. In this study, Ees/Ea was calculated via the single-beat pressure method using [1.65 × (mean pulmonary arterial pressure) - 7.79] as end-systolic pressure. SG-cath-derived Ees/Ea, β, and Eed were 0.89 ± 0.69 (mean ± standard deviation), 0.027 ± 0.002, and 0.16 ± 0.02 mmHg/ml, respectively. The mean differences (limits of agreement) between SG-cath and micromanometry-derived data were 0.13 (0.99, -0.72), 0.002 (0.020, -0.013), and 0.04 (0.20, -0.12) for Ees/Ea, β, and Eed, respectively. The intraclass correlation coefficients of the indices derived from the two catheterizations were 0.76, 0.71, and 0.57 for Ees/Ea, β, and Eed, respectively. In patients with confirmed or suspected PH, SG-cath-derived RV indices, especially Ees/Ea and β, exhibited a good correlation with micromanometry-derived reference values.

Right ventricular function as assessed by cardiac magnetic resonance imaging-derived strain parameters compared to high-fidelity micromanometer catheter measurements
Takahiro Sato, Bharath Ambale-Venkatesh, Stefan L. Zimmerman, Ryan J. Tedford, Steven Hsu, Ela Chamera, Tomoki Fujii, Christopher J. Mullin, Valentina Mercurio, Rubina Khair, Celia P. Corona-Villalobos, Catherine E. Simpson, Rachel L. Damico, Todd M. Kolb, Stephen C. Mathai, Joao A.C. Lima, David A. Kass, Ichizo Tsujino, Paul M. Hassoun
Pulmonary Circulation, 11, 4, 204589402110325, 204589402110325, SAGE Publications, Sep. 2021, [Peer-reviewed], [Lead author], ［Internationally co-authored］, [International Magazine]
English, Scientific journal, Right ventricular function has prognostic significance in patients with pulmonary hypertension. We evaluated whether cardiac magnetic resonance-derived strain and strain rate parameters could reliably reflect right ventricular systolic and diastolic function in precapillary pulmonary hypertension. End-systolic elastance and the time constant of right ventricular relaxation tau, both derived from invasive high-fidelity micromanometer catheter measurements, were used as gold standards for assessing systolic and diastolic right ventricular function, respectively. Nineteen consecutive precapillary pulmonary hypertension patients underwent cardiac magnetic resonance and right heart catheterization prospectively. Cardiac magnetic resonance data were compared with those of 19 control subjects. In pulmonary hypertension patients, associations between strain- and strain rate-related parameters and invasive hemodynamic parameters were evaluated. Longitudinal peak systolic strain, strain rate, and early diastolic strain rate were lower in PAH patients than in controls; peak atrial-diastolic strain rate was higher in pulmonary hypertension patients. Similarly, circumferential peak systolic strain rate was lower and peak atrial-diastolic strain rate was higher in pulmonary hypertension. In pulmonary hypertension, no correlations existed between cardiac magnetic resonance-derived and hemodynamically derived measures of systolic right ventricular function. Regarding diastolic parameters, tau was significantly correlated with peak longitudinal atrial-diastolic strain rate ( r = −0.61), deceleration time ( r = 0.75), longitudinal systolic to diastolic time ratio ( r = 0.59), early diastolic strain rate ( r = −0.5), circumferential peak atrial-diastolic strain rate ( r = −0.52), and deceleration time ( r = 0.62). Strain analysis of the right ventricular diastolic phase is a reliable non-invasive method for detecting right ventricular diastolic dysfunction in PAH.

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, Oct. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal

Multi-Beat Right Ventricular-Arterial Coupling Predicts Clinical Worsening in Pulmonary Arterial Hypertension.
Steven Hsu, Catherine E Simpson, Brian A Houston, Alison Wand, Takahiro Sato, Todd M Kolb, Stephen C Mathai, David A Kass, Paul M Hassoun, Rachel L Damico, Ryan J Tedford
Journal of the American Heart Association, 9, 10, e016031, 18 May 2020, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
English, Scientific journal, Background Although right ventricular (RV) to pulmonary arterial (RV-PA) coupling is considered the gold standard in assessing RV dysfunction, its ability to predict clinically significant outcomes is poorly understood. We assessed the ability of RV-PA coupling, determined by the ratio of multi-beat (MB) end-systolic elastance (Ees) to effective arterial elastance (Ea), to predict clinical outcomes. Methods and Results Twenty-six subjects with pulmonary arterial hypertension (PAH) underwent same-day cardiac magnetic resonance imaging, right heart catheterization, and RV pressure-volume assessment with MB determination of Ees/Ea. RV ejection fraction (RVEF), stroke volume/end-systolic volume, and single beat-estimated Ees/Ea were also determined. Patients were treated with standard therapies and followed prospectively until they met criteria of clinical worsening (CW), as defined by ≥10% decline in 6-minute walk distance, worsening World Health Organization (WHO) functional class, PAH therapy escalation, RV failure hospitalization, or transplant/death. Subjects were 57±14 years, largely WHO class III (50%) at enrollment, with preserved average RV ejection fraction (RVEF) (47±11%). Mean follow-up was 3.2±1.3 years. Sixteen (62%) subjects met CW criteria. MB Ees/Ea was significantly lower in CW subjects (0.7±0.5 versus 1.3±0.8, P=0.02). The optimal MB Ees/Ea cut-point predictive of CW was 0.65, defined by ROC (AUC 0.78, P=0.01). MB Ees/Ea below this cut-point was significantly associated with time to CW (hazard ratio 5.1, P=0.001). MB Ees/Ea remained predictive of outcomes following multivariate adjustment for timing of PAH diagnosis and PAH diagnosis subtype. Conclusions RV-PA coupling as measured by MB Ees/Ea has prognostic significance in human PAH, even in a cohort with preserved RVEF.

Functional Impact of Human Genetic Variants of COL18A1/Endostatin on Pulmonary Endothelium.
Alice M Goyanes, Aigul Moldobaeva, Mery Marimoutou, Lidenys C Varela, Lan Wang, Laura F Johnston, Meena M Aladdin, Grace L Peloquin, Bo S Kim, Mahendra Damarla, Karthik Suresh, Takahiro Sato, Todd M Kolb, Paul M Hassoun, Rachel L Damico
American journal of respiratory cell and molecular biology, 62, 4, 524, 534, Apr. 2020, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
English, Scientific journal, Pulmonary arterial hypertension (PAH) is an incurable disease characterized by disordered and dysfunctional angiogenesis leading to small-vessel loss and an obliterative vasculopathy. The pathogenesis of PAH is not fully understood, but multiple studies have demonstrated links between elevated angiostatic factors, disease severity, and adverse clinical outcomes. ES (endostatin), one such circulating angiostatic peptide, is the cleavage product of the proteoglycan COL18A1 (collagen α1[XVIII] chain). Elevated serum ES is associated with increased mortality and disease severity in PAH. A nonsynonymous variant of ES (aspartic acid-to-asparagine substitution at amino acid 104; p.D104N) is associated with differences in PAH survival. Although COL18A1/ES expression is markedly increased in remodeled pulmonary vessels in PAH, the impact of ES on pulmonary endothelial cell (PEC) biology and molecular contributions to PAH severity remain undetermined. In the present study, we characterized the effects of exogenous ES on human PEC biology and signaling. We demonstrated that ES inhibits PEC migration, proliferation, and cell survival, with significant differences between human variants, indicating that they are functional genetic variants. ES promotes proteasome-mediated degradation of the transcriptional repressor ID1, increasing expression and release of TSP-1 (thrombospondin 1). ES inhibits PEC migration via an ID1/TSP-1/CD36-dependent pathway, in contrast to proliferation and apoptosis, which require both CD36 and CD47. Collectively, the data implicate ES as a novel negative regulator of ID1 and an upstream propagator of an angiostatic signal cascade converging on CD36 and CD47, providing insight into the cellular and molecular effects of a functional genetic variant linked to altered outcomes in PAH.

A histopathological report of a 16-year-old male with peripheral pulmonary artery stenosis and Moyamoya disease with a homozygous RNF213 mutation.
Kei Takahashi, Junichi Nakamura, Shinya Sakiyama, Toshitaka Nakaya, Takahiro Sato, Taku Watanabe, Hiroshi Ohira, Keishi Makita, Utano Tomaru, Akihiro Ishizu, Ichizo Tsujino
Respiratory medicine case reports, 29, 100977, 100977, 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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.

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, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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.

卵円孔開存による慢性の右左シャントとplatypnea-orthodeoxia syndromeを合併した重症右心不全の1例　　　　　　　　　　　　　　　
佐藤 隆博, 伊東 直史, 魚住 健志, 児島 裕一, 須野 賢一郎, 佐藤 公治, 松名 伸記, 白井 真也, 若狭 哲, 神垣 光徳
KKR札幌医療センター医学雑誌, 16, 1, 59, 62, KKR札幌医療センター, Dec. 2019
Japanese

Factor Xa inhibitors for preventing recurrent thrombosis in patients with antiphospholipid syndrome: a longitudinal cohort study.
Sato T, Nakamura H, Fujieda Y, Ohnishi N, Abe N, Kono M, Kato M, Oku K, Bohgaki T, Amengual O, Yasuda S, Atsumi T
Lupus, 28, 13, 1577, 1582, Nov. 2019, [Peer-reviewed]

Ventricular mass as a prognostic imaging biomarker in incident pulmonary arterial hypertension.
Catherine E Simpson, Rachel L Damico, Todd M Kolb, Stephen C Mathai, Rubina M Khair, Takahiro Sato, Khalil Bourji, Ryan J Tedford, Stefan L Zimmerman, Paul M Hassoun
The European respiratory journal, 53, 4, Apr. 2019, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
English, Scientific journal

Pulmonary arterial hypertension and atrial arrhythmias: incidence, risk factors, and clinical impact
Valentina Mercurio, Grace Peloquin, Khalil I. Bourji, Nermin Diab, Takahiro Sato, Blessing Enobun, Traci Housten-Harris, Rachel Damico, Todd M. Kolb, Stephen C. Mathai, Ryan J. Tedford, Carlo G. Tocchetti, Paul M. Hassoun
Pulmonary Circulation, 8, 2, 204589401876987, 204589401876987, SAGE Publications, Apr. 2018, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
English, Scientific journal, Atrial arrhythmia (AA) occurrence in pulmonary arterial hypertension (PAH) may determine clinical deterioration and affect prognosis. In this study we assessed AA incidence in idiopathic (IPAH) and systemic sclerosis related PAH (SSc-PAH) and evaluated risk factors, management, and impact on mortality. We collected baseline data from consecutive IPAH or SSc-PAH patients prospectively enrolled in the Johns Hopkins Pulmonary Hypertension Registry between January 2000 and July 2016. During follow-up AA onset, treatment, and outcome were recorded. Among 317 patients (201 SSc-PAH, 116 IPAH), 42 developed AA (19 atrial fibrillation, 10 flutter-fibrillation, 9 atrial flutter, and 4 atrial ectopic tachycardia) with a 13.2% cumulative incidence. Most events were associated with hospitalization (90.5%). Electrical or pharmacological cardioversion was attempted in most cases. Patients with AA had higher right atrial pressure, pulmonary wedge pressure ( P < 0.005), NT-proBNP ( P < 0.05), and thyroid disease prevalence ( P < 0.005). Higher mortality was observed in patients with AA, though not statistically significant (LogRank P = 0.323). Similar long-term mortality between IPAH with AA and SSc-PAH without AA was observed (LogRank P = 0.098). SSc-PAH with AA had the worst prognosis. In PAH patients AA occurrence is a matter of significant concern. Therapeutic strategies aimed at restoring sinus rhythm may represent an important goal.

Amelioration of right ventricular systolic function and stiffness in a patient with idiopathic pulmonary arterial hypertension treated with oral triple combination therapy
Toshitaka Nakaya, Ichizo Tsujino, Hiroshi Ohira, Takahiro Sato, Taku Watanabe, Noriko Oyama-Manabe, Masaharu Nishimura
Pulmonary Circulation, 8, 2, 204589401876535, 204589401876535, SAGE Publications, Apr. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, Right ventricular (RV) function is an important determinant of the prognosis in patients with pulmonary arterial hypertension (PAH). In the context of recent therapeutic progress, there is an increasing need for better monitoring of RV function for management of PAH. We present the case of a 42-year-old woman with idiopathic PAH who was treated with three oral pulmonary vasodilators, i.e. tadalafil, ambrisentan, and beraprost. At the baseline assessment, the mean pulmonary arterial pressure (mPAP) was 45 mmHg, cardiac index (CI) was 1.36 L/min/m², and pulmonary vascular resistance (PVR) was elevated to 21.3 Wood units (WU). However, three months after the start of combination treatment, mPAP and PVR decreased to 42 mmHg and 7.5 WU, respectively, and conventional indices of RV function, such as CI, right atrial area, and right atrial pressure also improved. Beyond three months, however, there were no further improvements in mPAP, PVR, or indices of RV function. In addition, we calculated three recently introduced indices of intrinsic RV function: end-systolic elastance (Ees; an index of RV contractility), Ees/arterial elastance ratio (Ees/Ea; an index of RV/pulmonary arterial coupling), and β (an index of RV stiffness) using cardiac magnetic resonance imaging and Swan-Ganz catheterization measurements. Notably, in contrast to conventional parameters, Ees, Ees/Ea, and β showed persistent improvement during the entire two-year follow-up. The application of Ees, Ees/Ea, and β may play an additional role in a comprehensive assessment of RV function in PAH.

Improvement in Right Ventricular Strain with Ambrisentan and Tadalafil Upfront Therapy in Scleroderma-associated Pulmonary Arterial Hypertension.
Valentina Mercurio, Monica Mukherjee, Ryan J Tedford, Roham T Zamanian, Rubina M Khair, Takahiro Sato, Omar A Minai, Fernando Torres, Reda E Girgis, Kelly Chin, Rachel Damico, Todd M Kolb, Stephen C Mathai, Paul M Hassoun
American journal of respiratory and critical care medicine, 197, 3, 388, 391, 01 Feb. 2018, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
English, Scientific journal

The impact of ambrisentan and tadalafil upfront combination therapy on cardiac function in scleroderma associated pulmonary arterial hypertension patients: cardiac magnetic resonance feature tracking study
Takahiro Sato, Bharath Ambale-Venkatesh, Joao A.C. Lima, Stefan L. Zimmerman, Ryan J. Tedford, Tomoki Fujii, Olivia L. Hulme, Erica H. Pullins, Celia P. Corona-Villalobos, Roham T. Zamanian, Omar A. Minai, Reda E. Girgis, Kelly Chin, Rubina Khair, Rachel L. Damico, Todd M. Kolb, Stephen C. Mathai, Paul M. Hassoun
Pulmonary Circulation, 8, 1, 204589321774830, 204589321774830, SAGE Publications, Jan. 2018, [Peer-reviewed], [Lead author], ［Internationally co-authored］, [International Magazine]
Scientific journal, The aim of this study was to evaluate the effect of upfront combination therapy with ambrisentan and tadalafil on left ventricular (LV) and right ventricular (RV) function in patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH). LV and RV peak longitudinal and circumferential strain and strain rate (SR), which consisted of peak systolic SR (SRs), peak early diastolic SR (SRe), and peak atrial-diastolic SR (SRa) were analyzed using cardiac magnetic resonance imaging (CMRI) data from the recently published ATPAHSS-O trial (ambrisentan and tadalafil upfront combination therapy in SSc-PAH). Twenty-one patients completed the study protocol. Measures of RV systolic function (RV free wall [RVFW] peak longitudinal strain [pLS], RVFW peak longitudinal SRs [pLSRs]) and RV diastolic function (RVFW peak longitudinal SRa [pLSRa], RVFW peak circumferential SRe) were improved after treatment. LV systolic function (LV peak global longitudinal strain [pGLS]) and diastolic function (LV peak global longitudinal SRe [pGLSRe]) were also significantly improved at follow-up. Increased 6-min walk distance was significantly correlated with RVFW pLS and pLSRs, while the decrease in N-terminal pro-brain natriuretic peptide was correlated with LV pGLS. Increased cardiac index was associated with improved LV pGLSRe, and reduction in mean right atrial pressure was correlated with improved RVFW pLS and pLSRa. Combination therapy was associated with a significant improvement in both RV and LV function as assessed by CMR-derived strain and SR. Importantly, the improvement in RV and LV strain and SR correlated with improvements in known prognostic markers of PAH. (Approved by clinicaltrials.gov [NCT01042158] before patient recruitment.)

Performance of computed tomography-derived pulmonary vasculature metrics in the diagnosis and haemodynamic assessment of pulmonary arterial hypertension.
Kaoruko Shimizu, Ichizo Tsujino, Takahiro Sato, Ayako Sugimoto, Toshitaka Nakaya, Taku Watanabe, Hiroshi Ohira, Yoichi M Ito, Masaharu Nishimura
European journal of radiology, 96, 31, 38, Nov. 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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 <5mm2 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 AUCs 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.

Right ventricular longitudinal strain is diminished in systemic sclerosis compared with idiopathic pulmonary arterial hypertension.
Monica Mukherjee, Valentina Mercurio, Ryan J Tedford, Ami A Shah, Steven Hsu, Christopher J Mullin, Takahiro Sato, Rachel Damico, Todd M Kolb, Stephen C Mathai, Paul M Hassoun
The European respiratory journal, 50, 5, Nov. 2017, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
English, Scientific journal

Decreased haptoglobin levels inversely correlated with pulmonary artery pressure in patients with pulmonary arterial hypertension: A cross-sectional study.
Hiroyuki Nakamura, Masaru Kato, Toshitaka Nakaya, Michihiro Kono, Shun Tanimura, Takahiro Sato, Yuichiro Fujieda, Kenji Oku, Hiroshi Ohira, Toshiyuki Bohgaki, Shinsuke Yasuda, Ichizo Tsujino, Masaharu Nishimura, Tatsuya Atsumi
Medicine, 96, 43, e8349, Oct. 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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 19 mg/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 66 mg/dL) were significantly lower than those in CTEPH group (median 94 mg/dL, P = .03) and CTD-non-PAH group (median 79 mg/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.

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, May 2017, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal

Accuracy of echocardiographic indices for serial monitoring of right ventricular systolic function in patients with precapillary pulmonary hypertension.
Takahiro Sato, Ichizo Tsujino, Hiroshi Ohira, Noriko Oyama-Manabe, Yoichi M Ito, Chisa Takashina, Taku Watanabe, Masaharu Nishimura
PloS one, 12, 11, e0187806, 2017, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal, 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 pre-specified 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.

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, SAGE Publications, Dec. 2016, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal, 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/m²) 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/m²) 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. This study was approved by University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) on September 1, 2013 (UMIN000011541).

The effects of 18-h fasting with low-carbohydrate diet preparation on suppressed physiological myocardial (18)F-fluorodeoxyglucose (FDG) uptake and possible minimal effects of unfractionated heparin use in patients with suspected cardiac involvement sarcoidosis.
Osamu Manabe, Keiichiro Yoshinaga, Hiroshi Ohira, Atsuro Masuda, Takahiro Sato, Ichizo Tsujino, Asuka Yamada, Noriko Oyama-Manabe, Kenji Hirata, Masaharu Nishimura, Nagara Tamaki
Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology, 23, 2, 244, 52, Apr. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: (18)F-fluorodeoxyglucose (FDG) PET plays an important role in the detection of cardiac involvement sarcoidosis (CS). However, diffuse left ventricle (LV) wall uptake sometimes makes it difficult to distinguish between positive uptake and physiological uptake. The aims of this study were to evaluate the effects of 18-h fasting with low-carbohydrate diet (LCD) vs a minimum of 6-h fasting preparations on diffuse LV FDG uptake and free fatty acid (FFA) levels in patients with suspected CS. METHODS: Eighty-two patients with suspected CS were divided into 2 preparation protocols: one with a minimum 6-h fast without LCD preparation (group A, n = 58) and the other with a minimum 18-h fast with LCD preparation (group B, n = 24). All patients also received intravenous unfractionated heparin (UFH; 50 IU/kg) before the injection of FDG. RESULTS: Group A showed a higher percentage of diffuse LV uptake than did group B (27.6 vs 0.0%, P = .0041). Group B showed higher FFA levels (1159.1  ±  393.0, 650.5  ±  310.9 μEq/L, P < .0001) than did group A. Patients with diffuse LV uptake (n = 16) showed lower FFA levels than did other patients (n = 66) (432.1  ±  296.1, 888.4  ±  381.4 μEq/L, P < .0001). UFH administration significantly increased FFAs in both groups, even in the patients with diffuse LV FDG uptake. CONCLUSIONS: The 18-h fast with LCD preparation significantly reduced diffuse LV uptake and increased FFA levels. In particular, the FFA level was significantly lower in patients with LV diffuse uptake than in patients without LV diffuse uptake. Acutely increasing plasma FFA through the use of UFH may not have a significant role in reducing physiological LV FDG uptake.

Comparison of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) and cardiac magnetic resonance (CMR) in corticosteroid-naive patients with conduction system disease due to cardiac sarcoidosis.
Hiroshi Ohira, David H Birnie, Elena Pena, Jordan Bernick, Brian Mc Ardle, Eugene Leung, George A Wells, Keiichiro Yoshinaga, Ichizo Tsujino, Takahiro Sato, Osamu Manabe, Noriko Oyama-Manabe, Masaharu Nishimura, Nagara Tamaki, Alexander Dick, Carole Dennie, Ran Klein, Jennifer Renaud, Robert A deKemp, Terrence D Ruddy, Benjamin J W Chow, Ross Davies, Renee Hessian, Peter Liu, Rob S B Beanlands, Pablo B Nery
European journal of nuclear medicine and molecular imaging, 43, 2, 259, 269, Feb. 2016, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
English, Scientific journal, PURPOSE: Cardiac sarcoidosis (CS) is a cause of conduction system disease (CSD). (18)F-Fluorodeoxyglucose-positron emission tomography (FDG PET) and cardiac magnetic resonance (CMR) are used for detection of CS. The relative diagnostic value of these has not been well studied. The aim was to compare these imaging modalities in this population. METHODS: We recruited steroid-naive patients with newly diagnosed CSD due to CS. All CS patients underwent both imaging studies within 12 weeks of each other. Patients were classified into two groups: group A with chronic mild CSD (right bundle branch block and/or axis deviation), and group B with new-onset atrioventricular block (AVB, Mobitz type II or third-degree AVB). RESULTS: Thirty patients were included. Positive findings on both imaging studies were seen in 72 % of patients (13/18) in group A and in 58 % of patients (7/12) in group B. The remainder (28 %) of the patients in group A were positive only on CMR. Of the patients in group B, 8 % were positive only on CMR and 33 % were positive only on FDG PET. Patients in group A were more likely to be positive only on CMR, and patients in group B were more likely to be positive only on FDG PET (p = 0.02). Patients in group B positive only on FDG PET underwent CMR earlier relative to their symptomatology than patients positive only on CMR (median 7.0, IQR 1.5 - 34.3, vs. 72.0, IQR 25.0 - 79.5 days; p = 0.03). CONCLUSION: The number of positive FDG PET and CMR studies was different in patients with CSD depending on their clinical presentation. This study demonstrated that CMR can adequately detect cardiac involvement associated with chronic mild CSD. In patients presenting with new-onset AVB and a negative CMR study, FDG PET may be useful for detecting cardiac involvement due to CS.

Associations among the plasma amino acid profile, obesity, and glucose metabolism in Japanese adults with normal glucose tolerance.
Chisa Takashina, Ichizo Tsujino, Taku Watanabe, Shinji Sakaue, Daisuke Ikeda, Asuka Yamada, Takahiro Sato, Hiroshi Ohira, Yoshinori Otsuka, Noriko Oyama-Manabe, Yoichi M Ito, Masaharu Nishimura
Nutrition & metabolism, 13, 5, 5, 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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 β-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.

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, 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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/m2) 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.

Ambrisentan and Tadalafil Up-front Combination Therapy in Scleroderma-associated Pulmonary Arterial Hypertension.
Paul M Hassoun, Roham T Zamanian, Rachel Damico, Noah Lechtzin, Rubina Khair, Todd M Kolb, Ryan J Tedford, Olivia L Hulme, Traci Housten, Chiara Pisanello, Takahiro Sato, Erica H Pullins, Celia P Corona-Villalobos, Stefan L Zimmerman, Mohamed A Gashouta, Omar A Minai, Fernando Torres, Reda E Girgis, Kelly Chin, Stephen C Mathai
American journal of respiratory and critical care medicine, 192, 9, 1102, 10, 01 Nov. 2015, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
English, Scientific journal, BACKGROUND: Scleroderma-associated pulmonary arterial hypertension (SSc-PAH) is a rare disease characterized by a very dismal response to therapy and poor survival. We assessed the effects of up-front combination PAH therapy in patients with SSc-PAH. METHODS: In this prospective, multicenter, open-label trial, 24 treatment-naive patients with SSc-PAH received ambrisentan 10 mg and tadalafil 40 mg daily for 36 weeks. Functional, hemodynamic, and imaging (cardiac magnetic resonance imaging and echocardiography) assessments at baseline and 36 weeks included changes in right ventricular (RV) mass and pulmonary vascular resistance as co-primary endpoints and stroke volume/pulmonary pulse pressure ratio, tricuspid annular plane systolic excursion, 6-minute walk distance, and N-terminal pro-brain natriuretic peptide as secondary endpoints. RESULTS: At 36 weeks, we found that treatment had resulted in significant reductions in median (interquartile range [IQR]) RV mass (28.0 g [IQR, 20.6-32.9] vs. 32.5 g [IQR, 23.2-41.4]; P < 0.05) and median pulmonary vascular resistance (3.1 Wood units [IQR, 2.0-5.7] vs. 6.9 Wood units [IQR, 4.0-12.9]; P < 0.0001) and in improvements in median stroke volume/pulmonary pulse pressure ratio (2.6 ml/mm Hg [IQR, 1.8-3.5] vs. 1.4 ml/mm Hg [IQR 8.9-2.4]; P < 0.0001) and mean ( ± SD) tricuspid annular plane systolic excursion (2.2 ± 0.12 cm vs. 1.65 ± 0.11 cm; P < 0.0001), 6-minute walk distance (395 ± 99 m vs. 343 ± 131 m; P = 0.001), and serum N-terminal pro-brain natriuretic peptide (647 ± 1,127 pg/ml vs. 1,578 ± 2,647 pg/ml; P < 0.05). CONCLUSIONS: Up-front combination therapy with ambrisentan and tadalafil significantly improved hemodynamics, RV structure and function, and functional status in treatment-naive patients with SSc-PAH and may represent a very effective therapy for this patient population. In addition, we identified novel hemodynamic and imaging biomarkers that could have potential value in future clinical trials. Clinical trial registered with www.clinicaltrials.gov (NCT01042158).

Reduced Sympathetic Nervous Function is Useful Marker to Detect Cardiac Sarcoidosis among Patients with Extracardiac Sarcoidosis and Suspected Cardiac Involvement using C-11 Hydroxyephedrine PET/CT
Yoshinaga Keiichiro, Manabe Osamu, Tomiyama Yuuki, Ohira Hiroshi, Tsujino Ichizo, Sato Takahiro, Nishijima Ken-ichi, Nishimura Masaharu, Tamaki Nagara
JOURNAL OF NUCLEAR MEDICINE, 56, 3, 01 May 2015, [Peer-reviewed]

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
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 34, 3, 414, 23, Mar. 2015, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal, 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 PH-related 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.

Hemodynamic effects of ambrisentan-tadalafil combination therapy on progressive portopulmonary hypertension.
Yu Yamashita, Ichizo Tsujino, Takahiro Sato, Asuka Yamada, Taku Watanabe, Hiroshi Ohira, Masaharu Nishimura
World journal of hepatology, 6, 11, 825, 9, 27 Nov. 2014, [Peer-reviewed], [International Magazine]
English, Intravenous epoprostenol is recommended for World Health Organization functional class (WHO-FC) IV patients with pulmonary arterial hypertension (PAH) in the latest guidelines. However, in portopulmonary hypertension (PoPH) patients, advanced liver dysfunction and/or thrombocytopenia often makes the use of intravenous epoprostenol challenging. Here we report the cases of two WHO-FC IV PoPH patients who were successfully treated with a combination of two oral vasodilators used to treat PAH: ambrisentan and tadalafil. Oral vasodilator therapy using a combination of ambrisentan and tadalafil may be a safe and effective therapeutic option for WHO-FC IV PoPH patients and should be considered for selected patients with severe and rapidly progressing PoPH.

Right ventricular (18)F-FDG uptake is an important indicator for cardiac involvement in patients with suspected cardiac sarcoidosis.
Osamu Manabe, Keiichiro Yoshinaga, Hiroshi Ohira, Takahiro Sato, Ichizo Tsujino, Asuka Yamada, Noriko Oyama-Manabe, Atsuro Masuda, Keiichi Magota, Masaharu Nishimura, Nagara Tamaki
Annals of nuclear medicine, 28, 7, 656, 63, Aug. 2014, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, PURPOSE: Cardiac sarcoidosis is most commonly found in the left ventricular (LV) free wall. Presence in the right ventricle (RV) is less common but might be useful for detecting cardiac involvement of sarcoidosis. (18)F-fluorodeoxyglucose ((18)F-FDG) PET has been used to detect LV regions with cardiac sarcoidosis. However, the same has not been done for RV involvement. The aims of the current study were to evaluate RV (18)F-FDG uptake and its relationship to the distribution of LV wall (18)F-FDG-positive segments in the LV, and to evaluate whether patients with positive RV (18)F-FDG uptake met the 1993 diagnostic criteria of the Japanese Ministry of Health and Welfare (JMHW) guidelines regarding sarcoidosis with suspected cardiac involvement. METHOD: Fifty-nine biopsy-proven extra-cardiac sarcoidosis patients (age 56.1 ± 14.7 years) with suspected cardiac involvement based on abnormal electrocardiography or echocardiography findings underwent fasting (18)F-FDG PET or PET/CT. The LV wall was divided into 17 segments and RV uptake was also evaluated. RESULT: Among 59 patients, 35 (59.3%) showed some abnormal (18)F-FDG uptake in the RV and/or LV wall. With respect to the RV wall, 13 (22.0%) showed abnormal (18)F-FDG uptake. The number of LV-involved segments was 4.8 ± 2.4 in the patients with RV (18)F-FDG uptake, which was significantly higher than in the patients without RV uptake, 1.8 ± 2.2 (P < 0.0001). Patients with RV uptake more frequently met the diagnostic criteria of the 1993 JMHW guidelines (n = 27), than did those without RV uptake (84.6 vs. 34.8%, P = 0.0033). CONCLUSION: (18)F-FDG PET identified RV involvement less frequently than LV involvement in this study population. However, patients who had RV uptake showed a greater number of LV-involved segments and met the JMHW diagnostic criteria more frequently. Although RV uptake is less frequent, (18)F-FDG RV uptake may be useful in diagnosing cardiac involvement in sarcoidosis. CLINICAL TRIAL REGISTRATION: UMIN000006533.

Attenuated right ventricular energetics evaluated using ¹¹C-acetate PET in patients with pulmonary hypertension.
Keiichiro Yoshinaga, Hiroshi Ohira, Ichizo Tsujino, Noriko Oyama-Manabe, Lisa Mielniczuk, Rob S B Beanlands, Chietsugu Katoh, Katsuhiko Kasai, Osamu Manabe, Takahiro Sato, Satoshi Fujii, Yoichi M Ito, Yuuki Tomiyama, Masaharu Nishimura, Nagara Tamaki
European journal of nuclear medicine and molecular imaging, 41, 6, 1240, 50, Jun. 2014, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
English, Scientific journal, PURPOSE: The right ventricle (RV) has a high capacity to adapt to pressure or volume overload before failing. However, the mechanisms of RV adaptation, in particular RV energetics, in patients with pulmonary hypertension (PH) are still not well understood. We aimed to evaluate RV energetics including RV oxidative metabolism, power and efficiency to adapt to increasing pressure overload in patients with PH using (11)C-acetate PET. METHODS: In this prospective study, 27 patients with WHO functional class II/III PH (mean pulmonary arterial pressure 39.8 ± 13.5 mmHg) and 9 healthy individuals underwent (11)C-acetate PET. (11)C-acetate PET was used to simultaneously measure oxidative metabolism (k mono) for the left ventricle (LV) and RV. LV and RV efficiency were also calculated. RESULTS: The RV ejection fraction in PH patients was lower than in controls (p = 0.0054). There was no statistically significant difference in LV k mono (p = 0.09). In contrast, PH patients showed higher RV k mono than did controls (0.050 ± 0.009 min(-1) vs. 0.030 ± 0.006 min(-1), p < 0.0001). PH patients exhibited significantly increased RV power (p < 0.001) and hence increased RV efficiency compared to controls (0.40 ± 0.14 vs. 0.017 ± 0.12 mmHg·mL·min/g, p = 0.001). CONCLUSION: The RV oxidative metabolic rate was increased in patients with PH. Patients with WHO functional class II/III PH also had increased RV power and efficiency. These findings may indicate a myocardial energetics adaptation response to increasing pulmonary arterial pressure.

Increased left ventricular F-18 fluorodeoxyglucose uptake associated with cardiac sympathetic nervous dysfunction using C-11 hydroxyephedine PET/CT in patients with cardiac sarcoidosis
Yoshinaga Keiichiro, Tsujino Ichizo, Sato Takahiro, Yamada Aska, Tomiyama Yuuki, Ohira Hiroshi, Manabe Osamu, Nishijima Ken-ichi, Nishimura Masaharu, Tamaki Nagara
JOURNAL OF NUCLEAR MEDICINE, 55, May 2014, [Peer-reviewed]

The effects of the 18 hours fasting preparation on plasma free fatty acid and physiological myocardial F-18-FDG uptake in patients of suspected cardiac involvement sarcoidosis
Manabe Osamu, Yoshinaga Keiichiro, Ohira Hiroshi, Masuda Atsuro, Sato Takahiro, Tsujino Ichizo, Yamada Asuka, Oyama-Manabe Noriko, Nishimura Masaharu, Tamaki Nagara
JOURNAL OF NUCLEAR MEDICINE, 55, May 2014, [Peer-reviewed]

Reduced pulmonary blood flow using O-15 labeled water PET in patients with chronic thromboembolic pulmonary hypertension
Yoshinaga Keiichiro, Tomiyama Yuuki, Tsujino Ichizo, Sato Takahiro, Manabe Osamu, Katoh Chietsugu, Ohira Hiroshi, Nishimura Masaharu, Tamaki Nagara
JOURNAL OF NUCLEAR MEDICINE, 55, May 2014, [Peer-reviewed]

LEFT VENTRICULAR F-18 FLUORODEOXYGLUCOSE UPTAKE ASSOCIATED WITH MYOCARDIAL AUT ONOMIC DYSFUNCTION IN PATIENTS SUSPECTED WITH CARDIAC SARCOIDOSIS
Yoshinaga Keiichiro, Ohira Hiroshi, Tsujino Ichizo, Katoh Chietsugu, Kasai Katsuhiko, Tomiyama Yuuki, Sato Takahiro, Oyama-Manabe Noriko, Nishimura Masaharu, Tamaki Nagara
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 63, 12, A1018, 01 Apr. 2014, [Peer-reviewed]

Subcutaneous injection of 300 IU of glargine during a suicide attempt in a man with mitochondrial diabetes
Ichizo Tsujino, Akiko Hayashishita, Taku Watanabe, Asuka Yamada, Takahiro Sato, Satoshi Itaya, Chisa Takashina, Yoshinori Otsuka, Yusuke Shimizu, Masaharu Nishimura
Journal of the Japan Diabetes Society, 57, 9, 722, 728, Japan Diabetes Society, 2014
Japanese

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 (Tokyo, Japan), 53, 17, 1985, 90, 2014, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, 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.

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
The international journal of cardiovascular imaging, 29, 8, 1799, 805, Dec. 2013, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal, 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 × TAPSE + 0.6) and the simplified prediction equation (RVEF = 2 × TAPSE). Bland-Altman plot showed that the mean difference ± limits of agreement was 0.0 ± 10.6 for the original equation and -0.6 ± 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 ≥40% 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 × 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.

Low Agreement of 18F-Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) and Cardiac Magnetic Resonance (CMR) in Patients With Conduction Disease Due to Cardiac Sarcoidosis
Ohira Hiroshi, Birnie David, Mc Ardle Brian, Leung Eugene, Yoshinaga Keiichiro, Tsujino Ichizo, Sato Takahiro, Bernick Jordan, Manabe Osamu, Nishimura Masaharu, Tamaki Nagara, Davies Ross, Klein Ran, Guo Ann, Garrard Linda, Ruddy Terrence, Chow Benjamin, Hessian Renee, Kingsbury Kori, Beanlands Rob S, Nery Pablo
CIRCULATION, 128, 22, 26 Nov. 2013, [Peer-reviewed]

FIVE CASES WITH OUT-OF-PROPORTION GROUP 3 PULMONARY HYPERTENSION WITH FAVORABLE HEMODYNAMIC RESPONSE TO VASODILATORS
Akane Kuroki, Takahiro Sato, Ichizo Tsujino, Ayako Igarashi, Hiroshi Ohira, Asuka Yamada, Taku Watanabe, Masaru Suzuki, Satoshi Konno, Masaharu Nishimura
RESPIROLOGY, 18, 172, 172, Nov. 2013, [Peer-reviewed]
English

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
RESPIROLOGY, 18, 20, 20, Nov. 2013, [Peer-reviewed]
English

Right Atrial Volume and Reservoir Function are Novel Predictors of Clinical Worsening in Pulmonary Hypertension
Takahiro Sato, Ichizo Tsujino, Hiroshi Ohira, Noriko Oyama-Manabe, Yoichi M. Ito, Masaharu Nishimura
CIRCULATION, 128, 22, Nov. 2013, [Peer-reviewed]
English

FAVORABLE EFFECT OF ORAL COMBINATION VASODILATOR THERAPY FOR TWO CASES WITH SEVERE PORTOPULMONARY HYPERTENSION
Yu Yamashita, Takahiro Sato, Ichizo Tsujino, Itaya Satoshi, Akiko Hayashishita, Asuka Yamada, Taku Watanabe, Hiroshi Ohira, Masaharu Nishimura
RESPIROLOGY, 18, 21, 21, Nov. 2013, [Peer-reviewed]
English

Elevated (18)F-fluorodeoxyglucose uptake in the interventricular septum is associated with atrioventricular block in patients with suspected cardiac involvement sarcoidosis.
Osamu Manabe, Hiroshi Ohira, Keiichiro Yoshinaga, Takahiro Sato, Alisa Klaipetch, Noriko Oyama-Manabe, Yoichi M Ito, Ichizo Tsujino, Masaharu Nishimura, Nagara Tamaki
European journal of nuclear medicine and molecular imaging, 40, 10, 1558, 66, Oct. 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal, PURPOSE: Cardiac involvement in sarcoidosis is one of the leading causes of death associated with abnormalities of the conduction system. (18)F-FDG PET is useful for detecting inflammatory lesions in cardiac sarcoidosis. However, the relationship between ECG abnormalities and focal (18)F-FDG uptake has not been studied. The aim of this study was to evaluate the relationship between electrocardiogram (ECG) abnormalities and the location of elevated myocardial (18)F-FDG uptake in patients with sarcoidosis. METHODS: Included in the study were 50 patients (56.3 ± 14.9 years old) with histologically proven sarcoidosis with suspected cardiac involvement based on ECG or echocardiography. All patients had fasted for at least 6 h and were given unfractionated heparin (50 IU/kg) intravenously to reduce the physiological (18)F-FDG uptake in the myocardium. The left ventricle (LV) wall was divided into 17 segments by visual analysis. Obvious accumulation in each segment was defined as positive. RESULTS: Of the 50 patients, 33 showed some ECG abnormalities, including atrioventricular (AV) block in 13. Patients with abnormal ECG findings had a higher number of regions with (18)F-FDG uptake than patients without ECG abnormality (3.48 ± 2.73 vs. 1.41 ± 2.09 regions, p = 0.0051). Among ECG abnormalities, the predictor for interventricular septum wall (18)F-FDG involvement was AV block (p = 0.0025). CONCLUSION: Patients with ECG abnormalities showed a higher number of abnormal (18)F-FDG myocardial uptake regions than patients without ECG abnormalities. In particular, focal (18)F-FDG uptake in the interventricular septum in cardiac sarcoidosis was associated with AV block. Therefore, determination of regional (18)F-FDG distribution might contribute to patient management in cardiac sarcoidosis.

Right atrial volume and phasic function in pulmonary hypertension.
Takahiro Sato, Ichizo Tsujino, Noriko Oyama-Manabe, Hiroshi Ohira, Yoichi M Ito, Asuka Yamada, Daisuke Ikeda, Taku Watanabe, Masaharu Nishimura
International journal of cardiology, 168, 1, 420, 6, 20 Sep. 2013, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal, 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.

Accurate monitoring of the right ventricular ejection fraction by echocardiography in pulmonary hypertension
Sato Takahiro, Tsujino Ichizo, Oyama-Manabe Noriko, Ohira Hiroshi, Watanabe Taku, Nishimura Masaharu
EUROPEAN RESPIRATORY JOURNAL, 42, 01 Sep. 2013, [Peer-reviewed], [International Magazine]

Incidence, clinical manifestations and prognosis of cardiac sarcoidosis in patients with pulmonary sarcoidosis
Tomoe Abe, Takahiro Sato, Ichizo Tsujino, Hiroshi Ohira, Keiichiro Yoshinaga, Noriko Oyama-Manabe, Takeshi Hattori, Satoshi Konno, Masaharu Nishimura, Tomoe Karino
EUROPEAN RESPIRATORY JOURNAL, 42, Sep. 2013, [Peer-reviewed]
English

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, 3, Sep. 2013, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal, 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.

EFFECTS OF INTENSIFIED PULMONARY HYPERTENSION SPECIFIC VASODILATOR THERAPY ON MYOCARDIAL OXIDATIVE METABOLISM AASSESSED USING C-11 ACETATE PET IN PATIENTS WITH PULMONARY HYPERTENSION
Yoshinaga Keiichiro, Ohira Hiroshi, Tsujino Ichizo, Manabe Osamu, Sato Takahiro, Katoh Chietsugu, Kasai Katsuhiko, Tomiyama Yuuki, Oyama-Manabe Noriko, Nishimura Masaharu, Tamaki Nagara
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 61, 10, E1002, 12 Mar. 2013, [Peer-reviewed]

The strain-encoded (SENC) MR imaging for detection of global right ventricular dysfunction in pulmonary hypertension.
Noriko Oyama-Manabe, Takahiro Sato, Ichizo Tsujino, Kohsuke Kudo, Osamu Manabe, Fumi Kato, Nael F Osman, Satoshi Terae
The international journal of cardiovascular imaging, 29, 2, 371, 8, Feb. 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal, The aim of this study was to explore whether the regional peak longitudinal (LS) and circumferential strains (CS) at the right ventricular (RV) free wall could be used to identify global RV dysfunction in relation to RV ejection fraction (RVEF) and plasma concentration of brain natriuretic peptide (BNP) in pulmonary hypertension (PH). A total of 37 consecutive patients diagnosed with PH and 13 healthy control subjects were included. Fast strain encoded and routine cine MRI was performed. The LS and CS at three RV levels were quantified and their relations with RVEF and BNP were investigated. Receiver operating characteristic (ROC) analysis was employed to assess the diagnostic utility of strain encoded MRI for the detection of low RVEF. Significant correlations with LS were observed for RVEF and BNP. Compared to CS, LS showed better correlation with RVEF. The mid-ventricular level of RV was the most sensitive site for evaluation of RV dysfunction. According to our ROC analysis, LS showed higher sensitivity and specificity to detect low RVEF. Compared to CS, LS showed stronger correlations with RVEF and BNP and could be a good detector of RV dysfunction in PH.

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, 4, 7, 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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.

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, 2013, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal, 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 38±9 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.

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, 7, 28 Jun. 2012, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal

Regional F-18-FDG uptake in relation to ECG abnormalities in patients with cardiac sarcoidosis
Manabe Osamu, Yoshinaga Keiichiro, Ohira Hiroshi, Klaipetch Alisa, Oyama-Manabe Noriko, Tsujino Ichizo, Sato Takahiro, Magota Keiichi, Nishimura Masaharu, Tamaki Nagara
JOURNAL OF NUCLEAR MEDICINE, 53, 01 May 2012, [Peer-reviewed]

Relationship between the cardiac lesion and the other organ involvements of sarcoidosis using F-18-FDG PET
Manabe Osamu, Yoshinaga Keiichiro, Ohira Hiroshi, Klaipetch Alisa, Oyama-Manabe Noriko, Tsujino Ichizo, Sato Takahiro, Magota Keiichi, Nishimura Masaharu, Tamaki Nagara
JOURNAL OF NUCLEAR MEDICINE, 53, 01 May 2012, [Peer-reviewed]

Abnormal interventricular septal displacement reflects increased oxidative metabolism in right ventricular free wall but not interventricular septum in patients with pulmonary hypertension using C-11 acetate PET
Yoshinaga Keiichiro, Sato Takahiro, Ohira Hiroshi, Tsujino Ichizo, Manabe Osamu, Katoh Chietsuim, Kasai Katsuhiko, Nishimura Masaharu, Tamaki Nagara
JOURNAL OF NUCLEAR MEDICINE, 53, 01 May 2012, [Peer-reviewed]

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 : official publication of the American Society of Echocardiography, 25, 3, 280, 6, Mar. 2012, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal, 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.

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 : official journal of the Japanese Circulation Society, 76, 1, 238, 9, 2012, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Paradoxical Interventricular Septal Motion Predisposes to Late Gadolinium Enhancement of Ventricular Insertion Points in Pulmonary Hypertension
Takahiro Sato, Ichizo Tsujino, Hiroshi Ohira, Noriko Oyama-Manabe, Asuka Yamada, Masaharu Nishimura
CIRCULATION, 124, 21, Nov. 2011, [Peer-reviewed]
English

Utility of left ventricular systolic torsion derived from 2-dimensional speckle-tracking echocardiography in monitoring acute cellular rejection in heart transplant recipients.
Takahiro Sato, Tomoko S Kato, Kazuo Komamura, Shuji Hashimoto, Toshiaki Shishido, Akiko Mano, Noboru Oda, Ayako Takahashi, Hatsue Ishibashi-Ueda, Takeshi Nakatani, Masanori Asakura, Hideaki Kanzaki, Kazuhiko Hashimura, Masafumi Kitakaze
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 30, 5, 536, 43, May 2011, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal, BACKGROUND: Reduced left ventricular torsion (LV-tor) has been reported to be associated with acute rejection in heart transplant (HTx) recipients. We investigated the utility of LV-tor analysis derived from 2-dimensional speckle-tracking echocardiography (2D-STE) for detecting allograft rejection. METHODS: A total of 301 endomyocardial biopsies (EMBs), right heart catheterizations and echocardiograms were performed in 32 HTx recipients. Echocardiography was done within 3 hours from EMB or simultaneously with the procedures. The LV-tor was defined as the difference between apical and basal end-systolic rotations. The LV-tor values with and without cellular rejection were compared. In addition, we investigated whether the change in LV-tor values predicts the change in rejection grade in each patient. The baseline LV-tor value in each patient was defined as a mean value of the first 3 LV-tor measurements obtained when the patient was free from rejection. RESULTS: According to the conventional International Society for Heart and Lung Transplantation criteria, 274 biopsies showed a rejection Grade of 0, 1a or 1b (Group AR(-)), whereas 27 biopsies were Grade 2 or higher (Group AR(+)). LV-tor decreased more in Group AR(+) than in Group AR(-) (9.3 ± 0.7 vs 12.2 ± 0.2 degrees, p < 0.0001). In the LV-tor measurement for each patient, the 25% reduction in LV-tor value from baseline predicted Grade 2 or higher rejection with a predictive accuracy of 92.9%. CONCLUSION: LV-tor derived from 2D-STE could be of clinical value for non-invasive monitoring of acute rejection in HTx recipients.

Early detection of cardiac sarcoid lesions with (18)F-fluoro-2-deoxyglucose positron emission tomography.
Hiroshi Ohira, Ichizo Tsujino, Takahiro Sato, Keiichiro Yoshinaga, Osamu Manabe, Noriko Oyama, Masaharu Nishimura
Internal medicine (Tokyo, Japan), 50, 11, 1207, 9, 2011, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, In April 2005, a 72-year-old woman with pulmonary sarcoidosis exhibited focal (18)F-fluoro-2-deoxyglucose ((18)F-FDG) uptake in her heart on (18)F-FDG positron emission tomography (PET). Although Japanese guidelines for diagnosing cardiac sarcoidosis were not met at this point, electrocardiography, echocardiography, and magnetic resonance imaging became diagnostic for cardiac sarcoidosis 1 year later. In the present case report, the potential of (18)F-FDG PET in the early recognition of cardiac sarcoidosis in comparison with other imaging modalities is discussed.

Second left ventricular aneurysm newly developed in a patient with untreated cardiac sarcoidosis.
Takahiro Sato, Hideaki Kanzaki, Yoshio Ishida, Makoto Amaki, Takahiro Ohara, Takuya Hasegawa, Kazuhiko Hashimura, Satoshi Nakatani, Naoaki Yamada, Yoshihiko Ikeda, Hatsue Ueda-Ishibashi, Masafumi Kitakaze
Circulation journal : official journal of the Japanese Circulation Society, 74, 11, 2477, 8, Nov. 2010, [Peer-reviewed], [Lead author], [Domestic magazines]
English, Scientific journal

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, 10, Nov. 2006, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal, 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.

ペースメーカー感染により肺塞栓を繰り返したCTEPHの1例
佐藤隆博, 佐藤隆博, 小森卓, 島秀起, 中村順一, 直亨則, 中久保祥, 若林健人, 辻野一三, 辻野一三, 今野哲, 今野哲, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 10th, 2025

第4群肺高血圧症のBPA前後における合成心電図V3R,V4R,V5Rの検討
原田亜実, 佐藤隆博, 佐藤隆博, 三谷麻子, 岩井孝仁, 井上真美子, 中村順一, 今野哲, 今野哲, 辻野一三, 辻野一三, 山下直樹, 豊嶋崇徳, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 10th, 2025

肺病変合併肺動脈性肺高血圧症の臨床的特徴および予後
小森卓, 辻野一三, 吉川修平, 島秀起, 中村順一, 杉本絢子, 佐藤隆博, 今野哲, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 10th, 2025

CTEPHに対するBPA後の6分間歩行距離の変化と身体所見の関係
藤内宏典, 堀弘明, 小森卓, 島秀起, 中村順一, 杉本絢子, 佐藤隆博, 佐藤隆博, 辻野一三, 辻野一三, 今野哲, 今野哲, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 10th, 2025

慢性血栓塞栓性肺高血圧症患者における肺血管拡張薬の短期効果
島秀起, 佐藤隆博, 佐藤隆博, 小森卓, 吉川修平, 中村順一, 辻野一三, 辻野一三, 今野哲, 今野哲, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 10th, 2025

肺高血圧症(平均肺動脈圧>20mmHg)の心電図所見の検討
三谷麻子, 佐藤隆博, 佐藤隆博, 原田亜実, 岩井孝仁, 井上真美子, 中村順一, 今野哲, 今野哲, 辻野一三, 辻野一三, 山下直樹, 豊嶋崇徳, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 10th, 2025

エポプロステノールを離脱したSLEによる肺高血圧症の一例
吉川修平, 佐藤隆博, 小森卓, 島秀起, 中村順一, 辻野一三, 馬詰武, 安田充孝, 今野哲, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 10th, 2025

左右で病型が異なったCTEPHの2症例
中村順一, 小森卓, 吉川修平, 島秀起, 佐藤隆博, 佐藤隆博, 大岡智学, 辻野一三, 辻野一三, 今野哲, 今野哲, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 10th, 2025

Impact of cancer on the clinical course and outcome of patients with CTEPH
中村順一, 辻野一三, 辻野一三, 島秀起, 中谷資隆, 杉本絢子, 佐藤隆博, 佐藤隆博, 渡部拓, 大平洋, 鈴木雅, 横田勲, 今野哲, 今野哲, 日本呼吸器学会誌(Web), 13, 2024

気管支動脈瘤を伴った肺高血圧症の2例
玉槻大輔, 佐藤隆博, 辻野一三, 島秀起, 中村順一, 阿保大介, 今野哲, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 9th (CD-ROM), 2024

PAHにおける間質性肺疾患合併の割合および臨床的意義
小森卓, 島秀起, 中村順一, 杉本絢子, 佐藤隆博, 辻野一三, 今野哲, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 9th (CD-ROM), 2024

肺血管拡張療法がPAHと3群PHの右室機能および予後に与える影響
島秀起, 辻野一三, 辻野一三, 中村順一, 佐藤隆博, 佐藤隆博, 今野哲, 今野哲, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 9th (CD-ROM), 2024

呼吸機能検査と運動負荷心エコーを組合わせたPAHスクリーニング
鎌田和郎, 加藤将, 石坂傑, 久田諒, 河野通仁, 藤枝雄一郎, 佐藤隆博, 辻野一三, アメングアル オルガ, 渥美達也, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 9th (CD-ROM), 2024

深層学習を用いた心尖部四腔像からの右室駆出率の推定
村山迪史, 村山迪史, 加賀早苗, 加賀早苗, 向井葵, 永井優衣, 杉森博行, 吉村高明, 島秀起, 常田慧徳, 西野久雄, 中村順一, 佐藤隆博, 辻野一三, 日本超音波検査学会学術集会講演抄録集(Web), 49th, 2024

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, Oct. 2023
日本サルコイドーシス, Japanese

肺動脈性肺高血圧症における肺拡散能力低下の機序及び臨床的意義
杉本絢子, 辻野一三, 辻野一三, 島秀起, 中村順一, 佐藤隆博, 佐藤隆博, 清水薫子, 横田卓, 今野哲, 今野哲, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 8th, 2023

肺疾患合併肺高血圧症における右室機能と予後に関する検討
島秀起, 辻野一三, 辻野一三, 中村順一, 佐藤隆博, 佐藤隆博, 鈴木雅, 今野哲, 今野哲, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 8th, 2023

Disease specific vasculopathy and pathogenesis of pulmonary hypertension in interstitial lung disease
杉本絢子, 辻野一三, 辻野一三, 中村順一, 佐藤隆博, 佐藤隆博, 鈴木雅, 高村圭, 谷口浩二, 田中伸哉, 今野哲, 日本呼吸器学会誌(Web), 12, 2023

Pathological study on the pulmonary vasculopathy in autopsy cases of pulmonary hypertension associated with interstitial lung disease
杉本絢子, 辻野一三, 辻野一三, 中村順一, 佐藤隆博, 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, 今野哲, 日本呼吸器学会誌(Web), 12, 2023

Role of imaging studies in the diagnosis, classification, and severity evaluation of pulmonary hypertension.
佐藤隆博, 辻野一三, 月刊呼吸器内科, 41, 6, 2022

Contribution of microvessel-remodeling to the complication of pulmonary hypertension in interstitial lung disease
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, 日本呼吸器学会誌(Web), 11, 2022

PVODに関連した胸部CT所見を有する強皮症患者の循環呼吸動態
守谷悠, 加藤将, 蜷川慶太, 河野通仁, 藤枝雄一郎, 佐藤隆博, 辻野一三, 渥美達也, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 7th, 2022

右室収縮/拡張能の評価に最も適切な心エコー指標は何か?
島秀起, 辻野一三, 中谷資隆, 三浦瞬, 堀井洋志, 中村順一, 佐藤隆博, 大平洋, 千葉泰之, 今野哲, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 7th, 2022

肺高血圧合併間質性肺疾患における肺血管病変の病理学的解析
杉本絢子, 辻野一三, 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, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 7th, 2022

Nottingham型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, 島秀起, 中村順一, 中谷資隆, 渡部拓, 大平洋, 橋本大吾, 辻野一三, 今野哲, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 7th, 2022

肺高血圧症における心臓MRIによる右心機能評価
佐藤隆博, 佐藤隆博, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 7th, 2022

北海道大学病院におけるPVOD/PCH11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, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 7th, 2022

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, 大塚紀幸, 中村順一, 中谷資隆, 佐藤隆博, 渡部拓, 大平洋, 今野哲, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 6th, 2021

肺高血圧症の死因解析-各群の特徴を実臨床でどう活かすか
中村順一, 辻野一三, 中谷資隆, 杉本絢子, 佐藤隆博, 鈴木雅, 渡部拓, 大平洋, 今野哲, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 6th, 2021

目でみる肺高血圧症 右心評価におけるMRI
常田 慧徳, 佐藤 隆博, 大平 洋, 辻野 一三, Pulmonary Hypertension Update, 6, 2, 76, 80, Nov. 2020
(株)メディカルレビュー社, Japanese

【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, 67, 4, 574, 578, Nov. 2019
(株)医学書院, Japanese

Imaging of right heart and pulmonary circulation in pulmonary hypertension
佐藤隆博, 大平洋, 真鍋徳子, 辻野一三, 辻野一三, 日本臨床, 77, 7, 1102, 1107, Jul. 2019
(株)日本臨床社, Japanese

正常耐糖能日本人男性における体幹部脂肪分布パターンとインスリン抵抗性の関連　　　　　　　　　　　　　　　
高階 知紗, 辻野 一三, 坂上 慎二, 渡部 拓, 池田 大輔, 山田 安寿香, 佐藤 隆博, 大平 洋, 大塚 吉則, 大山 徳子[真鍋], 西村 正治, Diabetes Frontier Online, 5, np25, np25, Dec. 2018
(株)メディカルレビュー社, Japanese

【右室・肺循環の最前線】右室機能の画像評価 心臓MRI
佐藤 隆博, 辻野 一三, 真鍋 徳子, 循環器内科, 84, 2, 165, 170, Aug. 2018
(有)科学評論社, Japanese

C-11 Hydroxyephedrine PET/CTを用いた心交感神経機能検出による心サルコイドーシス診断の有用性　　　　　　　　　　　　　　　
吉永 恵一郎, 真鍋 治, 大平 洋, 辻野 一三, 佐藤 隆博, 加藤 千恵次, 西村 正治, 玉木 長良, 核医学, 53, Suppl., S305, S305, Oct. 2016
(一社)日本核医学会, Japanese

MRI計測による肺循環時間は肺高血圧重症度と相関するか
真鍋 徳子[大山], 佐藤 隆博, 大平 洋, 辻野 一三, 中谷 資隆, 加藤 扶美, 工藤 與亮, 玉木 長良, 日独医報, 61, 1, 133, 133, Sep. 2016
バイエル薬品(株), Japanese

肺高血圧症における右室stiffnessに関する検討
中谷 資隆, 辻野 一三, 佐藤 隆博, 渡部 拓, 大平 洋, 真鍋 徳子, 西村 正治, 呼吸と循環, 64, 5, S37, S37, May 2016
(株)医学書院, Japanese

重症3群肺高血圧症の右室形態と収縮能への肺血管拡張療法の効果　　　　　　　　　　　　　　　
杉本 絢子, 辻野 一三, 中村 順一, 佐藤 隆博, 大平 洋, 渡部 拓, 鈴木 雅, 今野 哲, 西村 正治, 呼吸と循環, 64, 5, S38, S38, May 2016
(株)医学書院, Japanese

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(Web), 53, Supplement, 2016

日本人における肥満と禁煙の関連について　　　　　　　　　　　　　　　
渡部 拓, 今野 哲, 辻野 一三, 伊藤 陽一, 高階 知紗, 佐藤 隆博, 谷口 正実, 秋山 一男, 赤澤 晃, 西村 正治, 糖尿病, 58, 9, 721, 721, Sep. 2015
(一社)日本糖尿病学会, Japanese

慢性血栓性肺高血圧症における両側肺血流量の低下 酸素15標識水ポジトロン断層撮像による定量的検出　　　　　　　　　　　　　　　
吉永 恵一郎, 富山 勇輝, 大平 洋, 辻野 一三, 佐藤 隆博, 真鍋 治, 加藤 千恵次, 西村 正治, 玉木 長良, 核医学, 52, 3, 257, 257, Sep. 2015
(一社)日本核医学会, Japanese

膠原病 心臓MRIは強皮症性肺高血圧症の予後予測に有用である　　　　　　　　　　　　　　　
野口 淳史, 保田 晋助, 河野 通仁, 加藤 将, 真鍋 徳子, 佐藤 隆博, 辻野 一三, 西村 正治, 渥美 達也, 呼吸と循環, 63, 8, S34, S34, Aug. 2015
(株)医学書院, Japanese

重症3群肺高血圧症9例に対する肺血管拡張剤の治療経験　　　　　　　　　　　　　　　
佐藤 隆博, 辻野 一三, 中谷 資隆, 板谷 利, 渡部 拓, 大平 洋, 西村 正治, 呼吸と循環, 63, 8, S56, S57, Aug. 2015
(株)医学書院, Japanese

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, Jun. 2015
English, Summary international conference

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(Web), 58, 9, 2015

日本人における肥満と喫煙状態の関連について
渡部 拓, 今野 哲, 辻野 一三, 伊藤 陽一, 中谷 資隆, 高階 知紗, 佐藤 隆博, 谷口 正実, 秋山 一男, 赤澤 晃, 西村 正治, 肥満研究, 20, Suppl., 180, 180, Oct. 2014
(一社)日本肥満学会, Japanese

自殺企図にてグラルギン300単位を自己注射したミトコンドリア病合併糖尿病の1例
辻野 一三, 林下 晶子, 渡部 拓, 山田 安寿香, 佐藤 隆博, 板谷 利, 高階 知紗, 大塚 吉則, 清水 祐輔, 西村 正治, 糖尿病, 57, 9, 722, 728, Sep. 2014
(一社)日本糖尿病学会, Japanese

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　　　　　　　　　　　　　　　
真鍋 治, 吉永 恵一郎, 大平 洋, 佐藤 隆博, 辻野 一三, 益田 淳朗, 渡部 拓, 真鍋 徳子, 西村 正治, 玉木 長良, 核医学, 51, 3, 322, 322, Sep. 2014
(一社)日本核医学会, Japanese

酸素15標識水ポジトロン断層撮像による慢性血栓性肺高血圧症における肺血流量の低下の定量的検出　　　　　　　　　　　　　　　
吉永 恵一郎, 富山 勇輝, 辻野 一三, 佐藤 隆博, 真鍋 治, 加藤 千恵次, 大平 洋, 西村 正治, 玉木 長良, 核医学, 51, 3, 332, 332, Sep. 2014
(一社)日本核医学会, Japanese

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, Sep. 2014
(一社)日本心臓病学会, Japanese

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, Jun. 2014
日本心臓核医学会, Japanese

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　　　　　　　　　　　　　　　
益田 淳朗, 真鍋 治, 吉永 恵一郎, 大平 洋, 佐藤 隆博, 辻野 一三, 渡部 拓, 真鍋 徳子, 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, Jun. 2014
日本心臓核医学会, Japanese

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, May 2014
(一社)日本老年医学会, Japanese

日本人における肥満と喫煙状態の関連について　　　　　　　　　　　　　　　
中谷 資隆, 渡部 拓, 辻野 一三, 今野 哲, 伊藤 陽一, 板谷 利, 高階 知紗, 佐藤 隆博, 山田 安寿香, 大塚 吉則, 谷口 正実, 秋山 一男, 赤澤 晃, 西村 正治, 糖尿病, 57, Suppl.1, S, 287, Apr. 2014
(一社)日本糖尿病学会, Japanese

胃切後ダンピング症状及び高血糖がシタグリプチンにより改善した2症例　　　　　　　　　　　　　　　
渡部 拓, 山田 安寿香, 板谷 利, 林下 晶子, 高階 知紗, 佐藤 隆博, 辻野 一三, 大塚 吉則, 西村 正治, 糖尿病, 57, 3, 220, 220, Mar. 2014
(一社)日本糖尿病学会, Japanese

自殺企図にてグラルギン300単位を自己注射したミトコンドリア糖尿病の1例
井口 大暢, 辻野 一三, 林下 晶子, 山田 安寿香, 板谷 利, 高階 知紗, 佐藤 隆博, 渡部 拓, 大塚 吉則, 西村 正治, 糖尿病, 57, 3, 222, 222, Mar. 2014
(一社)日本糖尿病学会, Japanese

肺静脈閉塞性疾患/肺毛細血管腫症に対してイマチニブが有効であった1例
中谷資隆, 佐藤隆博, 辻野一三, 板谷利, 高階知紗, 渡部拓, 大平洋, 日本循環器学会北海道地方会(Web), 111th, 2014

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, Oct. 2013
English, Summary international conference

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, Oct. 2013
日本サルコイドーシス, Japanese

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, Sep. 2013
English, Summary international conference

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, Suppl.I, 262, 262, Sep. 2013
(一社)日本心臓病学会, Japanese

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
吉永 恵一郎, 伊藤 陽一, 大平 洋, 辻野 一三, 真鍋 治, 加藤 千恵次, 佐藤 隆博, 真鍋 徳子, 藤井 聡, 西村 正治, 玉木 長良, 核医学, 50, 3, S204, S204, Sep. 2013
(一社)日本核医学会, Japanese

【肺高血圧症制圧のための完全ガイド】診る 肺高血圧症はどうやって診断する
佐藤 隆博, 辻野 一三, Heart View, 17, 7, 692, 699, Jul. 2013
(株)メジカルビュー社, Japanese

日本人における肥満と喫煙状態の関連について　　　　　　　　　　　　　　　
渡部 拓, 今野 哲, 辻野 一三, 高階 知紗, 佐藤 隆博, 山田 安寿香, 伊佐田 朗, 谷口 正実, 秋山 一男, 赤澤 晃, 西村 正治, 糖尿病, 56, Suppl.1, S, 362, Apr. 2013
(一社)日本糖尿病学会, Japanese

脳死肺移植を施行した重症の肺高血圧を伴う肺ランゲルハンス細胞組織球症の一例
吉田 貴之, 佐藤 隆博, 大平 洋, 長井 桂, 今野 哲, 辻野 一三, 西村 正治, 谷野 美智枝, 陳 豊史, 伊達 洋至, 日本呼吸器学会誌, 2, 増刊, 160, 160, Mar. 2013
(一社)日本呼吸器学会, Japanese

呼吸器疾患に伴う肺高血圧症に対する経口肺高血圧症治療薬の効果
五十嵐 絢子, 鈴木 雅, 佐藤 隆博, 辻野 一三, 大平 洋, 山田 安寿香, 高階 知紗, 渡部 拓, 吉田 貴之, 清水 健一, 長井 桂, 今野 哲, 西村 正治, 日本呼吸器学会誌, 2, 増刊, 179, 179, Mar. 2013
(一社)日本呼吸器学会, Japanese

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, Feb. 2013
(公社)日本医学放射線学会, English

高用量のインスリンからエキセナチドへの切り替えが成功した2型糖尿病の1例
老田 真佑子, 渡部 拓, 高階 知紗, 佐藤 隆博, 山田 安寿香, 大塚 吉則, 辻野 一三, 西村 正治, 糖尿病, 56, 1, 52, 52, Jan. 2013
(一社)日本糖尿病学会, Japanese

インスリン治療からエキセナチドに切り替えた2症例
後藤 知紗, 大平 洋, 佐藤 隆博, 山田 安寿香, 渡部 拓, 大平 恵, 辻野 一三, 大塚 吉則, 西村 正治, 糖尿病, 55, 10, 828, 828, Oct. 2012
(一社)日本糖尿病学会, Japanese

肺高血圧症患者の右室収縮能の心エコー指標の正確性の検討
佐藤 隆博, 辻野 一三, 大平 洋, 西村 正治, Therapeutic Research, 33, 10, 1469, 1471, Oct. 2012
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。, ライフサイエンス出版(株), Japanese

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, Suppl.I, 339, 339, Aug. 2012
(一社)日本心臓病学会, Japanese

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, S275, S275, Aug. 2012
(一社)日本核医学会, Japanese

中高用量インスリン治療からエキセナチドへの切り替えに成功した2症例
後藤 知紗, 大平 洋, 佐藤 隆博, 山田 安寿香, 渡部 拓, 大塚 吉則, 辻野 一三, 西村 正治, 糖尿病, 55, Suppl.1, S, 258, Apr. 2012
(一社)日本糖尿病学会, Japanese

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, Dec. 2011
バイエル薬品(株), Japanese

門脈肺高血圧症の急性増悪にAmbrisentanとTadalafilのCombination Therapyが著効した1例
佐藤 隆博, 辻野 一三, 大平 洋, 山田 安寿香, 後藤 知紗, 渡部 拓, 西村 正治, Therapeutic Research, 32, 10, 1214, 1216, Oct. 2011
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。, ライフサイエンス出版(株), Japanese

グリシン血中濃度とメタボリックシンドロームとの関係について　　　　　　　　　　　　　　　
佐藤 隆博, 坂上 慎二, 池田 大輔, 山田 安寿香, 大平 洋, 後藤 知紗, 渡部 拓, 大平 恵, 辻野 一三, 大塚 吉則, 西村 正治, 糖尿病, 54, 2, 143, 143, Feb. 2011
(一社)日本糖尿病学会, Japanese

当科で経験した肺動脈性肺高血圧症60例のまとめ
佐藤隆博, 辻野一三, 大平洋, 池田大輔, 坂上慎二, 西村正治, 日本循環器学会北海道地方会(Web), 103rd, 2010

Reduced Left Ventricular Torsion With Two-Dimensional Speckle Tracking Echocardiography Would Predict Acute Rejection in Heart Transplant Recipients
Takahiro Sato, Tomoko S. Kato, Shuji Hashimoto, Noboru Oda, Masanobu Yanase, Hideaki Kanzaki, Kazuhiko Hshimura, Hatsue Ueda, Kazuo Komamura, Toshiaki Shishido, Takeshi Nakatani, Masafumi Kitakaze, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 53, 10, A181, A182, Mar. 2009
English, Summary international conference

国立循環器病センターでコイル塞栓術を施行された成人肺動静脈瘻の臨床像
佐藤隆博, 小野文明, 京谷晋吾, 中西宣文, 山田修, 森崎裕子, 日本小児循環器学会雑誌, 24, 6, 2008

腎動脈下感染性腹部大動脈瘤3症例
曾澤佳昭, 佐藤隆博, 原田敏之, 大平浩司, 吉村治彦, 鈴木章彦, 松崎賢司, 国原孝, 椎谷紀彦, 岩見沢市立総合病院医誌, 33, 1, 2007

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, Therapeutic Research, 25, 6, 1236, 1239, Jun. 2004
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, ライフサイエンス出版(株), Japanese

beraprost(ドルナー)に対するSildenafil(バイアグラ)の相加効果を確認した慢性肺血栓塞栓性肺高血圧症の一例
佐藤 隆博, 池田 大輔, 大平 洋, 神垣 光徳, 石丸 伸司, 吉村 治彦, 坂上 慎二, 辻野 一三, 西村 正治, 工藤 敏行, Circulation Journal, 68, Suppl.II, 756, 756, Apr. 2004
(一社)日本循環器学会, Japanese